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Although this is beginning to change, the content of antenatal care has been relatively neglected in safe-motherhood program efforts. This appears in part to be due to an unwarranted belief that interventions over this period have far less impact than those provided around the time of birth. In this par, we review available evidence for 21 interventions potentially deliverable during pregnancy at high coverage to neglected populations in low income countries, with regard to effectiveness in reducing risk of: maternal mortality, newborn mortality, stillbirth, prematurity and intrauterine growth restriction. Selection was restricted to interventions that can be provided by non-professional health auxiliaries and not requiring laboratory support. In this narrative review, we included relevant Cochrane and other systematic reviews and did comprehensive bibliographic searches. Inclusion criteria varied by intervention; where available randomized controlled trial evidence was insufficient, observational study evidence was considered. For each intervention we focused on overall contribution to our outcomes of interest, across varying epidemiologies. In the aggregate, achieving high effective coverage for this set of interventions would very substantially reduce risk for our outcomes of interest and reduce outcome inequities. Certain specific interventions, if pushed to high coverage have significant potential impact across many settings. For example, reliable detection of pre-eclampsia followed by timely delivery could prevent up to ¼ of newborn and stillbirth deaths and over 90% of maternal eclampsia/pre-eclampsia deaths. Other interventions have potent effects in specific settings: in areas of high P falciparum burden, systematic use of insecticide-treated nets and/or intermittent presumptive therapy in pregnancy could reduce maternal mortality by up to 10%, newborn mortality by up to 20%, and stillbirths by up to 25-30%. Behavioral interventions targeting practices at birth and in the hours that follow can have substantial impact in settings where many births happen at home: in such circumstances early initiation of breastfeeding can reduce risk of newborn death by up to 20%; good thermal care practices can reduce mortality risk by a similar order of magnitude. Simple interventions delivered during pregnancy have considerable potential impact on important mortality outcomes. More programmatic effort is warranted to ensure high effective coverage.

Objective To address the opioid overdose epidemic, it is important to understand the broad scope of efforts under way in states, particularly states in which the rate of opioid-involved overdose deaths is declining. The primary objective of this study was to examine core elements of overdose prevention activities in 4 states with a high rate of opioid-involved overdose deaths that experienced a decrease in opioid-involved overdose deaths from 2016 to 2017. Methods We identified 5 states experiencing decreases in age-adjusted mortality rates for opioid-involved overdoses from 2016 to 2017 and examined their overdose prevention programs via program narratives developed with collaborators from each state’s overdose prevention program. These program narratives used 10 predetermined categories to organize activities: legislative policies; strategic planning; data access, capacity, and dissemination; capacity building; public-facing resources (eg, web-based dashboards); training resources; enhancements and improvements to prescription drug monitoring programs; linkage to care; treatment; and community-focused initiatives. Using qualitative thematic analysis techniques, core elements and context-specific activities emerged. Results In the predetermined categories of programmatic activities, we identified the following core elements of overdose prevention and response: comprehensive state policies; strategic planning; local engagement; data access, capacity, and dissemination; training of professional audiences (eg, prescribers); treatment infrastructure; and harm reduction. Conclusions The identification of core elements and context-specific activities underscores the importance of implementation and adaptation of evidence-based prevention strategies, interdisciplinary partnerships, and collaborations to address opioid overdose. Further evaluation of these state programs and other overdose prevention efforts in states where mortality rates for opioid-involved overdoses declined should focus on impact, optimal timing, and combinations of program activities during the life span of an overdose prevention program.

Precision medicine can significantly improve outcomes for patients with cancer, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here, we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy, resulting in long-term morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared with cells with monoallelic mutations. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first-line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for patients with cancer.

Background/Objectives: Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition that displays heterogeneity in both presentation and etiology, and often presents with concomitant communication difficulties. The hypothesis behind the New Jersey Language and Autism Genetic Study is that genetic heterogeneity for component phenotypes of ASD may be reduced relative to the disorder as a whole. We previously published an initial phase of this study with family recruitment that used very restricted inclusion/exclusion criteria for both autism and language deficits. Here, we present an expanded sample that includes a wider range of phenotypic presentations in the autism and language domains. Methods: Bioinformatics tools focusing on variant prioritization were used to identify candidate risk genes. Results: Our previous findings on 15q and 16q, connecting ASD and oral/written communication, are only relevant to the narrow ASD and language impairment phenotypes, though addition of families did reduce both critical regions. After variant and gene prioritization, we determined a set of ten and six top candidate risk genes with a strong association with language impairment and reading impairment, respectively. The top candidate genes include both genes previously implicated in neurodevelopmental disorders (e.g., ZNF774 and DNAH3) and genes not previously reported but with strong evidence of being involved in neurodevelopmental phenotypes. Conclusions: Our analysis elucidates the genetic architecture and interaction of ASD and language-related phenotypes. In addition, we reported a number of high-confidence candidate genes within the top linkage regions. These genes will provide insights into the genetic etiology of neurodevelopmental disorders.

Clinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings. To automatically extract acute brain pathological data and their features from head CT reports. This diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021. Performance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets. A total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%. These findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Alcohol has been shown to have a variety of effects on cognitive performance in humans; the present study tested the effects of alcohol on visual selective attention using three different paradigms. The effects of alcohol intoxication over a broad range of blood alcohol concentrations (average between 0.01 and 0.08) were evaluated for change blindness, inattentional blindness, and multiple object tracking. Alcohol was found to impair inattentional blindness performance, negatively affecting participants’ ability to notice the unexpected changes presented. This result is interpreted as support for the alcohol myopia theory. No significant effects of alcohol were found for change blindness or multiple object tracking.

Multinational corporations (MNCs) face the prospect of increased mandatory environmental, social, and governance (ESG) reporting requirements spurred by changing market demands from stakeholders for more sustainable products and services. MNCs must address this change while competing with mission-driven, social enterprises. The proactive exploration of an entrepreneurial strategy for social value creation to address this evolving role of business in society is imperative for MNC managers. This dissertation identified entrepreneurial strategy elements that support the creation of social value on a global scale within existing for-profit MNCs. An evidence-based, realist review methodology applying mixed evidence synthesis techniques was used to identify entrepreneurial strategy elements. Qualitative, quantitative, and mixed-method, peer-reviewed empirical studies were examined to determine which entrepreneurial strategy elements work for whom, how, and under what circumstances they can be applied. The findings indicated entrepreneurial elements supporting global social value creation include entrepreneurial ecosystem building, embedding within the issue’s social context, and persuasive marketing techniques to build awareness and collective action. When deployed within a proactive, innovative, and risk-taking organizational environment with an entrepreneurial management mindset, these strategy elements have an increased likelihood of achieving the intended value creation outcome. Based on these findings, an entrepreneurial strategy can be applied within the MNC context for the creation of global social value.

This randomized field experiment examined the effectiveness of a multifaceted, multilevel motivation intervention in a large, introductory engineering course for undergraduates. At the level of the individual, students (n = 682) were randomly assigned to complete a variety of intervention or control activities, including interventions designed to promote feelings of belonging, incremental theories of intelligence (the belief that abilities can grow with effort), and utility value (relevance or usefulness) for engineering coursework. Course instructors (n = 8) were randomly assigned to learn about strategies for supporting students’ motivation in the treatment condition or to learn about knowledge development in an active control condition. The study employed a 2 (TA training vs. control) × 2 (student-level utility value vs. control) × 3 (student-level incremental, belonging, or control) design to examine the main and interactive effects of the single and combined interventions. Random assignment resulted in individual students participating in up to three intervention conditions, or in up to three control conditions. Outcome measures included proximal outcomes assessed at the end of the semester (motivation and course grades) and distal measures of engineering identity, engineering major retention, and GPA assessed at the end of the following semester. Interactions with prior achievement were also examined to determine whether the intervention effects were stronger for low-achieving students. Overall, there were no statistically significant effects of interventions on the outcome measures, compared to control conditions, and no significant moderating effects based on prior achievement. Furthermore, fidelity and manipulation checks suggested that while the utility value intervention was successfully implemented, non-significant effects of the interventions may have been attributable to implementation limitations and existing motivational supports within the course. However, results point to the feasibility of multifaceted motivation interventions, which can be co-designed with teachers to leverage the complex, dynamic nature of motivation as it occurs with individuals and contexts.

Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown. Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU). The objective was to evaluate the association between platelet transfusions and adjudicated major bleeding events. Platelet transfusion episodes were reviewed for timing of administration, product type, and dose. Major bleeding with and without platelet transfusions was adjusted for severity of thrombocytopenia, use of anti‐platelet agents, surgery and other covariates. Secondary outcomes were thrombosis, death in ICU and platelet count increment. Among 2,256 patients, 71 (3.1%) received 190 platelet transfusions. Of those, 121 (63.7%) were administered to 54 non‐bleeding, thrombocytopenic patients. Adjusted rates of major bleeding were not statistically different with or without the administration of platelet transfusions (hazard ratio for transfused patients 0.85; 95% confidence interval, 0.42‐1.72). We did not find a significant association between platelet transfusion use and thrombosis or death in ICU in adjusted analyses. Thrombocytopenia, anemia, major or minor bleeding and use of anticoagulants were associated with platelet transfusion administration. The median post‐transfusion platelet count increment was 20×109/L at 3.5 hours post‐transfusion. Rates of major bleeding were not different for patients who did and did not receive platelet transfusions. Inferences were limited by the small number of transfused patients. Clinical trials are needed to better investigate the potential hemostatic benefit and potential harms of platelet transfusions for this high‐risk population.

A historic timber bridge over the Bonnet Carré Spillway near Norco LA is approaching the end of its service life. Built in 1935, the bridge has seen several spillway opening as well as many severe weather events, and it is no longer economical to continue repairing it. Canadian National Railway (CN) and its subsidiary Illinois Central Railroad (ICRR) decided in 2018 on a new 8,000-ft-long precast concrete replacement, which would leave the track alignment and base of the rail profile unchanged. The problem: At a preliminary permitting meeting, the US Army Corps of Engineers (USACE) revealed a tenuous oral history from the 1980s, which placed a potential Civil War-era cemetery on the site. Typically, this would require the excavation of large swaths of the site, a process that would be extremely expensive and could add months of delay to the $70 million project. The project team, environmental specialists from CN, and engineering firm HDR, got to work on finding a solution.