Improving detection and management of atrial fibrillation after ischaemic stroke in Glasgow (IMPROVE-AF): A quality improvement project.

BACKGROUND: The use of cardiac monitoring to detect atrial fibrillation (AF) is routine after ischaemic stroke but is often delayed leaving patients at risk from undetected AF. We sought to improve the detection of AF by delivering early prolonged 'in-house' cardiac monitoring. METHODS: We collected 3-months of data of people with stroke/transient ischaemic attack (TIA), but without AF, who underwent cardiac monitoring (Phase 1, pre-quality improvement project (QIP)). We then implemented an 'in-house' 7-day cardiac monitoring service for 12 months (Phase 2, during QIP). RESULTS: We included 244 people in Phase 1 and 172 in Phase 2. In Phase 1, 232 (95%) people completed cardiac monitoring. Of these, new AF was detected in 10 (4%). Median time from stroke/TIA onset to availability of the monitoring report in Phase 1 was 50 (interquartile range (IQR): 24-123) days. In Phase 2, 166 (97%) of people completed 7-day cardiac monitoring, with new AF detected in 17 (10%). Median time from onset to availability of the report in Phase 2 was 12 (IQR: 9-15) days. In people with AF detected, 'in-house' monitoring reduced the time of stroke/TIA onset to anticoagulant commencement from 41 (Phase 1) to 14 (Phase 2) days. DISCUSSION: The QIP has improved AF detection, reduced delays associated with conventional cardiac monitoring and prompted early initiation of oral anticoagulation.

Development of a Semiautomated Database for Patients With Adult Congenital Heart Disease.

BACKGROUND: Databases for Congenital Heart Disease (CHD) are effective in delivering accessible datasets ready for statistical inference. Data collection hitherto has, however, been labour and time intensive and has required substantial financial support to ensure sustainability. We propose here creation and piloting of a semiautomated technique for data extraction from clinic letters to populate a clinical database. METHODS: PDF formatted clinic letters stored in a local folder, through a series of algorithms, underwent data extraction, preprocessing, and analysis. Specific patient information (diagnoses, diagnostic complexity, interventions, arrhythmia, medications, and demographic data) was processed into text files and structured data tables, used to populate a database. A specific data validation schema was predefined to verify and accommodate the information populating the database. Unsupervised learning in the form of a dimensionality reduction technique was used to project data into 2 dimensions and visualize their intrinsic structure in relation to the diagnosis, medication, intervention, and European Society of Cardiology classification lists of disease complexity. Ninety-three randomly selected letters were reviewed manually for accuracy. RESULTS: There were 1409 consecutive outpatient clinic letters used to populate the Scottish Adult Congenital Cardiac Database. Mean patient age was 35.4 years; 47.6% female; with 698 (49.5%) having moderately complex, 369 (26.1%) greatly complex, and 284 (20.1%) mildly complex lesions. Individual diagnoses were successfully extracted in 96.95%, and demographic data were extracted in 100% of letters. Data extraction, database upload, data analysis and visualization took 571 seconds (9.51 minutes). Manual data extraction in the categories of diagnoses, intervention, and medications yielded accuracy of the computer algorithm in 94%, 93%, and 93%, respectively. CONCLUSIONS: Semiautomated data extraction from clinic letters into a database can be achieved successfully with a high degree of accuracy and efficiency.

Computational Model of Sclerotic Scatter.

PURPOSE: A clinical examination technique to detect pathology within the anterior eye is known as "sclerotic scatter" (SS). Its propagation pathway has not been thoroughly investigated. Although conventionally theorized to occur by "total internal reflection" (TIR) within the cornea, existing data suggest that this may be an incomplete explanation. METHODS: An anterior eye model representative of a human eye has been constructed using nonsequential ray tracing (OpticStudio 18.1). Three generations of the model were constructed to support the analyses of the pathway of light in SS. A design of experiment methodology involving the key parameters was used to determine the slit-lamp setup for optimum clinical visualization. RESULTS: Most of the light directed into the temporal limbus in SS is lost (52%) into the sclera or reemitted back to the clinician. Only 0.006% of light that transits the central cornea undergoes TIR off the anterior cornea and more significantly 0.000125% off the posterior cornea. The optimal slit-lamp setup parameters to maximize the clinician's visualization are also summarized. CONCLUSIONS: The propagation of light within SS primarily does not occur by TIR off the posterior cornea but rather the direct transcameral propagation of light. SS also represents an inefficient usage of light, with approximately half of the light creating a potential glare source for clinicians. We have formulated a recommended set of parameters for the slit-lamp setup to maximize clinical visualization. We also describe the transcameral pathways involved in SS that create a corneal "backlighting" effect. Almost a century after Graves original description, the optics of this phenomenon are described here.

How ecological processes shape the outcomes of stock enhancement and harvest regulations in recreational fisheries.

Fish stocking and harvest regulations are frequently used to maintain or enhance freshwater recreational fisheries and contribute to fish conservation. However, their relative effectiveness has rarely been systematically evaluated using quantitative models that account for key size- and density-dependent ecological processes and adaptive responses of anglers. We present an integrated model of freshwater recreational fisheries where the population dynamics of two model species affect the effort dynamics of recreational anglers. With this model, we examined how stocking various fish densities and sizes (fry, fingerlings, and adults) performed relative to minimum-length limits using a variety of biological, social, and economic performance measures, while evaluating trade-offs. Four key findings are highlighted. First, stocking often augmented the exploited fish population, but size- and density-dependent bottlenecks limited the number of fry and fingerlings surviving to a catchable size in self-sustaining populations. The greatest enhancement of the catchable fish population occurred when large fish that escaped early bottlenecks were stocked, but this came at the cost of wild-stock replacement, thereby demonstrating a fundamental trade-off between fisheries benefits and conservation. Second, the relative performance of stocking naturally reproducing populations was largely independent of habitat quality and was generally low. Third, stocking was only economically advisable when natural reproduction was impaired or absent, stocking rates were low, and enough anglers benefitted from stocking to offset the associated costs. Fourth, in self-sustaining fish populations, minimum-length limits generally outperformed stocking when judged against a range of biological, social and economic objectives. By contrast, stocking in culture-based fisheries often generated substantial benefits. Collectively, our study demonstrates that size- and density-dependent processes, and broadly the degree of natural recruitment, drive the biological, social, and economic outcomes of popular management actions in recreational fisheries. To evaluate these outcomes and the resulting trade-offs, integrated fisheries-management models that explicitly consider the feedbacks among ecological and social processes are needed.

Tuberculosis in healthcare workers, Scotland.

In an attempt to explore healthcare worker acquisition of tuberculosis infection, we conducted population-based surveillance of all cases recorded as healthcare workers reported to Enhanced Surveillance of Mycobacterial Infection from 2000 to 2015. Over the study period, the mean incidence rate of tuberculosis among all healthcare workers was 15.4 per 100,000 healthcare workers. However, the incidence rate of tuberculosis amongst those healthcare workers born outside the UK was 164.8 per 100,000 compared with 5.0 per 100,000 UK-born healthcare workers. Fifty-seven per cent of all non-UK-born healthcare workers were diagnosed within five years of their arrival in the UK and would have been new entrants to the NHS. An effective new entrant occupational health screening programme for latent tuberculosis infection may have prevented some of these active cases of infection.

Evolutionary impact assessment: accounting for evolutionary consequences of fishing in an ecosystem approach to fisheries management.

Managing fisheries resources to maintain healthy ecosystems is one of the main goals of the ecosystem approach to fisheries (EAF). While a number of international treaties call for the implementation of EAF, there are still gaps in the underlying methodology. One aspect that has received substantial scientific attention recently is fisheries-induced evolution (FIE). Increasing evidence indicates that intensive fishing has the potential to exert strong directional selection on life-history traits, behaviour, physiology, and morphology of exploited fish. Of particular concern is that reversing evolutionary responses to fishing can be much more difficult than reversing demographic or phenotypically plastic responses. Furthermore, like climate change, multiple agents cause FIE, with effects accumulating over time. Consequently, FIE may alter the utility derived from fish stocks, which in turn can modify the monetary value living aquatic resources provide to society. Quantifying and predicting the evolutionary effects of fishing is therefore important for both ecological and economic reasons. An important reason this is not happening is the lack of an appropriate assessment framework. We therefore describe the evolutionary impact assessment (EvoIA) as a structured approach for assessing the evolutionary consequences of fishing and evaluating the predicted evolutionary outcomes of alternative management options. EvoIA can contribute to EAF by clarifying how evolution may alter stock properties and ecological relations, support the precautionary approach to fisheries management by addressing a previously overlooked source of uncertainty and risk, and thus contribute to sustainable fisheries.

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans.

AIMS: Inhibition of neutral endopeptidases (NEP) results in a beneficial increase in plasma concentrations of natriuretic peptides such as ANP. However NEP inhibitors were ineffective anti-hypertensives, probably because NEP also degrades vasoconstrictor peptides, including endothelin-1 (ET-1). Dual NEP and endothelin converting enzyme (ECE) inhibition may be more useful. The aim of the study was to determine whether SLV-306 (daglutril), a combined ECE/NEP inhibitor, reduced the systemic conversion of big ET-1 to the mature peptide. Secondly, to determine whether plasma ANP levels were increased. MAIN METHODS: Following oral administration of three increasing doses of SLV-306 (to reach an average target concentration of 75, 300, 1200 ng ml(-1) of the active metabolite KC-12615), in a randomised, double blinded regime, big ET-1 was infused into thirteen healthy male volunteers. Big ET-1 was administered at a rate of 8 and 12 pmol kg(-1)min(-1) (20 min each). Plasma samples were collected pre, during and post big ET-1 infusion. ET-1, C-terminal fragment (CTF), big ET-1, and atrial natriuretic peptide (ANP) were measured. KEY FINDINGS: At the two highest concentrations tested, SLV-306 dose dependently attenuated the rise in blood pressure after big ET-1 infusion. There was a significant increase in circulating big ET-1 levels, compared with placebo, indicating that SLV-306 was inhibiting an increasing proportion of endogenous ECE activity. Plasma ANP concentrations also significantly increased, consistent with systemic NEP inhibition. SIGNIFICANCE: SLV-306 leads to inhibition of both NEP and ECE in humans. Simultaneous augmentation of ANP and inhibition of ET-1 production is of potential therapeutic benefit in cardiovascular disease.

Density-dependent life-history compensation of an iteroparous salmonid.

Over the course of a decade, the bull trout (Salvelinus confluentus) population in Lower Kananaskis Lake, Alberta, Canada, recovered from a heavily overexploited state, experiencing a 28-fold increase in adult abundance after the implementation of zero-harvest regulations. This system provided a unique opportunity to monitor the changes in life-history characteristics in a natural population throughout the recovery process. The purpose of this study was to examine the degree to which life-history traits were able to compensate for harvest-induced changes and the implications of this for management. Density-dependent changes in growth, survival, and reproductive life-history characteristics were observed. As density increased, maturation was delayed, and the frequency of skipped reproductive events, primarily by individuals of poor condition, increased. However, size at maturation and the proportion of fish skipping reproduction differed between the sexes, suggesting that life-history trade-offs differ between the sexes. The rapid response of these life-history traits to changes in density suggests that these changes were primarily due to phenotypic plasticity, although the importance of natural and artificial selection should not be discounted. The magnitude of the variation in the traits represents the degree to which the population was able to compensate for overharvest, although the overexploited state of the population at the beginning of the study demonstrates it was not able to fully compensate for this mortality. However, no evidence of depensatory processes was found. This, in combination with the plasticity of the life-history traits, has important implications for the resilience of the population to overharvest. Furthermore, density-dependent growth may have the unintended result of making size-based regulations less conservative at low levels of population abundance, as younger fish, perhaps even immature fish, become vulnerable to harvest. Finally, the variation in life-history traits in relation to evolutionary change is discussed. Results from this study demonstrate the importance of considering not only survival, but also changes in life-history characteristics for management and conservation.

Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding.

Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.

The clinical relevance of adrenomedullin: a promising profile?

Adrenomedullin (AM) is a peptide that possesses potentially beneficial properties. Since the initial discovery of the peptide by Kitamura et al. in 1993, the literature has been awash with reports describing its novel mechanisms of action and huge potential as a therapeutic target. Strong evidence now exists that AM is able to act as an autocrine, paracrine, or endocrine mediator in a number of biologically significant functions, including the endothelial regulation of blood pressure, protection against organ damage in sepsis or hypoxia, and the control of blood volume through the regulation of thirst. Its early promise as a potential mediator/modulator of disease was not, however, entirely as a result of the discovery of physiological functions but due more to the observation of increasing levels measured in plasma in direct correlation with disease progression. In health, AM circulates at low picomolar concentrations in plasma in 2 forms, a mature 52-amino acid peptide and an immature 53-amino acid peptide. Plasma levels of AM have now been shown to be increased in a number of pathological states, including congestive heart failure, sepsis, essential hypertension, acute myocardial infarction, and renal impairment. These earliest associations have been further supplemented with evidence of a role for AM in other pathologies including, most intriguingly, cancer. In this review, we offer a timely review of our current knowledge on AM and give a detailed account of the putative role of AM in those clinical areas in which the best therapeutic opportunities might exist.

Laboratory diagnosis of legionnaires' disease due to Legionella pneumophila serogroup 1: comparison of phenotypic and genotypic methods.

