357 research outputs found

    Data acquisition electronics and reconstruction software for directional detection of Dark Matter with MIMAC

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    Directional detection of galactic Dark Matter requires 3D reconstruction of low energy nuclear recoils tracks. A dedicated acquisition electronics with auto triggering feature and a real time track reconstruction software have been developed within the framework of the MIMAC project of detector. This auto-triggered acquisition electronic uses embedded processing to reduce data transfer to its useful part only, i.e. decoded coordinates of hit tracks and corresponding energy measurements. An acquisition software with on-line monitoring and 3D track reconstruction is also presented.Comment: 17 pages, 12 figure

    Standardization and validation of a novel and simple method to assess lumbar dural sac size

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    AimTo develop and validate a simple, reproducible method to assess dural sac size using standard imaging technology.Materials and methodsThis study was institutional review board-approved. Two readers, blinded to the diagnoses, measured anterior–posterior (AP) and transverse (TR) dural sac diameter (DSD), and AP vertebral body diameter (VBD) of the lumbar vertebrae using MRI images from 53 control patients with pre-existing MRI examinations, 19 prospectively MRI-imaged healthy controls, and 24 patients with Marfan syndrome with prior MRI or CT lumbar spine imaging. Statistical analysis utilized linear and logistic regression, Pearson correlation, and receiver operating characteristic (ROC) curves.ResultsAP-DSD and TR-DSD measurements were reproducible between two readers (r = 0.91 and 0.87, respectively). DSD (L1–L5) was not different between male and female controls in the AP or TR plane (p = 0.43; p = 0.40, respectively), and did not vary by age (p = 0.62; p = 0.25) or height (p = 0.64; p = 0.32). AP-VBD was greater in males versus females (p = 1.5 × 10−8), resulting in a smaller dural sac ratio (DSR) (DSD/VBD) in males (p = 5.8 × 10−6). Marfan patients had larger AP-DSDs and TR-DSDs than controls (p = 5.9 × 10−9; p = 6.5 × 10−9, respectively). Compared to DSR, AP-DSD and TR-DSD better discriminate Marfan from control subjects based on area under the curve (AUC) values from unadjusted ROCs (AP-DSD p < 0.01; TR-DSD p = 0.04).ConclusionIndividual vertebrae and L1–L5 (average) AP-DSD and TR-DSD measurements are simple, reliable, and reproducible for quantitating dural sac size without needing to control for gender, age, or height

    Relational Hidden Variables and Non-Locality

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    We use a simple relational framework to develop the key notions and results on hidden variables and non-locality. The extensive literature on these topics in the foundations of quantum mechanics is couched in terms of probabilistic models, and properties such as locality and no-signalling are formulated probabilistically. We show that to a remarkable extent, the main structure of the theory, through the major No-Go theorems and beyond, survives intact under the replacement of probability distributions by mere relations.Comment: 42 pages in journal style. To appear in Studia Logic

    Semiparametric estimation of the proportional rates model for recurrent events data with missing event category

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    Proportional rates models are frequently used for the analysis of recurrent event data with multiple event categories. When some of the event categories are missing, a conventional approach is to either exclude the missing data for a complete-case analysis or employ a parametric model for the missing event type. It is well known that the complete-case analysis is inconsistent when the missingness depends on covariates, and the parametric approach may incur bias when the model is misspecified. In this paper, we aim to provide a more robust approach using a rate proportion method for the imputation of missing event types. We show that the log-odds of the event type can be written as a semiparametric generalized linear model, facilitating a theoretically justified estimation framework. Comprehensive simulation studies were conducted demonstrating the improved performance of the semiparametric method over parametric procedures. Multiple types of Pseudomonas aeruginosa infections of young cystic fibrosis patients were analyzed to demonstrate the feasibility of our proposed approach

    Antibacterial Use Is Associated with an Increased Risk of Hematologic and Gastrointestinal Adverse Events in Patients Treated with Gemcitabine for Stage IV Pancreatic Cancer

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    Background: Preclinical evidence has demonstrated that common intratumor bacteria metabolize the chemotherapeutic drug gemcitabine. The significance of this bacterial metabolism pathway, relative to the known metabolic pathways by host enzymes, is not known. We hypothesized that bacterial metabolism is clinically significant and that “knockdown” by antibacterial therapy has the unintended effect of increasing the effective dose of gemcitabine, thereby increasing the risk for gemcitabine-associated toxicities. Materials and Methods: We reanalyzed the comparator arm of the MPACT trial (NCT01442974), made available through Project Data Sphere, LLC (CEO Roundtable on Cancer's Life Sciences Consortium, Cary, NC; www.projectdatasphere.org). In this arm, 430 patients with metastatic pancreatic adenocarcinoma were treated with gemcitabine. We used the Anderson-Gill survival model to compare the risk of developing an adverse event after antibacterial prescription with time unexposed to antibacterials. Adverse events of grade 3 and greater were considered at three levels of granularity: all aggregated into one endpoint, aggregated by class, and taken individually. Antibiotic exposures were analyzed in aggregate as well as by class. Results: Antibacterial exposure was associated with an increased risk of adverse events (hazard ratio [HR]: 1.77; confidence interval [CI]: 1.46–2.14), any hematologic adverse event (HR: 1.64; CI: 1.26–2.13), and any gastrointestinal adverse event (HR: 2.14; CI: 1.12–4.10) but not a constitutional (HR: 1.33; CI: 0.611–2.90) or hepatologic adverse event (HR: 0.99; CI: 0.363–2.71). Among specific adverse events, antibacterial exposure was associated with an increased risk of anemia (HR: 3.16; CI: 1.59–6.27), thrombocytopenia (HR: 2.52; CI: 1.31–4.85), leukopenia (HR: 3.91; CI: 1.46–10.5), and neutropenia (HR: 1.53; CI: 1.07–2.17) but not any other specific adverse events. Conclusion: Antibacterial exposure was associated with an increased risk of gemcitabine-associated, dose-limiting adverse events, including aggregate hematologic and gastrointestinal events, as well as four specific hematologic adverse events, suggesting that intratumor bacteria may be responsible for a clinically significant portion of gemcitabine metabolism. Alternative avenues of evidence will be necessary to confirm this preliminary finding and assess its generalizability. There is plentiful opportunity for similar analyses on other clinical trial data sets, where gemcitabine or other biomimetic small molecules were used. Implications for Practice: Patients treated with gemcitabine for metastatic pancreatic ductal adenocarcinoma have an increased rate of gemcitabine-associated toxicity during and after antibiotic therapy. This observation is consistent with preclinical evidence that intratumor bacteria metabolize gemcitabine to an inactive form. Further research is needed to determine whether this observation merits any changes in clinical practice

    Safety of dynamic intravenous iron administration strategies in hemodialysis patients

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    Background and objectives Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach (i.e., dose, frequency, and duration). Little is known about the safety of these protocols. Design, setting, participants, & measurements Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD aged ≥65 years who initiated and continued center-based hemodialysis for ≥90 days between 2009 and 2012, and initiated at least one of the five common intravenous iron administration strategies; ranked by intensity (the amount of iron given at moderate-to-high iron indices), the order of strategies was 3 (least intensive), 2 (less intensive), 1 (reference), 4 (more intensive), and 5 (most intensive). We estimated the effect of continuous exposure to these strategies on cumulative risks of mortality and infection-related events with dynamic Cox marginal structural models. Results Of 13,249 eligible patients, 1320 (10%) died and 1627 (12%) had one or more infection-related events during the 4-month follow-up. The most and least commonly initiated strategy was strategy 2 and 5, respectively. Compared with the reference strategy 1, more intensive strategies (4 and 5) demonstrated a higher risk of all-cause mortality (e.g., most intensive strategy 5: 60-day risk difference: 1.3%; 95% confidence interval [95% CI], 0.8% to 2.1%; 120-day risk difference: 3.1%; 95% CI, 1.0% to 5.6%). Similarly, higher risks were observed for infection-related morbidity and mortality among more intensive strategies (e.g., strategy 5: 60-day risk difference: 1.8%; 95% CI, 1.2% to 2.6%; 120-day risk difference: 4.3%; 95% CI, 2.2% to 6.8%). Less intensive strategies (2 and 3) demonstrated lower risks of all-cause mortality and infection-related events. Conclusions Among dialysis patients surviving 90 days, subsequent intravenous iron administration strategies promoting more intensive iron treatment at moderate-to-high iron indices levels are associated with higher risks of mortality and infection-related events

