Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate

Inflammation and oxidative stress cause renal impairment. Renal failure exacerbates the effect of oxidative stress on many organ systems. Antioxidants can prevent or treat renal failure in various experimental models and clinical situations. Pyruvate is an endogenous antioxidant with beneficial effects in animal models of oxidative stress. Because sodium pyruvate rapidly degrades in solution, a simple derivative of pyruvic acid, namely ethyl pyruvate, has been investigated as a therapeutic agent in preclinical studies. Ethyl pyruvate reduces organ system damage in ischaemia/reperfusion injury and haemorrhagic and endotoxic shock, at least in part through its antioxidant action. In addition, ethyl pyruvate appears to have direct beneficial effects on cytokine expression and proinflammatory gene regulation. The effect is long lasting and, importantly, even when it is administered after the onset of inflammation it can ameliorate organ damage and improve survival. Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment

Basal cell nuclear size in experimental oral mucosal carcinogenesis.

It has been suggested that the size of the nuclei of epithelial basal cells can be used in predicting the likelihood of malignant transformation of epithelium. This proposition was assessed in rat palatal epithelium after the carcinogen 4-nitroquinoline-1-oxide had been applied to the epithelium for varying periods of time. No consistent alterations in basal cell nuclear size, including area, perimeter, diameter and regularity of form were found with routine light microscopy as the epithelium passed through various stages of dysplasia to carcinoma. This finding casts doubt on the value of using a variation of basal cell nuclear size as a predictor of malignant transformation

Causal effects of an absent crowd on performances and refereeing decisions during Covid-19

The Covid-19 pandemic has induced worldwide natural experiments on the effects of crowds. We exploit one of these experiments that took place over several countries in almost identical settings: professional football matches played behind closed doors within the 2019/20 league seasons. We find large and statistically significant effects on the number of yellow cards issued by referees. Without a crowd, fewer cards were awarded to the away teams, reducing home advantage. These results have implications for the influence of social pressure and crowds on the neutrality of decisions

Laboratory earthquake forecasting. A machine learning competition

Earthquake prediction, the long-sought holy grail of earthquake science, continues to confound Earth scientists. Could we make advances by crowdsourcing, drawing from the vast knowledge and creativity of the machine learning (ML) community? We used Google’s ML competition platform, Kaggle, to engage the worldwide ML community with a competition to develop and improve data analysis approaches on a forecasting problem that uses laboratory earthquake data. The competitors were tasked with predicting the time remaining before the next earthquake of successive laboratory quake events, based on only a small portion of the laboratory seismic data. The more than 4,500 participating teams created and shared more than 400 computer programs in openly accessible notebooks. Complementing the now well-known features of seismic data that map to fault criticality in the laboratory, the winning teams employed unexpected strategies based on rescaling failure times as a fraction of the seismic cycle and comparing input distribution of training and testing data. In addition to yielding scientific insights into fault processes in the laboratory and their relation with the evolution of the statistical properties of the associated seismic data, the competition serves as a pedagogical tool for teaching ML in geophysics. The approach may provide a model for other competitions in geosciences or other domains of study to help engage the ML community on problems of significance

Poverty and the multiple stakeholder challenge for global leaders

The article presents a case study in which business leaders deal with challenging problems related to poverty, involving multiple stakeholders. This emphasizes the importance of training prospective global leaders to manage stakeholder relationships and engage in stakeholder dialogue. The authors highlight the stakeholder role played by nongovernmental organizations and include a simulation that develops stakeholder dialogue skills. They identify practical lessons and assumptions underlying business education that are not shared by all stakeholders in the context of poverty

Self-organized current transport through low angle grain boundaries in YBa2_2Cu3_3O7−δ_{7-\delta} thin films, studied magnetometrically

The critical current density flowing across low angle grain boundaries in YBa$_2$Cu$_3$O$_{7-\delta}$ thin films has been studied magnetometrically. Films (200 nm thickness) were deposited on SrTiO$_3$ bicrystal substrates containing a single [001] tilt boundary, with angles of 2, 3, 5, and 7 degrees, and the films were patterned into rings. Their magnetic moments were measured in applied magnetic fields up to 30 kOe at temperatures of 5 - 95 K; current densities of rings with or without grain boundaries were obtained from a modified critical state model. For rings containing 5 and 7 degree boundaries, the magnetic response depends strongly on the field history, which arises in large part from self-field effects acting on the grain boundary.Comment: 8 pages, including 7 figure

Phase I and pharmacokinetic study of XR11576, an oral topoisomerase I and II inhibitor, administered on days 1–5 of a 3-weekly cycle in patients with advanced solid tumours

XR11576 is an oral topoisomerase I and II inhibitor. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR11576 when administered orally on days 1-5 every 3 weeks to patients with advanced solid tumours. Patients were treated with escalating doses of XR11576 at doses ranging from 30

Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial

Introduction An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. Methods and analysis This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. Ethics and dissemination All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. Trial registration number NCT03653832