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1

Ohlig, Jasmin, Patrick Pötters, and Bert Leyendecker. "A3- versus 8D-Report." ZWF Zeitschrift für wirtschaftlichen Fabrikbetrieb 114, no. 11 (November 28, 2019): 734–36. http://dx.doi.org/10.3139/104.112178.

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2

Lubas Wahyudi, Pongky, and Anita Wulandari. "An Analysis of Product Dimensions Out of Specification as Quality Claim Improvement Activity : Application of 8D Method in the Injection Plastic Industry." JMPM (Jurnal Material dan Proses Manufaktur) 4, no. 2 (December 4, 2020): 80–90. http://dx.doi.org/10.18196/jmpm.v4i2.11358.

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Every company tries to find ways to maintain its market position in an increasingly competitive business environment. In order to be successful, companies need to achieve their objectives and goals to make their vision a reality while adhering to their mission. Company claims report in the few years still hasn’t solved yet. Such complaints are significant because customersatisfaction can only be improved if the root causes of the problem is clearly identified. In the plastic industry that produces parts for the automotive industry, a systematic method named 8D is used to analyze product conformity to specifications. The 8D method consists of nine disciplines problem-solving. The original purpose of 8D method was to eliminate the defect causing the problem, thus restoring customer satisfaction and level up the quality level of the company. This research established the suitability of the 8D for complaint settlement. 8D involves teamwork to solve the problem and using a 9-step structural approach. This case study resulted that the 8D is effective. The total customer claims at the end of last year until this year in Dec 2020 totaled zero (0) and process rejection for incorrect dimensions were reduced from 0.07 % to 0.01%.
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Mihalopoulos, Cathrine, Gang Chen, Angelo Iezzi, Munir A. Khan, and Jeffrey Richardson. "Assessing outcomes for cost-utility analysis in depression: comparison of five multi-attribute utility instruments with two depression-specific outcome measures." British Journal of Psychiatry 205, no. 5 (November 2014): 390–97. http://dx.doi.org/10.1192/bjp.bp.113.136036.

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BackgroundMany mental health surveys and clinical studies do not include a multi-attribute utility instrument (MAUI) that produces quality-adjusted life-years (QALYs). There is also some question about the sensitivity of the existing utility instruments to mental health.AimsTo compare the sensitivity of five commonly used MAUIs (Assessment of Quality of Life – Eight Dimension Scale (AQoL-8D), EuroQoL–five dimension (EQ-5D-5L), Short Form 6D (SF-6D), Health Utilities Index Mark 3 (HUI3), 15D) with that of disease-specific depression outcome measures (Depression Anxiety Stress Scales (DASS-21) and the Kessler Psychological Distress Scale (K10)) and develop ‘crosswalk’ transformation algorithms between the measures.MethodIndividual data from 917 people with self-report depression collected as part of the International Multi-Instrument Comparison Survey.ResultsAll the MAUIs discriminated between the levels of severity measured by the K10 and the DASS-21. The AQoL-8D had the highest correlation with the disease-specific measures and the best goodness-of-fit transformation properties.ConclusionsThe algorithms developed in this study can be used to determine cost-effectiveness of services or interventions where utility measures are not collected.
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Greatrex, Joan. "The Almonry School of Norwich Cathedral Priory in the Thirteenth and Fourteenth Centuries." Studies in Church History 31 (1994): 169–81. http://dx.doi.org/10.1017/s0424208400012869.

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In 1535 the monks of Norwich Cathedral Priory made the following report: Each year there are thirteen boys dwelling within the monastery and receiving free instruction in the scola grammaticalis or ‘almery scole’. They are also given food and clothing, which costs us 26s. 8d. per head per annum. In addition a master is provided to teach the boys, together with a servant to attend to their other needs; the former is paid an annual stipend of 53s. 4d., and the latter 20s. This school was founded by Herbert, the first bishop of the see of Norwich and the founder of the monastic cathedral community.
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Krasyuk, O. P. "Suppliers management tactics as a concept of sustainable enterprise development." Litiyo i Metallurgiya (FOUNDRY PRODUCTION AND METALLURGY), no. 4 (January 20, 2020): 68–71. http://dx.doi.org/10.21122/1683-6065-2019-4-68-71.

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The article deals with issues related to the work of OJSC “BSW Management Company of the Holding “BMC” with suppliers. Information on the developed concept of stakeholders between supplier and consumer is given. The types and structure of the procurement process are described, the gradation of the material in the procurement process is carried out. The method of evaluating supplier, starting with the calculation of the quality index of the material supplied, depending on the ratio value of the type of inconsistencies discussed logistics, but also on the basis of partnership relations provides information on the assessment of loyalty of the supplier. The report is also based on the developed activities, 8D, i.e. 8 step-by-step actions to eliminate inconsistencies. Perception of the supplier-consumer relationship is evaluated.
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HIRABAYASHI, Ryo, Hiroaki OOUCHI, Yuta TAKAHASHI, Tetsuo MAKI, and Hideo SAKAI. "8D-12 A Study on Differences of Mechanical Characteristics according to Preservation Method and Time of Soft Tissues (first report)." Proceedings of the Bioengineering Conference Annual Meeting of BED/JSME 2010.23 (2011): 75–76. http://dx.doi.org/10.1299/jsmebio.2010.23.75.

