MIDA boronates are hydrolysed fast and slow by two different mechanisms

MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base mediated and the other neutral. The former can proceed more than three orders of magnitude faster than the latter, and involves a rate-limiting attack by a hydroxide at a MIDA carbonyl carbon. The alternative 'neutral' hydrolysis does not require an exogenous acid or base and involves rate-limiting B-N bond cleavage by a small water cluster, (H2O)n. The two mechanisms can operate in parallel, and their relative rates are readily quantified by (18)O incorporation. Whether hydrolysis is 'fast' or 'slow' is dictated by the pH, the water activity and the mass-transfer rates between phases. These findings stand to enable, in a rational way, an even more effective and widespread utilization of MIDA boronates in synthesis

The equity dimension in evaluations of the quality and outcomes framework: A systematic review

<p>Abstract</p> <p>Background</p> <p>Pay-for-performance systems raise concerns regarding inequity in health care because providers might select patients for whom targets can easily be reached. This paper aims to describe the evolution of pre-existing (in)equity in health care in the period after the introduction of the Quality and Outcomes Framework (QOF) in the UK and to describe (in)equities in exception reporting. In this evaluation, a theory-based framework conceptualising equity in terms of equal access, equal treatment and equal treatment outcomes for people in equal need is used to guide the work.</p> <p>Methods</p> <p>A systematic MEDLINE and Econlit search identified 317 studies. Of these, 290 were excluded because they were not related to the evaluation of QOF, they lacked an equity dimension in the evaluation, their qualitative research focused on experiences or on the nature of the consultation, or unsuitable methodology was used to pronounce upon equity after the introduction of QOF.</p> <p>Results</p> <p>None of the publications (n = 27) assessed equity in access to health care. Concerning equity in treatment and (intermediate) treatment outcomes, overall quality scores generally improved. For the majority of the observed indicators, all citizens benefit from this improvement, yet the extent to which different patient groups benefit tends to vary and to be highly dependent on the type and complexity of the indicator(s) under study, the observed patient group(s) and the characteristics of the study. In general, the introduction of QOF was favourable for the aged and for males. Total QOF scores did not seem to vary according to ethnicity. For deprivation, small but significant residual differences were observed after the introduction of QOF favouring less deprived groups. These differences are mainly due to differences at the practice level. The variance in exception reporting according to gender and socio-economic position is low.</p> <p>Conclusions</p> <p>Although QOF seems not to be socially selective at first glance, this does not mean QOF does not contribute to the inverse care law. Introducing different targets for specific patient groups and including appropriate, non-disease specific and patient-centred indicators that grasp the complexity of primary care might refine the equity dimension of the evaluation of QOF. Also, information on the actual uptake of care, information at the patient level and monitoring of individuals' health care utilisation tracks could make large contributions to an in-depth evaluation. Finally, evaluating pay-for-quality initiatives in a broader health systems impact assessment strategy with equity as a full assessment criterion is of utmost importance.</p

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Future directions in personality, occupational and medical selection: myths, misunderstandings, measurement, and suggestions

This paper has two objectives: (1) presenting recent advances in the personality field concerning the conceptualization of personality arising from the dynamic interactions of behaviour, biology, context, and states, and (2) discussing the implications of these developments for medical selection. We start by presenting evidence that traits are not longer regarded as deterministic and stable. Instead, they are found to change across generations, the life span, and in response to environmental contingencies. Next, drawing on recent research (behavioural reaction norms and the density distribution model) we posit how the expression of trait relevant behaviour changes depending on the situation, such that personality reflects both stability and plasticity across situations. Thus there is an urgent need to explore how traits change as function of medical education. Third, we demystify that some traits are better than others showing that so-called “good” traits have a dark-side. Fourth, we show how these developments impact on how personality might be assessed, thereby presenting recent evidence on the use of contextualized personality measures, Situational Judgment Tests, other reports, and implicit measures. Throughout the paper, we outline the key implications of these developments for medical selection practices

Labor productivity growth: disentangling technology and capital accumulation

How much of the convergence in labor productivity that we observe in manufacturing is due to convergence in technology versus convergence in capital-labor ratios? To shed light on this question, we introduce a nonparametric counterfactual decomposition of labor productivity growth into growth of the capital-labor ratio (K/L), technological productivity (TEP) and total factor productivity (TFP). Our nonparametric specification enables us to model technology allowing for heterogeneity across all relevant dimensions (i.e. countries, sectors and time). Using data spanning from the 1960s to the 2000s, covering 42 OECD and non OECD countries across 11 manufacturing sectors, we find TEP and TFP to account for roughly 46 and −6% of labor productivity growth respectively, on average. While technological growth at the world level is driven primarily by the US and a handful of other OECD countries, we find strong evidence of convergence in both technology and capital-labor ratios. Interestingly, very few of the usual growth determinants are found to enhance the process of technological catching-up

Respiratory illness in children: Do deprived children have worse coughs?

Parents of a stratified random sample of 234 children from 21 general practices in North East England were interviewed at home. All these children had been reported in a postal questionnaire as having had a cough between six and ten weeks before the interview. Interviews covered social characteristics of the family, the severity of the child's cough and the reactions of the parents to hypothetical sets of symptoms. The parents of children in materially deprived circumstances appeared to report worse coughs than other parents. We confirmed this finding by constructing a scale of perceived cough severity. However, we found no evidence that the inequality was due to exaggeration of the severity of the cough by materially deprived parents. Our conclusion that materially deprived children suffer worse respiratory illness is the more important because previous evidence suggets that the after-effects persist into adulthood