A tool for evaluating the potential for cost-effective outcomes measurement

Cost related to higher-level outcomes measurement is often very high. However, the cost burden is felt even more by smaller, less well-funded continuing medical education (CME) programs. It is possible to overcome financial and participant-related barriers to measuring Level 6 outcomes, which are patient health outcomes. The Temple University School of Medicine’s Office for Continuing Medical Education developed a sequential tool for attaining cost-effective outcomes measurement for determining the likelihood of a CME intervention to produce significant changes in physician performance. The appropriate selection of the CME topic and specific practice change indictors drive this tool. This tool walks providers through a simple YES or NO decision-making list that guides them toward an accurate prediction of potential programmatic outcomes. Factors considered during the decision-making process include whether: (a) the intended change(s) will have a substantial impact on current practice; (b) the intended practice change(s) are well supported by clinical data, specialty organization/government recommendations, expert opinion, etc; (c) the potential change(s) affects a large population; (d) external factors, such as system pressures, media pressures, financial pressures, patient pressures, safety pressures, etc, are driving this intended change in performance; (e) there is a strong motivation on the part of physicians to implement the intended change(s); and (f) the intended change(s) is relatively easy to implement within any system of practice. If each of these questions can be responded to positively, there is a higher likelihood that the intended practice-related change(s) will occur. Such change can be measured using a simpler and less costly methodology

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies

Microfluidics Generation of Millimeter-sized Matrigel Droplets

Significant progress has been made to increase access to droplet microfluidics for labs with limited microfluidics expertise or fabrication equipment. In particular, using off-the-shelf systems has been a valuable approach. However, the ability to modify a channel design and, thus, the functional characteristics of the system is of great value. In this work, we describe the development of co-flow microfluidics and their fabrication methods for generating uniform millimeter-sized (0.5 - 2 mm) hydrogel droplets. Two complementary approaches based on desktop CO2 laser cutting were developed to prototype and build durable co-flow droplet microfluidics. After demonstrating the co-flow systems, water-in-oil experiments and dimensionless number analysis were used to examine the operational characteristics of the system. Specifically, the Capillary number analysis indicated that millimeter-sized droplet generators operated in the desirable geometry-controlled regime despite their length scales being larger than traditional microfluidics systems. Next, the tunable generation of Matrigel droplets was demonstrated. By adjusting the relative flow rates, the droplet size could be tuned. Finally, we demonstrated fibroblast encapsulation and cell viability for up to 7 days as a proof-of-concept experiment. The systems presented are simple and effective tools to generate robust hydrogel droplets and increase the accessibility of this technology to teaching labs or research settings with limited resources or access to microfluidics.Comment: 14 pages, 5 figures, 1 tabl

Health and Occupational Injury Experienced by Latinx Child Farmworkers in North Carolina, USA

Children as young as 10 years old are hired to work on farms in the United States (U.S.). These children are largely Latinx. Using interview data collected from 202 North Carolina Latinx child farmworkers in 2017, this analysis documents the heath characteristics and occupational injuries of Latinx child farmworkers and delineates characteristics associated with their health and occupational injuries. Latinx child farmworkers include girls (37.6%) and boys (62.4%), aged 10 to 17 years, with 17.8% being migrant farmworkers. Three-quarters reported receiving medical and dental care in the past year. Respiratory (15.8%) and vision (20.3%) problems were prevalent. Girls more than boys, and younger more than older children had greater health service utilization. Occupational injuries were common, with 26.2% reporting a traumatic injury, 44.1% a dermatological injury, 42.6% a musculoskeletal injury, and 45.5% heat-related illness in the past year. Age increased the odds of reporting work injuries and heat-related illness, and being a non-migrant reduced the odds of reporting work injuries. These results emphasize the need for greater documentation of child farmworker occupational health and safety. They underscore the need to change occupational safety policy to ensure that children working in agriculture have the same protections as those working in all other U.S. industries

Regime shifts and panarchies in regional scale social-ecological water systems

In this article we summarize histories of nonlinear, complex interactions among societal, legal, and ecosystem dynamics in six North American water basins, as they respond to changing climate. These case studies were chosen to explore the conditions for emergence of adaptive governance in heavily regulated and developed social-ecological systems nested within a hierarchical governmental system. We summarize resilience assessments conducted in each system to provide a synthesis and reference by the other articles in this special feature. We also present a general framework used to evaluate the interactions between society and ecosystem regimes and the governance regimes chosen to mediate those interactions. The case studies show different ways that adaptive governance may be triggered, facilitated, or constrained by ecological and/or legal processes. The resilience assessments indicate that complex interactions among the governance and ecosystem components of these systems can produce different trajectories, which include patterns of (a) development and stabilization, (b) cycles of crisis and recovery, which includes lurches in adaptation and learning, and (3) periods of innovation, novelty, and transformation. Exploration of cross scale (Panarchy) interactions among levels and sectors of government and society illustrate that they may constrain development trajectories, but may also provide stability during crisis or innovation at smaller scales; create crises, but may also facilitate recovery; and constrain system transformation, but may also provide windows of opportunity in which transformation, and the resources to accomplish it, may occur. The framework is the starting point for our exploration of how law might play a role in enhancing the capacity of social-ecological systems to adapt to climate change

Identification of Susceptibility Pathways for the Role of Chromosome 15q25.1 in Modifying Lung Cancer Risk

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer

I am hiQ—a novel pair of accuracy indices for imputed genotypes

Background: Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand. Results: Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2). Conclusion: We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data

Gene–gene interaction of AhRwith and within the Wntcascade affects susceptibility to lung cancer

Background: Aberrant Wnt signalling, regulating cell development and stemness, influences the development of many cancer types. The Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated with lung cancer susceptibility. Aim: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent. Methods: Odds ratios (OR) were estimated for genomic variants assigned to the Wnt agonist and the antagonistic genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer, at which other previously identified SNPs that have been robustly associated with lung cancer risk could also enter the model. Furthermore, decision trees were created to investigate variant × variant interaction. All analyses were performed for overall lung cancer and for subgroups. Results: No genome-wide significant association of AhR/Wnt-genes with overall lung cancer was observed, but within the subgroups of ever smokers (e.g., maker rs2722278 SFRP4; OR = 1.20; 95% CI 1.13–1.27; p = 5.6 × 10–10) and never smokers (e.g., maker rs1133683 Axin2; OR = 1.27; 95% CI 1.19–1.35; p = 1.0 × 10–12). Although predictability is poor, AhR/Wnt-variants are unexpectedly overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkably, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants. Conclusions: The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers