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1
AW, K. C., N. T. SALIM, WEI GAO, and K. PRINCE. "STUDY OF COPPER DIFFUSION IN LOW-k THIN FILM USING SIMS." International Journal of Modern Physics B 20, no. 25n27 (2006): 4165–70. http://dx.doi.org/10.1142/s0217979206041033.
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The aim of this paper is to study Cu diffusion in polymethylsiloxane (LKD-5109) low-k dielectric material manufactured by JSR Micro with respect to applied thermal energy acting alone. Previous study on low-k dielectric thin film uses a combination of electrical and thermal stress to study Cu diffusion producing a combined activation energy. In this paper, a secondary-ion mass spectrometry (SIMS) was used to determine copper diffusion into LKD-5109 thin film on samples baked/annealed at different temperatures ranging from 373K to 573K in forming gas (7% H 2/93% N 2). The results showed that the thermal activation energy (Ea) of Cu thermal diffusion is approximately 0.14eV for baking/annealing temperature ranging from 373K to 523K. The Ea will increase to greater than 0.58eV for temperature above 523K with Cu oxidation. The increase in Ea suggests a transport mechanism due to Cu oxidation where oxidized Cu is a source of copper ions that diffused through the low-k dielectric film.
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Eichelser, Corinna, Dieter Flesch-Janys, Jenny Chang-Claude, Klaus Pantel, and Heidi Schwarzenbach. "Deregulated Serum Concentrations of Circulating Cell–Free MicroRNAs miR-17, miR-34a, miR-155, and miR-373 in Human Breast Cancer Development and Progression." Clinical Chemistry 59, no. 10 (2013): 1489–96. http://dx.doi.org/10.1373/clinchem.2013.205161.
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BACKGROUND MicroRNAs (miRs) are small, noncoding RNAs that target genes involved in tumor development and progression. In the current study, we investigated the use of circulating miR concentrations as biomarkers in the serum of breast cancer patients. METHODS We analyzed serum samples from 120 patients with primary breast cancer after surgery and before chemotherapy (M0, classified into 3 subgroups of 40 patients with progesterone/estrogen-positive, HER2-positive, and triple-negative cancer), 32 patients with overt metastasis (M1), and 40 healthy women. Using quantitative TaqMan MicroRNA PCR, we measured the relative concentrations of 6 circulating microRNAs (miR-10b, -17, -34a, -93, -155, and -373) known to be relevant for tumor development and progression. The data were correlated with clinicopathologic risk factors, with particular reference to HER2 and hormone receptor status of the primary tumor and the presence of metastases. RESULTS The relative serum concentrations of circulating miR-34a [P = 0.013, area under the curve (AUC) 0.636], miR-93 (P = 0.001, AUC 0.699), and miR-373 (P = 0.0001, AUC 0.879) were significantly different between M0 breast cancer patients and healthy women, whereas miR-17 (P = 0.002, AUC 0.679) and miR-155 (P = 0.0001, AUC 0.781) were differently expressed between M0 and M1 patients. Increased concentrations of miR-373 were associated with negative HER2 status of the primary tumor (P = 0.0001). Deregulated concentrations of miR-17 (P = 0.019) and miR-34a (P = 0.029) were detected in patients with progesterone/estrogen receptor–positive and –negative status, respectively. CONCLUSIONS Our findings indicate that serum concentrations of deregulated microRNAs may be linked to a particular biology of breast carcinomas favoring progression and metastatic spread.
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Wu, Cheng Xuan, Jun Le Qu, Zhuo Lei, Lei Dong, and Jie Liu. "Overlapped Bubbles Recognition in Two-Phase Flow." Applied Mechanics and Materials 373-375 (August 2013): 400–403. http://dx.doi.org/10.4028/www.scientific.net/amm.373-375.400.
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We presented an algorithm to recognize overlapped bubbles in two-phase flow. We extracted bubble images from gray image by Background subtraction, and then converted them to binaries. Final images were segmented to compare them with the templates of bubble pattern. Finally, we obtained the recognition accuracy to compare their similarities. The recognition rate is to 93% and it is efficient in the field of the machine vision.
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Warshaw, Erin M., Thomas Bowman, Myron A. Bodman, John J. Kim, Stefanie Silva, and Susan D. Mathias. "Satisfaction with Onychomycosis Treatment." Journal of the American Podiatric Medical Association 93, no. 5 (2003): 373–79. http://dx.doi.org/10.7547/87507315-93-5-373.
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The purpose of this study, which involved two dermatology clinics and two podiatric medical clinics, was to determine whether a difference exists in patient-reported satisfaction and compliance between continuous terbinafine therapy and pulse-dose itraconazole therapy for the treatment of toenail onychomycosis. Patients in this multicenter, open-label, cross-sectional study had previously completed treatment with either oral terbinafine or oral itraconazole for toenail onychomycosis. Patients were interviewed by telephone to assess clinical outcomes, compliance, and satisfaction with treatment; clinical data were collected by medical chart review. Patients reported significantly greater ease and convenience of treatment and higher overall satisfaction with continuous terbinafine therapy compared with pulse-dose itraconazole therapy. (J Am Podiatr Med Assoc 93(5): 373-379, 2003)
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Sprague, Christy L., Donald Penner, and James J. Kells. "Physiological basis for tolerance of fourZea mayshybrids to RPA 201772." Weed Science 47, no. 6 (1999): 631–35. http://dx.doi.org/10.1017/s0043174500091256.
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Greenhouse and laboratory experiments were conducted to determine the physiological basis for differential tolerance of fourZea maysL. hybrids to RPA 201772. Differences inZea maystolerance were quantified by determining the herbicide rate required to injure and reduceZ. maysheight 50% (GR50). GR50values indicated that theZ. mayshybrids ‘Pioneer 3751’ and ‘Pioneer 3737’ were less tolerant to RPA 201772 than the hybrids ‘Pioneer 3394’ and ‘Pioneer 3963.’ Experiments using14C-RPA 201772 were conducted to determine if hybrid sensitivity was due to differential uptake, translocation, or metabolism of the herbicide. Differences in hybrid tolerance were primarily due to differential herbicide metabolism rates. The time required for 50% inactivation (T½) of RPA 201772 was 42 and 52 h for the more tolerant hybrids and 66 and 93 h for the more sensitive hybrids. Increased uptake of RPA 201772 was also a contributing factor to the sensitivity of one of the hybrids.
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Alobaid, Mohammad, Ben Hughes, Andrew Heyes, and Dominic O’Connor. "Determining the Effect of Inlet Flow Conditions on the Thermal Efficiency of a Flat Plate Solar Collector." Fluids 3, no. 3 (2018): 67. http://dx.doi.org/10.3390/fluids3030067.
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The main objective of this study was to investigate the effect of inlet temperature (Tin) and flowrate ( m ˙ ) on thermal efficiency ( η t h ) of flat plate collectors (FPC). Computational Fluid Dynamics (CFD) was employed to simulate a FPC and the results were validated with experimental data from literature. The FPC was examined for high and low level flowrates and for inlet temperatures which varied from 298 to 373 K. Thermal efficiency of 93% and 65% was achieved at 298 K and 370 K inlet temperature’s respectively. A maximum temperature increase of 62 K in the inlet temperature was achieved at a flowrate of 5 × 10−4 kg/s inside the riser pipe. Tin and m ˙ were optimised in order to achieve the minimum required feed temperature for a 10 kW absorption chiller.
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Lopes, Fernanda Souza, and Linconl Agudo Oliveira Benito. "Conhecimento de estudantes universitários sobre a cirurgia bariátrica (CB)." Universitas: Ciências da Saúde 15, no. 2 (2018): 107. http://dx.doi.org/10.5102/ucs.v15i2.4272.
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Trata-se de um estudo transversal, descritivo e de abordagem quantitativa que analisou o conhecimento de estudantes de uma instituição de ensino superior (IES) com sede em Brasília (D.F.) sobre a CB. Foram entrevistados quatrocentos (400) estudantes, sendo que 48% (n=192) cursavam “enfermagem”, 24% (n=96) cursavam “nutrição”, 15,50% (n=62) cursavam “medicina”, 8,25% (n=33) cursavam “biomedicina” e 4,25% (n=17) cursavam “biologia”. O perfil dos atores sociais participantes do presente estudo se constituiu de 78,75% (n=315) pessoas do sexo feminino, 87,75% (n=351) solteiras, 70,75% (n=283) não desenvolvem atividade remunerada, 93,25% (n=373) negam enfermidade(s), 94,50% (n=378) negam tabagismo, 78% (n=312) negam consumo medicamentoso, 93% (n=372) negam etilismo, 99,25% (n=397) negam hipertensão arterial (HA), 100% (n=400) negam diabetes mellitus (DM), 81,50% (n=326) negam sobrepeso e 95% (n=380) negam obesidade. Foi identificado ainda reduzido conhecimento dentre os entrevistados, apenas na categoria analítica relacionada a necessidade de suplementação alimentar utilizando polivitamínicos após a realização da CB.
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Kingdon, David. "Outcome-based providing and commissioning: pathways and standards." BJPsych Bulletin 43, no. 6 (2019): 282–86. http://dx.doi.org/10.1192/bjb.2019.36.
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Aims and methodImplementation of evidence-based psychosocial interventions in accordance with National Institute of Health and Care Excellence guidelines and quality standards has been incomplete. This project involved allocation of adults under mental health services to six guideline categories, completion of a clinician- and patient-rated outcome measure, and individual assessment against clinical standards.ResultsIn the first 3 months of the project, 5048 patients were allocated to a pathway and 3734 (73%) were assessed against at least one of the relevant standards. All were assessed using the Health of the Nation Outcome Scales (91–93% of scales completed) and 1866 (36%) completed the patient-rated outcome measure, DIALOG.Clinical implicationsClinicians will allocate patients to pathways, complete outcome measures and assess against standards, providing data to guide practice, service design and costing of mental health systems with supporting technology to assist data entry and presentation. This has the potential to provide much improved and readily accessible information about individual outcomes and standards for people with mental health problems and those working with them. It could also provide a method for payment for services which directly support good clinical practice.
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Oktavian, Rama, Bambang Poerwadi, Mochamad Reza Pahleva, Mochammad Wahyu Muharyanto, and Supriyono Supriyono. "Synthesis and performance assessment of coconut fiber solid adsorbent for waste cooking oil purification as biodiesel feedstock." Malaysian Journal of Fundamental and Applied Sciences 16, no. 3 (2020): 374–77. http://dx.doi.org/10.11113/mjfas.v16n3.1522.
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Waste cooking oil can be considered as an alternative biodiesel feedstock for replacing edible oils. However, this feedstock can not be directly used since it contains much impurities and high Free Fatty Acid (FFA) content. Thus, pre-treatment process is required to enhance the feedstock quality. Adsorption using activated carbon is one of various methods that can be applied to reduce FFA content which is relatively easy and cheap. Coconut fiber is biomass waste that can be utilized in activated carbon production. This work has successfully synthesized activated carbon from coconut fiber with activator medium of H3PO4 10% weight and carbonization temperature of 600 °C, indicated from yield, water content, ash content, and methylene blue adsorption capacity. The yield of carbonization process developed in this work reached 40% while the yield for water content, ash content, and methylene blue adsorption capacity were 2.5%, 2.3% and 1646.1 mg/g carbon, respectively which complied with SNI 06-3730-1995. This adsorbent was tested on fixed bed adsorption column with FFA reduction reached up to 93% at waste cooking oil flowrate of 3 ml/min for 45 minutes operation time.
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Ivanov, S. A., M. V. Kenarskaya, and K. A. Panfilov. "LIVER HYDATIDOSIS: OPTIMIZATION OF SURGICAL TREATMENT METHODS." Science and Innovations in Medicine 3, no. 4 (2018): 20–26. http://dx.doi.org/10.35693/2500-1388-2018-0-4-20-26.
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Objectives - optimization of hepatic echinococcosis treatment schemes based on the data analysis of the immediate and long-term results. Material and methods. The study included 373 clinical cases of patients with liver echinococcosis who received treatment in 2005-2018 in Samara Regional Clinical Hospital n. a. V.D. Seredavin. 342 patients underwent a traditional operation, the surgical puncture was performed in 31 patient. Starting from 2003 all patients received the antirelapse chemotherapy with albendazole according to the WHO's recommendations in the postoperative period. Results. The treatment tactics in patients with liver hydatidosis was defined according to the parasite's developmental stage, its localization, and the size of liver cyst. The traditional surgery was successful after one operation in more than 93% of cases, postoperative mortality was 1.46%, the number of postoperative complications - 12.5%, the number of relapses in 5 year follow-up period was 6.8%. In 31 patients we used the puncture surgery treatment of hepatic echinococcosis PAIR and PEVAC-methods. Conclusion. Modern approach to hepatic echinococcosis treatment should provide differentiated
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Nyaupane, Parashu R., Yasnahir Perez-Delgado, David Camejo, Lesley M. Wright, and Carlos E. Manzanares. "Cavity Ring-Down Absorption of O2 in Air as a Temperature Sensor for an Open and a Cryogenic Optical Cavity." Applied Spectroscopy 71, no. 5 (2016): 847–55. http://dx.doi.org/10.1177/0003702816657567.
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The A-band of oxygen has been measured at low resolution at temperatures between 90 K and 373 K using the phase shift cavity ring down (PS-CRD) technique. For temperatures between 90 K and 295 K, the PS-CRD technique presented here involves an optical cavity attached to a cryostat. The static cell and mirrors of the optical cavity are all inside a vacuum chamber at the same temperature of the cryostat. The temperature of the cell can be changed between 77 K and 295 K. For temperatures above 295 K, a hollow glass cylindrical tube without windows has been inserted inside an optical cavity to measure the temperature of air flowing through the tube. The cavity consists of two highly reflective mirrors which are mounted parallel to each other and separated by a distance of 93 cm. In this experiment, air is passed through a heated tube. The temperature of the air flowing through the tube is determined by measuring the intensity of the oxygen absorption as a function of the wavenumber. The A-band of oxygen is measured between 298 K and 373 K, with several air flow rates. To obtain the temperature, the energy of the lower rotational state for seven selected rotational transitions is linearly fitted to a logarithmic function that contains the relative intensity of the rotational transition, the initial and final rotational quantum numbers, and the energy of the transition. Accuracy of the temperature measurement is determined by comparing the calculated temperature from the spectra with the temperature obtained from a calibrated thermocouple inserted at the center of the tube. This flowing air temperature sensor will be used to measure the temperatures of cooling air at the input (cold air) and output (hot air) after cooling the blades of a laboratory gas turbine. The results could contribute to improvements in turbine blade cooling design.
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Baranova, E. I., V. A. Pavlova, V. A. Ionin, et al. "Atrial fibrillation and CHA2DS2VASc score of 1 - is there a problem in clinical practice?" Russian Journal of Cardiology 25, no. 3 (2020): 3738. http://dx.doi.org/10.15829/1560-4071-2020-3-3738.
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Aim. To study the incidence of nonvalvular atrial fibrillation (AF) in patients with a CHA2DS2VASc score of 1 in actual clinical practice, to determine the major and minor risk factors of thromboembolism and the frequency of oral anticoagulant therapy in these patients.Material and methods. We performed a retrospective analysis of 6575 medical records of patients hospitalized for five years in a therapeutic inpatient unit. To determine the stroke risk, major and minor modifying factors were assessed.Results. Of 1160 patients with nonvalvular AF, 93 (8,0%) patients had a CHA2DS2VASc score of 1: hypertension (87,1%), heart failure (4,3%), vascular diseases (4,3%), diabetes (2,15%) and age 65-74 years (2,2%); minor modifying factors were as follows: left atrial (LA) dilatation (81,7%), obesity (40,9%), persistent/permanent AF (37,6%), proteinuria (26,9%), chronic kidney disease (3,2%). A combination of minor risk factors was observed in 61,3%, the most common of which were obesity, LA dilatation, persistent/permanent AF. Anticoagulants were prescribed to 72% of patients with a CHA2DS2VASc score of 1.Conclusion. In actual clinical practice, patients with nonvalvular AF with a CHA2DS2VASc score of 1 are often found. The most common risk factors for stroke in these patients are hypertension, persistent or permanent AF, LA dilatation, and obesity. The use of anticoagulant therapy in these patients does not contradict current guidelines. However, further prospective follow-up is necessary to determine the effectiveness and safety of this therapy.
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Kim, Ho Jun. "Enhancement of Cleanliness and Deposition Rate by Understanding the Multiple Roles of the Showerhead Electrode in a Capacitively Coupled Plasma Reactor." Coatings 11, no. 8 (2021): 999. http://dx.doi.org/10.3390/coatings11080999.
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Increasing the productivity of a showerhead-type capacitively coupled plasma (CCP) reactor requires an in-depth understanding of various physical phenomena related to the showerhead, which is not only responsible for gas distribution, but also acts as the electrode. Thus, we investigated how to enhance the cleanliness and deposition rate by studying the multiple roles of the showerhead electrode in a CCP reactor. We analyzed the gas transport in a three-dimensional complex geometry, and the SiH4/He discharges were simulated in a two-dimensional simplified geometry. The process volume was installed between the showerhead electrode (radio frequency powered) and the heater electrode (grounded). Our aim of research was to determine the extent to which the heated showerhead contributed to increasing the deposition rate and to reducing the size of the large particles generated during processing. The temperature of the showerhead was increased to experimentally measure the number of particles transported onto the heater to demonstrate the effects thereof on the decrease in contamination. The number of particles larger than 45 nm decreased by approximately 93% when the showerhead temperature increased from 373 to 553 K.
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Wang, Jia-long. "A prediction of solar activities in the later phase of solar cycle 22 and in solar cycle 23AApS 12/4 (1992) 369–373." Chinese Astronomy and Astrophysics 17, no. 1 (1993): 120. http://dx.doi.org/10.1016/0275-1062(93)90060-3.
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McKee, James. "Families of Pisot numbers with negative trace." Acta Arithmetica 93, no. 4 (2000): 373–85. http://dx.doi.org/10.4064/aa-93-4-373-385.
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Hammond, N. G. L. "Plataea's relations with Thebes, Sparta and Athens." Journal of Hellenic Studies 112 (November 1992): 143–50. http://dx.doi.org/10.2307/632158.
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Plataea was an ancient city of ‘Boiotoi’ (Iliad ii 494 and 504; cf. Thuc. iii 61.2). Throughout its chequered history the citizens were always described as ‘Boiotoi’ (e.g. Thuc. iii 54.3; Isoc. Panath. 93; [D.] lix 95; Arr. An. i 8.8; Paus. i 15.3). The citizens were ‘the Plataeans’, whether they were in possession of their city or not. They figured as Πλαταιες on the serpent column of 479/8 (M-L 27, 7), as Πλαταιῆς in the list of Athens' allies in 431 (Thuc. ii 9.4), and as Πλαταιῆς ψιλοί fighting alongside Athenians in 424 BC when their city was in enemy hands (Thuc. iv 67.2 and 5). Although the majority of the Plataeans lived as refugees in Attica between 428 and 382, and again from 373 to 338, they continued to be ‘Plataeans’ and were never described in our sources as Athenians. The ability of the Plataeans to survive as a refugee community was paralleled, for example, by the ability of the Aeginetan refugees between 431 and 405 and the Samian refugees between 366 and 322 (Diod. xviii 18.9) to survive and ultimately to reoccupy their homeland. It was as such a community that ‘the Plataeans’ were brought back ‘from Athens’ to their ruined city in 382 (Paus. ix 1.4.).
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Attorri, Silvia, Sherry Dunbar, and Jill E. Clarridge. "Assessment of Morphology for Rapid Presumptive Identification of Mycobacterium tuberculosis andMycobacterium kansasii." Journal of Clinical Microbiology 38, no. 4 (2000): 1426–29. http://dx.doi.org/10.1128/jcm.38.4.1426-1429.2000.
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Mycobacterium tuberculosis often exhibits serpentine cording when grown in liquid medium, whereas Mycobacterium kansasii can be larger and cross-barred. We assessed the use of these morphologic characteristics as a cost-effective method for rapid presumptive identification of isolates from BACTEC bottles. Without specific training, using the Kinyoun acid-fast stain, definitive cording was found in 237 of 373 specimens positive forM. tuberculosis (64%) and cross-barring was recognized within 63 of 76 (83%) of the specimens positive for M. kansasii, giving sensitivities specificities, positive predictive values, and negative predictive values of 63.5, 96, 92, and 79%, respectively, for M. tuberculosis and 83, 95, 59, and 98%, respectively, for M. kansasii. With training and experience, these results improved to 74.5, 98, 96, and 84% and 93, 98, 79, and 98%, respectively. The major improvements were in distinguishing the pseudocording, or loose aggregation ofMycobacterium avium complex from M. tuberculosis and the long beaded forms of Mycobacterium gordonae from M. kansasii. Mycobacterium asiaticum and Mycobacterium szulgai, which rarely occur, are genetically related to M. kansasiiand morphologically difficult to distinguish. In defined circumstances, serpentine cording and cross-barring can be used for rapid presumptive identification of M. tuberculosisand M. kansasii, respectively, and as guides for initial probe selection to reduce costs.
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Amrikachi, Mojghan, Ibrahim Ramzy, Sheldon Rubenfeld, and Thomas M. Wheeler. "Accuracy of Fine-Needle Aspiration of Thyroid." Archives of Pathology & Laboratory Medicine 125, no. 4 (2001): 484–88. http://dx.doi.org/10.5858/2001-125-0484-aofnao.
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Abstract Context.—Fine-needle aspiration has become an accepted and cost-effective procedure for rapid diagnosis of thyroid lesions. The routine use of fine-needle aspiration has reduced the rate of unnecessary surgery for thyroid nodules. Objectives.—To determine the accuracy of fine-needle aspiration biopsy diagnosis and to discuss the possible pitfalls. Design, Setting, and Participants.—Reports of 6226 fine-needle aspiration biopsies of the thyroid performed during a period of 16 years (1982–1998) were reviewed. Computerized reports of the fine-needle aspiration biopsies were sent to the physicians who performed the procedures, and clinical follow-up information regarding the patients was requested. Twenty-four clinicians participated in the study. Histologic diagnoses were available for 354 cases. The cytopathologic diagnoses were correlated with the histologic findings or clinical outcomes. Results.—The cytologic diagnoses were as follows: 210 (3.4%) malignant, 450 (7.2%) suspicious, 3731 (60%) benign, and 1845 (29.5%) unsatisfactory. Most of the cases with negative or unsatisfactory aspirates were followed clinically or by repeat fine-needle aspiration. We identified 11 false-negative and 7 false-positive diagnoses. For aspirates considered sufficient for diagnosis, the sensitivity and specificity levels were 93% and 96%, respectively. Conclusions.—Fine-needle aspiration of the thyroid gland is highly accurate and has a low rate of false-negative and false-positive diagnoses. The major diagnostic problems are caused by diagnosis using a marginally adequate specimen, diagnosis of malignancy based on just 1 or 2 atypical cytologic features, or overlapping cytologic features of follicular neoplasm with those of follicular variant of papillary carcinoma.
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Kumar Prof, L., R. Hariprasad, S. Kumar, et al. "Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery versus upfront surgery followed by chemotherapy (CT) in advanced epithelial ovarian carcinoma (EOC): A prospective randomized study—Interim results." Journal of Clinical Oncology 25, no. 18_suppl (2007): 5531. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.5531.
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5531 Background: To determine the impact of NACT on surgical debulking rate, overall and disease-free survival and quality of life (QOL) in patients with advanced EOC. Methods: Between Oct 2001 and Dec 2006, 128 previously untreated EOC patients (median age- 50 years, range 30 to 65) with FIGO stage III C & IV (pleural effusion only) have been randomized into - Arm A (n=65) upfront debulking Surgery followed by 6 cycles of Paclitaxel & carboplatin (PC) and Arm B (n=63): NACT with 3 cycles of PC followed by debulking Surgery then 3 more cycles. Eligibility criteria include - age 18 to 65 years, biopsy / cytological proven EOC, adequate hematological, renal, liver & cardiac functions, normal upper & lower GI endoscopy & CEA levels. Both groups were compared for debulking rate, duration of surgery, blood loss, intra & postoperative morbidity & mortality, overall response to treatment and QOL (FACT- O questionnaire). Results: 100 of 128 patients have completed treatment (arm A- 56, B-44). 7 patients were not evaluable; (Germ cell tumor-1, mixed Mullerian tumor-2, dual primary-1 and krukenburg-3). 93 patients are evaluable. Patients’ characteristics are similar in both arms. Grade III-IV - GIT (3% vs. 4%) & bone marrow (9% Vs 7%, p=ns) toxicity was similar in arm A & B, among 463 CT cycles administered. Patients in NACT arm had higher optimum debulking rate, p<. 0001, decreased blood loss during surgery (mean vol 520 vs 373 ml p<0.003) and reduced postoperative infections 14.8 % vs. 2.5%, p<0.04. Mean operative time (110 vs 95 minutes, p=0.12) and hospital stay (12 Vs 9.4 days, p=0.1) were similar in arm A & B. The median overall survival (arm A & B: 42 vs 29 months, p=0.07) and disease free survival (20 vs 25 months, p=0.11) is not different at a median follow up of 41 months. QOL score was significantly better in NACT arm at the end of treatment. (93 vs 114, p<. 001). Conclusions: Neoadjuvant chemotherapy in advanced epithelial ovarian cancer is associated with higher optimum debulking rate with reduced postoperative morbidity and improved quality of life. No significant financial relationships to disclose.
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Liu, Jason J., Elizabeth K. Cahoon, Martha S. Linet, et al. "Relationship between plasma 25-hydroxyvitamin D and leucocyte telomere length by sex and race in a US study." British Journal of Nutrition 116, no. 6 (2016): 953–60. http://dx.doi.org/10.1017/s0007114516002075.
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AbstractA few studies have examined the association between vitamin D and telomere length, and fewer still have examined the relationship in black or male populations. We investigated the cross-sectional association between the vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) concentration in plasma and relative leucocyte telomere length (LTL) in 1154 US radiologic technologists who were 48–93 years old (373 white females, 278 white males, 338 black females, 165 black males). Plasma 25(OH)D concentration was measured by the chemiluminescence immunoassay, and relative LTL was measured by quantitative PCR. Logistic regression was used to obtain OR and 95 % CI for long v. short (based on median) LTL in relation to continuous 25(OH)D, quartiles of 25(OH)D and 25(OH)D deficiency. We found no significant association between continuous 25(OH)D and long LTL in all participants (Ptrend=0·440), nor in white females (Ptrend=0·845), white males (Ptrend=0·636), black females (Ptrend=0·967) or black males (Ptrend=0·484). Vitamin D deficiency (defined as 25(OH)D<30 nmol/l), however, was significantly associated with short LTL in whites (P=0·024), but not in other groups. In this population, we found little evidence to support associations between 25(OH)D and long LTL over the entire range of 25(OH)D in the overall study population or by sex and race.
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Gañán-Calvo, Alfonso M., Henry N. Chapman, Michael Heymann, et al. "The Natural Breakup Length of a Steady Capillary Jet: Application to Serial Femtosecond Crystallography." Crystals 11, no. 8 (2021): 990. http://dx.doi.org/10.3390/cryst11080990.
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One of the most successful ways to introduce samples in Serial Femtosecond Crystallography has been the use of microscopic capillary liquid jets produced by gas flow focusing, whose length-to-diameter ratio and velocity are essential to fulfill the requirements of the high pulse rates of current XFELs. In this work, we demonstrate the validity of a classical scaling law with two universal constants to calculate that length as a function of the liquid properties and operating conditions. These constants are determined by fitting the scaling law to a large set of experimental and numerical measurements, including previously published data. Both the experimental and numerical jet lengths conform remarkably well to the proposed scaling law. We show that, while a capillary jet is a globally unstable system to linear perturbations above a critical length, its actual and shorter long-term average intact length is determined by the nonlinear perturbations coming from the jet breakup itself. Therefore, this length is determined solely by the properties of the liquid, the average velocity of the liquid and the flow rate expelled. This confirms the very early observations from Smith and Moss 1917, Proc R Soc Lond A Math Phys Eng, 93, 373, to McCarthy and Molloy 1974, Chem Eng J, 7, 1, among others, while it contrasts with the classical conception of temporal stability that attributes the natural breakup length to the jet birth conditions in the ejector or small interactions with the environment.
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Hankard, R. G., D. Darmaun, B. K. Sager, D. D'Amore, W. R. Parsons, and M. Haymond. "Response of glutamine metabolism to exogenous glutamine in humans." American Journal of Physiology-Endocrinology and Metabolism 269, no. 4 (1995): E663—E670. http://dx.doi.org/10.1152/ajpendo.1995.269.4.e663.
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To determine whether exogenous glutamine affects whole body glutamine metabolism, preliminary experiments were performed to verify that L-[1-13C]-, L-[U-14C]-, and L-[3,4-3H]glutamine given simultaneously by vein provided similar estimates of glutamine appearance rates [Ra; 355 +/- 24, 373 +/- 19, and 393 +/- 24 (SE) mumol.kg-1.h-1, respectively, P = NS] in six healthy men; glutamine oxidation accounted for 32 +/- 3 and 51 +/- 5% (P < 0.01) of glutamine Ra when it was measured using L-[U-14C]- and L-[1-13C]glutamine, respectively. Five subjects received two 5-h intravenous infusions of L-[3,4-3H]glutamine and a simultaneous nasogastric infusion of L-[1-13C]glutamine on 2 separate days in the postabsorptive state, along with saline on 1 day and natural L-glutamine (856 +/- 45 mumol.kg-1.h-1) on another day in a randomized order. Splanchnic glutamine extraction (determined from [13C]glutamine appearance into systemic blood) reached 74 +/- 4 and 53 +/- 5% during the enteral infusion of tracer alone and in combination with a large load of glutamine, respectively. Glutamine infusion was associated with increased plasma glutamine concentration (from 630 +/- 50 to 1,297 +/- 75 microM), Ra (from 258 +/- 20 to 589 +/- 45 mumol.kg-1.h-1), and oxidation (from 179 +/- 20 to 477 +/- 47 mumol.kg-1.h-1, all P < 0.01), no change in glutamine release from proteolysis, and a decline in glutamine de novo synthesis (from 156 +/- 15 to 93 +/- 13 mumol.kg-1.h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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Zhang, Shu, Yasutake Tomata, Kemmyo Sugiyama, Yumi Sugawara, and Ichiro Tsuji. "Citrus consumption and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study." British Journal of Nutrition 117, no. 8 (2017): 1174–80. http://dx.doi.org/10.1017/s000711451700109x.
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AbstractAlthough some experimental biological studies have indicated that citrus may have preventive effects against cognitive impairment, no cohort study has yet examined the relationship between citrus consumption and incident dementia. In a baseline survey, we collected data on daily citrus intake (categorised as ≤2, 3–4 times/week or almost every day) and consumption of other foods using a FFQ, and used a self-reported questionnaire to collect data on other covariates. Data on incident dementia were retrieved from the Japanese Long-term Care Insurance database. A multivariate-adjusted Cox model was used to estimate the hazard ratios (HR) and 95 % CI for incident dementia according to citrus consumption. Among 13 373 participants, the 5·7-year incidence of dementia was 8·6 %. In comparison with participants who consumed citrus ≤2 times/week, the multivariate-adjusted HR for incident dementia among those did so 3–4 times/week and almost every day was 0·92 (95 % CI 0·80, 1·07) and 0·86 (95 % CI 0·73, 1·01), respectively (Ptrend=0·065). The inverse association persisted after excluding participants whose dementia events had occurred in the first 2 years of follow-up. The multivariate HR was 1·00 (reference) for ≤2 times/week, 0·82 (95 % CI 0·69, 0·98) for 3–4 times/week and 0·77 (95 % CI 0·64, 0·93) for almost every day (Ptrend=0·006). The present findings suggest that frequent citrus consumption was associated with a lower risk of incident dementia, even after adjustment for possible confounding factors.
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McCann, Mark J., Kunjana Rotjanapun, John E. Hesketh, and Nicole C. Roy. "Expression profiling indicating low selenium-sensitive microRNA levels linked to cell cycle and cell stress response pathways in the CaCo-2 cell line." British Journal of Nutrition 117, no. 9 (2017): 1212–21. http://dx.doi.org/10.1017/s0007114517001143.
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AbstractSe is an essential micronutrient for human health, and fluctuations in Se levels and the potential cellular dysfunction associated with it may increase the risk for disease. Although Se has been shown to influence several biological pathways important in health, little is known about the effect of Se on the expression of microRNA (miRNA) molecules regulating these pathways. To explore the potential role of Se-sensitive miRNA in regulating pathways linked with colon cancer, we profiled the expression of 800 miRNA in the CaCo-2 human adenocarcinoma cell line in response to a low-Se (72 h at <40 nm) environment using nCounter direct quantification. These data were then examined using a range ofin silicodatabases to identify experimentally validated miRNA–mRNA interactions and the biological pathways involved. We identified ten Se-sensitive miRNA (hsa-miR-93-5p, hsa-miR-106a-5p, hsa-miR-205-5p, hsa-miR-200c-3p, hsa-miR-99b-5p, hsa-miR-302d-3p, hsa-miR-373-3p, hsa-miR-483-3p, hsa-miR-512-5p and hsa-miR-4454), which regulate 3588 mRNA in key pathways such as the cell cycle, the cellular response to stress, and the canonical Wnt/β-catenin, p53 and ERK/MAPK signalling pathways. Our data show that the effects of low Se on biological pathways may, in part, be due to these ten Se-sensitive miRNA. Dysregulation of the cell cycle and of the stress response pathways due to low Se may influence key genes involved in carcinogenesis.
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Vahdat, Vahab, Jacqueline A. Griffin, James E. Stahl, and F. Clarissa Yang. "Analysis of the effects of EHR implementation on timeliness of care in a dermatology clinic: a simulation study." Journal of the American Medical Informatics Association 25, no. 7 (2018): 827–32. http://dx.doi.org/10.1093/jamia/ocy024.
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Abstract Objective Quantify the downstream impact on patient wait times and overall length of stay due to small increases in encounter times caused by the implementation of a new electronic health record (EHR) system. Methods A discrete-event simulation model was created to examine the effects of increasing the provider-patient encounter time by 1, 2, 5, or 10 min, due to an increase in in-room documentation as part of an EHR implementation. Simulation parameters were constructed from an analysis of 52 000 visits from a scheduling database and direct observation of 93 randomly selected patients to collect all the steps involved in an outpatient dermatology patient care visit. Results Analysis of the simulation results demonstrates that for a clinic session with an average booking appointment length of 15 min, the addition of 1, 2, 5, and 10 min for in-room physician documentation with an EHR system would result in a 5.2 (22%), 9.8 (41%), 31.8 (136%), and 87.2 (373%) minute increase in average patient wait time, and a 6.2 (12%), 11.7 (23%), 36.7 (73%), and 96.9 (193%) minute increase in length of stay, respectively. To offset the additional 1, 2, 5, or 10 min, patient volume would need to decrease by 10%, 20%, 40%, and &gt;50%, respectively. Conclusions Small changes to processes, such as the addition of a few minutes of extra documentation time in the exam room, can cause significant delays in the timeliness of patient care. Simulation models can assist in quantifying the downstream effects and help analyze the impact of these operational changes.
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Wu, Jintao, Guijun Yang, Xiaodong Yang, Bo Xu, Liang Han, and Yaohui Zhu. "Automatic Counting of in situ Rice Seedlings from UAV Images Based on a Deep Fully Convolutional Neural Network." Remote Sensing 11, no. 6 (2019): 691. http://dx.doi.org/10.3390/rs11060691.
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The number of rice seedlings in the field is one of the main agronomic components for determining rice yield. This counting task, however, is still mainly performed using human vision rather than computer vision and is thus cumbersome and time-consuming. A fast and accurate alternative method of acquiring such data may contribute to monitoring the efficiency of crop management practices, to earlier estimations of rice yield, and as a phenotyping trait in breeding programs. In this paper, we propose an efficient method that uses computer vision to accurately count rice seedlings in a digital image. First, an unmanned aerial vehicle (UAV) equipped with red-green-blue (RGB) cameras was used to acquire field images at the seedling stage. Next, we use a regression network (Basic Network) inspired by a deep fully convolutional neural network to regress the density map and estimate the number of rice seedlings for a given UAV image. Finally, an improved version of the Basic Network, the Combined Network, is also proposed to further improve counting accuracy. To explore the efficacy of the proposed method, a novel rice seedling counting (RSC) dataset was built, which consisted of 40 images (where the number of seedlings varied between 3732 and 16,173) and corresponding manually-dotted annotations. The results demonstrated high average accuracy (higher than 93%) between counts according to the proposed method and manual (UAV image-based) rice seedling counts, and very good performance, with a high coefficient of determination (R2) (around 0.94). In conclusion, the results indicate that the proposed method is an efficient alternative for large-scale counting of rice seedlings, and offers a new opportunity for yield estimation. The RSC dataset and source code are available online.
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Smirnov, V. A. "Online community of Russian volunteers (on the example of social network vkontakte)." Moscow State University Bulletin. Series 18. Sociology and Political Science 25, no. 3 (2019): 71–93. http://dx.doi.org/10.24290/1029-3736-2019-25-3-71-93.
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The article analyzes the features of the current stage of development of volunteerism in the Russian Federation. As the information base of the research data from online communities of the social network vkontakte are used. The total number of analyzed groups is 2894, the number of participants is 1446008 people. To extract data about online communities and participants, a script was written in the programming language Python3, which allowed to gather relevant information using the vkontakte API.Based on the analysis, the author’s typology of volunteer communities is proposed in the article, including franchise groups, online service communities and direct action groups. The author analyzes the distribution of communities on the subject of their activities. The dominant positions in terms of the number of participants and the number of groups are occupied by communities based on the search for missing people. The least represented in the space of the social network vkontakte community of volunteers — animal advocates.Based on the socio-demographic analysis of community members, the author draws conclusions about the features of their distribution in terms of age and sex. In particular, young people between the ages of 14 and 30 take the dominant position among group members. This is largely due to the underdevelopment of the mechanisms for including middle-aged and older people in volunteer activities. As for the gender of the participants, the main contingent of the communities are women, while their relationship with men changes with age.The article presents an analysis of the participants’ value orientations. Conclusions are drawn about the domination of individual values and interests, which are based on the desire for self-development and personal growth. On the basis of this, a conclusion is drawn on the need to develop new social technologies for involving Russian citizens in the volunteer activity.The article explores some dysfunctions in the development of volunteerism in the Russian Federation: the lack of mechanisms for involving middle-aged and older citizens, the imitative nature of many volunteer projects. Based on this, conclusions are drawn about the need to adjust the social, educational, youth policy in the field of volunteer development in Russia.
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Kolodeznikova, Inna V., Roman V. Kondurov, and Diana V. Galitskayа. "SOCIAL INSURANCE SYSTEMS IN RUSSIA AND GERMANY: SOCIOLOGICAL ANALYSIS." Moscow State University Bulletin. Series 18. Sociology and Political Science 25, no. 2 (2019): 93–115. http://dx.doi.org/10.24290/1029-3736-2019-25-2-93-115.
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Social insurance occupies a special place in the entire social policy of the state. Developed system of social insurance in the country provides citizens with effective protection mechanisms and thereby ensures economic stability and creates an atmosphere of social cohesion in society. At present, social insurance systems in Russia and Germany have significant differences that include both the structure and functioning of each type of insurance separately. These differences in the organization of social insurance systems in Russia and Germany are traceable from the very beginning. System of social insurance in modern Russia has been developing to a certain extent inconsistently and to the present time still is not completely formed. The German system developed gradually and improved with regard to the features of the interests of society at various stages of its development. The establishment of the Federal Republic of Germany as a social state determined the modern model of the social insurance system. Therefore, the study of the German model is interesting from the point of view of the subsequent possible introduction of its elements into Russian insurance practice. The article compares social insurance systems of Russia and Germany. The components of the systems are studied; their similarities and differences are revealed. Opinions of experts of the Federal Service for Labor and Employment on the prospects and problems of the development of the Russian model of the social insurance system and the possibility of using the German insurance experience in Russian practice are given.
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Lui, G., E. Noss, N. Singh, J. Andrews, J. Graf, and K. Wysham. "POS0459 UNSUPERVISED CLUSTERING IDENTIFIES UNIQUE SUBSETS OF PATIENTS IN A RACIALLY AND ETHNICALLY DIVERSE RHEUMATOID ARTHRITIS COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (2021): 460.2–461. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1946.
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Background:Single biomarkers have limited utility to date in guiding RA clinical care. Machine learning algorithms may better identify and stratify RA patients with differential outcomes.Objectives:To determine if unsupervised machine learning methods can be employed in a racially and ethnically diverse RA cohort to identify clusters of patients with different disease activity trajectories, as measured by DAS28ESR.Methods:Data are derived from the longitudinal, observational University of California, San Francisco RA Cohort. Along with routine labs, medications and disease activity assessments, a multiple biomarker of disease activity (MBDA) panel was obtained at each visit. The MBDA measures 12 serum biomarkers. Four patient clusters were identified by unsupervised K-prototype clustering after collapsing all observations into a cross sectional dataset. Plots were created to display longitudinal disease activity trajectories for each cluster. Lasso regression was applied to identify biomarkers associated with DAS28ESR.Results:We identified 4 distinct clusters in our cohort (Table 1) with visually different disease activity trajectories (Fig. 1). Cluster 1 (n=116) was older (63.6±9.7), had the highest proportion of Asian participants (n=73, 63%) with the most study visits and longest disease duration. Cluster 2 (n=70) had the highest mean DAS28ESR (5.5±0.7), and the highest mean dose of prednisone (8.6±4.9 mg/day). Cluster 3 had the lowest number of participants (n=14), study visits and lowest biologic use (28.6%). Cluster 4 was the largest cluster (n=173) with the shortest disease duration (4.9±3.8 years) and highest biologic use (61.3%). In the Lasso regressions, leptin was found to have significant positive associations with DAS28ESR in the whole group as well as Clusters 2 and 4. EGF had negative associations with DAS28ESR in the whole group, Cluster 1 and 4. CRP had positive associations with DAS28ESR in the whole group and Cluster 1. YKL40 and VCAM1 were found to have significant associations in Clusters 1 and 3, respectively.Conclusion:We identified 4 unique clusters of RA patients in a racially and ethnically diverse longitudinal cohort with different disease activity trajectories and biomarkers associated with disease activity. Although additional work is needed to explore longitudinal outcomes in each cluster, the application of machine learning methods may identify unique combinations of patient and disease characteristics influencing RA clinical outcomes.Table 1.Demographics and clinical characteristics of the RA cohort. Biomarkers significantly associated with DAS28ESR were determined by Lasso regression Values listed are per standard deviation of each biomarker.Overall(N=373)Cluster 1 (N=116)Cluster 2 (N=70)Cluster 3 (N=14)Cluster 4 (N=173)Demographics:Age54.8 ± 3.663.6 ± 9.750.8 ± 14.958.2 ± 15.850.3 ± 12.1Female Sex318 (85%)101 (87%)57 (81%)11 (79%)149 (86%)Race: Hispanic/Latino181 (49%)22 (19%)47 (67%)5 (36%)107 (62%) Asian123 (33%)73 (63%)8 (11%)6 (43%)36 (21%) Black35 (9%)12 (10%)8 (11%)2 (14%)13 (8%) White & Other34 (9%)9 (7%)7 (10%)1 (7%)17 (10%)Clinical Characteristics:Rheumatoid Factor315 (85%)104 (90%)56 (80%)13 (93%)142 (82%)ACPA297 (80%)98 (85%)54 (77%)12 (86%)133 (77%)Disease Duration7.8 ± 7.613.7 ± 9.75.4 ± 4.66.7 ± 5.74.9 ± 3.8csDMARD344 (92%)108 (93%)63 (90%)13 (93%)160 (93%)Biologic DMARD185 (50%)45 (39%)30 (43%)4 (29%)106 (61%)Prednisone Dose6.7 ± 3.86.0 ± 4.08.6 ± 4.95.8 ± 1.46.3 ± 2.8Body Mass Index28.2 ± 4.526.6 ± 3.828.7 ± 3.828.0 ± 6.229.1 ± 4.7DAS28ESR4.2 ± 1.14.2 ± 1.05.5 ± 0.83.9 ± 0.83.7 ± 0.9Lasso Results:EGF-0.16*-0.41***-----0.20**Leptin0.15**--0.21*--0.21**c-reactive protein0.34**0.51***------VCAM1-------0.73*--YKL40--0.26*-------EGF: epidermal growth factor; VCAM1: Vascular cell adhesion protein 1; YKL40: Chitinase-3-like protein 1.-*p<0.05, **p<0.01, ***p<0.001Figure 1.DAS28ESR trajectory plots with 95%CIs for the whole cohort and by cluster.Acknowledgements:This work was supported by the Rheumatology Research Foundation Scientist Development Award.Disclosure of Interests:None declared
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Liu, Chia-Jen, Kuo-Wei Chen, Yu-Wen Hu, et al. "Chronic Iron Deficiency Anemia and Cancer Risk." Blood 120, no. 21 (2012): 5172. http://dx.doi.org/10.1182/blood.v120.21.5172.5172.
