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Background Nutrients that support the desired growth and development of the fetus (i.e., micronutrients like folate, iron, and zinc) have been associated with birth outcomes, such as gestational age at delivery and birth weight. Objective We characterized the maternal dietary patterns that explain the maximum variation in folate, iron, and zinc intakes in pregnant Korean women using reduced-rank regression (RRR) and investigated the association of these patterns with small-for-gestational-age (SGA) risk. Methods A total of 1,158 pregnant Korean women at 12-28 weeks gestation and their newborns were recruited for the Mothers and Children's Environmental Health (MOCEH) study between 2006 and 2010. A semiquantitative food frequency questionnaire was collected from the women, and RRR was used to derive their dietary patterns. Log-transformed maternal intakes of folate, iron, and zinc were selected as the intermediate response variables to extract dietary patterns. Infant birth outcome measurements were obtained from hospital records. Associations were assessed by logistic regression with adjustment for confounding factors. Results Three dietary patterns were identified. Pattern 1, characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts, was associated with a lower risk of SGA in the highest quartile compared to the lowest quartile (odds ratio: 0.36; 95% confidence interval: 0.14, 0.94). Especially, maternal dietary pattern 1 was negatively related to high-sensitivity C-reactive protein in the blood and malondialdehyde levels in the urine. No association was observed for other dietary patterns with SGA. Conclusions Among pregnant Korean women, adherence to a dietary pattern characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts is associated with a lower risk of delivering SGA infants.

Introduction: Although psoriasis and obstructive sleep apnea syndrome (OSAS) are associated with systemic inflammation, studies on their potential bilateral relationship are not sufficient. Aim: To investigate vitamin D levels and receptor gene polymorphisms in patients with OSAS and psoriasis and the associations with these diseases. Material and methods: One hundred thirty-seven patients included in the study consisted of 4 different groups: group 1, those with both diseases; group 2, those with OSAS only; group 3, patients with psoriasis only; and group 4, healthy controls. The patients??? serum calcium, phosphorus, AHI, Epworth Sleepiness Scale, Psoriasis Area Severity Index, and VDR TagI, ApaI, BsmI polymorphisms were compared. Results: Vitamin D levels of groups 1, 2 and 3 were found to be lower than in controls. There was no statistically significant correlation between VDR TagI, ApaI, BsmI gene polymorphisms of the groups. Vitamin D levels were significantly higher in patients with heterozygous ApaI genotype (A/C) compared to patients with normal (A/A) or homozygous mutant (C/C) genotype (p < 0.05). No relationship was determined between VDR TagI, ApaI, BsmI, and the other parameters. Conclusions: In our study, 1,25(OH)2-vitamin D3 levels were significantly lower in all disease groups compared to the control group. Although there is no difference between the groups in terms of VDR gene polymorphism, we think that there may be a bidirectional relationship between these diseases based on the low vitamin D levels. Namik Kemal University Scientific Research Projects Coordination Unit [NKUBAP.02, 18.188] A this study was supported by Namik Kemal University Scientific Research Projects Coordination Unit (Project Number NKUBAP.02.GA.18.188).

International audience; Objectives: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication.Methods: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen.Results: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/μL (range 225-560) for switching patients, compared with 362 and 136 cells/μL for the other two patients.Conclusions: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy for myelodysplastic syndromes (MDS), although it is infrequently offered to older patients. The relative benefits of HCT over non-HCT therapy in older patients with higher-risk MDS have not been defined. METHODS We conducted a multicenter biologic assignment trial comparing reduced-intensity HCT to hypomethylating therapy or best supportive care in subjects 50-75 years of age with intermediate-2 or high-risk de novo MDS. The primary outcome was overall survival probability at 3 years. Between January 2014 and November 2018, we enrolled 384 subjects at 34 centers. Subjects were assigned to the Donor or No-Donor arms according to the availability of a matched donor within 90 days of study registration. RESULTS The median follow-up time for surviving subjects was 34.2 months (range: 2.3-38 months) in the Donor arm and 26.9 months (range: 2.4-37.2 months) in the No-Donor arm. In an intention-to-treat analysis, the adjusted overall survival rate at 3 years in the Donor arm was 47.9% (95% CI, 41.3 to 54.1) compared with 26.6% (95% CI, 18.4 to 35.6) in the No-Donor arm ( P = .0001) with an absolute difference of 21.3% (95% CI, 10.2 to 31.8). Leukemia-free survival at 3 years was greater in the Donor arm (35.8%; 95% CI, 29.8 to 41.8) compared with the No-Donor arm (20.6%; 95% CI, 13.3 to 29.1; P = .003). The survival benefit was seen across all subgroups examined. CONCLUSION We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host disease (GVHD), all grade I-II. The cumulative incidence (CI) of chronic GVHD at five-year was 34%. The CI of non-relapse mortality at one-year was 29%. Progression-free survival (PFS) rates at two-year and five-year were 49% (95% CI = 22-71%) and 39% (95% CI = 14-64%), respectively. The two-year and five-year overall survival (OS) rates were 65% (95% CI = 38-82%) and 40% (95% CI = 12-68%), respectively. The five-year rate for both PFS and OS was 80% in CR1 patients versus 0% in patients not in CR1. In conclusion, allo-HCT provides long-lasting remissions in BPDCN patients, particularly when performed in CR1.

