NuRadioMC is a Monte Carlo framework designed to simulate ultra-high energy neutrino detectors that rely on the radio detection method. This method exploits the radio emission generated in the ...electromagnetic component of a particle shower following a neutrino interaction. NuRadioMC simulates everything from the neutrino interaction in a medium, the subsequent Askaryan radio emission, the propagation of the radio signal to the detector and finally the detector response. NuRadioMC is designed as a modern, modular Python-based framework, combining flexibility in detector design with user-friendliness. It includes a state-of-the-art event generator, an improved modelling of the radio emission, a revisited approach to signal propagation and increased flexibility and precision in the detector simulation. This paper focuses on the implemented physics processes and their implications for detector design. A variety of models and parameterizations for the radio emission of neutrino-induced showers are compared and reviewed. Comprehensive examples are used to discuss the capabilities of the code and different aspects of instrumental design decisions.
Background
Several recent studies have investigated the role of C‐reactive protein (CRP) as an early marker of anastomotic leakage following colorectal surgery. The aim of this systematic review and ...meta‐analysis was to evaluate the predictive value of CRP in this setting.
Methods
A systematic literature search was performed using MEDLINE, Embase and PubMed to identify studies evaluating the diagnostic accuracy of postoperative CRP for anastomotic leakage following colorectal surgery. A meta‐analysis was carried out using a random‐effects model and pooled predictive parameters were determined along with a CRP cut‐off value at each postoperative day (POD).
Results
Seven studies, with a total of 2483 patients, were included. The pooled prevalence of leakage was 9·6 per cent and the median day on which leakage was diagnosed ranged from POD 6 to 9. The serum CRP level on POD 3, 4 and 5 had comparable diagnostic accuracy for the development of an anastomotic leak with a pooled area under the curve of 0·81 (95 per cent confidence interval 0·75 to 0·86), 0·80 (0·74 to 0·86) and 0·80 (0·73 to 0·87) respectively. The derived CRP cut‐off values were 172 mg/l on POD 3, 124 mg/l on POD 4 and 144 mg/l on POD 5; these corresponded to a negative predictive value of 97 per cent and a negative likelihood ratio of 0·26–0·33. All three time points had a low positive predictive value for leakage, ranging between 21 and 23 per cent.
Conclusion
CRP is a useful negative predictive test for the development of anastomotic leakage following colorectal surgery.
Day 3 to 5 levels helpful
ABSTRACT
Many scientific investigations of photometric galaxy surveys require redshift estimates, whose uncertainty properties are best encapsulated by photometric redshift (photo-z) posterior ...probability density functions (PDFs). A plethora of photo-z PDF estimation methodologies abound, producing discrepant results with no consensus on a preferred approach. We present the results of a comprehensive experiment comparing 12 photo-z algorithms applied to mock data produced for The Rubin Observatory Legacy Survey of Space and Time Dark Energy Science Collaboration. By supplying perfect prior information, in the form of the complete template library and a representative training set as inputs to each code, we demonstrate the impact of the assumptions underlying each technique on the output photo-z PDFs. In the absence of a notion of true, unbiased photo-z PDFs, we evaluate and interpret multiple metrics of the ensemble properties of the derived photo-z PDFs as well as traditional reductions to photo-z point estimates. We report systematic biases and overall over/underbreadth of the photo-z PDFs of many popular codes, which may indicate avenues for improvement in the algorithms or implementations. Furthermore, we raise attention to the limitations of established metrics for assessing photo-z PDF accuracy; though we identify the conditional density estimate loss as a promising metric of photo-z PDF performance in the case where true redshifts are available but true photo-z PDFs are not, we emphasize the need for science-specific performance metrics.
Aneurysmal subarachnoid hemorrhage (aSAH) is a form of hemorrhagic stroke that affects up to 30,000 individuals per year in the United States. The incidence of aSAH has been shown to be associated ...with numerous nonmodifiable (age, gender, ethnicity, family history, aneurysm location, size) and modifiable (hypertension, body mass index, tobacco and illicit drug use) risk factors. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease, with mortality approaching 50% and less than 60% of survivors returning to functional independence. As treatment modalities change and the percentage of minority and elderly populations increase, it is critical to maintain an up-to-date understanding of the epidemiology of SAH.
Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the reaction pathway, have been deployed extensively in the analysis of metabolic pathways and as candidate drugs. The ...inhibition of cytosine-C5-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism. Here, we describe the interaction between the C5 MTase from
Haemophilus haemolyticus (M.
HhaI) and an oligodeoxynucleotide duplex containing 2-H pyrimidinone, an analogue often referred to as zebularine and known to give rise to high-affinity complexes with MTases. X-ray crystallography has demonstrated the formation of a covalent bond between M.
HhaI and the 2-H pyrimidinone-containing oligodeoxynucleotide. This observation enables a comparison between the mechanisms of action of 2-H pyrimidinone with other mechanism-based inhibitors such as FdC. This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine.
Background Systemic inflammation has been implicated in the development of cognitive dysfunction following carotid endarterectomy (CEA). Neutrophil-lymphocyte ratio (NLR) is a reliable measure of ...systemic inflammation. We hypothesize that patients with elevated preoperative NLR have increased risk of cognitive dysfunction 1 day after CEA. Methods Five hundred fifty-one patients scheduled for CEA were enrolled at Columbia University in New York, NY from 1995 to 2012. NLR was retrospectively reviewed; only 432 patients had preoperative NLR values available within 2 weeks of CEA. NLR was analyzed as a continuous variable and categorically with a cutoff of ≥5 and <5 and equal tertiles, as done in previous studies. Results Patients with cognitive dysfunction had significantly higher NLR than those without cognitive dysfunction (4.5 ± 4.0 vs 3.2 ± 2.6; P < .001). The incidence of cognitive dysfunction was significantly higher in patients with NLR ≥5 than NLR <5 (34.7% vs 12.8%; P < .001). Significantly fewer patients in the low tertile had cognitive dysfunction than in the high tertile (6.9% vs 25.9%; P <.001) and middle tertile (6.9% vs 17.4%; P = .006). In the final multivariate model, diabetes mellitus (odds ratio OR, 2.03; 95% confidence interval CI, 1.08-3.75; P = .03) and NLR ≥5 (OR, 3.38; 95% CI, 1.81-6.27; P < .001) were significantly associated with higher odds of cognitive dysfunction, while statin use was significantly associated with lower odds (OR, 0.48; 95% CI, 0.27-0.84; P = .01). Conclusions Preoperative NLR is associated with cognitive dysfunction 1 day after CEA. NLR ≥5 and diabetes mellitus are significantly associated with increased odds of cognitive dysfunction whereas statin use is significantly associated with decreased odds.
Lung transplant recipients are encouraged to perform self‐management behaviors, including (i) monitoring health indicators, (ii) adhering to their regimen, and (iii) reporting abnormal health ...indicators to the transplant coordinator, yet performance is suboptimal. When hospital discharge was imminent, this two‐group trial randomized 201 recipients to use either the mobile health (mHealth) intervention (n = 99) or usual care (n = 102), to compare efficacy for promoting self‐management behaviors (primary outcomes) and self‐care agency, rehospitalization, and mortality (secondary outcomes) at home during the first year after transplantation. The mHealth intervention group performed self‐monitoring (odds ratio OR 5.11, 95% confidence interval CI 2.95–8.87, p < 0.001), adhered to medical regimen (OR 1.64, 95% CI 1.01–2.66, p = 0.046), and reported abnormal health indicators (OR 8.9, 95% CI 3.60–21.99, p < 0.001) more frequently than the usual care group. However, the two groups did not differ in rehospitalization (OR 0.78, 95% CI 0.36–1.66, p = 0.51) or mortality (hazard ratio 1.71, 0.68–4.28, p = 0.25). The positive impact of the mHealth intervention on self‐management behaviors suggests that the intervention holds promise and warrants further testing.
This randomized controlled trial of lung recipients followed for one year after transplant demonstrates that a mobile health intervention is superior to usual care in promoting self‐management behaviors, though the two groups did not differ in health outcomes, suggesting that mHealth interventions hold promise but warrant further testing.
BACKGROUND:Gene regulatory networks control tissue homeostasis and disease progression in a cell-type specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the ...mechanisms governing how tissue-specificity of their function is achieved are poorly understood. BRD4, a member of the BET (Bromo- and Extra-Terminal domain) family of ubiquitously expressed acetyl-lysine reader proteins, plays a pivotal role as a coactivator of enhancer signaling across diverse tissue types in both health and disease, and has been implicated as a pharmacologic target in heart failure. However, the cell-specific role of BRD4 in adult cardiomyocytes remains unknown.
METHODS:We combined conditional mouse genetics, unbiased transcriptomic and epigenomic analyses, and classical molecular biology and biochemical approaches to understand the role of BRD4 in adult cardiomyocyte homeostasis.
RESULTS:Here, we show that cardiomyocyte-specific deletion of Brd4 in adult mice leads to acute deterioration of cardiac contractile function with mutant animals demonstrating a transcriptomic signature enriched for decreased expression of genes critical for mitochondrial energy production. Genome-wide occupancy data show that BRD4 enriches at many downregulated genes (including the master co-activators Ppargc1a, Ppargc1b, and their downstream targets) and preferentially co-localizes with GATA4, a lineage determining cardiac transcription factor not previously implicated in regulation of adult cardiac metabolism. BRD4 and GATA4 form an endogenous complex in cardiomyocytes and interact in a bromodomain- independent manner, revealing a new functional interaction partner for BRD4 that can direct its locus and tissue specificity.
CONCLUSIONS:These results highlight a novel role for a BRD4-GATA4 module in cooperative regulation of a cardiomyocyte specific gene program governing bioenergetic homeostasis in the adult heart.
Summary
Background Reliable and validated measures of skin disease severity are needed for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), ...Dermatomyositis Skin Severity Index (DSSI) and Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments.
Objectives We sought to demonstrate reliability and validity of the CDASI, and to compare the CDASI with other potential tools for use in measuring disease severity in cutaneous dermatomyositis.
Patients and methods CDASI has four activity and two damage measures, with scores from 0 to 148. DSSI assesses activity based on body surface area and severity on a scale of 0–72. CAT uses 21 activity and damage items, for a range of 0–175 for activity and 0–33 for damage. Ten dermatologists used the instruments to score the same 12–16 patients in one session. Global validation measures were administered to physicians and patients.
Results Global validation measures correlated with the three outcome instruments (P < 0·0001). CAT displayed lower inter‐ and intrarater reliability relative to the CDASI. All scales correlate better with physician than patient global skin measures.
Conclusions It appears that the CDASI may be a useful outcome measure for studies of cutaneous DM. Further testing to compare responsiveness of all three measures is necessary.
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