Statistical Significance of spectral lag transition in GRB 160625B

Recently Wei et al (arXiv:1612.09425) have found evidence for a transition from positive time lags to negative time lags in the spectral lag data of GRB 160625B. They have fit these observed lags to a sum of two components: an assumed functional form for intrinsic time lag due to astrophysical mechanisms and an energy-dependent speed of light due to quadratic and linear Loren tz invariance violation (LIV) models. Here, we examine the statistical significance of the evidence for a transition to nega tive time lags. Such a transition, even if present in GRB 160625B, cannot be due to an energy dependent speed of light as th is would contradict previous limits by some 3-4 orders of magnitude, and must therefore be of intrinsic astrophysical origin . We use three different model comparison techniques: a frequentist test and two information based criteria (AIC and BIC). From the frequentist model comparison test, we find that the evidence for transition in the spectral lag data is favored at $3.05\sigma$ and $3.74\sigma$ for the linear and quadratic models respectively. We find that $\Delta$AIC and $\Delta$BIC have values $\gtrsim$ 10 for the spectral lag transition that was motivated as being due to quadratic Lorentz invariance vio lating model pointing to "decisive evidence". We note however that none of the three models (including the model of intr insic astrophysical emission) provide a good fit to the data.Comment: 6 pages, 1 figur

Pertactin-negative Bordetella pertussis strains in Canada: characterization of a dozen isolates based on a survey of 224 samples collected in different parts of the country over the last 20 years

SummaryObjectiveTo detect and characterize pertactin-negative Bordetella pertussis in Canada, especially for isolates collected in recent years.MethodsA total of 224 isolates from the years 1994–2013 were screened by Western immuno-blot for expression of pertactin. Pertactin-negative isolates were characterized by serotyping, pulsed-field gel electrophoresis (PFGE), and genotyping of their pertactin, fimbriae 3, pertussis toxin subunit 1, and pertussis toxin gene promoter region, as well as the complete sequence of the pertactin gene.ResultsTwelve isolates were pertactin-negative, giving an overall prevalence of 5.4%. However, no such isolate was found prior to 2011 and 17.8% of 62 isolates examined in 2012 were pertactin-negative. Ten pertactin-negative isolates contained a significant mutation in their pertactin (prn) genes. IS481 was found in the prn genes of eight isolates, while a single point mutation occurred either in the coding region (resulting in a premature stop codon) or in the promoter region (preventing gene transcription) in two other isolates. PFGE analysis also showed multiple profiles suggesting that several independent genetic events might have led to the emergence of these pertactin-negative strains rather than expansion of a single clone.ConclusionsAs reported elsewhere, pertactin-negative B. pertussis has emerged in Canada in recent years, notably in 2012. This coincided with an increase in pertussis activity in Canada. A further systematic study with a larger geographical representative sample is required to determine how these vaccine-negative strains may contribute to the overall changing epidemiology of pertussis in Canada

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Legal and administrative sources for Building and other Construction Workers (BOCW) Welfare fund in India and on the European Social Fund (ESF) in Italy

The study focuses on the phenomenon of hundreds of billions of Euros of unspent social special-purpose funds in both India and the EU (and, we suspect, globally). By “social special-purpose”, we mean funds that have been collected by law for a specific social purpose that would otherwise be the domain of discretionary state policy. These funds are held in some vehicle that reflects this social purpose (such as a trust or a fund) rather than simply being absorbed into ordinary administrative budget lines. By “unspent”, we refer to instances where a significant proportion of these funds remains both uncaptured by other interests (e.g. embezzled), and unspent during a discrete timeframe (e.g. the fiscal year) and for the purpose for which they are earmarked. In India, vast amounts of unspent funds exist in everything from welfare funds for construction workers and cooperatives for saltpan workers, to legal aid funds. A brief review of the literature on Europe reveals the widespread nature of unspent funds in EU structural funds as well. Interestingly, there is little systematic study of unspent funds, and even less comparative work on this intriguing phenomenon. We propose an initial study to map the extent and nature of this phenomenon and develop methodologies to study it. We propose to study unspent funds in India and Italy, and explore their institutional and regulatory preconditions along with their socio-political effects. This runs counter to conventional wisdom, which understands the state as a vehicle of resource distribution, and thus unspent funds as a symptom of temporary institutional blockage in the state. We explore specific case studies in two countries that have promising analytical potential in terms of similarities and differences in the modes and mechanisms of governance and institutional structures that underlie vast amounts of unspent funds