Search

Background Social anxiety disorder (SAD) is a chronic and disabling psychiatric disorder associated with low levels of help-seeking. To date, however, scarce research has examined the epidemiology of SAD in veterans. This study examined the prevalence, comorbidities and incremental burden of SAD in relation to suicidality and functioning in a representative sample of U.S. military veterans. Methods A nationally representative sample of 3,157 U.S. veterans completed a web survey containing measures of SAD symptoms, trauma history, psychiatric history and functioning. Multivariable analyses were conducted to examine associations between SAD and psychiatric comorbidities, suicidality and functioning. Results A total 9.5% (n = 272) of the sample screened positive for lifetime SAD. Veterans with SAD were more likely than those without SAD to be younger, female, single, racial/ethnic minorities and to have experienced childhood abuse. They also had substantially elevated rates of comorbid psychiatric disorders, particularly lifetime major depression (odds ratio [OR]=5.8) and posttraumatic stress disorder (OR=3.1), as well as current suicidal ideation (OR=3.3). Veterans with SAD scored lower on measures of functioning, particularly social, emotional and mental health functioning (d’s=0.21–0.34). Limitations Data were collected cross-sectionally using self-report. Conclusions SAD in U.S. veterans is prevalent and associated with psychiatric comorbidities, functional impairment and a more than 3-fold greater risk for suicidal ideation . Given that SAD is associated with low treatment seeking and engagement, it may be undetected and undertreated relative to other psychiatric morbidities. These results underscore the importance of screening, monitoring and treating SAD in this population along with other prevalent mental disorders.

Background Left-sided cardiac volume overload (LCVO) can cause fluid accumulation in lung tissue changing the distribution of ventilation, which can be evaluated by electrical impedance tomography (EIT). Objectives To describe and compare EIT variables in horses with naturally occurring compensated and decompensated LCVO and compare them to a healthy cohort. Animals Fourteen adult horses, including university teaching horses and clinical cases (healthy: 8; LCVO: 4 compensated, 2 decompensated). Methods In this prospective cohort study, EIT was used in standing, unsedated horses and analyzed for conventional variables, ventilated right (VAR) and left (VAL) lung area, linear-plane distribution variables (avg-max VΔZLine, VΔZLine), global peak flows, inhomogeneity factor, and estimated tidal volume. Horses with decompensated LCVO were assessed before and after administration of furosemide. Variables for healthy and LCVO-affected horses were compared using a Mann-Whitney test or unpaired t-test and observations from compensated and decompensated horses are reported. Results Compared to the healthy horses, the LCVO cohort had significantly less VAL (mean difference 3.02; 95% confidence interval .77-5.2; P = .02), more VAR (−1.13; −2.18 to −.08; P = .04), smaller avg-max VΔZLLine (2.54; 1.07-4.00; P = .003) and VΔZLLine (median difference 5.40; 1.71-9.09; P = .01). Observation of EIT alterations were reflected by clinical signs in horses with decompensated LCVO and after administration of furosemide. Conclusions and Clinical Importance EIT measurements of ventilation distribution showed less ventilation in the left lung of horses with LCVO and might be useful as an objective assessment of the ventilation effects of cardiogenic pulmonary disease in horses.

In autism research, the impact of the hidden curriculum within higher education remains neglected. The published experiences of undergraduate and postgraduate students with Autism Spectrum Disorder...

Background: esophageal cancer is increasingly common and carries a poor prognosis. The optimal treatment modality for locally advanced cancer is unknown, with current guidance recommending either neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) followed by surgery. There is a lack of adequately powered trials comparing CT against CRT. We retrospectively compared CT versus CRT using a propensity score weighting approach.Methods: demographic, disease, treatment and outcome data were retrieved from a local database for patients who received neoadjuvant CT or CRT followed by surgery. Inverse probability of treatment weighting (IPTW) was used to balance groups using a propensity score-weighting approach. Groups were assessed for differences in postoperative outcomes and survival. Kaplan-Meier and non-parametric tests were used to compare survival and outcome data as appropriate.Results: data for 284 patients were retrieved. Following IPTW groups were well matched. No significant differences were seen for postoperative complications (CT 64.9% vs. CRT 63.3%, p=0.807), including major complications (24.0% vs. 23.6%, p=0.943) and anastomotic leak (7.8% vs. 5.6%, p=0.526). Significantly higher rates of clinical regression and complete pathological response were seen following CRT (p=0.002 for both). Rates of R0 resection were higher with CRT, CT 79.1% vs. CRT 93.1%, p=0.006. There was no difference between groups for overall or disease-free survival.Conclusion: this study suggests that the significant improvements in local tumour response seen after neoadjuvant CRT compared to CT may not translate to different survival outcomes. However, it must be stressed that adequately powered prospective trials are sti

Objectives: A review of the literature demonstrates that relatively little is known about acute psychiatric presentations in children (0–12 years), compared with adolescents or young adults (12 years+). This study aims to review psychiatric presentations of children to a CAMHS Liaison Service at Children’s Hospital Ireland (CHI) at Tallaght University Hospital over a 10-year period. Methods: A retrospective study was undertaken of case notes of all children aged 12 years and under who were referred to the CAMHS Liaison Service between January 2009 and December 2018 (n = 318). Data were anonymised and inputted into SPSSv25 for analysis. The relationships between presentations and methods of self-harm over time were measured using Pearson’s correlation. Associations between categorical variables were analysed using chi-squared tests. Results: There was a significant increase in presentations of under-12s over the 10-year period (r(8)=0.66, p = 0.02). There was also a significant increase in children presenting with a disturbance of conduct and/or emotions over time (r(8) = 0.79, p < 0.001). There was a significant association between female gender and ingestion (X2 = 12.73, df = 1, p < 0.05) and between male gender and ligature as a method of self-harm (X2 = 5.54, df = 1, p < 0.05). Over half (53%) of children presented with suicidal thoughts and 22% presented with suicidal behaviours. The reported use of ligature as a method of self-harm emerged only from 2012 among cases studied. Conclusions: Children aged 12 years and under are presenting in increasing numbers with acute mental health difficulties, including suicidal thoughts and behaviours. There is a worrying trend in methods of self-harm, particularly in high lethality behaviours such as attempted strangulation.

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary of background data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

We report a disease and mortality event involving swans, seals, and a fox at a wildlife rehabilitation center in the United Kingdom during late 2020. Five swans had onset of highly pathogenic avian influenza virus infection while in captivity. Subsequently, 5 seals and a fox died (or were euthanized) after onset of clinical disease. Avian-origin influenza A virus subtype H5N8 was retrospectively determined as the cause of disease. Infection in the seals manifested as seizures, and immunohistochemical and molecular testing on postmortem samples detected a neurologic distribution of viral products. The fox died overnight after sudden onset of inappetence, and postmortem tissues revealed neurologic and respiratory distribution of viral products. Live virus was isolated from the swans, seals, and the fox, and a single genetic change was detected as a potential adaptive mutation in the mammalian-derived viral sequences. No human influenza-like illness was reported in the weeks after the event

Background This evidence summary synthesised the evidence relating to pharmacological and non-pharmacological interventions in the community to prevent COVID-19/progression to severe disease. An additional aim was to identify potentially modifiable lifestyle factors associated with reduced risk of infection/progression to severe disease. Methods A systematic search of published peer-reviewed articles and non-peer-reviewed pre-prints was undertaken from 1 January 2020 to 19 April 2021; no language restrictions were applied. All potentially eligible papers were exported to Covidence. Titles/abstracts and full texts were single screened for relevance. Data extraction and quality appraisal of included studies was completed by a single reviewer and checked by a second. Results In total, 50 studies, three randomised controlled trials (RCTs), one non-RCT and 46 cohort studies were included. The four included controlled trials tested variations of the pharmacological intervention, ivermectin. While these controlled trials reported a protective effect for ivermectin use, these trials were of poor quality and had serious risk of bias. Across 46 cohort studies, the modifiable lifestyle risk factors identified were obesity, smoking, vitamin D status, physical activity, alcohol consumption and processed meat consumption. These studies reported mixed results in terms of the association between modifiable lifestyle risk factors and poor COVID-19 outcomes. Conclusions At the time of writing there is no high quality evidence of benefit to support pharmacological interventions to prevent COVID-19. Although there were mixed results for the risk factors identified, maintenance of healthy weight, smoking cessation, engaging in physical activity and moderation of alcohol and processed meat consumption are likely to be beneficial to health and should continue to be encouraged.

Background Evidence based decision making is central to population health, particularly during a pandemic. Few studies examine the production and use of evidence in decision-making during crisis management. This study describes and evaluates the provision of rapid evidence products by a single agency to support national decision making. Methods Semi-structured interviews were conducted with a convenience sample of evidence providers (who gathered and disseminated the required evidence) and service users (policy makers). Interviews were transcribed verbatim and analysed using thematic analysis. Quantitative data of work activity were summarised descriptively. Results Three themes were generated from the data: the work, the use and the future, with a fourth theme cross-cutting across these: the team. The work followed clear protocols and was centrally managed. The scope and changing nature of the evidence were highlighted as issues. The service providers reported a strong sense of team work and ‘being in this together', however, the majority of the participants felt that the workload was huge and exhausting and not sustainable long-term. Overall the service users thought the rapid evidence synthesis was indispensable to the decision-making process and had trust and confidence in the work, largely based on existing working relationships with the team. While they recognised that the evidence synthesis support would be an essential component of the continued pandemic response, they did query the sustainability of the process and reflected on the amount of work the team performed. Conclusions This evaluation, drawing on qualitative data, has highlighted that, across the services users and evidence providers, the support provided by HIQA was generally perceived as positive. From the service users' perspective, having access to the team was indispensable to the decision making process. However, the sustainability of the work load was identified as a major challenge.

Byrne, LM, Byrne, PJ, Byrne, EK, Byrne, AP, and Coyle, C. Cross-sectional study of the physical fitness and anthropometric profiles of adolescent hurling, camogie, and Gaelic football players. J Strength Cond Res XX(X): 000-000, 2021-The primary aim of this study was to identify the physical fitness profile of Irish adolescents playing hurling, camogie, and Gaelic football according to age and gender. To establish relationships between the physical fitness tests and anthropometry for these male and female adolescents. This cross-sectional study design included 311 adolescents between age of 13-18 years. Subjects completed a physical fitness test battery of 9 tests which included the following: height, body mass, modified sit and reach (SR), seated medicine ball throw (MBT), countermovement jump (CMJ), standing long jump (SLJ), 15-m sprint, 505 agility, and a 6-minute modified Cooper test (m-CT). Female subjects scored significantly higher in the SR than males, and older adolescents scored significantly higher than younger adolescents (p < 0.05). In the remaining fitness tests (MBT, SLJ, CMJ, 15-m sprint, agility, and m-CT), males outperformed females, males had greater anthropometry scores than females, and older adolescents outperformed and had higher changes in anthropometry than younger counterparts (p < 0.05). Normative data for gender and age-specific percentile values (5th, 10th, 25th, 50th, 75th, 90th, and 95th) for these tests in these adolescent players are provided. These data are useful for clubs, parents, coaches, clinicians, and secondary schools in monitoring adolescents and to provide training programs that develop athletic performance.

Background: Cue Exposure Therapy (CET) has shown efficacy for treating alcohol use disorders (AUDs). Exposure therapy is highly effective for treating anxiety. Both techniques involve repeated, controlled exposures to alcohol or fear-related stimuli. Objectives: We considered the mechanisms of CET for AUDs by comparing it to exposure therapy for anxiety. Method: We conducted a narrative review contrasting theoretical literature examining the mechanisms of CET versus exposure therapy for anxiety. We reviewed RCTs and acute laboratory paradigms examining CET for AUDs. We considered common areas of emerging research, including the use of d-Cycloserine (DCS) and virtual reality (VR). Results: We found evidence that exposure therapy and CET at least partially achieve their effects through extinction learning. We found evidence that CET for AUDs is effective, with comparable benefits to other effective psychosocial treatments. DCS and VR have shown some limited success for augmenting CET for AUDs, so further research is needed to determine their value. Conclusions: There are theoretical and practical similarities between exposure to fear cues and cues of addiction, especially regarding extinction learning. However, these processes are also unique, particularly regarding the differing motivational properties of fear versus reward-related stimuli. We propose that unlike exposure for anxiety, CET takes effect by increasing self-control with each unreinforced exposure. We consider reasons for CET's limited use for AUDs, including its lower acceptability to clients and clinicians. We also note the limited evidence for CET for other substance use disorders, highlighting the need for continued investigation into its mechanisms and efficacy.

To estimate long-term mortality following major burn injury compared with matched controls.The effect of sustaining a major burn injury on long-term life expectancy is poorly understood.Using health administrative data, all adults who survived to discharge after major burn injury between 2003 and 2013 were matched to between 1 and 5 uninjured controls on age, sex, and the extent of both physical and psychological comorbidity. To account for socioeconomic factors such as residential instability and material deprivation, we also matched on marginalization index. The primary outcome was 5-year all-cause mortality, and all patients were followed until death or March 31, 2014. Cumulative mortality estimates were estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to estimate the association of burn injury with mortality.In total, 1965 burn survivors of mean age 44 (standard deviation 17) years with median total body surface area burn of 15% [interquartile range (IQR) 5-15] were matched to 8671 controls and followed for a median 5 (IQR 2.5-8) years. Five-year mortality was significantly greater among burn survivors (11 vs 4%, P0.001). The hazard ratio was greatest during the first year (4.15, 95% CI 3.17-5.42), and declined each year thereafter, reaching 1.65 (95% CI 1.02-2.67) in the fifth year after discharge. Burn survivors had increased mortality related to trauma (mortality rate ratio, MRR 9.8, 95% CI 5-19) and mental illness (MRR 9.1, 95% CI 4-23).Burn survivors have a significantly higher rate of long-term mortality than matched controls, particularly related to trauma and mental illness. Burn follow-up should be focused on injury prevention, mental healthcare, and detection and treatment of new disease.

To measure time to flap coverage after open tibia fractures and assess whether delays are associated with inpatient complications.Retrospective cohort study.One forty level I and II trauma centers in Canada and the United States.Adult patients (≥16 years) undergoing surgery for (1) an open tibia (including ankle) fracture and (2) a soft-tissue flap during their index admission between January 1, 2012, and December 31, 2015, were eligible for inclusion.Time from hospital arrival to definitive flap coverage (in days).The primary outcome was a composite of the following complications occurring during the index admission: (1) deep infection, (2) osteomyelitis, and/or (3) amputation. The primary analysis compared complications between early and delayed coverage groups (≤7 and7 days, respectively) after matching on propensity scores. We also used logistic regression with time to flap coverage as a continuous variable to examine the impact of the duration of delay on complications.There were 672 patients at 140 centers included. Of these, 412 (61.3%) had delayed coverage (7 days). Delayed coverage was associated with a significant increase in complications during the index admission after matching (16.7% vs. 6.2%, P0.001, number needed to harm = 10). Each additional week of delay was associated with an approximate 40% increased adjusted risk of complications (adjusted odds ratio 1.44, 95% confidence interval 1.13-1.82, for each week coverage was delayed, P = 0.003).This is the first multicenter study of flap coverage for tibia fractures in North America. Complications rose significantly when flap coverage was delayed beyond 7 days, consistent with current guideline recommendations. Because the majority of patients did not have coverage within this timeframe, initiatives are required to improve care for patients with these injuries.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Objective: To determine the relationship between body composition (BC), specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. Background: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however evidence is lacking in emergency surgery. Methods: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using pre-operative CT images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modelling. Results: Six hundred and ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs. 45.1%, p = 0.028; 57.5% vs. 42.6%, p = 0.014), 30-day (9.5% vs. 3.6%, p = 0.010; 14.9% vs. 3.4%, p < 0.001), and 1-year mortality (27.4% vs. 11.5%, p < 0.001; 29.7% vs.12.5%, p < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia (OR 2.56 (95%CI 1.12-5.84), p = 0.026) and myosteatosis (OR 4.26 (2.01-9.06), p < 0.001), similarly at 1-year (OR 2.66 (95%CI 1.57-4.52), p < 0.001; OR 2.08 (95%CI 1.26-3.41), p = 0.004). BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95%CI 0.835-0.84). Conclusion: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.

Aims We aimed to determine the effect of increasing body weight upon right ventricular (RV) volumes, energetics, systolic function, and stress responses using cardiovascular magnetic resonance (CMR). Methods and results We first determined the effects of World Health Organization class III obesity [body mass index (BMI) > 40 kg/m2, n = 54] vs. healthy weight (BMI < 25 kg/m2, n = 49) upon RV volumes, energetics and systolic function using CMR. In less severe obesity (BMI 35 ± 5 kg/m2, n = 18) and healthy weight controls (BMI 21 ± 1 kg/m2, n = 9), we next performed CMR before and during dobutamine to evaluate RV stress response. A subgroup undergoing bariatric surgery (n = 37) were rescanned at median 1 year to determine the effects of weight loss. When compared with healthy weight, class III obesity was associated with adverse RV remodelling (17% RV end-diastolic volume increase, P < 0.0001), impaired cardiac energetics (19% phosphocreatine to adenosine triphosphate ratio reduction, P < 0.001), and reduction in RV ejection fraction (by 3%, P = 0.01), which was related to impaired energetics (R = 0.3, P = 0.04). Participants with less severe obesity had impaired RV diastolic filling at rest and blunted RV systolic and diastolic responses to dobutamine compared with healthy weight. Surgical weight loss (34 ± 15 kg weight loss) was associated with improvement in RV end-diastolic volume (by 8%, P = 0.006) and systolic function (by 2%, P = 0.03). Conclusion Increasing body weight is associated with significant alterations in RV volumes, energetic, systolic function, and stress responses. Adverse RV modelling is mitigated with weight loss. Randomized trials are needed to determine whether intentional weight loss improves symptoms and outcomes in patients with obesity and heart failure.

Background & aims: Duodenal-jejunal bypass liners (DJBLs) prevent absorption in the proximal small intestine, the site of fatty acid absorption. We sought to investigate the effects of a DJBL on blood concentrations of essential fatty acids (EFAs) and bioactive polyunsaturated fatty acids (PUFAs). Methods: Sub-study of a multicentre, randomised, controlled trial with two treatment groups. Patients aged 18–65 years with type-2 diabetes mellitus and body mass index 30–50 kg/m 2 were randomised to receive a DJBL for 12 months or best medical therapy, diet and exercise. Whole plasma PUFA concentrations were determined at baseline, 10 days, 6 and 11.5 months; data were available for n = 70 patients per group. Results: Weight loss was significantly greater in the DJBL group compared to controls after 11.5 months: total body weight loss 11.3 ± 5.3% versus 6.0 ± 5.7% (mean difference [95% CI] = 5.27% [3.75, 6.80], p < 0.001). Absolute concentrations of both EFAs, linoleic acid and α-linolenic acid, and their bioactive derivatives, arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, were significantly lower in the DJBL group than in the control group at 6 and 11.5 months follow-up. Total serum cholesterol, LDL-cholesterol and HDL-cholesterol were also significantly lower in the DJBL group. Conclusion: One year of DJBL therapy is associated with superior weight loss and greater reductions in total serum cholesterol and LDL-cholesterol, but also depletion of EFAs and their longer chain derivatives. DJBL therapy may need to be offset by maintaining an adequate dietary intake of PUFAs or by supplementation. Trial registration: ClinicalTrials.gov Identifier NCT02459561.

We document substantial rigidity in household electricity demand in response to large price shocks. We partnered with an electricity retailer to run a field experiment in which randomly-selected households received discounts of up to 50% on their total electricity bill or up to 95% off their per unit cost of electricity for a full month. We show that the quantity of electricity consumed was unaffected by these discounts. Exploiting rich billing, smart meter, and survey data, we document responses that are much more inelastic than previously observed in scenarios that raise prices for a few hours or raise or lower prices for indefinitely-long periods of time. Our results hold even among subgroups that we ex-ante believed were most likely to respond.

STUDY OBJECTIVES: Veterans experience high levels of trauma, psychiatric, and medical conditions that may increase their risk for insomnia. To date, however, no known study has examined the prevalence, risk correlates, and comorbidities of insomnia in a nationally representative sample of veterans. METHODS: A nationally representative sample of 4,069 US military veterans completed a survey assessing insomnia severity; military, trauma, medical, and psychiatric histories; and health and psychosocial functioning. Multivariable analyses examined the association between insomnia severity, psychiatric and medical comorbidities, suicidality, and functioning. RESULTS: A total of 11.4% of veterans screened positive for clinical insomnia and 26.0% for subthreshold insomnia. Greater age and retirement were associated with a lower likelihood of insomnia. Adverse childhood experiences, traumatic life events, lower education and income were associated with greater risk for insomnia. A “dose-response” association was observed for health comorbidities, with increasing levels of insomnia associated with elevated odds of psychiatric and medical conditions (clinical vs no insomnia odds ratio = 1.8–13.4) and greater reductions in health and psychosocial functioning (clinical vs no insomnia Cohen’s d = 0.2–0.4). The prevalence of current suicidal ideation was 3–5 times higher in veterans with clinical and subthreshold insomnia relative to those without insomnia (23.9% and 13.6% vs 4.5%, respectively). CONCLUSIONS: Nearly 2 in 5 US veterans experience clinical or subthreshold insomnia, which is associated with substantial health burden and independent risk for suicidal ideation. Results underscore the importance of assessment, monitoring, and treatment of insomnia in veterans as they transition from the military. CITATION: Byrne SP, McCarthy E, DeViva JC, Southwick SM, Pietrzak RH. Prevalence, risk correlates, and health comorbidities of insomnia in US military veterans: results from the 2019–2020 National Health and Resilience in Veterans Study. J Clin Sleep Med. 2021;17(6):1267–1277.

Uncertainty in the response of clouds to warming remains a significant barrier to reducing the range in projected climate sensitivity. A key question is to what extent cloud feedbacks can be attributed to changes in circulation, such as the strengthening or weakening of ascent or changes in the areas of convecting vs subsiding air. Previous research has shown that, in general circulation models (GCMs), the ‘dynamic’ component of the cloud feedback – that which is due to changes in circulation rather than changes in the thermodynamic properties of clouds (Bony et al., 2006) – is generally small (Byrne and Schneider, 2018). An open question, however, is whether this extends to models at cloud resolving resolutions that explicitly simulate deep convection. Here, we utilize simulations from the Radiative-Convective Equilibrium Model Intercomparison Project (RCEMIP, Wing et al., 2018, 2020) to quantify the impact of circulation on tropical cloud feedbacks. RCE is a simple idealisation of the tropical atmosphere and we focus on simulations in a long channel configuration with uniform sea surface temperatures of 295, 300 and 305K. The dynamic component of the total cloud feedback is substantial for this suite of cloud resolving models (CRMs), and is driven by circulation changes and nonlinearity in the climatological relationship between clouds and circulation. The large spread in dynamic component across models is linked to the extent to which convection strengthens and narrows with warming. This strengthening/narrowing of convective regions is further linked to changes in clear-sky radiative cooling and mid-tropospheric static stability in subsiding regions.

Introduction In oesophageal adenocarcinoma with an apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) there remains debate as to whether oesophagectomy is required. Single Cell RNA sequencing (scRNAseq) enables identification and characterisation of cell populations at higher resolution than diagnostic techniques. Method ScRNAseq was used to determine transcriptomic profiles of cell populations in 24 OAC tumours and 13 matched normal samples. Five were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to validate pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three further patients was used to compare transcriptomic profiles before and after NAT. Cancer cells (CCs) were assigned a cancer stem cell (CSC) score curated from published gene sets. Result We analysed a total of 22,738 single cells forming 29 different cell phenotypes. In two samples with apparent pCR, IHC staining, bulk RNA sequencing and proteomics of post-treatment samples failed to identify CCs. ScRNAseq, conversely, revealed persistent CCs (12/978 and 45/774). Transcriptomic analysis identified upregulation of stem cell markers and high CSC scores in these cells. Conclusion We have shown that CCs persist beneath the lower detection limit of standard approaches in apparent pCR. These cells express marker genes and expression programs consistent with CSCs. CSCs are a critical subpopulation that drive tumour initiation, growth, invasion, metastasis and resistance to therapy. These gene expression programs are not enriched in non-responders and straight to surgery samples. Oesophagus sparing treatment algorithms in pCR may subject patients to unnecessary risk of progression. Take-home message Cancer cells remain within tumours after apparent complete pathological response. These cells express stem cell markers associated with resistance to therapy and cancer progression.

BACKGROUND One hundred thousand Americans are shot annually, and 39,000 die. State laws restricting firearm sales and use have been shown to decrease firearm deaths, yet little is known about what impacts their passage or repeal. We hypothesized that spending by groups that favor firearm restrictive legislation would increase new state firearm restrictive laws (FRLs) and that states increasing these laws would endure fewer firearm deaths. METHODS We acquired 2013 to 2018 state data on spending by groups against firearm restrictive legislation and for firearm restrictive legislation regarding lobbying, campaign, and independent and total expenditures from the National Institute on Money in State Politics. State-level political party representation data were acquired from the National Conference of State Legislatures. Mass shooting data were obtained from the Mass Shooter Database of the Violence Project, and firearm death rates were obtained from Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research and Federal Bureau of Investigation Uniform Crime Reporting databases. Firearm restrictive laws were obtained from the State Firearms Law Database. A univariate panel linear regression with fixed effect for state was performed with change in FRLs from baseline as the outcome. A final multivariable panel regression with fixed effect for state was then used. Firearm death rates were compared by whether states increased, decreased, or had no change in FRLs. RESULTS Twenty-two states gained and 13 lost FRLs, while 15 states had no net change (44%, 26%, and 30%; p = 0.484). In multivariable regression accounting for partisan control of state government, for-firearm restrictive legislation groups outspending against-firearm restrictive legislation groups had the largest association with increased FRLs (β = 1.420; 95% confidence interval, 0.63-2.21; p < 0.001). States that gained FRLs had significantly lower firearm death rates (p < 0.001). Relative to states with no change in FRLs, states that lost FRLs had an increase in overall firearm death of 1 per 100,000 individuals. States that gained FRLs had a net decrease in median overall firearm death of 0.5 per 100,000 individuals. CONCLUSION Higher political spending by groups in favor of restrictive firearm legislation has a powerful association with increasing and maintaining FRLs. States that increased their FRLs, in turn, showed lower firearm death rates. LEVEL OF EVIDENCE Epidemiological, level I.

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.

Introduction: Boerhaave's syndrome is a life-threatening spontaneous perforation of the esophagus associated with significant morbidity and mortality. Historically, thoracotomy has been the mainstay of treatment, but is associated with high morbidity and pain. Minimally invasive approaches provide alternative treatment possibilities. This systematic review together with inclusion of a case series from a tertiary esophagogastric unit assesses current evidence focused on minimally invasive surgical management of this condition. Methods: A systematic review was conducted in line with MOOSE (Meta-analyses Of Observational Studies in Epidemiology) guidelines. Electronic databases PubMed, MEDLINE, and Cochrane Library were searched, and articles focusing on the minimally invasive management of Boerhaave's syndrome were identified and scrutinized. We also report demographics and outcomes for a consecutive case series of patients with acute Boerhaave's syndrome managed via thoracoscopy. Results: Fifteen studies were included comprising 5 retrospective cohort studies and 10 case reports. Management strategies were divided into three categories: thoracoscopic, endoscopic, and laparoscopic. Overall mortality rates for each treatment modality were 2%, 13%, and 33%, and treatment success rates 98%, 38%, and 67%, respectively. Postoperative infective complications were seen in 79% of patients, with only 2 patients requiring salvage thoracotomy. In our local case series, we report 4 consecutive patients managed with thoracoscopy, with a 100% treatment success rate. Conclusion: Minimally invasive approaches in the management of Boerhaave's syndrome are safe and effective. We propose a selective management algorithm involving a minimally invasive approach to management of this life-threatening condition. Registered with local clinical outcomes team as service evaluation. (Approval number sev/0171).

This paper presents a systematic review of participatory methods used in energy system modelling and planning. It draws on a compiled database of fifty-nine studies at a local, regional, and national level detailing analysis on full energy systems down to sectors, modes, and single technologies. The initial aim of the paper is to consolidate and present this growing body of literature, providing a clear understanding of which stakeholder groups have been engaged and what methods have been used to link stakeholder engagement with quantitative analysis. On from this, the progress to date in democratising key decision-making processes is discussed, reflecting on the benefits and challenges of a participatory approach, as well as highlighting gaps within the current body of literature. During the review, two differing spatial levels at subnational (cities, municipalities, or regions) and national scale emerged as separate groups for analysis. A clear distinction between the two groups was the motivation for involving stakeholders. At a subnational level, researchers hoping to build local capacity to bring about real-world change engaged with community representatives, whereas national level studies concerned with generating more impactful energy policy measures involved industry, policymaking, and academic experts. One key finding from the review was that only ten out of the fifty-nine studies reviewed noted some form of collaboration with non-academic stakeholders, and moreover 36% of studies involved just a single interaction with participants. This indicates a lack of progress to date in process democratisation within energy system modelling and planning research.

Introduction Trimethylamine N-oxide (TMAO) is formed in the liver from trimethylamine, and is exclusively generated by gut microbiota from the metabolism of dietary carnitine and choline. Elevated plasma levels have been implicated in the pathogenesis of Type 2 Diabetes and cardiovascular disease. The Endobarrier is an endoscopically implanted duodenal jejunal bypass liner (DJBL) designed to mimic the effects of bariatric surgery leading to significant weight loss and improvements in glycaemic control and we present novel data of its effects on the plasma metabolic profile of these patients. Methods The Endobarrier Trial (NCT02459561) is a large multicentre, randomised, controlled trial across two sites in the UK which recruited 170 patients with Type 2 Diabetes and BMI 30–50 kg/m2. Participants were randomised to receive the DJBL (n=85) for one year or conventional medical therapy, diet and exercise (n=85). Plasma samples were collected from all participants at baseline, 6 months and 1 year and analysed using 1H NMR spectroscopy and multivariate statistical analysis to identify key metabolic perturbations between both patient cohorts. Results A total of 112 patients were followed up for one year. 309 plasma samples were processed and then analysed. A typical 1H NMR plasma spectrum is shown in figure 1. Reduction in plasma concentrations of trimethylamine N-oxide (TMAO) were found in the DJBL group at 6 months and 1 year compared with the control group. Conclusions Raised levels of Plasma TMAO have been associated with the development of diabetes and in this study were found to reduce following 6 months and 1 year of DJBL therapy compared with controls. This is the first study of its kind to explore alterations in the metabolic profiles of patients receiving the DJBL by utilising high field 1H nuclear magnetic resonance (NMR) spectroscopy technique. These results may provide a possible insight into the mechanisms of how this device may elicit its effect on weight loss and glycaemic improvement, by reducing plasma TMAO and potentially altering the gut microbial metabolic function.

We present an analysis of coronal mass ejections (CMEs) observed by the Heliospheric Imagers (HIs) onboard NASA’s Solar Terrestrial Relations Observatory (STEREO) spacecraft. Between August 2008 and April 2014 we identify 273 CMEs that are observed simultaneously, by the HIs on both spacecraft. For each CME, we track the observed leading edge, as a function of time, from both vantage points, and apply the Stereoscopic Self-Similar Expansion (SSSE) technique to infer their propagation throughout the inner heliosphere. The technique is unable to accurately locate CMEs when their observed leading edge passes between the spacecraft; however, we are able to successfully apply the technique to 151, most of which occur once the spacecraft-separation angle exceeds $180^{\circ }$ 180 ∘ , during solar maximum. We find that using a small half-width to fit the CME can result in inferred acceleration to unphysically high velocities and that using a larger half-width can fail to accurately locate the CMEs close to the Sun because the method does not account for CME over-expansion in this region. Observed velocities from SSSE are found to agree well with single-spacecraft (SSEF) analysis techniques applied to the same events. CME propagation directions derived from SSSE and SSEF analysis agree poorly because of known limitations present in the latter.

In esophageal adenocarcinoma (EAC) with apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) debate remains as to whether esophagectomy is required. Recurrence after pCR is not limited to distant metastases outside radiation or resection fields. It is unknown if cancer persists below the lower detection limit of current diagnostic technology. Trials randomising patients with apparent pCR to esophagectomy or active surveillance are currently recruiting in an attempt to spare patients the morbidity of esophagectomy. Methods Single cell (scRNAseq) was performed on fresh tissue taken at surgical resection to determine the transcriptomic profiles of cell populations in 24 EAC tumours and matched normal samples. Five tumour-normal pairs were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to confirm pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three patients was used to compare transcriptomic profiles before and after NAT. Cancer cells were assigned a cancer stem cell module score curated from published gene sets. Results We analysed a total of 22,738 single cells forming 29 different cell states. In two samples with pCR, we repeated the pathological analysis and performed IHC using antibodies to known cancer proteins and identified no residual cancer cells (figure 1A). Bulk tissue RNA (figure 1B) and proteomic analysis did not detect cancer genes or proteins in the pCR samples. ScRNAseq, conversely, revealed small populations of persistent cancer cells in both complete responders (12/978 and 45/774) (figure 1C). Transcriptomic analysis of these residual cells identified upregulation of stem cell markers and high cancer stem cell scores in these remaining cells (figure 1D). Conclusion We have determined the cell states present across multiple different EAC and normal esophageal samples. We have shown cancer cells persisting after NAT, in patients with apparent pCR, beneath the lower detection limit of standard diagnostic approaches. These cells express gene programs consistent with cancer stem cells. Cancer stem cells are a critical subpopulation that drive tumour initiation, growth, and resistance to therapy. Esophagus sparing approaches in pCR may subject patients to risk of progression.

Background Ireland has a high rate of doctor emigration. Difficult working conditions, particularly in the hospital sector, are often cited as a driver of doctor emigration. In October 2019, a random sample of Ireland's hospital doctors were invited to participate in an anonymous online survey about their working conditions. Methods The survey was distributed via the national Medical Register (with the assistance of the Medical Council of Ireland). Invitations were sent to 5356 hospital doctors, stratified by registration status (including interns, trainees, those not in training and consultants). An overall response rate of 20% was achieved (N = 1070). This paper focusses on responses to two free-text survey questions: (1) Do you have any other comments about your work-life balance? (N = 314). (2) Do you have any other comments on your working conditions as a hospital doctor? (N = 469). Results Respondent hospital doctors, at all levels of seniority, were struggling to achieve a balance between work and life. Of the free-text responses received, 8/10 were negative, with work-life balance/imbalance and work-overload being the issues arising most frequently. Respondents discussed how long and unpredictable working hours, combined with a high level of work intensity, meant that they often spent their personal time recovering from work. Conclusions Poor work-life balance has become normalised within Irish hospital medicine. The findings call to action to critically reflect on the sustainability of this way of working for the individual doctors, the wider workforce and the Irish health system.

There has been a revolution in the use of mobile health devices for monitoring physical health. There is more recent interest in whether these devices can also be used for monitoring symptoms of mental illness. This paper considers how stress increases risk of mental deterioration and individuals with mental illness are sensitive to the effects of stress. It discusses how an inexpensive mobile health device could be used for detecting physiological signs of stress: deviations in biometrics such as sleep, activity and arousal may reflect a stress response and increased risk of relapse. These biometrics can allow patients to self-monitor and clinicians to detect early warning signs. This paper reviews the measurement of electrodermal activity, actigraphy and heart rate to predict mental deterioration. It considers the advantages of continuous measurement and reviews studies using mobile health devices to monitor stress and psychosis. It describes the potential for using a mobile health device to manage and monitor severe mental illness in young adults. Finally, this paper considers challenges associated with this approach, particularly with regard to correctly interpreting the physiological data and integrating the mobile health device into clinical practice. This paper concludes a mobile health device has the potential to enhance care by improving detection of early warning signs and increasing the connection between clinicians and their patients.

Currently, nitrogen fertilizers are utilized to meet 48% of the total global food demand. The demand for nitrogen fertilizers is expected to grow as global populations continue to rise. The use of nitrogen fertilizers is associated with many negative environmental impacts and is a key source of greenhouse and harmful gas emissions. In recent years, urease and nitrification inhibitors have emerged as mitigation tools that are presently utilized in agriculture to prevent nitrogen losses and reduce greenhouse and harmful gas emissions that are associated with the use of nitrogen-based fertilizers. Both classes of inhibitor work by different mechanisms and have different physiochemical properties. Consequently, each class must be evaluated on its own merits. Although there are many benefits associated with the use of these inhibitors, little is known about their potential to enter the food chain, an event that may pose challenges to food safety. This phenomenon was highlighted when the nitrification inhibitor dicyandiamide was found as a residual contaminant in milk products in 2013. This comprehensive review aims to discuss the uses of inhibitor technologies in agriculture and their possible impacts on dairy product safety and quality, highlighting areas of concern with regards to the introduction of these inhibitor technologies into the dairy supply chain. Furthermore, this review discusses the benefits and challenges of inhibitor usage with a focus on EU regulations, as well as associated health concerns, chemical behavior, and analytical detection methods for these compounds within milk and environmental matrices.

Two species of eagles (Golden and White‐tailed) bred in Wales during prehistoric and historic times and became regionally extinct as breeding species in the mid‐1800s. They are iconic and charismatic, and discussions about reintroducing them back into the Welsh landscape have been ongoing for years. Reintroductions, however, can be risky, costly and/or contentious. To address these concerns, and to judge whether it is appropriate to reintroduce a regionally extinct species; the “International Union for Conservation of Nature (IUCN)” have produced criteria by which a proposed reintroduction can be assessed. A key criterion is that the potential reintroduction location lies within the former range of the species. In this study, we addressed this criterion by assessing the past distributions of Golden and White‐tailed Eagles within Wales. Using historic observational data, fossil/archaeological records and evidence from place‐names in the Welsh language, we demonstrated strong evidence for the presence of both of these eagle species in Wales in pre‐historic and historic times. We used kernel density functions to model the likely core distributions of each species within Wales. The resulting core distributions encompassed much of central and west‐north Wales for both species, with the White‐tailed Eagle exhibiting a wider core distribution extending into south Wales. Our results fill knowledge gaps regarding the historic ranges of both species in Britain, and support the future restoration of either or both species to Wales.

Background Internationally, systematic screening for sight-threatening diabetic retinopathy (STDR) usually includes annual recall. Researchers and policy-makers support extending screening intervals, citing evidence from observational studies with low incidence rates. However, there is little research around the acceptability to people with diabetes (PWD) and health care professionals (HCP) about changing eye screening intervals. Methods We conducted a qualitative study to explore issues surrounding acceptability and the barriers and enablers for changing from annual screening, using in-depth, semistructured interviews analysed using the constant comparative method. PWD were recruited from general practices and HCP from eye screening networks and related specialties in North West England using purposive sampling. Interviews were conducted prior to the commencement of and during a randomised controlled trial (RCT) comparing fixed annual with variable (6, 12 or 24 month) interval risk-based screening. Results Thirty PWD and 21 HCP participants were interviewed prior to and 30 PWD during the parallel RCT. The data suggests that a move to variable screening intervals was generally acceptable in principle, though highlighted significant concerns and challenges to successful implementation. The current annual interval was recognised as unsustainable against a backdrop of increasing diabetes prevalence. There were important caveats attached to acceptability and a need for clear safeguards around: the safety and reliability of calculating screening intervals, capturing all PWD, referral into screening of PWD with diabetic changes regardless of planned interval. For PWD the 6-month interval was perceived positively as medical reassurance, and the 12-month seen as usual treatment. Concerns were expressed by many HCP and PWD that a 2-year interval was too lengthy and was risky for detecting STDR. There were also concerns about a negative effect upon PWD care and increasing non-attendance rates. Amongst PWD, there was considerable conflation and misunderstanding about different eye-related appointments within the health care system. Conclusions Implementing variable-interval screening into clinical practice is generally acceptable to PWD and HCP with important caveats, and misconceptions must be addressed. Clear safeguards against increasing non-attendance, loss of diabetes control and alternative referral pathways are required. For risk calculation systems to be safe, reliable monitoring and clear communication is required.

BackgroundThe EndoBarrier®(GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98;p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47;p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost > 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0;p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48;p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

Background Trigeminal neuralgia (TGN) is a debilitating disorder, and in patients for whom medical management is not sufficient, there are several therapeutic options. Microvascular decompression (MVD) for TGN has been shown to be highly effective; however, pain does recur after MVD in some patients. Therapeutic options for recurrent TGN are the same as those for primary TGN, including re-exploration of MVD (re-MVD). In this study we review our practice of re-MVD, comparing it with alternative options and assessing its safety and efficacy. Methods Retrospective analysis of prospectively collected data of patients undergoing re-MVD between 2007 and 2016. Results Thirty-two patients underwent re-MVD, all with a Barrow Neurosurgical Institute Pain Index (BNPI) of IV or V. Postoperatively, 87% of patients reported an improvement in their BNPI to III or better, with 50% being BNPI 1 or 2. Eleven patients without distortion or vascular conflict at the time of re-exploration underwent intraoperative neurolysis, and 90% reported improvement in their BNPI. Kaplan-Meier analysis showed a median pain-free period of 36 months after re-MVD. There were no significant complications. Conclusions Re-MVD is a safe and effective method of treating recurrent TGN. Intraoperative neurolysis is an important tool in re-exploration and should be considered when there is no ongoing compression or distortion of the trigeminal nerve.

BACKGROUND: Although a delay of 24 hours for hip fracture repair is associated with medical complications and costs, it is unknown how long patients wait for surgery for hip fracture. We describe novel methods for measuring exact urgent and emergent surgical wait times (in hours) and the factors that influence them. METHODS: Adults aged 45 years and older who underwent surgery for hip fracture (the most common urgently performed procedure) in Ontario, Canada, between 2009 and 2014 were eligible. Validated data from linked health administrative databases were used. The primary outcome was the time elapsed from hospital arrival recorded in the National Ambulatory Care Reporting System until the time of surgery recorded in the Discharge Abstract Database (in hours). The influence of patient, physician and hospital factors on wait times was investigated using 3-level, hierarchical linear regression models. RESULTS: Among 42 230 patients with hip fracture, the mean (SD) wait time for surgery was 38.76 (28.84) hours, and 14 174 (33.5%) patients underwent surgery within 24 hours. Variables strongly associated with delay included time for hospital transfer (adjusted increase of 26.23 h, 95% CI 25.38 to 27.01) and time for preoperative echocardiography (adjusted increase of 18.56 h, 95% CI 17.73 to 19.38). More than half of the hospitals (37 of 72, 51.4%), compared with 4.8% of surgeons and 0.2% of anesthesiologists, showed significant differences in the risk-adjusted likelihood of delayed surgery. INTERPRETATION: Exact wait times for urgent and emergent surgery can be measured using Canada’s administrative data. Only one-third of patients received surgery within the safe time frame (24 h). Wait times varied according to hospital and physician factors; however, hospital factors had a larger impact.

In response to shoreline erosion and potentially more severe storm damage due to climate change and sea level rise, armouring of shorelines using traditional hard structures is likely to increase. An emerging alternative to seawalls and other hard structures is to create ‘living shorelines’ where natural habitats are incorporated into a resilient shoreline stabilization design. Research has shown that functional, multiuse living shorelines provide options for reducing erosion rates and sustaining shoreline stability while supporting intertidal and nearshore habitat. Drawing upon the scientific literature, shoreline management best practices, and the results from an expert opinion survey, we propose a spatial decision framework for multiclass suitability analysis of generic shoreline stabilization options with a focus on the unique challenges and opportunities of South Florida. The results have been incorporated into a web application that can facilitate decision-making in support of nature-based stabiliza...

BACKGROUND AND AIMS: Obesity associated with diabetes mellitus is a significant worldwide problem associated with considerable health care costs. Whilst surgical intervention is effective, it is invasive, costly and associated with complications. This study aims to evaluate the safety and efficacy of the EndoBarrier®, a duodenal-jejunal sleeve bypass as an alternative treatment of diabetes mellitus in obese patients. MATERIALS AND METHODS: This was a multi-centre, non-randomised trial recruiting obese patients with type 2 diabetes from three sites in the UK. Eligible participants had a BMI of 30-50 kg/m2and HbA1c levels of 7.5-10%. The study comprised a 12-month period with the EndoBarrier® inserted and a 6-month follow-up period after it had been explanted. The primary study outcomes were weight, BMI, HbA1c levels and fasting insulin and glucose levels. RESULTS: Forty-five patients were recruited and 31 patients (69%) completed the 12-month study period. Significant reductions in weight (95%CI 0.62-29.38; p

Peripheral nerve injury (PNI) is a rare but preventable complication of surgery. We sought to assess whether the use of minimally invasive surgery (MIS) affects the occurrence of PNI. Using the American College of Surgeons National Surgical Quality Improvement Program database, we examined rates of PNI among patients undergoing appendectomy, hysterectomy, colectomy, or radical prostatectomy between 2005 and 2012. We assessed the effect of MIS, as compared with open surgery, on PNI occurrence using logistic regression. Among 297,532 patients, of whom 175,884 (59.1%) underwent MIS, the rate of PNI was 0.03 per cent. Forty-four patients treated using MIS had PNI (0.03%) as compared with 63 who underwent open surgery (0.05%; P = 0.0002). There was a significant decrease in the proportion of surgeries resulting in PNI (P < 0.0001) over time. In univariate analysis, MIS was associated with a decreased occurrence of PNI (odds ratio 0.48, 95% confidence interval 0.33–0.71), but this became nonsignificant on multivariable analysis (odds ratio 0.71, 95% confidence interval 0.47–1.09). Increased operative time and smoking status were the only factors independently associated with an increased risk of PNI on multivariable analysis. MIS techniques during common abdominal-pelvic surgeries do not appear to increase the risk of PNI. Prolonged operative time and smoking are independently associated with an increased risk of PNI. Quality improvement initiatives to increase awareness of PNI and identify patients at increased risk of this preventable complication should be considered.

Burn-related mortality has decreased significantly over the past several decades. Although often attributed in part to regionalization of burn care, this has not been evaluated at the population level.We conducted a retrospective, population-based cohort study of all patients with 20% or higher total body surface area burn injury in Ontario, Canada. Adult (≥16 years) patients injured between 2003 and 2013 were included. Deaths in the emergency department were excluded. Logistic generalized estimating equations were used to estimate risk-adjusted 30-day mortality. Mortality trends were compared at burn and nonburn centers.Seven hundred seventy-two patients were identified at 84 centers (2 burn, 82 nonburn). Patients were 74% (n = 570) male, of median age 46 (interquartile range [IQR], 35-60) years and median total body surface area 35% (IQR, 25-45). Mortality at 30 days was 19% (n = 149). The proportion of patients treated at a burn center increased from 57% to 71% between 2003 and 2013 (p = 0.07). Average risk-adjusted 30-day mortality rates decreased over time; there were significantly reduced odds of death in 2010 to 2013 compared with 2003 to 2006 (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.25-0.61). Burn centers exhibited significantly reduced mortality from 2003-2006 to 2010-2013 (OR, 0.36; 95% CI, 0.34-0.38) compared with nonburn centers (OR, 0.41; 95% CI, 0.13-1.24).Mortality rates have decreased over time; significant improvements have occurred at burn centers, whereas mortality rates at nonburn centers vary widely. A high proportion of patients continue to receive care outside of burn centers. These data suggest that there are further opportunities to regionalize burn care and in so doing, potentially lower burn-related mortality.Epidemiological study, level III; Therapy, level IV.

BACKGROUND:Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a QuinteT Recruitment Intervention (QRI).PATIENTS/METHODS:The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio-recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization.RESULTS:Recruitment proved to be extremely difficult with only two patients recruited during the first two months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first two months (2/22) to 40% (26/65) in the four months thereafter. Center B, commencing recruitment three months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers.CONCLUSIONS:The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.International Journal of Obesity accepted article preview online, 03 July 2017. doi:10.1038/ijo.2017.153.

YouTube is a global medium used predominantly by young adults (aged 18–49 years). This study examined the quality of YouTube information regarding ACL injury and reconstruction. YouTube was searched on the 13th of June 2015 for “ACL” and “anterior cruciate ligament” with/without associated terms of “injury”, “reconstruction”, and “surgery”. Videos were evaluated by two independent reviewers [EF (Reviewer 1), (Reviewer 2)] using two recognized information scoring systems (Modified DISCERN (MD) 0–5 and JAMA Benchmark 0–4) and an adaptation of a score designed for written ACL information [ACL Specific Score (ASS) 0–25]. The ASS categorized scores as very good (21–25), good (16–20), moderate (11–15), poor (6–10), and very poor (0–5). Number of views/likes/dislikes, animation, and continent of origin and source (e.g., corporate/educational) were recorded. Correlation of video characteristics with number of views was examined using the analysis of variance (ANOVA) model. Agreement between reviewers was assessed by Interclass Correlation Co-efficient (ICC). Following a filtering process of the 964,770 identified videos, 39 videos were retained. The mean MD score was 2.3 (standard deviation (SD) ±0.9) for Reviewer 1 and 2.2 (SD ±0.9) for Reviewer 2 (ICC = 0.7). The mean JAMA score was 2.5(SD ±0.7) for Reviewer 1 and 2.3 (SD ±0.7) for Reviewer 2 (ICC = 0.8). The mean ASS was 6.3 (SD ±3.5) for Reviewer 1 and 4.6 (SD ±2.9) for Reviewer 2 (ICC = 0.9). Five videos achieved moderate score (13%), while 15 (38%) and 19 (49%) scored as poor and very poor, respectively. There was no correlation between number of views and video quality/video source for any scoring system. The majority of videos viewed on YouTube regarding ACL injury and treatment are of low quality.

Background Context Over the last decade, the emergence of social networking websites such as Facebook have revolutionized information dissemination and broadened opportunities to engage in discussions. In particular, having been widely adopted in the younger generation, the use of this medium has become more prevalent in health disorders such as scoliosis in the adolescent population. However, the quality of information on Facebook is unregulated and variable, which may mislead patients in their decision making. Purpose To document the various types of information available and assess the quality of information on Facebook discussion boards using recognized scoring systems. Study Design To evaluate the quality of information on the social network. Patient Sample A search for the keyword “scoliosis” on Facebook was performed and the first 100 pages generated were reviewed. Outcomes Measured SCSS and DISCERN score. Methods Content analysis was performed on discussion boards and personal blogs. Two independent examiners evaluated each site according to scoliosis-specific content score (SCSS) and the DISCERN criteria, both previously used instruments to judge the quality of information on the Internet pertaining to scoliosis. The SCSS range from 0 to 32 (higher score better) and the DISCERN 16 to 80 (higher score better). Results Of the 100 sites reviewed, 33 were discussion boards and personal blogs. Of these, the overall average SCSS was 5.7 (SD 5.8, range 0–20) and the DISCERN was 22.5 (SD 7.6, range 16–45), indicating that using general scoring systems the quality of information provided was overall poor. Conclusion Using recognized scoring systems to analyze Facebook pages used as discussion forums or blogs, we showed that the quality in general was poor. For modern practices to adapt to an era of information exchange via the social network, the orthopedic community should develop ways to incorporate the social media in future patient education.

Pulmonary embolism (PE) is a leading cause of delayed mortality in patients with severe injury. While low-molecular-weight heparin (LMWH) is often favored over unfractionated heparin (UH) for thromboprophylaxis, evidence is lacking to demonstrate an effect on the occurrence of PE. This study compared the effectiveness of LMWH versus UH to prevent PE in patients following major trauma.Data for adults with severe injury who received thromboprophylaxis with LMWH or UH were derived from the American College of Surgeons Trauma Quality Improvement Program (2012-2015). Patients who died or were discharged within 5 days were excluded. Rates of PE were compared between propensity-matched LMWH and UH groups. Subgroup analyses included patients with blunt multisystem injury, penetrating truncal injury, shock, severe traumatic brain injury, and isolated orthopedic injury. A center-level analysis was performed to determine if practices with respect to choice of prophylaxis type influence hospital PE rates.We identified 153,474 patients at 217 trauma centers who received thromboprophylaxis with LMWH or UH. Low-molecular-weight heparin was given in 74% of patients. Pulmonary embolism occurred in 1.8%. Propensity score matching yielded a well-balanced cohort of 75,920 patients. After matching, LMWH was associated with a significantly lower rate of PE compared with UH (1.4% vs. 2.4%; odds ratio, 0.56; 95% confidence interval, 0.50-0.63). This finding was consistent across injury subgroups. Trauma centers in the highest quartile of LMWH utilization (median LMWH use, 95%) reported significantly fewer PE compared with centers in the lowest quartile (median LMWH use, 39%; 1.2% vs. 2.0%; odds ratio, 0.59; 95% confidence interval, 0.48-0.74).Thromboprophylaxis with LMWH (vs. UH) was associated with significantly lower risk of PE. Trauma centers favoring LMWH-based prophylaxis strategies reported lower rates of PE. Low-molecular-weight heparin should be the anticoagulant agent of choice for prevention of PE in patients with major trauma.Therapeutic study, level III.

BackgroundKomagataella phaffiiis a yeast widely used in the pharmaceutical and biotechnology industries, and is one of the two species that were previously calledPichia pastoris. However, almost all laboratory work onK. phaffiihas utilized strains derived from a single natural isolate, CBS7435. There is little information about the sequence diversity ofK. phaffiior the genetic properties of this species.ResultsWe sequenced the genomes of all the known isolates ofK. phaffii.We made a genetic cross between derivatives of two isolates that differ at 44,000 single nucleotide polymorphism sites, and used this cross to analyze the rate and landscape of meiotic recombination. We conducted tetrad analysis by making use of the property thatK. phaffiihaploids do not mate in rich media, which enabled us to isolate and sequence the four types of haploid cell that are present in the colony that forms when a tetra-type ascus germinates.ConclusionsWe found that only four distinct natural isolates ofK. phaffiiexist in public yeast culture collections. The meiotic recombination rate inK. phaffiiis approximately 3.5 times lower than inSaccharomyces cerevisiae, with an average of 25 crossovers per meiosis. Recombination is suppressed, and genetic diversity among natural isolates is low, in a region around centromeres that is much larger than the centromeres themselves. Our work lays a foundation for future quantitative trait locus analysis inK. phaffii.

IntroductionSurgery (oesophagectomy), with neoadjuvant chemo(radio)therapy, is the main curative treatment for patients with oesophageal cancer. Several surgical approaches can be used to remove an oesophageal tumour. The Ivor Lewis (two-phase procedure) is usually used in the UK. This can be performed as an open oesophagectomy (OO), a laparoscopically assisted oesophagectomy (LAO) or a totally minimally invasive oesophagectomy (TMIO). All three are performed in the National Health Service, with LAO and OO the most common. However, there is limited evidence about which surgical approach is best for patients in terms of survival and postoperative health-related quality of life.Methods and analysisWe will undertake a UK multicentre randomised controlled trial to compare LAO with OO in adult patients with oesophageal cancer. The primary outcome is patient-reported physical function at 3 and 6 weeks postoperatively and 3 months after randomisation. Secondary outcomes include: postoperative complications, survival, disease recurrence, other measures of quality of life, spirometry, success of patient blinding and quality assurance measures. A cost-effectiveness analysis will be performed comparing LAO with OO. We will embed a randomised substudy to evaluate the safety and evolution of the TMIO procedure and a qualitative recruitment intervention to optimise patient recruitment. We will analyse the primary outcome using a multi-level regression model. Patients will be monitored for up to 3 years after their surgery.Ethics and disseminationThis study received ethical approval from the South-West Franchay Research Ethics Committee. We will submit the results for publication in a peer-reviewed journal.Trial registration numberNCT10386621.