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IntroductionLower tidal volume ventilation, facilitated by veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R), does not improve 90-day mortality in patients with acute hypoxaemic respiratory failure (AHRF). The aim of this analysis was to evaluate the effect of this therapeutic strategy on long-term outcomes.MethodsThis was a prespecified analysis of the REST trial, a UK-wide multicentre randomised clinical trial that compared lower tidal volume ventilation, facilitated by vv-ECCO2R (intervention), with standard care in the treatment of patients with moderate-to-severe AHRF. Mortality to 2 years was assessed, while respiratory function, post-traumatic stress disorder, cognitive function and health-related quality of life were evaluated in survivors at 1 year using standardised questionnaires.ResultsOf 412 patients enrolled into the REST trial, 391 (95%) had 2-year mortality outcome data available. There was no difference in the time to death between intervention and standard care (HR 1.08 (0.81, 1.44); log-rank test p=0.61). 161 patients alive at 1 year provided at least one questionnaire response. There was no difference in respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life between patients allocated to intervention or standard care.ConclusionLower-tidal volume ventilation facilitated by vv-ECCO2R does not affect 1-year mortality in patients with moderate-to-severe AHRF. Of the patients who provided questionnaire responses, there was no treatment effect on long-term respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life.Trial registration numberClinicalTrials.gov identifier: NCT02654327.

Despite increasing interest in pharmacogenomics, and the potential benefits to improve patient care, implementation into clinical practice has not been widespread. Recently, there has been a drive to implement genomic medicine into the UK National Health Service (NHS), largely spurred on by the success of the 100,000 Genomes Project. The UK Pharmacogenetics and Stratified Medicine Network, NHS England and Genomics England invited experts from academia, the healthcare sector, industry and patient representatives to come together to discuss the opportunities and challenges of implementing pharmacogenomics into the NHS. This report highlights the discussions of the workshop to provide an overview of the issues that need to be considered to enable pharmacogenomic medicine to become mainstream within the NHS.

Introduction Extracorporeal membrane carbon dioxide removal may have a role in treatment of patients with hypercapnic respiratory failure and refractory hypoxaemia and/or hypercapnia.Methods We report on the use, outcomes and complications in United Kingdom intensive care units reporting patients on the Extracorporal Life Support Organisation register.Results Of 60 patients, 42 (70%) had primarily hypoxic respiratory failure and 18 (30%) primarily hypercapnic respiratory failure. Use of veno-venous procedures increased compared to arterio-venous procedures. Following extracorporeal membrane carbon dioxide removal, ventilatory and blood gas parameters improved at 24 h. Twenty-seven (45%) of patients died before ICU discharge, while 27 (45%) of patients were discharged alive. The most common complications related to thrombosis or haemorrhage.Discussion There is limited use of extracorporeal membrane carbon dioxide removal in UK clinical practice and outcomes reflect variability in indications and the technology used. Usage is likely to increase with the availability of new, simpler, technology. Further high quality evidence is needed.

The standard of care (SoC) for medically operable patients with early-stage (stage I–IIIB) non-small cell lung cancer (NSCLC) is surgery combined with (neo)adjuvant systemic therapy for patients with II–IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. Following the success of targeted therapy (TT) in patients with advanced NSCLC (aNSCLC) harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC (eNSCLC). Adjuvant osimertinib is the only TT approved for use in the early-stage setting and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive eNSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.

Eating disorders and disordered eating are more common in high performance sports than the general population, and particularly so in high performance aesthetic sports. This paper presents some of the conceptual difficulties in understanding and diagnosing eating disorders in high performance gymnasts. It presents qualitative and quantitative data from a study designed to ascertain the pattern of eating disorder symptoms, depressive symptoms and levels of self-esteem among national and international level gymnasts from the UK in the gymnastic disciplines of sport acrobatics, tumbling, and rhythmic gymnastics.

Background:Acute Physiology and Chronic Health Evaluation (APACHE) III scores have been shown to correlate with outcomes for patients with burn injuries. It is unknown whether they can be used to compare outcomes between intensive care units that admit patients with burns in Australia and New Zealand.

CEPU-1/Neurotrimin is a neuronal glycoprotein thought to play a role in axon guidance and cell–cell recognition. It is a member of the IgLON family, has three C2 domains, and is attached to the plasma membrane by a GPI-anchor. We report here the characterisation of an alternatively-spliced isoform of CEPU-1 that is secreted. This isoform, termed CEPU-Se, is coexpressed with CEPU-1 in retina, cerebellum, and DRG neurons. In the cerebellum CEPU-1/CEPU-Se is expressed predominantly on granule cells and in the molecular layer. Divalent but not monovalent CEPU-Se interacts with CEPU-1 and other IgLONs, suggesting that the ability of CEPU-Se to modify the activity of the IgLON family may require an additional cofactor. CEPU-Se does not support the outgrowth of DRG neurons or the extension of established growth cones; however, neurite outgrowth on laminin is unaffected by CEPU-Se. Our data suggest that CEPU-Se may act to modulate the ability of CEPU-1, LAMP, and OBCAM to influence neurite outgrowth.

