Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Understanding research capacity and culture of nurses and midwives in two health services in Western Australia

Background: Health services with a strong research culture report better patient outcomes and organisational performance. Measuring research capacity and culture (RCC) is important for understanding baseline research capabilities of a health service and assessing the effectiveness of capacity-building and culture-improving interventions. Aim: To describe the RCC of nurses and midwives in two health services in Western Australia. Methods: A cross-sectional survey of nurses and midwives was undertaken using a previously validated RCC tool to measure RCC in individual, professional group, and organisational domains, and identify barriers, enablers, and research activity. Staff at each health service were recruited via email during a three-month period in 2022. Quantitative data were analysed for descriptive statistics. Qualitative comments underwent content analysis. Results: Three hundred nurses and midwives completed the survey. Research capacity was low to moderate at the individual and group domains and moderate in the organisational domain. Participation in research activities was generally low. Top barriers for research involved lack of time and backfill, and other work roles taking priority, whilst top enablers were skill development, job satisfaction, and addressing identified problems. The results appeared similar across the two services. Conclusions: The findings align with previous studies, indicating that research capacity continues to be limited for nurses and midwives. Organisations should acknowledge key barriers and enablers for research and implement targeted capacity-building and culture-improving strategies

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Health-related quality of life and physical recovery after a critical illness: a multi-centre randomised controlled trial of a home-based physical rehabilitation program

Introduction: Significant physical sequelae exist for some survivors of a critical illness. There are, however, few studies that have examined specific interventions to improve their recovery, and none have tested a home-based physical rehabilitation program incorporating trainer visits to participants' homes. This study was designed to test the effect of an individualised eight-week home-based physical rehabilitation program on recovery. Methods: A multi-centre randomised controlled trial design was used. Adult intensive care patients (length of stay of at least 48 hours and mechanically ventilated for 24 hours or more) were recruited from 12 Australian hospitals between 2005 and 2008. Graded, individualised endurance and strength training intervention was prescribed over eight weeks, with three physical trainer home visits, four follow-up phone calls, and supported by a printed exercise manual. The main outcome measures were blinded assessments of physical function; SF-36 physical function (PF) scale and six-minute walk test (6MWT), and health-related quality of life (SF-36) conducted at 1, 8 and 26 weeks after hospital discharge. Results: Of the 195 participants randomised, 183, 173 and 161 completed the 1, 8 and 26 weeks assessments, respectively. Study groups were similar at Week 1 post-hospital; for the intervention and control groups respectively, mean norm-based PF scores were 27 and 29 and the 6MWT distance was 291 and 324 metres. Both groups experienced significant and clinically important improvements in PF scores and 6MWT distance at 8 weeks, which persisted at 26 weeks. Mixed model analysis showed no significant group effects (P = 0.84) or group by time interactions (P = 0.68) for PF. Similar results were found for 6MWT and the SF-36 summary scores. Conclusions: This individualised eight-week home-based physical rehabilitation program did not increase the underlying rate of recovery in this sample, with both groups of critically ill survivors improving their physical function over the 26 weeks of follow-up. Further research should explore improving effectiveness of the intervention by increasing exercise intensity and frequency, and identifying individuals who would benefit most from this intervention. Trial registration: Australia and New Zealand Clinical Trials Register ACTRN1260500016667

Development of Australian clinical practice outcome standards for graduates of critical care nurse education

Aims and objectivesTo develop critical care nurse education practice standards.BackgroundCritical care specialist education for registered nurses in Australia is provided at graduate level. Considerable variation exists across courses with no framework to guide practice outcomes or evidence supporting the level of qualification.DesignAn eDelphi technique involved the iterative process of a national expert panel responding to three survey rounds.MethodsFor the first round, 84 statements, organised within six domains, were developed from earlier phases of the study that included a literature review, analysis of critical care courses and input from health consumers. The panel, which represented the perspectives of four stakeholder groups, responded to two rating scales: level of importance and level of practice.ResultsOf 105 experts who agreed to participate, 92 (88%) completed survey round I; 85 (92%) round II; and 73 (86%) round III. Of the 98 statements, 75 were rated as having a high level of importance – median 7 (IQR 6–7); 14 were rated as having a moderate level of importance – median 6 (IQR 5–7); and nine were rated as having a low level of importance – median 4 (IQR 4–6)–6 (IQR 4–6). The majority of the panel rated graduate level of practice as ‘demonstrates independently’ or ‘teaches or supervises others’ for 80 statements. For 18 statements, there was no category selected by 50% or more of the panel. The process resulted in the development of 98 practice standards, categorised into three levels, indicating a practice outcome level by the practitioner who can independently provide nursing care for a variety of critically ill patients in most contexts, using a patient‐ and family‐focused approach.Conclusion/relevance to clinical practiceThe graduate practice outcomes provide a critical care qualification definition for nursing workforce standards and can be used by course providers to achieve consistent practice outcomes

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexit