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IntroductionFaecal incontinence (FI) is a common condition with a significant impact on quality of life (QoL). Neuromodulation treatments delivered by members of the multidisciplinary team including sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS) are options for FI refractory to conservative management. The aim of this study was to assess whether a successful treatment with one neuromodulation modality corresponds with success in the other.MethodsA retrospective review of a prospectively managed neuromodulation database identified 15 patients who had undergone both PTNS and SNS. The definition of success of each treatment was a >50% improvement in any of The St. Mark's Incontinence Score, Manchester Health Questionnaire, or weekly faecal urgency or FI episodes.ResultsComplete data from 12 patients was available for assessment and PTNS was delivered as the first treatment in nine patients. Overall, seven patients (58%) had successful PTNS treatment, with 10 (83%) having a successful SNS trials. Of the seven patients who had successful PTNS treatment, six patients (85.4%) went on to have success with SNS. Of the five patients who failed PTNS, four (80%) went on to have SNS success. Five (71%) of those who had positive PTNS outcomes had permanent SNS implantation as their final treatment decision.ConclusionThis study suggests that there is no clear relationship between successful PTNS treatment and an SNS trial period which may be explained by differing mechanisms of action or the potential placebo effect of PTNS. Further work is required to investigate any association in larger studies to inform clinical practice.

Background Irritable bowel syndrome with diarrhoea is characterised by frequent, loose or watery stools with associated urgency, resulting in marked reduction of quality of life. Ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, has been shown to benefit patients with irritable bowel syndrome with diarrhoea. Objective To evaluate the effect of ondansetron in irritable bowel syndrome with diarrhoea. Design Phase III, parallel-group, randomised, double-blind, multicentre, placebo-controlled trial in 400 patients, with embedded mechanistic studies. Setting Hospital, primary care and community. Participants Eighty participants meeting Rome IV criteria for irritable bowel syndrome with diarrhoea. Intervention Ondansetron 4 mg (dose titrated up to two tablets three times a day) or matched placebo for 12 weeks. Main outcome measures Clinical – Primary patient-reported end point was % ‘Food and Drug Administration-defined responders’ over 12 weeks. Secondary end points were worst abdominal pain intensity, worst urgency, stool consistency, stool frequency, anxiety, depression and dyspepsia at 12 and 16 weeks. Main outcome measures Mechanistic – Whole gut transit time, faecal water, protease (FP), bile acids and assessment of rectal sensitivity using a barostat. Results Clinical – The study closed early due to slow recruitment. Between 1 January 2018 and 11 May 2020, 80 patients were recruited and randomised (20% of target), 37 to ondansetron, 43 to placebo. Discontinuations (4 ondansetron; 2 placebo) meant 75 completed the 12-week trial treatment. There were four protocol violations. In the intention-to-treat analysis, 15 (40.5%) on ondansetron were primary end-point responders (95% CI 24.7% to 56.4%), and 12 (27.9%) on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Pain intensity reduction occurred in 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32. Improvement in stool consistency occurred in 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07. Use of rescue medication, loperamide, was lower on ondansetron [7 (18.9%) vs. 17 (39.5%)]. Average stool consistency in the final month of treatment reduced significantly more on ondansetron, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved dyspepsia score (SFLDQ), adjusted mean difference –3.2 points [SE 1.43, 95% CI (–6.1 to –0.4), p = 0.028]. There were no serious adverse events. Mechanistic – mean (SD). Ondansetron increased whole gut transit time between baseline and week 12 by 3.8 (9.1) hours on ondansetron, significantly more than on placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8, p = 0.26. Ondansetron did not significantly alter protease, faecal water or bile acids. Changes in referral pathways substantially reduced referrals, impairing recruitment, which meant the study was underpowered. Conclusion Our results are consistent with previous studies and confirmed ondansetron improves stool consistency and urgency but showed minor effect on pain. We plan to undertake a simplified version of this trial overcoming the changed referral pathways by recruiting in primary care, using software linked to primary care records to identify and randomise patients with irritable bowel syndrome with diarrhoea to ondansetron or placebo and remotely follow their progress; thus minimising barriers to recruitment. Trial registration This trial is registered as ISRCTN17508514. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information. Plain language summary Background Irritable bowel syndrome with diarrhoea is characterised by frequent, loose, or watery bowel movements with marked reduction of quality of life. A previous small study suggested ondansetron benefits patients with irritable bowel syndrome with diarrhoea. Methods A clinical trial aiming to recruit 400 patients meeting established criteria for irritable bowel syndrome with diarrhoea from 18 centres throughout the UK. Patients received either ondansetron or placebo for 12 weeks but neither the investigator and nor patient could tell which they were receiving. They recorded their worst abdominal pain, stool frequency and consistency daily. The main end point was the proportion of patients meeting a standard recommended by the U.S. Food and Drug Administration (FDA). Being called a “FDA responder” meant they showed reductions to both pain and days with loose bowel movements. Other less important end points included pain intensity, stool consistency and frequency. We also measured the time for content to pass through the gut (whole gut transit time). Results The study closed early due to slow recruitment with 80 patients randomised. There were 40.5% of responders in the ondansetron group and 27.9% in the placebo group; however, due to low numbers these differences could be due to chance. Ondansetron produced a significant improvement in average stool consistency in the final month of treatment. Ondansetron slowed whole gut transit time which increased from baseline to 12 weeks by a mean of 3.8 hours, while it fell 2.2 hours on placebo, a difference unlikely to be due to chance. Conclusion These results are consistent with previous studies showing that ondansetron improves stool consistency and slows transit. However, because the numbers recruited were smaller than planned, the apparent improvement in “FDA responder” rate could have been due to chance. A further larger trial is needed to confirm the benefit of ondansetron which should be done in primary care where most patients are to be found. Scientific summary Background Irritable bowel syndrome (IBS), which affects around 10% of the population, accounts for 1.8 million consultations/year in primary care in England and Wales (0.6 million patients). Symptoms of IBS with diarrhoea (IBS-D) include frequent, loose or watery stools with associated urgency, which can severely limit socialising, travelling and eating out, with resulting marked reduction in quality of life and loss of work productivity. Around one-third of all IBS patients meet Rome criteria for IBS-D. When patients are asked to rank symptoms in order of importance, the erratic bowel habit is rated first, followed by abdominal pain and, for those with diarrhoea, urgency. Ondansetron, a 5-hydroxytryptamine-3 (5HT3) receptor antagonist, has an excellent safety record for over 20 years as an antiemetic, but is only exceptionally used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, crossover pilot study, benefited patients with IBS-D. While the current trial was ongoing, a separate trial in the USA using a fixed dose bimodal release formulation (3 mg ondansetron +9 mg delayed release formulation) also reported improvement in stool consistency but not pain. Objectives Our primary aim was to determine the efficacy of generic ondansetron compared to placebo in controlling the symptoms of IBS-D using the US FDA-recommended combined end point in which a responder is defined as a patient who met the response criteria for both pain and bowel habit for 6 out of 12 weeks of the trial. Secondary end points included its effect on the characteristic abnormalities of stool consistency, frequency and urgency as well as abdominal pain, satisfactory relief of IBS symptoms, mood and use of rescue medication and to determine the effect of 12 weeks ondansetron over the 1 month after discontinuation, as well as safety. The study also included mechanistic studies to examine the correlation of rectal sensitivity and compliance, faecal bile acids (FBAs) and proteases and postprandial sigmoid motility with the baseline symptoms of our IBS-D patients. We also attempted to determine whether ondansetron significantly altered these biomarkers compared to placebo. Methods Treatment of irritable bowel syndrome using titrated ondansetron trial (TRITON) was a multisite, parallel-group, randomised, double-blinded, placebo-controlled trial, with embedded mechanistic studies within selected sites. Our aim was to determine the superiority of ondansetron compared with placebo. We aimed to randomise 400 patients with IBS-D on a 1 : 1 basis to receive either ondansetron or placebo. Both treatments were administered for 12 weeks in oral doses ranging from 4 mg every third day to 24 mg daily. Dose titration was undertaken in the first 2 weeks of the study to avoid constipation, which at a standard dose occurs in one-quarter of patients. This was achieved by frequent consultation with the research nurse, starting with 1 × 4 mg tablet per day and increasing in increments every 2 days to a maximum of 2 tablets thrice daily. If constipation developed, the treatment was stopped to allow the return of bowel movements and then restarted at a lower dose, typically one every alternate day or one every second day. Rescue medication of loperamide was discouraged but allowed exceptionally for uncontrolled diarrhoea and was documented in the daily diary. The primary outcome of response for both reduction in pain intensity and improvement in stool consistency was assessed over the 12 weeks post randomisation. Secondary and safety outcomes were measured up to 16 weeks post randomisation. Symptoms that were recorded daily included (1) stool consistency and abdominal pain (measured by both paper diary and daily text message); (2) stool frequency, urgency of defaecation, use of rescue medication (defined as the use of loperamide) over 12 weeks of treatment and the answer to the question in the diary ‘Overall, have you had satisfactory relief from your IBS symptoms in the past week?’. Irritable bowel syndrome symptom severity [measured by the IBS Severity Scoring System (IBS-SSS)], dyspepsia [using the Short Form Leeds Dyspepsia Questionnaire (SFLDQ)], quality of life and mood [using the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression Scale (HADS) questionnaires], and somatic symptoms [using the Patient Health Questionnaire 12 Somatic Symptoms (PHQ-12) questionnaire] were assessed by patient-reported questionnaires at the baseline and 12 weeks post randomisation. The trial also assessed possible underlying mechanisms of any effect of ondansetron on changes in the primary and secondary end points. Whole gut transit was measured at baseline and 12 weeks using radio-opaque markers and an abdominal X-ray. High-resolution manometry was performed at baseline and after 8–11 weeks of treatment at two centres to assess whether ondansetron decreased the number of high-amplitude propagating contractions (HAPCs) or increased the percentage time occupied by cyclical retrograde propagated contractions. Barostat assessment was performed at baseline and after 8–11 weeks of treatment at two centres in order to assess if ondansetron increases rectal compliance or decreases sensitivity (manifested as increased pressure thresholds for pain and urgency). Stool samples were assessed for faecal water % (FW), faecal protease (FP) and FBAs. Clinical results The study closed early due to slow recruitment with just 80 patients randomised; 37 to ondansetron and 43 to placebo. Four patients discontinued ondansetron and one placebo during 12-week randomised treatment. Four were excluded from the per-protocol population due to major protocol violations. In the intention to treat (ITT) analysis, 15 patients (40.5%) on ondansetron achieved the primary end point response [95% confidence interval (CI) 24.7% to 56.4%], compared to 12 (27.9%) patients on placebo (95% CI 14.5% to 41.3%), p = 0.19, adjusted OR 1.93 (0.73, 5.11). Response for pain intensity reduction was achieved by 17 (46.0%) on ondansetron (95% CI 29.9% to 62.0%) and 16 (37.2%) on placebo (95% CI 22.8% to 51.7%), p = 0.32, adjusted OR 1.61 (0.63 to 4.12). Response for stool consistency improvement was reported by 25 (67.6%) on ondansetron (95% CI 52.5% to 82.7%) and 22 (51.2%) on placebo (95% CI 36.2% to 66.1%), p = 0.07, adjusted OR 2.45 (0.92, 6.52). Overall use of the rescue medication, loperamide, was 39.5% (n = 17) on placebo compared with 18.9% (n = 7) on ondansetron. However, by week 12, loperamide use fell to 13.5% on ondansetron versus 25.6% on placebo. Average stool consistency in the final month of treatment fell significantly more on ondansetron than placebo, adjusted mean difference –0.5 [standard error (SE) 0.25, 95% CI (–1.0 to –0.02), p = 0.042]. Ondansetron improved the dyspepsia score (SFLDQ) significantly more than placebo; the largest reduction being in symptoms of indigestion and nausea. The adjusted mean difference in the total score compared to placebo was –3.2 points [SE 1.43, 95% CI (–6.1, to –0.4), p = 0.028]. Ondansetron was well tolerated with most adverse reactions being mild or moderate and not significantly greater than on placebo. The commonest was constipation, reported in 32% on ondansetron and 23% on placebo, of which 75% and 80%, respectively, were rated as mild. Just two patients withdrew citing constipation as the cause. Mechanistic results Results are expressed as mean (SD). Comparing baseline and week 12 showed ondansetron increased average whole gut transit 3.78 (9.1) hours on ondansetron significantly more than placebo –2.2 (10.3), p = 0.01. Mean volume to reach urgency threshold using the barostat increased on ondansetron by 84 (61) ml and 38 (48) ml on placebo, n = 8; the difference was not significant, p = 0.26. Too few underwent manometry to allow meaningful assessment of the effect of ondansetron but anecdotally one patient who had a dramatic clinical improvement showed a loss of HAPCs and an increase in retrograde contractions, but this could have been due to chance. Ondansetron appeared not to significantly alter FP, though overall the increase in whole gut transit time from baseline to week 12 was correlated with a decrease in FP. There were no significant changes in FBAs and no evidence that ondansetron altered these though we did confirm that we had effectively excluded those with bile acid diarrhoea (BAD). The ratio of secondary to primary bile acids, a measure of bacterial metabolism of bile acids, increased substantially on ondansetron from 9.7 (7.08) to 21.4 (32.9) and less so on placebo from 22.84 (58.23) to 28.61 (31.42). However, owing to small numbers and wide variability these differences were not significant. Limitations Two previous studies in Nottingham had recruited 120 and 136 IBS-D patients within 2 years so we did not anticipate problems with recruitment. However, changes in referral pathways from primary to secondary care substantially reduced referrals to our coinvestigators who were all in secondary care, thus impairing recruitment. The power calculations required 400 to achieve 90% power to detect a 15% difference in primary end point, so the study is substantially underpowered. Use of loperamide did somewhat complicate interpretation since those on placebo used more rescue medication reducing the size of the effect on transit and stool consistency. Conclusion Despite being underpowered for our primary end point, our results are consistent with previous studies and confirmed ondansetron improves stool consistency but showed little effect on pain. Ondansetron significantly slowed whole gut transit time. Ondansetron reduced sensitivity to rectal distension more than placebo without altering compliance, but numbers were too small to achieve statistical significance. This could plausibly contribute to the reduction in urgency and stool frequency but needs repeating with larger numbers to be sure it was not due to chance. We found no evidence that rectal sensitivity was related to either faecal protease or bile acids. The manometry studies were underpowered but anecdotally ondansetron appeared to alter rectosigmoid motor patterns in a way that could reduce inflow of stool to the rectum. Future work We plan to do a simplified version of this trial, using an efficient and remote process, to overcome the changed referral pathways by recruiting in primary care. We will search for patients who have had a diagnosis of chronic diarrhoea and the recommended screening including a normal full blood count, a negative tissue transglutaminase (excluding coeliac disease) and a normal faecal calprotectin using software linked to primary care records. This will allow rapid screening of large numbers of patients to identify and approach patients with IBS-D who meet criteria to take part in a randomised trial of ondansetron or placebo, thus minimising barriers to recruitment. We would remove the pain threshold, which would increase the number of eligible patients and facilitate recruitment. Not allowing loperamide as rescue medication would simplify interpretation and dropouts would be treated as treatment failures. Further streamlining by removing all additional tests that were included in the current trial, as well as efficient trial processes, including e-consent, remote blood and stool samples (if required), and online questionnaires would also optimise recruitment. Study registration This trial is registered as ISRCTN17508514. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme and will be published in full in Efficacy and Mechanism Evaluation; Vol. 10, No. 9. See the NIHR Journals Library website for further project information.

