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Anashkin, S., A. Bovkun, L. Bindi, V. Garanin, and Y. Litvin. "Kudryavtsevaite, Na3MgFe3+Ti4O12, a new kimberlitic mineral." Mineralogical Magazine 77, no. 3 (2013): 327–34. http://dx.doi.org/10.1180/minmag.2013.077.3.06.
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AbstractKudryavtsevaite, ideally Na3MgFe3+Ti4O12, is a new mineral from kimberlitic rocks of the Orapa area, Botswana. It occurs as rare prismatic crystals, up to 100 μm m across, associated with Mg-rich ilmenite, freudenbergite and ulvöspinel. Kudryavtsevaite is opaque with a vitreous lustre and shows a black streak. It is brittle; the Vickers hardness (VHN100) is 901 kg mm−2 (range: 876–925) (Mohs hardness ∼6). In reflected light, kudryavtsevaite is moderately bireflectant and very weakly pleochroic from dark grey to a slightly bluish grey. Under crossed polars, it is very weakly anisotropic with greyish-bluish rotation tints. Internal reflections are absent. Reflectance values (%), Rmin and Rmax, are: 21.3, 25.4 (471.1 nm), 20.6, 24.1 (548.3 nm), 20.0, 23.5 (586.6 nm) and 19.1, 22.4 (652.3 nm).Kudryavtsevaite is orthorhombic, space group Pnma, with a = 27.714(1), b = 2.9881(3), c = 11.3564(6) Å, V = 940.5(1) Å3, and Z = 4. The crystal structure [R1 = 0.0168 for 819 reflections with I > 2σ(I)] consists of edge-sharing and corner-sharing chains composed of Mg, Fe3+ and Ti atoms coordinated by six atoms of oxygen and running along the b axis, with Na filling the tunnels formed by the chains. The eight strongest powder-diffraction lines [d in Å (I/I0) (hkl)] are: 7.17 (100) (301), 4.84 (70) (302), 2.973 (35) (901), 2.841 (50) (004), 2.706 (50) (902), 2.541 (50) (312), 2.450 (70) (611), and 2.296 (45) (612). The average results of 12 electron microprobe analyses gave (wt.%): Na2O 16.46(15), CaO 1.01(3), MgO 5.31(5), Fe2O3 22.24(32), Cr2O3 1.05(6), Al2O3 0.03(2), TiO2 53.81(50), total 99.91, corresponding to the empirical formula (Na2.89Ca0.10)Σ2.99(Ti3.67Fe1.523+Mg0.72Cr0.08)Σ5.99O12, or ideally Na3MgFe3+Ti4O12.The new mineral has been approved by the IMA-CNMNC and named for Galina Kudryavtseva (1947–2006), a well known Russian mineralogist and founder of the Diamond Mineralogy Laboratory and scientific school for investigation of diamond mineralogy and geochemistry at the Lomonosov State University in Moscow, Russia.
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Seregin, N. N., E. A. Narudtseva, A. N. Chistyakova, and S. S. Radovsky. "Yuan time metal mirror from the collection of the Altai State Museum of Local Lore." VESTNIK ARHEOLOGII, ANTROPOLOGII I ETNOGRAFII, no. 1(52) (February 26, 2021): 42–49. http://dx.doi.org/10.20874/2071-0437-2021-52-1-4.
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This article is concerned with the Chinese metal mirror, which, as it has been found during the study, has been stored for a long time in the collection of the Altai State Museum of Local Lore, but as yet has not attracted the attention of specialists and has not been introduced into scientific discourse. A special research has been required to determine the time and circumstances of its arrival to the museum, which involved working with the documentation of the Altai State Museum of Local Lore, stored both within the institute and in the State Archives of the Altai Territory. It has been concluded, that the mirror represents an occasional find and it came to the mu-seum in the first quarter of the 20th century from the Yenisei Province (currently, the southwestern part of Kras-noyarsk District. The article presents a detailed morphological characteristic of this artifact. The basis of the com-position in the ornamented part of the mirror is a stylized image of a single dragon. Its mouth is trying to grasp the holder, which symbolizes the “fire pearl”. The analysis of the specialised literature and catalogues showed that in Chinese mirrors such composition appeared only during the Tang Dynasty (618–907) and continued to exist dur-ing the Song Period (907–1279). It has been determined that the composition presented on such objects was reproduced for several centuries (Jin, Liao, and Yuan Dynasties), undergoing transformations associated with stylistic nuances (details of the image, shape of mirror, presence or absence of inscriptions) and size and quality of the objects. Based on the obtained data, the mirror from the Altai State Museum of Local Lore has been attrib-uted to the Yuan dynasty period. There are almost no analogies to such objects in Northern and Central Asia, despite the significant number of mirrors of the Mongolian time stored in collections of Siberian museums. There-fore, it seems possible to acknowledge the rarity of these very specimens; the fragmentarity of their distribution could possibly be explained by peculiarities of the history of specific craft centers that have yet to be investigated.
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Chi, M., and Y. Liu. "ANALYZING THE ROAD NETWORK STRUCTURE OF TANG-TIBET ROAD AND BUILDING A SPATIAL INFORMATION SYSTEM FOR ITS TIBET SECTION." International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XLVI-M-1-2021 (August 28, 2021): 125–31. http://dx.doi.org/10.5194/isprs-archives-xlvi-m-1-2021-125-2021.
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Abstract. Since the Tang Dynasty (618–907 AD), the Tang-Tibet Road has been the only way from inland China to Qinghai and Tibet, and even to other countries such as Nepal and India. It ties and bonds various ethnic groups and regions, integrates cultural memories and cross-cultural communication achievements from ancient times to the present, and witnesses the dynamic propagation of the culture. Affected by the environment, climate, and wars, Tang-Tibet Road was often impossible to travel on or through intermittently during its progressive development in history. Routes and lines of each of its sections changed from time to time; eventually, an ancient road network was formed, consisting of one trunk road, two subsidiary roads in the north and south, several branches, and scattered auxiliary routes separated from the system, among which there were both outward-oriented international passages and inward-oriented passages. Nonetheless, research on Tang-Tibet Road is insufficient at the current stage. Regarding the problems summarized based on the review of the research situation, the present work probes deeper into the network structure of Tang-Tibet Road. How historical corridor is generated and evolved is understood from a regional perspective. In particular, strategies to design a space information system for the Tibet section of Tang-Tibet Road are explained to promote the exploration and use of cultural heritages in Tibet, in an effort to preserve these heritages while developing Tibet’s society and economy.
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de Filette, Jeroen, Corina Andreescu, Filip Cools, Bert Bravenboer, and Brigitte Velkeniers. "A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors." Hormone and Metabolic Research 51, no. 03 (2019): 145–56. http://dx.doi.org/10.1055/a-0843-3366.
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AbstractMonoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9–8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2–1.2) and pembrolizumab (1.1%; 95% CI, 0.5–2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction – particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4–9.8; pembrolizumab, 8.5%; 95% CI, 7.5–9.7; PD-L1, 5.5%; 95% CI, 4.4–6.8; ipilimumab, 3.8%; 95% CI, 2.6–5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2–16.4%), hyperthyroidism (9.4–10.4%), hypophysitis (8.8–10.5%), and primary adrenal insufficiency (5.2–7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.
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Liu, Yachen, Xiuqi Fang, Junhu Dai, Huanjiong Wang, and Zexing Tao. "Could phenological records from Chinese poems of the Tang and Song dynasties (618–1279 CE) be reliable evidence of past climate changes?" Climate of the Past 17, no. 2 (2021): 929–50. http://dx.doi.org/10.5194/cp-17-929-2021.
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Abstract. Phenological records in historical documents have been proven to be of unique value for reconstructing past climate changes. As a literary genre, poetry reached its peak in the Tang and Song dynasties (618–1279 CE) in China. Sources from this period could provide abundant phenological records in the absence of phenological observations. However, the reliability of phenological records from poems, as well as their processing methods, remains to be comprehensively summarized and discussed. In this paper, after introducing the certainties and uncertainties of phenological information in poems, the key processing steps and methods for deriving phenological records from poems and using them in past climate change studies are discussed: (1) two principles, namely the principle of conservatism and the principle of personal experience, should be followed to reduce uncertainties; (2) the phenological records in poems need to be filtered according to the types of poems, background information, rhetorical devices, spatial representations, and human influence; (3) animals and plants are identified at the species level according to their modern distributions and the sequences of different phenophases; (4) phenophases in poems are identified on the basis of modern observation criteria; (5) the dates and sites for the phenophases in poems are confirmed from background information and related studies. As a case study, 86 phenological records from poems of the Tang Dynasty in the Guanzhong region in China were extracted to reconstruct annual temperature anomalies in specific years in the period between 600 and 900 CE. Following this, the reconstruction from poems was compared with relevant reconstructions in published studies to demonstrate the validity and reliability of phenological records from poems in studies of past climate changes. This paper reveals that the phenological records from poems could be useful evidence of past climate changes after being scientifically processed. This could provide an important reference for future studies in this domain, in both principle and methodology, pursuant of extracting and applying phenological records from poems for larger areas and different periods in Chinese history.
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Rivera Manrique, Solange Ivette, Felipe de Jesús Carrillo Romo, Antonieta García Murillo, Carlos Eduardo Rodríguez García, and Jorge Roberto Oliva Uc. "Blue, Green and Red Upconverted Emission of Controlled Hydrothermal Pressure Synthesized Y2O3: Er3+ (1%) Tm3+ (1%) and Different Yb3+ Ratio Conditions Nanophosphors." Current Physical Chemistry 9, no. 3 (2019): 226–31. http://dx.doi.org/10.2174/1877946809666190830151043.
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Introduction: Rare earth-doped Upconverting Nanoparticles (UCN's) can convert near-infrared photons into visible photons via multiphoton processes, which makes it a good material for generating white light. The production of luminescent materials for technology applications focuses on controlling powder characteristics such as chemical homogeneity and low impurity levels. Objective: In this research study, we synthesized Er3+ (1%) Tm3+ (1%) Yb3+ (at different percentages) by co-doping Y2O3 NPs, using the Controlled-Pressure Hydrothermal Method (CPHM), with nitrogen. The ratio used was chosen to conduct a detailed photolumniscence analysis. Methods: Samples of Y2O3: Er3+ (1%) Tm3+ (1%) Yb3+ (at 1.5%, 2%, and 2.5%) were prepared using the controlled-pressure hydrothermal method (CPHM). Each solution was transferred into a mini-clave drive Büchiglasuster with an inner Teflon vessel. In this case, the mini-clave was heated at 190°C for 3 h, and nitrogen was used to control the pressure. The initial pressure was 20 bars; it was increased during the process to 42 bars. The powders obtained were washed with distilled water using centrifugation at 4000 rpm for 15 min. The washed product was dried to 120°C, followed by subsequent heat treatment at 1000°C for 5 h. Results: The representative XRD patterns for the Y2O3: Er3+ (1%) Tm3+ (1%) and Yb3+ (at 1.5%, 2%, 2.5%) doped samples confirms the presence of a cubic Y2O3 crystal structure. Scanning Electron Microscope (SEM) images show that the morphology of these particles is spherical. Upconversion photoluminescence spectra of Y2O3:Er3+ (1% mol) Tm3+ (1% mol) Yb3+ (1.5% mol), Yb3+ (2.0% mol), and Yb3+ (2.5% mol), after 908-nm excitation. Blue, green, and red bands are centred at 440 nm, 469 nm, 618 nm, and 678 nm, respectively. Conclusion: The controlled-pressure hydrothermal method is a productive method for synthesizing rare earth-doped and codoped Y2O3; when Er3+, Yb3+, and Tm3+ ions are introduced into the host matrix, they do not cause any changes in the cubic structure nor influence the crystal structure. This method can used to synthesize any type of nanoparticle, because it involves low pressure (10-20 bars), low temperatures, and short time reactions.
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Caldwell, M. L., H. H. Richardson, and M. E. Kordesch. "Optical Properties of Manganese Doped Amorphous and Crystalline Aluminum Nitride Films." MRS Internet Journal of Nitride Semiconductor Research 5, S1 (2000): 159–66. http://dx.doi.org/10.1557/s1092578300004221.
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An aluminum nitride (AlN) film deposited on silicon (100) was used as the substrate for growing manganese (Mn) doped AlN film by metal organic chemical vapor deposition (MOVCD). The (15.78 µm) under layer of AlN was grown at 615°C at a pressure of 10−4 Torr. The (2.1 µm) top layer of Mn-AlN was grown at the same temperature and pressure but doped with pulse valve introduction of the manganese decacarbonyl (100 ms on, 100 ms off). The film was then characterized ex situ with IR reflectance microscopy, X-ray diffraction, scanning electron microscopy imaging, cathodoluminescence, and X-ray fluorescence. The IR reflectance measurements showed a strong (A1) LO mode for AlN at 920 cm−1 and 900 cm−1 with a shoulder at 849 cm−1. X-ray Diffraction yielded three diffraction peaks at a 2θ position of 33, 36 and 38 degrees corresponding to 100, 002, and 101 lattice planes respectively. Cathodoluminescence results show strong visible emitted light from incorporated manganese. The relative percentage of manganese to aluminum was below the detection limit (0.01 %) of the X-ray fluorescence spectrometer. Amorphous Mn doped AlN films have also been grown using a low temperature atomically abrupt sputter epitaxial system. The amorphous Mn doped AlN showed no cathodoluminescence.
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Clarke, Jonathan, Alice Murray, Sheraz Rehan Markar, Mauricio Barahona, and James Kinross. "New geographic model of care to manage the post-COVID-19 elective surgery aftershock in England: a retrospective observational study." BMJ Open 10, no. 10 (2020): e042392. http://dx.doi.org/10.1136/bmjopen-2020-042392.
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ObjectivesThe suspension of elective surgery during the COVID-19 pandemic is unprecedented and has resulted in record volumes of patients waiting for operations. Novel approaches that maximise capacity and efficiency of surgical care are urgently required. This study applies Markov multiscale community detection (MMCD), an unsupervised graph-based clustering framework, to identify new surgical care models based on pooled waiting-lists delivered across an expanded network of surgical providers.DesignRetrospective observational study using Hospital Episode Statistics.SettingPublic and private hospitals providing surgical care to National Health Service (NHS) patients in England.ParticipantsAll adult patients resident in England undergoing NHS-funded planned surgical procedures between 1 April 2017 and 31 March 2018.Main outcome measuresThe identification of the most common planned surgical procedures in England (high-volume procedures (HVP)) and proportion of low, medium and high-risk patients undergoing each HVP. The mapping of hospitals providing surgical care onto optimised groupings based on patient usage data.ResultsA total of 7 811 891 planned operations were identified in 4 284 925 adults during the 1-year period of our study. The 28 most common surgical procedures accounted for a combined 3 907 474 operations (50.0% of the total). 2 412 613 (61.7%) of these most common procedures involved ‘low risk’ patients. Patients travelled an average of 11.3 km for these procedures. Based on the data, MMCD partitioned England into 45, 16 and 7 mutually exclusive and collectively exhaustive natural surgical communities of increasing coarseness. The coarser partitions into 16 and seven surgical communities were shown to be associated with balanced supply and demand for surgical care within communities.ConclusionsPooled waiting-lists for low-risk elective procedures and patients across integrated, expanded natural surgical community networks have the potential to increase efficiency by innovatively flexing existing supply to better match demand.
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Zapesochnaya, Irina L., and A. G. Avtandilov. "Dynamics of characteristics of cerebral circulation during combined treatment with amlodipine and bisoprolol." Clinical Medicine (Russian Journal) 94, no. 12 (2017): 908–14. http://dx.doi.org/10.18821/0023-2149-2016-94-12-908-914.
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Objective: to assess dynamics of cerebral blood flow when starting combined therapy with amlodipine and bisoprolol in hypertensive patients working in the Far North under various labor schedules. Material and methods. We studied 140 patients with grade 1-2 hypertension divided into two groups depending on their work schedule. Group 1 (n=72) included subjects working only at daytime; group 2 (n=68) consisted of subjects working in shifts. All patients received combined therapy with amlodipine and bisoprolol. The final mean daily dose of amlodipine/bisoprolol amounted to 8,3±1,3/9,8±1,6 mg/day and 9,5±1,5/14,5±1,2 mg/day in groups 1 and 2 respectively. Doppler ultrasound of the common carotid, internal carotid and vertebral arteries (OCA, BCA and PA, respectively) was performed before, 12 weeks, and 6 months after onset of therapy. Results. At the end-point of intervention (6 months) patients of group 1 showed an increase in peak systolic velocity (Vps) in OCA, BCA and PA (by 4,1, 5,9 and 5,5% respectively) and maximum end-diastolic flow velocity (Ved) in ОCA and ВCA (by 5,8 and 5,2% respectively). Patients of group 2 showed an increase of Vps in OCA, BCA and PA by 6,3, 8,4 and 7,1% respectively; Ved in OCA and BCA by 6,4 and 14,5% respectively. All patients exhibited a pronounced downward trend of the peripheral resistance index of in all studied arteries. The tendency to a decrease in the thickness of the intima-media complex was documented: by 4,1%, in group 1, 6,8% in group 2, without reaching the normal level. Conclusion. 6-month starting combined therapy with amlodipine and bisoprolol in hypertensive patients has positive effect on cerebral hemodynamics manifest as the increase in parameters of cerebral blood flow velocity and reduced peripheral resistance index. Pronounced downward trend in the thickness of the intima-media monitoring in both groups was apparent but without reaching the standard level.
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Groves, Kelly M., Stuart L. Warren, and Ted E. Bilderback. "Irrigation Volume, Application, and Controlled-release Fertilizers: I. Effect on Plant Growth and Mineral Nutrient Content in Containerized Plant Production." Journal of Environmental Horticulture 16, no. 3 (1998): 176–81. http://dx.doi.org/10.24266/0738-2898-16.3.176.
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Abstract An experiment with four volumes of irrigation and five controlled-release fertilizers (CRFs) was conducted to evaluate effects on plant growth and mineral nutrient content. Rooted cuttings of Cotoneaster dammeri ‘Skogholm’ and seedlings of Rudbeckia fulgida ‘Goldsturm’ were grown in 3.8 liter (4 qt) containers in a pine bark:sand substrate (8:1, by vol) incorporated with 3.5 g (0.12 oz) N per container with one of the following five CRFs: Meister 21N–3.5P–11.1K (21–7–14), Osmocote 24N–2.0P–5.6K (24–4–7), Scotts 23N–2.0P–6.4K (23–4–8), Sustane 5N–0.9P–3.3K (5–2–4) or Woodace 21N–3.0P–9.5K (21–6–12). Irrigation volumes of 200 ml (0.3 in), 400 ml (0.6 in), 800 ml (1.1 in), or 1200 ml (1.7 in) were applied once daily (single) or in two equal applications with a two hr interval between irrigation allotments (cyclic). All measured variables were unaffected by irrigation application (cyclic or single). Top dry weight of cotoneaster increased quadratically with increasing irrigation volume for all CRFs. Maximum top dry weight was obtained with 612 ml (0.8 in), 921 ml (1.3 in), 928 ml (1.3 in), 300 ml (0.6 in), or 909 ml (1.3 in) for plants fertilized with Meister, Osmocote, Scotts, Sustane, and Woodace, respectively. Osmocote, Scotts, and Woodace produced 90% of maximum top weight over a wide range of irrigation volumes [≈ 550 ml (0.8 in) to 1200 ml (1.5 in)]. Stomatal conductance of cotoneaster fertilized with Osmocote 24–4–7 increased linearly with increasing volume of irrigation, whereas net photosynthetic rate increased quadratically and was highest at 800 ml (1.1 in). All CRFs, excluding Sustane, had similar dry weights when irrigated with 200 ml (0.3 in). At 800 ml (1.1 in) and 1200 ml (1.7 in), cotoneaster fertilized with Osmocote 24–4–7 and Scotts 23–4–8 produced greater top dry weight compared to Meister, Sustane, and Woodace. Top dry weight of rudbeckia increased quadratically with increasing irrigation volume regardless of CRFs. Maximum dry weight was produced with 1160 ml, 931 ml, 959 ml, 1091 ml, or 1009 ml for plants grown with Meister, Osmocote, Scotts, Sustane, or Woodace, respectively. Ninety percent of the maximum top dry weight of both species within each CRF could be obtained with a 40% reduction in irrigation volume. Nitrogen content of cotoneaster and rudbeckia were unaffected by irrigation volume, whereas P and K content, depending upon CRF and plant, was reduced at low irrigation volumes.
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Raz, Gil. "Stephen Eskildsen, Daoism, Meditation, and the Wonders of Serenity: From the Latter Han Dynasty (25–220) to the Tang Dynasty (618–907). Albany: SUNY Press, 2015. viii, 387 pp. Bibliography, Index. US$ 85 (HB). ISBN 978-1-4384-5823-6." Monumenta Serica 67, no. 1 (2019): 250–58. http://dx.doi.org/10.1080/02549948.2019.1603461.
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Drápelová, I., L. Menšík, J. Kulhavý, and I. Marková. "Sulphur and nitrogen concentrations and fluxes in bulk precipitation and throughfall in the mountain and highland spruce stands in the Czech Republic." Journal of Forest Science 56, No. 10 (2010): 429–41. http://dx.doi.org/10.17221/99/2009-jfs.
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Concentrations and fluxes of sulphur and nitrogen compounds in bulk precipitation and in throughfall were evaluated and compared for two experimental sites in the Czech Republic: one situated at R&aacute;jec (Drahansk&aacute; upland, 610 m a.s.l.) and the second one at B&iacute;l&yacute; Kř&iacute;ž (Moravian-Silesian Beskids, 908 m a.s.l.) both with similar stands of young Norway spruce. The three-year study performed during 2006&ndash;2008, revealed statistically significant differences in nitrate nitrogen concentrations in bulk precipitations and in ammonium nitrogen concentrations both in bulk precipitation and in throughfall between the two sites. Higher nitrogen compounds concentrations in bulk precipitation were found at R&aacute;jec. Differences between the two sites in sulphur concentrations were not found out neither in bulk precipitation nor in throughfall waters. Total sulphur deposition amounted to 8.1, 8.3 and 6.7 kg S&middot;ha<sup>&ndash;1</sup> at R&aacute;jec and to 14.8, 16.9 and 15.4 kg S&middot;ha<sup>&ndash;1</sup> at Beskids for the three years studied, respectively. Total inorganic nitrogen throughfall flux amounted to 12.1, 11.6 and 11.6 at R&aacute;jec and 13.8, 18.9 and 15.0 kg&middot;ha<sup>&ndash;1</sup> at B&iacute;l&yacute; Kř&iacute;ž for the years 2006, 2007 and 2008, respectively. &nbsp;
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Nandakumar, Vijayalakshmi, Christopher Dolan, Nikola A. Baumann, and Darci R. Block. "Effect of pH on the Quantification of Body Fluid Analytes for Clinical Diagnostic Testing." American Journal of Clinical Pathology 152, Supplement_1 (2019): S10—S11. http://dx.doi.org/10.1093/ajcp/aqz112.021.
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Abstract Background Body fluid samples (BFs) with low pH have demonstrated underrecovery of enzyme activity. The aims of this study were (1) measure the frequency of abnormal pH in BFs received for clinical chemistry testing, (2) calculate recovery of analytes in BFs undergoing pH titration, and (3) investigate the mechanism of pH interference. Methods Residual BFs submitted for physician-ordered testing to the Central Clinical Laboratory (Mayo Clinic) were utilized for this study. BFs were centrifuged 10 minutes (3,200 rpm) prior to pH measurement (pH meter, Accumet X15; Fisher Scientific) and analysis. A Roche Cobas c501 (Roche Diagnostics) analyzer was used to measure amylase, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, glucose, albumin, total protein, bilirubin (all Roche Diagnostics reagents), and lipase (Sekisui Diagnostics). pH was measured in 122 BFs received between 10/23/2018 and 10/26/2018 within 24 hours of receipt. pH titration was performed using pooled BFs of similar source/type. Each pool was titrated over a range of pH (≤2 to ≥10) in 1-unit increments by addition of a fixed volume of acid (6M HCL) or base (6M NaOH). Analytes were measured before and after acid/base addition. Average percent recovery was calculated (measured/expected × 100%) from n = 3 to 9 pH measurements. A low pH BF pool was spiked (<5% by volume) with a high-concentration BF to investigate mechanism of enzyme underrecovery. Additionally, low pH BF pool was neutralized by addition of base and % recovery calculated. For all titration/spiking experiments, a control sample having the same volume of diluent (7% bovine serum albumin or saline) was used to account for the effects of dilution. Results BFs received (n = 122) had mean (SD) pH = 8.0 (0.6) with 6.6% (n = 8) having pH <7.0 and 2.5% (n = 3) having pH <6.0. All recovery (%) and pH data are expressed as mean (range) values. Amylase recovery (initial pH = 8.4-8.9) was 1.3 (0.9-2.2)% at pH = 1.6 (1.0-2.2) (n = 6), 55.6 (37.4-67.0)% at pH = 4.4 (3.5-5.4) (n = 6), 81.4 (74.0-85.2)% at pH = 6.2 (6.1-6.5) (n = 3), 90.1 (84.4-95.4)% at pH = 7.5 (7.3-7.7) (n = 3), 98.8 (96.2-101.7)% at pH = 10.0 (9.8-10.2) (n = 3), and 14.5 (1.4-38.9)% at pH = 11.9 (11.5-12.1) (n = 3). LDH recovery (initial pH = 8.2-8.5) was 1.4 (0.1-3.7)% at pH = 1.7 (1.0-2.4) (n = 6), 18.3 (0.5-39.7)% at pH = 4.5 (3.5-5.4) (n = 6), 63.6 (54.9-68.4)% at pH = 6.2 (6.1-6.5) (n = 3), 85.9 (80.2-90.7)% at pH = 7.2 (6.8-7.4) (n = 3), 46.1 (36.4-61.0)% at pH = 10.0 (9.8-10.2) (n = 3), and 9.8 (0.0-28.9)% at pH = 11.3 (10.4-12.1) (n = 3). Lipase recovery (initial pH = 8.2-8.9) was 10.4 (<1-18)% at pH = 1.8 (1.0-2.4) (n = 6), 73.9 (62.6-85.5)% at pH = 4.2 (3.4-5.2) (n = 3), 92.4 (90.8-93.5)% at pH = 6.2 (6.0-6.5) (n = 3), 96.3 (95.6-96.8)% at pH = 7.3 (6.8-7.7) (n = 3), and 92.9 (89.3-96.8)% at pH = 9.9 (9.8-10.1) (n = 3) and 80.9 (0.0-78.6)% at pH = 11.3 (10.4-12.1) (n = 3). Creatinine, BUN, albumin, glucose, total protein, and bilirubin recovery were 97.9 (92.2-102.9)%, 100 (96.6-103.1)%, 99.9 (97.6-102.4)%, 100.2 (97.8-103)%, 100.2 (98.7-101.9)%, and 100.1 (92.-105.9)%, respectively, between pH 1.3-11.7 (n = 9). Recovery of amylase, LDH, or lipase was <1% after spiking enzymes into BF pool with pH <3. pH adjustment to normal (pH = 8.6-9.0) also resulted in recovery of <1%. Conclusion Enzyme activity in BFs was not affected (90%-110% recovery) when pH = 7.4-8.5 for LDH, pH = 7.3-10.2 for amylase, pH = 6.0-9.9 for lipase, and pH = 1.3-11.7 for all other analytes. An irreversible loss of enzyme activity occurs at low pH. Few clinical BFs have pH <7.0, but laboratories should have awareness.
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Mauzo, Shakuntala H., Michael T. Tetzlaff, Denái R. Milton, et al. "Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy." Cancers 11, no. 6 (2019): 754. http://dx.doi.org/10.3390/cancers11060754.
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Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm2; range, 543–2115;) than in those who died (median, 611 cells/mm2; range, 481–908; p = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (p = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.
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Martinez Lago, Nieves, Marta Covela Rúa, Elena Brozos Vazquez, et al. "The prognostic value of systemic inflammatory factors in BRAF (V600E) mutant metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 37, no. 4_suppl (2019): 622. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.622.
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622 Background: Multiple studies have reported prognostic association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLT) and albumin levels including patients with early and advanced metastatic colorectal cancer. However, it is unknown the prognostic impact in patients with BRAF (V600E) mutant metastatic colorectal cancer (mCRC). Methods: We conducted an observational, retrospective, multicentric study of patients with BRAF V600E-mt mCRC treated at nine university Spanish hospitals belonging to GITuD (Galician Research Group on Digestive Tumors). Demographic, clinic, pathological characteristics, overall survival (OS) and progression free survival (PFS) data were retrospectively analyzed. Results: Data from 65 pts. treated between November 2010 to June 2018 were recorded. Median age was 62.8 years (range 30-83), 55.4 % female, 75.4% ECOG PS0-1, 49.2% right-sided, 35.2% high grade, 69.2% synchronous presentation, 66.2% primary tumor resection and median metastatic locations was 2 (range 1-5). With a median follow up of 64.6 months, median OS was 12.9 months (95% CI, 9.8-16.0) and first line PFS was 4.1 months (95% CI, 2.7-5.5). NLR (HR 2.294; p = 0.004), PLR (HR 6.329; p = 0.028) and albumin levels (HR 2.575, p = 0.011) were independent prognostic factors for OS. Patients with higher NLR (> 3 vs. < 3): had a significantly lower OS 6.8 versus 17.5 months (HR 2.294; 95% CI 1.3-4.1, p = 0.004), which was also true for patients with higher PLR (> 200 vs. < 200): with OS 6.3 versus 14.5 months (HR 1.879; 95% CI 1.1-3.3, p = 0.028), while patients with low albumin had lower OS 6.8 versus 13.4 months (HR 2.575; 95% CI 1.2-5.5, p = 0.011). NLR was positively associated with PLR (p < 0.001). Neither NLR (p = 0.190) or PLR (p = 0.327) were associated with low albumin levels. A Systemic Inflammation Score (assigning one point for each factor) was predictive of survival: OS 0/1/2/3 factors were 17.7 versus 8.7 versus 9.7 versus 5.0 months (p < 0.001). Patients with Systemic Inflamation Score = 0 had significantly higher OS: 17.7 versus 8.2 months (HR 0.357; 95% CI 0.2-0.7, p = 0.001). Conclusions: NLR, PLR and albumin levels are significant prognostic factors in patients with BRAF V600E-mt mCRC.
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Xiao, S., M. Y. Wang, L. Yao, et al. "Strong atmospheric new particle formation in winter in urban Shanghai, China." Atmospheric Chemistry and Physics 15, no. 4 (2015): 1769–81. http://dx.doi.org/10.5194/acp-15-1769-2015.
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Abstract. Particle size distributions in the range of 1.34–615 nm were recorded from 25 November 2013 to 25 January 2014 in urban Shanghai, using a combination of one nano condensation nucleus counter system, one nano scanning mobility particle sizer (SMPS), and one long-SMPS. Measurements of sulfur dioxide by an SO2 analyzer with pulsed UV fluorescence technique allowed calculation of sulfuric acid proxy. In addition, concentrations of ammonia were recorded with a differential optical absorption spectroscopy. During this 62-day campaign, 13 new particle formation (NPF) events were identified with strong bursts of sub-3 nm particles and subsequent fast growth of newly formed particles. The observed nucleation rate (J1.34), formation rate of 3 nm particles (J3), and condensation sink were 112.4–271.0 cm−3 s−1, 2.3–19.2 cm−3 s−1, and 0.030–0.10 s−1, respectively. Subsequent cluster/nanoparticle growth (GR) showed a clear size dependence, with average values of GR1.35~1.39, GR1.39~1.46, GR1.46~1.70, GR1.70~2.39, GR2.39~7, and GR7~20 being 1.6±1.0, 1.4±2.2, 7.2±7.1, 9.0±11.4, 10.9±9.8, and 11.4±9.7 nm h−1, respectively. Correlation between nucleation rate (J1.34) and sulfuric acid proxy indicates that nucleation rate J1.34 was proportional to a 0.65±0.28 power of sulfuric acid proxy, indicating that the nucleation of particles can be explained by the activation theory. Correlation between nucleation rate (J1.34) and gas-phase ammonia suggests that ammonia was associated with NPF events. The calculated sulfuric acid proxy was sufficient to explain the subsequent growth of 1.34–3 nm particles, but its contribution became smaller as the particle size grew. Qualitatively, NPF events in urban Shanghai likely occur on days with low levels of aerosol surface area, meaning the sulfuric acid proxy is only a valid predictor when aerosol surface area is low.
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Ortega, R. M., E. Rodríguez-Rodríguez, A. Aparicio, et al. "Poor zinc status is associated with increased risk of insulin resistance in Spanish children." British Journal of Nutrition 107, no. 3 (2011): 398–404. http://dx.doi.org/10.1017/s0007114511003114.
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Zn plays a key role in the synthesis and action of insulin. The aim of the present work was to determine whether a poorer Zn status was associated with insulin resistance in a group of 357 Spanish schoolchildren. Zn intake was determined by using a 3 d food record (i.e. Sunday to Tuesday). The body weight, height and waist and hip circumferences of all subjects were recorded and fasting plasma glucose, insulin and Zn concentrations were determined. Insulin resistance was determined using the homoeostasis model assessment (HOMA) marker. Children (11·5 %) with Zn deficiency (serum Zn concentration < 10·7 μmol/l) had higher HOMA values than those with a more satisfactory Zn status (1·73 (sd0·93)) compared with 1·38 (sd0·90;P < 0·05). An inverse correlation was found between the HOMA value and the serum Zn concentration (r− 0·149,P < 0·05). The risk of having a greater insulin resistance value (HOMA greater than the 75th percentile) increased with age (OR 1·438; 95 % CI 1·021, 2·027) and BMI (OR 1·448; 95 % CI 1·294, 1·619) and decreased as Zn serum levels increased (OR 0·908; 95 % CI 0·835, 0·987;P < 0·001). Moreover, an inverse relationship was observed between HOMA values and Zn dietary density (r− 0·122), and the Zn intakes of male children with a HOMA value of >3·16 made a significantly smaller contribution to the coverage of those recommended (59·7 (sd14·7) %) than observed in children with lower HOMA values (73·6 (sd18·2) %;P < 0·05). Taking into account that Zn intake was below than that recommended in 89·4 % of the children, it would appear that increasing the intake of Zn could improve the health and nutritional status of these children, and thus contribute to diminish problems of insulin resistance.
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Ayuob, Atif, Babar Kayani, and Fares S. Haddad. "Musculotendinous Junction Injuries of the Proximal Biceps Femoris: A Prospective Study of 64 Patients Treated Surgically." American Journal of Sports Medicine 48, no. 8 (2020): 1974–82. http://dx.doi.org/10.1177/0363546520926999.
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Background: Injuries to the hamstring complex most commonly involve the proximal musculotendinous junction of the long head of the biceps femoris (MTJ-BFlh). Nonoperative management of these injuries is associated with prolonged rehabilitation and high risk of recurrence. To our knowledge, the surgical management of acute MTJ-BFlh injuries has not been previously reported. Hypothesis: Surgical repair of acute MTJ-BFlh injuries enables return to sporting activity with low risk of recurrence. Study Design: Case series; Level of evidence, 4. Methods: A total of 64 patients (42 male and 22 female) undergoing surgical repair of acute MTJ-BFlh injuries were included. Predefined outcomes were recorded at regular intervals after surgery. Mean follow-up time after surgery was 29.2 months (range, 24.0-37.1 months). Results: All study patients returned to their preinjury levels of sporting activity. Mean ± SD time from surgical intervention to return to sporting activity was 13.4 ± 5.1 weeks. Three patients had reinjury at the operative site: 1 (1.6%) with MTJ-BFlh injury and 2 (3.2%) with myofascial tears. At 3 months after surgery, patients had improved mean passive straight-leg raise (72.0° ± 11.4° vs 24.1° ± 6.8°; P < .001); increased mean isometric hamstring muscle strength at 0° (84.5 % ± 10.4% vs 25.9% ± 8.9%; P < .001), 15° (89.5% ± 7.3% vs 41.2% ± 9.7%; P < .001), and 45° (93.9% ± 5.1% vs 63.4% ± 7.6%; P < .001); higher mean Lower Extremity Functional Scale scores (71.5 ± 5.0 vs 29.8 ± 6.3; P < .001); and improved mean Marx activity rating scores (9.8 ± 2.2 vs 3.8 ± 1.9; P < .001), as compared with preoperative scores. High patient satisfaction and functional outcome scores were maintained at 1 and 2 years after surgery. Conclusion: Surgical repair of acute MTJ-BFlh injuries enables return to preinjury level of sporting function with low risk of recurrence at short-term follow-up.
