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Objectives To investigate the effects of an admission avoidance pathway within a new integrated respiratory service on the number of Chronic Obstructive Pulmonary Disease (COPD)-related hospital admissions in England. Methods We used interrupted time series analysis to estimate the effects of the admission avoidance pathway on COPD hospital admissions, length of stay, and 30-day readmissions. We included all unplanned admissions with COPD as primary diagnosis using Hospital Episode Statistics, comparing the intervention region with a demographically similar control region in the two years before and one year after the implementation of the new service. Results Unplanned hospital admissions for COPD exacerbations followed a clear seasonal pattern, peaking in early winter. We found no evidence that the admission avoidance pathway influenced the rate of hospital admissions or 30-day readmissions. We found weak evidence of a trend change in length of stay following the launch of the admission avoidance pathway. Conclusions Our study adds to the growing body of evidence that suggests that additional admission avoidance capacity alone does not lead to a measurable reduction in admissions or length of stay. Further investigation is required to understand the reasons why. A longer follow-up may be required to see some of the potential benefits.

This paper presents the results of analysis of the RRab type star, RX Eri, building on previous work to include light curves further into the infrared. This project has yielded light curve results which have determined the period to 0:587 +/- 0:005d, agreeing with prior research. The distance estimation using Period-Luminosity-Metallicity relationships, V: 612+/-27pc, i: 608+/-21pc, z: 613+/-23pc broadly agreed with Gaia DR2’s estimation of 605 +/- 11pc. These infrared filters yielded better estimations in terms of error than those in the V band, although they all fall within the margins of error of the measurements made.

Although the hawksbill turtle (Eretmochelys imbricata) nesting colony in Hawaiʻi may constitute one of the smallest hawksbill nesting populations in the world, it is also the largest in the U.S. Pacific Islands and the Central North Pacific Ocean. The isolated nature of the Hawaiian Archipelago has raised interest in the genetic characterization of the population, yet research remains lacking. In this study we use mitochondrial DNA (mtDNA) to provide the first genetic characterization of nesting (n = 108) and foraging (n = 29) hawksbills in the Hawaiian Islands. We combine our data with sequences previously published from the West and East Pacific to evaluate the genetic distinctiveness of the nesting assemblage in Hawaiʻi, and to gain insights into the origin of hawksbills found at foraging grounds around the archipelago. We found strong differentiation (FST > 0.238, P-value

Purpose The purpose of this study is to examine the consumer-side effects of “under new management” (UNM) signs. The authors integrate cue-utilization theory and relevance theory to guide hypotheses about the conditions under which these signs are and are not beneficial. Design/methodology/approach Two consumer-based experiments were used to examine the quality and reputation effects of restaurants signaling a management change on potential and existing customers. Findings The results suggest that positive and negative effects are possible. The direction of these effects is contingent upon consumers’ prior experience, type of service (i.e. search/experience) and the relevance of the signal. Research limitations/implications The study is limited to one industry (i.e. restaurants) and examines the effects of market signals on perceived quality and reputation. In addition, this research brought forth the notion of “signal relevance” and suggested that it may be explicitly tied to attributions. However, this assertion must examine multiple signals (relevant/irrelevant) and their contingent effects on consumer perceptions. Practical implications The findings advise businesses to use caution when using signals such as an “UNM” sign, as they appear to have different effects depending on the experience of the consumer with the service and the relevance of the signal. Originality/value This research contributes to the literature on cue utilization theory to understand the effects of marketplace cues on consumer perceptions. It contributes to marketing theory and practice by proposing a model of cue effects based on prior customer experience, type of service and cue relevance.

On August 16, 2021, the Tennessee Department of Health (TDH) was notified of a positive rabies test result from a South American collared anteater (Tamandua tetradactyla) in Washington County, Tennessee. Tamanduas, or lesser anteaters, are a species of anteater in which rabies has not previously been reported. The animal was living at a Tennessee zoo and had been recently translocated from a zoo in Virginia. TDH conducted an investigation to confirm the rabies result, characterize the rabies variant, and ascertain an exposure risk assessment among persons who came into contact with the tamandua. Risk assessments for 22 persons were completed to determine the need for rabies postexposure prophylaxis (rPEP); rPEP was recommended for 13 persons, all of whom agreed to receive it. Using phylogenetic results of the virus isolated from the tamandua and knowledge of rabies epidemiology, public health officials determined that the animal was likely exposed to wild raccoons present at the Virginia zoo. This report describes expansion of the wide mammalian species diversity susceptible to rabies virus infection and summarizes the investigation, highlighting coordination among veterinary and human public health partners and the importance of preexposure rabies vaccination for animal handlers and exotic zoo animals.

Low-level languages, which require manual memory management from the programmer, remain in wide use for performance-critical applications. Memory-safety bugs are common, and now a major source of exploits. In particular, a use-after-free bug occurs when an object is erroneously deallocated, whilst pointers to it remain active in memory, and those (dangling) pointers are later used to access the object. An attacker can reallocate the memory area backing an erroneously freed object, then overwrite its contents, injecting carefully chosen data into the host program, thus altering its execution and achieving privilege escalation. We present MineSweeper, a system to mitigate use-after-free vulnerabilities by retaining freed allocations in a quarantine, until no pointers to them remain in program memory, thus preventing their reallocation until it is safe. MineSweeper performs efficient linear sweeps of memory to identify quarantined items that have no dangling pointers to them, and thus can be safely reallocated. This allows MineSweeper to be significantly more efficient than previous transitive marking procedure techniques. MineSweeper, attached to JeMalloc, improves security at an acceptable overhead in memory footprint (11.1% on average) and an execution-time cost of only 5.4% (geometric mean for SPEC CPU2006), with 9.6% additional threaded CPU usage. These figures considerably improve on the state-of-the-art for non-probabilistic drop-in temporal-safety systems, and make MineSweeper the only such scheme suitable for deployment in real-world production environments.

Evaluating wildlife population trends is necessary for the development of effective management strategies, which are particularly relevant for highly threatened species. Hawksbill marine turtles (Eretmochelys imbricata) are considered endangered globally and are rare in Hawai‘i. Remnant hawksbill nesting beaches were identified in Hawai‘i in the late 1980s and the primary sites have been monitored since that time. In this study we summarize all available hawksbill nesting activity around the Hawaiian Islands between 1988 and 2018, highlighting relevant demographic and geographic data for the species. Because monitoring effort varied substantially across space and time, we implemented a predictive modeling approach that accounted for varying effort to explore potential trends in annual number of nesting females and nests over time. Field monitoring efforts documented an annual average of 14 ± 4.3 (range: 5–26) nesting females and 48 ± 19.0 (range: 12–93) nests, with a cumulative total of 178 individual nesting females and 1,280 nests recorded across all years. Nesting has been documented on four Hawaiian Islands, with the overwhelming majority of nesting females (78.4%) and nests (86.5%) recorded at four beaches along the southern coast of Hawai‘i Island. Recent monitoring (2018) at a beach on Moloka‘i Island revealed numbers similar to the most important beaches on Hawai‘i Island. Despite difficulty discerning obvious trends when looking solely at the raw tabulated numbers from field monitoring, our analysis suggests both the number of nesting females and nests have been positively trending since 2006, and this is supported by a higher percentage (57.1% of annual cohorts) of neophyte (vs. remigrant) nesters over the second half of the monitoring timeframe. The masking of obvious trends in the tabulated numbers is likely due to decreased overall monitoring effort as a result of reduced funding in recent years, coupled with a shift in focal monitoring effort from the historical primary nesting site of Kamehame, to the more recently established nesting site of Pōhue. Although the positive trend is encouraging, our findings highlight the precarious state of hawksbills in Hawai‘i and the need to enhance monitoring across all sites to support more robust population assessments and management decision making.

BackgroundUse of laboratory testing has increased in the UK over the past few decades, with considerable geographical variation.AimTo evaluate what laboratory tests are used to monitor people with hypertension, type 2 (T2) diabetes, or chronic kidney disease (CKD) and assess variation in test use in UK primary care.Design & settingLongitudinal cohort study of people registered with UK general practices between June 2013 and May 2018 and previously diagnosed with hypertension, T2 diabetes, or CKD.MethodClinical Practice Research Datalink (CPRD) primary care data linked to ethnic group and deprivation was used to examine testing rates over time, by GP practice, age, sex, ethnic group, and socioeconomic deprivation, with age–sex standardisation.ResultsNearly 1 million patients were included, and more than 27 million tests. The most ordered tests were for renal function (1463 per 1000 person-years), liver function (1063 per 1000 person-years), and full blood count (FBC; 996 per 1000 person-years). There was evidence of undertesting (compared with current guidelines) for HbA1c and albumin:creatinine ratio (ACR) or microalbumin, and potential overtesting of lipids, FBC, liver function, and thyroid function. Some GP practices had up to 27 times higher testing rates than others (HbA1c testing among patients with CKD).ConclusionTesting rates are no longer increasing, but they are not always within the guidelines for monitoring long-term conditions (LTCs). There was considerable variation by GP practice, indicating uncertainty over the most appropriate testing frequencies for different conditions. Standardising the monitoring of LTCs based on the latest evidence would provide greater consistency of access to monitoring tests.

IntroductionType 1 diabetes (T1D) is a chronic and incurable autoimmune disease, diagnosed in early childhood and managed initially in paediatric healthcare services. In many countries, including Australia, national audit data suggest that management and care of T1D, and consequently glycaemic control, are consistently poor. This can lead to adverse outcomes such as cardiovascular disease and nephropathy. T1D treatment is complex, multidisciplinary, multiagency and life-long and should involve patient-centred, developmentally appropriate care. Although an emerging body of literature describes T1D models of care, their components, implementation determinants and associated outcomes are poorly understood.ObjectivesTo provide a study protocol to describe methods to map existing models of care for children and young adults living with T1D. It will identify the gaps and needs in care delivery as viewed by healthcare providers and by children, young people and their families accessing care in metropolitan and rural or remote regions throughout Australia.Methods and analysisA mixed-method study that includes provider and consumer-specific surveys and interviews about current T1D care provisions. Data will be analysed thematically (qualitative) and statistically (quantitative) and synthesised to describe the key characteristics of effective and sustainable models of care for T1D and to identify gaps.Ethics and disseminationEthics approval was granted by the Macquarie University Human Research Ethics Committee in July 2022 (#520221154439676). Results will be disseminated via publication in peer-reviewed journals and at relevant conferences.

Background Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. Objectives To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. Search strategy Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. Selection criteria RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. Data collection and analysis One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. Main results Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design–outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. Conclusion None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. Systematic review registration This study is registered with PROSPERO, registration number CRD42015015941

Author(s): Hetherington, Elizabeth D; Kurle, Carolyn M; Benson, Scott R; Jones, T Todd; Seminoff, Jeffrey A

The explosive growth of subprime mortgage originations in the early 2000s coincided with the initial formation, and subsequent collapse, of the residential housing bubble. Given their rela...

Studies show that a driver of coastal debris is the rate between debris deposition and resuspension; however, the influence of beach zone topography on the distribution of debris remains poorly understood. Using five years of marine debris data collected by the COASST citizen science program, we explored the spatiotemporal trends in debris abundance within two regions of the United States Pacific Northwest and investigated whether higher debris loads are associated with beach zones that have a higher propensity to trap debris. We found that beaches with larger wood zones had higher debris loads, adding to the growing evidence that backshore areas of beaches act as sinks for debris. Higher debris loads were also associated with beaches that had larger wrack zones suggesting that onshore transport from the marine reservoir is a dominant source of debris. This study provides a long-term baseline of marine debris which managers could use to inform source reduction interventions.

Trophic position and niche width are fundamental components of a species’ ecology, reflecting resource use, and influencing key demographic parameters such as somatic growth, maturation, and survival. Concepts about a species’ trophic niche space have important implications for local management and habitat protection, and can shed light about resilience to changing climate for species occurring over broad spatial scales. For elusive marine animals such as sea turtles, trophic niche is challenging to study, and researchers often rely on other metrics, such as isotopic niche, as a proxy. Here, stable isotope analysis (δ13C and δ15N values) was conducted on bulk skin tissue of 718 green turtles (Chelonia mydas) distributed among 16 foraging areas in the eastern Pacific from the USA to Chile, a range spanning ~10,000 km. Compound‐specific nitrogen isotope analysis of amino acids (CSIA‐AA) was applied to 21 turtles among seven sites. Isotopic niche space was determined via Bayesian ellipse area (BEA) and convex hull area (CHA) analyses of bulk isotope values, which were also used along with amino acid δ15N values to determine trophic position (TP). Substantial variability in bulk tissue δ13C and δ15N values was found within and among sites, and amino acid δ15N values confirmed this was largely due to spatial differences in baseline nitrogen isotopic compositions, but also to a lesser extent from TP differences among the green turtle foraging populations. Isotope niche space varied among sites, influenced by the diversity of prey types and relative input of terrestrial‐ vs. marine‐derived nutrients; BEAs were the most suitable measurement of isotopic niche space due to the larger influence of outlying values with the CHA approach. Amino acid isotope‐derived TP estimates that accounted for local habitat conditions (e.g., mixed seagrass/macroalgae diet) performed the best among several approaches; TP ranged from 2.3 to 3.6, which indicates an omnivorous diet for most populations. In addition to providing additional spatial resolution for δ13C and δ15N isoscapes in the eastern Pacific, especially in coastal habitats, this study further establishes CSIA‐AA as an effective tool to study the trophic ecology of sea turtles across a variety of food webs and habitats.

Although hydrogen isotopes (δ2H) are commonly used as tracers of animal movement, minimal research has investigated the use of δ2H as a proxy to quantify resource and habitat use. While carbon and nitrogen are ultimately derived from a single source (food), the proportion of hydrogen in consumer tissues originates from two distinct sources: body water and food. Before hydrogen isotopes can be effectively used as a resource and habitat tracer, we need estimates of (net) discrimination factors (Δ2HNet) that account for the physiologically mediated differences in the δ2H values of animal tissues relative to that of the food and water sources they use to synthesize tissues. Here, we estimated Δ2HNet in captive green turtles (Chelonia mydas) by measuring the δ2H values of tissues (epidermis and blood components) and dietary macromolecules collected in two controlled feeding experiments. Tissue δ2H and Δ2HNet values varied systematically among tissues, with epidermis having higher δ2H and Δ2HNet values than blood components, which mirrors patterns between keratinaceous tissues (feathers, hair) and blood in birds and mammals. Serum/plasma of adult female green turtles had significantly lower δ2H values compared with juveniles, likely due to increased lipid mobilization associated with reproduction. This is the first study to quantify Δ2HNet values in a marine ectotherm, and we anticipate that our results will further refine the use of δ2H analysis to better understand animal resource and habitat use in marine ecosystems, especially coastal areas fueled by a combination of marine (e.g. micro/macroalgae and seagrass) and terrestrial (e.g. mangroves) primary production.

The mass, chemical composition and toxicological properties of fine particulates (PM

Aims The European Society of Cardiology recommends coronary computed tomography (CCT) for the assessment of low-risk patients with suspected stable angina. We aimed to assess in a real-life setting the relative clinical value of stress echocardiography (SE)- and CCT-guided management in this population. Methods and results Patients with stable chest pain and no prior history of coronary artery disease (CAD) who underwent CCT or SE as the initial investigative strategy were propensity-matched (990 patients each group-age: 59 ± 13.2 years, males: 47.9%) to account for baseline differences in cardiovascular risk factors. Inconclusive tests were 6% vs. 3% (P Conclusion Initial SE-guided management was similar for the detection of obstructive CAD, demonstrated better resource utilization, but was associated with reduced prescription of statins although with no difference in medium-term outcome compared to CCT in this very low-risk population. However, a randomized study with longer follow-up is needed to confirm the clinical value of our findings.

Background Recent recommendations by national and international societies advocate the use of coronary computed tomography (CCT) as the first-line test for the assessment of low-risk patients with suspected stable angina. However limited real-life data exist regarding its relative clinical value versus stress echocardiography (SE)-guided management. Purpose We aimed to assess in a real-life setting the clinical value of stress echocardiography (SE)-guided versus CCT-guided management in patients presenting with stable chest pain and no prior history of coronary artery disease (CAD). Methods We compared the relative feasibility, efficacy and the proportion of patients undergoing downstream testing including revascularisation and their impact on outcome (mortality and myocardial infarction) when CCT versus SE were used as the first line test for the assessment of stable chest pain. Of the patients who underwent CCT (N=2192) or SE (N=2081) between October 2013 and October 2014 only those with suspected stable angina and without previous CAD were selected. The population was propensity-matched (total 1980 patients-990 patients each group) to account for differences in the baseline cardiovascular risk factors. Results The mean age of the population was 59±13.2 years and 949 (47.9%) patients were male. Inconclusive tests were 6% versus 3% (p70%) luminal stenosis on CCT and inducible ischemia on SE detected obstructive CAD by invasive coronary angiography in 63% versus 57% patients (p=0.33). Over the entire follow-up period (median 717 (IQR 93–1069) days) significantly more patients underwent invasive coronary angiography (21.5% versus 7.3%, p Conclusions SE when used for the assessment of patients with stable angina and no prior CAD resulted in more conclusive tests, similar detection of obstructive CAD, less overall invasive coronary angiography and revascularization and less subsequent functional tests compared with CCT. Figure 1 Funding Acknowledgement Type of funding source: None

Background Evidence on the most effective and cost-effective management of ankle fractures is sparse but evolving. A recent large RCT in older patients with unstable fractures found that management with close-contact-casting was functionally equivalent and more cost-effective than internal fixation. We describe temporal and geographic variation in ankle fracture management and estimate the potential savings if close-contact-casting was used more often in older patients. Methods Patients admitted to hospital in England between 2007/08 and 2016/17 with an ankle fracture were identified using routine hospital episode statistics. We tested whether the use of internal fixation, and the proportion of internal fixations using intramedullary implants, changed over time. We estimated the potential annual cost savings if patients aged 60+ years were treated with close-contact-casting rather than internal fixation, in line with emerging evidence. Results Over the 10-year period, there were 223,465 hospital admissions with a primary ankle fracture diagnosis. The incidence (per 100,000) of internal fixation was fairly consistent over time in younger (33.2 in 2007/08, 30.9 in 2016/17) and older (36.5 in 2007/08, 37.4 in 2016/17) patients. The proportion of internal fixations which used intramedullary implants increased in both age groups (17.0–19.5% Conclusions Despite emerging evidence that non-surgical and surgical management achieve equivalent functional outcomes in older patients, the rate of surgical fixation has remained relatively stable over the decade. The health service could achieve substantial savings if a higher proportion of older patients were treated with close-contact-casting, in line with recent evidence.

Introduction Recent recommendations by national and international societies advocate the use of coronary computed tomography (CCT) as the first-line test for the assessment of low-risk patients with suspected stable angina. However limited real-life data exist regarding its relative clinical value versus stress echocardiography (SE)-guided management. We aimed to assess in a real-life setting the clinical value of stress echocardiography (SE)-guided versus CCT-guided management in patients presenting with stable chest pain and no prior history of coronary artery disease (CAD). Methods We compared the relative feasibility, efficacy and the proportion of patients undergoing downstream testing including revascularisation and their impact on outcome (mortality and myocardial infarction) when CCT versus SE were used as the first line test for the assessment of stable chest pain. Of the patients who underwent CCT (N=2192) or SE (N=2081) between October 2013 and October 2014 only those with suspected stable angina and without previous CAD were selected. The population was propensity-matched (total 1980 patients-990 patients each group) to account for differences in the baseline cardiovascular risk factors (Figure 1). Results The baseline characteristics of the propensity-matched population are shown in Table 1. The mean age of the population was 59±13.2 years and 949 (47.9%) patients were male. Inconclusive tests were 6% versus 3% (p 70%) luminal stenosis on CCT and inducible ischemia on SE detected obstructive CAD by invasive coronary angiography in 63% versus 57% patients (p=0.33). Over the entire follow-up period (median 717 (IQR 93-1069) days) significantly more patients underwent invasive coronary angiography (21.5% versus 7.3%, p Conclusions SE when used for the assessment of patients with stable angina and no prior CAD resulted in more conclusive tests, similar detection of obstructive CAD, less overall invasive coronary angiography and revascularization and less subsequent functional tests compared with CCT. These findings suggest that SE may be considered an equally appropriate test compared to CCT in the assessment of low-risk patients with chest pain and no prior CAD. Conflict of Interest None

The deep learning techniques namely Long Short Term Memory (LSTM) network and Bi-directional Gated Recurrent Unit (BGRU) network turn to be de facto to build an optimal assembly line for neural network models. The prevailing state-of-the-art approaches require a substantial amount of labeled data detailed to an unambiguous event in the training phase. In this paper, embedded bi-directional GRU and LSTM learning models is applied for disaster event prediction that uses deep learning techniques to categorize the tweets. The performance of the proposed neural network model is evaluated on CrisisLexT26 benchmarking dataset. The resulting validation accuracy is estimated by comparing LSTM and bi-directional GRU with and without word embeddings. The experiments demonstrate the model selector choose the deep learning techniques to predict the disaster event with reasonably high accuracy.

Between 2014 and 2017, widespread seabird mortality events were documented annually in the Bering and Chukchi seas, concurrent with dramatic reductions of sea ice, warmer than average ocean temperatures, and rapid shifts in marine ecosystems. Among other changes in the marine environment, harmful algal blooms (HABs) that produce the neurotoxins saxitoxin (STX) and domoic acid (DA) have been identified as a growing concern in this region. Although STX and DA have been documented in Alaska (US) for decades, current projections suggest that the incidence of HABs is likely to increase with climate warming and may pose a threat to marine birds and other wildlife. In 2017, a multispecies die-off consisting of primarily Northern Fulmars (Fulmarus glacialis) and Short-tailed Shearwaters (Ardenna tenuirostris) occurred in the Bering and Chukchi seas. To evaluate whether algal toxins may have contributed to bird mortality, we tested carcasses collected from multiple locations in western and northern Alaska for STX and DA. We did not detect DA in any samples, but STX was present in 60% of all individuals tested and in 88% of Northern Fulmars. Toxin concentrations in Northern Fulmars were within the range of those reported from other STX-induced bird die-offs, suggesting that STX may have contributed to mortalities. However, direct neurotoxic action by STX could not be confirmed and starvation appeared to be the proximate cause of death among birds examined in this study.

A 41-year-old woman was admitted with progressive paraesthesia and weakness and was diagnosed with Guillain-Barré syndrome. Following an initial period of recovery with intravenous immunoglobulin treatment, she developed acute chest pain associated with electrocardiographic changes. Investigations excluded acute coronary syndrome and instead confirmed a diagnosis of takotsubo cardiomyopathy, which was treated medically. The patient made an excellent neurological and cardiac recovery. Here we discuss the rarely described association between these two conditions and suggest that patients admitted with Guillain-Barré syndrome may benefit from routine screening with echocardiography.

Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population.To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes.Clinical Practice Research Datalink.We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used.People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval -0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups.Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population.Future research should investigate the decline in prescribing of smoking cessation products; develop an optimal treatment algorithm for smoking cessation; use methods for using instruments with survival outcomes; and develop methods for comparing multivariable-adjusted and instrumental variable estimates.Not all of our code lists were validated, body mass index and Index of Multiple Deprivation had missing values, our results may suffer from residual confounding, and we had no information on treatment adherence.This trial is registered as NCT02681848.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inSmoking is the number one avoidable cause of ill health and death. Experiments suggest that more smokers will quit after being given the drug varenicline than with any other smoking cessation treatment. However, most of the experiments used to license varenicline had a relatively short follow-up ( 1 year) and did not necessarily recruit participants who were representative of smokers seen in a general practice in the UK, who tend to be older, are sicker and more likely to have neuropsychiatric illnesses. In this study, we investigated the outcomes of 287,079 patients prescribed varenicline or nicotine replacement therapy (e.g. nicotine patches and gum). We followed each patient for up to 4 years after they received their prescriptions and matched their data to information on deaths from the Office for National Statistics and hospital admissions. We investigated how often these patients subsequently attended their general practitioner, and how often they received a diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression or anxiety in primary care. We found that patients who were prescribed varenicline were much more likely to quit smoking up to 4 years after they received treatment and subsequently attended their general practitioner less frequently. These findings were robust across the three different analysis methods we used. We also found that patients prescribed varenicline were much less likely to be ill or to die than those prescribed nicotine replacement therapy. However, these results may be because the patients who were prescribed varenicline were much healthier before they received the prescription. Therefore, these differences in health are unlikely to be caused by taking varenicline or quitting smoking. In conclusion, varenicline helped patients quit smoking, but there was little causal evidence that prescribing patients varenicline causally reduced rates of mortality or morbidity compared with prescribing nicotine replacement therapy.

Oil spills can cause severe impacts on seabirds, the extent of which varies by species. We investigated taxon-specific susceptibility using data from the Nestucca and Tenyo Maru oil spills in the northeast Pacific together with seasonally and spatially overlapping baseline beached bird abundance data collected over a 17-year time-period. Multivariate analyses revealed patterns of variation between spill and non-spill data, primarily driven by differences in the relative abundance of common murres (Uria aalge) and northern fulmars (Fulmarus glacialis). In subsequent susceptibility analyses, alcid (Alcidae spp.) carcasses were generally overrepresented in spill data, while gulls (Larus spp.), tubenoses (Procellariformes spp.), and cormorants (Phalacrocoracidae spp.) were generally under-represented. We found that the baseline data had high variability, suggesting a need for many years of baseline data. We propose that where appropriate baseline data exists, this method can be employed to investigate the seabirds most vulnerable to oiling.

BackgroundEvidence of an association between exposure to domestic violence and abuse (DVA) and use of emergency contraception (EC) is lacking in the UK.AimTo quantify the association between exposure to DVA and consultations for EC in general practice.Design and settingNested case-control study in UK general practice.MethodUsing the Clinical Practice Research Datalink, the authors identified all women all women aged 15–49 years registered with a GP between 1 January 2011 and 31 December 2016. Cases with consultations for EC (n = 43 570) were each matched on age and GP against four controls with no consultations for EC (n = 174 280). The authors calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between exposure to DVA in the previous year and consultations for EC. Covariates included age, ethnicity, socioeconomic status, pregnancy, children, alcohol misuse, and depression.ResultsWomen exposed to DVA were 2.06 times more likely to have a consultation for EC than unexposed women (95% CI = 1.64 to 2.61). Women aged 25–39 years with exposure to DVA were 2.8 times more likely to have a consultation for EC, compared with unexposed women (95% CI = 2.08 to 3.75). The authors found some evidence of an independent effect of exposure to DVA on the number of consultations for EC (OR 1.48, 95% CI = 0.99 to 2.21).ConclusionA request for EC in general practice can indicate possible exposure to DVA. Primary care consultation for EC is a relevant context for identifying and responding to DVA as recommended by the World Health Organization and National Institute for Health and Care Excellence guidelines. DVA training for providers of EC should include this new evidence.

Understanding and predicting patterns of spatial organization across ecological communities is central to the field of landscape ecology, and a similar line of inquiry has begun to evolve sub-tidal ...

As relationship marketing research evolved, a number of key constructs emerged. Some scholars have argued that these constructs are not conceptually or empirically distinct. We investigate this phe...

Existing models of short-term sequence memory can account for effects of long-term knowledge on the recall of individual items, but have rarely addressed the effects of long-term sequential constraints on recall. We examine syntactic constraints on the ordering of words in verbal short-term memory in four experiments. People were found to have better memory for sequences that more strongly conform to English syntax, and that errors in recall tended to make output sequences more syntactic (i.e., a syntactic bias). Model simulations suggest that the syntactic biasing in verbal short-term recall was more likely to be accounted for by a redintegration mechanism acting over multiple items in the sequence. The data were less well predicted by a model in which syntactic constraints operate via the chunking of sequences at encoding. The results highlight that models of short-term memory should be extended to include syntactic constraints from long-term representations—most likely via redintegration mechanisms acting over multiple items—but we also note the challenge of incorporating such constraints into most existing models.

Native American use of birds on the Oregon coast is not well known and has never been synthesized to present a regional understanding. We rectify this by analyzing data from 26 zooarchaeological as...

Climate change has exacerbated the occurrence of large-scale sea-surface temperature anomalies, or marine heatwaves (MHW) - extreme phenomena often associated with mass mortality events of marine organisms. Using a combination of citizen science and federal datasets, we investigated the causal mechanisms of the 2014/15 die-off of Cassin's Auklets (Ptychoramphus aleuticus), a small zooplanktivorous seabird, during the NE Pacific MHW of 2013-2015. Carcass deposition followed an effective reduction in the energy content of mesozooplankton, coincident with the loss of cold-water foraging habitat caused by the intrusion of the NE Pacific MHW into the nearshore environment. Models examining interannual variability in effort-controlled carcass abundance (2001-2014) identified the biomass of lipid-poor zooplankton as the dominant predictor of increased carcass abundance. In 2014, Cassin's Auklets dispersing from colonies in British Columbia likely congregated into a nearshore band of cooler upwelled water, and ultimately died from starvation following the shift in zooplankton composition associated with onshore transport of the NE Pacific MHW. For Cassin's Auklets, already in decline due to ocean warming, large-scale and persistent MHWs might represent a global population precipice.

Aims To investigate whether smokers prescribed varenicline had lower risks of serious ill-health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT). Design Observational cohort study of electronic medical records. Setting A total of 370 UK general practices sampled from the Clinical Practice Research Datalink. Participants A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014. Measurements Our primary outcome was all-cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause-specific mortality, all-cause, cause-specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding. Findings People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all-cause hospitalization, incident primary-care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently. Conclusions Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.