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The number of diagnoses of developmental disorders is on the rise and the use of labels for developmental disorders, such as attention-deficit/hyperactivity disorder and autism spectrum disorder, is widening. Diagnostic labels can play an important role in helping those who display atypical behaviour and their caregivers to cope with associated challenges and, possibly, to get treatment. But these labels are increasingly contested and associated with a variety of harmful effects. In this paper, we analyze the role diagnostic labels can play in four different contexts (scientific, therapeutic, social, and administrative) and identify what various stakeholders stand to gain or lose with continued, expanded, or abolished use of those labels. Our analysis reveals labels serve different purposes in each of these contexts, benefitting different stakeholders. Any overall evaluation, critique, or defence of labels needs to consider the interests of all stakeholders in these contexts.In this study, two (18.2%) clinically unaffected parents from 11 trios were identified with mosaic KRT14 variants.To our knowledge, this is the first report to study the proportion of low-level mosaicism in the clinically unaffected parents whose children were previously regarded as sporadic EBS cases.Recently in this journal, a new trichomycterine from eastern Brazil, Trichomycterus astromycterus, was described and considered possibly related to the Chilean Bullockia maldonadoi due to morphological similarities. Subsequently, osteological data supported T. astromycterus in the subgenus Psammocambeva of Trichomycterus, from eastern Brazil. Phylogenetic analyses, performed here, using a multigene data set for a broad trichomycterine sample, corroborate T. astromycterus as a member of Psammocambeva, reinforcing the importance of molecular data for inferring trichomycterine relationships but showing that osteological data alone may infer correctly phylogenetic placements when using broad comparative databases.Six out of 12 Sézary patients shared one clonotype (TRAV13-1*01-TRAJ49*01-TRBV20-1*01-TRBJ2-3*01). TRBV20-1*01 (also known as Vb2) that binds toxic shock syndrome toxin-1 was utilized by Sézary cells among half of the cohort, which would be expected for a common unifying origin.
Gene flow in riparian ecosystems is influenced by landscape features such as orography, climate, and salinity. The downstream increase in genetic diversity (DIGD) hypothesis states that the unidirectionality of the watercourse causes an accumulation of genetic diversity toward downstream populations, while upstream populations are more structured and less diverse, especially in water-dispersed organisms.
We used chloroplast and nuclear microsatellites to characterize genetic diversity, structure, and gene flow patterns among populations of Salix humboldtiana across an elevation and salinity gradient on three rivers (Actopan, Antigua, and Blanco) in Mexico. We used optimization of resistance surface methods to determine whether genetic distances between populations are correlated with landscape features.
Positive F
values evidenced biparental inbreeding in some populations, particularly at higher elevations where lower niche availability constrains colonization and persistence. Four genetic groups were distinguished, corresponding to populations on the Actopan and Antigua rivers and upstream and downstream on the Blanco, but with high admixture between populations on the Actopan and Antigua rivers. Higher gene flow rates were found among proximate populations on the same river than among different rivers. Genetic diversity increased toward the river mouths, in support of the DIGD hypothesis, probably due to greater niche availability and larger population size. Differences among rivers in precipitation patterns and salinity, as well as geographic distance, were significant predictors of gene flow.
Our results depict that the DIGD and gene flow patterns in S. humboldtiana result from the complex interaction among physiography, climate, river salinity, and life-history traits of the species.
Our results depict that the DIGD and gene flow patterns in S. humboldtiana result from the complex interaction among physiography, climate, river salinity, and life-history traits of the species.Passive surveillance systems are widely used to monitor diseases occurrence over wide spatial areas due to their cost-effectiveness and integration into broadly distributed healthcare systems. However, such systems are generally associated with imperfect ascertainment of disease cases and with heterogeneous capture probabilities arising from factors such as differential access to care. Augmenting passive surveillance systems with other surveillance efforts provides a way to estimate the true number of incident cases. We develop a hierarchical modeling framework for analyzing data from multiple surveillance systems that allows for individual-level covariate-dependent heterogeneous capture probabilities, and borrows information across surveillance sites to improve estimation of the true number of incident cases. Inference is carried out via a two-stage Bayesian procedure. Simulation studies illustrated superior performance of the proposed approach with respect to bias, root mean square error, and coverage compared to a model that does not borrow information across sites. We applied the proposed model to data from three surveillance systems reporting pulmonary tuberculosis (PTB) cases in a major center of ongoing transmission in China. The analysis yielded bias-corrected estimates of PTB cases from the passive system and led to the identification of risk factors associated with PTB rates, as well as factors influencing the operating characteristics of the implemented surveillance systems.
Upper airway endoscopy of thoroughbred (TB) yearlings is commonly used in an attempt to predict laryngeal function (LF) and its impact on future race performance. The aim of this study was to determine if different grading systems and laryngeal grades were correlated with future performance.
Postsale endoscopic recordings were obtained from an Australian TB yearling sale during a four-year period from 2008 to 2011. Horses were included if they had a diagnostic postsale video endoscopic recording and raced within Australia. Recordings were graded using the Havemeyer system and subsequently recategorised according to the Lane scale and two condensed scales. Performance data were sourced from Racing Australia and comparisons were made between groups.
A total of 1244 horses met the inclusion criteria. There were no significant differences in sex or sales price between groups. selleck chemicals llc There were no significant differences in the number of starts or wins between groups for any grading system. For the condensed Havemeyer scale, horses with intermediate LF were separated into two groups. Significant differences in earnings were found between 'normal' and 'abnormal' (P=0.02) and 'intermediate-low' and 'abnormal' grades (P=0.03). There were no significant differences between horses with 'intermediate-high' and 'abnormal' grades (P=0.40). No significant differences were found between the two intermediate grades (P=0.60) or between horses with normal LF and either 'intermediate-low' or 'intermediate-high' grades (P=0.99).
Resting LF in Australian yearling TBs assessed using a condensed Havemeyer grading scale had some predictive value for future racing performance. This information should be considered when performing yearling endoscopic examinations.
Resting LF in Australian yearling TBs assessed using a condensed Havemeyer grading scale had some predictive value for future racing performance. This information should be considered when performing yearling endoscopic examinations.The development of effective and safe treatments has significantly increased the life expectancy of persons with haemophilia (PWH). This has been accompanied by an increase in the comorbidities of ageing including cardiovascular disease, which poses particular challenges due to the opposing risks of bleeding from haemophilia and antithrombotic treatments versus thrombosis. Although mortality secondary to coronary artery disease in PWH is less than in the general population, the rate of atherosclerosis appears similar. The prevalence of atrial fibrillation in PWH and risk of secondary thromboembolic stroke are not well established. PWH can be safely supported through acute coronary interventions but data on the safety and efficacy of long-term antithrombotics are scarce. Increased awareness and research on cardiovascular disease in PWH will be crucial to improve primary prevention, acute management, secondary prevention and to best support ageing PWH.
Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS.
To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response.
Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed.
At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment responsics and immunohistochemistry. This research identifies lipocalin-2 (LCN2) in skin and IL-17A in serum as potential predictive biomarkers for treatment response. These data may help guide physicians in choosing the appropriate therapy for patients with moderate-to-severe HS. What is the translational message? IL-17RA blockade with brodalumab is an effective treatment for patients with moderate-to-severe HS. Assessing pathways that respond to treatment, rather than individual biomarkers, may be a superior approach for molecular characterization of the treatment response in HS therapeutic studies. Brodalumab modulates neutrophil-related pathways in the skin and blood, and known psoriasis pathways in the skin. We demonstrate that patients with high baseline expression of IL-17-regulated neutrophil-created LCN2 in the skin or IL-17A in the serum have a superior molecular response to treatment, allowing the possibility for physicians to select therapeutic treatment based on baseline molecular profiles.
Of the nearly 50,000 women in the United States who undergo treatment for ductal carcinoma in situ (DCIS) annually, many may not benefit from treatment. To better understand the impact of a DCIS diagnosis, patients self-identified as having had DCIS were engaged regarding their experience.
In July 2014, a web-based survey was administered through the Susan Love Army of Women breast cancer listserv. The survey included open-ended questions designed to assess patients' perspectives about DCIS diagnosis and treatment. Deductive and inductive codes were applied to the responses; common themes were summarized.
Among the 1832 women included in the analytic sample, the median age at diagnosis was 60 years. Four primary themes were identified 1) uncertainty surrounding a DCIS diagnosis, 2) uncertainty about DCIS treatment, 3) concern about treatment side effects, and 4) concern about recurrence and/or developing invasive breast cancer. When diagnosed, participants were often uncertain about whether they had cancer or not and whether they should be considered a "survivor.