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7

Landa, Blanca B., Luis F. Arias-Giraldo, Béatrice Henricot, Miguel Montes-Borrego, Lucas A. Shuttleworth, and Ana Pérez-Sierra. "Diversity of Phytophthora Species Detected in Disturbed and Undisturbed British Soils Using High-Throughput Sequencing Targeting ITS rRNA and COI mtDNA Regions." Forests 12, no. 2 (February 17, 2021): 229. http://dx.doi.org/10.3390/f12020229.

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Disease outbreaks caused by introduced Phytophthora species have been increasing in British forests and woodlands in recent years. A better knowledge of the Phytophthora communities already present in the UK is of great importance when developing management and mitigation strategies for these diseases. To do this, soils were sampled in “disturbed” sites, meaning sites frequently visited by the public, with recent and new plantings or soil disturbances versus more “natural” forest and woodland sites with little disturbance or management. Phytophthora diversity was assessed using high-throughput Illumina sequencing targeting the widely accepted barcoding Internal Transcribed Spacer 1 (ITS1) region of rRNA and comparing it with the mitochondrial cytochrome c oxidase I (COI) gene. Isolation of Phytophthora was run in parallel. Nothophytophthora spp. and Phytophthora spp. were detected in 79 and 41 of the 132 locations of the 14 studied sites when using ITS or COI, respectively. A total of 20 Phytophthora amplicon sequence variants (ASVs) were assigned to known Phytophthora species from eight clades (1a, 2, 2b, 3a, 5, 6b, 7a, 8b, 8c, 8d, 10a, and 10b) and 12 ASVs from six clades (1a, 2c, 3a, 3b, 6b, 7a, 8b, 8c, and 8d) when using ITS or COI, respectively. Only at two locations were the results in agreement for ITS, COI, and isolation. Additionally, 21 and 17 unknown Phytophthora phylotypes were detected using the ITS and COI, respectively. Several Phytophthora spp. within clades 7 and 8, including very important forest pathogens such as P. austrocedri and P. ramorum, were identified and found more frequently at “disturbed” sites. Additionally, eight ASVs identified as Nothophytophthora spp. were detected representing the first report of species within this new genus in Britain. Only three species not known to be present in Britain (P. castaneae, P. capsici, and P. fallax) were detected with the ITS primers and not with COI. To confirm the presence of these or any potential new Phytophthora species, sites should be re-sampled for confirmation. Additionally, there is a need to confirm if these species are a threat to British trees and try to establish any eradication measures required to mitigate Phytophthora spread in Britain.
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8

Lerchl, Alexander. "Breeding of Djungarian hamsters (Phodopus sungorus): influence of parity and litter size on weaning success and offspring sex ratio." Laboratory Animals 29, no. 2 (April 1, 1995): 172–76. http://dx.doi.org/10.1258/002367795780740258.

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The reproduction of 368 breeding pairs of Djungarian hamsters ( Phodopus sungorus) has been recorded and evaluated during 5 consecutive years. Three-hundred-and-eight pairs (=83.7%) were successful breeders giving birth to 2113 litters (up to 13 per dam) with a total of 12,591 offspring (mean: 6.0α2.2 [αSD] per litter). One-hundred-and-fifty dams delivered within 25 days after pairing, indicating a breeding success in the first oestrous cycle of 40.8% of all pairs (95% confidence interval: 35.7%-46.0%). The average number of offspring was higher in the 2nd than in the first litter, reaching a maximum in the 3rd (6.8α2.0), and decreasing thereafter. The loss of offspring (mean: 24.2%) was higher in older parents and influenced by the number of offspring per litter, indicating that experience and stress contribute to breeding success. A small, but significantly higher number of females was recorded only when no loss of offspring occurred until weaning (females: 2.36α1.75; males: 2.16α1.63, P<0.001). There was no indication of a shift of the offspring sex ratio towards favouring females with increased litter numbers, in contrast to the predictions of the Trivers-Willard hypothesis, at least with respect to the species and the breeding conditions as described in this report. Since all breeders were kept under long-day type photoperiods (16L : 8D), no signs of seasonality in breeding outcome were noted.
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Choueiri, E., F. Jreijiri, P. Chlela, G. Louvet, and P. Lecomte. "Occurrence of Grapevine Declines and First Report of Black Dead Arm Associated with Botryosphaeria obtusa in Lebanon." Plant Disease 90, no. 1 (January 2006): 115. http://dx.doi.org/10.1094/pd-90-0115a.

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Grapevine, cultivated mostly in the Bekaa Plain, is one of the most important fruit crops in Lebanon. During July 2004, a survey was made in 11 vineyards of local table or wine grapes to evaluate the sanitary status of the grapevine industry as far as wood declines are concerned. The most common grapevine decline was esca. The two forms of the disease (mild and severe) were observed. The mild form was characterized by leaf symptoms consisting of interveinal necrotic spots with yellow or red chlorotic blotches on white and red cultivars. The severe form was characterized by dieback of one or more shoots, leaf drop, shrivelling, and drying of fruit clusters. In west Bekaa, on cv. Cabernet Sauvignon, some vines showed symptoms identical to those of Eutypa dieback such as stunted chlorotic shoots with small, distorted leaves; moreover, symptoms corresponding to black dead arm (BDA) such as wine red spots on the margins of leaves and dry spots were seen as reported earlier (1). Diseased vines of various cultivars were collected: 10 Cabernet Sauvignon (7 esca, 3 BDA, and 1 Eutypa dieback), 4 Beitamouni, 3 Carignan, 2 Teifihi, 1 Zeitouni, 1 Mourverdre, 1 Caladoc, and 1 Merlot. In wood, cross sections through the trunk were made that showed mainly central necrosis, white heart rot, brown red wood, and black spotting. Wedge-shaped lesions were the least common. Particularly for BDA, peeling off the bark revealed a brown streaking of the external wood. Isolations were made on malt agar (MA) with wood chips cut from the different necroses described above. Fungal identifications were based on morphological characteristics in comparison with French isolates after subculturing at 20 to 22°C: Fomitiporia sp. (F85-1), Phaeomoniella chlamydospora (F85-2), Eutypa lata (BX1-10, 8D, and 8F), and Botryosphaeria obtusa (F99-1). The fungus most frequently isolated from central necrosis with white heart rot was the basidiomycete Fomitiporia sp. (35% of vines). Cultures of Fomitiporia sp. on MA reached 4 to 5 cm in diameter after 2 weeks and were yellowish to brownish without conidia. P. chlamydospora (associated with esca, black goo, or Petri disease) was isolated from only 9% of vines investigated. Cultures of P. chlamydospora on MA were slow growing and reached 7 to 8 mm in diameter in the dark after 8 days. Colonies were white but became light green and later became dark green. Sporulation was abundant. E. lata (causing Eutypa dieback) was isolated from the vine of cv. Cabernet Sauvignon showing typical symptoms and from two vines showing symptoms of esca only. Two strains produced characteristic pycniospores, and all strains were identified using polymerase chain reaction (Primer Scar 10A-10B) (2). Among the saprophytic fungi isolated from the different kinds of necroses, either central, wedge-shaped, or under the bark, B. obtusa associated with BDA was found most commonly (65% of vines). Cultures of B. obtusa were gray brown with dense aerial mycelium. Pycnidia started to form after 4 to 5 days and conidia (20 to 26 × 9 to 16 μm) were dark brown when mature. These results are consistent with previous descriptions. To our knowledge, this is the first report of black dead arm in Lebanon. References: (1) P. Larignon et al. Phytopathol. Mediterr. 40:S336, 2001. (2) P. Lecomte et al. Appl. Environ. Microbiol. 66:4475, 2000.
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Terhorst, Yannik, Lina Braun, Ingrid Titzler, Claudia Buntrock, Johanna Freund, Janika Thielecke, David Ebert, and Harald Baumeister. "Clinical and cost-effectiveness of a guided internet-based Acceptance and Commitment Therapy to improve chronic pain–related disability in green professions (PACT-A): study protocol of a pragmatic randomised controlled trial." BMJ Open 10, no. 9 (September 2020): e034271. http://dx.doi.org/10.1136/bmjopen-2019-034271.

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IntroductionChronic pain is highly prevalent, associated with substantial personal and economic burdens, and increased risk for mental disorders. Individuals in green professions (agriculturists, horticulturists, foresters) show increased prevalence of chronic pain and other risk factors for mental disorders. Available healthcare services in rural areas are limited. Acceptance towards face-to-face therapy is low. Internet and mobile-based interventions (IMIs) based on Acceptance and Commitment Therapy (ACT) might be a promising alternative for this population and may enable effective treatment of chronic pain. The present study aims to evaluate the clinical and cost-effectiveness of an ACT-based IMI for chronic pain in green professions in comparison with enhanced treatment as usual (TAU+).Methods and analysisA two-armed pragmatic randomised controlled trial will be conducted. Two hundred eighty-six participants will be randomised and allocated to either an intervention or TAU+ group. Entrepreneurs in green professions, collaborating spouses, family members and pensioners with chronic pain are eligible for inclusion. The intervention group receives an internet-based intervention based on ACT (7 modules, over 7 weeks) guided by a trained e-coach to support adherence (eg, by positive reinforcement). Primary outcome is pain interference (Multidimensional Pain Interference scale; MPI) at 9 weeks post-randomisation. Secondary outcomes are depression severity (Quick Inventory Depressive Symptomology; QIDS-SR16), incidence of major depressive disorder, quality of life (Assessment of Quality of Life; AQoL-8D) and possible side effects associated with the treatment (Inventory for the Assessment of Negative Effects of Psychotherapy; INEP). Psychological flexibility (Chronic Pain Acceptance Questionnaire, Committed Action Questionnaire, Cognitive Fusion Questionnaire) will be evaluated as a potential mediator of the treatment effect. Furthermore, mediation, moderation and health-economic analyses from a societal perspective will be performed. Outcomes will be measured using online self-report questionnaires at baseline, 9-week, 6-month, 12-month, 24-month and 36-month follow-ups.Ethics and disseminationThis study was approved by the Ethics Committee of the University of Ulm, Germany (file no. 453/17—FSt/Sta; 22 February 2018). Results will be submitted for publication in peer-reviewed journals and presented at conferences.Trial registration numberGerman Clinical Trial Registration: DRKS00014619. Registered on 16 April 2018.
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Wang, Sanbin, Xiaoli Huang, Lin Liu, and Yang Liang. "Outcome of Ruxolitinib and Sirolimus in Preventing aGVHD Post to HLA Matched Hemotopietic Stem Cell Transplantation." Blood 132, Supplement 1 (November 29, 2018): 5727. http://dx.doi.org/10.1182/blood-2018-99-119109.