    Increasing rates of fluoroquinolone resistance in escherichia coli isolated from the blood and urine of patients with hematologic malignancies and stem cell transplant recipients

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    Fluoroquinolone (FQ) antibiotics have been shown to reduce mortality and the number of febrile episodes when used as prophylaxis during neutropenia. Prior studies suggest that prophylaxis may result in increasing rates of FQ resistance. Fluoroquinolone non-susceptibility trends in Escherichia coli isolated from blood and urine cultures were evaluated over a 16-year period during which prophylaxis was initiated in patients with hematologic malignancies and stem cell transplants. Non-susceptibility rates increased after the introduction of prophylaxis, with yearly non-susceptibility rates rising from 30%–33% to 40%–88% in blood isolates. The high rates of non-susceptibility now observed raise concerns about the continued efficacy of FQ prophylaxis. This concern exists particularly in those patients undergoing stem cell transplants where the total FQ non-susceptibility rates over the study period were 82.3%. Further evaluation of the effect of FQ prophylaxis on antibiotic resistance and its efficacy in the setting of increased rates of resistance is warranted

    GDNF-expressing macrophages restore motor functions at a severe late-stage, and produce long-term neuroprotective effects at an early-stage of Parkinson's disease in transgenic Parkin Q311X(A) mice

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    There is an unmet medical need in the area of Parkinson's disease (PD) to develop novel therapeutic approaches that can stop and reverse the underlying mechanisms responsible for the neuronal death. We previously demonstrated that systemically administered autologous macrophages transfected ex vivo to produce glial cell line-derived neurotrophic factor (GDNF) readily migrate to the mouse brain with acute toxin-induced neuroinflammation and ameliorate neurodegeneration in PD mouse models. We hypothesized that the high level of cytokines due to inflammatory process attracted GDNF-expressing macrophages and ensured targeted drug delivery to the PD brain. Herein, we validated a therapeutic potential of GDNF-transfected macrophages in a transgenic Parkin Q311X(A) mice with slow progression and mild brain inflammation. Systemic administration of GDNF-macrophages at a severe late stage of the disease leaded to a near complete restoration of motor functions in Parkin Q311X(A) mice and improved brain tissue integrity with healthy neuronal morphology. Furthermore, intravenous injections of GDNF-macrophages at an early stage of disease resulted in potent sustained therapeutic effects in PD mice for more than a year after the treatment. Importantly, multiple lines of evidence for therapeutic efficacy were observed including: diminished neuroinflammation and α-synuclein aggregation, increased survival of dopaminergic neurons, and improved locomotor functions. In summary, GDNF-transfected macrophages represent a promising therapeutic strategy for PD at both late- and early-stages of the disease

    The organizational construction of hegemonic masculinity: the case of the US Navy

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    This article examines the construction of hegemonic masculinity within the US Navy. Based on life history interviews with 27 male officers, this study explores alternative discourses and identities of officers from three different communities in the Navy: aviation, surface warfare, and the supply corps. Definitions of masculinity are relationally constructed through associations of difference: aviators tend to draw upon themes of autonomy and risk taking; surface warfare officers draw upon themes of perseverance and endurance; and supply officers draw upon themes of technical rationality. Further,these masculinities depend upon various contrasting definitions of femininity. Finally,this article explores a series of contradictions that threaten the secure construction of masculinity within this military culture

    Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

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    We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC
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