TCR Convergence in Individuals Treated With Immune Checkpoint Inhibition for Cancer.

Tumor antigen-driven selection may expand T cells having T cell receptors (TCRs) of shared antigen specificity but different amino acid or nucleotide sequence in a process known as TCR convergence. Substitution sequencing errors introduced by TCRβ (TCRB) repertoire sequencing may create artifacts resembling TCR convergence. Given the anticipated differences in substitution error rates across different next-generation sequencing platforms, the choice of platform could be consequential. To test this, we performed TCRB sequencing on the same peripheral blood mononuclear cells (PBMC) from individuals with cancer receiving anti-CTLA-4 or anti-PD-1 using an Illumina-based approach (Sequenta) and an Ion Torrent-based approach (Oncomine TCRB-LR). While both approaches found similar TCR diversity, clonality, and clonal overlap, we found that Illumina-based sequencing resulted in higher TCR convergence than with the Ion Torrent approach. To build upon this initial observation we conducted a systematic comparison of Illumina-based TCRB sequencing assays, including those employing molecular barcodes, with the Oncomine assay, revealing differences in the frequency of convergent events, purportedly artifactual rearrangements, and sensitivity of detection. Finally, we applied the Ion Torrent-based approach to evaluate clonality and convergence in a cohort of individuals receiving anti-CTLA-4 blockade for cancer. We found that clonality and convergence independently predicted response and could be combined to improve the accuracy of a logistic regression classifier. These results demonstrate the importance of the sequencing platform in assessing TCRB convergence

Unveiling ethical product features: The importance of an elaborated information presentation

© 2017 Elsevier Ltd Despite growing consumer awareness of ethical consumption, market sales are not growing accordingly. Because the presentation of appropriate ethical product information may influence consumers to choose ethical products, this paper analyses the requirements necessary for the successful communication of ethical product features. Based on McGuire's (1976) information-processing model, and a review of current literature, the information's comprehensibility, meaningfulness, and credibility are investigated in an online survey of US American citizens (n = 595) for two product categories representing Fast Moving Consumer Goods, and durable goods. A generalized mixed logit model revealed that all three communication factors affect consumers' choices. The more concerns about, or expertise in, organic production and fair trade purchase the consumers expressed, the less important their price sensibility and the more they preferred a comprehensive addendum and credible sources (e.g., government certificate or traceability). The results strongly suggest that advertisers and marketers can customize product communications in order to better engage both the mass market, and ethically oriented consumers

A multicentre randomised controlled trial of day hospital-based falls prevention programme for a screened population of community-dwelling older people at high risk of falls

Objective: to determine the clinical effectiveness of a day hospital-delivered multifactorial falls prevention programme, for community-dwelling older people at high risk of future falls identified through a screening process

Improving safety for older public transport users (OPTU) - a feasibility study

On the whole, the UK public transport system is generally considered to provide a safe means of mobility. However, each year, around 6,000 people are reported by the UK police to be injured whilst using buses with more than 400 persons killed or seriously injured. Approximately 50% of those injured or killed are aged over 65 years (Department for Transport 2008). However it is thought that there are many more injured older bus-users who are not included in the national statistics and whom may now avoid travelling on public transport because of previous injuries and experiences. Whilst free travel (particularly on buses) has allowed senior citizens the freedom to travel for pleasure and social inclusion, injuries or near-falls that may occur during the journey can impact on future decisions to travel leading in some cases to anxiety/fear of sustaining further injury, loss of personal mobility and ultimately social isolation. This Feasibility Study was funded within the Medical Research Council (MRC) Lifelong Health and Wellbeing programme in order to examine the general safety (but not security) of older public transport users. It explores injury type and causation and proposes design interventions for injury prevention with an overall objective of exploring how public transport use could possibly be made safer for older transport-users. A mixed methods design was used to collect and collate data from a number of sources. These included published research literature, national accident datasets, bus-operator records, service user consultations and other stakeholder consultations with groups representing the 60+ year’s age group. The ultimate aim was to develop a pilot injury surveillance database that could in principle be used to determine vehicle design requirements, transport operator procedures and transport-user behaviors that could prevent injuries from occurring...(continues)

Injuries to older users of buses in the UK

The increasing age of the United Kingdom (UK) population coupled with enhanced life expectancy impacts on transport-user demographics and will affect transport planning in the years ahead. Whilst passenger car use is the ultimate means of personal independence, at some point the physiological and psychological impact of age-related conditions will inevitably shift people out of their vehicles and onto public transport systems. Overall, public transport is seen to be vital for social inclusion (Lucas et al 2008) and it is considered a safe means of mobility. However, it is important that the public and, in particular, the elderly perceive it to be so. Injuries (across a spectrum of severities) do occur during public transport use from time to time. In fact, over 5,000 people are injured on UK buses each year alone with over 300 bus-users killed/seriously injured (Department for Transport, 2012). This study was designed to examine the nature of injuries and their causes to older bus-users with the aim being to establish where design countermeasures may be indicated. The study uses descriptive statistics to analyse linked (accident and injury) data involving a sample of older bus-users. Most incidents in the linked dataset were non-collisions (62 per cent) resulting in 1,381 recorded injuries in those aged 60+ years, of which 46 per cent were 'slight' and 54 per cent 'serious'

Injuries to older users of public transport in the UK

Барнс Джо; Лоутон Клэр; Моррис Эндрю; Маршал Рус; Саммерскилл Стив; Кендрик Дениз; Логан Пип; Драмонд Аврил; Файлдс Брайан; Конрой Саймон; Белла Джули. Травмы для пожилых пользователей общественного транспорта в ВеликобританииThe increasing age of the United Kingdom (UK) population coupled with enhanced life expectancy impacts on transport-user demographics and will affect transport planning in the years ahead. Whist passenger car use is the ultimate means of personal independence, at some point the physiological and psychological impact of agerelated conditions will inevitably shift people out of their vehicles and onto public transport systems. Overall, public transport is seen to be vital for social inclusion (Lucas et al 2008, Rowntree Foundation) and it is considered a safe means of mobility. However, it is important that the public and in particular, the elderly perceive it to be so. Injuries (across a spectrum of severities) do occur during public transport use from time to time. In fact, over 5,000 people are injured on UK buses each year alone with over 300 bus-users killed/seriously injured (Department for Transport, 2012). This study was designed to examine the nature of injuries and their causes to older bus-users with the aim being to establish where design countermeasures may be indicated. The study uses linked (accident and injury) data involving a sample of older bus-users. Most incidents in the linked dataset were non-collisions (62 per cent) resulting in 1,381 recorded injuries in those aged 60+ years, of which 46 per cent were 'slight' and 54 per cent 'serious'

He Rourou Whai Painga, an Aotearoa New Zealand dietary pattern for metabolic health and whānau wellbeing: protocol for a randomized controlled trial

BackgroundCardiometabolic diseases are highly prevalent in Aotearoa New Zealand. Dietary intake is a modifiable risk factor for such diseases and certain dietary patterns, specifically the Mediterranean diet (MedDiet), are associated with improved metabolic health. This study aims to test whether an intervention including a Mediterranean dietary pattern incorporating high quality New Zealand foods (NZMedDiet pattern) and behavior change science can improve the metabolic health of participants and their household/whānau.Methods and analysisThis is a multi-center, three-stage trial with two parallel group superiority randomized controlled trials (RCTs), and a longitudinal cohort study embedded within the trial design. The first RCT (RCT 1) is a comparison of the NZMedDiet pattern compared to usual diet for 12 weeks. The Behavior Change Wheel was used to select and implement strategies to support participant adherence to the NZMedDiet, such as web-based nutrition education on healthy shopping and cooking. The second (RCT 2) compares online social support to no online social support for 12 weeks, administered to participants immediately following RCT 1. The third stage is a longitudinal cohort study where all participants are followed from the beginning of their start of the active intervention for 12 months in total. The primary outcome measure for each stage is the metabolic syndrome severity score (MetSSS). The duration of enrolment is 12–15 months. The total recruitment target is 200 index participants and their household/whānau members who participate with them, and the primary analyses will be intention to treat on index participants.DiscussionThe trial will test whether the NZMedDiet pattern and behavior change support improves the cardiometabolic health of people in Aotearoa New Zealand.Clinical trial registrationhttps://www.anzctr.org.au/Default.aspx, identifier ACTRN12622000906752 and https://www.isrctn.com/, identifier ISRCTN89011056 (Spirit 2)

Injuries to older users of buses in the UK

This is an Open Access article licensed under a Creative Commons Attribution 4.0 Unported Licence.The increasing age of the United Kingdom (UK) population coupled with enhanced life expectancy impacts on transport-user demographics and will affect transport planning in the years ahead. Whilst passenger car use is the ultimate means of personal independence, at some point the physiological and psychological impact of age-related conditions will inevitably shift people out of their vehicles and onto public transport systems. Overall, public transport is seen to be vital for social inclusion (Lucas et al 2008) and it is considered a safe means of mobility. However, it is important that the public and, in particular, the elderly perceive it to be so. Injuries (across a spectrum of severities) do occur during public transport use from time to time. In fact, over 5,000 people are injured on UK buses each year alone with over 300 bus-users killed/seriously injured (Department for Transport, 2012). This study was designed to examine the nature of injuries and their causes to older bus-users with the aim being to establish where design countermeasures may be indicated. The study uses descriptive statistics to analyse linked (accident and injury) data involving a sample of older bus-users. Most incidents in the linked dataset were non-collisions (62 per cent) resulting in 1,381 recorded injuries in those aged 60+ years, of which 46 per cent were 'slight' and 54 per cent 'serious'

Multifactorial day hospital intervention to reduce falls in high risk older people in primary care: a multi-centre randomised controlled trial [ISRCTN46584556]

Falls in older people are a major public health concern in terms of morbidity, mortality and cost. Previous studies suggest that multifactorial interventions can reduce falls, and many geriatric day hospitals are now offering falls intervention programmes. However, no studies have investigated whether these programmes, based in the day hospital are effective, nor whether they can be successfully applied to high-risk older people screened in primary care. The hypothesis is that a multidisciplinary falls assessment and intervention at Day hospitals can reduce the incidence of falls in older people identified within primary care as being at high risk of falling. This will be tested by a pragmatic parallel-group randomised controlled trial in which the participants, identified as at high risk of falling, will be randomised into either the intervention Day hospital arm or to a control (current practice) arm. Those participants preferring not to enter the full randomised study will be offered the opportunity to complete brief diaries only at monthly intervals. This data will be used to validate the screening questionnaire. Three day hospitals (2 Nottingham, 1 Derby) will provide the interventions, and the University of Nottingham's Departments of Primary Care, the Division of Rehabilitation and Ageing Unit, and the Trent Institute for Health Service Research will provide the methodological and statistical expertise. Four hundred subjects will be randomised into the two arms. The primary outcome measure will be the rate of falls over one year. Secondary outcome measures will include the proportion of people experiencing at least one fall, the proportion of people experiencing recurrent falls (>1), injuries, fear of falling, quality of life, institutionalisation rates, and use of health services. Cost-effectiveness analyses will be performed to inform health commissioners about resource allocation issues. The importance of this trial is that the results may be applicable to any UK day hospital setting. SITES: General practices across Nottinghamshire and Derbyshire. Day hospitals: Derbyshire Royal Infirmary (Southern Derbyshire Acute Hospitals NHS Trust) Sherwood Day Service (Nottingham City Hospital Trust) Leengate Day Hospital (Queen's Medical Centre Nottingham University Hospital NHS Trust

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead