Occupational exposure to welding fume in Australia: An online survey.

OBJECTIVE: This survey aimed to investigate exposure to welding fume in Australian workplaces and the use of protective and control measures among workers. METHODS: Data were collected via a cross-sectional online survey of workers and employers involved in welding in Australia. Survey questions focused on the determinants of exposure to welding fume, welding experience and qualifications, and use of control measures. RESULTS: There were 634 respondents to the survey across Australia of whom 577 (91%) were assessed as being exposed to welding fume, most at high levels. Welders undertook a wide range of types of welding, and higher-risk welding such as in confined and restricted spaces was common. Most workplaces did not have any form of mechanical ventilation, and use of air-supplied respiratory protection was poor even when ventilation was not used. CONCLUSION: Welders in Australia are exposed to several carcinogens, particularly welding fume, hexavalent chromium (CrVI) and nickel, and the use of control measures is sub-optimal. IMPLICATIONS FOR PUBLIC HEALTH: Higher-order controls are the best way to reduce exposure to carcinogens in the workplace. The lack of use of these controls by Australian welders is concerning and needs to be a focus of attention by regulators and companies.

Hypothesis: the generation of T cells directed against neoepitopes employing immune-mediating agents other than neoepitope vaccines.

The development of vaccines, especially RNA-based, directed against patient-specific tumor neoepitopes is an active and productive area of cancer immunotherapy. Promising clinical results in melanoma and other solid tumor types are emerging. As with all cancer therapy modalities, neoepitope vaccine development and delivery also has some drawbacks, including the level of effort to develop a patient-specific product, accuracy of algorithms to predict neoepitopes, and with the exception of melanoma and some other tumor types, biopsies of metastatic lesions of solid tumors are often not available. We hypothesize that in some circumstances the use of rationally designed combinations of "off-the-shelf" agents may prove an additional path to enable the patient to produce his/her own "neoepitope vaccine" in situ. These combination therapies may consist of agents to activate a tumor-associated T-cell response, potentiate that response, reduce or eliminate immunosuppressive entities in the tumor microenvironment, and/or alter the phenotype of tumor cells to render them more susceptible to immune-mediated lysis. Examples are provided in both preclinical and clinical studies in which combinations of "off-the-shelf" agents lead to the generation of T cells directed against tumor-derived neoepitopes with consequent antitumor activity.

The effect of virtual reality treadmill training on obstacle crossing parameters in older adults.

With increased age, walking without tripping requires greater cognitive demand. Therefore, it may be beneficial for training interventions to address and incorporate aspects of cognitive load. The purpose of this study was to compare a semi-immersive virtual reality treadmill training (VRTT) and conventional treadmill training (CTT) on obstacle clearance and trip hazard in older adults. Obstacle clearance parameters were measured with foot-mounted inertial measurement units (IMUs) and a Zeno pressure walkway. All data were processed and analyzed through custom Matlab scripts. Obstacle step height mean decreased (p = .003) in the lead limb following both training interventions. Additional significant changes were found in pre- and post-obstacle distance mean following both training interventions. Furthermore, significant correlations were found between demographic, cognitive, and functional mobility assessments and changes in dependent measures. The findings suggest that both the VRTT and CTT interventions may provide a reduction in trip risk in older adults, although through different methods.

Soluble immune checkpoints: implications for cancer prognosis and response to immune checkpoint therapy and conventional therapies.

Longitudinal sampling of tumor tissue from patients with solid cancers, aside from melanoma and a few other cases, is often unfeasible, and thus may not capture the plasticity of interactions between the tumor and immune system under selective pressure of a given therapy. Peripheral blood analyses provide salient information about the human peripheral immunome while offering technical and practical advantages over traditional tumor biopsies, and should be utilized where possible alongside interrogation of the tumor. Some common blood-based biomarkers used to study the immune response include immune cell subsets, circulating tumor DNA, and protein analytes such as cytokines. With the recent explosion of immune checkpoint inhibitors (ICI) as a modality of treatment in multiple cancer types, soluble immune checkpoints have become a relevant area of investigation for peripheral immune-based biomarkers. However, the exact functions of soluble immune checkpoints and their roles in cancer for the most part remain unclear. This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints - sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM - in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients.

Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.

