Event Weighted Tests for Detecting Periodicity in Photon Arrival Times

This paper treats the problem of detecting periodicity in a sequence of photon arrival times, which occurs, for example, in attempting to detect gamma-ray pulsars. A particular focus is on how auxiliary information, typically source intensity, background intensity, and incidence angles and energies associated with each photon arrival should be used to maximize the detection power. We construct a class of likelihood-based tests, score tests, which give rise to event weighting in a principled and natural way, and derive expressions quantifying the power of the tests. These results can be used to compare the efficacies of different weight functions, including cuts in energy and incidence angle. The test is targeted toward a template for the periodic lightcurve, and we quantify how deviation from that template affects the power of detection

Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit

Introduction: Absolute lymphocytopenia has been reported as a predictor of bacteremia in medical emergencies. Likewise, the neutrophil-lymphocyte count ratio (NLCR) has been shown a simple promising method to evaluate systemic inflammation in critically ill patients. Methods: We retrospectively evaluated the ability of conventional infection markers, lymphocyte count and NLCR to predict bacteremia in adult patients admitted to the Emergency Department with suspected community-acquired bacteremia. The C-reactive protein (CRP) level, white blood cell (WBC) count, neutrophil count, lymphocyte count and NLCR were compared between patients with positive blood cultures (n = 92) and age-matched and gender-matched patients with negative blood cultures (n = 92) obtained upon Emergency Department admission. Results: Significant differences between patients with positive and negative blood cultures were detected with respect to the CRP level (mean +/- standard deviation 176 +/- 138 mg/l vs. 116 +/- 103 mg/l; P = 0.042), lymphocyte count (0.8 +/- 0.5 x 10(9)/l vs. 1.2 +/- 0.7 x 10(9)/l; P < 0.0001) and NLCR (20.9 +/- 13.3 vs. 13.2 +/- 14.1; P < 0.0001) but not regarding WBC count and neutrophil count. Sensitivity, specificity, positive and negative predictive values were highest for the NLCR (77.2%, 63.0%, 67.6% and 73.4%, respectively). The area under the receiver operating characteristic curve was highest for the lymphocyte count (0.73; confidence interval: 0.66 to 0.80) and the NLCR (0.73; 0.66 to 0.81). Conclusions: In an emergency care setting, both lymphocytopenia and NLCR are better predictors of bacteremia than routine parameters like CRP level, WBC count and neutrophil count. Attention to these markers is easy to integrate in daily practice and without extra cost

Implementing quality indicators in intensive care units: exploring barriers to and facilitators of behaviour change

<p/> <p>Background</p> <p>Quality indicators are increasingly used in healthcare but there are various barriers hindering their routine use. To promote the use of quality indicators, an exploration of the barriers to and facilitating factors for their implementation among healthcare professionals and managers of intensive care units (ICUs) is advocated.</p> <p>Methods</p> <p>All intensivists, ICU nurses, and managers (n = 142) working at 54 Dutch ICUs who participated in training sessions to support future implementation of quality indicators completed a questionnaire on perceived barriers and facilitators. Three types of barriers related to knowledge, attitude, and behaviour were assessed using a five-point Likert scale (1 = strongly disagree to 5 = strongly agree).</p> <p>Results</p> <p>Behaviour-related barriers such as time constraints were most prominent (Mean Score, MS = 3.21), followed by barriers related to knowledge and attitude (MS = 3.62; MS = 4.12, respectively). Type of profession, age, and type of hospital were related to knowledge and behaviour. The facilitating factor perceived as most important by intensivists was administrative support (MS = 4.3; p = 0.02); for nurses, it was education (MS = 4.0; p = 0.01), and for managers, it was receiving feedback (MS = 4.5; p = 0.001).</p> <p>Conclusions</p> <p>Our results demonstrate that healthcare professionals and managers are familiar with using quality indicators to improve care, and that they have positive attitudes towards the implementation of quality indicators. Despite these facts, it is necessary to lower the barriers related to behavioural factors. In addition, as the barriers and facilitating factors differ among professions, age groups, and settings, tailored strategies are needed to implement quality indicators in daily practice.</p

An X-Ray Pulsar in the Oxygen-Rich Supernova Remnant G292.0+1.8

We report the discovery of pulsed X-ray emission from the compact object CXOU J112439.1-591620 within the supernova remnant (SNR) G292.0+1.8 using the High Resolution Camera on the Chandra X-ray Observatory. The X-ray period (P=0.13530915 s) is consistent with extrapolation of the radio pulse period of PSR J1124-5916 for a spindown rate of dP/dt=7.6E-13 s/s. The X-ray pulse is single peaked and broad with a FWHM width of 0.23P (83 degrees). The pulse-averaged X-ray spectral properties of the pulsar are well described by a featureless power law model with an absorbing column density, N_H= 3.1E21 atoms/cm^2; photon index, gamma = 1.6; and unabsorbed 0.3-10 keV band luminosity, L_X = 7.2E32 erg/s. We plausibly identify the location of the pulsar's termination shock. Pressure balance between the pulsar wind and the larger synchrotron nebula, as well as lifetime issues for the X-ray-emitting electrons, argues for a particle- dominated PWN that is far from the minimum energy condition. Upper limits on the surface temperature of the neutron star are at, or slightly below, values expected from ``standard'' cooling curves. There is no optical counterpart to the new pulsar; its optical luminosity is at least a factor of 5 below that of the Crab pulsar.Comment: 5 pages, including 3 postscript figs, LaTeX, submitted to ApJ Letter

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Spectral Irradiance Calibration in the Infrared. XIII. "Supertemplates" and On-Orbit Calibrators for SIRTF's Infrared Array Camera (IRAC)

We describe the technique used to develop on-orbit calibrators for IRAC and validate the method for either K0-M0III or A0-A5V stars. For SIRTF, the approach uses all available optical, NIR, and MIR photometry, and yields absolute spectra from UV to MIR. One set of stars is from Landolt's network of optical standards, the other from Carter-Meadows IR standards. Traceability to the Cohen-Walker- Witteborn framework of absolute photometry and spectra is assured. The method is based on using either "supertemplates" to represent the intrinsic shapes of the spectra of K0-M0IIIs from 1150A to 35 um, or Kurucz synthetic spectra for A0-5V stars. Each supertemplate/model is reddened according to a star's extinction and normalized by characterized optical photometry. This paper tests our ability to predict NIR (JHK) magnitudes from supertemplates or models constrained by Hippa- rcos/Tycho or precision ground-based optical data. We offer absolute calibrated spectra of 33 optical standards to demonstrate the viability of this technique for a set of IR calibrators 100-1000 times fainter than we have previously publ- ished. We calculate the absolute uncertainties associated with predicting IRAC mags for the faintest cool giant and hot dwarf in this new set of calibrators.Comment: 53 pages, Latex, AASTEX5 macro

Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen

Background: Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods: In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves. Results: No difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions: This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged

Rationale and design of the PRAETORIAN-COVID trial:A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2)–infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II–mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. Methods: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2–infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2–infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally