Open Science at PLOS

Delivered at the University of Cambridge as part of Open Access Week 201

Reliability of Threshold and Suprathreshold Methods for Taste Phenotyping: Characterization with PROP and Sodium Chloride

The present study aimed to compare the accuracy and reliability of four standard methods used for classification of people as taster or non-tasters based on their sensitivity to PROP (6-n-propylthiouracil). A panel consisting of 21 subjects was tested for threshold and suprathreshold sensitivity of sodium chloride, PROP, and genotyped for TAS2R38. Two threshold methods, staircase and modified Harris–Kalmus, were used to obtain detection and recognition thresholds and compared for accuracy and repeatability. Similarly, two suprathreshold techniques, the just noticeable differences (JND) and the general labeled magnitude scale (gLMS), were used to determine Weber fractions and individual psychophysical functions and compared for accuracy and repeatability. Results show both threshold methods have been able to correctly separate people into two groups of tasters and non-tasters, with the staircase method having a lower variability among subjects. On the suprathreshold front, we found differences in sensitivity between tasters and non-tasters when comparing Weber fractions and psychophysical functions; however, our data suggest that clustering people without previous knowledge of their taster status is less accurate when using Weber fractions. Intensity ratings are more reliable to classify people into tasters and non-tasters. Results show that the staircase for threshold measurement and the gLMS methods are more reliable methods than Harris–Kalmus and JND for phenotyping people and can be used in large-scale studies in the quest to discover new genotype–phenotype associations

Process evaluation of the implementation of Universal Free School Meals (UFSM) for P1 to P3: Research with Schools and Local Authorities

In January 2015, Scotland moved from a targeted system of Free School Meals (FSM) to a service providing universal free school meals (UFSM) for all children in Primaries 1 to 3 (P1-3). The targeted system remained for children in P4 and above. Since the launch of Hungry for Success in 2003, a series of policies and guidance has focused on school food reform and nutrient standards. The UFSM policy is set within this context alongside an increased policy focus on reducing health inequalities in Scotland. A theory of change was developed by NHS Health Scotland for UFSM provision. It was identified that key policy outcomes will be underpinned by a number of assumptions and that achievement of these outcomes will also be influenced by certain external factors. Further, it recognised that the implementation of UFSM may also generate positive and negative unintended consequences. NHS Health Scotland commissioned a research team from three universities to undertake a process evaluation of the implementation of the UFSM policy. The research was led by the Institute for Social Marketing at the University of Stirling, in collaboration with the MRC/CSO Social and Public Health Sciences Unit at the University of Glasgow, and the Centre for Public Health Nutrition Research at the University of Dundee. The process evaluation comprised three main strands: research with parents, schools and local authorities. This report focuses on the research with schools and local authorities. A detailed report on the research with parents was published in October 2015

Prevalence and socio-demographic correlates of cooking skills in UK adults: cross-sectional analysis of data from the UK National Diet and Nutrition Survey

Background Poor cooking skills may be a barrier to healthy eating and a contributor to overweight and obesity. Little population-representative data on adult cooking skills has been published. We explored prevalence and socio-demographic correlates of cooking skills among adult respondents to wave 1 of the UK National Diet and Nutrition Survey (2008–9).  Methods Socio-demographic variables of interest were sex, age group, occupational socio-economic group and whether or not respondents had the main responsibility for food in their households. Cooking skills were assessed as self-reported confidence in using eight cooking techniques, confidence in cooking ten foods, and ability to prepare four types of dish (convenience foods, a complete meal from ready-made ingredients, a main meal from basic ingredients, and cake or biscuits from basic ingredients). Frequency of preparation of main meals was also reported.  Results Of 509 respondents, almost two-thirds reported cooking a main meal at least five times per week. Around 90% reported being able to cook convenience foods, a complete meal from ready-made ingredient, and a main dish from basic ingredients without help. Socio-demographic differences in all markers of cooking skills were scattered and inconsistent. Where these were found, women and main food providers were most likely to report confidence with foods, techniques or dishes, and respondents in the youngest age (19–34 years) and lowest socio-economic group least likely.  Conclusions This is the only exploration of the prevalence and socio-demographic correlates of adult cooking skills using recent and population-representative UK data and adds to the international literature on cooking skills in developed countries. Reported confidence with using most cooking techniques and preparing most foods was high. There were few socio-demographic differences in reported cooking skills. Adult cooking skills interventions are unlikely to have a large population impact, but may have important individual effects if clearly targeted at: men, younger adults, and those in the least affluent social groups

Variability and effectiveness of comparator group interventions in smoking cessation trials : A systematic review and meta-analysis

Funding: This work was funded by Cancer Research UK (application number C50862/A18446). The systematic review protocol was previously peer-reviewed by Cancer Research UK as part of the funding process. The funder had no role in protocol design, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Shared decision-making for psychiatric medication : A mixed-methods evaluation of a UK training programme for service users and clinicians

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Background: Shared decision making (SDM) is recognised as a promising strategy to enhance good collaboration between clinicians and service users, yet it is not practised regularly in mental health. Aims: Develop and evaluate a novel training programme to enhance SDM in psychiatric medication management for service users, psychiatrists and care co-ordinators. Methods: The training programme design was informed by existing literature and local stakeholders consultations. Parallel group-based training programmes on SDM process were delivered to community mental health service users and providers. Evaluation consisted of quantitative measures at baseline and 12-month follow-up, post-programme participant feedback and qualitative interviews. Results: Training was provided to 47 service users, 35 care-coordinators and 12 psychiatrists. Participant feedback was generally positive. Statistically significant changes in service users’ decisional conflict and perceptions of practitioners’ interactional style in promoting SDM occurred at the follow-up. Qualitative data suggested positive impacts on service users’ and care co-ordinators confidence to explore medication experience, and group-based training was valued. Conclusions: The programme was generally acceptable to service users and practitioners. This indicates the value of conducting a larger study and exploring application for non-medical decisions.Peer reviewedFinal Published versio

Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

Background: The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design: This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion: This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been considered to try and compensate for any challenges encountered in recruiting the large sample, and the multicentre design means that knowledge can be shared between recruitment teams. The pragmatic study design means that results will give a realistic estimate of the success of the intervention if it were to be rolled out as part of standard smoking cessation service practice. Trial registration: Current Controlled Trials ISRCTN33031001. Registered 27 April 2012

Candida glabrata : a review of its features and resistance

Candida species belong to the normal microbiota of the oral cavity and gastrointestinal and vaginal tracts, and are responsible for several clinical manifestations, from mucocutaneous overgrowth to bloodstream infections. Once believed to be non-pathogenic, Candida glabrata was rapidly blamable for many human diseases. Year after year, these pathological circumstances are more recurrent and problematic to treat, especially when patients reveal any level of immunosuppression. These difficulties arise from the capacity of C. glabrata to form biofilms and also from its high resistance to traditional antifungal therapies. Thus, this review intends to present an excerpt of the biology, epidemiology, and pathology of C. glabrata, and detail an approach to its resistance mechanisms based on studies carried out up to the present.The authors are grateful to strategic project PTDC/SAU-MIC/119069/2010 for the financial support to the research center and for Celia F. Rodrigues' grant

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice