Resistance of rocky intertidal communities to oceanic climate fluctuations.

A powerful way to predict how ecological communities will respond to future climate change is to test how they have responded to the climate of the past. We used climate oscillations including the Pacific Decadal Oscillation (PDO), North Pacific Gyre Oscillation, and El Niño Southern Oscillation (ENSO) and variation in upwelling, air temperature, and sea temperatures to test the sensitivity of nearshore rocky intertidal communities to climate variability. Prior research shows that multiple ecological processes of key taxa (growth, recruitment, and physiology) were sensitive to environmental variation during this time frame. We also investigated the effect of the concurrent sea star wasting disease outbreak in 2013-2014. We surveyed nearly 150 taxa from 11 rocky intertidal sites in Oregon and northern California annually for up to 14-years (2006-2020) to test if community structure (i.e., the abundance of functional groups) and diversity were sensitive to past environmental variation. We found little to no evidence that these communities were sensitive to annual variation in any of the environmental measures, and that each metric was associated with < 8.6% of yearly variation in community structure. Only the years elapsed since the outbreak of sea star wasting disease had a substantial effect on community structure, but in the mid-zone only where spatially dominant mussels are a main prey of the keystone predator sea star, Pisaster ochraceus. We conclude that the established sensitivity of multiple ecological processes to annual fluctuations in climate has not yet scaled up to influence community structure. Hence, the rocky intertidal system along this coastline appears resistant to the range of oceanic climate fluctuations that occurred during the study. However, given ongoing intensification of climate change and increasing frequencies of extreme events, future responses to climate change seem likely.

Food insecurity in adults with severe mental illness living in Northern England: A co-produced cross-sectional study.

AIM: This study aimed to explore food insecurity prevalence and experiences of adults with severe mental illness living in Northern England. METHODS: This mixed-methods cross-sectional study took place between March and October 2022. Participants were adults with self-reported severe mental illness living in Northern England. The survey included demographic, health, and financial questions. Food insecurity was measured using the US Department of Agriculture Adult Food Security measure. Quantitative data were analysed using descriptive statistics and binary logistic regression; and qualitative data using content analysis. RESULTS: In total, 135 participants completed the survey, with a mean age of 44.7 years (SD: 14.1, range: 18-75 years). Participants were predominantly male (53.3%), white (88%) and from Yorkshire (50.4%). The food insecurity prevalence was 50.4% (n = 68). There was statistical significance in food insecurity status by region (p = 0.001); impacts of severe mental illness on activities of daily living (p = 0.02); and the Covid pandemic on food access (p < 0.001). The North West had the highest prevalence of food insecurity (73.3%); followed by the Humber and North East regions (66.7%); and Yorkshire (33.8%). In multivariable binary logistic regression, severe mental illness' impact on daily living was the only predictive variable for food insecurity (odds ratio = 4.618, 95% confidence interval: 1.071-19.924, p = 0.04). CONCLUSION: The prevalence of food insecurity in this study is higher than is reported in similar studies (41%). Mental health practitioners should routinely assess and monitor food insecurity in people living with severe mental illness. Further research should focus on food insecurity interventions in this population.

Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth.

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation, but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo. Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types. Here, we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model. In addition, we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells. The combined modeling reproduced severe hypoxic conditions and the Warburg effect, and we found that limitations in enzymatic capacity contribute to cancer cells' preferential use of glutamine as a substrate to the citric acid cycle. Furthermore, we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells. We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts, but when limiting to metabolites previously identified to participate in such collaboration, no growth advantage was observed. Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

Brain energy metabolism is optimized to minimize the cost of enzyme synthesis and transport.