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Abstract Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for hematological malignancies. Graft-versus-host disease (GVHD) is an important cause of graft failure and death. At present, the classic prevention program of GVHD is cyclosporine and calcineurin inhibitor (CNI; i.e. tacrolimus) plus methotrexate (CTX) or mycophenolate mofetil (MMF). However, the incidence of aGVHD is about 30-50%. Furthermore, the classic preventive regimen can also inhibit the graft-versus-leukemia effective (GVL) effect while reducing aGVHD, thereby increasing the recurrence rate, slowing the immune reconstitution, increasing the opportunistic infection. Ruxolitinib is a selective JAK1/2 small molecule kinase inhibitor, which has been reported to have a significant effect on the treatment of GVHD, while retaining the GVL effect with mild side effects. Sirolimus is a macrolide antibiotic with antifungal, immunosuppressive and antitumor effects. Based on the above studies, it can be speculated that the combination of ruxolitinib and sirolimus may have the function of immune inhibition, anti-tumor, while retaining the GVL effect, reducing the recurrence rate and reducing the risk of infection. Here we report our experience of using the combination of ruxolitinib and sirolimus to prevent the occurrence of aGVHD post to HLA matched hematopoietic stem cell transplantation and analyzed the incidence and prognosis of aGVHD. 1. Patients and Methods 1.1 Patients: There were five patients received HSCT enrolled in this study from March 2018 to July 2018, including 2 males and 3 female with a median age 30 (range: 13-46) years old. There were three patients with acute lymphocyte leukemia (ALL; one CR and two NR patients) and two cases were acute myeloid leukemia (AML; one CR and one NR patient). 1.2 Donor source: A high-resolution genotyping was applied to perform the HLA matching test. All the donors to the 5 patients were their siblings. The results are all HLA10/10. There were 3 cases indicated blood type mis-matching, 1 case with major side mis-match, and 1 case with minor side mis-match. 1.3 Conditioning: Two conditioning regimens were used per disease type, repspectively. Two patients with AML were treated with: fludarabine (Flu)30mg/m2×5d(d-7~-3)+ busulfan (Bu)130mg/m2×4d(d-6~-3)+semustine200mg/m2×1d(-8d); 3 patients with ALL were treated with fludarabine(Flu)30mg/m2×5d(d-7~-3) +melphalan(Mel)50mg/m2×4d(d-6~-3) +semustine 200mg/m2×1d(-8d) . 1.4 GVHD prophylaxis: the phophylaxis regimen consist of ruxolitinib and sirolimus. The ruxolitinib was give at d-6~+5 at 10mg bid, d+6~d+41 at 10mg qd, d+42~d+ 101 5mg qd, d+102~d+222 2.5mg qd. The dosage of ruxolitinib was decreased 50% when the patient's weight <25kg or combined with azole drugs; sirolimus is orally administered from day -2d to day 60. The loading dose was 3.6 mg/m2, the maintenance dose was 1.2 mg/m2, and the whole blood concentration was maintained at (10 ± 2) ng/ml. 2 Results 2.1 Hematopoietic Reconstitution: All 5 patients were successfully engrafted for hematopoietic reconstitution. The median time of platelet engraftment was +13d (10~14d), and the median time of neutrophil engraftment was +12d (9~12d). 2.2 The incidence of GVHD: Only one of the 5 patients developed grade II liver aGVHD, and the incidence of grade II to IV aGVHD was 20.0% (1/5). 2.2 Other transplant-related complications: 2 out of 5 patients developed engraftment syndrome and was relieved with small doses of glucocorticoids; 1 patient developed hemorrhagic cystitis, 3 patients developed mucositis, and 1 patient had concurrent Pulmonary fungal infection, 2 cases had cytomegalovirus infection, all the symptoms were improved through hydration, forced diuretic, voriconazole and ganciclovir administration. 2.3 Prognosis: The 100-day overall survival rate (OS) was 100%. All the 5 patients were alive at our follow-up on July 10. The engrafted state was completely donor type; MRD level was negative, and the general condition was good. 3 Conclusion This experimental study shows the prevention application of the combination of ruxolitib and sirolimus post to allogeneic hematopoietic stem cell transplantation is an innovative combination of immunosuppressive therapy, which is safe and tolerable. A randomized clinical trial is underway to evaluate the efficiency of this new approach for aGVHD. Disclosures No relevant conflicts of interest to declare.
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Kim, Andrew H., Afaf Girgis, Neda Karimi, Alexandra J. Sechi, Joseph Descallar, Jane M. Andrews, Corey A. Siegel, and Susan J. Connor. "A Web-Based Decision Aid (myAID) to Enhance Quality of Life, Empowerment, Decision Making, and Disease Control for Patients With Ulcerative Colitis: Protocol for a Cluster Randomized Controlled Trial." JMIR Research Protocols 9, no. 7 (July 10, 2020): e15994. http://dx.doi.org/10.2196/15994.