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Abstract Abstract 5172 Background Iron deficiency anemia (IDA) is a common initial manifestation of gastrointestinal malignancies, but the relationship between chronic IDA and further cancer development is not established. Aims We would like to investigate the cancer risk of chronic IDA over a 10-year period in Taiwan. Methods We enrolled patients with iron deficiency anemia from a nationwide health registry in Taiwan during the period 2000–2009. All patients received at least 2 related examinations and were treated with iron supplement. Since IDA is an initial manifestation of many underlying malignancies, we excluded patients whose cancer developed within 1 year after IDA diagnosis. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of chronic IDA patients to general population. The specific types of cancer were addressed. Results A total of 4, 373 patient with IDA were identified, and 132 (3. 02%) IDA patients developed cancer 1 year after enrollment (SIR 1. 52; 95% confidence interval [CI] 1. 27 – 1. 80, p < 0. 001). The risks of kidney (SIR 5. 47, 95% CI 2. 73 – 9. 78), bladder (SIR 3. 6, 95% CI 1. 64 – 6. 83), liver (SIR 2. 80, 95% CI 1. 82 – 4. 13), and colorectal malignancies (SIR 1. 93, 95% CI 1. 22 – 2. 90) elevated. The risk of hematological malignancies were not increased in current study (SIR 1. 13, 95% CI 0. 31 – 2. 89, p = 0. 758). Conclusions After exclusion of cancer development within the first year, IDA patients still had increased risk of cancer, especially kidney, bladder, liver, and colorectal malignancies. Disclosures: No relevant conflicts of interest to declare.
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Alexander, Swetha Ann, Vinay Mathew Thomas, David Wu, Radhika Kulkarni, and William Rabitaille. "Prevalence of advance care planning in a resident run clinic in an underserved community." Journal of Clinical Oncology 39, no. 15_suppl (2021): e24067-e24067. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e24067.
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e24067 Background: Advance Care Planning (ACP) ensures that patients receive care that is in line with their values and preferences. ACP is best done in the outpatient setting. Despite recognizing the importance of ACP, the rates of ACP completion continue to be low. We conducted a retrospective study to determine the rates of ACP in a resident run primary care clinic in Hartford, Connecticut, which serves the underserved community. We looked at patient characteristics to find correlation with ACP completion. We also aimed to determine the reasons which could decrease the completion of ACP. Methods: This was a retrospective chart review. Patients who met any of the inclusion criteria [i) Age>65 ii) End stage renal disease on dialysis iii) Metastatic/Recurrent cancer iv) End stage heart failure v) COPD Gold stage D] and were seen in the primary care clinic from September 1, 2019 to December 31, 2019 were selected. Their charts were reviewed to see if ACP was documented during primary care visits over the past two years. The demographics of the patients were noted. Subsequently, a survey was distributed to residents to determine the possible causes of low rates of ACP discussion. Results: The characteristics of the 373 patients included in the study are shown in Table 1. Only 14 (3.8%) of the 373 had documentation of ACP during their primary care visits. The characteristics of the 14 patients in whom ACP was done are as follows: Sex- Female 9/14 (64%); Ethnicity- Hispanic 10/14 (71%), African American 4/14 (29%); Religious Affiliation- Christian 13/14 (93%), None 1/14 (7%); Married/Partner 2/14 (14%). Patient demographics including sex (p 0.6), religious beliefs (p 0.8), and marital status (p 0.6) did not show any correlation with the likelihood of ACP completion. Of the 31 residents who answered the survey, the most commonly listed barriers to ACP completion were the following: lack of time to conduct these discussions (94%), forgetting to conduct ACP discussions (48%), and lack of training (19%). All the residents believed that ACP discussion was beneficial to patients and medical providers. Conclusions: The rates of ACP planning in our clinic are much lower than the national average. African American and Hispanics, who make up the majority of our clinic population, traditionally have had low rates of ACP completion. This is an important issue that needs to be addressed. Advance care planning training should be also be strengthened during residency. [Table: see text]
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Schaefer, M., M. Schneider, A. Graessler, W. Ochs, A. Zink, and A. Strangfeld. "OP0012 TNF INHIBITORS ARE ASSOCIATED WITH A REDUCED RISK OF VENOUS THROMBOEMBOLISM COMPARED TO CSDMARDS IN RA PATIENTS." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 8.2–9. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1505.
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Background:While the short-term use of bDMARDs up to 180 days has been associated with an increased risk of venous thromboembolism (VTE) compared to csDMARDs in patients with rheumatoid arthritis (RA), the long term use of more than 730 days has been associated with a decreased risk based on claims data [1]. Among patients with inflammatory bowel disease, observational data indicated that TNF inhibitors may have a protective effect regarding the VTE risk [2].Objectives:To assess the effects of TNF inhibitors and newer bDMARDs (including abatacept, rituximab, sarilumab, and tocilizumab) on the VTE risk based on observational data from RA patients.Methods:The German register RABBIT is a prospective longitudinally followed cohort of RA patients enrolled with a new start of a DMARD after at least one csDMARD failure. This analysis comprises patients who were enrolled with start of a bDMARD between 01/2009 and 04/2019 and had at least one follow-up.Cox regression models were used to calculate hazard ratios (HRs) for VTEs, for csDMARDs, TNF inhibitors and other bDMARDs. Propensity score weighting was used to adjust for confounding by indication.Results:Patients receiving TNF inhibitors or other bDMARDs on average had higher CRP levels and a higher prevalence of cardiovascular diseases at baseline than patients receiving csDMARDs. They also received more often glucocorticoids (Table 1).The HR of patients receiving TNF inhibitors for a serious VTE event was 0.53 (95% CI: 0.33 – 0.86) compared to csDMARDs, while the HR for patients receiving other bDMARDs was 0.66 (95% CI: 0.40 – 1.09). A CRP level of more than 5 mg/L (HR 2.09, 95% CI: 1.39 – 3.14) and an age above 65 years (HR 2.96, 95% CI: 1.94 – 4.52) increased the risk for a serious VTE event. Better physical function was associated with a decreased risk for VTEs (Table 2).Table 1.Patient characteristics at baseline for DMARD groupsParameter (at time of event/end of observation unless specified otherwise)Hazard ratio95% confidence intervalTNF inhibitors (reference: csDMARDs)0.530.330.86Other bDMARDs (reference: csDMARDs)0.660.401.09Age ≥ 65 years (baseline)2.961.944.52CRP ≥ 5 ml2.091.393.14> 5 mg and ≤ 10 mg glucocorticoids/day1.040.551.98> 10 mg and ≤ 15 mg glucocorticoids/day2.350.816.79> 15 mg glucocorticoids/day2.030.765.41% of full physical capacity (per 10 percentage points increase, time of event)0.850.780.92Current smoking (baseline)0.980.611.55Former smoking (baseline)0.800.451.43Table 2.Hazard ratios for VTE eventsParametercsDMARDsTNFiOther bDMARDsN350050602534VTE event38 (1.1)55 (1.1)23 (0.9)Age [years]58.8 (12.6)56.5 (12.9)58.1 (12.4)Female sex2575 (73.6)3734 (73.8)1933 (76.3)Disease duration [years]6.2 (7.2)9.4 (8.6)11.9 (9.2)Seropositivity2189 (62.6)3739 (73.9)2048 (80.8)Joint erosions1024 (31.0)2566 (52.4)1523 (63.3)Prior bDMARD therapies0 (0.2)0.3 (0.6)1.2 (1.2)CRP8.8 (8.1)11.6 (10.6)12.4 (11.8)DAS28-ESR4.4 (1.3)4.9 (1.2)5.1 (1.3)% of full physical capacity71.3 (21.8)66.2 (22.6)62.1 (23.5)Current glucocorticoid therapy2564 (73.3)3951 (78.1)2036 (80.4)Heart failure36 (1)113 (2.2)93 (3.7)Coronary artery disease196 (5.6)326 (6.4)183 (7.2)Cerebrovascular disease60 (1.7)86 (1.7)44 (1.7)Osteoporosis400 (11.4)771 (15.2)530 (20.9)Ever smoker1875 (53.6)2738 (54.1)1402 (55.3)Results are presented as mean ± SD or number (percentage).Conclusion:Treatment with TNF inhibitors (compared to csDMARDs) and better physical function significantly reduced the risk of serious VTE events, while age above 65 years and high CRP levels increased this risk.References:[1]Kim S. C. et al. Am. J. Med. 2015; 128(5): 539.e7–539.e17.[2]Desaj R.J. et al. CMAJ 2017; 189:E1438-47.Acknowledgments:RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, and UCB.Disclosure of Interests:Martin Schaefer: None declared, Matthias Schneider Grant/research support from: GSK, UCB, Abbvie, Consultant of: Abbvie, Alexion, Astra Zeneca, BMS, Boehringer Ingelheim, Gilead, Lilly, Sanofi, UCB, Speakers bureau: Abbvie, Astra Zeneca, BMS, Chugai, GSK, Lilly, Pfizer, Sanofi, Anett Graessler: None declared, Wolfgang Ochs: None declared, Angela Zink Speakers bureau: AbbVie, Amgen, BMS, Gilead, Hexal, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi Aventis, UCB, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis
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Noone, Imelda, Mary Kate Meagher, Naomi Davey, Diarmuid O'Shea, and Tim Cassidy. "86 Haemorrhagic Stroke: What's in a Bleed?" Age and Ageing 48, Supplement_3 (2019): iii17—iii65. http://dx.doi.org/10.1093/ageing/afz103.48.
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Abstract Background Intracerebral haemorrhage (ICH) accounts for approximately 20% of all strokes and is a leading cause of disability and mortality. The distribution of the ICH(Lobar v Deep) may be explained by the two major aetiologies of ICH, Cerebral Amyloid Angiopathy (CAA) versus hypertensive (HBP) respectively. The aim of our study was to look at outcomes of lobar versus deep ICH stroke patients. Methods We analyzed data of all ICH’s admitted in 2018 using SPSS. Demography, classification of haemorrhage, hypertension, atrial fibrillation (AF) and anticoagulation history, pre and post stroke Rankin and subsequent outcome were analyzed. Results 373 acute strokes were admitted of which 66(18%) were ICH. Mean age was 73yrs (52-93) and 50% were male. On neuroradiology imaging, 40(60%) were lobar and 26(39%) were deep. Lobar haemorrhages were significantly more likely to be older (p = 0.0001) however, there was no significant difference in pre-stroke Rankin. Post stroke the lobar haemorrhages had both a worse outcome from disability (p = 0.005) and mortality (p = 0.0001). 17(26%) patients with a ICH also had AF with 94% were on an oral anticoagulant(OAC).17.5% of the lobar bleeds were on an OAC versus 36% of the deep ICH. Of the lobar bleeds on OAC none died versus 4 of the deep ICH (p = .001). In total, 48(72%) of patients had a history of hypertension, but only 34(51%) were on HBP medication on admission. Conclusion There were a greater proportion of patients with lobar versus deep bleeds in our cohort which may be due to the older population in our area. Mortality and disability was far greater in the lobar cohort. None of the lobar bleeds with AF who were on OAC died in contrast to the deep ICH patients. This may suggest that more aggressive hypertensive treatment is required in this subpopulation.
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Ammori, John Brian, Nancy E. Kemeny, Andrea Cercek, et al. "Conversion to complete surgical treatment using hepatic artery infusional chemotherapy in patients with unresectable liver metastases from colorectal cancer." Journal of Clinical Oncology 30, no. 4_suppl (2012): 472. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.472.
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472 Background: Hepatic artery infusional (HAI) chemotherapy effectively treats colorectal liver metastases (CRLM). This study analyzes the combination of HAI and systemic chemotherapy for treating unresectable CRLM, focusing on the conversion to complete resection and/or ablation (R/A) and long term outcomes. Methods: All patients with initially unresectable CRLM treated with HAI and systemic chemotherapy from 2000-2009 were included. Patients who responded sufficiently to undergo complete R/A were compared to those who did not convert. Results: 373 patients were included. 296 (79 %) were previously treated and 77 (21 %) were chemo naïve. 115 (31 %) were on protocol and 258 (69 %) were not on protocol. 93 patients (25%) subsequently underwent complete R/A (conversion group). Of the 115 protocol patients, 47 (41 %) underwent complete R/A. The percentage of patients submitted to complete R/A increased from 16% during 2000-2003 to 30% during 2004-2009. 43% of patients who were chemotherapy-naïve prior to HAI therapy eventually underwent complete R/A, compared to 15% who were initially treated with systemic therapy (p<0.001). Factors associated with conversion on multivariate analysis were more recent treatment (2004-2009), no prior chemotherapy, and a clinical risk score < 3. Overall survival was greater in the conversion group, with a median and predicted 5-year survival from the time of HAI pump placement of 54 months and 49%, compared to 19 months and 6%, respectively (p<0.001). Conclusions: One-quarter of patients with unresectable CRLM responded sufficiently to undergo complete R/A following HAI plus systemic chemotherapy. Conversion was more likely in patients who were chemotherapy-naïve (43 %), had a clinical risk score < 3, and were treated in the more recent era. Survival in the conversion group was significantly better.
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Hünerberg, M., S. M. McGinn, K. A. Beauchemin, E. K. Okine, O. M. Harstad, and T. A. McAllister. "Effect of dried distillers’ grains with solubles on enteric methane emissions and nitrogen excretion from finishing beef cattle." Canadian Journal of Animal Science 93, no. 3 (2013): 373–85. http://dx.doi.org/10.4141/cjas2012-151.
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Hünerberg, M., McGinn, S. M., Beauchemin, K. A., Okine, E. K., Harstad, O. M. and McAllister, T. A. 2013. Effect of dried distillers’ grains with solubles on enteric methane emissions and nitrogen excretion from finishing beef cattle. Can. J. Anim. Sci. 93: 373–385. The objective of this study was to examine the impact of corn- or wheat-based dried distillers’ grains with solubles (CDDGS, WDDGS) on enteric methane (CH4) emissions from finishing beef cattle, and to determine if any observed reductions were a result of the fat content of CDDGS. A second objective was to compare the effect of CDDGS or WDDGS on N excretion. The experiment was designed as replicated 4×4 Latin square with 28-d periods using 16 ruminally fistulated crossbred heifers. The control diet contained 87% barley grain, 8% barley silage and 5% supplement (dry matter; DM basis). Treatment diets were formulated by replacing 40% DM of barley grain with CDDGS, WDDGS, or corn oil supplemented WDDGS (WDDGS+oil). For the WDDGS+oil diet 6.5% corn oil was added to WDDGS (3.4% fat DM) to achieve a similar fat level as in CDDGS (9.7% DM). All diets were fed as total mixed rations once daily ad libitum. Total collection of urine and faeces was conducted between days 18 and 21. Methane was measured between days 25 and 28 using four identical open circuit respiratory chambers. Compared with WDDGS, feeding CDDGS and WDDGS+oil reduced (P<0.05) CH4emissions as a percentage of gross energy intake (GEI) from 5.5 to 4.0 and 4.2%, respectively. Feeding CDDGS also reduced (P<0.05) CH4emissions compared with the control (5.0% of GEI), while WDDGS+oil tended (P=0.08) to elicit a similar response. Methane (% of GEI) between WDDGS and the control did not differ (P=0.29). Excretion of total N was greater (P<0.001) for CDDGS, WDDGS and WDDGS+oil (220, 253, and 265 g d−1) compared with the control (143 g d−1). Although oil appears to be responsible for reducing CH4emissions when DDGS is included in the diet, increased N excretion requires that a complete life cycle assessment be conducted to assess the full impact of DDGS on greenhouse gas emissions from finishing cattle.
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Rahman, Habibur. "Review: Breeding spring canola (Brassica napusL.) by the use of exotic germplasm." Canadian Journal of Plant Science 93, no. 3 (2013): 363–73. http://dx.doi.org/10.4141/cjps2012-074.
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Rahman, H. 2013. Review: Breeding spring canola ( Brassica napus L.) by the use of exotic germplasm. Can. J. Plant Sci. 93: 363–373. The need of broadening genetic diversity in spring canola (Brassica napus) breeding programs seems to be the general consensus among canola breeders and researchers. Diversity analysis by the use of molecular markers has identified several B. napus gene pools as well as allied Brassica species that are genetically distinct from spring canola B. napus; and these gene pools can be used for the improvement of this crop. Use of genetically diverse and un-adapted B. napus germplasm in the breeding of spring canola can be challenging, as introduction of several unwanted traits/alleles from exotic germplasm into spring canola occurs, and this would require repeated cycles of breeding for improvement. Similarly, use of allied species can be even more challenging due to the difficulties associated with interspecific hybrid production, sterility of hybrids, linkage drag, and the introduction of unwanted alleles. However, this can be compensated in the long-term perspective for the improvement of this crop. Some research efforts have been made in recent years to broaden allelic diversity in spring canola for the improvement of seed yield and other traits in open-pollinated and hybrid cultivars with promising results. Seed yield is a complex trait which is controlled by several gene loci with multiple alleles at these loci as well as interactions between loci and different alleles. This makes the identification of right allelic combinations an extremely challenging task. However, canola breeders have been able to make steady improvements in this crop in past decades based on the amount of allelic diversity present in existing breeding material. Introduction of favourable new alleles in breeding programs would allow breeders to create superior allelic combinations, enhancing the diversity in current breeding materials to further improve the crop. With the availability of the Brassica genome sequence, knowledge of sequence variation in specific genes and cost-effective high-throughput genotyping, it is expected that molecular plant breeding will play an important role in the breeding of canola cultivars. Discovery of favourable allele combinations in a short span of time is likely to be facilitated through the application of modern breeding tools.
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Mohyuddin, Ghulam Rehman, Shaun DeJarnette, Clint Divine, et al. "Outcomes of Autologous Stem Cell Transplantation for Lymphoma in the Elderly: A Single Center Experience." Blood 126, no. 23 (2015): 5505. http://dx.doi.org/10.1182/blood.v126.23.5505.5505.
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Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is a potentially curative option for lymphoma, yet there remains a bias against offering this therapy to the elderly. Patients above age 65 are nearly always excluded from clinical trials with ASCT, limiting our understanding of the efficacy and toxicities of ASCT in this population. This lack of data and bias against ASCT in the elderly may delay referral for patients who may benefit from a transplant. Here, we report our single institution outcomes from all patients aged 65 and greater who underwent autologous stem cell transplant for lymphoma at our institution. DESIGN AND METHODS : We identified 93 consecutive patients ³ 65 years of age (median age 68.6 years) with lymphoma who underwent autologous stem cell transplantation at University of Kansas Medical Center from 2000 to 2015. After IRB approval, data was extracted using the institutional database. These patients had frequently received at least two treatments, were often beyond first complete remission at the time of transplantation and received their transplants later after diagnosis. Table 1 below summarizes the pre-transplant characteristics of our patients. RESULTS: All patients received G-CSF mobilized peripheral blood stem cells. Engraftment data is available for 87 out of 93 patients. Median number of days to neutrophil recovery (Absolute neutrophil count >500) was 11 (range 9-14). Median number of RBC and platelet transfusion in this group was 2 (range 0-10) and 3 (range 0-39), respectively. Non-relapse mortality at 100 days for the entire group was 2.15%. Overall survival at 100-days was 96.8%. Three patients (3.2 %) developed grade IV pulmonary toxicity and one patient developed grade IV veno-occlusive disease. With a median follow up of 744 days (41-2431), a disease free survival of 373 days was noted. In 63 patients who underwent transplant prior to 2013, 1-year and 2-year overall survival was found to be 84.2% and 72.1 respectively. Of the deaths in first year, 6 (55%) were related to relapse/progression, two (18%) due to pulmonary toxicity, 2 (18%) due to cardiac toxicity and 1 (9%) due to infection. In 17 patients (18.2%), transplant was performed completely/partially as an outpatient procedure. CONCLUSIONS: Although retrospective in nature, these results suggest that transplant related mortality in elderly patients with lymphoma is similar to historic younger cohorts. Chronological age should not be used alone in evaluating lymphoma patients for autologous stem cell transplantation. Instead, a comprehensive evaluation using Hematopoietic cell transplant comorbidity index and geriatric assessment should be used to guide decision-making. As the elderly population grows, an individualized approach to each patient considering all available treatment options is needed to make a potentially curative ASCT for high risk or relapsed lymphoma available to more patients. Table 1. No of patients (%) GenderMale Female 60 (65) 33 (35) Age at ASCT, median (range) 68.6 ( range 65-80) Hodgkin Disease Non Hodgkin Disease 5 (5) 88 (95) NHL subtypes Diffuse Large B- Cell Lymphoma Mantle Follicular Other 35 (40) 18 (20) 16 (18) 19 (22) Disease Status at ASCTCR1 CR 2 or more CRU PR Relapse1 Relapse 2 or more Primary Refractory 29 (31.2) 29 (31.2) 6 (6.5) 19 (20.4) 5 (5.4) 2 (2.2) 3 (3.2) Response to most recent chemoComplete remission Partial remission Progressive disease 64 (68.9) 19 (20.4) 10 (10.8) HCT-CI (% from those with obtained data) 0 1-2 3 or more N/A 15(19.0) 23(29.1) 41(51.9) 14 Disclosures No relevant conflicts of interest to declare.
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Dzogbenuku, Robert Kwame, George Kofi Amoako, and Desmond K. Kumi. "Social media and student performance: the moderating role of ICT knowledge." Journal of Information, Communication and Ethics in Society 18, no. 2 (2019): 197–219. http://dx.doi.org/10.1108/jices-08-2019-0092.
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Purpose This study aims to determine the impact of social media usage on university student’s academic performance in Ghana. Design/methodology/approach A quantitative research method was used for the study. With the aid of a simple random sampling technique, quantitative data were obtained from 373 out of 400 respondents representing 93 per cent of volunteered participants. Data collected was analysed using structural equation modelling to establish the relationship among social media information, social media entertainment, social media innovation, social media knowledge generation and student performance. Findings The findings of this study indicate that social media information, social media innovation and social media entertainment all had a significant positive influence on social media knowledge generation, which has wide learning and knowledge management implications. Also, the study indicated that information computer technology knowledge moderates the relationship between social media and student performance. Research limitations/implications The sample taken was mainly cross-sectional in nature rendering the inference of causal relationships between the variables impossible. Future researchers should adopt a longitudinal research design to examine causality. Finally, the study was limited to only university students in Accra, Ghana. Future research can extend to a bigger student population and to other West African and African countries. Practical implications This paper will serve as a profitable source of information for managers and researchers who may embark on future research on social media and academic performance. The findings that social media information, innovation and entertainment can likewise enhance social media knowledge generation can help managers and university teachers to use the vehicle of innovation and entertainment to communicate knowledge. Social implications The findings of this study will help policymakers in education and other industries that engage the youth to realise the important factors that can make them get the best in the social media space. Originality/value Social media usage in academic performance is increasingly prevalent. However, little is known about how social media knowledge generation mediates between social media usage and academic performance and, furthermore, whether the information computer technology knowledge level of students moderates the relationship between social media knowledge generation and academic performance of university students in sub-Saharan Africa, particularly Ghana. Theoretically, the findings of this study provide clear research evidence to guide various investigations that can be done on the relationships of the variables under social media usage, knowledge generation and university student performance, which advances the diffusion of new knowledge.
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Dong, L., S. LI, Z. Wu, et al. "SAT0250 CLINICAL CHARACTERISTICS AND THE DISEASE ACTIVITY OF BEHCET’S DISEASE IN CHINA: A STUDY BASED ON SMART SYSTEM OF DISEASE MANAGEMENT (SSDM)." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1068.1–1068. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1470.
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Background:Behcet´s disease (BD) is a systemic autoimmune disease that affects multiple organ systems with recurrent oral ulcers, genital ulcers and skin lesions. Behcet´s Disease Current Activity Form (BDCAF) and Electronic Medical Record-based Activity Index (EMRAI) are commonly used internationally to evaluate the disease activity of BD.Objectives:This study aimed to analyze the clinical characteristics, the level of disease activity, and the incidence of anxiety and depression for Chinese BD patients. Patients can perform self-management of disease with SSDM.Methods:SSDM is a series of doctor-patient interactive applications for self-management of patients with chronic diseases. Patients can perform self-assessment with SSDM and upload the data to their authorized doctors. The SSDM patients’ application system integrates the BDCAF and EMRAI into one scoring system. Patients could obtain scores of BDCAF and EMRAI by responding to one questionnaire through SSDM.Results:From Apr 2017 to Jan 2020, 719 BD patients from 166 hospitals used SSDM, with a mean age of 38.97±12.71 (14~81) years old, and median disease duration of 20.8 months. 719 patients performed BDCAF and EMRAI self-assessment 1321 times, 252 patients repeat assessments for 855 times. The mean score of BDCAF and EMRAI are 3.57±2.17 and 3.44±1.90, respectively. The matching degree of the two score was 0.8747.The most common clinical characteristics were oral ulcers (83.73%), ocular symptoms (62.03%), joint pain (50.07%). The comparative study between males and females revealed significant difference in the aspects of epididymitis (10.94% vs 0, p<0.001), genital ulcer (35.09% vs 44.93%, p=0.01), headache (24.15% vs 33.92%, p=0.01) and superficial thrombophlebitis (24.15% vs 33.92%, p=0.01). Table 1.Table 1.Clinical Characteristics of different systems in Chinese BD patients.Presence of clinical characteristicsTotalMalesFemalesP valueOral ulcer83.73% (602)86.42% (229)82.16% (373)0.14Genital ulcer41.31% (297)35.09% (93)44.93% (204)0.01*Epididymitis4.03% (29)10.94% (29)0 (0)<0.001**Erythema29.49% (212)29.43% (78)29.52% (134)0.98Skin lesions26.84% (193)28.68% (76)25.77% (117)0.4Superficial thrombophlebitis30.32% (218)24.15% (64)33.92% (154)0.01*Headache30.32% (218)24.15% (64)33.92% (154)0.01*Joint pain50.07% (360)51.32% (136)49.34% (224)0.61Arthritis14.60% (105)14.72% (39)14.54% (66)0.95Gastrointestinal involvement24.90% (179)27.92% (74)23.13% (105)0.15Ocular symptoms62.03% (446)62.64% (166)61.67% (180)0.79Nervous involvement23.78% (171)25.66% (68)22.69% (103)0.37Vascular involvement15.72% (113)18.11% (48)14.32% (65)0.18*P values are for the comparison between the males and females.Conclusion:Chinese BD patients can effectively perform BDCAF and EMRAI self-assessment with SSDM. The results of the assessment conducted by the two scoring systems are similar. The clinical characteristics of Chinese BD were different depending on gender.Acknowledgments: :Smart system of disease management (SSDM) was developed by Shanghai Gothic Internet Technology Co., Ltd.Disclosure of Interests:None declared
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Gentilini, Chiara, Urte Hilbers, Susanne Ganepola, et al. "WT1-Specific T Cell Responses Are Frequent after Allogeneic Stem Cell Transplantation for Acute and Chronic Myeloid Leukemia." Blood 106, no. 11 (2005): 598. http://dx.doi.org/10.1182/blood.v106.11.598.598.
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Abstract The transcription factor WT1 is often overexpressed in leukemic cells and thus represents a tumor specific antigen which has already been used as a target for immunotherapeutic approaches. To investigate its role in graft-versus-leukemia effects after allogeneic stem cell transplantation (SCT), the frequency of T cells specific for WT1 was determined in 52 patients with myeloid malignancies before and after allogeneic SCT. Methods: Using unseparated PBMCs, T cell frequencies were assessed by the IFN-gamma ELISPOT assay at continuous intervals after dose reduced (n=15) or conventional transplantation (n=37). In case of HLA-A2.1-positive pts, a panel of 4 peptides (Db126126-134, WH187187-195, WH242240-250 and WT1 3737-45), known to represent HLA-A2.1-restricted epitopes of the WT1 protein was applied. In addition, we made use of a pool of overlapping peptides derived from the WT1 protein to assess responses in HLA-A2.1-negative patients and against other epitopes. HIV-specific (ILKEPVHGV) and CMVpp65-specific (NLVPMVATV) peptides served as negative and positive controls. In case of positive results in the ELISPOT, cells were further analyzed in tetramer binding assays. In order to detect the expression of the WT1 gene in tumor cells, a quantitative RT-PCR was carried out. Results: 11 patients with CML and 41 patients with AML/MDS were analyzed. In contrast to 17 conventionally treated patients with CML who showed no WT-1-specific reactivity, antigen-specific T cells were present in high frequency (up to 356:100.000) in 7 of 11 pts with CML up to 780 days after allogeneic transplantation. Further, T cell-responses against WT-1 peptides were found in 18 of 41 patients with AML after transplant with frequencies between 21 and 322 spots/100 000 PBMC (median 70) for Db126 and 20-356 spots/100 000 PBMC (median 93) for WH187. In contrast, only 20% of patients pre allo SCT (4/20) had a positive response against Db126 (median 144, range 111–160) and WH187 (median 151, range 122–174). Only 2 out of 17 normal subjects showed Db126 and WH187 specific CTLs with very weak frequencies (maximal T cell response 40 and 41 spots /100 000 PBMC). Reactivity against WT1 37 or WH 242 was exclusively observed following transplantation (in 2 and 5 out of 16 patients). In HLA A2.1 positive as well as negative recipients, the pool of overlapping WT1 peptides allowed us to detect WT1-reactive T cells in 3 of 9 patients. The number of WT1-reactive T cells increases soon after transplantation, and is maintained at different levels over a longer period of time. Concomitantly, the proportion and number of CD3+/Foxp3+ regulatory T cells was shown to be significantly reduced in all patients tested so far. Conclusion: T cell responses against WT1 are elicited short after allogeneic SCT. We speculate that the lack of regulatory T cells during the early phase after HSCT could be responsible for this phenomenon. To further enhance WT1 specific immune reactivity during this phase after HSCT, we have started a phase II clinical trial, in which patients with AML and MDS are vaccinated with the Db126 peptide.
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Tung, Shawndeep, William Decker, Simon Robinson, et al. "Third Party Umbilical Cord Blood Regulatory T Cells Prevents Graft Versus Host Disease In a Xenogenic Murine Model." Blood 116, no. 21 (2010): 3737. http://dx.doi.org/10.1182/blood.v116.21.3737.3737.
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Abstract Abstract 3737 Background: Umbilical Cord Blood (UUCB) Regulatory T cells (Tregs) co-expressing CD4/CD25 have been shown to inhibit alloreactive T cell function. We hypothesized that prophylactic infusion of 3rd party UCB Tregs can abrogate Graft versus Host Disease (GvHD). Methods: (a) Treg generation: Naturally occurring CD25+ Tregs, purified from thawed UCB units by magnetic activated cell sorting (MACS) using Miltenyi CD25 reagents (as per manufacturer's instructions), were cultured at 1×106 cells/ml in ExVivo medium (Gibco) containing interleukin (IL)-2 (100 IU/ml) with irradiated K562 cells engineered to express CD86, CD69, CD187c, IL-15, CD64 and OKT3 (provided by Dr. Laurence Cooper, MDACC) or with microbeads bearing CD3 and CD28 antibodies on their surface (T-Cell Expander, Invitrogen). Cultures were initiated at a ratio of 1 Treg: 4 engineered K562 cells or Invitogen beads and maintained at 1×106 cells/ml over a 14 day period by the addition of fresh medium. Fresh IL-2 was added to maintain 100 IU/ml on an every-other-day basis. Flow cytometry, Western blot analysis and demonstration of ability to reduce in vitro MLR reactions confirmed the Treg phenotype of the expanded cells. (b) Xenogeneic graft vs. host model: On day -1, NOD-SCID IL2Rgnull (NSG) mice were sublethally-irradiated (320 cGy) and received 107 Treg cells intravenously. On day 0, 107 human apheresis PBMCs were injected intravenously. Mice were regularly monitored, weighed and graded according to a GvHD scale developed by Dr. James Ferrara (University of Michigan Comprehensive Cancer Center). Results: (a) Ex vivo Treg expansion of up to 700 fold was achieved yielding approximately 2.5×108 Treg cells from an average frozen UCB unit. Analysis of the ex vivo expanded product after 14 days revealed: (i) 95% co-expressed FOXP3/CD4/CD25 (flow cytometry), and (ii) expression of peptidase inhibitor 16, known to be uniquely associated with FOXP3 expression (western blot, Figure 1). Further, addition of UCB Tregs showed suppression of two-way allo-MLR by 93% (measured by tritiated thymidine and CFSE studies). (b) In the NSG GvHD model, mice receiving PBMC showed: (i) a significant (P=0.0002, student's paired t-test) 30% reduction in body weight, (ii) gross evidence of GvHD (average Ferrara score of 6) and (iii) reduced survival, when compared to mice receiving intravenous injection of Tregs on day -1. By comparison, mice receiving Tregs on day -1: (i) did not lose weight, (ii) scored consistently lower on the Ferrara scale (average score of 3) and (iii) had significantly improved survival (70% survival vs. 15%; P < 10-4, figure 2). Xenogenic transplanted mice showed clear histopathological evidence of GvHD in skin, gut, liver, spleen, lung, esophagus, and bone marrow whereas histopathology remained comparable to controls in the Treg rescued mice. Conclusion: Infusion of 3rd party UCB Tregs markedly reduced the severity of xenoGVHD in a mouse transplant model. These preclinical data support the initiation of a phase I/II clinical trial to assess the efficacy of third party allogenic UCB Tregs in a traditional transplant setting. Disclosures: No relevant conflicts of interest to declare.
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Pophali, Priyanka, Melissa C. Larson, Cristine Allmer, et al. "Compliance with Age-Appropriate Screening for Malignancies and Influenza Vaccination in 3-Year Lymphoma Survivors." Blood 132, Supplement 1 (2018): 4791. http://dx.doi.org/10.1182/blood-2018-99-117822.
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Abstract Background: The frequency of preventive health practices (PHP), including age-appropriate screening for malignancies and immunizations, and compliance with PHP guidelines in lymphoma survivors is not known. We hypothesized that lymphoma survivors are more compliant with PHP than the general population but PHP rates may differ based on patient, disease and treatment characteristics. Methods: We identified eligible lymphoma patients from the SPORE Molecular Epidemiology Resource (MER) cohort, in which they were prospectively enrolled within <9 months of diagnosis. Survivors self-reported their PHP (colon, breast, and prostate cancer screening and influenza immunization) in the 3-year follow-up questionnaire (FU3). Per US Preventative Task Force guidelines, survivors were considered eligible for colon cancer screening if they were >50 years and compliant if they had fecal occult blood test <1 year or sigmoidoscopy/colonoscopy <10 years of FU3. Eligible female survivors age 50-75 were considered compliant if they had a mammogram after lymphoma diagnosis. Since USPTF recommended against PSA for prostate cancer screening in 2012, males aged 55-69 prior to 2012 were eligible and considered compliant if PSA test was <1 years of FU3. Survivors who received influenza vaccine <1 year of FU3 were considered compliant. Chi-square test was used to compare characteristics of compliant vs non-compliant patients; p value <0.05 was considered statistically significant. Results: Of 4248 lymphoma patients enrolled in the MER from 2002 to 2012, 2038 participants completed FU3. 1105 (54%) were male. The median age at diagnosis was 61 (IQR 51-69) years. There were equal numbers of indolent (N=1002) and aggressive (N=995) histologies with follicular (N=515, 25%) and diffuse large B-cell (N=427, 21%) being the most common. Majority (N=1221, 60%) had advanced stage (Ann Arbor III-IV) disease. 469 (23%) had events prior to FU3 and majority 1777 (88%) had received lymphoma treatment prior to FU3. Of 2038 survivors who completed FU3, 1576 (79%) reported having colon cancer screening in their lifetime. 1328 (91%) of 1570 eligible survivors were compliant, 124 (9%) were not and 118 had missing information. Survivors of age >60 years (93% vs 88%, p<0.001), those with indolent lymphomas (93% vs 90%, p=0.046), or diagnosed between 2010-2012 (94% vs 90% 2002-2009, p=0.007) were more likely to be compliant. There was no difference in colon cancer screening by sex, events prior to FU3 or treatment prior to FU3. 872 (96%) of 933 female survivors reported having a breast exam and 836 (91%) had a mammogram at least once in their lifetime. 495 (96%) of 561 eligible female survivors were compliant, 23 (4%) were not and 43 had missing information. There was no difference in mammographic screening based on age (<=60 vs >60), histology (indolent vs aggressive), events prior to FU3, treatment prior to FU3 or year of diagnosis (2010-2012 vs 2002-2009). 737 (78%) of 1105 male survivors had a PSA test at least once in their lifetime. 115 (71%) of 216 eligible men were compliant, 47 (29%) were not and 54 had missing information. There was no difference in PSA screening by age (<=60 vs >60), histology (indolent vs aggressive), events prior to FU3, and treatment prior to FU3. 1818/2038 (90%) survivors had received an influenza vaccine in their lifetime. 1567 (81%) were compliant, 373 (19%) were not and 98 had missing information. Survivors >60 years of age (87% vs 75%, p<0.001) and those with indolent lymphoma (83% vs 78%, p=0.015) were more likely to be compliant. There was no difference in influenza vaccination by sex, events prior to FU3, treatment prior to FU3, and year of diagnosis (2010-2012 vs 2002-2009). As a comparison in the US general population [Figure], between 2002-2015 the highest rates published by the Center for Disease Control are 62% for colon cancer screening (2015), 75% for mammography (insured, 2003) and influenza vaccination 42% (2015). Per the American Cancer Society, the highest rate of PSA screening was 54% (2010). Conclusion: Lymphoma survivors have high compliance with PHP recommendations compared to the general population. Although older individuals and those with indolent histologies were more likely to receive influenza vaccination and colon cancer screening, this difference was not seen in breast and prostate cancer screening practices. Lymphoma treatment and events did not seem to affect the frequency of PHP among survivors. Figure. Figure. Disclosures Cerhan: Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board; Celgene: Research Funding.
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Dreo, T., M. Pirc, M. Ravnikar, et al. "First Report of Pseudomonas syringae pv. actinidiae, the Causal Agent of Bacterial Canker of Kiwifruit in Slovenia." Plant Disease 98, no. 11 (2014): 1578. http://dx.doi.org/10.1094/pdis-05-14-0513-pdn.
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In May 2013, 20 plants in a production orchard of kiwifruit (Actinidia deliciosa) cv. Hayward in the seaside area of Primorska showed small, angular, coalescing necrotic leaf spots and cankers on green shoots. In the following 2 weeks, disease progressed to wilting and shoot dieback with exudates. Symptoms were consistent with Pseudomonas syringae pv. actinidiae. Circular, flat, granulated colonies with entire margins were isolated from leaf spots on King's medium B (KB) and on sucrose nutrient agar with boric acid, cephalexine, and cycloheximide. Strains were purified on KB and showed weak fluorescence upon a prolonged incubation (>10 days) and belonged to P. syringae LOPAT group Ia (+---+). DNA was extracted from strains and plant extracts with Chelex 100 resin and Bio-Nobile QuickPick Plant Kit (Turku, Finland), respectively. PCR products of expected sizes were generated by PCR assays (2,4) from all strains and plant extract, supporting the strains as being P. syringae pv. actinidiae. Two strains (NIB Z 1870 and 1871) were further identified by cytochrome C oxidase (negative), glucose metabolism (oxidative), aesculine (negative), and nitrate (negative). Their partial rpoD gene sequences (GenBank Accession Nos. KJ724117 and KJ724118) (3) were identical to the sequence of the P. syringae pv. actinidiae pathotype strain NCPPB 3739 (FN433222, 100% coverage) and to the sequence of P. syringae pv. theae at 96% coverage (FN433271). BOX-PCR fingerprinting and multilocus sequence analysis (MLSA) based on four housekeeping genes gapA (KJ733923 and KJ733924), gltA (KJ733925 and KJ733926), gyrB (KJ733927 and KJ733928), and rpoD identified both strains as biovar 3, a highly virulent biovar of P. syringae pv. actinidiae (5). The pathogenicity of the two strains was confirmed on four plants of A. deliciosa ‘Hayward’ for each strain. Six-month-old plants were sprayed on the abaxial sides of leaves with 30 ml cell suspension prepared from a 72-h-old culture of the appropriate strain (~8 × 106 CFU/ml in 0.01 M MgSO4), covered with plastic bags for 24 h, and incubated under high relative humidity (80%) with 14 h daylight and 24/21°C day/night temperature. Three positive and three negative control plants were inoculated with the Italian P. syringae pv. actinidiae virulent strain K9 (kindly provided by Dr. Gian Luca Bianchi of the Plant Health Service of Friuli Venezia Giulia region) and 0.01 M MgSO4, respectively. After 7 days, water-soaked brown spots with pale green halos were observed on all plants inoculated with bacteria. Re-isolated bacteria were identical to the original strains in their morphology, PCR products, and rpoD sequences. Negative control plants did not develop symptoms, and no growth was observed on media. This is the first laboratory confirmation of bacterial canker of kiwifruit in Slovenia. Visual inspections carried out by the plant health authorities in 2013 and laboratory analysis confirmed additional infection with P. syringae pv. actinidiae in a single, nearby orchard. The pest status of P. syringae pv. actinidiae in Slovenia is officially declared as present, subject to official control (1). References: (1) EPPO Reporting Service. Online publication: http://archives.eppo.int/EPPOReporting/2014/Rse-1402.pdf . No. 02 2014/026, 2014. (2) A. Gallelli et al. J. Plant Pathol 93:425, 2011. (3) N. Parkinson et al. Plant Pathol. 60:338, 2011. (4) J. Rees-George et al. Plant Pathol. 59:453, 2010. (5) J. L. Vanneste et al. Plant Dis. 97:708, 2013.
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Menor-Almagro, R., M. Argentina García, I. Rua-Figueroa, et al. "AB0428 ASSOCIATION BETWEEN GEOGRAPHIC AND CLIMATOLOGICAL CONDITIONS AND CUTANEOUS MANIFESTATIONS IN LUPUS PATIENTS FROM THE SPANISH RHEUMATOLOGY SOCIETY LUPUS REGISTRY (RELESSER) AND ARGENTINE RHEUMATOLOGY SOCIETY LUPUS REGISTRY (RELESSAR) COHORT." Annals of the Rheumatic Diseases 79, Suppl 1 (2020): 1513.2–1513. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3848.
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Background:Climatological conditions and ethnicity impact on the course of the disease in systemic lupus erythematosus patients.Objectives:We carry out a study to analyze cutaneous manifestations in SLE patients from Argentina and Spain.Methods:Patients data from Spanish Rheumatology Society Lupus Registry (RELESSER) and Argentina Rheumatology Society Lupus Registry (RELESSAR) were retrospectively analyzed for presence of cutaneous lesions (alopecia, photosensitivity, malar rash, discoid lesions, oral ulcers and subacute lesions). RELESSER-T and RELESSAR-T are multicenter, hospital-based registries, with retrospective cross-sectional collection of data about patients with SLE attending Spanish and Argentinian rheumatology services from the public national health system. Data about climatological conditions throughout the Spanish and Argentinian geography were provided by the Spanish Meteorological Agency and Argentine Meteorological Services.Results:A total of 5604 patients were included, median age 44.6 ± 15.3, 90.4 % female. Current smokers were 28,9%. Other climatological, geographical, biological and clinical data are shown in table 1. In the multivariable model, the presence of cutaneous lesion were significantly associated with temperature OR 1.116 (95% CI:1.042-1.196 p=0,002), altitude OR 1.001 (95% CI:1.000-1.001, p=0.012), hemolytic anemia OR 1.401 (95% CI:1.017-1.931 p=0.039) and serositis OR 1.509 (95% CI:1.215-1.875 p=0.000). Negative associations were observed between females OR 0.392 (95% CI:0.297-0.518, p=0.000), latitude OR 0.994 (95% CI:0.988-0.999, p=0.000), oceanic climate OR 0.566 (95% CI:0.381-0.842, p=0.005), leukopenia OR 0.790 (95% CI:0.643-0.970, p=0.025), renal disorder OR 0.761 (95% CI:0.600-0.966, p=0.025), glucocorticoids treatment OR 0.571 (95% CI:0.456-0.715, p=0.000) and antimalarial drugs OR 0.439 (95% CI:0.342-0.563, p=0.000).Table 1.Geographical, climatological and clinical/laboratory variables.No cutaneous manifestationsCutaneous manifestationspLatitude, median (interqualite range)40.47 (38.35-41.63)40.37 (-31.41-41.34)0.001Altitude, median (interqualite range)192.0 (37.0-698.0)156.0 (25.0-609.0)0.000Temperature, mean monthly ± SD15.2 ± 3.515.3 ± 3.60.000Humidity, mean monthly ± SD66.9 ± 7.267.4 ± 7.10.108Oceanic climate, n (%)307 (11)2406 (89)0.000Subhumid/altitude climate, n (%)17 (7)240 (93)0.002Mediterranean climate, n (%)292 (17)1434 (83)0.000Arthritis, n (%)523 (12)3722 (88)0,003Serositis, n (%)254 (16)1368 (84)0,000Renal disorder, ever, n (%)206 (11)1576 (89)0.015Hemolytic anemia, n (%)90 (17)426 (83)0,002Leukopenia, n (%)345 (11)2669 (89)0.000Thrombocytopenia, n (%)170 (15)986 (85)0.076Antiphospholipid antibodies, n (%)293 (15)1606 (85)0.000Anti DNA, n (%)522 (14)3279 (86)0.044Anti-Ro/SSA, n (%)189 (11)1563 (89)0.000Hypocomplementemia, n (%)510 (12)3736 (88)0.000Glucocorticoids mucocutaneous cause, ever, n (%)499 (11)3928 (89)0.000Antimalarial drug: ever, n (%)500 (11)4034 (89)0.000Conclusion:In the current analysis, taking RELESSAR and RELESSER data together, we observe positive association between higher temperature and skin lesion and negative association with living in southern hemisphere latitudes.References:Influence of Solar Radiation in Cutaneous Manifestations of Lupus: Data from the Gladel Cohort [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10).Disclosure of Interests:Raúl Menor-Almagro: None declared, Mercedes Argentina García: None declared, Iñigo Rua-Figueroa: None declared, Guillermo Pons Estel: None declared, Maria Auxiliadora Martin-Martinez: None declared, Alejandro Muñoz Jimenez.: None declared, María Galindo-Izquierdo: None declared, Jaime Calvo-Alen: None declared, Antonio Fernandez-Nebro: None declared, Alejandro Olive: None declared, Bernardo Pons-Estel Grant/research support from: GSK, Janssen, Consultant of: GSK, Janssen, Speakers bureau: GSK, Janssen, Jose M Pego-Reigosa: None declared
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Mamedov, Huseyn, Syed Ismat Shah, Archil Chirakadze, Vusal Mammadov, Vusala Mammadova, and Khumar Ahmedova. "Photovoltaic performance of p-Si/Cd1-xZnxO heterojunctions." Photonics Letters of Poland 10, no. 1 (2018): 26. http://dx.doi.org/10.4302/plp.v10i1.797.
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Heterojunctions of p-Si/Cd1-xZnxO were synthesized by depositing of Cd1-xZnxO films on p-Si substrates by electrochemical deposition. The morphological properties of the films were studied by scanning microscopy. The electric and photoelectrical properties of heterojunctions were investigated depending on the deposition potential and films composition. Heterojunctions of p-Si/Cd1-xZnxO, which deposited at cathode potential of -1.2 V, shows good rectification (k=1640). Under AM1.5 conditions the maximal values of open-circuit voltage, short-circuit current, fill factor and efficiency of our best nano-structured cell, were Uoc = 442 mV, Jsc = 19.9 mA/cm2, FF = 0.59 and n = 5.1 %, respectively. Full Text: PDF ReferencesX. Li, et al. "Role of donor defects in enhancing ferromagnetism of Cu-doped ZnO films", J. Appl. Phys., 105, 103914 (2009). CrossRef X. Han, K. Han and M. Tao, "Electrodeposition of Group-IIIA Doped ZnO as a Transparent Conductive Oxide", ECS Trans., 25, 93 (2010). CrossRef W. Liu et al. "Na-Doped p-Type ZnO Microwires", J. Am. Chem. Soc., 132, 2498 (2010). CrossRef R.A. Ismail and O.A. Abdulrazaq, "A new route for fabricating CdO/c-Si heterojunction solar cells", Sol. Energy Mater. Sol. Cells, 91, 903 (2007). CrossRef R.S. Mane, H.M. Pathan, C.D. Lokhande and S.H.Han, "An effective use of nanocrystalline CdO thin films in dye-sensitized solar cells", Sol. Energy, 80 185 (2006). CrossRef E. Martin et al. "Properties of multilayer transparent conducting oxide films", Thin Solid Films, 461, 309 (2004). CrossRef Y. Caglar, M. Caglar, S. Ilican and A. Ates, "Morphological, optical and electrical properties of CdZnO films prepared by sol?gel method", J. Phys. D: Appl. Phys., 42, 065421 (2009). CrossRef F. Wang, Z. Ye, D. Ma, L. Zhu and F. Zhuge, "Formation of quasi-aligned ZnCdO nanorods and nanoneedles", J. Cryst. Growth, 283, 373 (2005). CrossRef A. Abdinov, H. Mamedov, S. Amirova, "Investigation of Electrodeposited Glass/SnO2/CuInSe2/Cd1-xZnxS1-ySey/ZnO Thin Solar Cells", Jpn. J. Appl. Phys., 46, 7359 (2007). CrossRef A. Abdinov, H. Mamedov, H. Hasanov, and S. Amirova, "Photosensitivity of p,n-Si/n-Cd1?xZnxS heterojunctions manufactured by a method of electrochemical deposition", Thin Solid Films, 480-481, 388 (2005). CrossRef A. Abdinov, H. Mamedov, and S. Amirova, "Investigation of electrodeposited p-Si/Cd1 ? xZnxS1 ? ySey heterojunction solar cells", Thin Solid Films, 511-512, 140 (2006) CrossRef H. Mamedov, V. Mamedov, V. Mamedova, Kh. Ahmadova, "Investigation of p-GaAs/n-Cd1-xZnxS1-yTey/Cd1-xZnxO heterojunctions deposited by electrochemical deposition", J. Optoelectrom. Adv. M., 17, 67 (2015). DirectLink H. Mamedov et al. "Preparation and Investigation of p-GaAs/n-Cd1-xZnxS1-yTey Heterojunctions Deposited by Electrochemical Deposition", J. Solar Energy Engineering, 136, 044503 (2014). CrossRef S. Sadofev, S. Blumstengel, J. Cui, J. Puls, S. Rogaschewski, P. Schafer and F. Henneberger, "Visible band-gap ZnCdO heterostructures grown by molecular beam epitaxy", Appl. Phys. Lett., 89, 201907 (2006). CrossRef G. Torres-Delgado et al. "Percolation Mechanism and Characterization of (CdO)y(ZnO)1?y Thin Films", Adv. Funct. Mater., 12, 129 (2002). CrossRef H. Tabet-Derraz, N. Benramdane, D. Nacer, A. Bouzidi and M. Medles, "Investigations on ZnxCd1?xO thin films obtained by spray pyrolysis", Sol. Energy Mater. Sol. Cells, 73, 249 (2002). CrossRef M. Tortosa, M. Mollar and B. Mar?, "Synthesis of ZnCdO thin films by electrodeposition", J. Cryst. Growth, 304, 97 (2007). CrossRef A. Singh, D. Kumar, P. K. Khanna, M. Kumar, and B. Prasad, "Phase Segregation Limit in ZnCdO Thin Films Deposited by Sol?Gel Method: A Study of Structural, Optical and Electrical Properties", ECS Journal of Solid State Science and Technology, 2 (9), Q136 (2013). CrossRef F.Z. Bedia, A. Bedia, B. Benyoucef and S.Hamzaoui, "Electrical Characterization of n-ZnO/p-Si Heterojunction Prepared by Spray Pyrolysis Technique", Physics Procedia, 55, 61 (2014). CrossRef M. Jing-Jing et al. "Rectifying and Photovoltage Properties of ZnO:A1/p-Si Heterojunction", Chin. Phys. Lett., 27 (10), 107304 (2010). CrossRef
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Adess, Matthew E., Patrick Stiff, Tulio Rodriguez, et al. "Amelioration of Late Complications Following Unrelated Donor Bone Marrow Transplantation When Anti-Thymocyte Globulin Is Used as a Part of Conditioning." Blood 108, no. 11 (2006): 5319. http://dx.doi.org/10.1182/blood.v108.11.5319.5319.
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Abstract Polyclonal anti-thymocyte globulin (ATG) reduces the risk for primary graft rejection as well as acute graft-versus-host disease (GVHD) by depleting T cells in both the host and the infused allograft. However, the impact of ATG on late outcomes is less certain. We report the results of a retrospective landmark analysis of consecutive patients who underwent an unrelated donor bone marrow transplant at our center between January 2001 and October 2005 (n=45) and survived at least 90 days following transplant. We compared late outcomes in patients who either recieved ATG (n=25) or did not (n=20) as a part of their conditioning regimen. Conditioning was with either busulfan and cyclophosphamide (n= 28; 17 without ATG) or BCNU, etoposide, cytarabine, and melphalan (n=18; 3 without ATG). Most patients (20) received rabbit ATG at a median dose of 3 mg/kg (range: 1.5–9 mg/kg) on day -4 and -3. Others were given equine ATG. GVHD prophylaxis consisted of tacrolimus + methotrexate in both groups. Median age was 42 years (range 18–65; 14 female). Bone marrow from unrelated donors matched at HLA-A, B, C, and DRB1 (7/8 and 8/8 matches) was used as the stem cell source. Diseases treated were CML (11), HD (9), AML (8), MDS (6), NHL (3), MM (3), and other (5). A median of 3 prior therapies had been given before transplant (range 1–5). There was no significant difference (Pearson χ2) in the number of patients beyond CR1/CP1 (n=25) and those having failed a prior autograft (n=17) between the two groups. The median overall survival in the recipients of ATG was 1382 days (95% CI: 373– 2391 days) as opposed to 364 days (95% CI: 0–851) in those not receiving ATG (P=0.125 by Log-Rank test); with a 1-year overall survival of 76% (59%–93%) vs. 50% (28–72) in the ATG vs. no ATG cohorts respectively, and 69% (49–89) vs. 44% (22–66) at 2-years. The 1-year progression free survival was 84% (69–98) vs.90% (77–100) in the ATG vs. no ATG cohorts, and 84% (69–98) vs. 67% (37–97) at 2 years. Chronic GVHD developed in 15/20 (75%) patients not receiving ATG (45% extensive), and in 12/25 (48%) in those recieving ATG (16% extensive) (P=0.06 Pearson χ2). Graft rejection was seen in 2/20 patients in the non-ATG arm and 1/25 patients in the ATG arm. Despite a lower incidence of chronic GVHD, the relapse rate was similar in the two groups (16% in the ATG group vs. 20% in the non-ATG group; P=0.73). Lymphoid recovery was similar in the two groups. The absolute lymphocyte counts at day-90 and day-180 post transplant were 680 vs 800/microL and 1100 vs. 1500/microL in the no ATG vs. ATG cohorts (P=0.275 repeated measures ANOVA). Serious late infections requiring parenteral antimicrobial treatment occured in 8 patients (32%) receiving ATG, and in 9 patients (45%) in the non-ATG arm ((P=0.248). CMV reactivation was seen in 8 patients (32%) receiving ATG, and 7 (35%) in the non-ATG arm. Eleven patients (55%) have died in the no ATG cohort from either relapse (2), GVHD (4) or infection (5); whereas in the ATG cohort 9 (36%) have died of either relapse (4), GVHD (3) or infection (2). In conclusion, ATG appears to reduce delayed transplant related complications, such as chronic GVHD and infections, in patients receiving bone marrow from unrelated donors. This may lead to a favorable trend towards improved survival in patients recieving ATG as a part of non-total body irradiation based conditioning.
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Shah, Gunjan L., Aaron Winn, Andreas K. Klein, et al. "Cost-Implications Of Comorbidity For Autologous Hematopoietic Stem Cell Transplantation (Auto HSCT) In Elderly Patients With Multiple Myeloma (MM) Using The SEER-Medicare Database." Blood 122, no. 21 (2013): 1746. http://dx.doi.org/10.1182/blood.v122.21.1746.1746.
