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The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April–June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training. [ABSTRACT FROM AUTHOR]

Despite improved patient and clinical outcomes, living donor kidney transplantation is underutilized in the United Kingdom, particularly among minority ethnic groups, compared to deceased donor kidney transplantation. This may in part be due to the way in which kidney services present information about treatment options. With a focus on ethnicity, semi structured interviews captured the views of 19 kidney healthcare professionals from two renal centres in West Yorkshire, about the decisional needs and context within which people with advanced kidney disease make transplant decisions. Data were analysed using thematic analysis. Themes were categorized into three groups: 1) Kidney healthcare professionals: language, cultural awareness, trusted personnel, and staff diversity, 2) Patient information resources: timing and setting of education and suitability of patientfacing information and, 3) People with advanced kidney disease: knowledge, risk perception, and cultural/religious beliefs. To our knowledge, this is the first study in the United Kingdom to investigate in depth, healthcare professionals' views on living donor kidney transplantation decision making. Six recommendations for service improvement/delivery to support decision making around living donor kidney transplantation among minority ethnic groups are described. [ABSTRACT FROM AUTHOR]

Despite the growing number of international education programmes, students' response to various pedagogical tools used in these programmes has rarely been examined. Accordingly, business academics teaching on such programmes may not be sure as to which pedagogical tools to use. This study empirically investigates how various teaching tools affect undergraduate students' perception of the learning process. A self-administered survey was used to gather data from 461 undergraduate students in the Middle East, the United Kingdom and the United States. Findings demonstrate that the students from each region have a different opinion with regard to the impact of various teaching tools on their learning outcomes. The implications of this for business educators are discussed. (Contains 3 tables and 1 note.)

Aim: Bariatric‐metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric‐metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. Methods: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric‐metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. Results: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39–3.79); p < 0.001), hypertension (OR: 2.32 (2.19–2.45); p < 0.001) and liver disease (OR: 1.73 (1.58–1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric‐metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). Conclusion: NHS bariatric‐metabolic surgery is used for people with T2DM much later in the disease process when it is less effective. National guidance on bariatric‐metabolic surgery and data from multiple RCTs have had little impact on clinical practice. [ABSTRACT FROM AUTHOR]

Background: Patient information about living donor kidney transplantation is used to supplement conversations between health professionals, people with advanced kidney disease and potential kidney donors. It is not known if the information is designed to support decision‐making about renal replacement options and if it helps people discuss living kidney donation with family and friends. Objective: Critical review of resources used in outpatient kidney consultations to support patients' decision‐making about living kidney donor transplantation. Design: Mixed methods including an audit questionnaire and critical analysis of patient information leaflets. Participants and measurements: All kidney transplant centres and renal units in United Kingdom received a questionnaire to elicit by whom, how, and when information about living kidney donation is delivered. Copies of leaflets were requested. A coding frame was utilised to produce a quality score for each leaflet. Results: Thirty‐nine (54%) units participated. Patients discussed living donor kidney transplantation with nephrologists (100%), living donor nurse (94%), transplant co‐ordinator (94%), and predialysis nurse (86%). Twenty‐three leaflets were provided and reviewed, mean quality scores for inclusion of information known to support shared decision‐making was m = 2.82 out of 10 (range = 0–6, SD = 1.53). Readability scores indicated they were 'fairly difficult to read' (M = 56.3, range = 0–100, SD = 9.4). Few included cultural and faith information. Two leaflets were designed to facilitate conversations with others about donation. Conclusions: Leaflets are unlikely to adequately support decision‐making between options and discussions about donation. Services writing and updating patient leaflets may benefit from our six principles to guide their development. [ABSTRACT FROM AUTHOR]

The current study examines the association between earnings quality (EQ) and investment efficiency (IE) using the conditional effect of legal origin. Further, we assess the influence of the institutional ownership (IOW) on the relationship between EQ and IE within different legal environments, using a sample of 22,446 firm-year observations from the US, the UK, Germany and Japan over the period of 2001–2018. In general, the results provide cross-country evidence that a higher EQ enhances IE. Further, the results indicate that higher EQ can mitigate overinvestment and underinvestment problems by ensuring that firms move toward their optimal level of investment. In addition, the findings reveal that a country's legal environment affects IE with EQ having a stronger association with IE in common law countries as compared to code law economies. In terms of the conditional role of IOW, the findings illustrate that the effect of IOW on the relationship between EQ and IE varies within different legal origins. The results are robust to alternative measures for the main variables examined. This study provides policy implications for investors, managers, regulators, and theorists about the role of the institutional settings on the relation between certain properties of EQ and IE. [ABSTRACT FROM AUTHOR]

Background: After the declaration of COVID-19 as a pandemic last March 2020, several adjustments in surgical services were implemented. Plans are now being formulated for restarting bariatric surgery. The aim of this survey is to capture the practice during the pandemic and the readiness to restart to provide a framework to deal with the backlog of bariatric cases. Method: A survey was delivered to consultant surgeon members of the British Obesity and Metabolic Surgery Society and non-bariatric surgery consultant members of the Association of Upper GI Surgeons. Results: The survey elicited a response rate of 40% (n = 66) among bariatric surgeons and 15.5% (n = 34) between non-bariatric surgeons. The average question response rate was 93% (88–100%). Most of the elective bariatric surgeries and clinics were cancelled early after declaration of the pandemic. Remote technologies for patient education evolved and were used heavily during the pandemic. The average cancelled elective bariatric surgery operations per week was 9. Nearly a quarter of responders reported performing emergency bariatric surgery during the pandemic. Most of the bariatric surgeons reported being ready to restart the service within 1–2 months. Responders recommended using private sector beds to increase NHS capacity and using the link between obesity and poor COVID-19 outcomes to push for prioritisation of bariatric patients. Conclusion: This survey is an attempt to understand the impact of COVID-19 on UK bariatric service and the preparedness to restart. It expressed the bariatric surgery consultants' view of prioritisation of bariatric patients on clinical basis rather than the first-come-first-served basis. [ABSTRACT FROM AUTHOR]

Purpose: Earnings quality is of great concern to corporate stakeholders, including capital providers in international markets with widely varying regulatory pedigrees and ownership patterns. This paper aims to examine the association between the cost of equity capital and earnings quality, contextualised via tests that incorporate the potential for moderating effects around institutional settings. The analysis focuses on and compares evidence relating to (common law) UK/US firms and (civil law) German firms over the period 2005–2018 and seeks to identify whether, given institutional dissimilarities, significant differences exist between the two settings. Design/methodology/approach: First, the authors undertake a review of the extant literature on the link between earnings quality and the cost of capital. Second, using a sample of 948 listed companies from the USA, the UK and Germany over the period 2005 to 2018, the authors estimate four implied cost of equity capital proxies. The relationship between companies' cost of equity capital and their earnings quality is then investigated. Findings: Consistent with theoretical reasoning and prior empirical analyses, the authors find a statistically negative association between earnings quality, evidenced by information relating to accruals and the cost of equity capital. However, when they extend the analysis by investigating the combined effect of institutional ownership and earnings quality on financing cost, the impact – while negative overall – is found to vary across legal backdrops. Research limitations/implications: This paper uses institutional ownership as a mediating variable in the association between earnings quality and the cost of equity capital, but this is not intended to suggest that other measures may be of relevance here and additional research might usefully expand the analysis to incorporate other forms of ownership including state and foreign bases. Second, and suggestive of another avenue for developing the work presented in the study, the authors have used accrual measures of earnings quality. Practical implications: The results are shown to provide potentially important insights for policymakers, creditors and investors about the consequences of earnings quality variability. The results should be of interest to firms seeking to reduce their financing costs and retain financial viability in the wake of the impact of the Covid-19 pandemic. Originality/value: The reported findings extends the single-country results of Eliwa et al. (2016) for the UK firms and Francis et al. (2005) for the USA, whereby both reported that the cost of equity capital is negatively associated with earnings quality attributes. Second, in a further increment to the extant literature (particularly Francis et al., 2005 and Eliwa et al., 2016), the authors find the effect of institutional ownership to be influential, with a significantly positive impact on the association between earnings quality and the cost of equity capital, suggesting in turn that institutional ownership can improve firms' ability to secure cheaper funding by virtue of robust monitoring. While this result holds for the whole sample (the USA, the UK and Germany), country-level analysis shows that the result holds only for the common law countries (the UK and the USA) and not for Germany, consistent with the notion that extant legal systems are a determining factor in this context. This novel finding points to a role for institutional investors in watching and improving the quality of financial reports that are valued by the market in its price formation activity. [ABSTRACT FROM AUTHOR]

