Protocol for the health economic evaluation of increasing the weekend specialist to patient ratio in hospitals in England

Introduction: This protocol concerns the evaluation of increased specialist staffing at weekends in hospitals in England. Seven-day health services are a key policy for the UK government and other health systems trying to improve use of infrastructure and resources. A particular motivation for the 7-day policy has been the observed increase in the risk of death associated with weekend admission, which has been attributed to fewer hospital specialists being available at weekends. However, the causes of the weekend effect have not been adequately characterised; many of the excess deaths associated with the ‘weekend effect’ may not be preventable, and the presumed benefits of improved specialist cover might be offset by the cost of implementation. Methods/design: The Bayesian-founded method we propose will consist of four major steps. First, the development of a qualitative causal model. Specialist presence can affect multiple, interacting causal processes. One or more models will be developed from the results of an expert elicitation workshop and probabilities elicited for each model and relevant model parameters. Second, systematic review of the literature. The model from the first step will provide search limits for a review to identify relevant studies. Third, a statistical model for the effects of specialist presence on care quality and patient outcomes. Fourth, valuation of outcomes. The expected net benefits of different levels of specialist intensity will then be evaluated with respect to the posterior distributions of the parameters

Substrate-gated docking of pore subunit Tha4 in the TatC cavity initiates Tat translocase assembly

The twin-arginine translocase (Tat) transports folded proteins across tightly sealed membranes. cpTatC is the core component of the thylakoid translocase and coordinates transport through interactions with the substrate signal peptide and other Tat components, notably the Tha4 pore-forming component. Here, Cys–Cys matching mapped Tha4 contact sites on cpTatC and assessed the role of signal peptide binding on Tha4 assembly with the cpTatC–Hcf106 receptor complex. Tha4 made contact with a peripheral cpTatC site in nonstimulated membranes. In the translocase, Tha4 made an additional contact within the cup-shaped cavity of cpTatC that likely seeds Tha4 polymerization to form the pore. Substrate binding triggers assembly of Tha4 onto the interior site. We provide evidence that the substrate signal peptide inserts between cpTatC subunits arranged in a manner that conceivably forms an enclosed chamber. The location of the inserted signal peptide and the Tha4–cpTatC contact data suggest a model for signal peptide–gated Tha4 entry into the chamber to form the translocase

The molecular biology and regulation of plastid division

Min proteins mediate plastid division site selection by controlling the formation of the Z-ring, the initial event of plastid division. The Z-ring is formed by the polymerisation of the FtsZ proteins into a contractile ring at the future division site and acts as a scaffold for the assembly of the rest of the divisions machinery. This study aims to elucidate AtMinD1 function in Arabidopsis thaliana and demonstrates that AtMinD1 has Ca2+-dependent ATPase activity that is stimulated by AtMinE1. Site directed mutagenesis was used to create an active site mutant of AtMinD1, analysis of this mutant revealed loss of interaction with AtMinE1 and mis-localisation. The interaction of the stromal plastid division components was also investigated. Co-localisation and biomolecular fluorescence complementation assays revealed that AtFtsZ1-1 and AtFtsZ2-1 are capable of forming both homopolymeric and heteropolymeric filaments, AtMinD1 and AtMinE1 interact both with themselves and each other and ARC6 interacts specifically with AtFtsZ2-1. Many of the components involved in plastid division have yet to be identified. To identify novel plastid division components, yeast two-hybrid screening and co-immunoprecipitation were used to hunt for novel interacting partners of FtsZ proteins. Although much work has been dedicated to unravelling the machinery of plastid division, very little is known about the regulation of plastid division. DNA microarrays were used to investigate changes in nuclear gene expression upon chloroplast division inhibition. Quantitative PCR experiments demonstrate that the expression of AtFtsZ1-1, AtFtsZ2-1, AtMinD1 and AtMinE1 is light regulated and yeast one-hybrid screening was used to hunt for transcriptional activators/enhancers of AtMinD1 and AtMinE1.

Tat-dependent targeting of Rieske iron-sulphur proteins to both the plasma and thylakoid membranes in the cyanobacterium Synechocystis PCC6803

Cyanobacteria possess a differentiated membrane system and transport proteins into both the periplasm and thylakoid lumen. We have used green fluorescent protein (GFP)-tagged constructs to study the Tat protein transporter and Rieske Tat substrates in Synechocystis PCC6803. The Tat system has been shown to operate in the plasma membrane; we show here that it is also relatively abundant in the thylakoid membrane network, indicating that newly synthesized Tat substrates are targeted to both membrane systems. Synechocystis contains three Rieske iron-sulphur proteins, all of which contain typical twin-arginine signal-like sequences at their N-termini. We show that two of these proteins (PetC1 and PetC2) are obligate Tat substrates when expressed in Escherichia coli. The Rieske proteins exhibit differential localization in Synechocystis 6803; PetC1 and PetC2 are located in the thylakoid membrane, while PetC3 is primarily targeted to the plasma membrane. The combined data show that Tat substrates are directed with high precision to both membrane systems in this cyanobacterium, raising the question of how, and when, intracellular sorting to the correct membrane is achieved

The 'weekend effect' in acute medicine: a protocol for a team-based ethnography of weekend care for medical patients in acute hospital settings

on behalf of the HiSLAC study To cite: Tarrant C, Sutton E, Angell E, et al. The 'weekend effect' in acute medicine: a protocol for a team-based ethnography of weekend care for medical patients in acute hospital settings

Autonomic and trusted computing: Third international conference, ATC 2006, Wuhan, China, September 3-6, 2006 ; Proceedings

The thylakoid membrane forms stacked thylakoids interconnected by 'stromal' lamellae. Little is known about the mobility of proteins within this system. We studied a stromal lamellae protein, Hcf106, by targeting an Hcf106-GFP fusion protein to the thylakoids and photobleaching. We find that even small regions fail to recover Hcf106-GFP fluorescence over periods of up to 3 min after photobleaching. The protein is thus either immobile within the thylakoid membrane, or its diffusion is tightly restricted within distinct regions. Autofluorescence from the photosystem II light-harvesting complex in the granal stacks likewise fails to recover. Integral membrane proteins within both the stromal and granal membranes are therefore highly constrained, possibly forming 'microdomains' that are sharply separated

Quality and safety of in-hospital care for acute medical patients at weekends: a qualitative study.

BACKGROUND The increased mortality risk associated with weekend admission to hospital (the 'weekend effect') has been reported across many health systems. More recently research has focused on causal mechanisms. Variations in the organisation and delivery of in-hospital care between weekends and weekdays have been identified, but this is not always to the detriment of weekend admissions, and the impact on mortality is uncertain. The insights of frontline staff and patients have been neglected. This article reports a qualitative study of patients and clinicians, to explore their views on quality and safety of care at weekends. METHODS We conducted focus groups and interviews with clinicians and patients with experience of acute medical care, recruited from three UK hospital Trusts. We analysed the data using a thematic analysis approach, aided by the use of NVivo, to explore quality and safety of care at weekends. RESULTS We held four focus groups and completed six in-depth interviews, with 19 clinicians and 12 patients. Four threats to quality and safety were identified as being more prominent at weekends, relating to i) the rescue and stabilisation of sick patients; ii) monitoring and responding to deterioration; iii) timely accurate management of the therapeutic pathway; iv) errors of omission and commission. CONCLUSIONS At weekends patients and staff are well aware of suboptimal staffing numbers, skill mix and access to resources at weekends, and identify that emergency admissions are prioritised over those already hospitalised. The consequences in terms of quality and safety and patient experience of care are undesirable. Our findings suggest the value of focusing on care processes and systems resilience over the weekends, and how these can be better supported, even in the limited resource environment that exists in many hospitals at weekends

Sicker patients account for the weekend mortality effect among adult emergency admissions to a large hospital trust.

OBJECTIVE To determine whether the higher weekend admission mortality risk is attributable to increased severity of illness. DESIGN Retrospective analysis of 4 years weekend and weekday adult emergency admissions to a university teaching hospital in England. OUTCOME MEASURES 30-day postadmission weekend:weekday mortality ratios adjusted for severity of illness (baseline National Early Warning Score (NEWS)), routes of admission to hospital, transfer to the intensive care unit (ICU) and demographics. RESULTS Despite similar emergency department daily attendance rates, fewer patients were admitted on weekends (mean admission rate 91/day vs 120/day) because of fewer general practitioner referrals. Weekend admissions were sicker than weekday (mean NEWS 1.8 vs 1.7, p=0.008), more likely to undergo transfer to ICU within 24 hours (4.2% vs 3.0%), spent longer in hospital (median 3 days vs 2 days) and less likely to experience same-day discharge (17.2% vs 21.9%) (all p values <0.001).The crude 30-day postadmission mortality ratio for weekend admission (OR=1.13; 95% CI 1.08 to 1.19) was attenuated using standard adjustment (OR=1.11; 95% CI 1.05 to 1.17). In patients for whom NEWS values were available (90%), the crude OR (1.07; 95% CI 1.01 to 1.13) was not affected with standard adjustment. Adjustment using NEWS alone nullified the weekend effect (OR=1.02; 0.96-1.08).NEWS completion rates were higher on weekends (91.7%) than weekdays (89.5%). Missing NEWS was associated with direct transfer to intensive care bypassing electronic data capture. Missing NEWS in non-ICU weekend patients was associated with a higher mortality and fewer same-day discharges than weekdays. CONCLUSIONS Patients admitted to hospital on weekends are sicker than those admitted on weekdays. The cause of the weekend effect may lie in community services