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Background Patients with ulcerative colitis (UC) often face complex treatment decisions. Although shared decision making (SDM) is considered important, tools to facilitate this are currently lacking for UC. A recent pilot study of a novel Web-based decision aid (DA), my Actively Informed Decision (myAID), has suggested its acceptability and feasibility for informing treatment decisions and facilitating SDM in clinical practice. Objective This paper describes the study protocol of the myAID study to assess the clinical impact of systematic implementation of myAID in routine UC management. Methods The myAID study is a multicenter, cluster randomized controlled trial (CRCT) involving 22 Australian sites that will assess the clinical efficacy of routine use of myAID (intervention) against usual care without access to myAID (control) for UC patients. Participating sites (clusters) will be randomly allocated in a 1:1 ratio between the 2 arms. Patients making a new treatment decision beyond 5-aminosalicylate agents will be eligible to participate. Patients allocated to the intervention arm will view myAID at the time of recruitment and have free access to it throughout the study period. The effect of the myAID intervention will be assessed using the results of serial Web-based questionnaires and fecal calprotectin at baseline, 2 months, 6 months, and 12 months. A Web-based questionnaire within 2-4 weeks of referral will determine early change in quality of decision making and anxiety (both arms) and intervention acceptability (intervention arm only). Results Study recruitment and funding began in October 2016, and recruitment will continue through 2020, for a minimum of 300 study participants at baseline at the current projection. The primary outcome will be health-related quality of life (Assessment of Quality of Life-8D), and secondary outcomes will include patient empowerment, quality of decision making, anxiety, work productivity and activity impairment, and disease activity. In addition, we aim to determine the predictors of UC treatment decisions and outcomes and the cost-effectiveness of implementing myAID in routine practice. Feedback obtained about myAID will be used to determine areas for improvement and barriers to its implementation. Completion of data collection and publication of study results are anticipated in 2021. Conclusions myAID is a novel Web-based DA designed to facilitate SDM in UC management. The results of this CRCT will contribute new evidence to the literature in comparing outcomes between patients who routinely access such decision support intervention versus those who do not, across multiple large inflammatory bowel disease centers as well as community-based private practices in Australia. Trial Registration Australian New Zealand Clinical Trial Registry ACTRN12617001246370 http://anzctr.org.au/Trial/ Registration/TrialReview.aspx?ACTRN=12617001246370 International Registered Report Identifier (IRRID) DERR1-10.2196/15994
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Chakraverty, Ronjon, Maria Dimopoulou, Julie Glanville, Kirsty Thomson, Karl Peggs, Donald Milligan, Gordon Cook, et al. "De-Escalation of the Alemtuzumab Dose Prior to Nonmyeloablative HLA-Identical Sibling Transplantation: Crucial Role of Timing." Blood 108, no. 11 (November 16, 2006): 2901. http://dx.doi.org/10.1182/blood.v108.11.2901.2901.

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Abstract Nonmyeloablative conditioning with Fludarabine/Melphalan/Alemtuzumab prior to allogeneic stem cell transplantation is associated with low toxicity. In vivo T-cell depletion with Alemtuzumab is highly effective at preventing GVHD, but the antibody persists for several weeks post-transplantation and this contributes to high rates of viral infection. We reasoned that a reduction in the dose of Alemtuzumab (from the initial total dose of 100mg divided over 5 days from d-8 to d-4) would permit improved immune reconstitution post-transplantation. We report here an analysis of two consecutive multi-center trials in which the dose of Alemtuzumab was reduced to a total dose of 60mg or below. Eligibility criteria included patients with hematological malignancies who were aged 18–65yr, who had an HLA-identical sibling, life expectancy >3 months and who were not suitable for standard myeloablative conditioning. Primary endpoints included TRM, incidence of GVHD/infection and chimerism. The studies received IRB approval and all patients gave informed consent. Study 1 evaluated a dose reduction of Alemtuzumab to a total dose of 60mg split between day d-8 and d-7 and was terminated when stopping rules were invoked after accrual of 18 patients (median follow up 23mo). Study 2 evaluated de-escalation of the Alemtuzumab dose in three consecutive cohorts of patients: 60mg split between d-2 and d-1 (n=26, median follow-up 15mo); 40mg split between d-2 and d-1 (n=27, 9mo); 30mg d-1 (n=28, 4mo). 91/99 patients recruited to the 2 studies are evaluable. Median age is 50yr (range 18–64). Diagnoses were AML/ALL n=25, CLL n=12, NHL n=30, Hodgkins n=12, myeloma n=11, MDS n=1. 80.6% of patients had advanced disease at the time of transplantation. No significant differences were identified in patient characteristics between each study/cohort. Study 1 (60mg total, split d-8 and d-7) OS, PFS at 1 year and 100d TRM were 89%, 72% and 0% respectively. Cumulative incidences of acute GVHD II-IV and chronic GVHD were 28% and 17% respectively. All patients engrafted and 77% were full donor chimeras. In study 2, cohort 1 (60mg total, split d-2 and -1), OS, PFS at 1 year and 100d TRM were 84%, 57% and 4% respectively. Cumulative incidences of acute GVHD II-IV and chonic GVHD were 0% (p<0.005 versus study 1) and 14% respectively. All patients engrafted but only 18% of patients in this cohort were full chimeras (p<0.01 versus study 1). No differences in the cumulative incidences of CMV reactivation were observed (33% vs. 43%). Subsequent total dose reductions to 40mg and 30mg Alemtuzumab in cohorts 2 and 3 have shown no significant changes in the 100d TRM (3.7% and 0% respectively) or the incidence of acute GVHD (12% and 5% respectively). We conclude that significant de-escalation of the Alemtuzumab dose following HLA-identical sibling transplantation is feasible without increasing the toxicity of the procedure. However, there is a higher rate of acute GVHD if the antibody is administered 7–8d compared to 24–48h prior to stem cell infusion.
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Milpied, Noel, Bernard Dazey, Zoran Ivanovic, Pascale Duchez, Stephane Vigouroux, Reza Tabrizi, Arnaud Pigneux, et al. "Rapid and Sustained Engraftment of a Single Allogeneic Ex-Vivo Expanded Cord Blood Unit (CBU) After Reduced Intensity Conditioning (RIC) in Adults. Preliminary Results of a Prospective Trial." Blood 118, no. 21 (November 18, 2011): 486. http://dx.doi.org/10.1182/blood.v118.21.486.486.

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Abstract Abstract 486 CBU is a widely used source of stem cells for allogeneic transplantation (SCT). Engraftment rate and speed of a single CBU in adults remains unsatisfactory. Transplantation of 2 CBU may overcome this problem to the expense of an increased incidence of GVHD. Until now, attempts at using ex-vivo expanded CBU have been unsuccessful to promote long term engraftment of the expanded product. We report the results achieved in the first 8 Pts included in a PCT of transplantation of a single ex-vivo expanded allogeneic CBU. Eudract 2008–006665–81, Clinicaltrials.gov NCT 01034449. Methods: Adults patients with an indication for SCT and unable to tolerate MAC (age>45, comorbidities, previous high-dose therapy) were included after inform consent if no Id sibling, no MUD 9 (C or DQ mismatch accepted) to 10/10 HLA matches and no CBU fulfilling the HLA matching (≥ 4/6) and richness (≥ 3 to 4 × 107 TNC/kg before thawing) criteria were available. RIC consisted of Flu (40 mg/m2/d × 5d), Cyclophosphamide (50 mg/kg × 1d) ICT 2 Gy. GVHD prevention consisted of MMF (d-3 to d28) and CSA from d-3. Graft engineering: 1 CBU with > 2 TNC/kg < 3 and 4 to 6 HLA compatibilities was thawed, CD34+ cells were selected through magnetic device (Miltenyi) and submitted to ex-vivo expansion in SF medium ( HPO1-Macopharma) supplemented with SCF, Flt3l, G-CSF and TPO during 12 days, starting d-12 of the transplantation (Ivanovic, Cell Transplant 2011) CD34 neg cells were cryopreserved. On d0, expanded cells were washed and resuspended in HSA 4% and upon viability and sterility were injected to the pt. Cd34 neg cells were thawed and injected to the pt 3 h later. Results: From 03/2010 to 06./2011 8 pts have been included, med age 55y.o. (26–64) with AL: 3, Hodgkin's: 2, MDS: 3. Pts had received 1 to 3 lines of Tx (med:2). For 1 pt the expanded product was contaminated and this pt then received a back-up unmanipulated CBU. He engrafted correctly and is AW at 14 m with full donor chimerism. For the 7 other pts, the ex-vivo median fold expansion of CD34+ cells and TNC was 39 (29–75) and 390 (127–526) respectively, leading to a graft that contained 1.3 to 13 × 106 CD34+ cells/kg (med: 2 × 106/kg). The CD34 neg counterpart contained 3 × 106 CD3+/kg (1–5) and 0,9 × 106 CD19+ cells/kg (0,3–1,5). At d42, 6/7 pts who received the expanded graft engrafted with ≥99% donors cells. A 2d RIC was performed followed by a double CBU transplant in the patient who did not engraft. That 2d graft again failed to engraft. However the patient remains alive at 9m. For the 6 pts who engrafted with the expanded product the time to reach 500, 1000 PMN's and 20 000 plts/mm3 was 7d (6–19), 8d (6–21) and 24d (0–39) respectively. The chimerism on WBC and CD3+cells (evaluated on d 15, 42, 60, 100, 180, 365) remains full donor up to 1 year + after transplant (1y+: 2 pts; 6m+: 1pt; 180d+: 1 pt; 60d+: 1pt) or to relapse (at 1y) in the one pt who relapsed. Five pts experienced an AGVHd (grade III-IV: 1 pt). With a median FU of 10m (2 to 18m) 7 pts are alive, 6 wo disease. One pt died 1y after transplant from relapse. Conclusion: Ex-vivo expansion of a single CBU is feasible and reproducible. Transplantation of the expanded product together with the CD34 neg counterpart of the same CBU produces rapid, complete and sustained donor engraftment after RIC in adults. Disclosures: No relevant conflicts of interest to declare.
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15

Bischof, Danielle Anna, Yuhree Kim, Dan G. Blazer, Shishir Kumar Maithel, T. Clark Gamblin, Todd W. Bauer, Paul Jack Karanicolas, Calvin Law, Fayez A. Quereshy, and Timothy M. Pawlik. "Open versus minimally invasive management of gastric GIST: An international multi-institutional analysis of short- and long-term outcomes." Journal of Clinical Oncology 32, no. 3_suppl (January 20, 2014): 85. http://dx.doi.org/10.1200/jco.2014.32.3_suppl.85.

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85 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract. Overall surgical experience with minimally invasive surgery (MIS) has increased, however, published reports on MIS resection of GIST are currently limited to small, single institution experiences. Methods: 397 patients who underwent surgical resection of a gastric GIST between 1998 and 2012 were identified from an international, multi-center database. The impact of the MIS approach on recurrence and survival was analyzed by the use of propensity-score matching by comparing clinicopathologic factors between patients who underwent open vs MIS resection. Results: Median patient age was 65 years and 50% were female. Median tumor size was 4.3cm (IQR 3.0-7.6cm). A minority of patients received neoadjuvant therapy (6%). Overall, 186 (47%) patients had a MIS approach: laparoscopic (89%), laparoscopic hand assist (4%), combined laparo-endoscopic (3%) and robotic (4%). There were 19 (10%) conversions to open; the most common reasons for conversion were tumor more extensive than anticipated (26%) and unclear anatomy (16%). Patients who underwent MIS resections had smaller tumors (MIS: 3.5cm vs open: 5.8cm; p<0.01). MIS resections were associated with minimal blood loss (MIS: 50 cc vs open: 225 cc) and shorter operative time (MIS: 160 min vs open: 201 min) (both p<0.01). There was no difference in rates of tumor rupture (MIS: 1.1% vs open: 0.9%; p=0.81). An R0 resection was achieved in the majority of patients (MIS: 98% vs open: 92%; p=0.07). MIS patients had a lower incidence of grade 3 or 4 complications (MIS: 3% vs open: 10%; p=0.01) and a shorter length of stay (MIS: 3d vs open: 8d; p<0.01). After propensity score matching for age, sex, tumor size, mitotic rate and tumor rupture, there was no difference in risk of recurrence or overall survival for the MIS treated group vs. the open group (HR 0.65 & HR 0.76, respectively; both p>0.05). Conclusions: An MIS approach for gastric GIST is associated with a low incidence of complications and a comparable R0 resection rate. The long-term oncological outcome following MIS is excellent and therefore the MIS approach should be considered preferable.
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16

Kulkarni, Ravindra, Krishna Kompalli, Naveen Gaddam, Chandrashekar V, Bikshupati Darna, Achaiah Garlapati, Dileep Kumar, and Baswaraju Machha. "Synthesis, characterization, antitubercular and anti-inflammatory activity of new pyrazolo[3,4-d]pyrimidines." Combinatorial Chemistry & High Throughput Screening 23 (September 18, 2020). http://dx.doi.org/10.2174/1386207323999200918114905.

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Aims and Objective: Copious proinflammatory cytokines including TNF-α and IL-1β are involved in progression of inflammation in human body. Inhibition of signaling mediated by proinflammatory cytokines offer effective in the treatment of inflammatory diseases. The treatment of dreadful infectious disease mycobacterium tuberculosis still remains a challenge owing to resistance to multiple drugs hence an urgent need for newer drugs. Pyrazolo[3,4-d]pyrimidines have been disclosed to possess numerous pharmacological activities including anti-inflammatory, antimicrobial and antitubercular activities. Here in we report the synthesis of pyrazolo[3,4-d]pyrimidines for anti-inflammatory and antitubercular activities. Materials and Methods: The targeted compounds having pyrazolo[3,4-d]pyrimidines 8a-m were synthesized in three step reactions with the formation of key intermediate 5-amino-4-cyno-1-phenyl pyrazole which upon cyclization resulted in 4amino pyrazolo[3,4-d]pyrimidine for subsequent benzoylation with substituted benzoyl chlorides to form 8a-m. Antiinflammatory activity of 8a-m was assessed at 25 mg/Kg dose and minimum inhibitory concentration against gram positive, gram negative and mycobacteria was also performed. Binding interactions were also measured in binding pocket of p38 kinase. Results: Four compounds 8a, 8b, 8e and 8i significant anti-inflammatory activity in rat paw edema model induced by carrageenan and among all 8b was potent with 80.6% activity. Numerous compounds exhibited potent activity against fungal strains than bacterial strains, compound 8k was most potent against gram negative bacteria Klebsiella pneumoniae. Compounds 8d, 8e and 8f exhibited antitubercular activity with MIC value of 6.25 μg/mL Conclusion: Substituted N-benzoylated amino pyrazolo[3,4-d]pyrimidines endowed significant and potent anti-inflammatory and antimicrobial activities. Molecular docking studies also revealed favorable interactions in active site of p38 kinase.
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17

Will, E., J. R. Tuell, J. Park, W. Wang, H. W. Cheng, and Y. H. B. Kim. "Effect of Different Photoperiods on Quality Attributes and Oxidative Stability of Breast Meat (M. Pectoralis Major) from Broilers." Meat and Muscle Biology 3, no. 2 (December 1, 2019). http://dx.doi.org/10.22175/mmb.10814.

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ObjectivesIn the broiler industry, high photoperiod (the duration of light exposure per day) regimes have traditionally been utilized to increase yield of breast meat, as well as maximize feed intake and growth rate in the growing period. However, recent literature reports this practice may have adverse effects on broiler welfare, resulting in impaired mobility and increased incidence of leg abnormalities. However, little information available in the current literature regarding effects of photoperiod on meat quality attributes and oxidative stability of broiler meat. Thus, the objective of this study was to evaluate the quality characteristics and lipid/protein oxidative stability of breast meat from broilers that were exposed to different photoperiod combinations.Materials and MethodsA total of 432 Ross 308 broiler chicks were allocated among 4 rooms each subjected to one of the following photoperiod treatments (hours Light: Dark): 20L:4D, 18L:6D, 16L:8D and 12L:12D, with 6 pens per treatment. At d 42, 2 broilers per pen (12 broilers/treatment) were randomly selected, harvested and air chilled for 24 h at 2°C. At l day postmortem, paired breast muscles (M. pectoralis) were collected for the meat quality analyses such as, water-holding capacity (drip/purge/cook loss), Warner-Bratzler shear force (WBSF), and display color for 7 d under fluorescent light (1450 lx). Lipid oxidation was assessed via the TBARS assay and protein oxidation by thiol content measured at d 1 and d 7 of display. The experimental design was randomized complete block design. Data were analyzed using the PROC MIXED procedure of SAS, and means were separated using least significant differences (P < 0.05).ResultsPhotoperiod had no effect on fillet yield and pH (P > 0.05). No significant difference in WBSF was found between treatments, although 12L:12D had a trend of higher WBSF (P = 0.08). Higher moisture loss during carcass chilling was found in carcasses from 20L:4D compared to 16L:8D and 12L:12D treatments (P < 0.05). No other measure of water-holding capacity was affected, though the 16L:8D treatment demonstrated a trend of higher freezing/thawing loss compared to other treatments (P = 0.06). Proximate moisture, protein and lipid contents were unaffected by photoperiod (P > 0.05), but higher ash was observed in 16L:8D over 20L:4D and 18L:6D (P < 0.05). Different photoperiod combinations affected color stability of breast meat during display (P < 0.05). Of note, fillets from 20L:4D maintained highest L* and hue angle, and least a* values (P < 0.05), indicating inferior color stability compared to other treatments. Oxidation increased with display, and fillets from 20L:4D and 18L:6D had higher TBARS over 12L:12D (P < 0.05); no photoperiod effect was observed in thiol content (P > 0.05).ConclusionResults suggest 20L:4D photoperiod regimes may be detrimental to meat quality, as carcasses from this treatment group had higher moisture loss during chilling, and color measurements characterized these fillets as being paler and more discolored than other treatments. Fillets from 12L:12D maintained lower TBARS than 20L:4D and 18L:6D, suggesting photoperiod regimes allowing more hours of dark may be beneficial in improving oxidative stability. Further studies determining the effects of photoperiod on quality and protein functionality of chicken meat for processing technological would be highly warranted.
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