Background: Although bariatric surgery is well established as an effective treatment for patients with obesity and type 2 diabetes mellitus (T2DM), there exists reluctance to increase its availability for patients with severe T2DM. The aims of this study were to examine the impact of bariatric surgery on T2DM resolution in patients with obesity and T2DM requiring insulin (T2DM-Ins) using data from a national database and to develop a health economic model to evaluate the cost-effectiveness of surgery in this cohort when compared to best medical treatment (BMT).Methods and Findings: Clinical data from the National Bariatric Surgical Registry (NBSR), a comprehensive database of bariatric surgery in the United Kingdom, were extracted to analyse outcomes of patients with obesity and T2DM-Ins who underwent primary bariatric surgery between 2009 and 2017. Outcomes for this group were combined with data sourced from a comprehensive literature review in order to develop a state-transition microsimulation model to evaluate cost-effectiveness of bariatric surgery versus BMT for patients over a 5-year time horizon. The main outcome measure for the clinical study was insulin cessation at 1-year post-surgery: relative risks (RR) summarising predictive factors were determined, unadjusted, and after adjusting for variables including age, initial body mass index (BMI), duration of T2DM, and weight loss. Main outcome measures for the economic evaluation were total costs, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) at willingness-to-pay threshold of GBP£20,000. A total of 2,484 patients were eligible for inclusion, of which 1,847 had 1-year follow-up data (mean age of 51 years, mean initial BMI 47.2 kg/m2, and 64% female). 67% of patients no longer required insulin at 1-year postoperatively: these rates persisted for 4 years. Roux-en-Y gastric bypass (RYGB) was associated with a higher rate of insulin cessation (71.7%) than sleeve gastrectomy (SG; 64.5%; RR 0.92, confidence interval (CI) 0.86-0.99) and adjustable gastric band (AGB; 33.6%; RR 0.45, CI 0.34-0.60; p < 0.001). When adjusted for percentage total weight loss and demographic variables, insulin cessation following surgery was comparable for RYGB and SG (RR 0.97, CI 0.90-1.04), with AGB having the lowest cessation rates (RR 0.55, CI 0.40-0.74; p < 0.001). Over 5 years, bariatric surgery was cost saving compared to BMT (total cost GBP£22,057 versus GBP£26,286 respectively, incremental difference GBP£4,229). This was due to lower treatment costs as well as reduced diabetes-related complications costs and increased health benefits. Limitations of this study include loss to follow-up of patients within the NBSR dataset and that the time horizon for the economic analysis is limited to 5 years. In addition, the study reflects current medical and surgical treatment regimens for this cohort of patients, which may change.Conclusions: In this study, we observed that in patients with obesity and T2DM-Ins, bariatric surgery was associated with high rates of postoperative cessation of insulin therapy, which is, in turn, a major driver of overall reductions in direct healthcare cost. Our findings suggest that a strategy utilising bariatric surgery for patients with obesity and T2DM-Ins is cost saving to the national healthcare provider (National Health Service (NHS)) over a 5-year time horizon. [ABSTRACT FROM AUTHOR]

