A New Era in the Quest for Dark Matter

There is a growing sense of `crisis' in the dark matter community, due to the absence of evidence for the most popular candidates such as weakly interacting massive particles, axions, and sterile neutrinos, despite the enormous effort that has gone into searching for these particles. Here, we discuss what we have learned about the nature of dark matter from past experiments, and the implications for planned dark matter searches in the next decade. We argue that diversifying the experimental effort, incorporating astronomical surveys and gravitational wave observations, is our best hope to make progress on the dark matter problem.Comment: Published in Nature, online on 04 Oct 2018. 13 pages, 1 figur

The fire toxicity of polyurethane foams [Review]

Polyurethane is widely used, with its two major applications, soft furnishings and insulation, having low thermal inertia, and hence enhanced flammability. In addition to their flammability, polyurethanes form carbon monoxide, hydrogen cyanide and other toxic products on decomposition and combustion. The chemistry of polyurethane foams and their thermal decomposition are discussed in order to assess the relationship between the chemical and physical composition of the foam and the toxic products generated during their decomposition. The toxic product generation during flaming combustion of polyurethane foams is reviewed, in order to relate the yields of toxic products and the overall fire toxicity to the fire conditions. The methods of assessment of fire toxicity are outlined in order to understand how the fire toxicity of polyurethane foams may be quantified. In particular, the ventilation condition has a critical effect on the yield of the two major asphyxiants, carbon monoxide and hydrogen cyanid

Development and implementation of clinical guidelines : an artificial intelligence perspective

Clinical practice guidelines in paper format are still the preferred form of delivery of medical knowledge and recommendations to healthcare professionals. Their current support and development process have well identified limitations to which the healthcare community has been continuously searching solutions. Artificial intelligence may create the conditions and provide the tools to address many, if not all, of these limitations.. This paper presents a comprehensive and up to date review of computer-interpretable guideline approaches, namely Arden Syntax, GLIF, PROforma, Asbru, GLARE and SAGE. It also provides an assessment of how well these approaches respond to the challenges posed by paper-based guidelines and addresses topics of Artificial intelligence that could provide a solution to the shortcomings of clinical guidelines. Among the topics addressed by this paper are expert systems, case-based reasoning, medical ontologies and reasoning under uncertainty, with a special focus on methodologies for assessing quality of information when managing incomplete information. Finally, an analysis is made of the fundamental requirements of a guideline model and the importance that standard terminologies and models for clinical data have in the semantic and syntactic interoperability between a guideline execution engine and the software tools used in clinical settings. It is also proposed a line of research that includes the development of an ontology for clinical practice guidelines and a decision model for a guideline-based expert system that manages non-compliance with clinical guidelines and uncertainty.This work is funded by national funds through the FCT – Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within project PEst-OE/EEI/UI0752/2011"

The Dynamic Landscape of Novel Psychoactive Substance (NPS) Use in Ireland: Results from an Expert Consultation

In Ireland, legislators encountered a new phenomenon in 2005 onwards with the advent of ‘legal highs’ sold in headshops. Use of ‘legal highs’ containing herbal and synthetic new psychoactive substances (NPS) was not confined to problematic drug users, and included social recreational users. Legislative controls were enacted in 2010, 2011 and 2015. The study aimed to investigate expert perspectives on the NPS situation with regard to changing and emergent trends in use, health and social consequences and service implications. This brief report presents descriptive findings from a national consultation using a structured guide with experts in 2016. Four themes emerged and centred on; ‘Definitions of NPS used within Professional Roles’; ‘Professional Experiences of NPS‘; ‘Types of NPS Users, Sourcing and Consequences of Use’; and ‘Service Response.’ Findings underscored the mental health and addiction related consequences of NPS use, with prevention, clinical and treatment services ill- equipped to deal with the particular characteristics of this form of drug abuse. Enhanced strategies, services and clinical responses are warranted to address the challenges encountered. © 2016 Springer Science+Business Media New Yor

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of Two-Year Efficacy and Safety Outcomes in Two Phase 3 Trials

Rationale & Objective: Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a complement C5 inhibitor (C5i) approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS. Study Design: This analysis reports 2-year data from two phase 3, single-arm studies. Setting & Participants: One study included C5i-naive adults (NCT02949128) and the other included two cohorts of pediatric patients (C5i-naive and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219). Exposure(s): Patients received intravenous ravulizumab every 4–8 weeks, with the dose depending on body weight. Outcomes: The primary endpoint in the studies of C5i-naive patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, at two consecutive assessments at least 4 weeks apart. Analytical Approach: All analyses used descriptive statistics. No formal statistical comparisons were performed. Results: In total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naive adults and pediatric patients, respectively. The median increase in eGFR from baseline was maintained over 2 years in C5i-naive adults (35 mL/min/1.73m2 ) and pediatric patients (82.5 mL/min/1.73m2 ). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy – Fatigue score achieved by 26 weeks was maintained over 2 years. Journal Pre-proof 3 Limitations: Limitations were the small sample of pediatric switch patients and limited availability of genetic data. Conclusions: Long-term treatment with ravulizumab is well tolerated and associated with improved hematological and renal parameters and quality of life in adults and pediatric patients with aHUS

Clinicians’ response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2

Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit. All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved. The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO2) was > 16 kPa (120 mmHg). In only 25% of the tests with PaO2 > 16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower. Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxi

From the Trenches: A Cross-Sectional Study Applying the GRADE Tool in Systematic Reviews of Healthcare Interventions

Background: GRADE was developed to address shortcomings of tools to rate the quality of a body of evidence. While much has been published about GRADE, there are few empirical and systematic evaluations. Objective: To assess GRADE for systematic reviews (SRs) in terms of inter-rater agreement and identify areas of uncertainty. Design: Cross-sectional, descriptive study. Methods: We applied GRADE to three SRs (n = 48, 66, and 75 studies, respectively) with 29 comparisons and 12 outcomes overall. Two reviewers graded evidence independently for outcomes deemed clinically important a priori. Inter-rater reliability was assessed using kappas for four main domains (risk of bias, consistency, directness, and precision) and overall quality of evidence. Results: For the first review, reliability was: k = 0.41 for risk of bias; 0.84 consistency; 0.18 precision; and 0.44 overall quality. Kappa could not be calculated for directness as one rater assessed all items as direct; assessors agreed in 41 % of cases. For the second review reliability was: 0.37 consistency and 0.19 precision. Kappa could not be assessed for other items; assessors agreed in 33 % of cases for risk of bias; 100 % directness; and 58 % overall quality. For the third review, reliability was: 0.06 risk of bias; 0.79 consistency; 0.21 precision; and 0.18 overall quality. Assessors agreed in 100 % of cases for directness. Precision created the most uncertainty due to difficulties in identifying ‘‘optimal’ ’ information size and ‘‘clinica