BACKGROUND: We previously demonstrated the successful use of in vivo CRISPR gene editing to delete 4-hydroxyphenylpyruvate dioxygenase (HPD) to rescue mice deficient in fumarylacetoacetate hydrolase (FAH), a disorder known as hereditary tyrosinemia type 1 (HT1). The aim of this study was to develop an ex vivo gene-editing protocol and apply it as a cell therapy for HT1. METHODS: We isolated hepatocytes from wild-type (C57BL/6J) and Fah-/- mice and then used an optimized electroporation protocol to deliver Hpd-targeting CRISPR-Cas9 ribonucleoproteins into hepatocytes. Next, hepatocytes were transiently incubated in cytokine recovery media formulated to block apoptosis, followed by splenic injection into recipient Fah-/- mice. RESULTS: We observed robust engraftment and expansion of transplanted gene-edited hepatocytes from wild-type donors in the livers of recipient mice when transient incubation with our cytokine recovery media was used after electroporation and negligible engraftment without the media (mean: 46.8% and 0.83%, respectively; p=0.0025). Thus, the cytokine recovery medium was critical to our electroporation protocol. When hepatocytes from Fah-/- mice were used as donors for transplantation, we observed 35% and 28% engraftment for Hpd-Cas9 ribonucleoproteins and Cas9 mRNA, respectively. Tyrosine, phenylalanine, and biochemical markers of liver injury normalized in both Hpd-targeting Cas9 ribonucleoprotein and mRNA groups independent of induced inhibition of Hpd through nitisinone, indicating correction of disease indicators in Fah-/- mice. CONCLUSIONS: The successful liver cell therapy for HT1 validates our protocol and, despite the known growth advantage of HT1, showcases ex vivo gene editing using electroporation in combination with liver cell therapy to cure a disease model. These advancements underscore the potential impacts of electroporation combined with transplantation as a cell therapy.

Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Young people's alcohol use in and around water: A scoping review of the literature.

ISSUES: The surrounding social and commercial context, including alcohol advertising, heavily influences alcohol consumption. Alcohol use is a major risk factor for both fatal and non-fatal drowning, particularly for young people. APPROACH: We conducted a scoping review to explore the peer-reviewed literature on the use of alcohol by young people (aged 15-34 years) in the context of aquatic environments. Five electronic academic databases were searched for English-language studies conducted in high-income countries and published in the last 15 years (since 2008). The MetaQAT framework was used to assess methodological quality of included studies. KEY FINDINGS: The review included a total of 24 studies, including those addressing the prevalence of and/or risk factors for alcohol use in aquatic environments among young people (n = 13); the epidemiology of alcohol-related unintentional drowning in young people (n = 9); and interventions to reduce alcohol-related harm around water (n = 3). Findings suggest that young people commonly consume alcohol around water, particularly young men. We found multiple influences on this behaviour, including the perception of risk, location of aquatic activity and presence of others, particularly peers. IMPLICATIONS: Understanding the literature addressing alcohol use around water among young people will assist in identifying and setting priorities for drowning prevention, including the need to mitigate the effects of alcohol advertising which promotes drinking in and around water. CONCLUSION: There is a clear imperative to address the use of alcohol by young people in aquatic environments. These findings have key implications for public health policy, advocacy and practice.

Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade.

The paradigm of non-small cell lung cancer (NSCLC) treatment has been profoundly influenced by the development of immune checkpoint inhibitors (ICI), but the range of clinical responses observed among patients poses significant challenges. To date, analyses of tumor biopsies are the only parameter used to guide prognosis to ICI therapy. Tumor biopsies, however, are often difficult to obtain and tissue-based biomarkers are limited by intratumoral heterogeneity and temporal variability. In response, there has been a growing emphasis on the development of "liquid biopsy"‒ derived biomarkers, which offer a minimally invasive means to dynamically monitor the immune status of NSCLC patients either before and/or during the course of treatment. Here we review studies in which multiple blood-based biomarkers encompassing circulating soluble analytes, immune cell subsets, circulating tumor DNA, blood-based tumor mutational burden, and circulating tumor cells have shown promising associations with the clinical response of NSCLC patients to ICI therapy. These investigations have unveiled compelling correlations between the peripheral immune status of patients both before and during ICI therapy and patient outcomes, which include response rates, progression-free survival, and overall survival. There is need for rigorous validation and standardization of these blood-based assays for broader clinical application. Integration of multiple blood-based biomarkers into comprehensive panels or algorithms also has the potential to enhance predictive accuracy. Further research aimed at longitudinal monitoring of circulating biomarkers is also crucial to comprehend immune dynamics and resistance mechanisms and should be used alongside tissue-based methods that interrogate the tumor microenvironment to guide treatment decisions and may inform on the development of novel therapeutic strategies. The data reviewed here reinforce the opportunity to refine patient stratification, optimize treatments, and improve outcomes not only in NSCLC but also in the wider spectrum of solid tumors undergoing immunotherapy.

Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-ß and PD-L1, in patients with advanced non-small cell lung cancer.