Recent compelling evidence showed that innate immune effector cells could recognize allogeneic grafts and prime an adaptive immune response. Signal regulatory protein α (SIRPα) is an immunoglobulin superfamily receptor that is expressed on myeloid cells; the interaction between SIRPα and its ubiquitously expressed ligand CD47 elicits an inhibitory signal that suppresses macrophage phagocytic function. Additional studies showed that donor-recipient mismatch in SIRPα variants might activate monocytic allorecognition, possibly as the result of non-self SIRPα-CD47 interaction. However, the frequency of SIRPα variation and its role in hematopoietic stem cell transplantation (HSCT) remains unexplored. We studied 350 patients with acute myeloid leukemia/myelodysplastic syndrome who underwent HLA-matched related HSCT and found that SIRPα allelic mismatches were present in 39% of transplantation pairs. SIRPα variant mismatch was associated with a significantly higher rate of chronic graft-versus-host disease (GVHD; hazard ratio [HR], 1.5; P = .03), especially de novo chronic GVHD (HR, 2.0; P = .01), after adjusting for other predictors. Those with mismatched SIRPα had a lower relapse rate (HR, 0.6; P = .05) and significantly longer relapse-free survival (RFS; HR, 0.6; P = .04). Notably, the effect of SIRPα variant mismatch on relapse protection was most pronounced early after HSCT and in patients who were not in remission at HSCT (cumulative incidence, 73% vs 54%; HR, 0.5; P = .01). These findings show that SIRPα variant mismatch is associated with HSCT outcomes, possibly owing to innate allorecognition. SIRPα variant matching could provide valuable information for donor selection and risk stratification in HSCT.

Relapse after allogeneic hematopoietic cell transplantation (HCT) leads to poor survival in patients with acute myeloid leukemia (AML). A second HCT (HCT2) may achieve durable remission. To determine the outcomes of patients who received an HCT2 for relapsed AML and to evaluate the predictors of overall survival (OS) and progression-free survival (PFS). We retrospectively reviewed medical records of adult patients who underwent an HCT2 for relapsed AML at our institution during 2000 to 2019. Ninety-one patients were identified with a median age of 44 years (range 18-73) at HCT2. Donor types were HLA-identical sibling (n = 37 [41%]), HLA-matched–unrelated (n = 34 [37%]), haploidentical (n = 19 [21%]), and cord blood (n=1 [1%]). Donors were different at HCT2 in 53% of patients. The majority of patients received reduced intensity conditioning (n = 71 [78%]) and were in remission (n = 56 [61%]) at HCT2. The median remission duration after HCT1 was 8.4 months (range 1-70) and the median time between transplants was 14 months (range 3-73). The median follow-up of surviving patients after HCT2 was 66 months (range 2-171), with 32% alive at time of analysis. The most common cause of death was disease recurrence (n = 45 [73%]). At 2 years, the rates of OS, PFS, progression, and nonrelapse mortality were 36%, 27%, 42%, and 18%, respectively. The development of chronic graft-versus-host disease (GVHD) after first HCT and HCT comorbidity index (HCT-CI) ≥2 at HCT2 were associated with inferior PFS and OS after HCT2. A second HCT is feasible in selected patients with AML who have relapsed after HCT1. Long-term survival benefit is possible in patients without chronic GVHD after HCT1 and HCT-CI

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.

Risk yönetimi, risk iletişiminde önemli role sahiptir. Günümüzde sosyal medyanın da etkisiyle birlikte kitle iletişim araçlarının etkin kullanımına ihtiyaç vardır. Bu açıdan hızlı şekilde topluma ulaşım sağlayan ve kolay yönetilebilir iletişim araçlarının başında sosyal medya gelmektedir. Zamanında, eyleme geçirilebilir ve güvenilir bilgi kanalları, özellikle yüksek korku ve belirsizlik içeren durumlarda hayati öneme sahiptir. Acil durumlarda bilgi akışı ve yüksek şeffaflığın tesis edilebilmesi için iletişime açık ve esnek bir yaklaşım gereklidir. Araştırmanın amacı, günümüz koşullarında yaşadığımız salgın ve ardından aynı dönemde meydana gelen deprem afetleri kapsamında AFAD’ın risk yönetimi açısından iletişim stratejisini nasıl ele aldığının sosyal medya hesapları üzerinden incelenmesidir. Çalışma, Twitter’da zaman dilimi olarak 11 Mart 2020-31 Aralık 2020 tarihleri arasında AFAD tarafından paylaşılan tweetlerden oluşmaktadır. Elde edilen veriler içerik analizi yöntemiyle incelenmiştir. Kurumun mesaj içerikleri risk iletişim sürecinde bilgilendirme, önleyici mesaj, acil durum ve iyileştirme şeklinde gruplandırılmıştır. İncelenen tweetler; deprem, meteoroloji, kaza-zehirlenme-yangın-patlama, Covid-19, yardım faaliyetleri, yapılan etkinlikler, uluslararası tanınırlık çalışmaları, anma-özel gün-bayram mesajları şeklinde sınıflandırılmışlardır. Bu kapsamda AFAD’ın konu içeriklerine göre kullandığı risk iletişim teknikleri incelenmiştir. Sonuç olarak AFAD’ın risk iletişimi bağlamında sosyal medya araçlarını eş zamanlı olarak etkin kullanmasının kriz süreçlerinde toplumun yaşamış olduğu kaygı ve belirsizliğin giderilmesinde önemli bir etkiye sahip olduğu söylenebilir.

Background/aim The aim of this study is to present our experience on various endovascular treatment modalities of basilar fenestration aneurysms and to review our findings along with the literature data. Materials and methods A total of 24 patients with 26 BAF aneurysms who have admitted to our clinics were endovascularly treated, and two centers were used for this purpose. All patients were evaluated with computed tomography (CT), CT angiography (CTA) and digital subtraction angio graphy (DSA) before the procedure. Results Whole aneurysms were successfully occluded with 100 per cent rate of technical success. Procedure-related complications were encountered in two patients. Our comprehensive literature research has revealed that most of the papers related with the topic were case reports. In the literature, it has been reported from 46 studies that 101 patients with 113 BAF aneurysms were endovascularly treated between years 1993 and 2019. The overall positive outcome, clinical success, and the complication rate values of the studies in the literature were 97, 91 and 8.8 percent, respectively, whereas these values were 100%, 92% and 7.6% in our study. Conclusions Despite the low number of cases in the current study, it is by far the most comprehensive series in the literature to date. Our results suggest that BAF aneurysms can be successfully and safely treated with different endovascular techniques, with the gradually increased use of stents in recent years.

Requirements specifications are essential to properly communicate requirements among the software development team members. However, each role in the team has different informational needs in order to perform their activities. Thus, the requirements engineer should provide the necessary information to meet each team member's necessities to reduce errors in software development due to inadequate or insufficient communication. Although some research is concerned with communicating requirements among clients and analysts, no related research has been found to evaluate and improve requirements communication within the software development team. With this in mind, we present the ReComP framework, which assists in the identification of problems in the artifacts used to communicate requirements, identification of informational requirements for each role of the development team, and provide improvement suggestions to address requirements communication problems. ReComP was developed using the Design Science Research (DSR) method and this paper presents the results of two DSR cycles considering the use of ReComP for the developer and tester roles by using, respectively, user stories and use cases as requirements specifications. The results provide evidence that ReComP helps software development teams to identify and improve issues in the requirements specifications used for project communication. In two independent studies, ReComP was able to decrease the frequency of problems by 77% in user stories identified by developers and the frequency of all (100%) problems in use cases identified by testers.

In the 2015 Iqaluit Declaration, the Arctic Council created a Task Force on Arctic Marine Cooperation (TFAMC) ‘to assess future needs for a regional seas programme or other mechanism, as appropriat...

Clonal hematopoiesis (CH) is associated with older age and an increased risk of myeloid malignancies and cardiovascular complications. We analyzed donor DNA samples in patients with AML/MDS who underwent first allogeneic stem cell transplant (SCT) to investigate the association between donor CH and transplant outcomes. We performed targeted deep sequencing of 300 genes on donor blood samples and identified CH with the minimum variant allele frequency of 2%. Among 363 donors, 65 (18%) had CH. The most frequently mutated genes were DNMT3A (31 of 65; 48%), TET2 (16 of 65; 25%), PPM1D (5 of 65, 8%), and ASXL1 (7 of 65; 11%). Transplant outcomes: time to neutrophil and platelet recovery, relapse incidence, transplant-related mortality and progression-free survival, were comparable by donor CH. However, risk of grade II-IV and III-IV acute graft versus host disease (aGvHD) at 6 months after transplant was higher with donor CH vs. without donor CH (hazard ratio (HR) = 2.4, 95% Confidence Interval (CI) = 1.6-3.6, p < 0.001 and HR = 3.8, 95% CI = 1.6-8.9, p = 0.003). In this homogenous population of AML/MDS patients, donor CH was associated with increased risk of grade II-IV and III-IV aGvHD. Further studies to investigate the mechanisms of increased aGvHD and therapeutic interventions to improve aGvHD in the context of donor CH are warranted.

Massively parallel sequencing (MPS) has become a viable diagnostic tool to interrogate genetic profiles of numerous tumors but has yet to be routinely adopted in the setting of lymphoma. Here, we report the empirical application of a targeted 40-gene panel developed for use in mature lymphoid neoplasms (MLNs) and report our experience on over 500 cases submitted for MPS during the first year of its clinical use. MPS was applied to both fresh and fixed specimens. The most frequent diagnoses were diffuse large B-cell lymphoma (116), chronic lymphocytic leukemia/small lymphocytic lymphoma (60), marginal zone lymphoma (52), and follicular lymphoma (43), followed by a spectrum of mature T-cell neoplasms (40). Of 534 cases submitted, 471 generated reportable results in MLNs, with disease-associated variants (DAVs) detected in 241 cases (51.2%). The most frequent DAVs affected TP53 (30%), CREBBP (14%), MYD88 (14%), TNFRSF14 (10%), TNFAIP3 (10%), B2M (7%), and NOTCH2 (7%). The bulk of our findings confirm what is reported in the scientific literature. While a substantial majority of mutations did not directly impact diagnosis, MPS results were utilized to either change, refine, or facilitate the final diagnosis in ~10.8% of cases with DAVs and 5.5% of cases overall. In addition, we identified preanalytic variables that significantly affect assay performance highlighting items for specimen triage. We demonstrate the technical viability and utility of the judicious use of a targeted MPS panel that may help to establish general guidelines for specimen selection and diagnostic application in MLNs in routine clinical practice.

Symbols have become the most important tool for the human being’s self-expression from the first cave paintings to architecture. Each symbol has formed with values such as a message, thought and wish. In the memory of almost in every culture, the definition of weaving has been done over concepts such as eternity, immortality and plentifulness, however there is scarcely any data about their starting point. Archetype concept can be used to fill in these data blanks. Archetypes, propounded by the Swiss Psychiatrist Carl Gustav Jung, modelling the human character and collective unconscious relations, have been efficient in bringing the mythological elements to come in sight. Concepts such as great mother and mother goddess, showing similarity in many geographies, is the biggest example of the mythologies shaped with collective unconscious. Many motifs in weaving involve mythological elements. Therefore, the relation between motif and archetype will provide benefits for defining the output sources of symbols. One of the most important archetypes developed by Jung is the “Mother” archetype. The motif which corresponds to mother archetype is the Hands on Hips in Anatolian weavings. Literature survey has been conducted in this study, emphasizing the relation between one of the symbolic building blocks of Turkish weaving arts; Hands on Hips motif and the mother archetype and as a result of the study, it is surmised that mother archetype has been a precipitating element in motherhood concept in reflecting to the motifs. Key Words: Hands on Hips Motif, Mother Archetype, Weaving, Carl Gustav Jung.

