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The Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.1(HJHSv2.1) in adults with hemophilia. A secondary aim was to define age‐related normative adult HJHSv2.1 reference values. We studied 192 adults with hemophilia, and 120 healthy adults in four age‐matched groups—18 to 29, 30 to 40, 41 to 50, and >50 years—at nine centers. Trained physiotherapists scored the HJHS and World Federation of Hemophilia (WFH) joint score. Health history, the Functional Independence Scale of Hemophilia (FISH), Hemophilia Activities List (HAL), and Short‐Form McGill Pain Questionnaire (SF‐MPQ) were also collected. The median age was 35.0 years. Of participants with hemophilia, 68% had severe, 14% moderate, and 18% mild disease. The HJHS correlated strongly with WFH score (Spearman’s rho [rs] = .95, P < .001). Moderate correlations were seen between the FISH (rs = .50, P < .001) and SF‐MPQ Present Pain Intensity (rs = .50, P < .001), while a modest correlation was found with the HAL (rs = −.37, P < .001). The HJHS significantly differentiated between age groups (Kruskal‐Wallis T = 35.02, P < .001) and disease severity in participants with hemophilia. The HJHS had high internal reliability (Cronbach’s α = .88). We identified duration of swelling as a redundant item in the HJHS. The HJHS shows evidence of strong convergent and discriminant construct validity to detect arthropathy in adults with hemophilia and is well suited for use in this population.

This randomized trial involving young boys with severe hemophilia showed that prophylaxis with regular infusions of recombinant factor VIII was associated with clinically and statistically significant reductions in joint damage, as compared with episodic infusions at the time of a clinically evident hemarthrosis. Because of the high cost of recombinant factor VIII, its widespread use for prophylaxis may be impractical. Prophylaxis with regular infusions of recombinant factor VIII was associated with clinically and statistically significant reductions in joint damage, as compared with episodic infusions. Before the development of cryoprecipitate, a plasma fraction that contains concentrated factor VIII, boys with severe hemophilia A had a diminished life expectancy. 1 – 3 These children are at risk for many types of hemorrhages, but the predominant source of chronic coexisting disease is crippling, painful arthritis due to hemarthrosis. 4 Small trials were conducted in the 1960s to determine whether routine administration of factor VIII concentrate was effective as prophylaxis against hemophilic arthropathy. 5 – 8 Clinically effective prophylactic schedules were developed empirically, without the benefit of data from controlled trials, 9 and many clinicians began to recommend prophylaxis with factor VIII. 10 In the . . .

Recombinant adeno-associated virus (rAAV) is a promising gene delivery vector and has recently been used in patients with hemophilia. One limitation of AAV application is that most humans have experienced wild-type AAV serotype 2 exposure, which frequently generates neutralizing antibodies (NAbs) that may inhibit rAAV2 vector transduction. Employing alternative serotypes of rAAV vectors may circumvent this problem. We investigated the development of NAbs in early childhood by examining sera gathered prospectively from 62 children with hemophilia A, participating in a multi-institutional hemophilia clinical trial (the Joint Outcome Study). Clinical applications in hemophilia therapy have been suggested for serotypes AAV2, AAV5 and AAV8, therefore NAbs against these serotypes were serially assayed over a median follow-up of 4 years. NAbs prevalence increased during early childhood for all serotypes. NAbs against AAV2 (43.5%) were observed more frequently and at higher titers compared with both AAV5 (25.8%) and AAV8 (22.6%). NAbs against AAV5 or AAV8 were rarely observed in the absence of co-prevalent and higher titer AAV2 NAbs, suggesting that NAbs to AAV5 and AAV8 were detected following AAV2 exposure due to partial cross-reactivity of AAV2-directed NAbs. The results may guide rational design of clinical trials using alternative AAV serotypes and suggest that younger patients who are given AAV gene therapy will benefit from the lower prevalence of NAbs.

For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation. A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point‐of‐care musculoskeletal ultrasound (POC‐MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted. Next, an in‐person meeting of an international group of hemophilia health care professionals and patient representatives was held, with the objective of achieving consensus regarding the acquisition and interpretation of POC‐MSKUS and full diagnostic ultrasound for use in the assessment of musculoskeletal (MSK) pathologies in persons with hemophilia. The recommendations were that clear definitions of the types of ultrasound examinations should be adopted and that a standardized ultrasound scoring/measurement system should be developed, tested, and implemented. The scoring/measurement system should be tiered to allow for a range of complexity yet maintain the ability for comparison across levels. Ultrasound is an evolving technology increasingly used for the assessment of MSK outcomes in persons with hemophilia. As adoption increases globally for clinical care and research, it will become increasingly important to establish clear guidelines for image acquisition, interpretation, and reporting to ensure accuracy, consistency, and comparability across groups.

Both of the above beliefs require a personal choice, which political party to support or to accept Jesus Christ as your Saviour.

If the Bible is to be quoted by Ms. [Dawne Taylor], then she should also quote from Philippians 2:10-11: \"At the name of Jesus every knee should bow and every tongue should confess that Jesus Christ is Lord.\" I can find no reference to the sun, moon or stars or any other prophet long since in the grave and decayed as being the way to salvation. But throughout the Bible there are plenty of references to false gods.

Sharon (Funk) Dobler Gloria & Len Kuhn Jody (Lang) Rawlyck Lori Hayden & George Spencer Beth (McRae) Reed Wayne Rumohr

Modeling clinically relevant tissue responses using cell models poses a significant challenge for drug development, in particular for drug induced liver injury (DILI). This is mainly because existing liver models lack longevity and tissue-level complexity which limits their utility in predictive toxicology. In this study, we established and characterized novel bioprinted human liver tissue mimetics comprised of patient-derived hepatocytes and non-parenchymal cells in a defined architecture. Scaffold-free assembly of different cell types in an in vivo-relevant architecture allowed for histologic analysis that revealed distinct intercellular hepatocyte junctions, CD31+ endothelial networks, and desmin positive, smooth muscle actin negative quiescent stellates. Unlike what was seen in 2D hepatocyte cultures, the tissues maintained levels of ATP, Albumin as well as expression and drug-induced enzyme activity of Cytochrome P450s over 4 weeks in culture. To assess the ability of the 3D liver cultures to model tissue-level DILI, dose responses of Trovafloxacin, a drug whose hepatotoxic potential could not be assessed by standard pre-clinical models, were compared to the structurally related non-toxic drug Levofloxacin. Trovafloxacin induced significant, dose-dependent toxicity at clinically relevant doses (≤ 4uM). Interestingly, Trovafloxacin toxicity was observed without lipopolysaccharide stimulation and in the absence of resident macrophages in contrast to earlier reports. Together, these results demonstrate that 3D bioprinted liver tissues can both effectively model DILI and distinguish between highly related compounds with differential profile. Thus, the combination of patient-derived primary cells with bioprinting technology here for the first time demonstrates superior performance in terms of mimicking human drug response in a known target organ at the tissue level.

East Africa is a drought prone, food and water insecure region with a highly variable climate. This complexity makes rainfall estimation challenging, and this challenge is compounded by low rain gauge densities and inhomogeneous monitoring networks. The dearth of observations is particularly problematic over the past decade, since the number of records in globally accessible archives has fallen precipitously. This lack of data coincides with an increasing scientific and humanitarian need to place recent seasonal and multi-annual East African precipitation extremes in a deep historic context. To serve this need, scientists from the UC Santa Barbara Climate Hazards Group and Florida State University have pooled their station archives and expertise to produce a high quality gridded ‘Centennial Trends’ precipitation dataset. Additional observations have been acquired from the national meteorological agencies and augmented with data provided by other universities. Extensive quality control of the data was carried out and seasonal anomalies interpolated using kriging. This paper documents the CenTrends methodology and data. Design Type(s) observation design • time series design • data integration objective Measurement Type(s) atmospheric precipitation Technology Type(s) meterological observation Factor Type(s) Sample Characteristic(s) Tanzania • Kenya • Ethiopia • Uganda • Rwanda • Burundi • Eritrea • Somalia • atmospheric water vapour Machine-accessible metadata file describing the reported data (ISA-Tab format)