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Abstract Background Medicare coverage of Auto HSCT for patients > 65 years with multiple myeloma (MM) began in 2000. In the decade that followed, both the number and cost of Auto HSCT increased dramatically. By 2009, patients over the age of 60 accounted for 40% of the Auto HSCT with MM being the leading indication (Center for International Blood and Marrow Research, 2011). The cost implications of the increased use of Auto HSCT are not well described. The majority of studies looking at the economics of HSCT are single institutional studies focusing on younger patients for which a wide range of costs and indications are reported. Using the SEER-Medicare database, we examined the costs and life year benefit of Auto HSCT for MM patients over age 65 by evaluating the difference over time relative to comorbidity burden. Methods Patients were identified as having an Auto HSCT based on ICD-9 or HCPCS codes (i.e., ICD-9 41.00, 41.01, 41.04, 41.07, and 41.09; or HCPCS 38241) and were 66 years of age or older at the time of diagnosis. Two time periods were used: 10/00-6/04 (Early) and 7/04-1/08 (Late). Costs and survival were calculated for the first 100 days (d), 1 year (yr), and 3 yrs of follow-up post-Auto HSCT. Data on comorbidities, based on the Charleston Comorbidity Index (CCI), were recorded at the time of diagnosis and HSCT. Patients were classified as CCI0 if they had no comorbidity or CCI1+ if they had one or more comorbid conditions. All cost data were reported in 2009 dollars, adjusted using the medical care component of the Consumer Price Index. Results 10,832 patients were found to have multiple myeloma, with 275 receiving an Auto HSCT between 10/00 and 1/08. 129 (47%) Auto HSCTs occurred in the Early and 146 (53%) in Late periods. Patients in both time periods were primarily Caucasian; the majority were male; and the median age was 70 yrs (range 66-93). Median time from diagnosis to transplant was 368d and 373 d, with 100d post transplant survival 91% and 97% (p=0.07), 1-yr 83% and 89% (p=0.14), and 3-yr 53% and 60% (p=0.28), respectively. Median costs for each follow-up time increased between Early and Late, even after accounting for inflation. While the distribution of CCI at Auto HSCT was similar in both time periods (CCI0, 62% and 64%, respectively), two key differences were noted in post transplant survival. One-yr survival in the early period was significantly higher for patients with CCI0 than CCI1+ (p=0.006). Similarly, 100-day survival in the Late period was significantly better for those without comorbidities (p=0.035). Furthermore, 3 yr survival for CCI1+ increased from 41% to 60% (p= 0.061) between the Early and Late periods. Median 100-day costs were greater for CCI0 than CCI1+ in both Early ($85696 vs $74381) and Late ($84774 vs $77081); however, by 3 years, the cumulative cost for CCI1+ was greater ($213,757 vs $228,974 in Early and $208,410 vs $339,827 in Late). Conclusion Over the past decade, there has been an increase in the utilization of Auto HSCT for MM in the elderly population along with an overall increase in health care cost. With a similar distribution of comorbidity over time, there was significantly increased survival in the later period with an associated increase in cost. Timing and components of the cost will be identified and may help in determining care decisions. This analysis highlights the interconnected nature of utilization, cost, and survival for patients receiving Auto HSCT, and any evaluation of one of these outcomes must also consider the others. Disclosures: No relevant conflicts of interest to declare.
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Watkins, Dale B., Chung Hoow Kok, Richard J. D'Andrea, Timothy P. Hughes, and Deborah L. White. "Global DNA Methylation Analysis Identifies Key Pathway Differences Between Poor (Low OCT-1 Activity) and Standard Risk CP-CML Patients At Diagnosis." Blood 120, no. 21 (2012): 3730. http://dx.doi.org/10.1182/blood.v120.21.3730.3730.
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Abstract Abstract 3730 Background: DNA methylation, specifically CpG methylation, is an essential mediator of epigenetic gene expression which is of vital importance to many biological processes and human malignancies. DNA hypermethylation has been previously described in a small number of genes in chronic myeloid leukemia (CML); however, current published studies have only examined the methylation status of selected genes, often based on the results of studies in other malignancies. Therefore, the global DNA methylation profile of chronic phase-CML (CP-CML) remains poorly understood, as does the impact of the epigenome on patient response to tyrosine kinase inhibitors (TKIs) including imatinib. The organic cation transport-1 (OCT-1) protein is the major active protein involved in imatinib transport, and we have previously demonstrated that measuring its function in leukemic mononuclear cells, expressed as OCT-1 activity (OA), in patient cells prior to imatinib therapy, provides a strong prognostic indicator. Notably, very low OA (poor risk cohort) is associated with patients at significant risk for poor molecular response, mutation development and leukemic transformation on imatinib therapy. Therefore, it is of particular interest to ascertain whether epigenetic changes are distinct and potentially biologically relevant in these poor risk patients. Aim: To investigate the global DNA methylation profile in CP-CML patients with a particular focus on poor risk patients (very low OCT-1 activity), and to ascertain whether aberrant epigenetic programming may underlie their poor response. Method: Cells were isolated from the blood of 55 CP-CML patients at diagnosis and 5 normal individuals. CP-CML patients were classified according to their OA values, with 29 classified as poor (very low OA) and 26 standard risk (high OA). Whole genome DNA methylation analysis was performed using the Illumina Infinium® HumanMethylation450 BeadChip. Analysis of array data was performed with R v2.15.0, using the minfiBioconductor package. Results: The methylation profile of CP-CML was significantly different to that of normal individuals, as shown in Table 1. GeneGo enrichment analysis revealed a significant enrichment in CML for genes known to be involved in other leukemias (p=4.92e−26) particularly AML and CLL, suggesting similar pathways may be under epigenetic control in CML. A significant number of polycomb group (BMI1 and EZH2) target genes were also identified, suggesting the likely involvement of this pathway in CML. Table 1: Summary of significant CpGs and corresponding genes when comparisons of CP-CML to normal individuals, and poor to standard risk patients, are made using methylation profiles. A significant difference was also observed when the methylation profiles of poor and standard risk CP-CML patients were analysed (Table 1). GeneGo analysis again identified polycomb group (SUZ12 and EZH2) target enrichment and significant enrichment of NOTCH, Hedgehog and WNT signalling (p=7.93e−9, p=2.42e−5 and p=3.66e−5 respectively) in poor risk patients, indicating these pathways may play a significant role in the unfavourable responses observed in many of these patients. Of particular interest were the ten CpGs where a fold change >4 was observed between the methylation profiles of poor and standard risk patients. Using the Prediction Analysis of Microarrays supervised learning algorithm, a classifier for patient OA prediction based on this 10 CpG signature was evaluated. This classifier had an overall accuracy of 94% (sensitivity: 95%, specificity: 93%). Conclusion: We present a comprehensive global DNA methylation analysis of CP-CML that indicates significant and widespread changes to the CML epigenome, compared with that of normal individuals. Importantly, we have generated a classifier, which identifies the poor risk patient subgroup (very low OA) with 94% accuracy. Validation of this classifier is currently in progress. The epigenetic changes identified here may contribute to CML pathogenesis, and also to the response heterogeneity observed between CP-CML patients treated with TKI therapy. Disclosures: Hughes: Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. White:Novartis Oncology: Honoraria, Research Funding; BMS: Research Funding; CSL: Research Funding.
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Ono, Keiko, Hideki Tsujimura, Akiyasu Satou, et al. "Retrospective Study of the Optimal CHOP Dose for Elderly Patients with Diffuse Large B-Cell Lymphoma." Blood 128, no. 22 (2016): 4211. http://dx.doi.org/10.1182/blood.v128.22.4211.4211.
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Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma, and the number of elderly patients with DLBCL is increasing. While rituximab plus CHOP (R-CHOP) therapy is considered as the standard first-line treatment for DLBCL, elderly patients are often frail and unable to tolerate the standard dose of R-CHOP. Fifteen years ago, we conducted a prospective study to investigate optimal reduced doses of CHOP therapy for patients aged 65-79 years and those older than 79 years. We concluded that 5/6 (83%) and 7/12 (58%) doses of standard CHOP are effective and tolerable for these two age groups, respectively (Mori M, et al. Leuk Lymphoma. 2001;41:359-66). Since then, we have applied this strategy with the standard dose of rituximab. To evaluate the efficacy and tolerability of reduced R-CHOP therapy for elderly patients, we performed a retrospective analysis. Methods: We reviewed medical records of patients aged 65 years or older with newly diagnosed DLBCL, who underwent R-CHOP therapy from August 2010 to December 2013. Intravascular large B-cell lymphoma and primary central nervous system lymphoma were excluded from this study because R-CHOP therapy alone is not considered as standard for these diseases. We calculated the relative dose intensity (RDI), dividing the actually used doses of cyclophosphamide and doxorubicin by the interval between each course compared with the standard doses (750 mg/m2 cyclophosphamide and 50 mg/m2 doxorubicin every 21 days). Results: During the study period, data were collected from 100 patients (56 males and 44 females) with a median age of 74 (65-86) years. Sixty patients had advanced stages, 40 patients had a score of at least one in the Charlson comorbidity index (Charlson ME, et al. J Chronic Dis. 1987;40:373-83), 18 patients had a poor performance status (Eastern Cooperative Oncology Group performance status: ≥2), and 14 patients were older than 79 years. The overall response rate was 93%, and the complete response (CR) rate was 81%. Three-year overall survival (3-yr OS) was 78%. In comparison with the international prognostic index (IPI), 3-yr OS was 100% (IPI: low, n=26), 94% (IPI: low-intermediate, n=17), 71% (IPI: high-intermediate, n=24), and 58% (IPI: high, n=33). Hematologically adverse events were generally tolerable. No patient experienced a grade 4 hemoglobin decrease, and only four patients experienced a grade 4 platelet decrease. Although 55 patients received granulocyte colony-stimulating factor, a grade 4 leukocyte decrease was common (n=38) and febrile neutropenia (FN) was often seen (n=21). Patients who experienced FN had a significantly shorter OS (p=0.04). With a median follow up of 44.4 months, 20 patients experienced disease progression and 15 patients died after progression. Five patients remained in CR but died of other types of cancer. The other seven patients died of other causes. The median RDI was 0.81 in patients aged 65-79 years and 0.58 in patients older than 79 years. These doses were very similar to the originally intended doses of 5/6 (0.83) for younger patients and 7/12 (0.58) for older patients. The older group tended to show shorter OS (3-yr OS: 64%). However, recurrence rates of the two groups were very similar. Conclusions: This study demonstrates that rituximab plus 5/6 or 7/12 doses of CHOP therapy are effective and tolerable for elderly patients aged 65-79 years and those older than 79 years, respectively. It is noteworthy that the prognosis of patients with an IPI score of ≤2 was very satisfactory. Based on these results, the dose intensity does not have to be increased for these low risk groups. It is possible that increasing the dose intensity in high risk (IPI score: ≥3) patients improves the outcome. However, high risk patients tend to have much tumor burden and a poor performance status. In this group, higher dose chemotherapy will also increase the risk of developing FN and might be associated with inferior OS. Treatment of frail elderly patients with high-risk DLBCL is extremely challenging, and we need to gain further experience. Disclosures No relevant conflicts of interest to declare.
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Evens, Andrew M., Irene Helenowski, Chadi Nabhan, et al. "Multicenter Analysis of Elderly Hodgkin Lymphoma (eHL): Outcomes and Prognostic Factors in the Modern Era." Blood 118, no. 21 (2011): 2625. http://dx.doi.org/10.1182/blood.v118.21.2625.2625.
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Abstract Abstract 2625 Purpose. Survival rates for eHL (most commonly defined as age over 60 years) are significantly and disproportionately inferior to those achieved in younger patients (pts). Reported 5-year event-free survival (EFS) rates for advanced-stage eHL have historically ranged from 30%–45% with 5-year overall survival (OS) rates of 40%–55%. Potential explanations for these discrepant inferior outcomes include co-morbidities precluding delivery of chemotherapy, treatment-related toxicities, and biology of disease. Data examining toxicity, survival, and prognostication for eHL in the modern era are lacking. Methods. We report a multicenter collaboration that retrospectively investigated a large cohort of eHL pts treated over a recent 12-year period (June 1999 December 2010). We examined clinical characteristics, treatment-related toxicities, and outcomes. Furthermore, comorbidities were assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) scale. Patients were also classified as “fit” vs “not fit” (i.e., loss of activities of daily living (ADLs), >3 grade 3 CIRS-G, any grade 4, and/or presence of geriatric syndrome). Univariate associations with survival were determined, while a multivariate Cox proportional hazards model was completed. Additionally, a prognostic model was constructed by classification and regression tree (CART) analysis. Results. 113 eligible pts were identified, while 95 had full data and were analyzed. Among these 95 pts (58M:37F), median age was 67 years (range, 60–89), with 33% of pts ages 70–79 years, while 7% were 80–89 years. 27% of pts had a prior malignancy at a median of 8.4 years (range, 1–25 years) prior to HL diagnosis, for which most had received radiation. At HL diagnosis, there were presence of B symptoms in 54%, performance status 2–4 in 27%, 21% with history of coronary artery disease, and 16% had diabetes. In terms of functional status, 61% of pts had a CIRS-G grade 3 or 4 in at least 1 category, while 46% had a cumulative score >6. Further, 17% had presence of a geriatric syndrome, 26% were classified as 'not fit', and 13% had loss of ADLs at time of HL diagnosis. 25% of pts had bone marrow involvement, while 20% had other extranodal disease (most common: bone and lung). Altogether, 64% of pts had stage III/IV disease, of which 58% had an international prognostic score (IPS) of 4–7. HL histology was nodular sclerosis in 47%, mixed cellularity 31%, NOS 16%, lymphocyte predominant 5%, and lymphocyte depleted 1%. Primary treatment consisted of: ABVD-based (n=67), MOPP-based (n=6), BCVPP (n=6), ChlVPP (n=5), radiation alone (n=4), CHOP (n=3), hospice (n=2), BEACOPP (n=1), and watchful waiting (n=1). 78% of pts received granulocyte-colony stimulating factor (G-CSF) with therapy. The overall response rate (ORR) among treated pts was 85% (73% complete remission (CR) rate). In terms of toxicity, the incidence of bleomycin lung toxicity (BLT) was 32%, which had an associated mortality rate of 25%. Notably, the incidence of BLT was 37% vs 0% among pts who received G-CSF vs not, respectively (p=0.041). With a median follow-up of 66 months (6–154) months, the 5-year EFS and OS for all eHL pts were 44% and 58%, respectively (stage I/II: 61% and 79%; and stage III/IV: 36% and 46%; p=0.009 and p=0.001, respectively). Prognostic factors that predicted survival on univariate analysis are detailed in Table 1. On multivariate regression analysis, 2 factors were associated with inferior survival: 1) age ≥ 70 years (EFS: 1.76 (95%CI 0.98–3.16), p=0.06; and OS: 2.24 (95%CI 1.16–4.33), p=0.02) and 2) Loss of ADLs (EFS: 2.47 (95%CI 0.98–6.21), p=0.055; and OS: 2.71 (95%CI 1.07–6.84), p=0.04). Furthermore, a survival model by multivariate CART analysis, based on number of these 2 adverse factors (0, 1, 2), was formed: 5-year EFS 73%, 51%, 0%, respectively (p<0.0001), and 5-year OS 93%, 68%, 11%, respectively (p<0.0001) (Figure 1). Conclusions. This large, retrospective multicenter analysis of eHL found a high ORR and CR rate, but poor long-term outcomes. As shown previously, a significant percentage of eHL pts suffered BLT, which was fatal in 25% and appeared strongly related to use of growth factors. Further, several geriatric specific variables, including loss of ADL's, was highly predictive of outcome and should be prospectively incorporated into clinical trials. Finally, we developed a new prognostic model for eHL that identifies pt populations with markedly divergent outcomes. Disclosures: No relevant conflicts of interest to declare.