In this paper the authors explore the implications for higher education of the disruptions caused by changes in the retail sector resulting from rapid developments in technology. Industry 4.0 technologies such as big data, the Internet of Things, blockchain, automation, robotics, artificial intelligence and virtual reality are increasingly evident in the retail sector. While predictions vary as to the extent of the disruption, retailers agree that embracing technology is now a necessity. The evidence in the paper is taken from a diverse sample of 60 senior managers across 24 retail companies in Ireland. The authors adopt a mixed-methods approach to data collection. They report that the skills required to perform in retail now and in the future will be a combination of human, digital and traditional skills. What emerges from the study is that advances in technology necessitate the provision of new hard skills, but importantly reinforce the necessity for soft skills so that the potential of the new technology can be fully understood and utilised. Helping retail employees upskill and future proof is a major challenge for higher education. Retailers need to proactively develop their employees by identifying clear progression pathways and promoting careers in retail.

Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3–6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.

Wind turbines are made of several electrical and mechanical components that are subject to several types of failures. Thus, the proper assessment of different failure modes and the selection of proper corrective actions will ensure the continuous and reliable functionality of wind turbines. In this research, the authors introduce a combined hybrid “Failure Modes and Effects Analysis” and “Analytic Hierarchy Process” (FMEA-AHP) method. This hybrid approach will be used to identify and analyze failure risk factors of wind turbine components. Firstly, FMEA is used to assess the impact of each component failure. Secondly, AHP is used to prioritize the severity of failures and the best measures aiming to reduce the risk of individual failures. The proposed measures, in this article, will enhance reliability and reduce operational costs of power generation using a wind turbine.

PurposeThis paper explores the implications for higher education of the rapid development in technology used by the manufacturing sector. Higher education programmes change or new courses are introduced in attempts to match labour market demands. However, the pace of change in the manufacturing industry challenges the authors to reconceive how programmes and modules can and should be designed and delivered.Design/methodology/approachThis study is based on interviews with 26 senior management representatives from manufacturing companies in Ireland. The 26 senior managers and their companies represent the wide diversity of Ireland's manufacturing sector. All the interviews were face to face, complimented by a short questionnaire. Follow-up interviews focussed on the emergent findings were carried out to aid the writing of recommendations for the best practice in programme design and delivery.FindingsWhat emerges from this study is that the manufacturing industry needs skills at three distinct levels. The authors define and classify the skill requirements at entry, competent and expert level. The authors place an emphasis on upskilling as an aid to movement between the three levels. In addition, and significantly, the desired time frame for delivery of these skills and/or upskilling is very short.Originality/valueAccelerated reskilling programmes with faster, shorter bursts of work-based learning (WBL) and experiential training are required. With a growing demand for those at competent and expert level, it is necessary to promote WBL to facilitate the upskilling of those employed in manufacturing roles, particularly in small and medium-sized enterprises (SMEs).

Efforts to promote collaboration between practitioners and analysts in establishing and administering governance systems to address largescale environmental challenges regularly fall victim to a two cultures problem. As a popular saying has it: analysts look at issues from 30,000 feet, while practitioners are down in the weeds. This article considers prospects for overcoming this problem. Using the concept of the policy cycle as a framing device, it examines contributions practitioners and analysts can make during the stages of agenda formation, collective choice, implementation and administration, and evaluation and reform. The article then turns to practical steps for overcoming the barriers to productive engagement between the two communities caused by the lack of a common language for thinking about specific needs for governance and by the influence of negative stereotypes about each other’s contributions that color the day-to-day activities of practitioners and analysts alike. The empirical focus of the article is on efforts to create effective governance systems to address largescale environmental challenges. But many features of the two cultures problem are generic. The ideas this article articulates may apply as well to efforts to foster collaboration between practitioners and analysts in other issue domains.

Background A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. Methods Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f-Bu) dosed to achieve an area under the curve of 20,000 μmol per minute (f-Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 μmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m2 intravenously for 4 days. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression-free survival. Results Roughly one-half of the patients were aged >65 years, approximately 40% had poor-risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression-free survival was significantly improved in the f-Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4-0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3-0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7-3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3-0.9; P = .01). Conclusions A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.

Steroids remain the initial therapy for acute graft-vs.-host disease (AGVHD). Strategies to improve response and minimize steroid exposure are needed. We report results of a randomized, adaptive, Bayesian-designed, phase II trial of prednisone with or without extracorporeal photopheresis (ECP) as an initial therapy for patients with newly diagnosed AGVHD. The primary endpoint was success at day 56 defined as: alive, in remission, achieving AGVHD response without additional therapy, and on

BACKGROUND CONTEXT Positive psychosocial factors early after surgery, such as resilience and self-efficacy, may be important characteristics for informing individualized postoperative care. PURPOSE To examine the association of early postoperative resilience and self-efficacy on 12-month physical function, pain interference, social participation, disability, pain intensity, and physical activity after lumbar spine surgery. STUDY DESIGN/SETTING Pooled secondary analysis of prospectively collected trial data from two academic medical centers. PATIENT SAMPLE Two hundred and forty-eight patients who underwent laminectomy with or without fusion for a degenerative lumbar condition. OUTCOME MEASURES Physical function, pain inference, and social participation (ability to participate in social roles and activities) were measured using the Patient Reported Outcomes Measurement Information System. The Oswestry Disability Index, Numeric Rating Scale, and accelerometer activity counts were used to measure disability, pain intensity, and physical activity, respectively. METHODS Participants completed validated outcome questionnaires at 6 weeks (baseline) and 12 months after surgery. Baseline positive psychosocial factors included resilience (Brief Resilience Scale) and self-efficacy (Pain Self-Efficacy Questionnaire). Multivariable linear regression analyses were used to assess the associations between early postoperative psychosocial factors and 12-month outcomes adjusting for age, sex, study site, randomized group, fusion status, fear of movement (Tampa Scale for Kinesiophobia), and outcome score at baseline. This study was funded by Patient-Centered Outcomes Research Institute and Foundation for Physical Therapy Research. There are no conflicts of interest. RESULTS Resilience at 6 weeks after surgery was associated with 12-month physical function (unstandardized beta=1.85 [95% confidence interval [CI]: 0.29; 3.40]), pain interference (unstandardized beta=−1.80 [95% CI: −3.48; −0.12]), social participation (unstandardized beta=2.69 [95% CI: 0.97; 4.41]), and disability (unstandardized beta=−3.03 [95% CI: −6.04; −0.02]). Self-efficacy was associated with 12-month disability (unstandardized beta=−0.21 [95% CI: −0.37; −0.04]. CONCLUSIONS Postoperative resilience and pain self-efficacy were associated with improved 12-month patient-reported outcomes after spine surgery. Future work should consider how early postoperative screening for positive psychosocial characteristics can enhance risk stratification and targeted rehabilitation management in patients undergoing spine surgery.

