The role of primary care in cancer diagnosis via emergency presentation: qualitative synthesis of significant event reports

Background: Patients diagnosed with cancer in the context of an emergency presentation (EP) have poorer outcomes. It is often assumed that such patients present to the emergency department without consulting their general practitioner (GP). Little work has been done to identify primary care involvement before hospital attendance. Methods: Participating primary care practices completed a significant event audit (SEA) report for the last patient diagnosed with cancer as a result of an EP. Accounts were synthesised and a qualitative approach to analysis undertaken. Results: SEAs for 222 patients were analysed. A range of cancers were included, the most common being lung (32.4%) and upper gastrointestinal (19.8%). In most cases, patients had contact with their practice before diagnosis, primarily in the period immediately before admission. In only eight cases had there been no input from primary care. Accounts of protracted primary care contact generally demonstrated complexity, often related to comorbidity, patient-mediated factors or reassurance provided by negative investigations. Learning points identified by practices centred on the themes of presentation and diagnosis, consultation and safety-netting, communication and system issues, patient factors and referral guidelines. Conclusions: There is extensive primary care input into patients whose diagnosis results from EP, and for the most part potential ‘delay’ in referral can be reasonably explained by the complexity of the presentation or by coexisting patient factors

Rupture Energetics in Crustal Rock From Laboratory‐Scale Seismic Tomography

The energy released during earthquake rupture is partly radiated as seismic waves and mostly dissipated by frictional heating on the fault interface and by off‐fault fracturing of surrounding host rock. Quantification of these individual components is crucial to understand the physics of rupture. We use a quasi‐static rock fracture experiment combined with a novel seismic tomography method to quantify the contribution of off‐fault fracturing to the energy budget of a rupture and find that this contribution is around 3% of the total energy budget and 10% of the fracture energy Gc. The off‐fault dissipated energy changes the physical properties of the rock at the early stages of rupture, illustrated by the 50% drop in elastic moduli of the rock near the fault, and thus is expected to greatly influence later stages of rupture and slip. These constraints are a unique benchmark for calibration of dynamic rupture models

Protocol for the 'e-Nudge trial' : a randomised controlled trial of electronic feedback to reduce the cardiovascular risk of individuals in general practice [ISRCTN64828380]

Background: Cardiovascular disease (including coronary heart disease and stroke) is a major cause of death and disability in the United Kingdom, and is to a large extent preventable, by lifestyle modification and drug therapy. The recent standardisation of electronic codes for cardiovascular risk variables through the United Kingdom's new General Practice contract provides an opportunity for the application of risk algorithms to identify high risk individuals. This randomised controlled trial will test the benefits of an automated system of alert messages and practice searches to identify those at highest risk of cardiovascular disease in primary care databases. Design: Patients over 50 years old in practice databases will be randomised to the intervention group that will receive the alert messages and searches, and a control group who will continue to receive usual care. In addition to those at high estimated risk, potentially high risk patients will be identified who have insufficient data to allow a risk estimate to be made. Further groups identified will be those with possible undiagnosed diabetes, based either on elevated past recorded blood glucose measurements, or an absence of recent blood glucose measurement in those with established cardiovascular disease. Outcome measures: The intervention will be applied for two years, and outcome data will be collected for a further year. The primary outcome measure will be the annual rate of cardiovascular events in the intervention and control arms of the study. Secondary measures include the proportion of patients at high estimated cardiovascular risk, the proportion of patients with missing data for a risk estimate, and the proportion with undefined diabetes status at the end of the trial

The smoking cessation in pregnancy incentives trial (CPIT): study protocol for a phase III randomised controlled trial

Background: Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Methods: The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, < 24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth. The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK? Discussion: This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women. Trial registration: Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017

Plastic shrinkage cracking of concrete - Roles of osmotic suction

Plastic shrinkage cracking of concrete occurs when the stresses arising in the concrete, due to a combination of suction and restraints of deformation such as reinforcement or formwork, equal its strength. However, three different types of suctions should be distinguished, namely total, matric and osmotic suctions. Although the total suction comprises matric and osmotic suctions, it is often used interchangeably with matric suction, with the underlying unconfirmed assumption that either the osmotic suction or its effect is negligible. In this paper, after a discussion of the pore moisture suctions and strength of unsaturated early-age concrete, experimental investigations of the suctions arising in, and the tensile strength and shear strength of, fly ash mixed with solutions of different osmotic suctions are described. It was found that osmotic suction has negligible effect on the shear and tensile strength, and hence, by inference, the inter-particle stresses in the fly ash mixture and early-age concrete. This strongly suggests that the role played by osmotic suction in the plastic shrinkage cracking of concrete is minimal and, accordingly, justifies the focus of earlier researchers on matric suction only

Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury

The article reviews agents in clinical use or in development as radioprotectors and mitigators of radiation-induced normal tissue injury

Complex patterns of human antisera reactivity to novel 2009 H1N1 and historical H1N1 influenza strains

Background: During the 2009 influenza pandemic, individuals over the age of 60 had the lowest incidence of infection with approximately 25% of these people having pre-existing, cross-reactive antibodies to novel 2009 H1N1 influenza isolates. It was proposed that older people had pre-existing antibodies induced by previous 1918-like virus infection(s) that cross-reacted to novel H1N1 strains. Methodology/Principal Findings: Using antisera collected from a cohort of individuals collected before the second wave of novel H1N1 infections, only a minority of individuals with 1918 influenza specific antibodies also demonstrated hemagglutination-inhibition activity against the novel H1N1 influenza. In this study, we examined human antisera collected from individuals that ranged between the ages of 1 month and 90 years to determine the profile of seropositive influenza immunity to viruses representing H1N1 antigenic eras over the past 100 years. Even though HAI titers to novel 2009 H1N1 and the 1918 H1N1 influenza viruses were positively associated, the association was far from perfect, particularly for the older and younger age groups. Conclusions/Significance: Therefore, there may be a complex set of immune responses that are retained in people infected with seasonal H1N1 that can contribute to the reduced rates of H1N1 influenza infection in older populations. © 2012 Carter et al

Sodium and Health: Old Myths and a Controversy Based on Denial

Purpose of Review The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the burden of CVD. Recent Findings Yet, since as long ago as 1988, and more recently in eight articles published in the European Heart Journal in 2020 and 2021, some researchers have propagated a myth that reducing sodium does not consistently reduce CVD but rather that lower sodium might increase the risk of CVD. These claims are not well-founded and support some food and beverage industry’s vested interests in the use of excessive amounts of salt to preserve food, enhance taste, and increase thirst. Nevertheless, some researchers, often with funding from the food industry, continue to publish such claims without addressing the numerous objections. This article analyzes the eight articles as a case study, summarizes misleading claims, their objections, and it offers possible reasons for such claims. Summary Our study calls upon journal editors to ensure that unfounded claims about sodium intake be rigorously challenged by independent reviewers before publication; to avoid editorial writers who have been co-authors with the subject paper’s authors; to require statements of conflict of interest; and to ensure that their pages are used only by those who seek to advance knowledge by engaging in the scientific method and its collegial pursuit. The public interest in the prevention and treatment of disease requires no less

Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p><it>Cryptococcus neoformans </it>(<it>C. neoformans</it>) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.</p> <p>Methods</p> <p>Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated <it>in vitro </it>with encapsulated or acapsular <it>C. neoformans </it>cultivated at room temperature or 37°C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.</p> <p>Results</p> <p>Viable <it>C. neoformans </it>is a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsular <it>C. neoformans </it>that was grown at 37°C. <it>C. neoformans </it>was also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/β) in BEAS-2B cells. NHBE was highly responsive to stimulation with <it>C. neoformans</it>; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of <it>C. neoformans</it>.</p> <p>Conclusion</p> <p>This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to <it>C. neoformans </it>and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and <it>in vitro </it>fungal culture conditions modulate the host inflammatory response to <it>C. neoformans</it>. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense <it>in vivo</it>.</p

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions