DACC Resting State Functional Connectivity as a Predictor of Pain Symptoms Following Motor Vehicle Crash: A Preliminary Investigation

There is significant heterogeneity in pain outcomes following motor vehicle crashes (MVCs), such that a sizeable portion of individuals develop symptoms of chronic pain months after injury while others recover. Despite variable outcomes, the pathogenesis of chronic pain is currently unclear. Previous neuroimaging work implicates the dorsal anterior cingulate cortex (dACC) in adaptive control of pain, while prior resting state functional magnetic resonance imaging studies find increased functional connectivity (FC) between the dACC and regions involved in pain processing in those with chronic pain. Hyper-connectivity of the dACC to regions that mediate pain response may therefore relate to pain severity. The present study completed rsfMRI scans on N=22 survivors of MVCs collected within two weeks of the incident to test whole-brain dACC-FC as a predictor of pain severity six months later. At two weeks, pain symptoms were predicted by positive connectivity between the dACC and the premotor cortex. Controlling for pain symptoms at two weeks, pain symptoms at six months were predicted by negative connectivity between the dACC and the precuneus. Previous research implicates the precuneus in the individual subjective awareness of pain. Given a relatively small sample size, approximately half of which did not experience chronic pain at six months, findings warrant replication. Nevertheless, this study provides preliminary evidence of enhanced dACC connectivity with motor regions and decreased connectivity with pain processing regions as immediate and prospective predictors of pain following MVC. Perspective: This article presents evidence of distinct neural vulnerabilities that predict chronic pain in motor vehicle crash survivors based on whole-brain connectivity with the dorsal anterior cingulate cortex

Divide and Conquer: Progress in the Molecular Stratification of Cancer

Cancer remains an outstanding cause of global morbidity and mortality, despite intensive research and unprecedented insights into the basic mechanisms of cancer development. A plethora of clinical and experimental evidence suggests that cancers from individual patients are likely to be molecularly heterogeneous in their use of distinct oncogenic pathways and biological programs. Efforts to significantly impact cancer patient outcomes will almost certainly require the development of robust strategies to subdivide such heterogeneous panels of cancers into biologically and clinically homogenous subgroups, for the purposes of personalizing treatment protocols and identifying optimal drug targets. In this review, I describe recent progress in the development of both targeted and genome-wide approaches for the molecular stratification of cancers, drawing examples from both the haematopoietic and solid tumor malignancies

Is detection of enteropathogens and human or animal faecal markers in the environment associated with subsequent child enteric infections and growth: an individual participant data meta-analysis.

BACKGROUND: Quantifying contributions of environmental faecal contamination to child diarrhoea and growth faltering can illuminate causal mechanisms behind modest health benefits in recent water, sanitation, and hygiene (WASH) trials. We aimed to assess associations between environmental detection of enteropathogens and human or animal microbial source tracking markers (MSTM) and subsequent child health outcomes. METHODS: In this individual participant data meta-analysis we searched we searched PubMed, Embase, CAB Direct Global Health, Agricultural and Environmental Science Database, Web of Science, and Scopus for WASH intervention studies with a prospective design and concurrent control that measured enteropathogens or MSTM in environmental samples, or both, and subsequently measured enteric infections, diarrhoea, or height-for-age Z-scores (HAZ) in children younger than 5 years. We excluded studies that only measured faecal indicator bacteria. The initial search was done on Jan 19, 2021, and updated on March 22, 2023. One reviewer (AM) screened abstracts, and two independent reviewers (AM and RT) examined the full texts of short-listed articles. All included studies include at least one author that also contributed as an author to the present Article. Our primary outcomes were the 7-day prevalence of caregiver-reported diarrhoea and HAZ in children. For specific enteropathogens in the environment, primary outcomes also included subsequent child infection with the same pathogen ascertained by stool testing. We estimated associations using covariate-adjusted regressions and pooled estimates across studies. FINDINGS: Data from nine published reports from five interventions studies, which included 8603 children (4302 girls and 4301 boys), were included in the meta-analysis. Environmental pathogen detection was associated with increased infection prevalence with the same pathogen and lower HAZ (ΔHAZ -0·09 [95% CI -0·17 to -0·01]) but not diarrhoea (prevalence ratio 1·22 [95% CI 0·95 to 1·58]), except during wet seasons. Detection of MSTM was not associated with diarrhoea (no pooled estimate) or HAZ (ΔHAZ -0·01 [-0·13 to 0·11] for human markers and ΔHAZ -0·02 [-0·24 to 0·21] for animal markers). Soil, children's hands, and stored drinking water were major transmission pathways. INTERPRETATION: Our findings support a causal chain from pathogens in the environment to infection to growth faltering, indicating that the lack of WASH intervention effects on child growth might stem from insufficient reductions in environmental pathogen prevalence. Studies measuring enteropathogens in the environment should subsequently measure the same pathogens in stool to further examine theories of change between WASH, faecal contamination, and health. Given that environmental pathogen detection was predictive of infection, programmes targeting specific pathogens (eg, vaccinations and elimination efforts) can environmentally monitor the pathogens of interest for population-level surveillance instead of collecting individual biospecimens. FUNDING: The Bill & Melinda Gates Foundation and the UK Foreign and Commonwealth Development Office

Behavior of Escherichia coli in a heterogeneous gelatin-dextran mixture

In a gelatin-dextran mixture, changing the (relative and/or absolute) concentration of the components leads to the formation of different microstructures. Confocal laser scanning microscopy illustrated that the nature of the microstructure determines the location and morphology of Escherichia coli colonies. Observations indicate that bacterial growth preferentially occurs in the dextran phase, regardless of the microstructure.status: publishe

An application of the Causal Roadmap in two safety monitoring case studies: Causal inference and outcome prediction using electronic health record data.

BACKGROUND: Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions transparently and objectively to assess and ensure that analyses meet their intended goals. METHODS: The Causal Roadmap is an established framework that can guide and document analytic decisions through each step of the analytic pipeline, which will help investigators generate high-quality real-world evidence. RESULTS: In this paper, we illustrate the utility of the Causal Roadmap using two case studies previously led by workgroups sponsored by the Sentinel Initiative - a program for actively monitoring the safety of regulated medical products. Each case example focuses on different aspects of the analytic pipeline for drug safety monitoring. The first case study shows how the Causal Roadmap encourages transparency, reproducibility, and objective decision-making for causal analyses. The second case study highlights how this framework can guide analytic decisions beyond inference on causal parameters, improving outcome ascertainment in clinical phenotyping. CONCLUSION: These examples provide a structured framework for implementing the Causal Roadmap in safety surveillance and guide transparent, reproducible, and objective analysis

Modelling the effects of copper on soil organisms and processes using the free ion approach: towards a multi-species toxicity model

The free ion approach has been previously used to calculate critical limit concentrations for soil metals based on point estimates of toxicity. Here, the approach was applied to dose–response data for copper effects on seven biological endpoints in each of 19 European soils. The approach was applied using the concept of an effective dose, comprising a function of the concentrations of free copper and ‘protective’ major cations, including H+. A significant influence of H+ on the toxicity of Cu2+ was found, while the effects of other cations were inconsistent. The model could be generalised by forcing the effect of H+ and the slope of the dose–response relationship to be equal for all endpoints. This suggests the possibility of a general bioavailability model for copper effects on organisms. Furthermore, the possibility of such a model could be explored for other cationic metals such as nickel, zinc, cadmium and lead