The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML expert panel, consisting of both transplant and nontransplant experts, was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by the American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate- and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed.

We study the evolution of premixed methane-air flames in large-scale obstructed channels using reactive CFD simulations. We vary the channel height d, the blockage ratio br, and the scaled distance between obstacles L/d to study their effects on the distance to DDT, LDDT, and the distance to the shock-flame complex, LSF. The results of simulations show two main effects. On one hand, the increase of br and decrease of L/d promote the flame acceleration and reduce LSF and LDDT. On the other hand, some configurations with higher br and smaller L/d prevent the detonation development. As a result, the leading shock and the flame never merge, and continue to propagate as a quasi-steady-state shock-flame complex. A collision of this complex with solid structures generates high pressures and strong reflected shocks that can ignite a detonation. This detonation would propagate in a shock-compressed material and result in extremely high pressures exceeding pressures of a regular detonation. Thus, the distance LSF at which the shock-flame complex forms provides an important measure of a destructive potential in addition to LDDT. This is particularly relevant for channels with high br where LSF can be significantly shorter than LDDT.

Diabetes mellitus and obesity are very similar in terms of pathogenesis and pathophysiology. Most obese patients have adipose tissue dysfunction caused by genetic and environmental factors. Adipose tissue is the source of adipokines secreted from adipocytes. Vaspin, Visfatin and Chemerin are adipokines discovered in recent years. The study consists of 43 non-diabetic obese and 51 diabetic obese individuals. The PCR-RFLP method and agarose gel electrophoresis techniques were used to detect gene polymorphisms of Chemerin rs17173608, Vaspin rs2236242 and Visfatin rs2110385 from DNA samples. In our study, when diabetic obese and non-diabetic obese patient groups were examined in terms of Vaspin gene polymorphism, statistically significant results were obtained (22% → 7%, p=0.048, respectively). The distribution of Chemerin or Visfatin gene variants were not different in study groups (p>0.05). Our results indicate that Chemerin rs17173608 and Visfatin rs2110385 gene polymorphisms were not risk factors for development of diabetes in obese individuals, however, Vaspin rs2236242 gene polymorphism may be a contributory risk of development of diabetes in obese individuals.

Objective: Iron deficiency (ID) is a frequent complication in end stage renal insufficiency. These patients have to be diagnosed and treated to reduce the prevalence of anemia. Functional iron deficiency (FID) is a situation that can disrupt biochemical iron tests and mask an eventual association with ID. In this study, we tried to prove the ability of extended parameters of red cells and reticulocytes to diagnose ID without being influenced by FID. Design and methods: 164 chronic hemodialysis patients (CHP) in end stage renal disease were enrolled. Research parameters of red cells and reticulocytes determined on ADVIA 2120i were studied in the diagnosis of ID associated or not with chronic inflammation. Results: Parameters such as corpuscular hemoglobin of mature red cells (CHm), corpuscular hemoglobin of reticulocytes (CHr), cellular concentration of hemoglobin in mature red cells (CHCMm), cellular concentration of hemoglobin in reticulocytes (CHCMr) and percentage of microcytic and hypochromic red cells (HYMI) showed a high sensitivity to diagnose ID. However, the distinction of combined iron deficiency (CID) from other entities was not possible with all parameters. In chronic inflammatory states, the decrease of CHm, CHCMm and CHCMr with the rise of percentage hypochromic mature red cells (HYPOm) and reticulocytes (HYPOr) is in favor of CID. So, determination of inflammatory state is needed to complete research parameters of blood count in CHP. Conclusion: Extended erythrocyte and reticulocyte parameters can be useful to check iron status in CHP.

Women with substance abuse disorders have lower use of contraception. Unplanned pregnancies increase risk of fetal exposure to addictive and teratogenic substances. Postpartum inpatient periods for these women can be challenging times to facilitate contraception planning. To explore postnatal contraceptive planning practices, patient preferences for contraception, and supply challenges, and to identify how clinical pharmacists may best provide care in this context. A tertiary maternity referral hospital in metropolitan Victoria, Australia (January 2015—December 2018). A retrospective cohort study was conducted on postnatal women with substance abuse disorders. Patients were excluded if they had delivered at another health service, had inadequate documented evidence of a substance abuse disorder, or had incomplete or unavailable medical records. Records were reviewed for demographic data, admission details, and documented contraceptive planning. Documented contraceptive planning, patient contraception preferences and identified supply challenges. Ninety-three women were included. Seventy-one (76.3%) had psychiatric disorders or impairments, and 92 (98.9%) had identifiable follow-up challenges (eg. Homelessness). Nine (9.7%) self-discharged/absconded. Eighty-seven (93.5%) had documented postnatal contraception discussions. Sixty-two of 87 (71.3%) considered a medicine/device, three (3.4%) preferred condoms, 10 (11.5%) considered sterilisation, 2 (2.3%) preferred no contraception, and 16 (18.4%) undecided. Etonogestral 68 mg implants were most commonly prescribed (28 of 42; 66.7%). Inpatient postpartum periods for this cohort were characterised by psycho-social complexities, inconsistent contraceptive planning documentation, and patients seemingly unprepared to consider contraception. This study highlights a need for an earlier decision-making process and pragmatic counselling with antenatal pharmacists.

Recently, the thermal performance of the parabolic trough collector (PTC), augmented to be more applicable and efficient, received intensive research. These studies aimed to improve heat transfer in the receiver part, in order to decrease the heat loss, and enhance the heat transfer to the thermal fluid. Many previous review papers focused on the numerical sides rather than the experimental side. Several research papers recommended doing more research in the experimental field; in order to decrease the gap between the numerical and experimental results, as well as increase the confidence level of what has been done in the theoretical field researches. Regarding the recommendations of the recent papers to decrease the gap between numerical and experimental aspects, this review paper focused on the recent experimental research related to thermal enhancement performance in the receiver part of the parabolic solar collector. In this research, different categories of the enhancement methods are discussed in detail through this review, namely nanofluids, surface modifications, and inserts models or the two categories combined together. We discussed these categories for different parabolic troughs considering only the recent experimental research between the period from 2014 up to 2019. Some parameters were discussed, such as the main dimensions of the examined receiver and parabolic collector. Moreover, types of nanoparticle specifications and preparation methods with different base fluids were highlighted. In addition, we discussed different aspects of using inserts models and inlet and outlet surface modification methods. Finally, the main thermal efficiency and thermal performance enhancement results for each work were presented.

This study investigated the efficacy and safety of azacitidine maintenance in the posttransplant setting based on the encouraging phase 1/2 reports for azacitidine maintenance in patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Between 2009 and 2017, a total of 187 patients aged 18 to 75 years were entered into a randomized controlled study of posttransplant azacitidine if they were in complete remission. Patients randomized to the treatment arm (n = 93) were scheduled to receive azacitidine, given as 32 mg/m2 per day subcutaneously for 5 days every 28 days for 12 cycles. The control arm (n = 94) had no intervention. Eighty-seven of the 93 patients started azacitidine maintenance. The median number of cycles received was 4; a total of 29 patients relapsed on study, and 23 patients withdrew from the study due to toxicity, patient’s preference, or logistical reasons. Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs 1.28 years in the control group (P = .43). There was also no significant difference for overall survival, with a median of 2.52 years vs 2.56 years in the azacitidine and control groups (P = .85), respectively. Multivariate Cox regression analysis revealed no improvement in RFS or overall survival with the use of azacitidine as maintenance compared with the control group (hazard ratios of 0.73 [95% confidence interval, 0.49-1.1; P = .14] and 0.84 [95% confidence interval, 0.55-1.29; P = .43]). This randomized trial with azacitidine maintenance showed that a prospective trial in the posttransplant setting was feasible and safe but challenging. Although RFS was comparable between the 2 arms, we believe the strategy of maintenance therapy merits further study with a goal to reduce the risk of relapse in patients with AML/MDS. This trial was registered at www.clinicaltrials.gov as #NCT00887068.

STUDY DESIGN Secondary analysis of randomized controlled trial data. OBJECTIVE The aim of this study was to examine whether preoperative physical performance is an independent predictor of patient-reported disability and pain at 12 months after lumbar spine surgery. SUMMARY OF BACKGROUND DATA Patient-reported outcome measures (PROMs) are commonly used to assess clinical improvement after lumbar spine surgery. However, there is evidence in the orthopedic literature to suggest that PROMs should be supplemented with physical performance tests to accurately evaluate long-term outcomes. METHODS A total of 248 patients undergoing surgery for degenerative lumbar spine conditions were recruited from two institutions. Physical performance tests (5-Chair Stand and Timed Up and Go) and PROMs of disability (Oswestry Disability Index: ODI) and back and leg pain (Brief Pain Inventory) were assessed preoperatively and at 12 months after surgery. RESULTS Physical performance tests and PROMs significantly improved over 12 months following lumbar spine surgery (P

Background Mycoplasma and Ureaplasma have been extensively studied for their possible impact on pregnancy, and their involvement in newborn diseases. This work examined Mycoplasma and Ureaplasma carriage among gravidas women and newborns in Israel, as well as associations between carriage and demographic characteristics, risk factors, pregnancy outcomes, and newborn morbidity rates. Methods A total of 214 gravidas women were examined for vaginal pathogen carriage through standard culture and polymerase chain reaction assay. Pharyngeal swabs were collected from newborns of carrier mothers. Clinical and demographic data were collected and infected newborn mortality was monitored for 6 months. Results Nineteen mothers were carriers, with highest prevalence among younger women. Pathogen carriage rates were 2.32% for Mycoplasma genitalium (Mg), 4.19% for Ureaplasma parvum (Up) and 2.32% for Ureaplasma urealyticum (Uu). Arab ethnicity was a statistically significant risk factor (p = 0.002). A higher prevalence was seen among women residing in cities as compared to villages. Thirteen (68%) newborns born to carrier mothers were carriers as well, with a higher prevalence among newborns of women delivering for the first time, compared to women that had delivered before. Infection rates among newborns were 20% for Mg (p = 0.238), 100% for Up (p Uu (p = 0.058), with more male than female newborns being infected. No association was found between maternal carriage and newborn morbidity. Conclusions Maternal Mycoplasma or Ureaplasma carriage may be associated with ethnicity and settlement type. Further studies will be needed to identify factors underlying these associations and their implications on delivery.

The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage. Analysis of the immune systems of the organisms revealed that the numbers of tumor-infiltrating dendritic cells (TIDC) drastically decreased with time. Further, in contrast to the current paradigm, once melanoma was established, TIDC did not migrate into sentinel lymph nodes. Instead, they underwent local cell death due to excessive phagocytosis of lysosomes. Importantly, TIDC were required to license the cytotoxic activity of tumor CD8+ T cells, and in their absence, T cells did not lyse melanoma cells. Our results offer a paradigm shift regarding the role of TIDC and a framework to increase the efficacy of immunotherapies. Significance: This work redefines the role of monocyte-derived dendritic cells in melanoma and provides a novel strategy to increase the efficacy of T-cell–based immunotherapies in nonresponding individuals.

A unique feature of the flow-diverting stent (FDS) has rendered it useful in the endovascular treatment of selected intracranial aneurysms for the last decade. Delayed aneurysmal rupture and intracranial parenchymal bleeding are two leading hemorrhagic complications after FDS. It has recently been shown for the first time that there is a relationship between FDS and reduced level of vWF activity in patients undergoing endovascular cerebral aneurysm treatment. Here, the current literature is reviewed in the context of this novel finding to propose an illustrative scenario that conceptually links implantation of FDS to delayed intracranial bleeding, through the mechanism of shear-induced activation of vWF. In this scenario, after FDS implantation, sustained release of activated vWF in association with platelets plays a pivotal role in the mechanisms of delayed intracranial hemorrhages.

In recent decades, the prevalence of diabetes has rapidly increased worldwide. Medical nutrition therapy has been identified as a major therapeutic support for diabetic patients, while preventive strategies in prediabetic or high-risk individuals have mainly focused on supplementation with bioactive compounds. Recently, meal-based interventions have been investigated as novel and safe long-term strategies for improving glucose regulation. However, evaluation of meal-based interventions is difficult since it requires analysis of sensitive markers. Biomarkers can also be used to identify individuals at risk for diabetes, which is important for disease prevention. In this review, we summarize current evidence from meal-based intervention studies conducted with the aim of improving glucose homeostasis in individuals at risk of diabetes using clinical biomarkers currently used to assess diabetic risk. Very low-calorie diets have significantly improved glucose regulation in obese adults and in adults with type 2 diabetes mellitus. In particular, changing the ratios of macronutrients through calorie restriction reduces fasting glucose level and hemoglobin A1c levels in patients with diabetes mellitus. However, this effect is limited in both obese and healthy adults. To date, multiple glucose-related markers have been identified as clinical biomarkers of diabetes. Additional clinical biomarkers include cholesterol levels, hematological markers, and inflammatory markers. Taken together, the evidence presented in this review may help for selection of clinical biomarkers for meal-based preventive approaches for non- or pre-diabetic individuals to prevent onset of diabetes.

We sought to examine the role of preoperative and 2nd postoperative day albumin levels as predictors for postoperative course in infants undergoing repair of congenital heart disease. This retrospective, single-center, observational study comprised consecutive infants younger than 1 year who had undergone repair of tetralogy of Fallot, ventricular septal defect, complete atrioventricular canal or transposition of the great arteries over a 25 months period. We correlated preoperative and postoperative day (POD) #2 albumin level to vaso-inotropic score (VIS) and intensive care unit (ICU) length of stay (LOS) as markers for degree and duration of postoperative cardiac support. A composite outcome was defined as maximal vaso-inotropic score of > 10 and ICU LOS > 96 h. Preoperative albumin level negatively correlated with VIS and ICU LOS. Compared to preoperative albumin level of > 4 g/dL, the relative risk of meeting composite criteria was 1.5 for preoperative albumin of 3.1–4 g/dL and 2.6 for preoperative albumin ≤ 3 g/dL. Compared to POD#2 albumin level > 3 g/dL, the relative risk of meeting composite criteria was 1.8 for albumin of 2.6–3 g/dL, and 2.5 for albumin ≤ 2.5 g/dL. In summary, we found that preoperative and POD#2 albumin levels predicted prolonged and complicated postoperative course. These finding may help clinicians to inform the patient’s parents, early in the ICU hospitalization, as to the predicted risks and difficulties of their infant’s postoperative course.

Craniocervical arterial dissection is an important cause of arterial ischemic stroke in children. Recognition of dissections is of particular importance both in determining the risk of recurrence and in bringing about different treatment alternatives. We report a 10-year-old girl who presented with acute ischemic stroke due to spontaneous long segment dissection involving the parasellar internal carotid artery up to the distal M1 portion of the middle cerebral artery. Three-dimensional digital subtraction angiography with flat panel detector revealed the presence of major vessels originating from both true and false lumens and had a critical role in the treatment decision of the case.

The optimal conditioning regimen for older patients with acute myeloid leukemia (AML) remains unclear. In this study, we compared outcomes of AML patients >60 years of age undergoing allogenic hematopoietic stem cell transplantation at our institution. All 404 consecutively treated patients received 1 of the following conditioning regimens: (1) fludarabine+melphalan 100 mg/m2 (FM100), (2) fludarabine+melphalan 140 mg/m2 (FM140), (3) fludarabine+IV busulfan AUC ≥ 5000/d × 4 d (Bu≥20000), and (4) fludarabine+IV busulfan AUC 4000/d × 4 d (Bu16000). A propensity score analysis (PSA) was used to compare outcomes between these 4 groups. Among the 4 conditioning regimens, the FM100 group had a significantly better long-term survival with 5-year progression-free survival of 49% vs 30%, 34%, and 23%, respectively. The benefit of the FM100 regimen resulted primarily from the lower nonrelapse mortality associated with this regimen, an effect more pronounced in patients with lower performance status. The PSA confirmed that FM100 was associated with better posttransplantation survival, whereas no significant differences were seen between the other regimen groups. In summary, older patients with AML benefited from a reduced-intensity conditioning regimen with lower melphalan doses (FM100), which was associated with better survival, even though it was primarily used in patients who could not receive a more intense conditioning regimen.

