Motorcycle Helmet Effectiveness in Reducing Head, Face and Brain Injuries by State and Helmet Law

Background: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S. Methods: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System\u27s General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative risks (RR) and 95 % confidence intervals (CIs) for head, facial, traumatic brain, and moderate to severe head/facial injuries associated with helmet use within each helmet law setting using generalized log-binomial regression. Results: Reported helmet use was higher in universal law states (88 % vs. 42 %). Median charges, adjusted for inflation and differences in state-incomes, were higher in partial law states (emergency department $1987 vs.$1443; inpatient $31,506 vs.$25,949). Injuries to the head and face, including traumatic brain injuries, were more common in partial law states. Effectiveness estimates of helmet use were higher in partial law states (adjusted-RR (CI) of head injury: 2.1 (1.9-2.2) partial law single vehicle; 1.4 (1.2, 1.6) universal law single vehicle; 1.8 (1.6-2.0) partial law multi-vehicle; 1.2 (1.1-1.4) universal law multi-vehicle). Conclusions: Medical charges and rates of head, facial, and brain injuries among motorcyclists were lower in universal law states. Helmets were effective in reducing injury in both helmet law settings; lower effectiveness estimates were observed in universal law states

Patient decision-making about emergency and planned stoma surgery for IBD: a qualitative exploration of patient and clinician perspectives

Background: Many IBD patients worry about stoma forming surgery (SFS), sometimes enduring poor bowel-related quality of life to avoid it. Anticipation of SFS and whether expectations match experience is under-reported. This qualitative study explored influences on patients’ SFS decision-making, and compared pre-operative concerns with post-operative outcomes. Methods: We purposively recruited participants with IBD from UK hospital outpatient and community sources, and IBD clinicians from public hospitals. Four focus groups and 29 semi-structured patient participant interviews, and 18 clinician interviews were audio recorded, transcribed, and analysed thematically. Participants had a current temporary, recently-reversed, or permanent stoma, or were stoma naïve. Results: Four themes emerged: Pre-operative concerns and expectations, Patient decision-making, Surgery and recovery, and Long-term outcomes. Participants and clinicians agreed about most pre-operative concerns, that outcomes were often better than expected, and support from others with a stoma is beneficial. Patient decision-making involves multiple factors, including disease status. Some clinicians avoid discussing SFS, and the phrase ‘last resort’ can bias patient perceptions; others recommend early discussion, increasing dialogue when medical management becomes ineffective. The post-operative period is particularly challenging for patients. Stoma acceptance is influenced by personal perceptions and pre- and post-operative clinical and social support. Conclusion: Patients need balanced information on all treatment options, including surgery, from an early stage. Early multi-disciplinary team dialogue about SFS, and contact with others living well with a stoma, could enable informed decision-making. Life with a stoma is often better than anticipated, improving quality of life and control. Ongoing specialist nursing support aids recovery and adjustment

Differing patterns in thermal injury incidence and hospitalisations among 0–4 year old children from England

Objective: To describe patterns in thermal injury incidence and hospitalisations by age, gender, calendar year and socioeconomic status among 0–4 year olds in England for the period 1998–2013. Participants: 708,050 children with linked primary care and hospitalisation data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), respectively. Analysis: Incidence rates of all thermal injuries (identified in CPRD and/or HES), hospitalised thermal injuries, and serious thermal injuries (hospitalised for ≥72 h). Adjusted incidence rate ratios (IRR) and 95% confidence intervals (95%CI), estimated using Poisson regression. Results: Incidence rates of all thermal injuries, hospitalised thermal injuries, and serious thermal injuries were 59.5 per 10,000 person-years (95%CI 58.4–60.6), 11.3 (10.8–11.8) and 2.15 (1.95–2.37), respectively. Socioeconomic gradients, between the most and least deprived quintiles, were steepest for serious thermal injuries (IRR 3.17, 95%CI 2.53–3.96). Incidence of all thermal injuries (IRR 0.64, 95%CI 0.58–0.70) and serious thermal injuries (IRR 0.44, 95%CI 0.33–0.59) reduced between 1998/9 and 2012/13. Incidence rates of hospitalised thermal injuries did not significantly change over time. Conclusion: Incidence of all thermal injuries and those hospitalised for ≥72 h reduced over time. Steep socioeconomic gradients support continued targeting of preventative interventions to those living in the most deprived areas

The ER-Bound RING Finger Protein 5 (RNF5/RMA1) Causes Degenerative Myopathy in Transgenic Mice and Is Deregulated in Inclusion Body Myositis

Growing evidence supports the importance of ubiquitin ligases in the pathogenesis of muscular disorders, although underlying mechanisms remain largely elusive. Here we show that the expression of RNF5 (aka RMA1), an ER-anchored RING finger E3 ligase implicated in muscle organization and in recognition and processing of malfolded proteins, is elevated and mislocalized to cytoplasmic aggregates in biopsies from patients suffering from sporadic-Inclusion Body Myositis (sIBM). Consistent with these findings, an animal model for hereditary IBM (hIBM), but not their control littermates, revealed deregulated expression of RNF5. Further studies for the role of RNF5 in the pathogenesis of s-IBM and more generally in muscle physiology were performed using RNF5 transgenic and KO animals. Transgenic mice carrying inducible expression of RNF5, under control of β-actin or muscle specific promoter, exhibit an early onset of muscle wasting, muscle degeneration and extensive fiber regeneration. Prolonged expression of RNF5 in the muscle also results in the formation of fibers containing congophilic material, blue-rimmed vacuoles and inclusion bodies. These phenotypes were associated with altered expression and activity of ER chaperones, characteristic of myodegenerative diseases such as s-IBM. Conversely, muscle regeneration and induction of ER stress markers were delayed in RNF5 KO mice subjected to cardiotoxin treatment. While supporting a role for RNF5 Tg mice as model for s-IBM, our study also establishes the importance of RNF5 in muscle physiology and its deregulation in ER stress associated muscular disorders

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD. Using a dot-blot assay and cultured N2a cells, we observed that TBSA inhibited Aβ42 aggregation and increased cell survival more effectively than did TPVA. These TBSA-induced benefits were extended to C. elegans expressing Aβ42 and to the 5xFAD mouse model of AD. Oral administration of 0.5 mg/kg dose of TBSA or an equivalent amount of methylcellulose vehicle to groups of six- and 12-month-old 5xFAD or wild-type mice over a two-month period prevented recognition- and spatial-memory deficits in the novel-object recognition and Morris-water-maze memory tasks, respectively, and reduced the number of pyknotic and degenerated cells, Aβ plaques, and GFAP and Iba-1 immunoreactivity in the hippocampus and cortex of these mice. These findings indicate that TBSA exerts neuroprotective properties by decreasing amyloid plaque burden and neuroinflammation, thereby preventing neuronal death and preserving memory function in the 5xFAD mice

artVIS: an interactive visualization for painting collections

Painting galleries typically provide a wealth of data composed of several data types. Those multivariate data are too complex for laymen like museum visitors to first, get an overview about all paintings and to look for specific categories. Finally, the goal is to guide the visitor to a specific painting that he wishes to have a more closer look on. In this paper we describe an interactive visualization tool that first provides such an overview and lets people experiment with the more than 41,000 paintings collected in the web gallery of art. To generate such an interactive tool, our technique is composed of different steps like data handling, algorithmic transformations, visualizations, interactions, and the human user working with the tool with the goal to detect insights in the provided data. We illustrate the usefulness of the visualization tool by applying it to such characteristic data and show how one can get from an overview about all paintings to specific paintings