Unexpected Multiple Coordination Modes in Silyl-Bridged Bis(phosphinine) Complexes

The bis­(phosphinine) [bis­{3-methyl-6-(tri­methyl­silyl)­phosphinine-2-yl}­dimeth­yl­silane] (1) was synthesized and its coordination chemistry explored. Molybdenum and chromium carbonyl complexes were crystallographically characterized featuring 1 bound η6 through one phosphinine [Mo­(CO)3­(η6-1)] (2Mo), η6 through both phosphinines to two metal centers [{M­(CO)3}2­(μ-η6:​η6-1)] (3M2, M = Cr, Mo), and chelating with η1 coordination through both phosphines [M­(CO)4­(κ:η1:​η1-1)] (4M, M = Cr, Mo). However, only 3Mo2 could be isolated analytically pure. Heating species 3Mo2 in the presence of [Pd­(COD)­Cl2] removed one CO ligand and generated [{Mo­(CO)2}­(μ-κ:​η1η6-η6-1)­{Mo­(CO)3}] (5), which is the first crystallized example of a bis­(phos­phinine) featuring chelating η1 and η6 coordination, as well as a metal center bound to two phosphinines with different binding modes. In order to enforce a chelating bis-η1 binding mode, the Ru complex [Ru­(Cp*)­(Cl)­(κ:η1:η1-1)] (6) was prepared, demonstrating that judicious choice of metal fragment can dictate the coordination mode of a bis­(phos­phinine). Conversion of 6 to the hydride species [Ru­(Cp*)­(H)­(κ:η1:​η1-1)] (7) afforded the first crystallographically characterized example of a complex with both phosphinine and hydride ligands at the same metal center

Why and how back pain interventions work: What can we do to find out?

Mediation analysis is a useful research method that potentially allows identification of the mechanisms through which treatments affect patient outcomes. This chapter reviews the theoretical framework, research designs and statistical approaches used in mediation analysis. It describes what can be learnt from previous mediation research, much of which has investigated mediating factors of psychosocial interventions in other health conditions. It also summarises the few treatment-mediation studies of psychosocial interventions conducted in back pain. This chapter shows that there is emerging evidence about the role of some psychological factors as potential treatment mediators, such as self-efficacy and catastrophising. Mediation analysis can equally be applied to non-psychological factors. Pre-planned and appropriately conducted mediation analysis in adequately powered clinical trials would be a step forward in understanding treatment effects in back pain and improving patient management

Exercise metabolism in non-obese patients with type 2 diabetes following the acute restoration of normoglycaemia

This study investigated how acute restoration of normoglycaemia affected energy metabolism during exercise in nonobese patients with type 2 diabetes. Six subjects (mean ± SEM) aged 56.2 ± 2.7 years, with a BMI of 24.5 ± 1.5 kg/m2 and a VO2 peak of 28.7 ml/kg/min, attended the lab on two randomised occasions for a four-hour resting infusion of insulin or saline, followed by 30 minutes cycling at 50% VO2 peak. During the 4 h resting infusion, there was a greater (P < 0 0001) reduction in blood glucose in insulin treatment (INS) (from 11.2 ± 0.6 to 5.6 ± 0.1 mmol/l) than in saline treatment/control (CON) (from 11.5 ± 0.7 to 8.5 ± 0.6 mmol/l). This was associated with a lower (P < 0 05) resting metabolic rate in INS (3.87 ± 0.17) than in CON (4.39 ± 0.30 kJ/min). During subsequent exercise, blood glucose increased significantly in INS from 5.6 ± 0.1 at 0 min to 6.3 ± 0.3 mmol/l at 30 min (P < 0 01), which was accompanied by a lower blood lactate response (P < 0 05). Oxygen uptake, rates of substrate utilization, heart rate, and ratings of perceived exertion were not different between trials. Insulin-induced normoglycaemia increased blood glucose during subsequent exercise without altering overall substrate utilization

A test of the core process account of psychopathology in a heterogenous clinical sample of anxiety and depression: A case of the blind men and the elephant?

Many cognitive and behavioral processes, such as selective attention to threat, self-focused attention, safety-seeking behaviors, worry and thought suppression, have their foundations in research on anxiety disorders. Yet, they are now known to be transdiagnostic, i.e. shared across a wide range of psychological disorders. A more pertinent clinical and theoretical question is whether these processes are themselves distinct, or whether they reflect a shared 'core' process that maintains psychopathology. The current study utilized a treatment-seeking clinical adult sample of 313 individuals with a range of anxiety disorders and/or depression who had completed self-report measures of widely ranging processes: affect control, rumination, worry, escape/avoidance, and safety-seeking behaviors. We found that only the first factor extracted from a principal components analysis of the items of these measures was associated with symptoms of anxiety and depression. Our findings supported the 'core process' account that had its origins in the field of anxiety disorders, and we discuss the implications for theory, clinical practice and future research across psychological disorders

Impact of practice leadership management style on staff experience in services for people with intellectual disability and challenging behaviour: a further examination and partial replication

Background and Aims Practice leadership (PL) style of frontline management has been shown to be associated with better experiences for staff working with people who may exhibit challenging behaviours (Anonymous, 2014). This study aimed to examine additional staff experience factors with a different, larger sample and to partially replicate the findings of (Anonymous, 2014). Methods This study was a survey of staff self-reported data collected as part of a larger study. Information was collected on PL and staff experiences of: stress, turnover, job satisfaction and positive work experiences. Results and Conclusions The results broadly supported Deveau & McGill (2014) and demonstrated an association between PL and greater job satisfaction and positive experiences for staff. Results on staff turnover were inconsistent. The positive impact of PL on staff experience was further supported by this study. Suggestions are made for further research. Implications These findings suggest further research is needed to examine the potential of interventions in frontline management/leadership practice to improve staff experience of working in challenging environments. What this paper adds. Firstly, to the somewhat limited research literature on management/leadership in intellectual and developmental disabilities. Secondly, contributes additional evidence that a PL style of frontline management has beneficial effects upon frontline staff’s experience of working in challenging environments i.e. suggests a new intervention in an important area of policy and practice. Thirdly, suggests that the IDD sector needs to place more emphasis upon frontline management development and practice

The impact of diabetes-related complications on preference-based measures of health-related quality of life in adults with Type I diabetes

Introduction: This study estimates health-related quality of life (HRQoL) or utility decrements associated with type 1 diabetes mellitus (T1DM) using data from a UK research programme on the Dose Adjustment For Normal Eating (DAFNE) education programme. Methods: A wide range of data was collected from 2,341 individuals who undertook a DAFNE course in 2009-12, at baseline and for two subsequent years. We use fixed and random effects linear models to generate utility estimates for T1DM using different instruments: EQ-5D, SF-6D and EQ-VAS. We show models with and without controls for HbA1c and depression, which may be endogenous (if, for example, there is reverse causality in operation). Results: We find strong evidence of an unobserved individual effect, suggesting the superiority of the fixed effects model. Depression shows the greatest decrement across all the models in the preferred fixed effects model. The fixed effects EQ-5D model also finds a significant decrement from retinopathy, BMI and HbA1c(%). Estimating a decrement using the fixed effects model is not possible for some conditions where there are few new cases. In the random effects model diabetic foot disease shows substantial utility decrements, yet these are not significant in the fixed effects models. Conclusion: Utility decrements have been calculated for a wide variety of health states in T1DM which can be used in economic analyses. However, despite the large dataset, the low incidence of several complications leads to uncertainty in calculating the utility weights. Depression and diabetic foot disease result in a substantial loss in HRQoL for patients with T1DM. HbA1c(%) appears to have an independent negative impact upon HRQoL, although concerns remain regarding the potential endogeneity of this variable

Different bacterial gene expression patterns and attenuated host immune responses are associated with the evolution of low-level vancomycin resistance during persistent methicillin-resistant Staphylococcus aureus bacteraemia