Dünyada küreselleşme sürecinde bir taraftan küreselleşme sistemi sayesinde günümüze kadar görülmemiş kadar başarılı bir performans elde edilecek olan yeni bir dünya düzeni kurulmaya çalışıldığı veya dünyadaki bütün ülkelerin aynı yararlı sonuçlara ulaşacağı iddia edilmektedir. Diğer taraftan küreselleşme sistemi içinde sadece çok uluslu denilen devasa büyüklükteki şirketler ile bu şirketlerin ait oldukları çok gelişmiş ülkelerin ticari olanaklarına yönelik düzenlemelerle ilgili eleştirilerden bahsedilmektedir. Sonuç olarak yaşanmaya başlanan etkiler ortaya çıktıkça gerçek amacın bütün dünyada birleşme ve bütünleşme sağlanmış olduğu açıkça anlaşılmaktadır çünkü ancak çeyrek asır sonra aslında bu sürecin fazla yarar sağlayanları olarak gelişmekte olan ülkeler tarafından bazı açılardan çok önemli yararlar elde edileceği görülmektedir. Bu çalışma kapsamında küreselleşme sisteminde aslında çok uluslu şirketler tarafından sağlanan olumlu sonuçlar üzerinde küreselleşmenin etkileri ile bu etkiler arasında hangileri üzerinde ülke yönetimlerinden doğan sonuçlar elde edildiği araştırılmaktadır. Jel Kodları: F6

BACKGROUND AND PURPOSE: Vascular devices generating high shear stress can cause type 2A acquired von Willebrand disease, which is characterized by low von Willebrand factor activity accompanied by hemorrhagic complications. The braided mesh structure of flow-diverting stents with a relatively small strut size can create abnormally high shear stress while arterial blood flows through the stent struts into the aneurysm, and flow-diverting stent may be associated with reduced von Willebrand factor activity. MATERIALS AND METHODS: Aneurysmal morphologic parameters and patient data were examined retrospectively among patients who had an unruptured intracranial aneurysm treated with a flow-diverting stent. The RISTOtest (test for whole blood ristocetin-induced platelet aggregation) for von Willebrand factor activity, as well as tests for aspirin and clopidogrel/prasugrel effectiveness, were performed immediately before the endovascular procedure and 24 hours later by multiple electrode aggregometry. RESULTS: A total of 39 patients with 56 aneurysms were recruited, and statistical analyses were performed in 32 patents with 49 aneurysms. Compared with the baseline values, von Willebrand factor activity was reduced in 16 patients but increased in 23 patients. Aneurysmal variables (eg, neck area, volume, volume-to-neck area ratio, size ratio, and morphologic index) clearly distinguished patients with reduced von Willebrand factor activity from those with nonreduced von Willebrand factor activity. The receiver operating characteristic curve showed that the morphologic index and volume had the highest discriminative power, with an area under the curve of 0.99. CONCLUSIONS: In high-volume/large-neck aneurysms, flow-diverting stent implantation can cause reduced von Willebrand factor activity, which may be linked causally to acquired von Willebrand disease.

Background Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

Requirements communication is essential in software development projects since customer needs must be communicated to the development team clearly and effectively. Although the use case (UC) specifications are used to communicate requirements in detail, developers do not always follow them. This study presents an empirical study carried out to understand the reasons why developers do not follow UC specifications and their difficulties using UC specifications in generating prototypes. Results show that the four reasons why developers fail to follow UC specifications are the existence of specification errors, ambiguous information, lack of detailed specification, or incomplete information, and due to improvement suggestions. Also, the specification defects types that impacted prototypes creation the most were an omission, ambiguity, and incorrect fact. The authors noted that 6 out of 25 (24%) defects in the UC specifications caused discrepancies in prototypes, 12 (48%) were corrected during the prototypes creation, and 7 (28%) were not propagated to the prototypes.

Background Increased oxidative stress has been shown to lead to muscle damage and reduced physical performance. The antioxidant mechanism is most likely to reduce these relationships, but in the context of the action of carotenoids, more research is needed. This cross-sectional study aims to investigate whether carotenoids modify the association between plasma malondialdehyde (MDA) and physical performance in Korean adolescents. Methods The study sample consisted of 381 participants (164 boys, 217 girls) aged 13−18, who participated in the 2018 National Fitness Award Project. We quantified α-carotene, β-carotene, β-cryptoxanthin, lutein, zeaxanthin, lycopene, and MDA levels in plasma using HPLC with photodiode array detection. Physical performance was measured by determining the absolute and relative hand grip strength, 20-m progressive aerobic cardiovascular endurance run, estimated maximal oxygen consumption, curl-up, and sit-and-reach. Results In boys, the multiple linear regression model adjusted for age, BMI, smoking, drinking, and physical activity showed that the MDA level was negatively associated with absolute hand grip strength; this association was observed only in groups with α-carotene, β-cryptoxanthin, zeaxanthin, and total carotenoid values below the median. Conclusion These results suggest that carotenoids may act as an effect modifier of the association between MDA and physical performance in Korean male adolescents.

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose

Requirements engineering is a crucial stage for the success of any software, as it allows a better understanding of the needs and desires of the customers or future users. In software development for autistic users, inexperienced software engineers face difficulties in the requirements engineering stage, as there are few specific techniques and artifacts to gather requirements in such context. The challenges increase when considering low-functioning autistic people, who have the most severe limitations of the disorder. Considering the above, in this paper, we present two artifacts to support the elicitation of requirements in software projects for autistic users. We developed a set of interviewing questions based on the opinion of both software development practitioners and caregivers. Also, we have drawn inspiration in a commercial canvas model to synthesize relevant data obtained with the interviews. When validating the artifacts, we got indicators of the feasibility of applying the artifacts in an actual development project. By developing and integrating these artifacts, we intend to support the requirements engineering stage and continue their development and study in further contexts.