Associative learning and thiamine based flavor preference

The current experiment explored the extent to which thiamine deficiency at the time of conditioning is important as well as the importance of thiamine deficiency at the time of testing. This experiment controlled for previous experiments' flaws. Our experiment controlled for the time of thiamine deprivation, whether it was during the time of conditioning or at the time of test. Based on our results, thiamine deficiency did not influence consumption of a flavored solution that had been paired with thiamine. This was true for thiamine deficiency at the time of conditioning pairings and at the time of testing

The ability of an extinguished CS and a CS given conditioned inhibition training to pass tests for inhibition

Conditioned inhibition (CI) is a classical conditioning procedure that results in a conditioned stimulus (CS) that predicts the absence of an unconditioned stimulus (US). A procedure known as Pavlovian conditioned inhibition training is the most common procedure for producing CI. In this procedure, a nontarget CS (CS A) is paired with the US and then CS A is presented with the target CS (CS X) without the US. Therefore, AUS trials and AX-noUS trials are given. CS X acquires inhibitory properties during these AX trials. Research has shown that extinction also produces CI. Extinction occurs when a CS (CS X) is paired with the US during conditioning and then this CS is presented alone without the US. The Rescorla-Wagner model predicts that the two CSs during AX-noUS trials will compete for learning and this should lead to slow and limited learning about those cues (a loss of excitation for CS A and inhibition acquired for CS X) due to this competition. During extinction trials, CS X does not compete for learning, so the subject should learn rapidly about the CS. The following experiments found that extinction produced less inhibition than Pavlovian conditioned inhibition training.Includes bibliographical reference

A measure of nature connectedness for children and adults: Validation, performance, and insights

With benefits to both human well-being and pro-nature conservation behaviors, nature connectedness is emerging as an important psychological construct for a sustainable future. The growing research and applied and policy-related interests require a straightforward measure of nature connectedness that is suitable for both children and adult populations. To establish the reliability of the new Nature Connection Index (NCI) three factor analyses were conducted. One was based on a large Monitor of Engagement with the Natural Environment (MENE) dataset for adults (n = 3568) with a replication from data sets collected online (n = 553), and a third used MENE data from children (n = 351). To validate the NCI as a measure for nature connectedness an online comparison study (n = 153) included the NCI alongside other established measures. The results showed that the NCI was a reliable and valid scale that offers a short, simple alternative to other measures of nature connectedness, particularly for populations including both children and adults, measured face to face or online. The utility of the NCI is also supported, with variations associated with various pro-environmental and pro-conservation behaviors observed, and importantly the NCI also revealed changes in nature connectedness across the lifespan.N/

Roadmap Report and Executive Summary

Women’s Aid Federation England (WAFE) and SafeLives (SL) collaborated over five years (2016-21) to develop and implement the Roadmap Programme which aimed to transform the lives of women and girls through systemic change to policy, practice and commissioning by promoting early intervention and reducing the prevalence, impact and tolerance of domestic violence and abuse (DVA). Funded by the Big Lottery’s Women and Girls Initiative, WAFE and SL collaborated with DVA survivors and expert partners in specialist frontline services to develop and implement two contrasting interventions in five different sites in England. Both organisations were committed to making DVA services more accessible and responsive to survivors’ needs and both aimed to achieve wider system change in the sites where the programmes were delivered. However, the two organisations chose different but complementary routes by which to reach these broad goals:WAFE’s Change That Lasts (CtL) Programme1 aimed at developing a ‘whole community response’ that would increase responsiveness to DVA services at three levels: i) the community ii) frontline professionals in organisations that were not specialist DVA organisations and iii) services delivered by DVA specialist organisations. The programme comprised three interventions targeted on these three different audiences and delivered in three sites – Sunderland, Nottingham and Nottinghamshire (Nottingham/shire) and Surrey. Ask Me aimed to address cultural and attitudinal barriers to change through training and supporting Community Ambassadors who volunteered toincrease awareness and responsiveness to DVA in their local communities. Trusted Professionalcombined training with organisational development to improve expertise and responsiveness among frontline professionals. The VOICES intervention was designed to re-connect specialist DVA services to a strengths-based, needs-led, trauma-informed approach centred on the survivor for practitioners in specialist DVA organisations. The SafeLives Programme, designed by SafeLives, alongside Pioneers (survivors and experts by experience) and specialist frontline DVA partners, comprised an integrated suite of multiple interventions that would allow survivors and their families to access five different interventions within the same organisation. Two independent services, in Norwich and West Sussex (Worthing, Adur, and Crawley), were commissioned to deliver the interventions, hereafter referred to as the SafeLives Co-Designed Pilots (SLCDPs). These interventions were tailored to the needs of different groups so that survivors and their families could move between and through them on their journey to recovery. The intervention aimed to break down silos between services and deliver a ‘whole family’ service informed by DVA survivors’ views. The SLCDPs were targeted at those assessed as at medium risk of harm; people who wanted to remain in their relationships; those with complex needs; survivors recovering from abuse and children and young people. A wide range of individual and group interventions was utilised and training and skills development were provided to partner agencies

Bayesian approach to determining penetrance of pathogenic SDH variants.

BACKGROUND: Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C (SDHA-C) genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL). METHODS: Two cohorts were 575 unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA-C variants was calculated by comparing allelic frequencies in cases versus controls from ExAC (removing those variants contributed by The Cancer Genome Atlas). RESULTS: Pathogenic SDHA-C variants were identified in 106 subjects (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC), 13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting for 21% of subjects with SDHA-C variants. Combining data from both cohorts, estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to 3.8%) for SDHA variants. CONCLUSION: Pathogenic variants in SDHB are more penetrant than those in SDHC and SDHA. Our findings have important implications for counselling and surveillance of subjects carrying these pathogenic variants

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy