Geometry of Control-Affine Systems

Motivated by control-affine systems in optimal control theory, we introduce the notion of a point-affine distribution on a manifold X - i.e., an affine distribution F together with a distinguished vector field contained in F. We compute local invariants for point-affine distributions of constant type when dim(X)=n, rank(F)=n-1, and when dim(X)=3, rank(F)=1. Unlike linear distributions, which are characterized by integer-valued invariants - namely, the rank and growth vector - when dim(X)<=4, we find local invariants depending on arbitrary functions even for rank 1 point-affine distributions on manifolds of dimension 2

Geometry of Optimal Control for Control-Affine Systems

Motivated by the ubiquity of control-affine systems in optimal control theory, we investigate the geometry of point-affine control systems with metric structures in dimensions two and three. We compute local isometric invariants for point-affine distributions of constant type with metric structures for systems with 2 states and 1 control and systems with 3 states and 1 control, and use Pontryagin's maximum principle to find geodesic trajectories for homogeneous examples. Even in these low dimensions, the behavior of these systems is surprisingly rich and varied

Does an interactive trust-enhanced electronic consent improve patient experiences when asked to share their health records for research? A randomized trial

Objective In the context of patient broad consent for future research uses of their identifiable health record data, we compare the effectiveness of interactive trust-enhanced e-consent, interactive-only e-consent, and standard e-consent (no interactivity, no trust enhancement). Materials and Methods A randomized trial was conducted involving adult participants making a scheduled primary care visit. Participants were randomized into 1 of the 3 e-consent conditions. Primary outcomes were patient-reported satisfaction with and subjective understanding of the e-consent. Secondary outcomes were objective knowledge, perceived voluntariness, trust in medical researchers, consent decision, and time spent using the application. Outcomes were assessed immediately after use of the e-consent and at 1-week follow-up. Results Across all conditions, participants (N = 734) reported moderate-to-high satisfaction with consent (mean 4.3 of 5) and subjective understanding (79.1 of 100). Over 94% agreed to share their health record data. No statistically significant differences in outcomes were observed between conditions. Irrespective of condition, black participants and those with lower education reported lower satisfaction, subjective understanding, knowledge, perceived voluntariness, and trust in medical researchers, as well as spent more time consenting. Conclusions A large majority of patients were willing to share their identifiable health records for research, and they reported positive consent experiences. However, incorporating optional additional information and messages designed to enhance trust in the research process did not improve consent experiences. To improve poorer consent experiences of racial and ethnic minority participants and those with lower education, other novel consent technologies and processes may be valuable

Paracetamol, NSAIDS and opioid analgesics for chronic low back pain: A network meta-analysis (Protocol)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To answer the clinical question: ‘what analgesic medicine shall I prescribe this patient with chronic low back pain to reduce their pain?’. The objectives are to determine the analgesic effects, safety, effect on function, and relative rank according to analgesic effect, safety and effect on function of a single course of opioid analgesics, NSAIDs or paracetamol or combinations of these medicines

Do health education initiatives assist socioeconomically disadvantaged populations? : a systematic review and meta-analyses

Background: Health education interventions are considered critical for the prevention and management of conditions of public health concern. Although the burden of these conditions is often greatest in socio-economically disadvantaged populations, the effectiveness of interventions that target these groups is unknown. We aimed to identify and synthesize evidence of the effectiveness of health-related educational interventions in adult disadvantaged populations. Methods: We pre-registered the study on Open Science Framework https://osf.io/ek5yg/. We searched Medline, Embase, Emcare, and the Cochrane Register from inception to 5/04/2022 to identify studies evaluating the effectiveness of health-related educational interventions delivered to adults in socio-economically disadvantaged populations. Our primary outcome was health related behaviour and our secondary outcome was a relevant biomarker. Two reviewers screened studies, extracted data and evaluated risk of bias. Our synthesis strategy involved random-effects meta-analyses and vote-counting. Results: We identified 8618 unique records, 96 met our criteria for inclusion – involving more than 57,000 participants from 22 countries. All studies had high or unclear risk of bias. For our primary outcome of behaviour, meta-analyses found a standardised mean effect of education on physical activity of 0.05 (95% confidence interval (CI) = -0.09–0.19), (5 studies, n = 1330) and on cancer screening of 0.29 (95% CI = 0.05–0.52), (5 studies, n = 2388). Considerable statistical heterogeneity was present. Sixty-seven of 81 studies with behavioural outcomes had point estimates favouring the intervention (83% (95% CI = 73%-90%), p < 0.001); 21 of 28 studies with biomarker outcomes showed benefit (75% (95%CI = 56%-88%), p = 0.002). When effectiveness was determined based on conclusions in the included studies, 47% of interventions were effective on behavioural outcomes, and 27% on biomarkers. Conclusions: Evidence does not demonstrate consistent, positive impacts of educational interventions on health behaviours or biomarkers in socio-economically disadvantaged populations. Continued investment in targeted approaches, coinciding with development of greater understanding of factors determining successful implementation and evaluation, are important to reduce inequalities in health

The RESOLVE Trial for people with chronic low back pain: Statistical analysis plan

Background: Statistical analysis plans describe the planned data management and analysis for clinical trials. This supports transparent reporting and interpretation of clinical trial results. This paper reports the statistical analysis plan for the RESOLVE clinical trial. The RESOLVE trial assigned participants with chronic low back pain to graded sensory-motor precision training or sham-control. Results: We report the planned data management and analysis for the primary and secondary outcomes. The primary outcome is pain intensity at 18-weeks post randomization. We will use mixed-effects models to analyze the primary and secondary outcomes by intention-to-treat. We will report adverse effects in full. We also describe analyses if there is non-adherence to the interventions, data management procedures, and our planned reporting of results. Conclusion: This statistical analysis plan will minimize the potential for bias in the analysis and reporting of results from the RESOLVE trial. Trial registration: ACTRN12615000610538 (https://www.anzctr.org.au/Trial/Registration/ TrialReview.aspx?id=368619). © 2020 Associac¸ao˜ Brasileira de Pesquisa e Pos-Graduac ´ ¸ao˜ em Fisioterapia. Published by Elsevier Editora Ltda. All rights reserved

Downregulation of the citrullinating enzyme Peptidyl-arginine deiminase type-2 in ovarian cancer indicates poor prognosis

Background Peptidyl-arginine deiminase enzymes have been implicated in several tumour types where expression regulates tumour cell growth and survival. We hypothesised that PAD2 may play an important role in ovarian cancer and may provide utility as an independent prognostic marker. Method Using tissue microarrays of primary ovarian cancers and compiling a comprehensive database of clinicopathological variables, the expression of PAD2 was assessed by immunohistochemistry in discovery (n=194) and validation (n=360) cohorts using a monoclonal antibody specific for PAD2. Results Kaplan-Meier analysis indicated that there was an association of PAD2 expression with overall survival in discovery (p=0.033) and validation cohorts (p=0.026). Upregulated expression of PAD2 was protective and in a multivariate model PAD2 expression remained an independent prognostic factor (p=0.029). PAD2 expression was associated with known regulators of autophagy (HMGB1 and BCL2) and immune surveillance (HLA and IFGR1). Conclusion Low PAD2 expression is an independent predictor of poor survival in ovarian cancer. PAD2 is a positive regulator of citrullination within the cell and high levels of citrullinated proteins may flag the immune system to target ovarian tumors. This work suggests that targeting citrullination pathways in ovarian cancer may represent a viable therapeutic target

Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.

Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mouse model demonstrate that the methionine salvage pathway is a regulator of sepsis that can accurately predict prognosis in patients. Pathway-based genome-wide association analysis of nontyphoidal Salmonella bacteremia showed a strong enrichment for single-nucleotide polymorphisms near the components of the methionine salvage pathway. Measurement of the pathway's substrate, methylthioadenosine (MTA), in two cohorts of sepsis patients demonstrated increased plasma MTA in nonsurvivors. Plasma MTA was correlated with levels of inflammatory cytokines, indicating that elevated MTA marks a subset of patients with excessive inflammation. A machine-learning model combining MTA and other variables yielded approximately 80% accuracy (area under the curve) in predicting death. Furthermore, mice infected with Salmonella had prolonged survival when MTA was administered before infection, suggesting that manipulating MTA levels could regulate the severity of the inflammatory response. Our results demonstrate how combining genetic data, biomolecule measurements, and animal models can shape our understanding of disease and lead to new biomarkers for patient stratification and potential therapeutic targeting

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy