Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses.

RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues

Why clothes don’t fall apart : tension transmission in staple yarns

The problem of how staple yarns transmit tension is addressed within abstract models in which the Amontons-Coulomb friction laws yield a linear programing (LP) problem for the tensions in the fiber elements. We find there is a percolation transition such that above the percolation threshold the transmitted tension is in principle unbounded. We determine that the mean slack in the LP constraints is a suitable order parameter to characterize this supercritical state. We argue the mechanism is generic, and in practical terms, it corresponds to a switch from a ductile to a brittle failure mode accompanied by a significant increase in mechanical strength

Phenotype standardization for drug-induced kidney disease.

Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition

Caffeine enhances upper body strength in resistance-trained women

BACKGROUND: Research has indicated that low-to-moderate dosages of caffeine supplementation are ergogenic for sustained endurance efforts as well as high-intensity exercise. The effects of caffeine supplementation on strength-power performance are equivocal, with some studies indicating a benefit and others demonstrating no change in performance. The majority of research that has examined the effects of caffeine supplementation on strength-power performance has been carried out in both trained and untrained men. Therefore, the purpose of this study was to determine the acute effects of caffeine supplementation on strength and muscular endurance in resistance-trained women. METHODS: In a randomized manner, 15 women consumed caffeine (6 mg/kg) or placebo (PL) seven days apart. Sixty min following supplementation, participants performed a one-repetition maximum (1RM) barbell bench press test and repetitions to failure at 60% of 1RM. Heart rate (HR) and blood pressure (BP) were assessed at rest, 60 minutes post-consumption, and immediately following completion of repetitions to failure. RESULTS: Repeated measures ANOVA indicated a significantly greater bench press maximum with caffeine (p CONCLUSIONS: These findings indicate a moderate dose of caffeine may be sufficient for enhancing strength performance in resistance-trained women

Salvage of failed free flaps used in head and neck reconstruction

Free flap success rates are in excess of 95%. Vascular occlusion (thrombosis) remains the primary reason for flap loss, with venous thrombosis being more common than arterial occlusion. The majority of flap failures occur within the first 48 hours. With early recognition and intervention of flap compromise salvage is possible. Successful salvage rates range from 28% to over 90%. Rapid re-exploration in this clinical setting is crucial to maximise the chances of flap salvage. If salvage is not feasible or unsuccessful then non-surgical methods of salvage may be employed with some possibility of success. The purpose of this article is to review the causes of free flap failure and to highlight the available options for salvage

Does ethnic diversity erode trust? Putnams hunkering down thesis reconsidered

We use a multi-level modelling approach to estimate the effect of ethnic diversity on measures of generalized and strategic trust using data from a new survey in Britain with a sample size approaching 25,000 individuals. In addition to the ethnic diversity of neighbourhoods, we incorporate a range of indicators of the socio-economic characteristics of individuals and the areas in which they live. Our results show no effect of ethnic diversity on generalized trust. There is a statistically significant association between diversity and a measure of strategic trust, but in substantive terms, the effect is trivial and dwarfed by the effects of economic deprivation and the social connectedness of individuals

Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin. A position paper of the Acute Cardiovascular Care Association (ACCA) of the ESC.

Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts' opinions, for all emergency medical services' health providers involved in the pre-hospital management of acute cardiovascular care.Peer reviewe

A new minimally invasive heart surgery instrument for atrial fibrillation treatment : first in vitro and animal tests.

International audienceThe paper presents a new robotic system for beating heart surgery. The final goal of this project is to develop a tele-operated system for the thoracoscopic treatment of patients with atrial fibrillation. The system consists of a robot that moves an innovative end-effector used to perform lines as in the Cox-Maze technique. This device is an electrode mesh that is introduced in the thorax through a trocar and is deployed inside the left atrium, where it can create selective ablation lines at any atrial region, using radio frequency. The current version of the umbrella has 22 electrodes. Using visual feedback from an ultrasound based navigation system, the surgeon can choose which electrodes on the mesh to activate. Once the umbrella is in contact with the endocardium of the left atrium, at the expected position, the surgeon activates the chosen electrodes sequentially. The umbrella can then be moved to another position. In vitro and in vivo animal tests have been carried out in order to test and improve the instrument, the robotic system and the operative procedure