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BYKERK, VIVIAN P., SHAHIN JAMAL, GILLES BOIRE, et al. "The Canadian Early Arthritis Cohort (CATCH): Patients with New-onset Synovitis Meeting the 2010 ACR/EULAR Classification Criteria But Not the 1987 ACR Classification Criteria Present with Less Severe Disease Activity." Journal of Rheumatology 39, no. 11 (2012): 2071–80. http://dx.doi.org/10.3899/jrheum.120029.
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Objective.Our objective was to describe characteristics of Canadian patients with early arthritis and examine differences between those fulfilling 1987 and 2010 rheumatoid arthritis (RA) classification criteria.Methods.The Canadian Early Arthritis Cohort (CATCH) is a national, multicenter, observational, prospective cohort of patients with early inflammatory arthritis, receiving usual care, recruited since 2007. Inclusion criteria include age > 16 years; symptom duration 6–52 weeks; swelling of ≥ 2 joints or ≥ 1 metacarpophalangeal/proximal interphalangeal joint; and 1 of rheumatoid factor ≥ 20 IU, positive anticitrullinated protein antibodies (ACPA), morning stiffness ≥ 45 min, response to nonsteroidal antiinflammatory drug, or positive metatarsophalangeal joint squeeze test. Data from patients enrolled to March 15, 2011, were analyzed.Results.In total, 1450 patients met the eligibility criteria (1187 were followed). At baseline, mean age was 53 ± 15 years, symptom duration was 6.1 ± 3.2 months, Disease Activity Score (DAS28) was 4.9 ± 1.6, Health Assessment Questionnaire-Disability Index was 1.0 ± 0.7. Forty-one percent (n = 450) of patients had moderate (3.2 < DAS28 ≤ 5.1) and 46% (n = 505) had high (DAS28 > 5.1) disease activity; 28% of those with baseline radiographs (n = 250/908) had radiographic evidence of erosions. ACPA status was available for 70% (n = 831) of patients; 55% (n = 453) tested positive. Sixty percent (n = 718) of patients were treated with methotrexate (MTX) initially. Of 612 patients without erosions, 63% and 83% fulfilled 1987 and 2010 RA classification criteria, respectively. Seventy-three percent (n = 166) of those who did not fulfill 1987 criteria were newly identified by the 2010 criteria. These patients had less severe disease and more were MTX-naive compared to those satisfying the 1987 criteria. Forty-seven percent of all patients achieved remission at 1 year.Conclusion.Patients with early RA present with moderate high disease activity; < 50% achieve remission at 1 year, despite MTX treatment in the majority. The 2010 RA classification criteria identify more patients with RA who would previously have been designated as having undifferentiated disease. However, these patients have lower disease activity at the time of identification.
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Lanman, Todd H. "174 Comparison of 7-Year Results of One-Level versus Two-Level Cervical Disc Arthroplasty and Fusion." Neurosurgery 64, CN_suppl_1 (2017): 245. http://dx.doi.org/10.1093/neuros/nyx417.174.
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Abstract INTRODUCTION Two independent clinical trials concluded that cervical disc arthroplasty (CDA) is as safe and effective as anterior cervical discectomy and fusion (ACDF) for treating cervical disc disease (CDD) at one and two levels. This study compared the safety and effectiveness at 7-year follow-up for subjects treated with CDA versus ACDF at 1 and 2-levels. METHODS Retrospective analysis of combined data from 1 and 2-level FDA IDE clinical trials. Outcomes were compared between 1-level and 2-level CDA and ACDF subjects. Propensity score method was used for an adjusted means analysis. RESULTS >There were no preoperative differences between 1 and 2-level CDA and ACDF patients for NDI, neck/arm pain, and SF-36 PCS. Comparing 1 vs 2-level CDA: there were no differences between 1 and 2-level CDA for NDI improvement (38.2 vs 39.0, P = 0.768), neck pain (11.7 vs 12.3, P = 0.374), arm pain (11.3 vs 11.0, P = 0.736), SF-36 PCS (12.6 vs 14.5, P = 0.220), or rates of neurological success (92.8% vs 91.6%, P = 0.867). Secondary surgeries were numerically higher for 1-than 2-level CDA at index and adjacent levels (7.3% vs 4.2%, P = 0.566) and (11.6% vs 6.5%, P = 0.056) respectively. Rates of serious AEs were significantly higher for 1 than 2-level CDA (67.8% vs 56.7%, P = 0.004). Comparison of 1 vs 2-level ACDF: there were no differences between 1 and 2-level ACDF for NDI improvement (31.1 vs 31.6, P = 0.859), neck pain (9.7 vs 9.9, P = 0.796), arm pain (9.9 vs 10.1, P = 0.848), SF-36 PCS (10.8 vs 12.1, P = 0.424), rates of neurological success (79.7% vs 82.1%, P = 0.421), or rates of secondary surgeries at index levels (13.6% vs 14.7%, P = 0.631) or adjacent levels (10.9% vs 12.5%, P = 0.366). Rates of serious AEs were similar for 1 and 2-level ACDF (61.8% vs 68.2%, P = 0.200) but rates of all AEs (94.5% vs 98.2%, P < 0.001) and device-related AEs (18.9% vs. 27.7%, P = 0.036) were significantly lower for 1 versus 2-level ACDF. CONCLUSION One and 2-level CDA appear to be equally safe and effective in the treatment of CDD at 7-years. Two-level ACDF was equally effective as 1-level, but 2-level ACDF had a higher rate of device-related AEs.
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Seguin, Aurélie, Robert Brian Haynes, Sebastian Carballo, Alfonso Iorio, Arnaud Perrier, and Thomas Agoritsas. "Translating Clinical Questions by Physicians Into Searchable Queries: Analytical Survey Study." JMIR Medical Education 6, no. 1 (2020): e16777. http://dx.doi.org/10.2196/16777.
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Background Staying up to date and answering clinical questions with current best evidence from health research is challenging. Evidence-based clinical texts, databases, and tools can help, but clinicians first need to translate their clinical questions into searchable queries. MacPLUS FS (McMaster Premium LiteratUre Service Federated Search) is an online search engine that allows clinicians to explore multiple resources simultaneously and retrieves one single output that includes the following: (1) evidence from summaries (eg, UpToDate and DynaMed), (2) preappraised research (eg, EvidenceAlerts), and (3) non-preappraised research (eg, PubMed), with and without validated bibliographic search filters. MacPLUS FS can also be used as a laboratory to explore clinical questions and evidence retrieval. Objective Our primary objective was to examine how clinicians formulate their queries on a federated search engine, according to the population, intervention, comparison, and outcome (PICO) framework. Our secondary objective was to assess which resources were accessed by clinicians to answer their questions. Methods We performed an analytical survey among 908 clinicians who used MacPLUS FS in the context of a randomized controlled trial on search retrieval. Recording account log-ins and usage, we extracted all 1085 queries performed during a 6-month period and classified each search term according to the PICO framework. We further categorized queries into background (eg, “What is porphyria?”) and foreground questions (eg, “Does treatment A work better than B?”). We then analyzed the type of resources that clinicians accessed. Results There were 695 structured queries, after exclusion of meaningless queries and iterations of similar searches. We classified 56.5% (393/695) of these queries as background questions and 43.5% (302/695) as foreground questions, the majority of which were related to questions about therapy (213/695, 30.6%), followed by diagnosis (48/695, 6.9%), etiology (24/695, 3.5%), and prognosis (17/695, 2.5%). This distribution did not significantly differ between postgraduate residents and medical faculty physicians (P=.51). Queries included a median of 3 search terms (IQR 2-4), most often related to the population and intervention or test, rarely related to the outcome, and never related to the comparator. About half of the resources accessed (314/610, 51.5%) were summaries, 24.4% (149/610) were preappraised research, and 24.1% were (147/610) non-preappraised research. Conclusions Our results, from a large sample of real-life queries, could guide the development of educational interventions to improve clinicians’ retrieval skills, as well as inform the design of more useful evidence-based resources for clinical practice. Trial Registration ClinicalTrials.gov NCT02038439; https://www.clinicaltrials.gov/ct2/show/NCT02038439
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Lefkou, Eleftheria, Kiran Parmar, Apostolos Mamopoulos, Sevasti Masouridou, Vassilios Karagiannis, and Beverley J. Hunt. "Peripartum Haemostatic Changes in Women in Labour." Blood 112, no. 11 (2008): 5475. http://dx.doi.org/10.1182/blood.v112.11.5475.5475.
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Abstract Introduction: Obstetric haemorrhage (OH) is a major cause of maternal mortality and morbidity worldwide. Appropriate management requires understanding of normal peripartum haemostatic changes during labour, and yet there are few studies. Aim: In this pilot study we aimed to evaluate peripartum haemostatic changes in healthy women. Methods: We collected blood samples from 20 women peripartum, into 0.102 M trisodium citrate tubes (ratio9:1) (Becton Dickinson) from the antecubital fossa using flawless venepuncture at the following time-points: antepartum; after delivery of the placenta; 24hrs post-partum and 48hrs post-partum. Plasma was aliquoted and stored in −70°C until the following ELIZA assays were performed: D-Dimer levels (Dade Behring, Sysmex UK), prothrombin fragments 1+ 2 (PF 1+2) (Dade Behring, Sysmex, UK) and tissue plasminogen activator antigen (t-PA:Ag) (Biopool, Trinity Biotech, UK). Prothrombin time (PT) (PT-Fib HS), activated partial thromboplastin time (APTT) (APTT micronized silica) and clauss fibrinogen (Fib-C), reagents were from Instrumentation Laboratories Ltd UK. Statistical analysis was performed using XLSTAT 2008. Results: The median (range) age was 28 (19–36) years and the body mass index (BMI) 28.9 (21.7– 35.3). Table 1: To show the median (range) for the haemostatic assays Assay (normal ranges) D-dimers (4–52ug/l) PF1+2 (0.2–1.2 pmol/l) t-PA:Ag: 3–11 ng/ml) PT (12–16s) APTT (26–38s) Fibrinogen (1.52–4.12 g/l) * p&lt;0.05 using the Mann Whitney U test between the 1st and each of the other three samples Antepartum 231 (122–900) 570 (352–1533 12 (7.2–23) 12 (10–14) 31 (24–36) 5.2 (3.1–8.7) Post Labour 482 (117–1044) 968 (480–1858)* 18 (8.6–40.6)* 13 (10–15) 30 (24–36) 5.3 (2.2–9.8) 24h 309 (65–931) 568 (264–1080)* 7 (4–23)* 13 (10–16)* 33 (27–41)* 5.3 (4–11) 48hrs 235 (85–614) 648 (371–2287) 7 (3–18)* 12 (10–16) 31 (23–43) 5.7 (3.5–11) Conclusion: These findings demonstrate that peripartum haemostasis is prothrombotic with shortened PT, APTT and prolonged fibrinogen. There is increased thrombin generation and fibrinolytic activity. t-PA antigen is most notably elevated immediately post delivery.
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Smit, E. F., M. A. Socinski, B. P. Mullaney, et al. "Pharmacogenomic analysis from a phase III study of pemetrexed plus carboplatin (PC) versus etoposide plus carboplatin (EC) in chemonaive patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC)." Journal of Clinical Oncology 27, no. 15_suppl (2009): 8030. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.8030.
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8030 Background: We have reported results of a randomized phase III trial in chemonaive patients with ED-SCLC comparing PC to EC. Study enrollment was closed for futility but pharmacogenomic endpoints were not reported. Here we report the results of immunohistochemistry (IHC) analysis from tumor tissues and single nucleotide polymorphism (SNP) analysis of selected genes implicated in pemetrexed, carboplatin, or etoposide activity. Methods: Proteins studied by validated IHC on Benchmark XT were thymidylate synthase (TS), excision repair cross complementing-1 (ERCC1), glycinamide ribonucleotide formyl transferase (GARFT), and folylpolyglutamate synthetase (FPGS). SNP data from whole blood were genotyped by massArray mass spectrometry from 611 samples. One hundred fifty-eight SNPs were genotyped for TS, FPGS, γ-glutamyl hydrolase (GGH), methylene tetrahydrofolate reductase (MTHFR), folate receptor- α (FR-α), solute carrier 19A1 (SLC19A1) and adjacent regions. Allele frequency and Hardy-Weinberg equilibrium were calculated for each SNP. Results: Of 408 tissue samples (from 908 enrolled pts) available for IHC, 336 samples were assayed for > 1 assay target. The IHC analyses showed improved OS in the EC arm relative to the PC arm for patients with low TSnuclear (12.9 vs 7.5 month, p < 0.001, interaction p value = 0.017). There was no differential treatment effect within the PC arm for low vs. high TS. High vs low ERCC1 levels did not predict outcome following C exposure. GARFT was not associated with outcome by treatment. SNP rs2838952 (adjacent to SLC19A1) was significant for improved OS (HR = 0.590, p = 0.01) in both study arms. SNP rs12379987 (FPGS) was significantly associated with treatment for OS (interaction p value = 0.036). Exploratory analyses found associations between additional SNPs and PFS within and across treatments. Conclusions: Pharmacogenomic analyses of tumor samples show that low TSnuclear expression correlates with OS in the EC arm. Two germline SNPs in regions including FPGS and SLC19A1 were associated with better OS. Further analysis of these pharmacogenomic results is ongoing. [Table: see text]
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Michelena, X., S. S. Zhao, S. Dubash, G. T. Jones, L. Dean, and H. Marzo-Ortega. "FRI0287 BIOLOGIC DRUG RESPONSE DOES NOT APPEAR RELATED TO RADIOGRAPHIC STATUS IN AXIAL SPONDYLOARTHRITIS: DATA FROM THE BSRBR-AS REGISTRY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 732.2–732. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3147.
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Background:The concept of axial spondyloarthritis (axSpA) incorporates the full range of inflammatory spinal disease. In the absence of specific immuno-genetic biomarkers, classification criteria differentiate two groups (non-radiographic [nr-axSpA] and radiographic axSpA [r-axSpA]) based on the presence of structural damage of the sacroiliac joints. Controversy remains as to whether nr-axSpA represents a milder form with biologic DMARD (bDMARD) treatment restrictions still in place in many countries.Table 1.Baseline characteristics of nr-axSpA and r-axSpA patients starting biologics.VariablesLevelnr-axSpAn=418r-axSpAn=727p-valueAge, mean (SD), years39.7 (12.4)46.1 (13.4)<0.001Sex, n (%)Male239 (57%)529 (73%)<0.001Symptom duration, mean (SD), years11.2 (10.9)16.7 (12.9)<0.001Diagnostic delay, median (IQR), years3.0 (1.0, 10.0)3.0 (0.0, 11.0)0.83HLA-B27(missing=325)227 (73%)387 (76%)0.40Inflammatory back pain, n (%)384 (92%)619 (92%)0.95Uveitis, n (%)92 (22%)205 (30%)0.003Crohn’s / Colitis, n (%)55 (13%)113 (17%)0.11Psoriasis, n (%)79 (19%)115 (17%)0.43Smoking status, n (%)Never smoked148 (43%)218 (38%)0.040Ex-smoker95 (28%)207 (36%)Current smoker100 (29%)154 (27%)NSAID use, n (%)311 (75%)560 (77%)0.43CRP, median (IQR), mg/dL0.5 (0.1, 1.3)0.9 (0.3, 2.5)<0.001BMI, mean (SD)27.5 (5.6)28.2 (5.8)0.10BASDAI, median (IQR)6.7 (5.4, 7.8)6.5 (5.0, 7.7)0.12BASFI, median (IQR)5.9 (4.2, 7.8)6.5 (4.4, 8.3)0.043VAS-G, mean (SD)7.0 (2.0)6.8 (2.0)0.056ASDAS-CRP, mean (SD)2.8 (0.8)2.8 (0.9)0.32ASQOL, median (IQR)13.0 (9.0, 16.0)13.0 (9.0, 15.5)0.29Biologic (to start), n (%)Adalimumab238 (57%)436 (60%)0.20Etanercept131 (31%)220 (30%)Certolizumab35 (8%)47 (6%)Golimumab5 (1%)12 (2%)Secukinumab7 (2%)10 (1%)Infliximab2 (<1%)2 (<1%)Objectives:To describe the baseline characteristics and bDMARD response at one year in axSpA patients in the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) according to radiographic status.Methods:BSRBR-AS is a national prospective cohort including participants who fulfil the ASAS classification criteria for axSpA. In this analysis, cross-sectional baseline data of patients starting bDMARDs including clinical, demographic and patient-reported outcomes (PROs) were compared. Follow-up data at one year was identified if 12±4 months from baseline and PROs completed within 2 months of visit date. Ankylosing Spondylitis Disease Activity Scores (ASDAS) for low disease status, clinically important improvement (CII) and major improvement (MI) were used to assess treatment response.Results:Baseline characteristics were available for 1,145 patients. Those with r-axSpA were more likely to be male, were older, and had longer disease duration (Table 1). Follow-up ASDAS was available in 290 patients. Two thirds of the patients achieved ASDAS low disease state at one year regardless of radiographic status (nr-axSpA: 64.2% vs r-axSpA: 66.1, Diff: -1.9%, 95% CI -13.7 to 9.8). Further, no significant differences were seen between the groups in attaining ASDAS CII (nr-axSpA: 50.7% vs r-axSpA: 44.7%, Diff: 6.0%, 95% CI -7.8 to 19.8%) or MI (nr-axSpA: 20% vs r-axSpA: 18.7%, Diff: 1.3%, 95% CI -9.7 to 12.3%).Conclusion:Although there appeared to be some differences in the baseline characteristics when exploring this cohort, according to radiographic status, which are likely related to the natural history of the disease; the level of biologic response was comparable between the groups supporting the concept of axSpA as a single disease entity.Acknowledgments:This project is supported by a FOREUM fellowship.Disclosure of Interests:Xabier Michelena: None declared, Sizheng Steven Zhao: None declared, Sayam Dubash: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene and GSK., Linda Dean: None declared, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis, Consultant of: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Speakers bureau: Abbvie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Takeda, UCBDOI:10.1136/±annrheumdis-2020-eular.3147
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Ruscheweyh, Ruth, Gregor Broessner, Gudrun Goßrau, et al. "Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts." Cephalalgia 40, no. 14 (2020): 1574–84. http://dx.doi.org/10.1177/0333102420949866.
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Objective To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. Background Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. Methods Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. Results The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2–11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by −9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody ( p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (−6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (−9.8 ± 7.6, p < 0.001) and pain intensity during attacks (−1.2 ± 2.0, numerical rating scale (NRS) [0–10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was −8.0 ± 8.4 ( p = 0.004) and −9.1 ± 10.0 ( p = 0.024), respectively. Conclusion Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.
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Backus, Varda Peller. "The Psychiatric Therapies: Part 1, The Somatic Therapies, and Part 2, The Psychosocial Therapies—compiled by the American Psychiatric Association Commission on Psychiatric Therapies, chaired by Toksoz B. Karasu, M.D.; American Psychiatric Association, Washington, D.C., 1984, 908 pages, hardcover, $49.95. Also available as a two-volume softcover set:The Somatic Therapies,366 pages, $17.50, andThe Psychosocial Therapies,617 pages, $25." Psychiatric Services 36, no. 1 (1985): 82–83. http://dx.doi.org/10.1176/ps.36.1.82.
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Gabriel, Ian H., Ruhena Sargent, Hugues de Lavallade, et al. "Presence of the Killer Immunoglobulin-Like Gene KIR3DS1 Is Associated with Poor Progression Free and Overall Survival Following Autologous Stem Cell Transplantation in Patients with Myeloma." Blood 114, no. 22 (2009): 2840. http://dx.doi.org/10.1182/blood.v114.22.2840.2840.
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Abstract Abstract 2840 Poster Board II-816 Multiple myeloma (MM) remains incurable with a median survival of 3–4 years. Despite high dose therapy and autologous stem cell transplant (ASCT) most patients relapse with median progression-free survival (PFS) of 2.5–4 years and overall survival (OS) of 4–5 years. Although allogeneic SCT (allo-SCT) is potentially curative due to a graft-versus-myeloma effect, its applicability is significantly limited by high transplant related mortality (TRM). Therefore, the identification of additional independent biological predictors of outcome is required in order to tailor therapy to disease. Natural killer (NK) cells provide first line defence against tumors. NK cells have been shown to recognize and kill myeloma cells both in the allogeneic and autologous settings and donor NK genotype has been shown to influence leukemia free survival following allo-SCT. The aim of this study was to investigate the impact of KIR genotype on event-free (EFS) and OS following ASCT for MM. We performed KIR genotyping on 190 patients with MM receiving a first autologous transplant. KIR genotype and haplotype frequencies were comparable to those published for normal controls. Factors found on univariate analysis to be associated with a shorter EFS included haplotype Bx (containing at least 1 of the KIR B haplotype-defining loci- KIR2DL5, 2DS1, 2DS2, 2DS3, 2DS5, or 3DS1) (median 547 vs 656 days, P = 0.036), ≥3 activating KIR genes (median 547 vs 615 days, P = 0.046), the presence of activating KIR genes KIR2DS1 and KIR3DS1 (median 456 vs 589 days, and 464 vs 619 days, P=0.045 and 0.01 respectively). Disease status at ASCT was the most highly predictive factor for EFS. In patients with good risk disease (CR or PR at ASCT) KIR3DS1 status was highly predictive for EFS 464 days (341–586) vs 731 days (599–862) (P = 0.003) and OS 807days (713-901) vs 967 (925-1009) (P=0.023). KIR3DS1 was not predictive in patients with poor risk disease (P=0.36). Of note KIR3DS1+ve patients were equally represented in good risk (CR and PR) and poor risk (refractory or relapsed) groups at ASCT (around 30% in both groups). Notably the median EFS for KIR3DS1+ good risk patients was not significantly different to poor risk disease patients (P = 0.061). ASCT outcome was then determined according to 3 main groups based on disease status and KIR3DS1 status; A: Good Risk, KIR3DS1-ve; B: Good Risk, KIRDS1+ ve; and C Poor risk (KIR3DS1+ve or -ve). The RR of relapse or death was 1.0, 1.9 (P=0.002, 95% CI 1.3-3.1), and 3.0 (P=0.0001, 95% CI 1.9-4.8) respectively. By multivariate analysis, after adjusting for the presence of adverse cytogenetics and serum albumin and β2m, the KIR3DS1 status and grouping remained highly predictive of poor EFS, RR of 1.0, 2.7 (P= 0.021, 95%CI 1.2-6.2) and 5.3 (P= < 0.0001, 95%CI 2.4-11.7) respectively. The prognostic value of KIR3DS1 however, was greatest in patients in whom the ligand for the corresponding inhibitory KIR3DL1, Bw4 was missing. KIR3DS1+ KIR3DL1+ HLA-Bw4 negative patients had significantly reduced median EFS of 400d (315-495) vs 615 (545-684) for all other patients (P=0.048). Again this was most striking in good risk patients. Patients who had the genotype KIR3DS1+ KIR3DL1+ HLA-Bw4 –ve had a significantly shorter EFS survival of 372 days compared to 509 days in KIR3DS1+KIR3DL1+HLA-Bw4+ patients and 793 days for KIR3DS1 negative individuals (P=0.004). In conclusion: Our data from 190 patients with MM suggests that KIR3DS1, a gene previously linked to an increase risk of progression to invasive cervical carcinoma, independently predicts for poor EFS and OS following ASCT. A significant proportion (30%) of patients who are defined as good risk at ASCT (CR and PR) are KIR3DS1+ve and have an EFS which is not significantly different from patients who have refractory/relapsed disease at ASCT. This effect of KIR3DS1 is more significant in the absence of HLA-Bw4, the ligand for the inhibitory receptor KIR3DL1. The mechanism for this is effect is unclear and we are currently performing functional studies to further understand these findings. Disclosures: Apperley: Novartis: Consultancy, Honoraria. Marin:Novartis: Consultancy, Research Funding.
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Gorman, Matthew F., Scott C. Kogan, James Huang, and Gillian Stephens. "Evaluation of Patients with Bleeding Symptoms Using a Novel Perfusion Chamber Assay (PCA)." Blood 120, no. 21 (2012): 3295. http://dx.doi.org/10.1182/blood.v120.21.3295.3295.
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Abstract Abstract 3295 Patients with abnormal bleeding are frequently referred to specialists for evaluation of bleeding diatheses. For many patients with strong clinical evidence of a bleeding disorder (positive personal and family history of bleeding), a clear diagnosis remains elusive even after exhaustive laboratory evaluation. Yet, failure to fully characterize these patients may lead to inadequate therapy and serious complications including severe anemia requiring transfusion, postpartum hemorrhage, and unnecessary surgical procedures (e.g. hysterectomy, cautery). Moreover, even in patients with a diagnosed bleeding disorder, the current testing technology is suboptimal. Platelet aggregometry, the gold standard for the diagnosis of platelet disorders, is technically cumbersome, requires a large volume of blood, and is poorly standardized. In the case of Von Willebrand disease (VWD) the current diagnostic assays have large coefficients of variation and have relatively poor reproducibility and bleeding symptoms vary greatly between patients with similar antigen levels, even within the same subtype. Therefore, there remains a need to develop assays with greater sensitivity to detect hemostatic defects and specificity for platelet dysfunction. The purpose of this study was to explore the use of perfusion chamber technology (adapted to permit real time continuous measurement of the kinetics of thrombosis) to evaluate the thrombotic process in pediatric patients with known bleeding disorders compared to normal adult controls. Thrombosis was initiated by perfusion of Factor Xa-inhibitor anti-coagulated whole blood through a collagen coated capillary at arterial (1600s−1) and venous (600s−1) shear rates. Thrombosis was measured by the rate of thrombus growth (platelet deposition over time) and endpoint thrombosis (thrombus size). Results and discussion Rate of thrombus growth (AU) Endpoint thrombosis (MFI/mm2) 600s−1 1600s−1 600s−1 1600s−1 Normal controls (n=101) 857 ± 64 1526 ± 169 378455 ± 45974 383690 ± 56030 Glanzmanns (n=2) 42 ± 13 22 ± 12 23598 ± 20063 26618 ± 1543 Low vWF (n=4) 615 ± 184 923 ± 543 280842 ± 87725 238657 ± 133115 Type 1 VWD (n=3) 802 ± 1 933 ± 463 377126 ± 16872 247719 ± 117475 Type 2A VWD (n=2) 790 ± 118 564 ± 756 357134 ± 60413 148450 ± 191337 Type 2B VWD (n=2) 140 ± 15 129 ± 34 71180 ± 6300 36471 ± 8138 Platelet dysfunction (n=4) 475 ± 176 902 ± 329 210767 ± 66440 236889 ± 82017 All data are presented as mean ± SD (limited n/patient group prevents statistical analysis). Platelet dysfunction can be identified using PCA. Clear abnormalities in rate and extent of thrombosis were demonstrated in Glanzmanns patients at both arterial and venous shear. VWD thrombotic process was altered and within individuals, correlated with severity of disease; in addition, PCA identified pathology with Type 2B VWD, a finding that may aid in the diagnosis of 2B patients with normal VWD panel. Interestingly, the response to DDAVP in low vWF patient was detected by PCA and correlated with improvement in vWD panel. Perfusion chamber technology adapted for use in a clinical setting could provide a rapid, simple, low blood volume method to evaluate patients with abnormal bleeding. With additional patient studies this methodology may provide a useful screening tool prior to moving to more complex, expensive, detailed platelet function studies. Disclosures: Stephens: Portola Pharmaceuticals Inc: Employment.
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Капранов, Олександр. "The Framing of Dementia in Scientific Articles Published in ‘Alzheimer’s and Dementia’ in 2016." East European Journal of Psycholinguistics 3, no. 2 (2016): 32–48. http://dx.doi.org/10.29038/eejpl.2016.3.2.kap.
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The present article involves a qualitative study of the framing of dementia in ‘Alzheimer’s and Dementia’, the Journal of the Alzheimer’s Association, published in 2016. The aim of this study is to elucidate how dementia is framed qualitatively in the corpus consisting of scientific articles involving dementia published in ‘Alzheimer’s and Dementia’. The results of the qualitative analysis indicate that dementia is represented in ‘Alzheimer’s and Dementia’ in 2016 as the frames associated with gender, age, costs, caregiver and care-recipients, disability and death, health policy, spatial orientation, medical condition, and ethnic groups. These findings are further discussed in the article.
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Kremer, J. M., A. Winkler, L. Anatale-Tardiff, et al. "FRI0100 COMPARISON OF PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) AMONG DISEASE ACTIVITY CATEGORIES AFTER 6 MONTHS OF TREATMENT WITH A TUMOUR NECROSIS FACTOR INHIBITOR (TNFI): RESULTS FROM THE CORRONA® RA REGISTRY." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 629. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1698.
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Background:Targeting remission (REM) or low disease activity (LDA) is a widely accepted treatment strategy for RA. However, there are limited data on the proportion of pts who achieve these targets, or remain in moderate (MDA) or high disease activity (HDA) following advanced therapy.Objectives:To estimate the proportion of RA pts in disease activity states (REM, LDA, MDA, and HDA) who were biologic-naïve at initiation and had continuous treatment with a TNFi for 6–12 months in the Corrona RA registry.Methods:Eligible pts were aged ≥18 years, biologic-naïve, initiated TNFi treatment between January 1, 2010 and July 31, 2019, and had continuous use of a TNFi for 6–12 months. Disease activity was defined based on Clinical Disease Activity Index (CDAI) at the visit closest to 6-month follow-up: REM, ≤2.8; LDA, >2.8–10; MDA, >10–22; and HDA, >22. Disease characteristics, disease activity measures, and pt-reported outcomes (PROs) were reported at TNFi initiation and at the 6-month follow-up visit.Results:2586 biologic-naïve pts who initiated a TNFi and had continuous use for 6–12 months were included. At TNFi initiation, 167 (6%) were in REM, 479 (19%) had LDA, 907 (35%) had MDA, and 1033 (40%) had HDA. After 6–12 months of treatment, 563 (21.8%) were in REM, 923 (35.7%) had LDA, 674 (26.1%) had MDA, and 426 (16.5%) had HDA. Pts with HDA/MDA at 6–12 months were more likely to have a history of hypertension (32.7% HDA; 34.0% MDA; vs 23.6% REM) and had higher mean body mass index (BMI) (30.9 HDA; 31.1 MDA; vs 29.0 REM) at baseline compared with pts in REM. Disease activity measures and PROs were worse in pts with MDA and HDA vs LDA and REM after 6–12 months (Table). Pt Global Assessment was higher than Physician Global Assessment across all groups.Conclusion:While 57.4% of pts who initiated a TNFi experienced a favorable outcome, >40% required additional or alternative intervention to achieve REM/LDA. Pts who remained in MDA/HDA continued to have an inadequate response to TNFi (as measured by disease activity measures and PROs) after 6–12 months of treatment compared with those who achieved REM/LDA.TableSummary of disease activity measures and PROs in previously biologic-naïve pts at the 6–12-month follow-up visit, stratified by disease activity category at the 6–12-month follow-up visitCharacteristics at 6–12 months, mean (standard deviation)Disease activity category at 6–12 monthsREM (n=563)LDA (n=923)MDA (n=674)HDA (n=426)CDAI1.2 (0.8)6.2 (2.1)15.4 (3.4)32.7 (9.2)Tender joint count (28)0.1 (0.3)1.0 (1.3)4.3 (3.3)13.4 (7.0)Swollen joint count (28)0.1 (0.3)1.1 (1.6)4.0 (3.6)9.1 (5.9)C-reactive protein6.4 (22.7)7.0 (10.6)11.1 (19.9)12.6 (22.1)Modified health assessment questionnaire0.1 (0.2)0.3 (0.4)0.5 (0.5)0.8 (0.5)Pt global assessment6.6 (6.8)28.6 (20.9)43.7 (25.7)58.0 (22.7)Physician global assessment3.6 (4.3)12.1 (10.4)27.4 (15.9)44.9 (19.8)Pt pain assessment8.7 (11.0)30.3 (23.5)46.1 (27.0)59.9 (24.4)Pt fatigue assessment15.7 (19.2)34.5 (26.6)48.3 (28.0)59.4 (27.5)Morning stiffness (min)16.5 (36.5)55.4 (146.3)96.9 (197.5)143.6 (260.0)Disclosure of Interests:Joel M Kremer Shareholder of: May own stocks and opinions, Grant/research support from: Research and consulting fees from AbbVie Inc., Consultant of: AbbVie, Amgen, BMS, Genentech, Inc., Gilead, GSK, Lilly, Pfizer, Regeneron and Sanofi, Employee of: Corrona, LLC employee, Anne Winkler Consultant of: AbbVie, Pfizer, and Novratis, Speakers bureau: AbbVie, Janssen, Sanofi, Genentech, Celgene, Eli Lilly, and Novartis., Laura Anatale-Tardiff Employee of: Corrona, LLC employee, Robert McLean Employee of: Corrona, LLC, Ying Shan Employee of: Corrona, LLC employee, Page Moore Employee of: Corrona, LLC employee, Namita Tundia Shareholder of: May own stocks and options, Employee of: AbbVie employee, Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., John Tesser Consultant of: Sanofi/Regeneron, Speakers bureau: Sanofi/Regeneron
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Li, N., J. Zhang, L. Yang, M. D. Wu, and G. Q. Li. "First Report of Botrytis pseudocinerea Causing Gray Mold on Tomato (Lycopersicon esculentum) in Central China." Plant Disease 99, no. 2 (2015): 283. http://dx.doi.org/10.1094/pdis-03-14-0256-pdn.
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A tomato field in Qianjiang County, Hubei Province, China, was surveyed for gray mold in April 2013. Diseased leaves with V-shaped lesions along the margin and masses of grayish hyphae and conidia on the surface were collected from different plants. Eight Botrytis isolates were obtained from eight symptomatic leaves by plating the conidia from each leaf onto potato dextrose agar (PDA). A representative isolate (No. 116) was compared to two reference isolates, B. cinerea B05.10 (from Z. H. Ma, Zhejiang University, China) and B. pseudocinerea 10091 (from A. S. Walker, INRA, France) for morpho-cultural and molecular features. On PDA at 20°C, isolate 116 grew 13.8 mm/day (n = 9), which was similar to those of isolates 10091 (13.7 mm/day), and B05.10 (14.6 mm/day). The isolates all formed black sclerotia of similar shape and size (2 to 13 × 1 to 7 mm). To induce conidia production, the isolates each were inoculated onto tomato fruit (cv. Hezuo 903, Jiangsu Seed Co., China) using colonized agar plugs (each 6 mm in diameter), with four plugs per fruit and four fruits tested per isolate. After incubation of the fruit for 10 days (20°C), abundant conidia were produced on the fruit surface. The conidial size of isolate 116 (6.8 to 14.3 × 6.1 to 10.2 μm) was similar to that of isolates 10091 (7.7 to 12.2 × 7.0 to 9.8 μm) and B05.10 (7.0 to 14 × 6.6 to 10.5 μm). The three isolates were indistinguishable morphologically. The sequences of each of four nuclear genes (Bc-hch, G3PDH, HSP60, and MS547) and the microsatellite Bc6 locus (1,4) were determined and analyzed for each isolate. DNA was extracted from mycelium of each isolate and used as a template to amplify each gene by PCR using specific primers (1,2,4). Bc-hch-RFLP genotyping of the 1,171-bp amplicon (2,4) showed that isolates 116 and 10091 had a 601-bp DNA product, whereas B05.10 had a 517-bp product. The G3PDH, HSP60, and MS547 sequences of isolate 116 (GenBank Accession Nos. KJ534270, KJ534271, and KJ534273, respectively) and those of B. aclada, B. calthae, B. cinerea, B. pseudocinerea, and Sclerotinia sclerotiorum (3) were used for phylogenetic analysis. Isolate 116 and eight B. pseudocinerea isolates formed a subclade with 100% bootstrap support. Furthermore, two DNA markers, 86 bp for isolates 116 and 10091 vs. 170 bp for B05.10 were identified at the Bc6 locus. These results suggest that isolate 116 belongs to B. pseudocinerea (1,4). Pathogenicity of each isolate was tested by inoculation of each of five newly expanded tomato leaves on a 50-day-old plant (cv. Hezuo 903, Jiangsu Seed Co) with a 20-μl droplet of a conidial suspension (1 × 105 conidia/ml), using a pipette. Five noninoculated control leaves were treated similarly with water. The plants were all maintained at 20°C and 100% RH for 72 h, and lesion diameter was then measured. While control leaves remained asymptomatic, leaves inoculated with isolates 116, 10091, and B05.10 developed necrotic lesions averaging 19 to 20 mm in diameter. A fungus re-isolated from the lesions on isolate-116–inoculated leaves formed colonies with morphology identical to that of the original isolate 116. To our knowledge, this is the first report of B. pseudocinerea on tomato in China. The remaining seven isolates were identified as B. cinerea based on Bc-hch-RFLP genotyping (data not shown), suggesting that B. pseudocinerea may infect tomato plants at a low frequency in this region of China. References: (1) E. Fournier et al. Mol. Ecol. Notes 2:253, 2002. (2) E. Fournier et al. Mycologia 95:251, 2003. (3) P. R. Johnston et al. Plant Pathol. 63:888, 2014. (4) A. S. Walker et al. Phytopathology 101:1433, 2011.
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Lu, M., L. Guo, L. Zou, and Y. Xu. "FRI0463 IDENTIFICATION OF EARLY CLINICAL AND LABORATORY CHARACTERISTICS OF MACROPHAGE ACTIVATION SYNDROME ASSOCIATED WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 829.1–829. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1142.
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Background:Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of systemic juvenile idiopathic arthritis (SJIA). However, early recognition of MAS remains challenging. Because it is clinically heterogeneous, hemophagocytosis is often not detected, and histopathological features lack the specificity associated with hemophagocytic syndromes. In addition, it is often difficult to distinguish early MAS from SJIA or sepsis-like syndromes.Objectives:To identify early clinical and laboratory characteristics of MAS associated with SJIA.Methods:This is a retrospective cohort study of 149 SJIA patients treated at the Children’s Hospital of Zhejiang University School of Medicine between January 2010 to December 2017. All patients fulfilled 2001 ILAR criteria for SJIA, and 27 fulfilled 2016 Classification Criteria for MAS. We evaluated the clinical and laboratory features of SJIA patients with MAS and compared them to those without MAS. We focused our analysis on early MAS, which was defined as the time when the initial clinical and/or laboratory abnormalities suggestive of MAS were first detected.Results:The clinical features associated with early MAS were hypotension, absence of arthritis and lymphadenopathy, bone marrow hemophagocytosis, central nervous system dysfunction, and gastrointestinal involvement. The best laboratory parameters for early MAS detection were platelet counts ≤275.0 × 109/L, lactate dehydrogenase >596.0 U/L, aspartate aminotransferase >47.0 U/L, erythrocyte sedimentation rates ≤41.0 mm/h, ferritin >1400.0 ng/mL, D-dimer >1.40 mg/L, triglyceride >1.30 mmol/L, alanine aminotransferase >33.0 U/L, C-reactive protein ≤68.0 mg/L, fibrinogen ≤4.1 g/L, absolute neutrophil counts ≤5.2 × 109/L, serum total protein ≤66.0 g/L, and white blood cell ≤9.8 × 109/L. The combination of cytokines of IFN-γ >17.1 pg/mL and IL-10 >7.8 pg/mL were found to be a specific and good prognostic cytokine pattern for early recognition of MAS, the sensitivity and specificity as 71.4% and 98.2%.(Table 1, Fig 1, 2)Table 1.Identification of clinical and Cytokine characteristics differentiating patients with MAS onset from SJIA patients without MASCharacteristicsSensitivity (%)Specificity (%)OR (95% CI)p valueClinical characteristicsHypotension35.598.433.0 (6.8–160.1)0.000Absence of Arthritis77.485.219.8 (7.4–52.7)0.000Hemophagocytosis in the bone marrow28.697.314.5 (2.0–107.5)0.009Central nervous system involvement25.891.03.5 (1.3–9.7)0.015Gastrointestinal involvement22.691.83.3 (1.1–9.4)0.029Absence of lymphadenopathy77.451.62.6 (1.1–6.1)0.027Cytokine levelsIFN-γ >17.1 pg/mL82.183.649.5 (15.6–156.9)0.000IL-10 >7.8 pg/mL78.693.123.5 (7.9–69.5)0.000IFN-γ >17.1 pg/mL and IL-10 >7.8 pg/mL71.498.2142.5 (28.2–720.6)0.000OR, odds ratio. CI, confidence interval. PLT, platelet. LDH, lactate dehydrogenase. AST, aspartate aminotransferase. ESR, erythrocyte sedimentation rate. FER, ferritin. D-D, D-dimer. TG, triglycerides. ALT, alanine aminotransferase. CRP, C-reactive protein. FIB, fibrinogen. ANC, absolute neutrophil count; TP, total protein. WBC, white blood cells. ALB, albumin. IL, interleukin. IFN, interferon.Fig 1.Comparison of clinical characteristics in the MAS process. * P < 0.05. ** P < 0.01. CNS involvement: Central nervous system involvement.Fig 2.Comparison of serum cytokine levels in the MAS process. * P < 0.05. ** P < 0.01.Conclusion:Sudden hypotension, absence of arthritis, and significantly increased IFN-γ and IL-10 levels are important clinical and laboratory markers for early MAS identification in addition to the traditional features of SJIA-associated MAS.References:(not show references here)Disclosure of Interests:None declared
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Pereira, Matheus P., Taemin Oh, Rushikesh S. Joshi, et al. "Clinical characteristics and outcomes in elderly patients undergoing transsphenoidal surgery for nonfunctioning pituitary adenoma." Neurosurgical Focus 49, no. 4 (2020): E19. http://dx.doi.org/10.3171/2020.7.focus20524.
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OBJECTIVELife expectancy has increased over the past century, causing a shift in the demographic distribution toward older age groups. Elderly patients comprise up to 14% of all patients with pituitary tumors, with most lesions being nonfunctioning pituitary adenomas (NFPAs). Here, the authors evaluated demographics, outcomes, and postoperative complications between nonelderly adult and elderly NFPA patients.METHODSA retrospective review of 908 patients undergoing transsphenoidal surgery (TSS) for NFPA at a single institution from 2007 to 2019 was conducted. Clinical and surgical outcomes and postoperative complications were compared between nonelderly adult (age ≥ 18 and ≤ 65 years) and elderly patients (age > 65 years).RESULTSThere were 614 and 294 patients in the nonelderly and elderly groups, respectively. Both groups were similar in sex (57.3% vs 60.5% males; p = 0.4), tumor size (2.56 vs 2.46 cm; p = 0.2), and cavernous sinus invasion (35.8% vs 33.7%; p = 0.6). Regarding postoperative outcomes, length of stay (1 vs 2 days; p = 0.5), extent of resection (59.8% vs 64.8% gross-total resection; p = 0.2), CSF leak requiring surgical revision (4.3% vs 1.4%; p = 0.06), 30-day readmission (8.1% vs 7.3%; p = 0.7), infection (3.1% vs 2.0%; p = 0.5), and new hypopituitarism (13.9% vs 12.0%; p = 0.3) were similar between both groups. Elderly patients were less likely to receive adjuvant radiation (8.7% vs 16.3%; p = 0.009), undergo future reoperation (3.8% vs 9.5%; p = 0.003), and experience postoperative diabetes insipidus (DI) (3.7% vs 9.4%; p = 0.002), and more likely to have postoperative hyponatremia (26.7% vs 16.4%; p < 0.001) and new cranial nerve deficit (1.9% vs 0.0%; p = 0.01). Subanalysis of elderly patients showed that patients with higher Charlson Comorbidity Index scores had comparable outcomes other than higher DI rates (8.1% vs 0.0%; p = 0.006). Elderly patients’ postoperative sodium peaked and troughed on postoperative day 3 (POD3) (mean 138.7 mEq/L) and POD9 (mean 130.8 mEq/L), respectively, compared with nonelderly patients (peak POD2: mean 139.9 mEq/L; trough POD8: mean 131.3 mEq/L).CONCLUSIONSThe authors’ analysis revealed that TSS for NFPA in elderly patients is safe with low complication rates. In this cohort, more elderly patients experienced postoperative hyponatremia, while more nonelderly patients experienced postoperative DI. These findings, combined with the observation of higher DI in patients with more comorbidities and elderly patients experiencing later peaks and troughs in serum sodium, suggest age-related differences in sodium regulation after NFPA resection. The authors hope that their results will help guide discussions with elderly patients regarding risks and outcomes of TSS.
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Williams, Brent A., Bishoy Dief, Xing-Hua Wang, and Armand Keating. "NK-92 Preferentially Targets Acute Myeloid Leukemia Stem Cells." Blood 116, no. 21 (2010): 4300. http://dx.doi.org/10.1182/blood.v116.21.4300.4300.
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Abstract Abstract 4300 Introduction: Outcome of patients with acute myeloid leukemia (AML) remains poor because many relapse from residual leukemic stem cells (LSCs) enriched in the CD34+CD38- fraction of AML blasts. NK-92 is a human permanent natural killer (NK) cell line in phase I clinical trials for relapsed and refractory malignancies. We recently showed that NK-92 targets LSCs preferentially over bulk leukemia in the cell line KG1 (Cytotherapy. 2010 Mar 15). Here, we evaluate the action of NK-92 and another NK cell line, KHYG-1, against five AML cell lines and five primary AML samples by the chromium release and methylcellulose cytotoxicity assays to determine the mechanism of recognition and killing and the effect on leukemic stem cells. Results: Using a 4 hour chromium release assay (CRA), the highest effector:target (E:T) ratio tested (25:1) for NK-92 and KHYG-1 against cell line targets revealed % lysis as follows: K562: 81.2+/−5.4%; 82.2 +/−3.9%; KG1: 41.0+/−7.2%; 37.3% +/−3.6; OCI/AML2: 37.3+/−22.7%; 33.0+/−13.9%; OCI/AML3: 33.8+/−4.5%; 51.0+/− 6.8% and OCI/AML5: 99.0+/−4.9%; 52.9 +/− 5.6%, respectively. Killing by NK-92 and KHYG-1 was completely inhibited by calcium chelation using 4 mM EGTA for all cell lines tested. Blockade of class I HLA on target cells using 10 ug/ml of anti-class I monoclonal antibody did not affect killing by NK-92 and KHYG-1 except for a decrease in killing of OCI/AML5 by both NK-92 and KHYG-1 from 99.0 +/− 4.9% to 39.0 +/−3.2% and 52.9+/−5.6% to 19.6 +/− 6.25%, respectively. Blockade of NKG2D using 10 ug/ml of anti-NKG2D monoclonal antibody did not significantly affect killing of AML cell lines by NK-92 or KHYG-1. Five primary AML blast samples treated with NK-92 at 25:1 E:T yielded only slight to moderate degrees of cytotoxicity by CRA: 15.6 +/−12.7%, 42.3+/−3.6%, 29.8 +/−3.6%, 43.9 +/− 1.47%, 42.6 +/− 0.1%lysis. KHYG-1 at 25:1 E:T had minimal killing of this panel of AML blasts by CRA: 1.27 +/−21.9%, 9.8+/−2.2%, 5.2+/−2.5%, 17.1+/−2.8%, 8.5+/−3.3% lysis. Blockade of class I HLA did not affect killing of primary AML blasts by NK-92, but the fourth sample only was rendered more sensitive to killing by KHYG-1 from 17.1 +/−2.8% to 35.8 +/−1.2% lysis. Blockade of NKG2D with 10 ug/ml anti-NKG2D monoclonal antibody did not significantly affect killing of primary AML samples by NK-92 or KHYG-1. To further assess killing by NK-92 of LSCs from primary AML, we used a methylcellulose cytotoxicity assay (MCA) established previously by our lab. The MCA showed that NK-92 at 25:1 E:T eliminated clonogenic growth of 3/5 primary AML blast samples with minimal colony growth in 2/5 with % cytotoxicity of 100 +/−0%, 86.3 +/− 2.3%, 98.4 +/−2.8%, 100 +/− 0% and 100 +/−0%, demonstrating higher toxicity than obtained with the CRA. Primary AML derived CD34+CD38- sorted LSCs were more sensitive to killing than CD34+CD38+ blasts by NK-92 in a 4 hour CRA at 1:1 E:T: 58.9+/−11.5%, 20.3 +/−1.71%; 5:1: 78.3 +/−9.7%, 43.5+/−11.1% and 10:1: 72.9+/−5.6%, 38.5 +/−2.4% lysis. Summary and conclusion: We demonstrate cytotoxicity of NK-92 and KHYG-1 against a range of AML targets and show greater killing of primary AML blasts by NK-92. The mechanism of cytotoxicity for both cell lines is primarily by granule exocytosis and is NKG2D independent. Unexpectedly, blockade of class I HLA resulted in reduced killing of OCI/AML5 by both NK-92 and KHYG-1, suggesting the presence of an activating KIR receptor common to both cell lines. One of five primary AML samples had increased killing by KHYG-1, suggesting KIR mediated inhibition. Further assessment of NK-92 against LSCs by the MCA demonstrated greater cytotoxicity than with the CRA and indicated preferential killing of LSCs. This finding was confirmed using the CRA with sorted immunophenotypically defined CD34+CD38- LSCs and CD34+CD38+ blasts. Our findings support the use of NK-92 in the treatment of AML. Disclosures: No relevant conflicts of interest to declare.
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Felten, R., M. Dubois, M. F. Ugarte-Gil, et al. "POS1190 EXPECTATIONS AND POTENTIAL CONCERNS OF PATIENTS WITH AUTOIMMUNE AND RHEUMATIC DISEASES REGARDING VACCINATION AGAINST SARS-CoV-2 (COVID-19): THE WORLDWIDE ONLINE VAXICOV STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 877. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1503.
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Background:Vaccination is an important and effective tool to prevent infections in the general population as well as in patients with systemic autoimmune or inflammatory rheumatic diseases (AIIRDs) who may be at increased risk of serious infection. While the global race for vaccines against COVID-19 has already lead to first authorizations and vaccinations in some countries, multiple questions arise for access and provisions as well as for the acceptance of vaccine policies by immunocompromised patients.Objectives:We conducted an international survey about expectations and potential concerns regarding SARS-CoV-2 vaccine in patients with AIIRDs and healthcare professionals.Methods:The online study consisted of 57 questions which addressed determinants associated with SARS-2-CoV-2 vaccine willingness. Dissemination was ensured through social media and patient associations between December 12 and December 21, 2020.Results:The study included 1266 patients with AIIRDs and 265 healthcare professionals from 56 countries. SARS-CoV-2 vaccine willingness was reported by 54.2% of AIIRD patients (uncertainty in 32.2% and unwillingness in 13.6%) and 74.0% of healthcare professionals. In patients, the willingness to get vaccinated increased significantly with age (p<0.0001) and was strongly associated with the fear to be infected by SARS-CoV-2 (p<0.0001) or to develop severe COVID19 (p<0.0001) but not with presence of additional comorbidities (p=0.71) or immunocompromised status (p=0.94). The most trusted healthcare professional regarding the recommendation to get vaccinated against COVID-19 was their specialist (rheumatologist, internist, etc.) for 69.9%. Vaccine unwillingness was low (7.9%) among healthcare professionals and willingness was significantly increased in those who had been vaccinated against influenza in the last 3 years (p=0.01).Subject groupsPatientsHealthcare professionalsN1266265Age (years), median [IQR25-75]50 [40-61]40 [32.5-53]Female, n (%)1141 (90.1%)150 (56.6%)Male, n (%)115 (9.9%)115 (43.4%)Country, n (%) France320 (25.3%)159 (60%) UK345(27.3%)4 (1.5%) Chile123 (9.7%)4 (1.5%) USA114 (9.0%)7 (2.6%) Venezuela43 (3.4%)26 (9.8%) Spain57 (4.5%)3 (1.1%) Mexico53 (4.2%)3 (1.1%) Argentina45 (3.6%)8 (3.0%) Other*166 (13.1%)51 (19.2%)Rheumatic diagnosis, n (%)1266- Systemic lupus erythematosus492 (38.9%)- Spondyloarthritis176 (13.9%)- Rheumatoid arthritis160 (12.6%)- Giant cell arteritis / Polymyalgia rheumatica144 (11.4%)- Primary anti-phospholipid syndrome64 (5.1%)- Inflammatory myositis62 (4.9%)- Relapsing polychondritis45 (3.6%)- Other**123 (9.7%)--Health professionals, n (%)-265 Doctor-203 (76.6%) Nurse (or equivalent)-23 (8.7%) Nursing assistant-11 (4.2%) Other***-28 (10.6%)Associated comorbidities, n (%) Diabetes69 (5.5%)6 (2.3%) Hypertension267 (21.1%)24 (9.1%) Myocardial infarction, stroke, transient stroke60 (4.7%)1 (0.4%) Respiratory disease (asthma, chronic bronchitis, emphysema, etc.)169 (13.3%)13 (4.9%)Renal failure47 (3.7%)1 (0.4%)Obesity (BMI > 30)228 (18.0%)18 (6.8%)At least one associated comorbidity, n (%)588 (46.4%)50 (18.9%)Smoker, n (%)128 (10.2%)22 (8.3%) Current411 (32.7%)51 (19.2%) Past719 (57.1%)192 (72.5%) NeverUse of oral glucocorticoids, n (%)551 (56.1%)3 (1.1%)Immunocompromised$, n (%)770 (60.8%)0On a 0 to 10 scale, median8 (6-10)5 (3-8)[IQR25-75]9 (7-10)5 (1-8)−Afraid to get infected by SARS-CoV-2−Afraid to get a severe COVID-19Willing to get vaccinated (Yes / uncertain / No), %54.2 / 32.2 / 13.674.0 / 18.1 / 7.9Vaccine hesitancy, n (%)357 (28.2%)59 (22.3%)Conclusion:Data from this study are crucial to understand the main expectations and concerns regarding SARS-CoV-2 vaccination in patients with AIIRDs and healthcare workers and allow the identification of valuable strategies to increase vaccine coverage in those populations.Acknowledgements:We wish to acknowledge the crucial role of the following patient associations: LupusEurope (tweeter: @LupusEurope), Agrupacion Lupus Chile (@Lupus_Chile), RarasNoInvisibles (@Noinvisibles), Lupus UK, Lupus France, SPONDYL’ASSO, Spondyl(O)action, AFL+, in the dissemination of the survey. We are indebted to Gonzalo Tobar Carrizo (@pinkycito) for the Spanish translation of the survey, all patients, families, and health professionals for their kind participation in our study. We wish to thank Ms. Sylvie Thuong for her invaluable assistance.Disclosure of Interests:Renaud FELTEN Speakers bureau: Pfizer, Maxime Dubois: None declared, Manuel F. Ugarte-Gil Speakers bureau: Janssen and Pfizer, Jérémy Fort: None declared, Luc PIJNENBURG: None declared, Aurore Chaudier: None declared, Lou Kawka: None declared, Charlotte Costecalde: None declared, Hugo Bergier: None declared, Emmanuel Chatelus: None declared, Rose-Marie Javier: None declared, Christelle Sordet: None declared, Jacques-Eric Gottenberg Speakers bureau: Pfizer and Astra-Zeneca, Jean Sibilia Speakers bureau: Pfizer, Yurilis Fuentes-Silva: None declared, Laurent Arnaud Speakers bureau: Pfizer and Astra-Zeneca.
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Porter, John B., Alan R. Cohen, John M. Ford, and Maria Domenica Cappellini. "Impact of Dose Adjustments on Serum Ferritin (SF) Levels during Long-Term Treatment with Once-Daily, Oral Deferasirox (Exjade®, ICL670)." Blood 110, no. 11 (2007): 2778. http://dx.doi.org/10.1182/blood.v110.11.2778.2778.
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Abstract Background: In deferasirox 1-yr core trials, doses were initially assigned according to baseline liver iron concentration. However, these trials demonstrated that transfusional iron intake has a profound impact on the outcome of chelation therapy and should therefore be considered when assigning deferasirox dose. A large number of patients (pts) were initially assigned 5 and 10 mg/kg/d doses, which were insufficient to balance iron intake from ongoing transfusions. Generally, deferasirox 20/30 mg/kg/d effectively maintained/reduced body iron. This analysis from the 4-yr extension trials evaluates the impact on serum ferritin (SF) of subsequent dose increases in pts who initially received 5/10 mg/kg/d, and the long-term effects of 20 and 30 mg/kg/d doses. Methods: Data for this analysis were pooled from 4 extension trials (106–109E). In the extensions, deferasirox doses were modified based on efficacy and safety markers, including iron burden and transfusional iron intake. SF was measured monthly. Results: In total, 227 pts initially received deferasirox 5 or 10 mg/kg/d, while 182 and 243 received 20 and 30 mg/kg/d, respectively. Underlying diseases included β-thalassemia (n=421), sickle cell disease (n=132), MDS (n=47) and other anemias (n=52). To date, pts have been receiving treatment for a median 3.4 (range: 0–4.5) yrs. Overall, median SF was maintained in the 20 mg/kg/d cohort (Table). In the 30 mg/kg/d cohort, SF levels decreased overall from baseline to month 42 (3734 ng/mL to 2025 ng/mL). However, levels plateaued at around 24 mos in this cohort, reflecting a decrease in mean dose to around 25 mg/kg/d. Median baseline SF in the 5/10 mg/kg/d dose group was 2051 ng/mL, which steadily increased during the first 18 mos of treatment. Subsequent dose increases during the extension phase generally resulted in decreased SF levels, which returned to baseline and below during the remainder of the study. Conclusions: In regularly transfused pts who initially received deferasirox 5/10 mg/kg/d in the core 1-yr clinical trials, SF steadily decreased below baseline once doses were increased to an appropriate level in the extensions. This highlights the importance of ensuring that pts receive the correct deferasirox dose to achieve the goal of therapy, based on iron burden and transfusional iron intake. If a pt is not achieving their therapeutic goal based on SF trends, deferasirox dose should be increased in steps of 5 or 10 mg/kg/d. This analysis confirms that deferasirox 30 mg/kg/d effectively reduces body iron, whereas doses of 20–25 mg/kg/d are generally effective in maintaining iron levels. Median change from baseline in SF (ng/mL) during deferasirox treatment of up to 3.4 years Initial dose, mg/kg/d 5/10 (n=227*) 20 (n=182*) 30 (n=243*) Month Mean dose ± SD† Change in SF (ng/mL) Mean dose ± SD† Change in SF (ng/mL) Mean dose ± SD† Change in SF (ng/mL) *Baseline; †At time point Baseline 2051 2375 3734 1 9.4 ± 1.7 90 19.5 ± 2.6 30 29.2 ± 4.3 −212 6 10.3 ± 3.9 399 18.9 ± 3.5 −15 28.2 ± 5.7 −532 12 13.0 ± 5.4 613 19.0 ± 4.0 −118 26.8 ± 6.6 −716 18 18.5 ± 6.7 831 18.2 ± 7.7 174 23.1 ± 8.6 −676 24 21.7 ± 6.6 635 21.5 ± 6.5 −125 24.5 ± 7.6 −901 30 22.6 ± 7.0 317 22.0 ± 8.5 −205 24.4 ± 8.0 −959 36 21.1 ± 8.7 −211 22.8 ± 7.7 −159 24.3 ± 8.5 −1002 42 21.8 ± 9.3 −65 23.2 ± 8.2 −204 25.8 ± 9.8 −955 EOS 1345 1667 2025
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Sinegre, Thomas, Cedric Duron, Marc G. Berger, Armand Abergel, and Aurelien Lebreton. "Hypercoagulability in Cirrhotic Patients; Impact of Acquired Protein C Deficiency and Factor VIII Increase in Low Sensitivity to Thrombomodulin." Blood 128, no. 22 (2016): 1420. http://dx.doi.org/10.1182/blood.v128.22.1420.1420.
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Abstract Context: Cirrhosis impacts all the steps of haemostasis including coagulation. Levels of both inhibitors (including protein C (PC)) and prococagulants factors are decreased excepted factor VIII (FVIII) who is increased. Cirrhotic patients are exposed to thromboembolic diseases and cirrhosis induced hypercoagulability is a major determinant of this thrombotic process. A procoagulant state in cirrhotic patients has been demonstrated using modified thrombin generation assays (TGA) with thrombomodulin (TM), a cofactor for PC activation. With such assays, a low sensitivity to the action of TM has been highlighted in the cirrhotic population, increasing with the severity assessed by the Child-Pugh score. Studies showed that PC deficiency is one of the main determinants of this procoagulant state but the implication of the increased FVIII levels has not been yet accurately evaluated. The aim of this study was to investigate the impact of in vitro normalization of FVIII and PC levels on the procoagulant imbalance in cirrhotic patients using TGA in the presence of TM to precisely determine their role in the cirrhosis induced procoagulant state. Method: One hundred and six patients and 35 healthy controls were prospectively included in this study. Patients were confirmed cirrhotic patients, free of hepatocellular carcinoma and were not anticoagulated. TGA were performed using the calibrated automated thrombinography method in platelet poor plasma using 5 pM tissue factor, 4 nM TM. Plasma were tested before/after normalization of PC levels by in vitro addition of PC and before/after normalization of FVIII levels by the use of human anti-FVIII C2 domain monoclonal antibody (ESH8). All ethical requirements were obtained. Groups were compared using ANOVA, or the Kruskal-Wallis test when the ANOVA conditions were not met followed by the appropriate multiple comparisons post-hoc tests. Results are expressed as median (Q1 - Q3). Results:Among cirrhotic patients 68 were Child-Pugh A, 21 Child-Pugh B and 17 Child-Pugh C). TGA performed with TM show a gradually increased of endogenous thrombin potential (ETP) from healthy controls to Child-Pugh C patients with respectively 508 nM.min (410-725) and 1071 nM.min (701-1232) (p<0.0001) confirming the hypercoagulable state of cirrhosis in these conditions. After normalization, PC levels increase from 50% (41-76) to 100% (94-110) and become similar to controls (109% (100-122), p>0.05). Modified TGA with TM performed before and after PC normalization showed a decrease of the ETP values from 776 nM.min (626-991) to 566 nM.min (369-779), from 1120 nM.min (1062-1184) to 790 nM.min (617- 972) and from 995 nM.min (913-1443) to 790 nM.min (698 - 909) (p<0.0001) for Child-Pugh A, B and C patients respectively (p<0.0001). No significant difference was found between controls versus Child-Pugh A class patients (p=0.63) whereas higher significant ETP values persist in Child-Pugh B and C class when compared to healthy controls (p<0.01 and p<0.05 respectively) in these conditions. After normalization of FVIII increase by in vitro addition of anti-FVIII antibodies, FVIII levels decrease from 196% (165-222) to 94% (77-107) and became similar to controls (p>0.05). TGA performed before and after FVIII normalization showed a decrease of the ETP values from 929 nM.min (784-1086) to 621 nM.min (517-863), from 1122 nM.min (1035-1360) to 1081 nM.min (890-1171) and from 1221 (910-1407) to 1143 nM.min (892-1323) for Child-Pugh A, B and C patients respectively. There is no significant difference between healthy controls and Child-Pugh A patients but a difference persists with Child-Pugh B and C patients. When plasma levels of PC and FVIII are simultaneously corrected to normal ranges by in vitro addition of both PC and anti-FVIII monoclonal antibody, ETP decrease from 929 nM.min (784-1086) to 302 nM.min (167-583) in Child-Pugh A patients (p<0.0001), from 1122 nM.min (1035-1360) to 597 nM.min (285-686) for Child-Pugh B (p<0.0001) and from 1226 nM.min (1108-1488) to 586 (471-771) for Child-Pugh C. For all patients, ETP values were not significantly different when compared to healthy controls (p>0.05) after both PC and FVIII normalization. Fig 1 Conclusions: Low sensitivity to TM induced by cirrhosis is not only related to PC deficiency but also to FVIII increase. When PC deficiency and FVIII increase are in vitro redressed, no hypercoagulable state was found in cirrhotic patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Torikai, E., Y. Hirano, D. Suzuki, and Y. Kanayama. "FRI0137 Discontinuation of baricitinib after achieving low disease activity in patients with rheumatoid arthritis in clinical practice; a multicenter observational study." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 651.2–651. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1546.
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Background:Baricitinib (bari) is an oral Janus kinase (JAK) 1/JAK2 selective inhibitor that has shown good efficacy in patients with RA and adequate response to conventional synthetic DMARDs in some clinical trials [1,2]. However, concerning the high cost and long-term safety related to the inhibition of particular molecules, we would like to discontinue bari after achieving long low disease activity (LDA).Objectives:To evaluate the clinical outcomes in patients with RA who discontinued bari after achieving LDA for 24 weeks in real-world multicenter clinical data.Methods:Japanese 67 patients with RA who show an inadequate response to csDMARDs or bDMARDs were scheduled to receive bari 4 or 2 mg/day once daily dose as a monotherapy or in combination with other csDMARDs. We included 51 patients who achieved and maintained LDA at least for 24 weeks after baricitinib therapy. They were allowed to decrease baricitinib after discontinuation of prednisolone. Bari was either discontinued or continued after study enrolment. The decision of discontinuation and continuation of baricitinib was determined based on patient-physician decision making with informed consent. We divided patients into two groups: a discontinuation group (D group; n = 23) and a continuation group (C group; n = 28). We evaluated the proportion of patients who remained LDA for 24 weeks in both groups. Clinical outcomes including Clinical Disease Activity Index (CDAI), and HAQ-DI were compared between both groups. The last observational carried forward method was used for patients who could not discontinue baricitinib due to flare before 24 weeks. In D group, patients were treated with re-initiation of bari or initiation of the other DMARDs in the event of flare. We investigated the serial changes of patients treated with re-initiation of bari in CDAI after flare.Results:The baseline characteristics of the patients are summarized in Table. The titer of RF was lower in D group than that in C group. There were no significant differences in any other items. Ten of 23 (43.4%) in D group remained bari-free without disease activity flare. Serial changes of CDAI were summarized in Figure. CDAI in D group significantly increased from 3.6 at baseline to 9.8 at last observation. LDA rates in C group were 92.9% at last observation. CDAI in C group did not change throughout the follow-up period. CDAI at last observation was higher in D group than that in C group. HAQ-DI in D group changed from 0.28 at baseline to 0.45 at last observation. There was no significant change in HAQ-DI between both groups (P = 0.28). In D group, rescue by re-administration of bari or other DMARDs induced improvement, reducing CDAI from 15.5 at disease flare to 6.8. Especially, all patients treated with re-initiation of bari resulted in re-introduction of LDA in this study.Table.Characteristics of patients at baricitinib initiationD group (n=23)C group (n=28)p-valueAge (years)66.9 (8.6)67.9 (12.7)0.31Gender, female, n (%)6 (73.9)24 (85.7)0.49Disease duration (years)7.6 (10.3)8.3 (9.9)0.37Prior use of biologics, n (0/1/2/≥3)(21/2/0/0)(17/6/4/1)------MTX (mg/w)5.5 (3.8)4.9 (4.3)0.62PSL (mg/d)1.4 (1.9)0.9 (0.9)0.51RF, U/ml99 (141)187 (214)0.04ACPA, U/ml135 (173)194 (214)0.11CDAI24.4 (9.2)22.5 (9.7)0.36HAQ-DI0.83 (0.49)0.83 (0.52)0.98Conclusion:It was possible to discontinue bari without flare in about 43% of patients with RA. Overall the patients treated with re-initiation of bari could result in re-introduction of LDA without deterioration of HAQ-DI.References:[1]Tanaka Y et al. Mod Rheumatol. 2018;28:583-91[2]Tanaka Y et al. Mod Rheumatol. 2018;28:20-9Disclosure of Interests:Eiji Torikai: None declared, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Daisuke Suzuki: None declared, Yasuhide Kanayama: None declared
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Drasar, Emma, Emer Fitzpatrick, Kate Gardner, et al. "Noninvasive Assessment of Liver Fibrosis in Patients with Sickle Cell Disease." Blood 126, no. 23 (2015): 3406. http://dx.doi.org/10.1182/blood.v126.23.3406.3406.
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Abstract Complications affecting multiple organs, including the liver, contribute to early mortality in patients with sickle cell disease (SCD). Earlier diagnosis and monitoring of "sickle hepatopathy", preferably using non-invasive methods, would enable earlier intervention and therefore, potentially a better outcome for patients. In many non-SCD chronic liver diseases, fibrosis stage is the most important predictor of morbidity and mortality. Two non-invasive methods of assessing liver fibrosis are used: Transient Elastography (TE, Echosens) and Enhanced Liver Fibrosis Score™ (ELF, iQUR). TE detects fibrosis using ultrasound and low frequency elastic waves with a propagation velocity directly related to the stiffness of the liver. The ELF score examines the balance between matrix deposition and degradation using levels of three proteins analysed using a patented formula. We report a prospective study correlating liver function tests (LFTs) with the level of liver fibrosis (as ascertained by TE and ELF) in a cohort of patients with SCD. Ethical approval for this study was obtained from the NHS ethics committee (11/LO/0005) and patients were consecutively recruited in the steady-state sickle cell clinic at Kings' College Hospital, London, during 2012. Patients were excluded if they had viral hepatitis or were pregnant. Clinical (transfusion and hydroxyurea therapy), imaging (liver iron concentration, LIC) and laboratory data were collected during steady-state. TE and ELF were performed on 194 patients. The patients ranged from 17-72 years (mean age 35 years); 78 (40%) were male, 134 (68%) had HbSS or HbSb0 (SCA), 48 (26%) Hb SC, and the remainder, Hb Sβ+ (excluded due to low numbers). Statistical analysis was undertaken in IBM SPSS version 20. There was significant correlation between both TE and ELF with age, when corrected for sickle genotype (TE β = 0.19, p = 0.006 and ELF β = 0.2, p = 0.005) (Figure). Patients with SCA had significantly higher TE results and mean ELF scores than those with HbSC (TE, 6.8 vs 5.3, p<0.0001 and ELF, 9.2 vs 8.6 p <0.0001) (Table). In SCA patients, TE correlated significantly with all serum LFTs (Albumin R = -0.35 p<0.0001, AST R = 0.44 p<0.0001, ALP R = 0.29 p<0.0001, GGT R = 0.40 p<0.0001, conjugated bilirubin R = 0.26 p = 0.004). Positive correlation was found with LDH (R = 0.24 p = 0.004) and negative correlation with Hb (R= -0.25 p = 0.002). In the Hb SC group, TE correlations were weaker for AST (R = 0.39 p = 0.004), ALP (R = 0.30 p = 0.03), WBC (R = 0.39 p = 0.02) and reticulocyte count (R = 0.35 p = 0.01). All markers of iron loading correlated with TE values, when corrected for sickle genotype (serum ferritin β = 0.25, p <0.0001, total top-up units β = 0.22, p = 0.001, total units transfused β = 0.25, p <0.0001 and LIC β = 0.32, p = 0.046). In SCA patients, ELF score correlated with serum LFTs (Albumin R = -0.30 p<0.0001, AST R = 0.39 p<0.0001, ALP R = 0.25 p = 0.003, GGT R = 0.28 p = 0.001, conjugated bilirubin R = 0.36 p<0.0001). Positive correlation was seen with LDH (R = 0.26 p = 0.002) and negative correlation with Hb (R = -0.25 p = 0.004). Negative correlation was also seen with HbF levels (R = -0.24 p = 0.01). In the HbSC group, there were no significant correlations between ELF and serum LFTs. However associations were seen between ELF score and LDH (R = 0.40 p = 0.004) and Hb level (R = -0.31 p = 0.01). ELF score correlated with serum ferritin (β = 0.25 p <0.0001), and total blood transfusion units (β = 0.24 p = 0.001). These data show significant levels of liver dysfunction in our SCD population using both TE and ELF score which correlated significantly with abnormal LFTs and markers of hemolysis and iron overload. The role of TE and ELF in monitoring liver dysfunction in SCD needs to be further validated, preferably with longitudinal, and if possible histological data. Table 1. Range and mean TE results and ELF score for whole cohort and subgroups. Whole cohort n = 194 (%) SCA n = 134 (%) Hb SC n = 48 (%) p value FibroScan results (kPa) Mean (range) 6.3 (2.0 - 21.3) 6.8 (2.0 - 21.3) 5.3 (2.0 - 16.0) < 0.0001 None/mild (0-7.65) 153 (79) 98 (73) 43 (90) Moderate (7.66-13.00) 33 (17) 29 (22) 4 (8) Severe (≥13.01) 8 (4) 7 (5) 1 (2) ELF score Mean (range) 9.1 (7.1 - 11.6) 9.2 (7.1 - 11.6) 8.6 (7.5 - 10.3) <0.0001 None/mild (≤9.7) 164 (84) 107 (79) 46 (96) Moderate (9.8 - 11.2) 27 (14) 24 (19) 2 (4) Severe (≥11.3) 3 (2) 3 (2) 0 (0) Disclosures No relevant conflicts of interest to declare.
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Hill, Wolfgang, Karl Sotlar, Heinz Diem, Andreas Hausmann, and Hans Jochem Kolb. "Bone Marrow Reaction in Chronic Graft-Versus-Host Disease." Blood 112, no. 11 (2008): 1166. http://dx.doi.org/10.1182/blood.v112.11.1166.1166.
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Abstract Hematopoiesis of the host is a primary target organ of the graft-versus-host reaction. However histological analyses of the bone marrow are rarely reported. Here we report histological changes in the bone marrow of patients (pts) with and without chronic graft-versus-host disease (cGvHD). Bone marrow biopsies were obtained between 101 days and 4623 days (median:419 days) after transplantation as part of a controlled prospective phase ll study of patients with osteopenia/osteoporosis after allogeneic hematopoietic stem cell transplantation (HCT). Previously we reported an increased density of microvessels using an antibody against v. Willebrand factor (vW) (Hill W. et al Blood110, abstract No 1963; 2007). Here we report additional immunohistological and immunocytological findings in marrow and blood. We analyzed the number of CD34+ and vW+ microvessels as well as CD8+ suppressor/cytotoxic T-cells/mm² (T-S) in sequential biopsies of pts with (n=9) or without (n=6) cGvHD after median 2 years apart. Biopsies of 3 pts without HCT and without lymphoma involvement served as controls. Simultaneously lymphocyte subpopulations were evaluated in peripheral blood samples of pts with (n=16) or without (n=8) cGvHD. The pts were divided in 5 groups: neither aGvHD nor cGvHD; no cGvHD but acute GvHD before entry; cGvHD limited; cGvHD extensive without immunosuppression; cGvHD extensive with immunosuppression. Results: In the first biopsies the content of CD34+, vW+ microvessels and T-S cells were significantly higher in pts with cGvHD (group 3–5) than in those without cGvHD (group 1–2) (21,3 vs 8,2 p=0,03; 22,0 vs 9,2 p=0,002 respectively 106,2 vs 32,1 p=0,04). In the second biopsies these parameters were also increased in cGvHD: CD34+ (18,3 vs 11,2 p=0,02), vW+ (17,3 vs 9,0 p=0,08) microvessels and T-S cells (63,2 vs 37,8 p=0,27). The increased density of CD34+ and vW+ microvessels correlated with the number of T-S cells (p=0,05). As compared to normal controls we observed a significantly higher content of vW+ microvessels in all groups of transplanted pts (16,9 vs 4,2 p=0,03). In pts with cGvHD (group 3–5) CD34+ and vW+ microvessels were further increased (p=0,02 respectively p=0,002). At the time of the first biopsy the absolute T-S cell content in peripheral blood was moderately increased in group 5 (1124/ul) and minimally increased in group 2 (993/ul) (normal 270 – 880), whereas the overall T cell (CD3) content was normal in all groups. The percentage of activated T-S (HLA-DR+) cells was increased in all groups of transplanted pts (61,8% vs normal =33%; p=0,05). After two years T-S cells content was reduced in pts under immunosuppressive therapy (group 5) (1415 vs 900/ul; p=0.000) but remained increased over the norm. In group 4 T-S cell content was increased over the norm (800 vs 920/ul; p=0,043). In conclusion, sequential immunohistology and immunocytology analyses on bone marrow biopsies and peripheral blood provide evidence for the existence of a chronic graft-versus-host reaction of the bone marrow in pts with cGvHD. This is characterized by an increased content of CD34+ and vW+ microvessels and an increased content of T-S cells at least initially. However this reaction does not lead to a generalized hematopoietic insufficiency.
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Sasaki, Koji, Ildefonso Ismael Rodriguez-Rivera, Hagop M. Kantarjian, et al. "Correlation of Lymphocyte Count with Treatment Response to Tyrosine Kinase Inhibitors in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase." Blood 124, no. 21 (2014): 4538. http://dx.doi.org/10.1182/blood.v124.21.4538.4538.
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Abstract Background: Total lymphocyte count (TLC) has been shown to correlate with outcomes in patients (pts) with acute leukemia. The clinical correlation to TLC in pts with chronic myeloid leukemia in chronic phase (CML-CP) who were treated with a tyrosine-kinase inhibitor (TKI) is unclear. Methods: Lymphocyte data in pts with newly diagnosed CML-CP who were enrolled in consecutive or parallel clinical trials with front-line imatinib (IM), nilotinib (Nilo), or dasatinib (Dasa) were collected at the time of diagnosis, and 3 and 6 months (M) after the start of TKI. Relative lymphocytrosis (RLC) was defined as lymphocyte >150% at 3 or 6M compared with baseline at diagnosis. Absolute lymphocytosis (ALC) was defined as lymphocyte > 4,000 /µL at 3 or 6M after the start of TKI. Pts were assessed for response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS) based on ALC and RLC. The Kaplan-Meier method was used to calculate OS, EFS, TFS, and FFS. A log-rank test and Cox regression were used for univariate (UVA) and multivariate analysis (MVA), respectively. Results: A total of 483 pts were enrolled in this study: 271 in IM, 105 in Nilo, and 107 in Dasa. Patient characteristics and outcomes are summarized in Table 1. Median age at diagnosis was 48 years, and median follow-up was 85M and ongoing (5-154+). Time from diagnosis to start of TKI, Sokal risk score, and ALC at baseline between groups did not differ clinically. Of 481 pts, 93 (19%) developed RLC at 3 or 6M; IM, 38 (14%); Nilo, 23 (22%); Dasa, 32 (30%) (p= .001). ALC at 3 or 6M was observed in 15 (3%); IM, 3 (1%); Nilo, 1 (1%); Dasa, 11 (10%) (p<.001). Overall, cumulative incidence of complete cytogenetic response (CCyR) at 6M, major molecular response (MMR) at 12M, molecular response with 4.5 log reduction by IS (MR4.5) at 24M did not differ significantly between RLC and non-RLC (3 or 6M), or between ALC and non-ALC (3 or 6M). 5-y TFS, EFS and OS in ALC group were significantly worse than those in non-ALC group (p= .002, p=.016, p=.008, respectively). By UVA and MVA related to OS, age [p <.001; Hazard ratio (HR), 1.062; 95% confidence interval (95%CI), 1.036-1.089], presence of ALC at 3 or 6M [p = .028; HR, 10.948; 95%CI, 1.297-92.415], absence of MMR at 24M [p=.016; HR, 2.263; 95%CI, 1.165-4.393] were identified as adverse prognostic factors for OS. Conclusion: The presence of ALC ≥4,000/µL at 3 or 6M of TKI therapies is rare but is adversely associated with overall survival. Table 1. Patient Characteristics and Outcomes (N=483)a Overall [n= 481] IM [n= 271] Nilo [n= 105] Dasa [n= 107] Age, (year) 48 (15-85) 48 (15-85) 49 (17-82) 48 (16-83) Sokal Risk, No. (%) Low 334 (69) 175 (65) 79 (75) 80 (75) Intermediate 114 (24) 74 (27) 18 (17) 22 (21) High 32 (7) 20 (7) 8 (8) 4 (4) Time from diagnosis to start of TKI, (M) 0.9 (0-12.6) 1.0 (0-12.6) 0.5 (0-5.6) 0.7 (0.1-7.8) ALC at baseline, (/109L) 2.5 (0-86.6) 2.4 (0-16.7) 2.6 (0.4-9.2) 2.7 (0.3-86.6) Incidence of Relative Lymphocytosis, No. (%) At 3M 65 (14) 25 (9) 16 (15) 24 (22) At 6M 76 (16) 32 (12) 20 (19) 24 (22) Overall 93 (19) 38 (14) 23 (22) 32 (30) Incidence of Absolute Lymphocytosis, No. (%) At 3M 8 (2) 1 (0) 0 7 (7) At 6M 11 (2) 3 (1) 1 (1) 7 (7) Overall 15 (3) 3 (1) 1 (1) 11 (10) Outcomes of RLC and ALC at any time in each group, +/- (%/%) (p) <10% BCR-ABL/ABL at 3M RLC 36/40 (.596) 22/44 (.213) 50/37 (.280) 31/38 (.537) ALC 38/39 (.952) 0/42 (.394) 100/39 (.214) 36/35 (.952) Cumulative CCyR at 6M RLC 75/75 (.288) 50/66 (.063) 96/90 (.413) 90/87 (.628) ALC 67/75 (.711) 33/64 (.276) 0/92 (.001) 82/89 (.599) Cumulative MMR at 12M RLC 67/74 (.406) 53/70 (.030) 83/82 (.921) 72/74 (.903) ALC 60/73 (.488) 33/68 (.197) 0/83 (.033) 73/74 (.745) Cumulative MR4.5 at 24M RLC 46/52 (.564) 37/50 (.139) 57/55 (.889) 50/57 (.729) ALC 33/52 (.332) 33/48 (.610) 0/56 (.264) 36/57 (.252) 5-y FFS RLC 61/71 (.133) 56/69 (.167) 62/70 (.710) 61/74 (.285) ALC 50/69 (.076) 0/68 (<.001) 0/70 (<.001) 71/70 (.974) 5-y TFS RLC 90/93 (.369) 88/93 (.597) 91/88 (.115) 91/99 (.213) ALC 72/93 (.002) 67/93 (.014) 0/90 (<.001) 80/97 (.121) 5-y EFS RLC 80/86 (.213) 71/83 (.154) 84/87 (.450) 86/93 (.486) ALC 64/85 (.016) 33/82 (<.001) 0/87 (<.001) 80/92 (.574) 5-y OS RLC 89/93 (.068) 81/94 (.007) 100/84 (.126) 96/99 (.207) ALC 82/93 (.008) 67/93 (.001) 100/88 (.847) 83/99 (.040) a Two in IM and 1 in Dasa were not evaluable due to lack of differential data at 3 and 6M. Figure 1. OS in Pts with ALC Figure 1. OS in Pts with ALC Disclosures O'Brien: Amgen, Celgene, GSK: Consultancy; CLL Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Emergent, Genentech, Gilead, Infinity, Pharmacyclics, Spectrum: Consultancy, Research Funding; MorphoSys, Acerta, TG Therapeutics: Research Funding.
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Hehlmann, Rüdiger, Susanne Jung-Munkwitz, Michael Lauseker, et al. "Superior CMR-Rates with Tolerability-Adapted Imatinib 800 Mg Vs. 400 Mg Vs. 400 Mg + IFN In CML: The Randomized German CML-Study IV." Blood 116, no. 21 (2010): 357. http://dx.doi.org/10.1182/blood.v116.21.357.357.
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Abstract Abstract 357 Treatment of CML with imatinib of 400 mg can be unsatisfactory. Treatment optimization is warranted. The German CML-Study group has therefore conducted a randomized study comparing imatinib 800 mg vs 400 mg vs 400 mg + IFN. A significantly faster achievement of MMR at 12 months has been observed with imatinib 800 mg in a tolerability adapted manner and MMR by 12 months has been found to translate into better overall survival. Since stable CMR has been associated with durable off-treatment remissions we sought to analyse the impact of tolerability-adapted imatinib 800 mg on CMR and survival. Standardized determinations of molecular response and evaluation of its impact on outcome are goals of CML-Study IV. CMR4 is defined as a BCR-ABL/ABL ratio of <0,01 on the International Scale. From July 2002 – April 30, 2009 1022 newly diagnosed patients with CML in chronic phase were randomized, 1012 were evaluable (338 with imatinib 800 mg, 324 with imatinib 400 mg, 350 with imatinib plus IFN). Median observation time was 40 months. The median average daily imatinib doses were 628 mg in the 800 mg arm and 400 mg in the 400 mg based arms. The actual median daily doses in the 800 mg arm per 3-months periods were: 555 mg, 737 mg, 613 mg, 600 mg, and 600 mg thereafter, reflecting the run–in period with imatinib 400 mg for 6 weeks in the first period and the adaptation to tolerability from the third 3-months period onwards. Median daily imatinib doses in the 400 mg arms were 400 mg throughout. Adaptation of imatinib dose in the 800 mg arm according to tolerability is reflected by similar higher-grade adverse events rates (WHO grades 3 and 4) with all treatments. Significantly higher remission rates were achieved with imatinib 800 mg by 12 months. The cumulative incidences of CCR by 12 months were 63% [95%CI:56.4-67.9] with imatinib 800 mg vs 50% [95%CI:43.0-54.5] with the two 400 mg arms. The cumulative incidences of MMR by 12 months were 54.8% [95%CI:48.7-59.7] with imatinib 800 mg vs 30.8% [95%CI:26.6-36.1] with imatinib 400 mg vs 34.7% [95%CI:29.0-39.2] with imatinib + IFN. The cumulative incidences of CMR4 compared with the MMR incidences over the first 36 months are shown in Table 1. Imatinib 800 mg shows superior CMR4 rates over the entire 36 months period, CMR4 is reached significantly faster with imatinib 800 mg as compared to the 400 mg arms. The CMR4 rates reach 56.8% by 36 months [95%CI:49.4-63.5] as compared to 45.5% with imatinib 400 mg [95%CI:38.7-51.0] and 40.5% with imatinib plus IFN [95%CI:34.6-46.3]. Most patients have stable CMR4 over the entire period. Time after start of treat-ment (months) Cumulative incidences MMR(%) CMR4 (%) IM400 n=306 D IM800 n=328 D IM400 +IFN n=336 IM400 n=306 D IM800 n=328 D IM400 +IFN n=336 6 8.6 9.5 18.1 9.7 8.4 3 0.7 3.7 1.3 2.4 12 30.8 24.0 54.8 20.1 34.7 7.5 12.3 19.8 7.4 12.4 18 50.3 18.1 68.4 14.3 54.1 21.2 12.2 33.4 9.8 23.6 24 63 13.0 76.0 13.2 62.8 30.7 12.3 43 13 30.0 36 79.3 2.3 81.6 10.9 70.7 45.5 11.3 56.8 16.3 40.5 In summary, superior CMR4 rates are achieved with high-dose imatinib adapted to good tolerability, and more patients in the tolerability-adapted 800 mg arm have stable CMR4 qualifying for treatment discontinuation as compared to the 400 mg based arms. With improved application imatinib remains first choice for early CML. Disclosures: Koschmieder: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. German CML-Study Group:Deutsche Krebshilfe: Research Funding; Novartis: Research Funding; Roche: Research Funding; BMBF: Research Funding; Essex: Research Funding.
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Hutchinson, Valerie J. "The cult of Dionysos/Bacchus in the Graeco-Roman world: new light from archaeological studies - C. GASPARRI , “BACCHUS,” LIMC III.1 (1986) 540–566, with III.2, 428-456. - C. AUGÉ , “DIONYSOS (IN PERIPHERIA ORIENTALI),” LIMC III.1 (1986) 514-31, with III.2, 406-19 - S. BOUCHER , “BACCHUS (IN PERIPHERIA OCCIDENTALI),” LIMC IV.1 (1988) 908-23, with IV.2, 612-31. - S. F. SCHRÖDER , RÖMISCHE BACCHUSBILDER IN DER TRADITION DES APOLLON LYKEIOS. STUDIEN ZUR BILDFORMULIERUNG UND BILDBEDEUTUNG IN SPÄTHELLENISTISCH-RÖMISCHER ZEIT (Giorgio Bretschneider, Roma 1989). Pp. xii + 216, 31 black and white plates. ISBN 88-7689-020-3. - I. MANFRINI-ARAGNO , BACCHUS DANS LES BRONZES HELLÉNISTIQUES ET ROMAINS: LES ARTISANS ET LEUR RÉPERTOIRE (Bibliothèque historique vaudoise, Lausanne 1987). Pp. 190, 84 p. of black and white plates. ISBN 28-8028-034-6. - B. HUNDSALZ , DAS DIONYSISCHE SCHMUCKRELIEF (Tuduv-Studien, Reihe Archäologie, Band 1, München 1987). Pp. xvii + 311, 32 p. of black and white plates. ISBN 3-88073-236-1." Journal of Roman Archaeology 4 (1991): 222–30. http://dx.doi.org/10.1017/s104775940001566x.
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Zhao, Bin. "On the Enterprise Dynamic Management in the COVID-19 Pandemic." Biomedical Research and Clinical Reviews 1, no. 2 (2020): 01–16. http://dx.doi.org/10.31579/2692-9406/010.
Full textAbstract:
Background: With the worldwide spread of the novel coronavirus (COVID-19), the global economy has entered a cold winter, and the International Monetary Fund predicts that the global economy will shrink by about 3% in 2020. The outbreak of the epidemic has also caused heavy losses to the Chinese economy. In the first quarter of 2020, actual GDP fell sharply for the first time by 6.8% year-on-year for the first time. This is the first decline since record. Then, according to the data from the business survey in March, China's economy has improved compared with February, which shows that the economy has rebounded under the influence of policies. Judging from the current situation, although China has passed the peak period of the epidemic, affected by the high cases abroad, it can only be carried out slowly for the resumption of production. Enterprises, as micro-individuals under the macro economy, need to pass through analyzing the dynamic management of the enterprise to deepen the reform of the commercial system and stimulate the vitality of the enterprise. This will also provide data support for the government formulating relevant policies, which is conducive to the synergy of various policies and enhance the momentum of economic recovery. On the other hand, we choose tourism as our specific research object. Thus, we need to set different scenarios according to the development situation of the epidemic, evaluate the impact of the novel coronavirus epidemic on China's tourism industry, and discuss tourism development and opportunities in the post-epidemic era from the aspects of tourism's response to the epidemic and the development trend of the tourism after the epidemic4. Methods: This dissertation first discusses the issue of enterprise dynamic management in the post covid-19 epidemic era, establishes the Difference-in-Difference model (DID model), and improves the model reasonably. It puts forward the dynamic management plan of different regions, and judges the effect of the policy on the implementation of the epidemic. At the same time, it also aims at the impact of the epidemic on the tourism industry at the important time points. The elasticity method and linear regression are used to evaluate and forecast.Using transportation data as a leading indicator, the elasticity of the total number of tourists Et1 and the elasticity of total tourism revenue Ei1 during the Spring Festival and Spring Festival are calculated to be 1.39 and 1.60 respectively. The impact of COVID-19 on the Spring Festival tourism market is evaluated through the Spring Festival elasticity; During the period, the elasticity of the International Workers’ Day tourism market relative to the Spring Festival tourism market Et2 、Ei2 is calculated to be 1.14 and 0.9024 respectively through data over the years. Combining the forecast results of the Spring Festival tourism market and the data calibration of different forecast scenarios, the International Workers’ Day is predicted. The total number of tourist trips and total tourism revenue during the period; for the National Holiday, the above ideas are used to calculate the elasticity of the National Holiday tourism market relative to the Spring Festival and International Workers’ Day tourism markets Et3 、 Ei3 , which are 0.69 and 0.94, respectively , predicting the total number of tourists and total tourism revenue during the National Holiday period. Findings: The results based on DID model analysis show that the significance level of the policy to the GDP of Jiangsu Province is 32%. The saliency level in Hubei province is 37%. In the first quarter of the year 2020, the total travel time and total tourism revenue of the first quarter of the year 2020 are predicted, and the logarithmic linear regression equation is established based on the total tourist arrivals and the total tourism revenue in the year 2020 as the explanatory variables of total tourism trips and total tourism revenue in the first quarter. The total number of tourist trips in the first quarter of the year 2020 is 394 million, a decrease of 74.42% over the same period last year, and the total value of tourism revenue is 319 billion 565 million yuan, a decrease of 77.01% over the same period last year. The counter-factual prediction value of the total number of tourists in the first quarter of the year 2020 is 1 billion 676 million, and the counter-factual prediction value of the total tourism revenue is 1 trillion and 580 billion yuan. During the first half of the year 2020, the total number of tourists and the total tourism revenue in the first half of the year are predicted. The total number of tourists in the first quarter and the International Workers’ Day is used as the explanatory variables of the total travel time in the first half of the year. Logarithmic linear regression equations are established respectively and replaced by the estimated values. The predicted value of the total tourist arrivals in the first half of the year 2020 is 1 billion 440 million, which is 53.25% lower than that in the same period last year. The forecast value of total tourism revenue is 1 trillion and 165 billion 98 million yuan, with a decrease of 58.09%. Compared with the same period last year, the potential decline of the total number of tourists in the first half of the year 2020 is 1 billion 911 million, with a decrease of 57.03%, resulting in a potential loss of 1 trillion and 994 billion 902 million yuan and a loss ratio of 63.13% for tourism total revenue. Under the optimistic forecast, the total number of tourist trips in the year 2020 is 4 billion 659 million. A decrease of 23.12% compared with the same period last year, and the total value of tourism revenue is 4 trillion and 807 billion 295 million yuan, 26.27% lower than that of the same period last year. Under the prudent forecast, the total number of tourist trips in the year 2020 is 3 billion 941 million, a decrease of 34.97% over the same period last year, and the total value of tourism revenue is 3 trillion and 922 billion 883 million yuan, a decrease of 39.83%, over the same period of the last year. Interpretation: China's economy has been affected by the epidemic to varying degrees in all sectors, especially in the tertiary sector. And because the outbreak situation in China did not look good in the first quarter of 2020, almost all companies made a loss in the first quarter of 2020. To address the economic downturn, the Chinese government has taken various measures, such as issuing coupons to stimulate consumption, discounting promotions, etc. And as the domestic epidemic situation in China continues to improve, more and more companies have resumed normal operations in the last two months. It is believed that in the near future, China's economic situation will be significantly better than in the first quarter.
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Landgren, Ola, Katja Weisel, Laura Rosinol Dachs, et al. "Evaluation of Minimal Residual Disease (MRD) Negativity in Patients with Relapsed or Refractory Multiple Myeloma Treated in the Candor Study." Blood 136, Supplement 1 (2020): 32–34. http://dx.doi.org/10.1182/blood-2020-141291.
Full textAbstract:
Introduction: CANDOR is a multicenter, phase 3, randomized study of adult patients with relapsed or refractory multiple myeloma (RRMM) previously treated with 1-3 prior lines of therapy (NCT03158688). 466 patients received carfilzomib, dexamethasone, and daratumumab (KdD) or carfilzomib and dexamethasone (Kd) in 2:1 randomization (KdD: 312; Kd: 154). Based on the primary endpoint, KdD demonstrated superior progression-free survival (PFS) vs Kd (hazard ratio [HR], 0.63 [95% CI, 0.46-0.85]; P=0.0014). Deep responses and minimal residual disease (MRD) negativity have been associated with improved PFS for patients with RRMM. Herein, we present an analysis of MRD results from CANDOR. Methods: Details of the dose and schedule were previously reported (Dimopoulos et al., Lancet 2020). The rate of patients with confirmed CR which were MRD negative (MRD[-]CR) in bone marrow aspirate at 12 months (± 4 weeks) measured by next-generation sequencing (NGS; threshold, 1 tumor cell/10-5 white blood cells) was a prespecified key secondary endpoint. Exploratory analyses included MRD[-]CR at increasing sensitivity (10-4, 10-5, 10-6) and best overall response MRD[-] status at any time point. All reported responses were by Independent Review Committee and were analyzed for the Intent-to-Treat population. MRD[-] status is at &lt;10-5 unless otherwise specified. Results: The best overall MRD[-]CR rate at any time was 13.8% vs 3.2% in the KdD vs Kd arm (Odds ratio [OR], 4.95; P&lt;0.0001) and the MRD[-] rate regardless of overall response status was 22.8% vs 5.8% (OR, 5.15; P&lt;0.0001). At the 12-month landmark, the MRD[-]CR rate was 12.5% vs 1.3% in the KdD vs Kd arm (OR, 11.3; P&lt;0.0001) and the MRD[-] rate was 17.6% vs 3.9% (OR, 5.76; P&lt;0.0001) with the proportion of patients with MRD[-]VGPR being 4.2% vs 2.6%, respectively. The MRD[-]CR rates at the 12-month landmark for KdD vs Kd were consistent across clinically relevant subgroups (Table). At the 12-month landmark, KdD treatment resulted in a greater proportion of CR rates (26.9% vs 9.7%) and deeper MRD responses than Kd. Among patients in CR, the depth of response as measured by NGS MRD level at the 12-month landmark was deeper for KdD relative to Kd: cutoff of &gt;10-4, 36.9% vs 73.3%; 10-4 to 10-5, 16.7% vs 13.3%; 10-5 to 10-6, 23.8% vs 13.3%; &lt;10-6, 22.6% vs 0% for KdD vs Kd, respectively (Figure). Similar to the results at the 12-month landmark, MRD responses independent of the landmark were deeper among patients in the KdD compared to the Kd arm. With median follow-up of 6 months from the 12-month landmark, no patient with MRD[-]CR response progressed or died. Additional post hoc analyses were conducted within patients randomized to KdD to explore prognostic characteristics for MRD[-]CR. Importantly, prior lenalidomide exposure did not meaningfully impact the MRD[-]CR rate at the 12-month landmark; 13.2% (25/189), 11.4% (14/123), and 13.1% (13/99) for naïve, exposed, and refractory subgroups, respectively. For prior bortezomib, the MRD[-]CR rates were 24% (6/25), 11.5% (33/287), and 6.8% (6/88) for naïve, exposed, and refractory subgroups, respectively. The rates of MRD[-]CR at the 12- month landmark within the KdD arm were consistent across subgroups: patients refractory to the last prior therapy (yes vs no, 10.9% vs 14.3%), number of prior regimens (1-2 vs 3 prior regimens; 13.2% vs 10.1%), prior transplant (yes vs no, 11.8% vs 13.7%), duration of first remission (≤2 vs &gt;2 years, 12.3% vs 13% and ≤1 vs &gt;1 year, 10.7% vs 13.4%), baseline creatinine clearance (≥15 to &lt;50, ≥50 to &lt;80, and ≥80 mL/min, 10.5%, 14.4%, and 11.9%, respectively), age (≤75 vs &gt;75 years, 12.9% vs 8.0%), or dose intensity (&lt; vs ≥ median) for carfilzomib or daratumumab (10.5% vs 14.9% and 9.8% vs 15.6%, respectively). Data on cytogenetics will be included at the time of presentation. Conclusion: At the primary analysis, patients treated with KdD achieved significantly higher MRD[-]CR rates vs Kd at the 12-month landmark. Among patients with an MRD[-]CR, the depth of MRD was deeper with KdD vs Kd. With a median of 6 months follow-up, no patient with an MRD[-]CR has progressed; duration of response will be updated at time of presentation. Within the KdD arm, lenalidomide exposure or refractoriness did not diminish the MRD[-]CR rate. These findings support the efficacy of the KdD regimen as an effective treatment for RRMM, including patients who have become lenalidomide refractory. Disclosures Landgren: Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Seattle Genetics: Research Funding; Juno: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Other. Weisel:Roche: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Rosinol Dachs:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Moreau:Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Honoraria; Takeda: Honoraria; Abbvie: Consultancy, Honoraria. Hajek:PharmaMar: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; Oncopeptides: Consultancy; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Mollee:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Zhang:Amgen: Current Employment. Go:Amgen: Current Employment. Morris:Amgen: Current Employment. Usmani:Celgene: Other; Takeda: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Janssen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; SkylineDX: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Incyte: Research Funding; Pharmacyclics: Research Funding; Array Biopharma: Research Funding; GSK: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; BMS, Celgene: Consultancy, Honoraria, Other: Speaking Fees, Research Funding; Amgen: Consultancy, Honoraria, Other: Speaking Fees, Research Funding.
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Aliev, Ziya S. "THE AV–BVI–I TERNARY SYSTEMS: A BRIEF REVIEW ON THE PHASE EQUILIBRIA REVIEW." Kondensirovannye sredy i mezhfaznye granitsy = Condensed Matter and Interphases 21, no. 3 (2019): 338–49. http://dx.doi.org/10.17308/kcmf.2019.21/1149.
Full textAbstract:
This paper presents a brief review on the ternary phase equilibria in the ternary AV–BVI–I systems (AV = Sb, Bi; BVI = S, Se, Te). These systems includes the series of ternary compounds those are very attractive source materials for photo-, thermos- and ferroelectric energy transformation along the recently discovered semiconductors that exhibit Rashba-type spin splitting in their surface states. In the Rashba semiconductors, a unique toroidal 3D Fermi surface appears on the crystal surface, which leads to unusual properties that make it possible to realize unique electronic devices based on these compounds. The thorough knowledge on the ternary phase diagram of these systems shed light on the chemical and structural design of new multifunctional materials with tunable properties. This knowledge is very important whenfocusing on the chemistry of such multifunctional materials based on complex element systems.
 
 
 
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Anjali, Anjali, and Manisha Sabharwal. "Perceived Barriers of Young Adults for Participation in Physical Activity." Current Research in Nutrition and Food Science Journal 6, no. 2 (2018): 437–49. http://dx.doi.org/10.12944/crnfsj.6.2.18.
Full textAbstract:
This study aimed to explore the perceived barriers to physical activity among college students Study Design: Qualitative research design Eight focus group discussions on 67 college students aged 18-24 years (48 females, 19 males) was conducted on College premises. Data were analysed using inductive approach. Participants identified a number of obstacles to physical activity. Perceived barriers emerged from the analysis of the data addressed the different dimensions of the socio-ecological framework. The result indicated that the young adults perceived substantial amount of personal, social and environmental factors as barriers such as time constraint, tiredness, stress, family control, safety issues and much more. Understanding the barriers and overcoming the barriers at this stage will be valuable. Health professionals and researchers can use this information to design and implement interventions, strategies and policies to promote the participation in physical activity. This further can help the students to deal with those barriers and can help to instil the habit of regular physical activity in the later adult years.
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Deepika, Fnu, Karla Bermudez Saint Andre, and Abhishek Kansara. "SUN-908 Mediastinal Paraganglioma: A Rare Presentation of a Rare Tumor." Journal of the Endocrine Society 4, Supplement_1 (2020). http://dx.doi.org/10.1210/jendso/bvaa046.562.
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Abstract BACKGROUND Paragangliomas (PPGL’s) are extra-adrenal chromaffin-cell originating tumors that arise from the para-aortic ganglia and are exceptionally rare making up only 1% of the mediastinal tumors. They are slowly growing and highly vascular tumors associated with high morbidity and mortality due to proximity and invasion into the heart, great vessels. The majority of them are asymptomatic and hence discovered incidentally. Surgical resection remains the standard of care with good long term survival. We describe a case of a young male with middle mediastinal PPGL who remained asymptomatic despite large functional tumor. CLINICAL CASE A 38-year old Arab male with no previous smoking history was referred to our hospital for evaluation of mediastinal mass that was incidentally noted on an echocardiogram done 1 year ago in his home country when he presented with intermittent exertional shortness of breath for 10 years. The workup done there with CT chest revealed a large mediastinal mass measuring 10.4×8.8×8.6 cm extending into ascending aorta, right pulmonary artery, right superior pulmonary vein, right and left atria as well as the main bronchi bilaterally invading the superior vena cava. However, he had no further treatment until he was seen 1 year later in the US at another institution where biochemical testing showed elevated plasma norepinephrine of 2697 (70-750 pg/ml, supine), dopamine 7667 (&lt;30 pg/ml). 24hr-urine studies showed elevated normetanephrine of 3418 (111-419 mcg/24hr), metanephrine 3488 (200-614 mcg/24hr), and Homovanillic acid (HVA) 51.5 (&lt;0.8 mg/24hr). He underwent endobronchial ultrasound with mediastinal tissue biopsy of the mass that revealed pheochromocytoma. The patient was subsequently referred for cardiovascular intervention at our hospital and endocrinology was consulted for pre-operative preparation. One week before surgery, he was started on doxazosin 2mg daily followed 3 days later by propranolol 10 mg twice daily and recommend high salt and fluid intake. The patient underwent surgical resection of the mass and pathology showed mediastinal PPGL. The postoperative course was complicated by bradycardia with the placement of a permanent pacemaker. He recovered well after surgery with the resolution of symptoms and a significant decline in catecholamines to urine normetanephrine of 385 mcg/24hr and metanephrine 497 mcg/24hrs. There was no evidence of metastatic or residual disease on follow-up CT chest 5 months later. CONCLUSION There are limited case reports of PPGL in the middle mediastinum. This case highlights that mediastinal PPGL’s can remain clinically silent for many years prior to the presentation which can lead to delayed diagnosis, yet a strong collaborative team approach between oncology, cardiovascular surgery and endocrinology can confer favorable clinical outcome.
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Kwak, Leigh, Julia Caroline Wingate Lake, Simrun Bal, Andrew Robert Crawford, and Sushela S. Chaidarun. "SUN-907 Dual Ectopic Gastrin and ACTH Secretion Leading to Combined Zollinger-Ellison Syndrome and Cushing’s Syndrome in a Patient with Metastatic Neuroendocrine Pancreatic Tumor." Journal of the Endocrine Society 4, Supplement_1 (2020). http://dx.doi.org/10.1210/jendso/bvaa046.1775.
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Abstract Background: Zollinger-Ellison Syndrome (ZES) is caused by ectopic secretion of gastrin from a gastrinoma. The annual incidence of gastrinomas is 0.5 to 2 per million population1. Although 17-30% of gastrinomas will stain positive for both gastrin and ACTH, the clinical manifestation of both ZES and Cushing’s syndrome is rare. In a study by Maton et al., 3 of 59 patients (5%) with sporadic ZES (not MEN1) had Cushing’s syndrome as well2. Clinical Case: A 63yo woman with DM2 presented with persistent diarrhea for 2 years, and was diagnosed with ZES with a gastrin level of 1359 pg/mL (&lt;100 pg/mL). A CT A/P showed a 3.8 cm pancreatic tail mass with multiple liver lesions. These lesions showed positive uptake on octreoscan, and a biopsy was positive a pancreatic neuroendocrine (NE) tumor. Her diarrhea was controlled with a PPI and no other intervention was made. 7 months later, she experienced severe worsening of her DM control despite aggressive medication titration. Due to new confusion and lethargy, she presented acutely to the ED. Labs showed metabolic alkalosis and profound hypokalemia with a CO2 38 mmol/L (22 - 31 mmol/L), venous pH 7.58 (7.32 - 7.42) and K 2.1 mmol/L (3.5 – 5.0 mmol/L). Her skin was diffusely hyperpigmented, and she had numerous cushingoid features on exam including supraclavicular fat pads, round face, thin skin and thin extremities. A subsequent cortisol level was found to be 125 mcg/dL (AM [6-10 am] 4.8 – 19.5 mcg/dL) with an ACTH of 1081 pg/mL (6-50 pg/mL). She was not an optimal candidate for adrenalectomy given previous abdominal surgeries. After an octreotide drip (total 1475 mcg in 24 hrs) failed to reduce cortisol levels, metyrapone 250 mg q6h was started which led to an immediate and significant reduction in cortisol (209 to 38 mcg/dL), improved quality of life and significant reduction in her insulin and K supplementation requirement. Conclusion: We present a rare case of a dual gastrin and ACTH-secreting metastatic pancreatic NE cancer, in which overt ZES preceded the relatively abrupt onset of clinical Cushing’s syndrome. Similar to Babu et al., the initial presentation was dominated by worsening DM control3. Despite the octreoscan positivity, cortisol production was not appreciably blocked by octreotide but was well controlled by metyrapone. As seen in other cases, we again highlight the pluripotency of NE tumors and the ability to change hormone production. We also present the unique circumstance this patient faced for treatment options as she was not an optimal candidate for surgery. Reference: 1. Oberg K. Pancreatic endocrine tumors. Semin Oncol. 2010 Dec;37(6):594-618. 2. Maton PN, Gardner JD, Jensen RT. Cushing’s syndrome in patients with the Zollinger-Ellison syndrome. N Engl J Med. 1986 Jul 3;315(1):1-5. 3. Babu AR, Dwarakanathan AA. Cushing’s syndrome from ectopic production of corticotropin by a metastatic gastrinoma. Endocr Pract. 2003 May-Jun;9(3):229-32.
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Caldwell, M. L., H. H. Richardson, and M. E. Kordesch. "Optical Properties of Manganese Doped Amorphous and Crystalline Aluminum Nitride Films." MRS Proceedings 595 (1999). http://dx.doi.org/10.1557/proc-595-f99w3.26.
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AbstractAn aluminum nitride (AlN) film deposited on silicon (100) was used as the substrate for growing manganese (Mn) doped AlN film by metal organic chemical vapor deposition (MOVCD). The (15.78 [.proportional]m) under layer of AlN was grown at 615°C at a pressure of 10−4 Torr. The (2.1 [.proportional]m) top layer of Mn-AlN was grown at the same temperature and pressure but doped with pulse valve introduction of the manganese decacarbonyl (100 ms on, 100 ms off). The film was then characterized ex situ with IR reflectance microscopy, X-ray diffraction, scanning electron microscopy imaging, cathodoluminescence, and X-ray fluorescence. The IR reflectance measurements showed a strong (A1) LO mode for AlN at 920 cm−1 and 900 cm−1 with a shoulder at 849 cm−1. X-ray Diffraction yielded three diffraction peaks at a 2ø position of 33, 36 and 38 degrees corresponding to 100, 002, and 101 lattice planes respectively. Cathodoluminescence results show strong visible emitted light from incorporated manganese. The relative percentage of manganese to aluminum was below the detection limit (0.01 %) of the Xray fluorescence spectrometer. Amorphous Mn doped AlN films have also been grown using a low temperature atomically abrupt sputter epitaxial system. The amorphous Mn doped AlN showed no cathodoluminescence.