Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland

The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data

Current and projected heatwave-attributable occupational injuries, illnesses, and associated economic burden in Australia

Introduction: The costs of global warming are substantial. These include expenses from occupational illnesses and injuries (OIIs), which have been associated with increases during heatwaves. This study estimated retrospective and projected future heatwave-attributable OIIs and their costs in Australia. Materials and methods: Climate and workers’ compensation claims data were extracted from seven Australian capital cities representing OIIs from July 2005 to June 2018. Heatwaves were defined using the Excess Heat Factor. OIIs and associated costs were estimated separately per city and pooled to derive national estimates. Results were projected to 2030 (2016–2045) and 2050 (2036–2065). Results: The risk of OIIs and associated costs increased during heatwaves, with the risk increasing during severe and particularly extreme heatwaves. Of all OIIs, 0.13% (95% empirical confidence interval [eCI]: 0.11–0.16%) were heatwave-attributable, equivalent to 120 (95%eCI:70–181) OIIs annually. 0.25% of costs were heatwaveattributable (95%eCI: 0.18–0.34%), equal to $AU4.3 (95%eCI: 1.4–7.4) million annually. Estimates of heatwaveattributable OIIs by 2050, under Representative Concentration Pathway [RCP]4.5 and RCP8.5, were 0.17% (95% eCI: 0.10–0.27%) and 0.23% (95%eCI: 0.13–0.37%), respectively. National costs estimates for 2030 under RCP4.5 and RCP8.5 were 0.13% (95%eCI: 0.27-0.46%) and 0.04% (95%eCI: 0.66-0.60), respectively. These estimates for extreme heatwaves were 0.04% (95%eCI: 0.02–0.06%) and 0.04% (95%eCI: 0.01–0.07), respectively. Cost-AFs in 2050 were, under RCP4.5, 0.127% (95%eCI: 0.27-0.46) for all heatwaves and 0.04% (95%eCI: 0.01-0.09%) for extreme heatwaves. Attributable fractions were approximately similar to baseline when assuming theoretical climate adaptation. Discussion: Heatwaves represent notable and preventable portions of preventable OIIs and economic burden. OIIs are likely to increase in the future, and costs during extreme heatwaves in 2030. Workplace and public health policies aimed at heat adaptation can reduce heat-attributable morbidity and costs.Matthew A. Borg, Jianjun Xiang, Olga Anikeeva, Bertram Ostendorf, Blesson Varghese, Keith Dear, Dino Pisaniello, Alana Hansen, Kerstin Zander, Malcolm R. Sim, Peng B

Incretin-based therapy: a powerful and promising weapon in the treatment of type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease that increases significantly cardiovascular morbidity and mortality. It is associated with obesity, insulin resistance, beta-cell dysfunction, and hyperglucagonemia, the combination of which typically leads to hyperglycemia. Incretin-based treatment modalities, and in particular glucagon-like peptide 1 (GLP-1) receptor agonists, are able to successfully counteract several of the underlying pathophysiological abnormalities of T2DM. The pancreatic effects of GLP-1 receptor agonists include glucose-lowering effects by stimulating insulin secretion and inhibiting glucagon release in a strictly glucose-dependent manner, increased beta-cell proliferation, and decreased beta-cell apoptosis. GLP-1 receptors are widely expressed throughout human body; thus, GLP-1-based therapies exert pleiotropic and multisystemic effects that extend far beyond pancreatic islets. A large body of experimental and clinical data have suggested a considerable protective role of GLP-1 analogs in the cardiovascular system (decreased blood pressure, improved endothelial and myocardial function, functional recovery of failing and ischemic heart, arterial vasodilatation), kidneys (increased diuresis and natriuresis), gastrointestinal tract (delayed gastric emptying, reduced gastric acid secretion), and central nervous system (appetite suppression, neuroprotective properties). The pharmacologic use of GLP-1 receptor agonists has been shown to reduce bodyweight and systolic blood pressure, and significantly improve glycemic control and lipid profile. Interestingly, weight reduction induced by GLP-1 analogs reflects mainly loss of abdominal visceral fat. The critical issue of whether the emerging positive cardiometabolic effects of GLP-1 analogs can be translated into better clinical outcomes for diabetic patients in terms of long-term hard endpoints, such as cardiovascular morbidity and mortality, remains to be elucidated with prospective, large-scale clinical trials

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

Psychology and aggression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68264/2/10.1177_002200275900300301.pd

Justify your alpha

In response to recommendations to redefine statistical significance to p ≤ .005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level

Automatic Execution of Test Cases on UML Models of Embedded Systems

Part 1: Design MethodologiesInternational audienceDuring the design of an embedded system, fixing errors discovered only in later stages is a very expensive activity. In order to decrease such costs, the engineers have to identify and fix the introduced errors as soon as possible. Therefore, it makes sense to facilitate the errors detection during the whole the design cycle, including the initial specification stages. This work proposed a test-based approach to aid the early verification of embedded and real-time systems. The proposed approach applies test cases on the system behavior described in the high-level specifications. A tool to automate the execution of the test cases upon UML models has been created. Its initial goal is to improve the errors detection on the system behavior before the implementation phase, since test cases are based on the system requirements. Test cases are platform independent and describe: runtime scenarios; the behaviors to be tested along with their input; and the expected results. The tool executes automatically each test case, in which the specified behavior is simulated Thereafter, the obtained results are compared with the expected ones, indicating the success or failure of the test case. A case study was performed to validate the proposed approach. The achieved results demonstrate that it is feasible to test the system behavior even though when the implementation is still not available