The energy metabolism of the brain is poorly understood partly due to the complex morphology of neurons and fluctuations in ATP demand over time. To investigate this, we used metabolic models that estimate enzyme usage per pathway, enzyme utilization over time, and enzyme transportation to evaluate how these parameters and processes affect ATP costs for enzyme synthesis and transportation. Our models show that the total enzyme maintenance energy expenditure of the human body depends on how glycolysis and mitochondrial respiration are distributed both across and within cell types in the brain. We suggest that brain metabolism is optimized to minimize the ATP maintenance cost by distributing the different ATP generation pathways in an advantageous way across cell types and potentially also across synapses within the same cell. Our models support this hypothesis by predicting export of lactate from both neurons and astrocytes during peak ATP demand, reproducing results from experimental measurements reported in the literature. Furthermore, our models provide potential explanation for parts of the astrocyte-neuron lactate shuttle theory, which is recapitulated under some conditions in the brain, while contradicting other aspects of the theory. We conclude that enzyme usage per pathway, enzyme utilization over time, and enzyme transportation are important factors for defining the optimal distribution of ATP production pathways, opening a broad avenue to explore in brain metabolism.

Use of co-production to explore food insecurity in adults with severe mental illness living in Northern England: a mixed-methods study.

BACKGROUND: People living with severe mental illness experience premature mortality from diet-related preventable illnesses. Yet, little research focuses on food insecurity with adults with severe mental illness. This coproduced study aimed to understand the experiences of adults with severe mental illness and food insecurity and strategies to help. METHODS: Following a pragmatism philosophical foundation, we undertook a mixed-methods study involving a survey (online and paper versions) and one-to-one semi-structured interviews (online and telephone) during March 7 to Dec 16, 2022. We recruited participants via existing severe mental illness service user groups and social media in Northern England. Eligible participants were adults (≥18 years) self-reporting a diagnosis of severe mental illness. Ethics approval was obtained from Teesside University and the Health Research Authority (Reference: 22/NR/0010; IRAS ID: 306281), with informed consent given. The target sample size, accounting for a typical survey response rate for people with severe mental illness of 10-20%, was 135. A target sample of 20 interviews was agreed to capture a range of views. Food insecurity was defined as the lack of financial resources needed to ensure someone has reliable access to enough food to meet their dietary, nutritional, and social needs. It is sometimes called food poverty. Quantitative data were analysed using descriptive statistics and binary logistic regression and qualitative data using thematic analysis. FINDINGS: 135 participants completed the survey (mean age 44·67 years [SD 14·1]). Participants were predominantly male (53%, n=72), white (87%, n=117), and from the Yorkshire region (50%, n=68). Overall, prevalence of food insecurity was 50·4% (n=68). Discussion across 13 interviews found food insecurity being a long-rooted experience, including familial and intergenerational experiences of food insecurity: "I grew up… with this insecurity around food" (P002). Recommendations for tackling food insecurity centred on food banks, increasing accessibility, and reducing stigma: "I would like to get more information on where the centres are..." (P006) and "I was referred to, erm, a foodbank … but it's still the stigma that's attached to it." (P002). INTERPRETATION: We found a higher prevalence of food insecurity in this study than in the general population (being 15%), yet limited research with adults with severe mental illness perpetuates food insecurity intergenerational injustices. Food insecurity should be eliminated. However, in the meanwhile, there should be widespread easy access to food banks offering nutritional foods. Limitations of this research include not reaching target sample size and a lack of ethnic diversity. FUNDING: National Institute of Health and Care Research (NIHR) Research for Patient Benefit.

Same but different: The latency of a shared expectation signal interacts with stimulus attributes.

Predictive coding theories assert that perceptual inference is a hierarchical process of belief updating, wherein the onset of unexpected sensory data causes so-called prediction error responses that calibrate erroneous inferences. Given the functionally specialised organisation of visual cortex, it is assumed that prediction error propagation interacts with the specific visual attribute violating an expectation. We sought to test this within the temporal domain by applying time-resolved decoding methods to electroencephalography (EEG) data evoked by contextual trajectory violations of either brightness, size, or orientation within a bound stimulus. We found that following ∼170 ms post stimulus onset, responses to both size violations and orientation violations were decodable from physically identical control trials in which no attributes were violated. These two violation types were then directly compared, with attribute-specific signalling being decoded from 265 ms. Temporal generalisation suggested that this dissociation was driven by latency shifts in shared expectation signalling between the two conditions. Using a novel temporal bias method, we then found that this shared signalling occurred earlier for size violations than orientation violations. To our knowledge, we are among the first to decode expectation violations in humans using EEG and have demonstrated a temporal dissociation in attribute-specific expectancy violations.

Body as First Teacher: The Role of Rhythmic Visceral Dynamics in Early Cognitive Development.

Embodied cognition-the idea that mental states and processes should be understood in relation to one's bodily constitution and interactions with the world-remains a controversial topic within cognitive science. Recently, however, increasing interest in predictive processing theories among proponents and critics of embodiment alike has raised hopes of a reconciliation. This article sets out to appraise the unificatory potential of predictive processing, focusing in particular on embodied formulations of active inference. Our analysis suggests that most active-inference accounts invoke weak, potentially trivial conceptions of embodiment; those making stronger claims do so independently of the theoretical commitments of the active-inference framework. We argue that a more compelling version of embodied active inference can be motivated by adopting a diachronic perspective on the way rhythmic physiological activity shapes neural development in utero. According to this visceral afferent training hypothesis, early-emerging physiological processes are essential not only for supporting the biophysical development of neural structures but also for configuring the cognitive architecture those structures entail. Focusing in particular on the cardiovascular system, we propose three candidate mechanisms through which visceral afferent training might operate: (a) activity-dependent neuronal development, (b) periodic signal modeling, and (c) oscillatory network coordination.

Yoga and Multiple Sclerosis: Maintaining engagement in physical activity.

BACKGROUND: Physical activity is encouraged for people with Multiple Sclerosis. Yoga is a popular form of physical activity and is chosen by some people with Multiple Sclerosis. However, little is known about the impact of yoga for this population, alongside what influences ongoing engagement. AIM: The aim of this study is to qualitatively explore the impact of online home-based yoga on people with Multiple Sclerosis and to explore factors that influence engagement. METHODS: A qualitative study using semi-structured interviews and focus groups with people with Multiple Sclerosis and a yoga teacher. Thematic analysis was used to analyse the data. Ethical Approval was gained from Northumbria University. FINDINGS: Three overarching themes emerged from the analysis. 'Yoga as engagement in physical activity' captured the reasoning for participating in yoga and how this method of physical activity was an alternative to physical activity done prior to diagnosis. Frustration was apparent within this theme that some individuals were unable to engage in the range of physical activity that they wished to. 'Yoga is a personalised approach' demonstrated the flexibility and inclusivity of yoga, for individuals with varying symptoms to be able to engage with. Finally, 'yoga impacts individuals both physically and psychologically' captured the focus on the psychological impact of yoga, improving wellbeing and control. CONCLUSIONS: Yoga gives people with Multiple Sclerosis the feeling of control over their symptoms and a means to engage with meaningful physical activity. Prior involvement in physical activity influenced engagement in yoga and wanting to push themselves. There was reluctance among this group to engage with aerobic activity, which warrants future investigation and support from health and exercise professionals.

Did people really drink bleach to prevent COVID-19? A guide for protecting survey data against problematic respondents.

Survey respondents who are non-attentive, respond randomly, or misrepresent who they are can impact the outcomes of surveys. Prior findings reported by the CDC have suggested that people engaged in highly dangerous cleaning practices during the COVID-19 pandemic, including ingesting household cleaners such as bleach. In our attempts to replicate the CDC's results, we found that 100% of reported ingestion of household cleaners are made by problematic respondents. Once inattentive, acquiescent, and careless respondents are removed from the sample, we find no evidence that people ingested cleaning products to prevent a COVID-19 infection. These findings have important implications for public health and medical survey research, as well as for best practices for avoiding problematic respondents in all survey research conducted online.

Is it ethical to use Mechanical Turk for behavioral research? Relevant data from a representative survey of MTurk participants and wages.

To understand human behavior, social scientists need people and data. In the last decade, Amazon's Mechanical Turk (MTurk) emerged as a flexible, affordable, and reliable source of human participants and was widely adopted by academics. Yet despite MTurk's utility, some have questioned whether researchers should continue using the platform on ethical grounds. The brunt of their concern is that people on MTurk are financially insecure, subject to abuse, and earn inhumane wages. We investigated these issues with two representative probability surveys of the U.S. MTurk population (N = 4094). The surveys revealed: (1) the financial situation of people on MTurk mirrors the general population, (2) most participants do not find MTurk stressful or requesters abusive, and (3) MTurk offers flexibility and benefits that most people value above other options for work. People reported it is possible to earn more than $10 per hour and said they would not trade the flexibility of MTurk for less than $25 per hour. Altogether, our data are important for assessing whether MTurk is an ethical place for research.

Infection prevention and control measures for preterm infants discharged into the community: a scoping review protocol.

BACKGROUND: Infection prevention and control (IPC) is an evidence-based and practical approach to prevention of harm by infection (Infection prevention and control https://www.who.int/health-topics/infection-prevention-and-control#tab=tab_1 ). IPC recommendations targeted at community-acquired infection aim to prevent illness and subsequent hospital readmission. Cohesive guidance for parents of preterm infants has not been clearly established. The review objectives are to identify and map the global characteristics of IPC measures/recommendations for parents of preterm infants discharged home to the community. METHODS: The scoping review will be conducted using the JBI methodological approach for scoping reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension (PRISMA ScR) and the PRISMA extension for reporting literature searches in systematic reviews. Electronic databases will be searched and limited by publication year (2013-present day). Grey literature, reference lists and expert-provided sources will be searched against predetermined criteria. A minimum of two authors will independently screen evidence sources and chart evidence on a predetermined charting form. Sources including IPC measures, or recommendations for parents of preterm infants during discharge planning or in the community/home, will be permitted within inclusion criteria. Limits include human studies only and evidence from 2013-present day. Recommendations aimed at professional implementation will be excluded. A descriptive summary of findings will be presented, with diagrammatic and tabular representation. DISCUSSION: Collated evidence will guide future research which will subsequently aim to develop policy and enhance clinical approaches. SYSTEMATIC REVIEW REGISTRATION: This review has been registered on the Open Science Framework (OSF) 4th May 2021, available at https://osf.io/9yhzk .

Non-pharmacological and non-invasive interventions for chronic pain in people with chronic obstructive pulmonary disease: A systematic review without meta-analysis.

OBJECTIVES: Chronic Obstructive Pulmonary Disease (COPD) is complicated by chronic pain. People with COPD report higher pain prevalence than the general population. Despite this, chronic pain management is not reflected in current COPD clinical guidelines and pharmacological treatments are often ineffective. We conducted a systematic review that aimed to establish the efficacy of existing non-pharmacological and non-invasive interventions on pain and identify behaviour change techniques (BCTs) associated with effective pain management. METHODS: A systematic review was conducted with reference to Preferred Reporting Items for Systematic Review (PRISMA) [1], Systematic review without Meta analysis (SWIM) standards [2] and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines [3]. We searched 14 electronic databases for controlled trials of non-pharmacological and non-invasive interventions where the outcome measure assessed pain or contained a pain subscale. RESULTS: Twenty-nine studies were identified involving 3,228 participants. Seven interventions reported a minimally important clinical difference in pain outcomes, although only two of these reached statistical significance (p < 0.05). A third study reported statistically significant outcomes, but this was not clinically significant (p = 0.0273). Issues with intervention reporting prevented identification of active intervention ingredients (i.e., BCTs). CONCLUSIONS: Pain appears to be a meaningful issue for many individuals with COPD. However, intervention heterogeneity and issues with methodological quality limit certainty about the effectiveness of currently available non-pharmacological interventions. An improvement in reporting is required to enable identification of active intervention ingredients associated with effective pain management.

Application of occupational justice concepts to children who are born preterm or admitted to neonatal intensive care and their parents: a scoping review protocol.

OBJECTIVE: This review aims to identify and map the usage, application, and context of occupational justice concepts and related terms by occupational therapists and occupational scientists in relation to parents and children when children are born preterm or admitted to a neonatal intensive care unit. INTRODUCTION: Occupational justice concepts and related terms can inform occupational therapy practice at the individual level or as a wider social approach. However, the extent to which these concepts have been applied to parents and children, when children are born preterm or admitted to neonatal intensive care, is unknown. INCLUSION CRITERIA: Studies must include 1 or more occupational justice concepts or associated terms in relation to the named population groups. Sources must be related to occupational therapy or occupational science. METHODS: The review will follow the JBI methodology for scoping reviews and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and the PRISMA-S extension for reporting literature searches in systematic reviews. Several electronic databases and sources of gray literature will be searched, limited by publication year (2000 till the present day). The review will only include human studies and studies with a title or abstract in English. Book chapters will be excluded. Reference lists of included studies will be searched against pre-determined criteria. Evidence sources will be independently screened by a minimum of 2 authors, and evidence will be mapped on a pre-determined template. DETAILS OF THE REVIEW AVAILABLE AT: Open Science Framework https://osf.io/fgd7n.

Generation and analysis of context-specific genome-scale metabolic models derived from single-cell RNA-Seq data.

Single-cell RNA sequencing combined with genome-scale metabolic models (GEMs) has the potential to unravel the differences in metabolism across both cell types and cell states but requires new computational methods. Here, we present a method for generating cell-type-specific genome-scale models from clusters of single-cell RNA-Seq profiles. Specifically, we developed a method to estimate the minimum number of cells required to pool to obtain stable models, a bootstrapping strategy for estimating statistical inference, and a faster version of the task-driven integrative network inference for tissues algorithm for generating context-specific GEMs. In addition, we evaluated the effect of different RNA-Seq normalization methods on model topology and differences in models generated from single-cell and bulk RNA-Seq data. We applied our methods on data from mouse cortex neurons and cells from the tumor microenvironment of lung cancer and in both cases found that almost every cell subtype had a unique metabolic profile. In addition, our approach was able to detect cancer-associated metabolic differences between cancer cells and healthy cells, showcasing its utility. We also contextualized models from 202 single-cell clusters across 19 human organs using data from Human Protein Atlas and made these available in the web portal Metabolic Atlas, thereby providing a valuable resource to the scientific community. With the ever-increasing availability of single-cell RNA-Seq datasets and continuously improved GEMs, their combination holds promise to become an important approach in the study of human metabolism.

Effectiveness of a neonatal COVID-19 response project: A mixed-methods evaluation using the Donabedian model.

Objective: This article outlines notable findings of a service evaluation of a COVID-19 response project, the Nurture Project (July 2020-March 2021). Method: The Donabedian structure-process-outcome model was used. Mixed-methods online surveys and organisational data were analysed using reflexive thematic analysis and statistical analysis methods. Results: Most staff and service users were satisfied with the project, reporting positive benefits to mental health, child development, and wellbeing. However, project outcome measures (Generalised Anxiety Disorder Scale GAD-7 and the Patient Health Questionnaire PHQ-9) were statistically non-significant. Conclusion: Although the project was considered successful, recommendations for future service evaluation methods, outcome measurement, and future research are provided.

Foraging for the self: Environment selection for agency inference.

Sometimes agents choose to occupy environments that are neither traditionally rewarding nor worth exploring, but which rather promise to help minimise uncertainty related to what they can control. Selecting environments that afford inferences about agency seems a foundational aspect of environment selection dynamics - if an agent can't form reliable beliefs about what they can and can't control, then they can't act efficiently to achieve rewards. This relatively neglected aspect of environment selection is important to study so that we can better understand why agents occupy certain environments over others - something that may also be relevant for mental and developmental conditions, such as autism. This online experiment investigates the impact of uncertainty about agency on the way participants choose to freely move between two environments, one that has greater irreducible variability and one that is more complex to model. We hypothesise that increasingly erroneous predictions about the expected outcome of agency-exploring actions can be a driver of switching environments, and we explore which type of environment agents prefer. Results show that participants actively switch between the two environments following increases in prediction error, and that the tolerance for prediction error before switching is modulated by individuals' autism traits. Further, we find that participants more frequently occupy the variable environment, which is predicted by greater accuracy and higher confidence than the complex environment. This is the first online study to investigate relatively unconstrained ongoing foraging dynamics in support of judgements of agency, and in doing so represents a significant methodological advance.

Evaluating CloudResearch's Approved Group as a solution for problematic data quality on MTurk.

