National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

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Subcortical Source and Modulation of the Narrowband Gamma Oscillation in Mouse Visual Cortex

Primary visual cortex exhibits two types of gamma rhythm: broadband activity in the 30-90 Hz range and a narrowband oscillation seen in mice at frequencies close to 60 Hz. We investigated the sources of the narrowband gamma oscillation, the factors modulating its strength, and its relationship to broadband gamma activity. Narrowband and broadband gamma power were uncorrelated. Increasing visual contrast had opposite effects on the two rhythms: it increased broadband activity, but suppressed the narrowband oscillation. The narrowband oscillation was strongest in layer 4 and was mediated primarily by excitatory currents entrained by the synchronous, rhythmic firing of neurons in the lateral geniculate nucleus (LGN). The power and peak frequency of the narrowband gamma oscillation increased with light intensity. Silencing the cortex optogenetically did not abolish the narrowband oscillation in either LGN firing or cortical excitatory currents, suggesting that this oscillation reflects unidirectional flow of signals from thalamus to cortex

Modelling and development of sustainable energy systems

Due to the recent climate change, organizations all over the globe are developing plans for reducing carbon emissions by developing clean energy technologies and energy efficient devices. However, the path for transition to green energy system is still unclear and in general, the representation of green energy supply for transition pathways is limited. Therefore, this study outlines a plan for getting Swedish energy sector completely carbon neutral by 2050. The approach can also be applicable to the majority of nations worldwide. Computer based simulations are performed on Energy PLAN software for making clean, green and sustainable energy system that can balance every component of entire energy system during the study period 2022 to 2050. This study takes into account the sustainable use of renewable sources for all economic sectors as well as the interchange of energy with nearby nations under the two scenarios. Additionally, the energy system works in tandem with other industries to create a fully carbon-free environment. The results revealed that, 50% de-carbonization is possible till 2035 and 100% de-carbonization is possible till 2050. This enables a discussion of how ambitious 10-year goals might serve as a first step toward the mid-century elimination of fossil fuels from the energy sector

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Screening for glucose intolerance and development of a lifestyle education programme for prevention of Type 2 diabetes in a population with intellectual disabilities

Background: The prevalence of type 2 diabetes mellitus (T2DM) and of cardiovascular disease (CVD) is believed to be higher among people with intellectual disability (ID) than in the general population. However, research on prevalence and prevention in this population is limited. Objectives: The objectives of this programme of work were to establish a programme of research that would significantly enhance the knowledge and understanding of impaired glucose regulation (IGR) and T2DM in people with ID; to test strategies for the early identification of IGR and T2DM in people with ID; and to develop a lifestyle education programme and educator training protocol to promote behaviour change in a population with ID and IGR (or at a high risk of T2DM/CVD). Setting: Leicestershire, UK. Participants: Adults with ID were recruited from community settings, including residential homes and family homes. Adults with mild to moderate ID who had an elevated body mass index (BMI) of ≥ 25 kg/m2 and/or IGR were invited to take part in the education programme. Main outcome measures: The primary outcome of the screening programme was the prevalence of screen-detected T2DM and IGR. The uptake, feasibility and acceptability of the intervention were assessed. Data sources: Participants were recruited from general practices, specialist ID services and clinics, and through direct contact. Results: A total of 930 people with ID were recruited to the screening programme: 58% were male, 80% were white and 68% were overweight or obese. The mean age of participants was 43.3 years (standard deviation 14.2 years). Bloods were obtained for 675 participants (73%). The prevalence of previously undiagnosed T2DM was 1.3% [95% confidence interval (CI) 0.5% to 2%] and of IGR was 5% (95% CI 4% to 7%). Abnormal IGR was more common in those of non-white ethnicity; those with a first-degree family history of diabetes; those with increasing weight, waist circumference, BMI, diastolic blood pressure or triglycerides; and those with lower high-density lipoprotein cholesterol. We developed a lifestyle educational programme for people with ID, informed by findings from qualitative stakeholder interviews (health-care professionals, n = 14; people with ID, n = 7) and evidence reviews. Subsequently, 11 people with ID (and carers) participated in pilot education sessions (two groups) and five people attended education for the feasibility stage (one group). We found that it was feasible to collect primary outcome measures on physical activity and sedentary behaviour using wrist-worn accelerometers. We found that the programme was relatively costly, meaning that large changes in activity or diet (or a reduction in programme costs) would be necessary for the programme to be cost-effective. We also developed a quality development process for assessing intervention fidelity. Limitations: We were able to screen only around 30% of the population and involved only a small number in the piloting and feasibility work. Conclusions: The results from this programme of work have significantly enhanced the existing knowledge and understanding of T2DM and IGR in people with ID. We have developed a lifestyle education programme and educator training protocol to promote behaviour change in this population. Future work: Further work is needed to evaluate the STOP Diabetes intervention to identify cost-effective strategies for its implementation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Being a Muslim in College

What are the differences in the way Muslim students live on college and most non-Muslims? I interviewed people and got their opinions regarding alcohol and premarital sex. I did an observation on what a typical weekend night is like.unpublishe