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Objective: Juvenile idiopathic arthritis (JIA)–associated uveitis (JIAU) is a serious JIA comorbidity that can result in vision impairment. This study aimed to identify genetic risk factors within the major histocompatibility complex for JIAU and evaluate their contribution for improving risk classification when combined with clinical risk factors. Methods: Data on single nucleotide polymorphisms, amino acids, and classical HLA alleles were available for 2,497 patients with JIA without uveitis and 579 patients with JIAU (female 2,060, male 1,015). Analysis was restricted to patients with inferred European ancestry. Forward conditional logistic regression identified genetic markers exceeding a Bonferroni‐corrected significance (6 × 10−6). Multivariable logistic regression estimated the effects of clinical and genetic risk factors, and a likelihood ratio test calculated the improvement in model fit when adding genetic factors. Uveitis risk classification performance of a model integrating genetic and clinical risk factors was estimated using area under the receiver operator characteristic curve and compared with a model of clinical risk factors alone. Results: Three genetic risk factors were identified, mapping to HLA‐DRB1, HLA‐DPB1, and HLA‐A. These markers were statistically independent from clinical risk factors and significantly improved the fit of a model when included with clinical risk factors (P = 3.3 × 10−23). The addition of genetic markers improved the classification of JIAU compared with a model of clinical risk factors alone (area under the curve 0.75 vs 0.71). Conclusion: Integration of a genetic and clinical risk prediction model outperforms a model based solely on clinical risk factors. Future JIAU risk prediction models should include genetic risk factors. [ABSTRACT FROM AUTHOR]

Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, [CD163.sup.+] macrophages were associated with plaque progression, microvascularity, and a high level of HIF1[alpha] and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by [CD163.sup.+] macrophages. Within these cells, activation of HIF1[alpha] via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. [CD163.sup.+] macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1[alpha]/VEGF-A pathway., Introduction Macrophages play a critical role in atherogenesis but are a heterogeneous group of immune cells (1). The atherosclerotic plaque microenvironment is an important stimulus driving their differentiation into distinct [...]

Objective: To explore vigilance task performance, cerebral blood flow velocity (CBFV), workload, and stress in a within-subjects, two-session experiment. Background: Vigilance, or sustained attention, tasks are often characterized by a decline in operator performance and CBFV with time on task, and high workload and stress. Though performance is known to improve with practice, past research has not included measures of CBFV, stress, and workload in a within-subjects multi-session design, which may also provide insight into ongoing theoretical debate. Method: Participants performed a vigilance task on two separate occasions. Performance, CBFV, workload, and self-reported stress were measured. Results: Within each session, results were consistent with the vigilance profile found in prior research. Across sessions, performance improved but the time on task decrement remained. Mean CBFV and workload ratings did not differ between sessions, but participants reported significantly less distress, worry, and engagement after session two compared to one. Conclusion: Though practice may not disrupt the standard vigilance profile, it may serve to improve overall performance and reduce stress. However, repeated exposure may have negative implications for engagement and mind-wandering. Application: It is important to better understand the relationship between experience, performance, physiological response, and self-reported stress and workload in vigilance because real-world environments often require operators to do the same task over many occasions. While performance improvement and reduced distress is an encouraging result, the decline in engagement requires further research. Results across sessions fail to provide support to the mind-wandering theory of vigilance. [ABSTRACT FROM AUTHOR]

Objectives: Juvenile idiopathic arthritis (JIA) is the most prevalent form of juvenile rheumatic disease. Our understanding of the genetic risk factors for this disease is limited due to low disease prevalence and extensive clinical heterogeneity. The objective of this research is to identify novel JIA susceptibility variants and link these variants to target genes, which is essential to facilitate the translation of genetic discoveries to clinical benefit.Methods: We performed a genome-wide association study (GWAS) in 3305 patients and 9196 healthy controls, and used a Bayesian model selection approach to systematically investigate specificity and sharing of associated loci across JIA clinical subtypes. Suggestive signals were followed-up for meta-analysis with a previous GWAS (2751 cases/15 886 controls). We tested for enrichment of association signals in a broad range of functional annotations, and integrated statistical fine-mapping and experimental data to identify target genes.Results: Our analysis provides evidence to support joint analysis of all JIA subtypes with the identification of five novel significant loci. Fine-mapping nominated causal single nucleotide polymorphisms with posterior inclusion probabilities ≥50% in five JIA loci. Enrichment analysis identified RELA and EBF1 as key transcription factors contributing to disease risk. Our integrative approach provided compelling evidence to prioritise target genes at six loci, highlighting mechanistic insights for the disease biology and IL6ST as a potential drug target.Conclusions: In a large JIA GWAS, we identify five novel risk loci and describe potential function of JIA association signals that will be informative for future experimental works and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: A dual-task study was performed to explore the performance effects for swimming, word recall, and the combination of the two tasks performed simultaneously.Background: Dual-task interference studies have been performed for a variety of tasks; however, there has not been much dual-task interference research where one of the tasks is a naturalistic physically strenuous task. Swimming is a unique physical task that requires spatial orientation on three dimensional axes, similar to that of flying, but has no risk of falling. Previous studies have been conducted in other activity combinations with word-free recall, such as running and climbing, but swimming has yet to be explored.Method: A verbal memory recall task and swimming task were performed in isolated (single-task) and simultaneous conditions. A comparison of effects across these different activities was also explored.Results: Swimming and the word-recall task resulted in significant dual-task interference: almost as much as when word recall was paired with another verbal task, but more than running and less than climbing.Conclusion: Consistent with other dual-task studies, this study observed dual-task interference between the physical swimming task and the cognitive verbal memory task.Application: Future technologies and training for personnel who engage in water rescue or commercial diving, such as underwater welding and fiber optic cable, may be improved by these findings. [ABSTRACT FROM AUTHOR]

Vigilance, or the ability to sustain attention for extended periods of time, has been of interest to the human factors and ergonomics community for 70 years. During this time, several theories have attempted to account for the performance effects commonly associated with vigilance (i.e. the decrement, which manifests in fewer correct detections and longer response times to targets over time). We provide a cohesive review of the current empirical support for the three major theories explaining the vigilance decrement and describe the limitations of each theory herein. The three overarching theories of vigilance performance and the vigilance decrement include: cognitive resource theory, mindlessness theory and mind-wandering theory. Importantly, each of these theories relies on unique definitions of task engagement to understand operator overload or underload. The differences in the operationalisation of task engagement are problematic in the application of vigilance research to the real world. In this article, we describe the utility of a unified definition of task engagement and demonstrate how resource theory is better poised to account for cognitive task engagement than physical task engagement, which is emphasised in other theories. [ABSTRACT FROM AUTHOR]

4 Tongue JR, Epps HR, Forese LL. Communication skills for patient-centered care: research-based, easily learned techniques for medical interviews that benefit orthopaedic surgeons and their patients. We've both been patients. It's a small wonder that one survey found that while 75% of orthopaedic surgeons believed they were communicating effectively with patients, only 21% of those patients agreed [[4]]. [Extracted from the article]