871 research outputs found

    Optimizing Atraumatic Emergency Care in Child Sexual Abuse

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    Child sexual abuse has been identified as a common problem. According to the United States Department of Health and Human Services, in 2010 it was estimated that child victims of sexual abuse accounted for 9.2% (69,368) of the 573,794 children under the age of 12 years who were the victims of maltreatment. The emergency department (ED) is often the point of entry into the healthcare system for child sexual abuse victims, which adds to the resource burden of this department nationwide. The purpose of this evidence-based project was to develop a best-practice screening tool for medical providers to guide the care of the sexually abused female child and also to assess their educational preparation to care for this population. Ajzen’s Theory of Planned Behavior and Rogers’ Diffusion of Innovations Model guided this project at a large multi-center hospital system in Indiana. A critical appraisal of the literature was conducted to establish best-practice. To determine if implementation of a screening tool into the electronic health record changed medical provider practice, a matched case-control study design was applied. Education on best-practice recommendations was presented for nurses and medical providers. Pre- and post-intervention data were collected from medical records of female pediatric patients examined in the ED for sexual abuse and reviewed to determine the necessity of an anogenital exam. The odds of receiving an anogenital exam were greater prior to the implementation of the screening tool (OR 16; AR 75%). These findings support that a screening tool intervention decreased unnecessary anogenital exams in these female children. A survey of the medical providers was completed demonstrating 64.9% reporting no training to care for this vulnerable population of children. A Pearson Chi-Square was calculated to compare MD and PA providers educational preparation in the area of child sexual abuse (X2 =12.067, df =1, p \u3c .001) demonstrating more preparation in the MD group. Enhanced educational preparation in best-practice care would benefit all medical providers caring for these children in various settings

    Future Practices and Technologies in Anthropometrics and Body Scanning

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    There have also been great strides in software development, to convert and manipulate 3D scan data, to make mannequins, lasts, patterns, tooling files, etc. The presenters invited to this special topic session are at the forefront of these research spaces, either through evaluating or utilizing these technologies for product design and developmen

    Single-cell analysis reveals regional reprogramming during adaptation to massive small bowel resection in mice

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    BACKGROUND & AIMS: The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or adapt ; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS. METHODS: Single-cell RNA sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH. RESULTS: Uniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factor Creb3l3 drive proximalization of cell identity in response to SBR. CONCLUSIONS: Adaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes-conceivably by engaging the retinoid metabolism pathway-merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS

    A non-experimental study of oral anticoagulation therapy initiation before and after national patient safety goals

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    ObjectivesThe Joint Commission revised its National Patient Safety Goals (NPSGs) to include oral anticoagulation therapy (OAT) in 2008. We sought to examine the effect of including OAT in The Joint Commission's NPSGs on historically low rates of OAT initiation for individuals with incident atrial fibrillation (AF).SettingSoutheastern state in the USA.ParticipantsNorth Carolina State Health Plan claims data from 944 500 individuals enrolled between 1 January 2006 and 31 December 2010, supplemented with data from the Area Resource File and Online Survey, Certification and Reporting data network. We evaluated OAT initiation before and after the 2008 NPSGs revisions in a retrospective cohort new user design with an AF intervention group and two control groups: a positive control—patients estimated to be at very high risk of thromboembolism (mechanical heart valve and pulmonary embolism); and a negative control—patients with very low perceived risk of thromboembolism (paroxysmal AF). We developed multivariable models using a difference-in-difference parameterisation. Effects were estimated with generalised estimating equations.Primary outcome measureOAT initiation, a binary outcome defined as having a prescription drug claim for warfarin within 30 days of the index claim.ResultsOAT initiation was low (26.8%) for eligible individuals with incident AF in 2006–2008 but increased after NPSGs implementation (31.7%, p=0.022). OAT initiation was high but decreased in the positive control group (67.5% vs 62.0%, p=0.003). Multivariate analysis resulted in a relative 11% (95% CI (4% to 18%), p<0.01) increase in OAT initiation for incident AF patients.ConclusionsWe document a substantial increase in guideline concordant OAT initiation in incident AF after the establishment of NPSGs, suggesting that regulatory healthcare agency initiatives can influence clinical practice

