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Elizabeth Holliday and colleagues report a genome-wide association study for ischemic stroke. They identify common variants at 6p21.1 associated with large artery atherosclerosis (LAA), a major subtype of ischemic stroke. Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10 −8 ) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10 −4 ; discovery and replication combined OR = 1.21, P = 4.7 × 10 −8 ). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.

Background Pediatric traumatic brain injury (TBI) is a major cause of disability and long-term sequelae in children and adolescents worldwide. To facilitate understanding of the emotional, cognitive, and somatic symptoms following pediatric TBI, the present study aims to assess the prevalence of post-concussion-like symptoms (PCLS) in children and adolescents aged 8 to 17 years in Germany and to investigate the associations between risk factors and the occurrence of symptoms. Methods A web-based survey included two age-appropriate versions of the Postconcussion Symptom Inventory (PCSI; for children: 8–12 years, for adolescents: 13–17 years), a self-report questionnaire recommended for post-concussion symptom assessment in young patients. Classification of participants according to symptom impairment occurred using different cut-offs. We used logistic regression to examine the influence of sociodemographic and health-related factors. Results A total of 1.997 respondents completed the survey. The most commonly reported symptom in the 8–12 age group was irritability (49.8%) and in the 13–17 age group drowsiness (51.6%). More than half (58.3%) of children and up to 66.5% of adolescents were classified as impaired despite not having experienced TBI, using the most liberal cut-off score that considered impairment if at least three PCSI symptoms indicated at least a mild problem. Chronic health conditions were found to be a significant risk factor for reporting impairment. Conclusions We found a high prevalence of PCLS in children and adolescents from the general German population, suggesting that these symptoms are not exclusively TBI-specific. Therefore, the evaluation of post-concussion symptoms after TBI should be done with caution, taking into account the individual’s premorbid health status and medical history. Trial registration The study is registered retrospectively in German Clinical Trials Register and in International Clinical Trials Registry Platform (DRKS00032854||12/10/2023).

No previous qualitative exploration of urinary incontinence (UI) or post-stroke urinary incontinence (PSUI) has been undertaken in an Australian population. The purpose of this study is to explore the experiences of community-dwelling stroke survivors who were living with UI/PSUI and understand how context shaped those experiences. A pragmatic approach using thematic analysis was employed for this study. Four themes emerged from the data: \"I've got to go\": onset and daily experience of UI; \"No one ever mentioned it\": lack of advice and information from the health system; \"You can't enjoy something if you've got to go the toilet\": experience of occupational restrictions; and \"It's just a matter of planning\": management strategies. UI continued well beyond discharge and was shaped by limited advice, distress, and role loss. Occupational therapists are encouraged to engage in assessment, management, and treatment of UI, including the provision of education that promotes continence, attenuates negative experiences, and enhances community participation.

Music educated human understanding before it served as a way to create art for its own sake, to build a career, or to entertain. In spite of budget challenges in modern times, research repeatedly shows that exposure to the arts, and training in them, contributes life skills of great value beyond the specific skills acquired within each art form. The value of the arts as a central component ofthe complete education of a human mind falls behind the entertainment, the show, the exhibit, the glitz and glamour. Since an education in the arts is not a prerequisite to attaining the glitz and glamour, the need to support it with civic expenditures feels less urgent. State budget allocations, school district budget priorities, budget inequities across districts, underlying issues of race and ethnic inequalities, emphasis upon STEM disciplines in an era of global technological advance, No Child Left Behind and its increased focus upon successful standardized testing-all have been scrutinized as researchers look for causal connections.

Research has shown that vaccination with Streptococcus pneumoniae reduced the extent of atherosclerosis in experimental animal models. It is thought that phosphorylcholine lipid antigens in the S. pneumoniae cell wall induce the production of antibodies that cross-react with oxidized low-density lipoprotein, a component of atherosclerotic plaques. These antibodies may bind to and facilitate the regression of the plaques. Available data provide evidence that similar mechanisms also occur in humans, leading to the possibility that pneumococcal vaccination protects against atherosclerosis. A systematic review and meta-analysis, including 8 observational human studies, of adult pneumococcal polysaccharide vaccination for preventing cardiovascular disease in people older than 65 years, showed a 17% reduction in the odds (odds ratio 0.83, 95% CI 0.71-0.97) of having an acute coronary syndrome event. The AUSPICE is a multicenter, randomized, placebo-controlled, double-blind, clinical trial to formally test whether vaccination with the pneumococcal polysaccharide vaccine protects against cardiovascular events (fatal and nonfatal acute coronary syndromes and ischemic strokes). Cardiovascular outcomes will be obtained during 4 to 5 years of follow-up, through health record linkage with state and national administrative data sets. This is the first registered randomized controlled trial (on US, World Health Organization, Australia and New Zealand trial registries) to be conducted to test whether vaccination with the pneumococcal polysaccharide vaccine will reduce cardiovascular events. If successful, vaccination can be readily extended to at-risk groups to reduce the risk of cardiovascular diseases.

The complexity of bioprocesses and the variability inherent in biological systems pose challenges for manufacturing processes.Recent advances in bioprocessing technology have enabled more efficient and effective bioprocess development and monitoring.The implementation of quality-by-design principles and the use of computational approaches have also contributed to improved bioprocess robustness and regulatory compliance.The propagation of variances and interactions of different operations along a manufacturing process have an important role in determining the robustness of the whole process. Therefore, it is suggested to consider simultaneously as many of them as feasibly possible to reach a holistic understanding of process robustness.To understand and control bioprocess robustness, an investigation of every unit-processing operation, including robust downstream processing, is necessary. The robustness of bioprocesses is becoming increasingly important. The main driving forces of this development are, in particular, increasing demands on product purities as well as economic aspects. In general, bioprocesses exhibit extremely high complexity and variability. Biological systems often have a much higher intrinsic variability compared with chemical processes, which makes the development and characterization of robust processes tedious task. To predict and control robustness, a clear understanding of interactions between input and output variables is necessary. Robust bioprocesses can be realized, for example, by using advanced control strategies for the different unit operations. In this review, we discuss the different biological, technical, and mathematical tools for the analysis and control of bioprocess robustness.

We know that, in times past, male dominance in the field of music performance brought with it an emphasis upon the music of male composers. White dominance in the field at the same time similarly yielded a bias against people of color and their creative efforts. Te reality, that is increasingly addressed by authors and speakers across America, is that \"times present\" are not dramatically different.3 As of four years ago, only 2% of American orchestra conductors were Black or Latine, as were only 1% of orchestral executive directors, and in that year almost no music by BIPOC composers was programmed by major orchestras. While evidence is appearing over the past two years of initial efforts to explore diverse programming, and to express more tangibly the importance of diversity in the arts, this article focuses upon three specific gateways to a career in classical music that still hold too closely to traditions, and need review and revision.

ObjectivesVitamin B12 is crucial for neurologic function, red blood cell production, and DNA synthesis. Deficiency can lead to a wide spectrum of haematologic and neuropsychiatric disorders including subacute combined degeneration of the cord. This report presents a case of a 47 y.o female who presented with subacute combined degeneration of the spinal cord with a normal active B12 level.ResultsMRI demonstrated high T2 signal throughout the dorsal columns of the cervical and upper thoracic cord without enhancement consistent with subacute combined degeneration of the cord. Her blood count revealed a mild macrocytic anaemia. Total vitamin B12 was <80 pmol/L and active B12 was >128 pmol/L, confirmed on repeat testing. Functional vitamin B12 deficiency was confirmed by an elevated homocysteine level of 38.6 umol/L (reference range 4.4 to 13.6 umol/L) and elevated serum methylmalonic acid of 20.75 umol/L (reference range <0.32 umol/L). Intrinsic factor and gastric parietal cell antibodies were detected.ConclusionOur patient had a clinical presentation consistent with B12 deficiency with an erroneously high active B12 level. Functional assays confirmed B12 deficiency, and a serological diagnosis of pernicious anaemia was made. This case illustrates the importance of not relying on any single test to exclude B12 deficiency.

Background: Handicap is rarely comprehensively examined after stroke. We examined handicap among 5-year stroke survivors from an ‘ideal’ stroke incidence study. Methods: Survivors were assessed with the London Handicap Scale [LHS, score range: 0 (greatest handicap) to 100 (least handicap)]. Multivariable regression was used to examine demographic, risk and stroke-related factors associated with handicap. Results: 351 of 441 (80%) survivors were assessed. Those assessed were more often Australian born than those not assessed (p < 0.05). The mean LHS score was 73 (SD = 21). The greatest handicap was present for physical independence and occupation/leisure items. Handicap was associated with older age, manual occupations, smoking, initial stroke severity, recurrent stroke and mood disorders. Conclusion: Reducing recurrent stroke, through better risk factor management, is likely to reduce handicap. The association between handicap and mood disorders, which are potentially modifiable, warrants further investigation.

Background Stroke-specific outcome measures and descriptive measures of health-related quality of life (HRQoL) are unsuitable for informing decision-makers of the broader consequences of increasing or decreasing funding for stroke interventions. The quality-adjusted life year (QALY) provides a common metric for comparing interventions over multiple dimensions of HRQoL and mortality differentials. There are, however, many circumstances when – because of timing, lack of foresight or cost considerations – only stroke-specific or descriptive measures of health status are available and some indirect means of obtaining QALY-weights becomes necessary. In such circumstances, the use of regression-based transformations or mappings can circumvent the failure to elicit QALY-weights by allowing predicted weights to proxy for observed weights. This regression-based approach has been dubbed 'Transfer to Utility' (TTU) regression. The purpose of the present study is to demonstrate the feasibility and value of TTU regression in stroke by deriving transformations or mappings from stroke-specific and generic but descriptive measures of health status to a generic preference-based measure of HRQoL in a sample of Australians with a diagnosis of acute stroke. Findings will quantify the additional error associated with the use of condition-specific to generic transformations in stroke. Methods We used TTU regression to derive empirical transformations from three commonly used descriptive measures of health status for stroke (NIHSS, Barthel and SF-36) to a preference-based measure (AQoL) suitable for attaching QALY-weights to stroke disease states; based on 2570 observations drawn from a sample of 859 patients with stroke. Results Transformations from the SF-36 to the AQoL explained up to 71.5% of variation in observed AQoL scores. Differences between mean predicted and mean observed AQoL scores from the 'severity-specific' item- and subscale-based SF-36 algorithms and from the 'moderate to severe' index- and item-based Barthel algorithm were neither clinically nor statistically significant when 'low severity' SF-36 transformations were used to predict AQoL scores for patients in the NIHSS = 0 and NIHSS = 1–5 subgroups and when 'moderate to severe severity' transformations were used to predict AQoL scores for patients in the NIHSS ≥ 6 subgroup. In contrast, the difference between mean predicted and mean observed AQoL scores from the NIHSS algorithms and from the 'low severity' Barthel algorithms reached levels that could mask minimally important differences on the AQoL scale. Conclusion While our NIHSS to AQoL transformations proved unsuitable for most applications, our findings demonstrate that stroke-relevant outcome measures such as the SF-36 and Barthel Index can be adequately transformed to preference-based measures for the purposes of economic evaluation.