Recent years have witnessed a significant shift in the financial reporting frameworks available in the UK and Ireland affecting entities of all sizes with the Financial Reporting Council issuing three financial reporting standards replacing the extant UK GAAP. This paper reports the results of a content analysis of 151 comment letters sent to the standard-setter in response to its policy proposal. The paper explains why the standard-setter stepped back from its controversial proposal to enforce IFRS for SMEs based on the absence of public accountability. Additionally, the standard-setter addressed all concerns positively apart from two, representing two anomalies. First, despite being opposed by the majority of the respondents, the standard-setter published a new framework for wholly-owned subsidiaries of listed companies allowing them to make substantially less disclosure. Second, the standard-setter is yet to respond to the call by the accounting profession and the Not-for-profit sector to publish a sector-specific framework. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to evaluate vitamin D levels, in correlation with age, body mass index (BMI), gender and ethnicity, in patients with gastrointestinal disorders (GID). Background: Vitamin D deficiency (VDD) is a global health issue, affecting over 1 billion people. A great body of evidence has shown that it can lead to increased morbidity and mortality. Furthermore, latitude, sedentary lifestyle, limited sunlight exposure, ageing and the presence of comorbidities and chronic illnesses, places patients at an increased risk of VDD. Methods: 305 consecutive patients, with GID, were assessed for vitamin D levels, using a two-step competitive binding immunoenzymatic assay. Patients were then classified as adequate (50-150nmol/l), insufficient (25-50nmol/l) and deficient (<25nmol/l). Results: 62% of the investigated subjects had low vitamin D levels. From this group, 132 patients (43.3%) had insufficient vitamin D levels, 57 (18.7%) had deficient levels and 116 (38%) had adequate levels. Age was not significantly different in the 3 groups (p=0.29). Interestingly, vitamin D levels were significantly lower in men (39.23±23.62) compared to women (50.68±24.46) (p=0.0001). The BMI was significantly higher in patients with insufficient vitamin D levels. Being of Asian ethnicity had a positive influence on vitamin D levels (B=0.076) (p<0.0001). 71.4% of patients, with IBD, and 60% of patients, with abnormal liver function, had low vitamin D levels. Conclusion: VDD has a high prevalence in patients with GID in particular IBD and liver disease in the United Kingdom. Routine vitamin D testing and supplementations in the case of deficiency and suboptimal level of vitamin D for patients with hepatobiliary, pancreatic, kidney, malabsorptive and restrictive diseases/surgeries is recommended. [ABSTRACT FROM AUTHOR]

Background: An excessively long-blind end of the alimentary limb following a Roux-en-Y gastric bypass (RYGB), known as a 'candy cane' (CC), may cause symptoms including abdominal pain, regurgitation and vomiting. Very few studies have examined the efficacy of surgical resection of the CC.Objectives: The aim of this study was to assess sensitivity of preoperative diagnostic tools for CC, as well as perioperative outcomes and symptom resolution after CC revision surgery.Setting: High volume bariatric centre of excellence, United Kingdom.Methods: Observational study of CC revisions from 2010 to 2017.Results: Twenty-eight CC revision cases were identified (mean age 45 ± 9 years, female preponderance 9:1). Presenting symptoms were abdominal pain (86%), regurgitation/vomiting (43%), suboptimal weight loss (36%) and acid reflux (21%). Preoperative tests provided correct diagnosis in 63% of barium contrast swallows, 50% of upper gastrointestinal endoscopies and 29% computed tomographies. Patients presenting with pain had significantly higher CC size as compared with pain-free group (4.2 vs. 2 cm, p = 0.001). Perioperative complications occurred in 25% of cases. Complete or partial symptom resolution was documented in 73% of patients undergoing CC revision. Highest success rates were recorded in the regurgitation/vomiting group (67%).Conclusion: Surgical revision of CC is associated with good symptom resolution in the majority of patients, especially those presenting with regurgitation/vomiting. However, it carries certain risk of complications. CC diagnosis may frequently be missed; hence more than one diagnostic tool should be considered when investigating symptomatic patients after RYGB. [ABSTRACT FROM AUTHOR]

The Brexit referendum will remain as a milestone in contemporary European history. The British exit from the EU is not going only to shape future relations between the EU and the UK, but it will shape the relation between Brussels and other member states as well. This study aims to investigate the main claims for the leave campaigns which affected the general opinion to vote for the exit. The two main points investigated in this paper are: first, the historical background regarding the UK and the EU, the reasons for the first refusal to the European integration projects during the 1950, and the changes in the British situation which pushed the UK to seek the membership for a decade before being able to join the EEC in the 1970s; and second, national identity, which affected Britain's late entry to the EU, and shaped relations between London and Brussels during the British membership. The paper concludes that, unfortunately, British citizens in general were not aware of the full facts regarding the above two points. [ABSTRACT FROM AUTHOR]

Background: The objective of the study is to analyze procedural and safety outcomes associated with bariatric surgery and describe the characteristics of patients undertaking bariatric procedures in England between April 2006 and March 2012.Methods: This is a retrospective cohort study of all adult patients in England diagnosed with obesity and undergoing bariatric surgery as a primary procedure in NHS-funded sites between April 2006 and March 2012 using data sourced from the Hospital Episode Statistics dataset. Length of stay (LOS), 30-day readmission, and post-surgery complication were analyzed as primary outcomes. Socio-demographic background, provider type, procedure volume, and comorbidities were all analyzed as potential explanatory variables.Results: Gastric bypass (GBP, 12,628) was the most utilized procedure, followed by gastric banding (GB, 6872) and sleeve gastrectomy (SG, 3251). The most prevalent comorbidity was type 2 diabetes (23%). Inpatient mortality was low (≤ 0.15%) for all procedure types. LOS and the risks of both post-operative complication and 30-day readmission were significantly lower for GB, relative to those for GBP and SG. Ethnicity, geographical area, surgery type, and volume were all associated with LOS, risk of readmission, and complication. Provider type and deprivation were further associated with LOS while age correlated with readmission only. An increasing comorbidity burden was associated with an increased risk of both readmission and complication.Conclusions: Gastric bypass was the most frequently reported procedure in England across the observation period. While utilization across all procedure types increased between 2007 and 2010, overall uptake of bariatric surgery in England represents only a small proportion of the eligible population. Readmission and complication rates were lower for gastric banding relative to those for either gastric bypass or sleeve gastrectomy. The observed inpatient mortality rate was low across all procedure types. [ABSTRACT FROM AUTHOR]

Summary: Baseline demographic characteristics and operations undertaken for patients having bariatric surgery in the United Kingdom are largely unknown. This study aimed to describe the profile of patients having primary bariatric surgery in the National Health Service (NHS) or by self‐pay, and associated operations performed for both pathways. The National Bariatric Surgery Registry dataset for 5 years between January 2015 and December 2019 was used. 34 580 patients underwent primary bariatric surgery, of which 75.9% were NHS patients. Mean patient age and initial body mass index were significantly higher for NHS compared to self‐pay patients (mean age 45.8 ± 11.3 [SD] vs. 43.0 ± 12.0 years and initial body mass index 48.0 ± 7.9 vs. 42.9 ± 7.3 kg/m2, p <.001). NHS patients were more likely to have obesity‐related complications compared to self‐pay patients: prevalence of Type 2 diabetes mellitus 27.7% versus 8.3%, hypertension 37.1% versus 20.1%, obstructive sleep apnoea 27.4% versus 8.9%, severely impaired functional status 19.3% versus 13.9%, musculoskeletal pain 32.5% versus 20.1% and being on medication for depression 31.0% versus 25.9%, respectively (all p <.001). Gastric bypass was the most commonly performed primary NHS bariatric operation 57.2%, but sleeve gastrectomy predominated in self‐pay patients 48.7% (both p <.001). In contrast to self‐pay patients, NHS patients are receiving bariatric surgery only once they are older and at a much more advanced stage of obesity‐related disease complications. [ABSTRACT FROM AUTHOR]

Since December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),causative pathogen of coronavirus disease 2019 (COVID-19), has triggered a pandemic with challenges for health care systems around the world. Researchers have studied and published on the subject of SARS-CoV-2 and the disease extensively. What is the significance of articles published, shared and cited in the early stages of such a pandemic? A systematic literature search in a time frame of 12 months and analysis rating using Principle Component Analysis (PCA) and Multiple Factor Analysis (MFA) were performed. The 100 most cited COVID-19 articles were identified. The majority of these articles were from China (n ​= ​54), followed by United States of America (USA) (n ​= ​21) and United Kingdom (UK) (n ​= ​8). All articles were published in high-ranked, peer-reviewed journals, with research focusing onthe the diagnosis, transmission and therapy of COVID-19. The level of evidence of the 100 most cited COVID-19 articles on average was low. In the early stages of a pandemic, new and innovative research can emerge and be highly cited, regardless of the level of evidence. [ABSTRACT FROM AUTHOR]

Background: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown., Objectives: The aims of this study were to determine patient awareness, views and priorities for outcome reporting in bariatric surgery, and to provide recommendations for future surgeon-specific outcome reporting through the United Kingdom National Bariatric Surgery Registry., Setting: Bariatric surgical unit in a UK university teaching hospital., Methods: We adapted a previously validated questionnaire and surveyed the views of 150 patients in a single bariatric surgical unit. We collected data concerning awareness, views, and future priorities for outcome reporting., Results: A full 73% of participants were unaware they could access SSOR. Of the participants that were unaware, 75% stated that they would have accessed SSOR had they been aware they could. Of the participants that had previously accessed SSOR, 86% stated they understood the data, although 61% indicated it did not influence their choice of surgeon. The majority of participants favored public release of outcome reports at the surgeon-level (75%) and hospital-level (83%). The 3 main priorities indicated by participants for future outcome reporting were complication rates (91%), patient reported outcome measures (90%), and reoperation rate (89%), all at the surgeon level., Conclusion: Patient awareness of outcome reporting is poor. Efforts must be made to increase awareness of SSOR. Patients should be incorporated as key stakeholders in determining future outcome reporting in bariatric surgery., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Bile acids (BA) regulate postprandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The postprandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effects of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on postprandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon, and ghrelin. Twelve healthy volunteers underwent a mixed meal test 60 min after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg), or no BA in a randomized crossover study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin, and fibroblast growth factor 19 were measured prior to BA administration at -60 and 0 min (just prior to mixed meal) and 15, 30, 60, 120, 180, and 240 min after the meal. UDCA and CDCA provoked differential gut hormone responses; UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced postprandial secretion of GIP, with an associated reduction in postprandial insulin secretion. Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmed in obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions. NEW & NOTEWORTHY Oral CDCA and UDCA have different effects on gut and pancreatic hormone secretion. A single dose of CDCA increased fasting secretion of the hormones GLP-1 and OXM with an accompanying increase in insulin secretion. CDCA also reduced postprandial GIP secretion, which was associated with reduced insulin. In contrast, UDCA did not change gut hormone secretion fasting or postprandially. Oral CDCA could be beneficial to patients with obesity and diabetes.

Next-generation sequencing (NGS) efforts have established catalogs of mutations relevant to cancer development. However, the clinical utility of this information remains largely unexplored. Here, we present the results of the first eight patients recruited into a clinical whole-genome sequencing (WGS) program in the United Kingdom. We performed PCR-free WGS of fresh frozen tumors and germline DNA at 75× and 30×, respectively, using the HiSeq2500 HTv4. Subtracted tumor VCFs and paired germlines were subjected to comprehensive analysis of coding and noncoding regions, integration of germline with somatically acquired variants, and global mutation signatures and pathway analyses. Results were classified into tiers and presented to a multidisciplinary tumor board. WGS results helped to clarify an uncertain histopathological diagnosis in one case, led to informed or supported prognosis in two cases, leading to de-escalation of therapy in one, and indicated potential treatments in all eight. Overall 26 different tier 1 potentially clinically actionable findings were identified using WGS compared with six SNVs/indels using routine targeted NGS. These initial results demonstrate the potential of WGS to inform future diagnosis, prognosis, and treatment choice in cancer and justify the systematic evaluation of the clinical utility of WGS in larger cohorts of patients with cancer., (© 2018 Schuh et al.; Published by Cold Spring Harbor Laboratory Press.)