    A novel patient-derived intra-femoral xenograft model of bone metastatic prostate cancer that recapitulates mixed osteolytic and osteoblastic lesions

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    <p>Abstract</p> <p/> <p>Prostate cancer metastasizes to bone in the majority of patients with advanced disease leading to painfully debilitating fractures, spinal compression and rapid decline. In addition, prostate cancer bone metastases often become resistant to standard therapies including androgen deprivation, radiation and chemotherapy. There are currently few models to elucidate mechanisms of interaction between the bone microenvironment and prostate cancer. It is, thus, essential to develop new patient-derived, orthotopic models. Here we report the development and characterization of PCSD1 (Prostate Cancer San Diego 1), a novel patient-derived intra-femoral xenograft model of prostate bone metastatic cancer that recapitulates mixed osteolytic and osteoblastic lesions.</p> <p>Methods</p> <p>A femoral bone metastasis of prostate cancer was removed during hemiarthroplasty and transplanted into <it>Rag2<sup>-/-</sup>;γ<sub>c</sub><sup>-/- </sup></it>mice either intra-femorally or sub-cutaneously. Xenograft tumors that developed were analyzed for prostate cancer biomarker expression using RT-PCR and immunohistochemistry. Osteoblastic, osteolytic and mixed lesion formation was measured using micro-computed tomography (microCT).</p> <p>Results</p> <p>PCSD1 cells isolated directly from the patient formed tumors in all mice that were transplanted intra-femorally or sub-cutaneously into <it>Rag2<sup>-/-</sup>;γ<sub>c</sub><sup>-/- </sup></it>mice. Xenograft tumors expressed human prostate specific antigen (PSA) in RT-PCR and immunohistochemical analyses. PCSD1 tumors also expressed AR, NKX3.1, Keratins 8 and 18, and AMACR. Histologic and microCT analyses revealed that intra-femoral PCSD1 xenograft tumors formed mixed osteolytic and osteoblastic lesions. PCSD1 tumors have been serially passaged in mice as xenografts intra-femorally or sub-cutaneously as well as grown in culture.</p> <p>Conclusions</p> <p>PCSD1 xenografts tumors were characterized as advanced, luminal epithelial prostate cancer from a bone metastasis using RT-PCR and immunohistochemical biomarker analyses. PCSD1 intra-femoral xenografts formed mixed osteoblastic/osteolytic lesions that closely resembled the bone lesions in the patient. PCSD1 is a new primary prostate cancer bone metastasis-derived xenograft model to study metastatic disease in the bone and to develop novel therapies for inhibiting prostate cancer growth in the bone-niche.</p

    Comparison of geometric morphometric outline methods in the discrimination of age-related differences in feather shape

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    BACKGROUND: Geometric morphometric methods of capturing information about curves or outlines of organismal structures may be used in conjunction with canonical variates analysis (CVA) to assign specimens to groups or populations based on their shapes. This methodological paper examines approaches to optimizing the classification of specimens based on their outlines. This study examines the performance of four approaches to the mathematical representation of outlines and two different approaches to curve measurement as applied to a collection of feather outlines. A new approach to the dimension reduction necessary to carry out a CVA on this type of outline data with modest sample sizes is also presented, and its performance is compared to two other approaches to dimension reduction. RESULTS: Two semi-landmark-based methods, bending energy alignment and perpendicular projection, are shown to produce roughly equal rates of classification, as do elliptical Fourier methods and the extended eigenshape method of outline measurement. Rates of classification were not highly dependent on the number of points used to represent a curve or the manner in which those points were acquired. The new approach to dimensionality reduction, which utilizes a variable number of principal component (PC) axes, produced higher cross-validation assignment rates than either the standard approach of using a fixed number of PC axes or a partial least squares method. CONCLUSION: Classification of specimens based on feather shape was not highly dependent of the details of the method used to capture shape information. The choice of dimensionality reduction approach was more of a factor, and the cross validation rate of assignment may be optimized using the variable number of PC axes method presented herein

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

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    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

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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

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    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
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