Laboratory results of 67 cases of legionnaires' disease caused by Legionella pneumophila serogroup (Sg) 1 spanning a 6-year period were analysed by both phenotypic and genotypic methods. The methods compared were urinary antigen enzyme immunoassay (EIA), an immunofluorescent antibody (IFA) test, direct fluorescent antibody (DFA), culture and a 5S rRNA PCR with Southern blotting confirmation. Urine was available in 53 cases, of which 35 (66%) were positive, with an antigen peak observed at 5-10 days after onset of disease symptoms. The IFA test was positive in 62 (92.5%) cases, with 56 (90.3%) cases producing a greater than fourfold rise in titre and 6 (9.7%) giving presumptive high titres of > or =1:128. There were two antibody peaks, one at 10-15 days and another at >25 days after onset. In 23 cases where samples were available, DFA and culture were respectively positive in 5 (22%) and 10 (48%) cases. There was a peak in culture-positives 5-10 days after onset of disease. A Legionella-specific 5S rRNA PCR on patient serum was positive in 54 (80.5%) cases, with a peak in PCR positivity at 6-10 days after disease onset. In 22 of the 67 cases, the full panel of diagnostic methods was available for comparison. The relative sensitivity and specificity of the urinary antigen EIA and the serum PCR was 100%. The IFA gave relative sensitivity and specificity values of 93.8 and 95%. DFA and culture, although 100% specific, produced only low sensitivities, of 19 and 42.8%, respectively. This study has shown that urinary antigen and serum PCR are valuable tests in the acute phase of disease, with excellent sensitivity and specificity values. At present, the Legionella species causing infection requires to be verified by IFA serology and/or culture, but this could become unnecessary as new antigen and L. pneumophila Sg 1-specific PCR tests become available.

Is the pregnancy hormone relaxin also a vasodilator peptide secreted by the heart?

BACKGROUND: It has been shown recently that the pregnancy and parturition hormone, relaxin, is secreted by the heart. This study examined the effects of relaxin in small human resistance arteries from the systemic and pulmonary circulations. METHODS AND RESULTS: Arteries were obtained from gluteal biopsies and resected lung tissue and studied with the use of wire myography. Cumulative concentration relaxation curves were constructed in systemic arteries with substance P, epoprostenol, atrial natriuretic peptide, and relaxin (concentration range 10(-13) -10(-7)M). The maximal responses were 88(+/-5)%, 67(+/-10)%, 52(+/-16)% and 66(+/-16)%, respectively. Endothelium removal virtually abolished the action of relaxin. Relaxin had no vasodilator effect in pulmonary arteries. CONCLUSIONS: Relaxin is a powerful dilator of systemic resistance arteries secreted by the heart that may contribute to cardiovascular regulation.

Endothelial function is preserved in pregnant women with well-controlled type 1 diabetes.

OBJECTIVE: Pregnant women with diabetes mellitus have a higher incidence of adverse pregnancy outcomes. Vascular, and in particular, endothelial function may be significantly modified in diabetes resulting in impaired endothelium-dependent relaxation. This study aims to investigate endothelium-dependent relaxation in pregnant women with pre-existing type I diabetes mellitus. METHODS: Small arteries (mean luminal diameter approximately 295 microm) were isolated from biopsies of subcutaneous fat from pregnant women with pre-existing type I diabetes mellitus, non-diabetic pregnant women, and non-diabetic non-pregnant women. Endothelial and smooth muscle function were determined using wire myography, and the contributions of nitric oxide, vasodilator prostanoid and endothelial hyperpolarisation were studied using specific inhibitors. RESULTS: Arteries obtained from the diabetic pregnant women did not demonstrate any difference in either endothelial or smooth muscle function when compared with non-diabetic pregnant women. The contribution of nitric oxide to endothelium-dependent relaxation was approximately 20% in the pregnant women regardless of whether they were diabetic, and approximately 11% in the non-pregnant women. Endothelial hyperpolarisation appeared to contribute largely to vasorelaxation in human subcutaneous arteries, and was at least twice that of nitric oxide in pregnant women and fivefold greater in non-pregnant women. CONCLUSIONS: This study provides evidence that pregnant women with well-controlled pre-existing type 1 diabetes mellitus have both normal endothelial and smooth muscle function. Endothelium-dependent hyperpolarisation appears to play a large role in vascular relaxation in human subcutaneous resistance arteries. This study suggests that the problems associated with diabetic pregnancies are unlikely to be due to vascular dysfunction.