BACKGROUND: Low-level vancomycin resistance in Staphylococcus aureus (vancomycin-intermediate S. aureus (VISA) and hetero-VISA [hVISA]) emerges during persistent infection and failed vancomycin therapy. Up-regulation of genes associated with the "cell wall stimulon" and mutations in the vraSR operon have both been implicated in the development of resistance, however the molecular mechanisms of resistance are not completely understood. To further elucidate the mechanisms leading to resistance transcriptome comparisons were performed using multiple clinical pairs of vancomycin-susceptible S. aureus (VSSA) and hVISA/VISA (n = 5), and three VSSA control pairs from hospitalized patients with persistent bacteraemia that did not develop hVISA/VISA. Based on the transcriptome results multiple genes were sequenced and innate immune system stimulation was assessed in the VSSA and hVISA/VISA pairs. RESULTS: Here we show that up-regulation of vraS and the "cell wall stimulon" is not essential for acquisition of low-level vancomycin resistance and that different transcriptional responses occur, even between closely related hVISA/VISA strains. DNA sequencing of vraSR, saeSR, mgrA, rot, and merR regulatory genes and upstream regions did not reveal any differences between VSSA and hVISA/VISA despite transcriptional changes suggesting mutations in these loci may be linked to resistance in these strains. Enhanced capsule production and reduced protein A expression in hVISA/VISA were confirmed by independent bioassays and fully supported the transcriptome data. None of these changes were observed in the three control pairs that remained vancomycin-susceptible during persistent bacteremia. In a macrophage model of infection the changes in cell surface structures in hVISA/VISA strains were associated with significantly reduced NF-kappaB activation resulting in reduced TNF-alpha and IL-1beta expression. CONCLUSION: We conclude that there are multiple pathways to low-level vancomycin resistance in S. aureus, even among closely related clinical strains, and these can result in an attenuated host immune response. The persistent infections associated with hVISA/VISA strains may be a consequence of changes in host pathogen interactions in addition to the reduced antibiotic susceptibility

The Burden of Revision Sinonasal Surgery in the UK – Data from the Chronic Rhinosinusitis Epidemiology Study (CRES); a cross sectional study

Objectives/Hypothesis The aim of this study was to investigate the surgical revision rate in patients with Chronic Rhinosinusitis (CRS) in the UK CRS Epidemiology Study (CRES). Previous evidence from national Sinonasal Audit showed that 1459 CRS patients demonstrated a surgical revision rate 19.1% at 5 years, with highest rates seen in those with polyps (20.6%). Setting Thirty secondary care centres around the UK. Participants A total of 221 controls and 1249 patients with CRS were recruited to the study including those with polyps (CRSwNPs), without polyps (CRSsNPs) and with allergic fungal rhinosinusitis (AFRS). Interventions Self-administered questionnaire. Primary outcome measure The need for previous sinonasal surgery. Results A total of 651 patients with CRSwNPs, 553 with CRSsNPs and 45 with AFRS were included. A total of 396 (57%) of patients with CRSwNPs/AFRS reported having undergone previous endoscopic nasal polypectomy (ENP), of which 182 of the 396 (46%) reported having received more than one operation. The mean number of previous surgeries per patient in the revision group was 3.3 (range 2 to 30) and a mean duration of time of 10 years since the last procedure. The average length of time since their first operation up to inclusion in the study was 15.5 years (range 0-74). Only 27.9% of all patients reporting a prior ENP had received concurrent endoscopic sinus surgery (ESS) (n=102). For comparison, surgical rates in patients with CRSsNPs were significantly lower; 13% of cases specifically reported ESS and of those only 30% reported multiple procedures (chi-squared p < 0.001). Conclusions This study demonstrated there is a high burden of both primary and revision surgery in patients with CRS, worst in those with AFRS and least in those with CRSsNPs. The burden of revision surgery appears unchanged in the decade since the Sinonasal Audit