IntroductionThe increasing number of dams approaching obsolescence drives a need for knowledge about riparian restoration associated with dam removal. Restoring woody vegetation on exposed reservoir beds following dam removal is essential to stabilizing sediment, reconnecting riverine and terrestrial systems, and providing future sources of shade, nutrients, and wood. Revegetation after dam removal on many rivers can be challenging due to rapidly drying sediment, low sediment nutrient content, and heavy ungulate browse pressure. Revegetation in Elwha River restoration, the largest dam removal to date, used large woody debris (LWD) to mitigate moisture and nutrient limitation but ungulate browsing has constrained woody plant growth in many coarse sediment deposits. We evaluated potential for LWD to reduce ungulate browsing following Elwha dam removal.MethodsWe studied LWD mitigation of browsing in the largest former reservoir and a comparable valley upriver with a natural floodplain. We measured browse intensity in randomly located plots stratified by four levels of LWD extent, from no LWD to complete LWD enclosure.ResultsLWD reduced browse intensity four-fold in the former reservoir, but only in plots fully surrounded by LWD. Partial LWD enclosure provided little browse reduction. We obtained similar results in the upriver valley, where browse intensity was somewhat lower except within wood clusters. Wood-mediated browse reduction was slightly greater in the former reservoir than in the upriver valley. Protection from browse was greatest for plant species preferred by ungulates.DiscussionThese results suggest forest restoration after dam removal can be expedited by surrounding young trees with large logs. Planting within LWD clusters or placing LWD clusters in restoration sites can facilitate establishment of forest islands in strategic locations. These forest islands can support dispersal of seeds and marine derived nutrients, reconnect established forest to the river, and potentially advance restoration by decades.

Objective Barrett’s oesophagus (BO) is a precursor lesion, via dysplastic phases, to oesophageal adenocarcinoma. Although overall risk from BO is low, it has been shown to adversely affect health-related quality of life (HRQOL). The aim was to compare dysplastic BO patients’ HRQOL pre-endoscopic therapy (pre-ET) and post-ET. The pre-ET BO group was also compared with other cohorts: non-dysplastic BO (NDBO), those with colonic polyps, gastro-oesophageal reflux disease (GORD) and healthy volunteers.Design Participants in the pre-ET cohort were recruited prior to their endotherapy and HRQOL questionnaires provided pre-ET and post-ET. Wilcoxon rank test was used to compare the pre-ET and post-ET findings. The Pre-ET group was compared to the other cohorts’ HRQOL results using multiple linear regression analysis.Results Pre-ET group of 69 participants returned the questionnaires prior to and 42 post-ET. Both the pre-ET and post-ET group showed similar levels of cancer worry, despite the treatment. No statistical significance was found for symptoms scores, anxiety and depression or general health measures with the Short Form-36 (SF-36) Score. Education for the BO patients was overall lacking with many of the pre-ET group still reporting unanswered questions about their disease.The Pre-ET group was compared with NDBO group (N=379), GORD (N=132), colonic polyp patients (N=152) and healthy volunteers (N=48). Cancer worry was similar between the NDBO group and the Pre-ET group, despite their lower risk of progression. GORD patients had worse symptom scores from a reflux and heartburn perspective. Only the healthy group has significantly better scores in the SF-36 and improved hospital anxiety and depression scores.Conclusion These findings suggest that there is a need to improve HRQOL for patients with BO. This should include improved education and devising-specific patient-reported outcome measures for BO to capture relevant areas of HRQOL in future studies.

Abstract Quantification and monitoring of lean body mass is an important component of nutrition assessment to determine nutrition status and muscle loss. The negative impact of reduced muscle mass and muscle function is increasingly evident across acute and chronic disease states but is particularly pronounced in patients with cancer. Ultrasound is emerging as a promising tool to directly measure skeletal muscle mass and quality. Unlike other ionizing imaging techniques, ultrasound can be used repeatedly at the bedside and may compliment nutritional risk assessment. This review aims to describe the current use of skeletal muscle ultrasound (SMUS) to measure muscle mass and quality in patients with acute and chronic clinical conditions and its ability to predict functional capacity, severity of malnutrition, hospital admission, and survival. Databases were searched from their inception to August 2021 for full‐text articles in English. Relevant articles were included if SMUS was investigated in acute or chronic clinical contexts and correlated with a defined clinical outcome measure. Data were synthesized for narrative review due to heterogeneity between studies. This review analysed 37 studies (3100 patients), which met the inclusion criteria. Most studies (n = 22) were conducted in critical care. The clinical outcomes investigated included functional status at discharge (intensive care unit‐acquired weakness), nutritional status, and length of stay. SMUS was also utilized in chronic conditions such as chronic obstructive pulmonary disease, chronic heart failure, and chronic renal failure to predict hospital readmission and disease severity. Only two studies investigated the use of SMUS in patients with cancer. Of the 37 studies, 28 (76%) found that SMUS (cross‐sectional area, muscle thickness, and echointensity) showed significant associations with functional capacity, length of stay, readmission, and survival. There was significant heterogeneity in terms of ultrasound technique and outcome measurement across the included studies. This review highlights that SMUS continues to gain momentum as a potential tool for skeletal muscle assessment and predicting clinically important outcomes. Further work is required to standardize the technique in nutritionally vulnerable patients, such as those with cancer, before SMUS can be widely adopted as a bedside prognostic tool.

Abstract Background Bile acid diarrhoea (BAD) can be severely debilitating and negatively affect patients’ quality of life (QoL). We carried out a multi-centre prospective study exploring QoL outcomes in patients with BAD after treatment with colesevelam. Methods Patients with or without a positive 23-seleno-25-homotaurocholic acid (SeHCAT) scan were recruited and categorised into four groups: SeHCAT negative control group (CG), idiopathic BAD, post-cholecystectomy (PC) and post-terminal ileal resection for Crohn’s disease (CD). Patients with a positive SeHCAT were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL was evaluated by EQ-5D-3L, SF-36, IBDQ-32 at each visit (where relevant). Patients with a negative SeHCAT (CG cohort) completed one set of questionnaires before being discharged from the study. Results 47 patients (BAD = 24, PC = 12, CD = 11) completed paired QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. There was a significant improvement in IBDQ-32 mean scores before and after treatment in CD patients [134.6 (95%CI 112.5–156.6) and 158.4 (136.1–180.6), respectively (p = 0.007). Following treatment, BAD patients had significantly improved mean SF-36 scores in the “Role limitation due to physical health” dimension (p = 0.02) and in the overall mental component summary (p = 0.03). Prior to starting treatment, BAD patients had the lowest scores in the ‘activity’ dimension of the EQ-5D-3L (p = 0.04), which improved significantly after treatment (p = 0.002). Overall, the BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, while the PC cohort showed a general decline in mean scores after treatment. 55% of patients clinically responded to treatment of which 41.7%, 58.3% and 81.8% responded from the BAD, PC and CD groups respectively. Correlations between those deemed as responders with improvements on the SF-36 and EQ-5D dimensions were not statistically significant. Conclusion Our results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists. Trial registration Ethical approval REC Ref: 16/LO/1325.

Abstract Limited efforts have been made in assessing the effect of genome-wide profiling of RNA splicing-related variation on lung cancer risk. In the present study, we first identified RNA splicing-related genetic variants linked to lung cancer in a genome-wide profiling analysis and then conducted a two-stage (discovery and replication) association study in populations of European ancestry. Discovery and validation were conducted sequentially with a total of 29,266 cases and 56,450 controls from both the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium as well as the OncoArray database. For those variants identified as significant in the two datasets, we further performed stratified analyses by smoking status and histological type and investigated their effects on gene expression and potential regulatory mechanisms. We identified three genetic variants significantly associated with lung cancer risk: rs329118 in JADE2 (P = 8.80E−09), rs2285521 in GGA2 (P = 4.43E−08), and rs198459 in MYRF (P = 1.60E−06). The combined effects of all three SNPs were more evident in lung squamous cell carcinomas (P = 1.81E−08, P = 6.21E−08, and P = 7.93E−04, respectively) than in lung adenocarcinomas and in ever smokers (P = 9.80E−05, P = 2.70E−04, and P = 2.90E−05, respectively) than in never smokers. Gene expression quantitative trait analysis suggested a role for the SNPs in regulating transcriptional expression of the corresponding target genes. In conclusion, we report that three RNA splicing-related genetic variants contribute to lung cancer susceptibility in European populations. However, additional validation is needed, and specific splicing mechanisms of the target genes underlying the observed associations also warrants further exploration.

Abstract This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the 75selenium-homotaurocholic acid (SeHCAT) scan. A prospective observational study was undertaken. Patients with chronic diarrhoea (> 6 weeks) being investigated for potential BAD with SeHCAT scan provided stool samples for measurement of FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group, post-cholecystectomy, idiopathic BAD and post-operative terminal ileal resected Crohn’s disease. Stool samples were collected at baseline and 8-weeks post treatment to determine whether FBA measurement could be used to monitor therapeutic response. 113 patients had a stool sample to directly compare with their SeHCAT result. FBA concentrations (μmol/g) and interquartile ranges in patients in the control group (2.8; 1.6–4.2), BAD (3.6; 1.9–7.2) and post-cholecystectomy cohort 3.8 (2.3–6.8) were similar, but all were significantly lower (p 15% (2.6; 1.6–4.2); (p

IntroductionBile acid diarrhoea (BAD) is a common disorder that results from an increased loss of primary bile acids and can result in a change in microbiome. The aims of this study were to characterise the microbiome in different cohorts of patients with BAD and to determine if treatment with a bile acid sequestrant, colesevelam, can alter the microbiome and improve microbial diversity.Materials and methodsPatients with symptoms of diarrhoea underwent 75-selenium homocholic acid (75SeHCAT) testing and were categorised into four cohorts: idiopathic BAD, post-cholecystectomy BAD, post-operative Crohn’s disease BAD and 75SeHCAT negative control group. Patients with a positive 75SeHCAT (

Summary: Background: There is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. Methods: A prospective cohort study of adults (≥18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. Findings: Independent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR) = 0.42 (95%CI: 0.34–0.52), P 5 [RR = 0.33 (95%CI: 0.21–0.50), P 3 days [RR = 0.84 (95%CI: 0.76–0.92), P

Background/Aims Epidemiological associations have implicated factors associated with Westernization, including the Western diet, in the development of inflammatory bowel disease (IBD). The role of diet in IBD etiopathogenesis, disease control and symptom management remains incompletely understood. Few studies have collected data on the dietary habits of immigrant populations living with IBD. Our aim was to describe the dietary practices and beliefs of British South Asians with IBD. Methods A 30-item questionnaire was developed and consecutively administered to 255 British South Asians with IBD attending gastroenterology clinics in the United Kingdom. Results Fifty-one percent of participants believed diet was the initiating factor for their IBD and 63% felt diet had previously triggered disease relapse. Eighty-nine percent avoided certain dietary items in the belief that this would prevent relapse. The most commonly avoided foods and drinks were spicy and fatty foods, carbonated drinks, milk products, alcohol, coffee, and red meat. A third of patients had tried a whole food exclusion diet, most commonly lactose- or gluten-free, and this was most frequently reported amongst those with clinically active IBD (P = 0.02). Almost 60% of participants avoided eating the same menu as their family, or eating out, at least sometimes, to prevent IBD relapse. Conclusions British South Asians with IBD demonstrate significant dietary beliefs and food avoidance behaviors with increased frequency compared to those reported in Caucasian IBD populations. Studies in immigrant populations may offer valuable insights into the interaction between diet, Westernization and cultural drift in IBD pathogenesis and symptomatology.

Introduction Barrett’s oesophagus (BO) is common and is a precursor to oesophageal adenocarcinoma with a 0.33% per annum risk of progression. Surveillance and follow-up services for BO have been shown to be lacking, with studies showing inadequate adherence to guidelines and patients reporting a need for greater disease-specific knowledge. This review explores the emerging role of dedicated services for patients with BO.Methods A literature search of PubMed, MEDLINE, Embase, Emcare, HMIC, BNI, CiNAHL, AMED and PsycINFO in regard to dedicated BO care pathways was undertaken.Results Prospective multicentre and randomised trials were lacking. Published cohort data are encouraging with improvements in guideline adherence with dedicated services, with one published study showing significant improvements in dysplasia detection rates. Accuracy of allocation to surveillance endoscopy has been shown to hold cost savings, and a study of a dedicated clinic showed increased discharges from unnecessary surveillance. Training modalities for BO surveillance and dysplasia detection exist, which could be used to educate a BO workforce. Qualitative and quantitative studies have shown patients report high levels of cancer worry and poor disease-specific knowledge, but few studies have explored follow-up care models despite being a patient and clinician priority for research.Conclusions Cost–benefit analysis for dedicated services, considering both financial and environmental impacts, and more robust clinical data must be obtained to support this model of care in the wider health service. Greater understanding is needed of the root causes for poor guideline adherence, and disease-specific models of care should be designed around clinical and patient-reported outcomes to address the unmet needs of patients with BO.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

Abstract Background Irritable bowel syndrome (IBS) with diarrhoea (IBS-D) is a common and chronic condition that can significantly impair quality of life. The emergence of new drugs for IBS-D has been slow and there is a need for new treatments, including drug-free treatments, which are easy to use and suitable for different patient groups. Currently available drug-free treatments include Enterosgel®, an intestinal adsorbent approved for use in IBS-D and acute diarrhoea and available over-the-counter in the UK and 30 countries worldwide. The aim of this randomised, double-blind, placebo-controlled, multi-centre study is to test the efficacy and safety of Enterosgel® compared to placebo in symptomatic treatment in IBS-D. Methods/design We will recruit 430 participants with IBS-D from approximately 30 primary and secondary care sites in England. Participants meeting the required abdominal pain and stool consistency criteria over a 2-week screening period will be randomly allocated to receive blinded treatment (Enterosgel® or placebo) for 8 weeks. This will be followed by an 8-week open-label treatment phase with Enterosgel®. Participants will be allowed to adjust their daily dosage during both phases based on their symptoms. Participants will then return to standard care and those who responded to treatment will receive a follow-up call 8 weeks later. Co-medication with loperamide will be permitted and use recorded. The primary outcome measure is the percentage of participants defined as responders for abdominal pain and stool consistency during at least 4 weeks in the 8-week blinded phase. Secondary outcome measures include stool frequency, stool consistency, abdominal pain, bloating, urgency, adequate relief, questionnaire scores and rescue medication use. Exploratory outcomes will be assessed in subsets of participants including qualitative and quantitative data on faecal microorganisms and biomarkers and gut-related measurements from magnetic resonance imaging data. Discussion This is the first large scale randomised controlled trial investigating Enterosgel® in IBS-D. A study design with blinded phase followed by an open-label phase was chosen to encourage participation and study completion. Demonstrating that Enterosgel® is effective and safe in IBS-D could encourage adoption by patients and healthcare professionals and foster future clinical trials assessing its use in related conditions. Trial registration ISRCTN17149988. Prospectively registered on 14 November 2017.

Background: Chronic constipation affects 1–2% of adults and significantly affects quality of life. Beyond the use of laxatives and other basic measures, there is uncertainty about management, including the value of specialist investigations, equipment-intensive therapies using biofeedback, transanal irrigation and surgery. Objectives: (1) To determine whether or not standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback is more clinically effective than standardised specialist-led habit training alone, and whether or not outcomes of such specialist-led interventions are improved by stratification to habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or habit training alone based on prior knowledge of anorectal and colonic pathophysiology using standardised radiophysiological investigations; (2) to compare the impact of transanal irrigation initiated with low-volume and high-volume systems on patient disease-specific quality of life; and (3) to determine the clinical efficacy of laparoscopic ventral mesh rectopexy compared with controls at short-term follow-up. Design: The Chronic Constipation Treatment Pathway (CapaCiTY) research programme was a programme of national recruitment with a standardised methodological framework (i.e. eligibility, baseline phenotyping and standardised outcomes) for three randomised trials: a parallel three-group trial, permitting two randomised comparisons (CapaCiTY trial 1), a parallel two-group trial (CapaCiTY trial 2) and a stepped-wedge (individual-level) three-group trial (CapaCiTY trial 3). Setting: Specialist hospital centres across England, with a mix of urban and rural referral bases. Participants: The main inclusion criteria were as follows: age 18–70 years, participant self-reported problematic constipation, symptom onset > 6 months before recruitment, symptoms meeting the American College of Gastroenterology’s constipation definition and constipation that failed treatment to a minimum basic standard. The main exclusion criteria were secondary constipation and previous experience of study interventions. Interventions: CapaCiTY trial 1: group 1 – standardised specialist-led habit training alone (n = 68); group 2 – standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (n = 68); and group 3 – standardised radiophysiological investigations-guided treatment (n = 46) (allocation ratio 3 : 3 : 2, respectively). CapaCiTY trial 2: transanal irrigation initiated with low-volume (group 1, n = 30) or high-volume (group 2, n = 35) systems (allocation ratio 1 : 1). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy performed immediately (n = 9) and after 12 weeks’ (n = 10) and after 24 weeks’ (n = 9) waiting time (allocation ratio 1 : 1 : 1, respectively). Main outcome measures: The main outcome measures were standardised outcomes for all three trials. The primary clinical outcome was mean change in Patient Assessment of Constipation Quality of Life score at the 6-month, 3-month or 24-week follow-up. The secondary clinical outcomes were a range of validated disease-specific and psychological scoring instrument scores. For cost-effectiveness, quality-adjusted life-year estimates were determined from individual participant-level cost data and EuroQol-5 Dimensions, five-level version, data. Participant experience was investigated through interviews and qualitative analysis. Results: A total of 275 participants were recruited. Baseline phenotyping demonstrated high levels of symptom burden and psychological morbidity. CapaCiTY trial 1: all interventions (standardised specialist-led habit training alone, standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback and standardised radiophysiological investigations-guided habit training alone or habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback) led to similar reductions in the Patient Assessment of Constipation Quality of Life score (approximately –0.8 points), with no statistically significant difference between habit training alone and habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (–0.03 points, 95% confidence interval –0.33 to 0.27 points; p = 0.8445) or between standardised radiophysiological investigations and no standardised radiophysiological investigations (0.22 points, 95% confidence interval –0.11 to 0.55 points; p = 0.1871). Secondary outcomes reflected similar levels of benefit for all interventions. There was no evidence of greater cost-effectiveness of habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or stratification by standardised radiophysiological investigations compared with habit training alone (with the probability that habit training alone is cost-effective at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year gain; p = 0.83). Participants reported mixed experiences and similar satisfaction in all groups in the qualitative interviews. CapaCiTY trial 2: at 3 months, there was a modest reduction in the Patient Assessment of Constipation Quality of Life score, from a mean of 2.4 to 2.2 points (i.e. a reduction of 0.2 points), in the low-volume transanal irrigation group compared with a larger mean reduction of 0.6 points in the high-volume transanal irrigation group (difference –0.37 points, 95% confidence interval –0.89 to 0.15 points). The majority of participants preferred high-volume transanal irrigation, with substantial crossover to high-volume transanal irrigation during follow-up. Compared with low-volume transanal irrigation, high-volume transanal irrigation had similar costs (median difference –£8, 95% confidence interval –£240 to £221) and resulted in significantly higher quality of life (0.093 quality-adjusted life-years, 95% confidence interval 0.016 to 0.175 quality-adjusted life-years). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy resulted in a substantial short-term mean reduction in the Patient Assessment of Constipation Quality of Life score (–1.09 points, 95% confidence interval –1.76 to –0.41 points) and beneficial changes in all other outcomes; however, significant increases in cost (£5012, 95% confidence interval £4446 to £5322) resulted in only modest increases in quality of life (0.043 quality-adjusted life-years, 95% confidence interval –0.005 to 0.093 quality-adjusted life-years), with an incremental cost-effectiveness ratio of £115,512 per quality-adjusted life-year. Conclusions: Excluding poor recruitment and underpowering of clinical effectiveness analyses, several themes emerge: (1) all interventions studied have beneficial effects on symptoms and disease-specific quality of life in the short term; (2) a simpler, cheaper approach to nurse-led behavioural interventions appears to be at least as clinically effective as and more cost-effective than more complex and invasive approaches (including prior investigation); (3) high-volume transanal irrigation is preferred by participants and has better clinical effectiveness than low-volume transanal irrigation systems; and (4) laparoscopic ventral mesh rectopexy in highly selected participants confers a very significant short-term reduction in symptoms, with low levels of harm but little effect on general quality of life. Limitations: All three trials significantly under-recruited [CapaCiTY trial 1, n = 182 (target 394); CapaCiTY trial 2, n = 65 (target 300); and CapaCiTY trial 3, n = 28 (target 114)]. The numbers analysed were further limited by loss before primary outcome. Trial registration: Current Controlled Trials ISRCTN11791740, ISRCTN11093872 and ISRCTN11747152. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 14. See the NIHR Journals Library website for further project information.

Background: Air pollution has been associated with increased mortality. However, updated evidence from cohort studies with detailed information on various risk factors is needed, especially in regions with low air pollution levels. We investigated the associations between long-term exposure to air pollution and mortality in a prospective cohort. Methods: We studied 88,615 participants aged ≥30 years from an ongoing cohort study in Ontario, Canada from 2009 to 2017. Exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) was estimated at participants’ residence. Cox proportional hazard models were used to investigate the associations between air pollution and non-accidental, cardiovascular, and respiratory mortality, adjusted for a wide array of individual-level and contextual covariates. Potential effect modification by socio-demographic and behavioral factors was also examined in exploratory stratified analyses. Results: The fully adjusted hazard ratios (HRs) per 1 µg/m3 increment in PM2.5 were 1.037 [95% confidence interval (CI): 1.018, 1.057]¸ 1.083 (95% CI: 1.040, 1.128) and 1.109 (95% CI: 1.035, 1.187) for non-accidental, cardiovascular, and respiratory mortality, respectively. Positive associations were also found for NO2; the corresponding HRs per 1 ppb increment were 1.027 (95% CI: 1.021, 1.034), 1.032 (95% CI: 1.019, 1.046) and 1.044 (95% CI: 1.020, 1.068). We found suggestive evidence of stronger associations in physically active participants, smokers, and those with lower household income. Conclusions: Long-term exposure to PM2.5 and NO2 was associated with increased risks for non-accidental, cardiovascular, and respiratory mortality, suggesting potential benefits of further improvement in air quality even in low-exposure environments.

The majority of the world’s biodiversity occurs in the tropics, but human actions in these regions have precipitated an extinction crisis due to habitat degradation, overexploitation, and climate change. Understanding which ecological, biogeographical, and life-history traits predict extinction risk is critical for conserving species. The Philippines is a hotspot of biodiversity and endemism, but it is a region that also suffers from an extremely high level of deforestation, habitat degradation, and wildlife exploitation. We investigated the biological correlates of extinction risk based on the IUCN Red List threat status among resident Philippine birds using a broad range of ecological, biogeographical, and life history traits previously identified as correlates of extinction risk in birds. We found strong support across competing models for endemism, narrower elevational ranges, high forest dependency, and larger body size as correlates significantly associated with extinction risk. Additionally, we compared observed threat status with threat status fitted by our model, finding fourteen species that are not currently recognized by the IUCN Red List as threatened that may be more threatened than currently believed and therefore warrant heightened conservation focus, and predicted threat statuses for the four Philippine Data Deficient bird species. We also assessed species described in recent taxonomic splits that are recognized by BirdLife International, finding 12 species that have a fitted threat status more severe than their IUCN-designated ones. Our findings provide a framework for avian conservation efforts to identify birds with specific biological correlates that increase a species’ vulnerability to extinction both in the Philippine Archipelago and elsewhere on other tropical islands.

Abstract Background Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond. Trial registration ISRCTN, ISRCTN17508514, Registered on 2 October 2017.

Gut microbiota has been implicated as a modifier of childhood growth. Here, 16S rRNA sequencing-based fecal microbiota profiles of 18-24 month old Indian children were evaluated (n = 41), in relation to their anthropometric parameters, intestinal permeability, body composition and total energy expenditure. Pathway analyses were conducted to assess microbial functions related to stunting, underweight and wasting. The fecal microbiota was enriched in Prevotella 9, Bifidobacterium and Escherichia-Shigella. Weight, weight-for-age Z-scores (WAZ) and weight-for-length Z-scores (WLZ), along with age, acted as covariates of microbiota variation specifically in boys (n = 23). Bifidobacterium longum subsp longum abundance was positively associated with WAZ while Bifidobacterium bifidum and Bifidobacterium breve abundances were negatively associated with age. The lipopolysaccharide biosynthesis pathway was upregulated in stunted (n = 16) and wasted (n = 8) children. Findings from this study indicate that child sex may be a critical modifier of the role of gut microbiota on childhood growth.

Family history (FH) of a first-degree relative with colorectal cancer (CRC) is associated with two to fourfold increased risk, yet screening uptake is suboptimal despite proven mortality reduction. We developed a FH-based CRC Risk Triage/Management tool for family physicians (FPs), and educational booklet for patients with CRC FH. This report describes physician referral and patient screening behavior 5 and 10 years post-educational intervention, and factors associated with screening.Longitudinal cohort study. FPs/patients in Ontario and Newfoundland, Canada were sent questionnaires at baseline (2005), 5 and 10 years (2015) following tool/booklet receipt. FPs were asked about CRC screening, patients about FH, screening type and timing. “Correct” screening was concordance with tool recommendations.Results reported for 29/121 (24%) FPs and 98/297 (33%) patients who completed all 3 questionnaires. Over 10 years 2/3 patients received the correct CRC screening test at appropriate timing (baseline 75%, 5-year 62%, 10-year 65%). About half reported their FP recommended CRC screening (5-year 51%, 10-year 63%). Fewer than half the patients correctly assessed their CRC risk (44%, 40%, 41%). Patients were less likely to have correct screening timing if female (RR 0.78; 95% CI 0.61, 0.99; p = 0.045). Patients were less likely to have both correct test and timing if moderate/high CRC risk (RR 0.66; 95% CI 0.47, 0.93; p = 0.017) and more likely if their physician recommended screening (RR1.69; 95% CI 1.15, 2.49; p = 0.007).Physician discussion of CRC risk and screening can positively impact patient screening behavior. Efforts are particularly needed for women and patients at moderate/high CRC risk.

The chromosome 15q25.1 locus is a leading susceptibility region for lung cancer. Here, the authors interrogate three GWAS cohorts with 42,901 individuals to investigate potential pathological pathways such as gated channel activity and neuroactive ligand receptor interaction in lung cancer etiology.

Perianal Crohn’s Disease (pCD) is a common manifestation of Crohn’s Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn’s Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

A survey of the monogeneans of fishes from the lagoon flats of Palmyra Atoll detected 16 species already reported from the Indo-West Pacific faunal region. A total of 653 individual fish from 44 species were collected from the sand flats bordering the lagoon of the atoll. Eighteen species of fish were infected with monogeneans. The monogenean species recovered were: Benedenia hawaiiensis on Acanthurus xanthopterus, Chaetodon auriga, Chaetodon lunula, Mulloidichthys flavolineatus, Pseudobalistes flavimarginatus and Rhinecanthus aculeatus; Ancyrocephalus ornatus on Arothron hispidus; Euryhaliotrema annulocirrus on Chaetodon auriga and Chaetodon lunula; Euryhaliotrema chrysotaeniae on Lutjanus fulvus; Euryhaliotrema grandis on Chaetodon auriga and Chaetodon lunula; Haliotrema acanthuri on Acanthurus triostegus; Haliotrema aurigae on Chaetodon auriga and Chaetodon lunula; Haliotrema dempsteri on Acanthurus xanthopterus; Haliotrema minutospirale on Mulloidichthys flavolineatus; Haliotrematoides patellacirrus on Lutjanus monostigma; Neohaliotrema bombini on Abudefduf septemfasciatus and Abudefduf sordidus; Acleotrema girellae and Acleotrema parastromatei on Kyphosus cinerascens; Cemocotylella elongata on Caranx ignobilis, Caranx melampygus and Caranx papuensis; Metamicrocotyla macracantha on Crenimugil crenilabris; and Pseudopterinotrema albulae on Albula glossodonta. All these monogenean–host combinations represent new geographical records. The monogenean species composition of the Palmyra Atoll is similar to that of the Hawaiian Islands. However, the number of species recovered was lower compared with other localities within the Indo-West Pacific, perhaps due to the geographical isolation of Palmyra Atoll.

Abstract The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling events mediated by TCPTP. Mutations and genetic variants of some genes in the TCPTP pathway are associated with lung cancer risk and survival. In the present study, we first investigated associations of 5,162 single nucleotide polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by using summary data of six published genome-wide association studies (GWAS) of 12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight genes after correction for multiple comparisons by a false discovery rate

The importance of natural ecosystem processes is often overlooked in urban areas. Green Infrastructure (GI) features have been constructed in urban areas as elements to capture and treat excess urban runoff while providing a range of ancillary benefits, e.g., ecosystem processes mediated by microorganisms that improve air and water quality, in addition to the associations with plant and tree rhizospheres. The objective of this study was to characterize the bacterial community and diversity in engineered soils (Technosols) of five types of GI in New York City; vegetated swales, right of way bioswales (ROWB; including street-side infiltration systems and enhanced tree pits), and an urban forest. The design of ROWB GI features directly connects with the road to manage street runoff, which can increase the Technosol saturation and exposure to urban contaminants washed from the street and carried into the GI feature. This GI design specifically accommodates dramatic pulses of water that influence the bacterial community composition and diversity through the selective pressure of contaminants or by disturbance. The ROWB had the highest biodiversity, but no significant correlation with levels of soil organic matter and microbially-mediated biogeochemical functions. Another important biogeochemical parameter for soil bacterial communities is pH, which influenced the bacterial community composition, consistent with studies in non-urban soils. Bacterial community composition in GI features showed signs of anthropogenic disturbance, including exposure to animal feces and chemical contaminants, such as petroleum products. Results suggest the overall design and management of GI features with a channeled connection with street runoff, such as ROWB, have a comprehensive effect on soil parameters (particularly organic matter) and the bacterial community. One key consideration for future assessments of GI microbial community would be to determine the source of organic matter and elucidate the relationship between vegetation, Technosol, and bacteria in the designed GI features.

The ingestion of fructose is of interest due to previously reported differences in gastrointestinal, appetite, and metabolic effects when compared to glucose ingestion when ingested in liquid solution. The aim of this study was to examine these variables when fructose and glucose are added to a semi-solid meal. Seven healthy male participants completed three experimental trials involving the ingestion of 300 mL of semi-skimmed milk mixed with 40 g of instant porridge mix (CON) and with the addition of either 40 g of glucose (GLU) or fructose (FRU). Subjective feelings of appetite were assessed for 2 h after ingestion with blood samples collected at regular intervals. Gastric emptying rate was assessed using the 13C breath test method. Half emptying time was not different between trials (CON = 159 ± 51 min; GLU = 197 ± 46 min; FRU = 198 ± 67 min: P = 0.117). No differences were observed for any subjective measurements of appetite (P > 0.05) while blood glucose was elevated (P < 0.05) 20 min after ingestion on both GLU and FRU with this tending to be higher on GLU than FRU. FRU resulted in greater (P < 0.05) blood lactate concentrations than on the other trials. The results of this study demonstrate that gastric emptying rate of glucose and fructose is similar when ingested in a semi-solid meal. In addition, there is little difference in appetite response between these sugars, however, there are some differences in metabolic response which deserve further study.

