The Steinhaus-Weil property: I. Subcontinuity and amenability

The Steinhaus-Weil theorem that concerns us here is the simple, or classical, 'interior-points' property - that in a Polish topological group a non-negligible set B has the identity as an interior point of Bˆ-1B: There are various converses; the one that mainly concerns us is due to Simmons and Mospan. Here the group is locally compact, so we have a Haar reference measure η. The Simmons-Mospan theorem states that a (regular Borel) measure has such a Steinhaus-Weil property if and only if it is absolutely continuous with respect to the Haar measure. This the first of four companion papers (we refer to the others as II [BinO11], III, [BinO12], and IV, [BinO13], below). Here (Propositions 1-7 and Theorems 1-4) we exploit the connection between the interior-points property and a selective form of infinitesimal invariance afforded by a certain family of selective reference measures σ, drawing on Soleckiís amenability at 1 (and using Fuller's notion of subcontinuity). In II, we turn to a converse of the Steinhaus-Weil theorem, the Simmons- Mospan theorem, and related results. In III, we discuss Weil topologies, linking the topological group-theoretic and measure-theoretic aspects. We close in IV with some other interior-point results related to the Steinhaus- Weil theorem

The validity and reliability of school-based fundamental movement skills screening to identify children with motor difficulties

Aim Assess whether school-based teacher-led screening is effective at identifying children with motor difficulties. Methods Teachers tested 217 children aged between 5 and 11 years old, after a one hour training session, using a freely available tool (FUNMOVES). Four classes (n = 91) were scored by both researchers and teachers to evaluate inter-rater reliability. Researchers assessed 22 children using the Movement Assessment Battery for Children (MABC-2; considered to be the ‘gold standard’ in Europe for use as part of the diagnostic process for Developmental Coordination Disorder) to assess concurrent and predictive validity. Results Inter-rater reliability for all individual activities within FUNMOVES ranged from 0.85–0.97 (unweighted Kappa; with 95%CI ranging from 0.77–1). For total score this was lower (κ = 0.76, 95%CI = 0.68–0.84), however when incorporating linear weighting, this improved (κ = 0.94, 95%CI = 0.89–0.99). When evaluating FUNMOVES total score against the MABC-2 total score, the specificity (1, 95%CI = 0.63–1) and positive predictive value (1; 95%CI = 0.68–1) of FUNMOVES were high, whereas sensitivity (0.57, 95%CI = 0.29–0.82) and negative predictive values (0.57, 95%CI = 0.42–0.71) were moderate. Evaluating only MABC-2 subscales which are directly related to fundamental movement skills (Aiming &amp; Catching, and Balance) improved these values to 0.89 (95%CI = 0.52–1) and 0.93 (95%CI = 0.67– 0.99) respectively. Interpretation Teacher-led screening of fundamental movement skills (via FUNMOVES) is an effective method of identifying children with motor difficulties. Such universal screening in schools has the potential to identify movement difficulties and enable earlier intervention than the current norm.</p

Developing and validating a school-based screening tool of Fundamental Movement Skills (FUNMOVES) using Rasch analysis

Background A large proportion of children are not able to perform age-appropriate fundamental movement skills (FMS). Thus, it is important to assess FMS so that children needing additional support can be identified in a timely fashion. There is great potential for universal screening of FMS in schools, but research has established that current assessment tools are not fit for purpose. Objective To develop and validate the psychometric properties of a FMS assessment tool designed specifically to meet the demands of universal screening in schools. Methods A working group consisting of academics from developmental psychology, public health and behavioural epidemiology developed an assessment tool (FUNMOVES) based on theory and prior evidence. Over three studies, 814 children aged 4 to 11 years were assessed in school using FUNMOVES. Rasch analysis was used to evaluate structural validity and modifications were then made to FUNMOVES activities after each study based on Rasch results and implementation fidelity. Results The initial Rasch analysis found numerous psychometric problems including multidimensionality, disordered thresholds, local dependency, and misfitting items. Study 2 showed a unidimensional measure, with acceptable internal consistency and no local dependency, but that did not fit the Rasch model. Performance on a jumping task was misfitting, and there were issues with disordered thresholds (for jumping, hopping and balance tasks). Study 3 revealed a unidimensional assessment tool with good fit to the Rasch model, and no further issues, once jumping and hopping scoring were modified.Implications The finalised version of FUNMOVES (after three iterations) meets standards for accurate measurement, is free and able to assess a whole class in under an hour using resources available in schools. Thus FUNMOVES has the potential to allow schools to efficiently screen FMS to ensure that targeted support can be provided and disability barriers removed.</p

Global Brain Dynamics during Social Exclusion Predict Subsequent Behavioral Conformity

Individuals react differently to social experiences; for example, people who are more sensitive to negative social experiences, such as being excluded, may be more likely to adapt their behavior to fit in with others. We examined whether functional brain connectivity during social exclusion in the fMRI scanner can be used to predict subsequent conformity to peer norms. Adolescent males (n = 57) completed a two-part study on teen driving risk: a social exclusion task (Cyberball) during an fMRI session and a subsequent driving simulator session in which they drove alone and in the presence of a peer who expressed risk-averse or risk-accepting driving norms. We computed the difference in functional connectivity between social exclusion and social inclusion from each node in the brain to nodes in two brain networks, one previously associated with mentalizing (medial prefrontal cortex, temporoparietal junction, precuneus, temporal poles) and another with social pain (dorsal anterior cingulate cortex, anterior insula). Using predictive modeling, this measure of global connectivity during exclusion predicted the extent of conformity to peer pressure during driving in the subsequent experimental session. These findings extend our understanding of how global neural dynamics guide social behavior, revealing functional network activity that captures individual differences

Association between urinary biomarkers of total sugars intake and measures of obesity in a cross-sectional study

Obesity is an important modifiable risk factor for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative sample of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24 h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between biomarker-based estimated intake and measures of obesity (body mass intake (BMI), waist circumference and waist-to-hip ratio) and obesity risk, respectively. Estimated sugar intake was significantly associated with BMI, waist circumference and waist-to-hip ratio; these associations remained significant after adjustment for estimated protein intake as a marker of non-sugar energy intake. Estimated sugar intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95%CI 1.00-1.04 per 10g), waist-circumference (1.03; 1.01-1.05) and waist-to-hip ratio (1.04; 1.02-1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results strongly support positive associations between total sugar intake, measures of obesity and likelihood of being obese. It is the first time that such an association has been shown in a nationally-representative sample of the general population using a validated biomarker. This biomarker could be used to monitor the efficacy of public health interventions to reduce sugar intake

Main nutrient patterns and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Much of the current literature on diet-colorectal cancer (CRC) associations focused on studies of single foods/nutrients, whereas less is known about nutrient patterns. We investigated the association between major nutrient patterns and CRC risk in participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Among 477 312 participants, intakes of 23 nutrients were estimated from validated dietary questionnaires. Using results from a previous principal component (PC) analysis, four major nutrient patterns were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for the association of each of the four patterns and CRC incidence using multivariate Cox proportional hazards models with adjustment for established CRC risk factors. RESULTS: During an average of 11 years of follow-up, 4517 incident cases of CRC were documented. A nutrient pattern characterised by high intakes of vitamins and minerals was inversely associated with CRC (HR per 1 s.d.=0.94, 95% CI: 0.92-0.98) as was a pattern characterised by total protein, riboflavin, phosphorus and calcium (HR (1 s.d.)=0.96, 95% CI: 0.93-0.99). The remaining two patterns were not significantly associated with CRC risk. CONCLUSIONS: Analysing nutrient patterns may improve our understanding of how groups of nutrients relate to CRC

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival