Cost effectiveness of personally assigned "take home" patrol vehicles

Examines the costs and benefits of implementing a take home vehicle progra

Mesenchymal gene expression subtyping analysis for early-stage human papillomavirus-negative head and neck squamous cell carcinoma reveals prognostic and predictive applications

Patients with oral cavity squamous cell carcinoma (OCSCC) are predominantly human papillomavirus (HPV)(-), and treatment typically involves surgical resection ± neck dissection, followed by radiation ± chemotherapy. We previously described four mRNA expression patterns (classical, atypical, basal, and mesenchymal), each with unique genomic features and prognosis. Here, we examine the clinical utility of gene expression subtyping in head and neck squamous cell carcinoma (HNSCC) and introduce potentially predictive applications in HPV(-) OCSCC. A retrospective genomic database analysis was performed including 562 HNSCC patients from MD Anderson (MDA-GSE41116) and The Cancer Genome Atlas (TCGA). Samples were assigned molecular subtypes (classical, atypical, basal, and mesenchymal) using an 88-gene classifier. HPV status was determined by gene expression. The clinical endpoint was overall survival censured at 36 months. The Kaplan-Meier plots and log-rank tests were used to investigate associations between clinical variables and survival. Of the 418 TCGA training patients who met analysis criteria, nearly 20% presented as stage I/II. Among node(-) OCSCC patients, the mesenchymal subtype is associated with worse survival (hazard ratio (HR) = 2.4, p = 0.021), offering a potentially actionable biomarker in otherwise early-stage, low-risk disease. This was confirmed in the MDA validation cohort. Node(-) non-mesenchymal OCSCC patients had far better survival compared to node(-) mesenchymal, and all node(+) patients had similarly poor survival. These findings suggest that the mesenchymal subtype is associated with poor survival in surgically resected, early-stage, node(-) OCSCC otherwise expected to have favorable outcomes. These findings highlight the potential value of gene expression subtyping as a pathology adjunct for prognostication and treatment decision-making in OCSCC patients

Antitumor activity of an anti-CD98 antibody.

CD98 is expressed on several tissue types and specifically upregulated on fast-cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98-specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell-line derived xenograft models and was as efficacious as standard of care carboplatin in patient-derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase-3 and -7-mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors

Aerosol chemical composition and distribution during the Pacific Exploratory Mission (PEM) Tropics

Distributions of aerosol-associated soluble ions over much of the South Pacific were determined by sampling from the NASA DC-8 as part of the Pacific Exploratory Mission (PEM) Tropics campaign. The mixing ratios of all ionic species were surprisingly low throughout the free troposphere (2-12 km), despite the pervasive influence from biomass burning plumes advecting over the South Pacific from the west during PEM-Tropics. At the same time, the specific activity of 7Be frequently exceeded 1000 fCi m-3 through much of the depth of the troposphere. These distributions indicate that the plumes must have been efficiently scavenged by precipitation (removing the soluble ions), but that the scavenging must have occurred far upwind of the DC-8 sampling regions (otherwise 7Be activities would also have been low). This inference is supported by large enhancements of HNO3 and carboxylic acids in many of the plumes, as these soluble acidic gases would also be readily scavenged in any precipitation events. Decreasing mixing ratios of NH4 + with altitude in all South Pacific regions sampled provide support for recent suggestions that oceanic emissions of NH3 constitute a significant source far from continents. Our sampling below 2 km reaffirms the latitudinal pattern in the methylsulfonate/non-sea-salt sulfate (MSA/nss SO4 =) molar ratio established through surface-based and shipboard sampling, with values increasing from \u3c0.05 in the tropics to nearly 0.6 at 70°S. However, we also found very high values of this ratio (0.2-0.5) at 10 km altitude above the intertropical convergence zone near 10°N. It appears that wet convective pumping of dimethylsulfide from the tropical marine boundary layer is responsible for the high values of the MSA/nss SO4 = ratio in the tropical upper troposphere. This finding complicates use of this ratio to infer the zonal origin of biogenic S transported long distances. Copyright 1999 by the American Geophysical Union

pTDP-43 aggregates accumulate in non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis : a case series linking archival surgical biopsies with clinical phenotypic data

Acknowledgements The authors would like to thank the staff at the NHS Lothian BioResource (Vishad Patel and Craig Marshall) and the NHS Grampian biorepository (Joan Wilson) and the staff and corefunded resources of the imaging and histology core facility at the Institute of Medical Sciences (Gillian Milne, Lucinda Wight, and Debbie Wilkinson). This study was funded by the Pathological Society/Jean Shanks Foundation (JSPS CLSG 202002 to JMG and JO’S), The Royal Society (RGS\R1\221396 to JMG) and the Wellcome Trust (108890/Z/15/Z to OR). Funders had no role in study design, data collection, data analyses, interpretation, or writing the manuscriptPeer reviewedPostprin

Surgical Management of Ipsilateral Fracture of the Femur and Tibia in Adults (the Floating Knee): Postoperative Clinical, Radiological, and Functional Outcomes

Background: This study evaluated the outcomes of surgical management of ipsilateral femoral and tibial fractures in adults. Methods: Fifteen patients (13 men, 2 women; mean age, 34.8 years; range, 18 to 65 years) were enrolled in this study. The fracture

Fidelity of Interventions to Reduce or Prevent Stress and/or Anxiety from Pregnancy up to Two Years Postpartum: A Systematic Review

IntroductionIntervention fidelity refers to whether an intervention is delivered as intended and can enhance interpretation of trial outcomes. Fidelity of interventions to reduce or prevent stress and anxiety during pregnancy and postpartum has yet to be examined despite inconsistent findings for intervention effects. This study systematically reviews use and/or reporting of intervention fidelity strategies in trials of interventions, delivered to (expectant) parents during pregnancy and postpartum, to reduce or prevent stress and/or anxiety.MethodsMEDLINE, Embase, CINAHL, PsychINFO, and Maternity and Infant Care were searched from inception to March 2019. Studies were included if they were randomised controlled trials including pregnant women, expectant fathers and/or partners during pregnancy, and/ or parents within the first two years postpartum. The National Institutes of Health Behavior Change Consortium checklist was used to assess fidelity across five domains (study design, provider training, delivery, receipt, enactment).ResultsSixteen papers (14 interventions) were identified. Average reported use of fidelity strategies was ‘low’ (45%), ranging from 17.5 to 76%. Fidelity ratings ranged from 22% for provider training to 54% for study design.ConclusionsLow levels of intervention fidelity may explain previous inconsistent effects of stress and anxiety reduction interventions. Important methodological areas for improvement include intervention provider training, fidelity of comparator conditions, and consideration of non-specific treatment effects. Increased methodological rigour in fidelity enhancement and assessment will improve intervention implementation and enhance examination of stress and anxiety reduction and prevention interventions delivered during pregnancy and the postpartum

(Non)Existence of Pleated Folds: How Paper Folds Between Creases

We prove that the pleated hyperbolic paraboloid, a familiar origami model known since 1927, in fact cannot be folded with the standard crease pattern in the standard mathematical model of zero-thickness paper. In contrast, we show that the model can be folded with additional creases, suggesting that real paper “folds” into this model via small such creases. We conjecture that the circular version of this model, consisting simply of concentric circular creases, also folds without extra creases. At the heart of our results is a new structural theorem characterizing uncreased intrinsically flat surfaces—the portions of paper between the creases. Differential geometry has much to say about the local behavior of such surfaces when they are sufficiently smooth, e.g., that they are torsal ruled. But this classic result is simply false in the context of the whole surface. Our structural characterization tells the whole story, and even applies to surfaces with discontinuities in the second derivative. We use our theorem to prove fundamental properties about how paper folds, for example, that straight creases on the piece of paper must remain piecewise-straight (polygonal) by folding.National Science Foundation (U.S.) (CAREER Award CCF-0347776