Background: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. Methods: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N = 12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. Results: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR = 0.48, 95%CI = 0.30–0.75, p = 0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR = 0.68, 95%CI = 0.61–0.77, p = 4.9 ∗ 10–10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. Conclusion: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7 years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.

Background: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings: Significant dose–response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5–9 years to 89%quit_for_≥20 years declined SCLC risk vs. subjects who had quit smoking

Background: Linaclotide, a guanylate cyclase C agonist, has been shown in clinical trials to improve symptoms of irritable bowel syndrome with constipation (IBS-C). Here we report data from a real-world study of linaclotide in the UK. Methods: This 1-year, multicentre, prospective, observational study in the UK enrolled patients aged 18 years and over initiating linaclotide for IBS-C. The primary assessment was change from baseline in IBS Symptom Severity Scale (IBS-SSS) score at 12 weeks, assessed in patients with paired baseline and 12-week data. Change from baseline in IBS-SSS score at 52 weeks was a secondary assessment. Adverse events were recorded. Results: In total, 202 patients were enrolled: 185 (91.6%) were female, median age was 44.9 years (range 18.1–77.2) and 84 (41.6%) reported baseline laxative use. Mean (standard deviation) baseline IBS-SSS score was 339 (92), with most patients ( n = 129; 66.8%) classified as having severe disease (score ⩾300). In patients with paired data, there was a significant mean (95% confidence interval) decrease in IBS-SSS score from baseline to 12 weeks [−77.0 (−96.3, −57.7); p < 0.001; n = 124] and baseline to 52 weeks [−70.7 (−95.0, −46.5); p < 0.001; n = 76]. Overall, 174 adverse events were reported in 77 (38.1%) patients, most commonly diarrhoea ( n = 54; 26.7%), abdominal pain ( n = 21; 10.4%) and abdominal distension ( n = 13; 6.4%). Conclusion: Linaclotide significantly improved IBS-SSS score at 12 and 52 weeks. These results provide insights into outcomes with linaclotide treatment over 1 year in patients with IBS-C in real-world clinical practice.

Gastric emptying rate in humans is subject to large individual variability, but previous research on the influence of genetics is scarce. Variation in the glucagon-like peptide-1 receptor (GLP1R) gene is a plausible candidate gene to partially explain the high variance. This study aimed to investigate the influence of genetic variation in the GLP1R gene on gastric emptying rate of a glucose solution in humans. Forty eight healthy Caucasian males took part in this investigation. Gastric emptying rate of a 6% glucose solution was assessed using the 13C breath test method and a venous blood sample was obtained from each participant. Participants were genotyped for 27 Tag single nucleotide polymorphisms (SNPs) in the GLP1R locus using Sequenom MassARRAY iPLEX GOLD analysis and MALDI-TOF mass spectrometry. The time at which maximal emptying rate occurred (Tlag) was faster in participants with the CC genotype than in TT and TC genotypes for SNP rs742764: [median (quartiles) CC, 35 (30–36) min vs. TT, 43 (39–46) min, and TC, 41 (39–45) min; P < 0.01]. Tlag was also slower in participants with the AA genotype compared to the TT and TA genotypes for SNP rs2254336: [AA, 43 (39–49) min vs. TT, 36 (34–41) min, and TA, 39 (35–42) min; P < 0.05]. Analysis by phenotype also showed differences in half-emptying time (T12) and Tlag for SNPs rs9283907, rs2268657, and rs2254336. Several neighboring Tag SNPs within the GLP1R gene were found to be associated with gastric emptying rate, and should be further investigated.

Introduction Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder (NDD) that presents with a high degree of heterogeneity (e.g., co-occurrence of other NDDs and other co-morbid conditions), contributing to differential health system needs. Genetics are known to play an important role in ASD and may be associated with different disease trajectories. Objectives and Approach In this proof of principle project, our objective is to link >2,200 children with a confirmed diagnosis of a NDD from the Province of Ontario Neurodevelopmental (POND) Study to administrative health data and electronic medical record (EMR) data in order to identify subgroups of ASD with unique health system trajectories. POND includes detailed phenotype and whole genome sequencing (WGS) data. Identified subgroups will be characterized based on clinical phenotype and genetics. To meet this goal, consideration of WGS-specific privacy and data issues is needed to implement processes which are above and beyond traditional requirements for analyzing individual-level administrative health data. Results Linkage of WGS data with administrative health data is an emerging area of research. As such it has presented a number of initial challenges for our study of ASD. Privacy concerns surrounding the use of WGS data and rare-variant analysis are of particular importance. Practical issues required the need for analysts with expertise in administrative data, EMR data and genetic analyses, and specialized software and sufficient processing power to analyze WGS data. Transdisciplinary discussions of the scope and significance of research questions addressed through this linkage were crucial. The identification of genetic determinants of phenotypes and trajectories in ASD could support targeted early interventions; EMR linkage may inform algorithms to identify ASD in broader populations. These approaches could improve both patient outcome and family experience. Conclusion/Implications As the cost of genetic sequencing decreases, WGS data will become part of the routine clinical management of patients. Linkage of WGS, EMR and administrative data has tremendous potential that has largely not been realized; including population-level ASD research to improve our ability to predict long-term outcomes associated with ASD.

This paper explores the relationship between architectural design and research in the context of a particular example, the development of the Irish pavilion for the 14th architectural biennale in Venice 2014 (Infra-Éireann) and its reiteration and expansion in Ireland for the State’s centennial celebrations 1916–2016 (Making Ireland Modern). Originally responding to Rem Koolhaas’s call to investigate the international absorption of modernity, the pavilion sought to engage with the properties of the architectures of infrastructure in twentieth and twenty-first-century Ireland. Central to this proposition was that infrastructure is simultaneously a technological and cultural construct, one that for Ireland occupied a critical position in the building of a new, independent post-colonial nation state. Presupposing infrastructure as consisting of both visible and invisible networks, the idea of a matrix became a central theoretical and visual tool in the curatorial and design process for both the pavilion and its contents. To begin with this was a two-dimensional grid used to identify and order what became described as a series of ten infrastructural episodes. These were determined chronologically across the decades between 1916 and 2016 and their spatial manifestations articulated in terms of scale: micro, meso and macro. What emerged in the design and research process was a dialectic relationship between the pavilion and its content as logistical and conceptual concerns merged to realise an adaptive framed modular structure, imagined as an embodied manifesto and, analogous to infrastructure, as having no fixed form.

An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study.Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens.The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61-2.09); ESeC OR 1.53 (95% CI 1.44-1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20-1.98); ESeC OR 1.34 (95% CI 1.19-1.52)).SES remained a risk factor for lung cancer after adjustment for smoking behavior.

OBJECTIVES: Working in mines and quarries has been associated with an elevated lung cancer risk but with inconsistent results for coal miners. This study aimed to estimate the smoking-adjusted lung cancer risk among coal miners and compare the risk pattern with lung cancer risks among ore miners and quarrymen. METHODS: We estimated lung cancer risks of coal and ore miners and quarrymen among 14 251 lung cancer cases and 17 267 controls from the SYNERGY pooled case–control study, controlling for smoking and employment in other at-risk occupations. RESULTS: Ever working as miner or quarryman (690 cases, 436 controls) was associated with an elevated odds ratio (OR) of 1.55 [95% confidence interval (95% CI) 1.34–1.79] for lung cancer. Ore miners (53 cases, 24 controls) had a higher OR (2.34, 95% CI 1.36-4.03) than quarrymen (67 cases, 39 controls; OR 1.92, 95% CI 1.21–3.05) and coal miners (442 cases, 297 controls; OR 1.40, 95% CI 1.18–1.67), but CI overlapped. We did not observe trends by duration of exposure or time since last exposure. CONCLUSIONS: This pooled analysis of population-based studies demonstrated an excess lung cancer risk among miners and quarrymen that remained increased after adjustment for detailed smoking history and working in other at-risk occupations. The increase in risk among coal miners were less pronounced than for ore miners or quarrymen.