Maintaining data quality on Amazon Mechanical Turk (MTurk) has always been a concern for researchers. These concerns have grown recently due to the bot crisis of 2018 and observations that past safeguards of data quality (e.g., approval ratings of 95%) no longer work. To address data quality concerns, CloudResearch, a third-party website that interfaces with MTurk, has assessed ~165,000 MTurkers and categorized them into those that provide high- (~100,000, Approved) and low- (~65,000, Blocked) quality data. Here, we examined the predictive validity of CloudResearch's vetting. In a pre-registered study, participants (N = 900) from the Approved and Blocked groups, along with a Standard MTurk sample (95% HIT acceptance ratio, 100+ completed HITs), completed an array of data-quality measures. Across several indices, Approved participants (i) identified the content of images more accurately, (ii) answered more reading comprehension questions correctly, (iii) responded to reversed coded items more consistently, (iv) passed a greater number of attention checks, (v) self-reported less cheating and actually left the survey window less often on easily Googleable questions, (vi) replicated classic psychology experimental effects more reliably, and (vii) answered AI-stumping questions more accurately than Blocked participants, who performed at chance on multiple outcomes. Data quality of the Standard sample was generally in between the Approved and Blocked groups. We discuss how MTurk's Approval Rating system is no longer an effective data-quality control, and we discuss the advantages afforded by using the Approved group for scientific studies on MTurk.

Muscle recovery after total hip arthroplasty: prospective MRI comparison of anterior and posterior approaches.

INTRODUCTION: The direct anterior approach (DAA) and the posterior approach (PA) are 2 common total hip arthroplasty (THA) exposures. This prospective study quantitatively compared changes in periarticular muscle volume after DAA and PA THA. MATERIALS: 19 patients undergoing THA were recruited prospectively from the practices of 3 fellowship-trained hip surgeons. Each surgeon performed a single approach, DAA or PA. Enrolled patients underwent a preoperative MRI of the affected hip and two subsequent postoperative MRIs at around 6 weeks and 6 months after surgery. Clinical evaluations were done by Harris Hip Score at each follow-up interval. RESULTS: MRIs or 10 DAA and 9 PA patients were analysed. Groups did not differ significantly with regard to BMI, age, or preoperative muscle volume. 1 DAA patient suffered a periprosthetic fracture and was excluded from the study. DAA hips showed significant atrophy in the obturator internus (-37.3%) muscle at early follow-up, with persistent atrophy of this muscle at the final follow-up. PA hips showed significant atrophy in the obturator internus (-46.8%) and externus (-16.0%), piriformis (-8.12%), and quadratus femoris muscles (-13.1%) at early follow-up, with persistent atrophy of these muscles at final follow-up. Loss of anterior capsular integrity was present at final follow-up in 2/10 DAA hips while loss of posterior capsular integrity was present in 5/9 PA hips. There was no difference in clinical outcomes. DISCUSSION: This study demonstrates that DAA showed less persistent muscular atrophy than PA. Regardless of surgical approach, a muscle whose tendon is detached from its insertion is likely to demonstrate persistent atrophy 6 months following THA. Although the study was not powered to compare clinical outcomes, it should be noted that no significant difference in patient outcomes was observed.

Do you know the Wooly Bully? Testing era-based knowledge to verify participant age online.

People in online studies sometimes misrepresent themselves. Regardless of their motive for doing so, participant misrepresentation threatens the validity of research. Here, we propose and evaluate a way to verify the age of online respondents: a test of era-based knowledge. Across six studies (N = 1543), participants of various ages completed an age verification instrument. The instrument assessed familiarity with cultural phenomena (e.g., songs and TV shows) from decades past and present. We consistently found that our instrument discriminated between people of different ages. In Studies 1a and 1b, self-reported age correlated strongly with performance on the instrument (mean r = .8). In Study 2, the instrument reliably detected imposters who we knew were misrepresenting their age. For impostors, self-reported age did not correlate with performance on the instrument (r = .077). Finally, in Studies 3a, 3b, and 3c, the instrument remained robust with African Americans, people from low educational backgrounds, and recent immigrants to the United States. Thus, our instrument shows promise for verifying the age of online respondents, and, as we discuss, our approach of assessing "insider knowledge" holds great promise for verifying other identities within online studies.

Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision.

BACKGROUND: Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1-2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84-99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. METHODS: Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. FINDINGS: Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67-80] vs 65 years [61-71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6-12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. INTERPRETATION: The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. FUNDING: Cancer Research UK.