Publication patterns in the leading journals of chemistry, economics, philosophy, and sociology between 1960 and 1985 are examined Patterns of institutional stratification are indicated by the dispersion of institutional affiliations among authors, peripheral status of authors, and the extent of the bureaucratization of knowledge produced within the respective disciplines. The data show that patterns of institutional stratification vary across indicators and among the disciplines examined; that is, on some indicators, certain disciplines appear more relatively open than others. The relative openness among the leading journals in these disciplines, however, should not obscure the fact that institutional representation in these leading journals is generally restricted to an inner circle of prestigious academic institutions.

This article examines the impact of editor-author networks of institutional ties on publication patterns in three leading sociology journals between 1960 and 1985. The "invisible college," a social network of elite scholars, is discussed as the major contributor to the editor-author connection. Results suggest a pattern of institutional connections between editors and authors over time beyond random chance alone. It appears, however, that fluctuations in academic labor markets have weakened this network, resulting in a reduction in the strength of the institutional connections in journal publication.

This paper examines the construction of external environments on the part of the Du Pont Company through the four stages of capital accumulation: monopolization, diversification, research and development, and foreign expansion. This construction is viewed as a rationalizing strategy to reduce environmental uncertainty. Two main types of environmental uncertainty are identified. Material uncertainty pertains to uncertain ty regarding the flow of resources through the organization. Symbolic uncertainty pertains to uncertainties of meaning attached to organizational activities. Material construction of environmental conditions provided the Du Pont Company with a means of capital accumulation, while symbolic construction of environmental conditions provided the Du Pont Company with a means of capital legitimation

Agents which increase the intracellular concentration of cyclic adenosine-5'-monophosphate, induce a highly arborised morphology in a proportion of sub-confluent Swiss 3T3 fibroblasts. During this process the organisation of actin filaments progessively changes from a characteristic stress fibre pattern to leave a network of actin filaments within each and every arborisation. Despite this massive reorganisation of the actin cytoskeleton no changes are observed in the extent of polymerisation of actin during arborisation. The proportion of cells in asynchronous cultures undergoing arborisation at maximal concentrations of agents reaches a maximum of 30%; suggesting that the effect might be mediated only in cells during a restricted period of the cell cycle. More than 80% of serum-starved cells responded to these agents between 1 and 8 hours after readdition of serum, but not at other times, suggesting that the arborisation response can occur only in the G1 phase of the cell cycle. Copyright 1995, 1999 Academic Press

AbstractA theory for the population behavior of the eastern blackheaded budworm is presented. The qualitative properties and key processes of the system are identified and a description of the theory as a simulation model is given. Two domains of stability exist for the insect; one is caused by bird predation, the second by the effects of food limitation. The model predicts that the budworm’s cyclical population fluctuations are produced by the disappearance and reappearance of these stable domains and consequent movement of densities to new levels. Parasitism is identified as the principal mechanism causing this behavior. A qualitative comparison of model behavior with historical behavior is made and a critical field experiment to test the validity of the theory is proposed. Finally it is suggested that the population behavior of many forest defoliators may be explained using this theory.

There is no pharmacological treatment for the acute respiratory distress syndrome (ARDS). Platelets play an important role in the pathophysiology of ARDS. Pre-clinical, observational and clinically relevant models of ARDS indicate aspirin as a potential therapeutic option.

The author reflects on the importance of the spirit of sport in the development of the anti-doping policy in sports, the World Anti-Doping Code. He discusses the difficulty in giving a meaning to several concepts relative to every language or culture and its similarity in the spirit of sport. He offers insights to anti-doping personnel on how to justify the lists of values in the Code which include health, teamwork, and respect for rules and laws.

Bronchoesophageal fistula are commonly caused by a lung or esophageal malignancy eroding into the neighboring structure. Benign forms of bronchoesophageal fistula are less common and may have a congenital nature. Congenital bronchoesophageal fistula usually present in adult life with chronic symptoms of lung suppuration. We present a case of congenital bronchoesophageal fistula in an octogenarian and review the literature on this subject. We also suggest an extrapleural approach to the fistula to lessen the possibility of postoperative empyema.