Cholecystokinin (CCK) is an archetypal incretin hormone secreted by intestinal enteroendocrine cells (EEC) in response to ingested nutrients. The aim of this study was to determine whether CCK modulates enterocyte fatty acid uptake by primary mouse duodenal cells. Exposure of primary mouse duodenal cells to 10 pM sulfated CCK-8 caused a two fold increase in dodecanoic acid fatty acid (FA) uptake. The selective CCK A receptor antagonist loxiglumide (100 μM) completely abolished the CCK-8 induced FA uptake. The CD36 fatty acid translocase-specific inhibitor sulfo-N-succinimidyl oleate (1 μM) also completely inhibited CCK-8 induced FA uptake, as did treatment with 200 μM phloretin. Together these data show CCK induces FA uptake into duodenal enterocytes; this action involves the CCK-RA receptor and is carrier mediated by CD36.

INTRODUCTION:Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease. METHODS:We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS:META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A). CONCLUSIONS:We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary.

A community garden is a great way to unite a group of people in a common goal. In addition to providing fresh herbs, vegetables, and fruit, community gardens can also increase self-esteem, beautify a neighborhood, and create an opportunity for socializing and improving health. This revised 4-page fact sheet outlines the importance of community gardens and how to develop and manage a community garden. Written by Adrian Hunsberger, Eva C. Worden, and John McLaughlin, and published by the Environmental Horticulture Department, April 2016. ENH 966/EP124: Starting a Community Garden (ufl.edu)

BACKGROUND/OBJECTIVE: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn’s disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed.

This study aimed to examine gastric emptying rate and gastrointestinal hormone responses to fructose and glucose ingestion following 3 days of dietary fructose supplementation. Using the 13C-breath test method, gastric emptying rates of equicaloric fructose and glucose solutions were measured in 10 healthy men with prior fructose supplementation (fructose supplement, FS; glucose supplement, GS) and without prior fructose supplementation (fructose control, FC; glucose control, GC). In addition, circulating concentrations of acylated ghrelin (GHR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin were determined, as well as leptin, lactate, and triglycerides. Increased dietary fructose ingestion resulted in accelerated gastric emptying rate of a fructose solution but not a glucose solution. No differences in GIP, GLP-1, or insulin incremental area under curve (iAUC) were found between control and supplement trials for either fructose or glucose ingestion. However, a trend for lower ghrelin iAUC was observed for FS compared to FC. In addition, a trend of lower GHR concentration was observed at 45 min for FS compared to FC and GHR concentration for GS was greater than GC at 10 min. The accelerated gastric emptying rate of fructose following short-term supplementation with fructose may be partially explained by subtle changes in delayed postprandial ghrelin suppression.

This pilot study aimed to investigate the effect of simple sugar ingestion, in amounts typical of common ingestion, on appetite and the gut-derived hormone response. Seven healthy men ingested water (W) and equicaloric solutions containing 39.6 g glucose monohydrate (G), 36 g fructose (F), 36 g sucrose (S), and 19.8 g glucose monohydrate + 18 g fructose (C), in a randomised order. Serum concentrations of ghrelin, glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide-1 (GLP-1), insulin, lactate, triglycerides, non-esterified fatty acids (NEFA), and d-3 hydroxybutyrate, were measured for 60 min. Appetite was measured using visual analogue scales (VAS). The ingestion of F and S resulted in a lower GIP incremental area under the curve (iAUC) compared to the ingestion of G (p < 0.05). No differences in the iAUC for GLP-1 or ghrelin were present between the trials, nor for insulin between the sugars. No differences in appetite ratings or hepatic metabolism measures were found, except for lactate, which was greater following the ingestion of F, S, and C, when compared to W and G (p < 0.05). The acute ingestion of typical amounts of fructose, in a variety of forms, results in marked differences in circulating GIP and lactate concentration, but no differences in appetite ratings, triglyceride concentration, indicative lipolysis, or NEFA metabolism, when compared to glucose.

Numerous human diseases can lead to atrophy of skeletal muscle, and loss of this tissue has been correlated with increased mortality and morbidity rates. Clinically addressing muscle atrophy remains an unmet medical need, and the development of preclinical tools to assist drug discovery and basic research in this effort is important for advancing this goal. In this report, we describe the development of a bioluminescent gene reporter rat, based on the zinc finger nuclease-targeted insertion of a bicistronic luciferase reporter into the 3' untranslated region of a muscle specific E3 ubiquitin ligase gene, MuRF1 (Trim63). In longitudinal studies, we noninvasively assess atrophy-related expression of this reporter in three distinct models of muscle loss (sciatic denervation, hindlimb unloading and dexamethasone-treatment) and show that these animals are capable of generating refined detail on in vivo MuRF1 expression with high temporal and anatomical resolution.

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

INTRODUCTION: The etiology of ovarian cancer is largely unknown. One hypothesis is that the inefficient removal of the blood clots and fibrin products which are deposited in the vicinity of the ovary by retrograde menstruation might be associated with an increased risk of ovarian cancer. Several single nucleotide polymorphisms within genes which comprise the fibrinolytic system have been shown to have functional effects on the rate of blood clot degradation. These were considered to be candidate genes in the present study. AIM: We studied the genotype distributions of 12 functional SNPs of four genes (tPA, uPA PAI1 and TAFI) among 775 ovarian cancer cases and 889 controls. RESULTS: No significant associations were seen between any of the ten SNPs and the risk of ovarian cancer as a whole, or in any histologic subgroup. DISCUSSION: Germline known functional variants of genes in the fibrinolytic system are not associated with risk of ovarian cancer.

HS-1127, an 11-page illustrated fact sheet by John McLaughlin, Carlos Balerdi, and Jonathan Crane, describes this tropical fruit, suitable climate for optimum growth, propagation, production and spacing for the home landscape, soils, planting, care, and pruning, harvest, ripening, storage, and use and nutritional value of the cashew apple. Includes references. Published by the UF Department of Horticultural Sciences, April 2008. HS1127/HS377: Cashew Apple Fruit Growing in the Florida Home Landscape (ufl.edu)

Este documento, HS1041, es uno de una serie de publicaciones del Horticultural Sciences, Servicio de Extensión Cooperativa de la Florida, Instituto de Alimentos y Ciencias Agrícolas, Universidad de la Florida (UF/IFAS). Fecha de primera publicación: octubre 2004. Repasado noviembre 2005. HS1041/HS291: El Maranon (Anacardium occidentale) en Florida (ufl.edu)

A previous publication, ENH854 (http://edis.ifas.ufl.edu/EP107), listed over 350 native and non-native plant species for south Florida. This new publication was developed as a supplement to ENH854, but it is also a good stand-alone reference for people wishing to add native plants to their private yards or public landscapes, or simply to learn more about them. This document is ENH 875, one of a series of the Environmental Horticulture Department, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Original publication date April 29, 2003. https://edis.ifas.ufl.edu/ep222

A community garden is a collaborative greenspace in which the participants share in both the maintenance and the rewards. There is a long tradition of community gardening in various parts of the United States and around the world. This publication has been developed to assist those who wish to form a community garden in Florida. This document is ENH 966, one of a series of the Environmental Horticulture Department, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Original publication date June 28, 2002. Reviewed: October 2003. ENH 966/EP124: Starting a Community Garden (ufl.edu)

Abstract The name of the Inyo Mountains and of Inyo County in California was reported in 1860 to mean ‘dwelling place of a great spirit’ in a local Indian language, but this etymology was later disputed. It is now confirmed that the name is derived from Panamint iuml;niuml;-yun ‘ ‘it's dangerous’.