BACKGROUND: Bintrafusp alfa, a first-in-class bifunctional fusion protein targeting transforming growth factor-ß (TGF-ß) and programmed cell death ligand 1, has demonstrated encouraging efficacy as second-line treatment in patients with non-small cell lung cancer (NSCLC) in a dose expansion cohort of the phase 1, open-label clinical trial (NCT02517398). Here, we report the safety, efficacy, and biomarker analysis of bintrafusp alfa in a second expansion cohort of the same trial (biomarker cohort). METHODS: Patients with stage IIIb/IV NSCLC who were either immune checkpoint inhibitor (ICI)-naïve (n=18) or ICI-experienced (n=23) were enrolled. The primary endpoint was the best overall response. Paired biopsies (n=9/41) and peripheral blood (n=14/41) pretreatment and on-treatment were studied to determine the immunological effects of treatment and for associations with clinical activity. RESULTS: Per independent review committee assessment, objective responses were observed in the ICI-naïve group (overall response rate, 27.8%). No new or unexpected safety signals were identified. Circulating TGF-ß levels were reduced (>97%; p<0.001) 2 weeks after initiation of treatment with bintrafusp alfa and remained reduced up to 12 weeks. Increases in lymphocytes and tumor-associated macrophages (TAMs) were observed in on-treatment biospies, with an increase in the M2 (tumor trophic TAMs)/M1 (inflammatory TAMs) ratio associated with poor outcomes. Specific peripheral immune analytes at baseline and early changes after treatment were associated with clinical response. CONCLUSIONS: Bintrafusp alfa was observed to have modest clinical activity and manageable safety, and was associated with notable immunologic changes involving modulation of the tumor immune microenvironment in patients with advanced NSCLC.

Impact of extreme weather events on healthcare utilization and mortality in the United States.

Climate change is intensifying extreme weather events. Yet a systematic analysis of post-disaster healthcare utilization and outcomes for severe weather and climate disasters, as tracked by the US government, is lacking. Following exposure to 42 US billion-dollar weather disasters (severe storm, flood, flood/severe storm, tropical cyclone and winter storm) between 2011 and 2016, we used a difference-in-differences (DID) approach to quantify changes in the rates of emergency department (ED) visits, nonelective hospitalizations and mortality between fee-for-service Medicare beneficiaries in affected compared to matched control counties in post-disaster weeks 1, 1-2 and 3-6. Overall, disasters were associated with higher rates of ED utilization in affected counties in post-disaster week 1 (DID of 1.22% (95% CI, 0.20% to 2.25%; P < 0.020)) through week 2. Nonelective hospitalizations were unchanged. Mortality was higher in affected counties in week 1 (DID of 1.40% (95% CI, 0.08% to 2.74%; P = 0.037)) and persisted for 6 weeks. Counties with the greatest loss and damage experienced greater increases in ED and mortality rates compared to all affected counties. Thus, billion-dollar weather disasters are associated with excess ED visits and mortality in Medicare beneficiaries. Tracking these outcomes is important for adaptation that protects patients and communities, health system resilience and policy.

E-cigarettes on Instagram: Exploring vape content via an Australian vaping influencer.

INTRODUCTION: Mounting evidence suggests that electronic cigarettes (e-cigarettes) are extensively promoted and marketed using social media, including through user-generated content and social media influencers. This study explores how e-cigarettes are being promoted on Instagram, using a case-study approach, and the extent to which Meta's Restricted Goods and Services Policy (Meta's policy) is being applied and enforced. METHODS: We identified the accounts followed by an Australian Instagram influencer who primarily posts e-cigarette-related content. The main foci of these 855 accounts were coded and 369 vaping-focused accounts were identified. These vaping-focused accounts were then further coded by two trained coders. RESULTS: All (n=369; 100.0%) of the vape content posted by these accounts was positive in sentiment. One-third of the vape accounts (n=127; 34.4%) had a shared focus, indicating that vape content may permeate into other online communities through shared interests. A total of 64 accounts (17.3%) potentially violated Meta's policy by attempting to purchase, sell, raffle or gift e-cigarette products. CONCLUSIONS: The findings of this study suggest that pro-vaping information is available and accessible on Instagram. Much of the content identified in this study promoted the purchase or gifting of e-cigarette products and potentially violates Meta's policy. Greater regulation and/or stronger enforcement of e-cigarette content on social media platforms such as Instagram is necessary to prevent the ongoing promotion of these harmful products.

Strategies for Creating Multidisciplinary Community Care Teams to Address Barriers to Providing Family Based Treatment of Eating Disorders.

Eating disorders, especially anorexia nervosa, are complex and devastating illnesses. Although eating disorders have a high mortality rate and are relatively common, there are many barriers for those seeking treatment. Provider training and education, weight bias among health care providers, geographical and language barriers, and a lack of options because of insurance restrictions prevent many families from receiving appropriate care, especially in smaller or rural communities. In those areas, providers are left to piece together treatment using a small number of other providers from different disciplines who have a willingness to work with this population. Outpatient family based treatment is an evidenced-based treatment of anorexia nervosa and relies on a multidisciplinary approach to care. Community-based care teams can be an effective way to treat those with eating disorders seeking family based treatment. There are several strategies for building collaborative teams that can provide comprehensive and accessible care to those with few options. [Pediatr Ann. 2024;53(1):e22-e27.].

Neighborhood Environmental Burden and Cardiovascular Health in the US.

Importance: Cardiovascular disease is the leading cause of death in the US. However, little is known about the association between cumulative environmental burden and cardiovascular health across US neighborhoods. Objective: To evaluate the association of neighborhood-level environmental burden with prevalence of cardiovascular risk factors and diseases, overall and by levels of social vulnerability. Design, Settings, and Participants: This was a national cross-sectional study of 71 659 US Census tracts. Environmental burden (EBI) and social vulnerability indices from the US Centers for Disease Control and Prevention (CDC) and Agency for Toxic Substances and Disease Registry were linked to the 2020 CDC PLACES data set. Data were analyzed from March to October 2023. Exposures: The EBI, a measure of cumulative environmental burden encompassing 5 domains (air pollution, hazardous or toxic sites, built environment, transportation infrastructure, and water pollution). Main Outcomes and Measures: Neighborhood-level prevalence of cardiovascular risk factors (hypertension, diabetes, and obesity) and cardiovascular diseases (coronary heart disease and stroke). Results: Across the US, neighborhoods with the highest environmental burden (top EBI quartile) were more likely than those with the lowest environmental burden (bottom EBI quartile) to be urban (16 626 [92.7%] vs 13 414 [75.4%]), in the Midwest (5191 [28.9%] vs 2782 [15.6%]), have greater median (IQR) social vulnerability scores (0.64 [0.36-0.85] vs 0.42 [0.20-0.65]), and have higher proportions of adults in racial or ethnic minority groups (median [IQR], 34% [12-73] vs 12% [5-30]). After adjustment, neighborhoods with the highest environmental burden had significantly higher rates of cardiovascular risk factors than those with the lowest burden, including hypertension (mean [SD], 32.83% [7.99] vs 32.14% [6.99]; adjusted difference, 0.84%; 95% CI, 0.71-0.98), diabetes (mean [SD], 12.19% [4.33] vs 10.68% [3.27]; adjusted difference, 0.62%; 95% CI, 0.53-0.70), and obesity (mean [SD], 33.57% [7.62] vs 30.86% [6.15]; adjusted difference, 0.77%; 95% CI, 0.60-0.94). Similarly, neighborhoods with the highest environmental burden had significantly higher rates of coronary heart disease (mean [SD], 6.66% [2.15] vs 6.82% [2.41]; adjusted difference, 0.28%; 95% CI, 0.22-0.33) and stroke (mean [SD], 3.65% [1.47] vs 3.31% [1.12]; adjusted difference, 0.19%; 95% CI, 0.15-0.22). Results were consistent after matching highest and lowest environmentally burdened neighborhoods geospatially and based on other covariates. The associations between environmental burden quartiles and cardiovascular risk factors and diseases were most pronounced among socially vulnerable neighborhoods. Conclusions and Relevance: In this cross-sectional study of US neighborhoods, cumulative environmental burden was associated with higher rates of cardiovascular risk factors and diseases, although absolute differences were small. The strongest associations were observed in socially vulnerable neighborhoods. Whether initiatives that address poor environmental conditions will improve cardiovascular health requires additional prospective investigations.

Gender and socioecological level differences in stakeholders' perceptions of athlete attrition factors in an Australian high-performance pathway system.

OBJECTIVES: This study aimed to build on previous work by the authors. It examines how socioecological level and gender influence high-performance sport system (HPSS) stakeholders' perspectives of the relative importance and feasibility to address athlete attrition factors within an Australian high-performance pathway system (HPPS). DESIGN: Mixed methods. METHODS: Sub-analysis was conducted of rating data from 30 participants who had contributed to identifying 83 statements in 13 clusters in a previous Concept Mapping study. The 13 clusters were statistically analysed in 'R' using cumulative link mixed models (CLMMs) to determine differences in perceived importance and feasibility between 1) socioecological levels, and 2) genders. RESULTS: Mean ratings for 11 and three of the 13 clusters were statistically significantly different between at least two of the five socioecological levels, for importance and feasibility, respectively. Athletes had the largest variation in mean ratings from the most (athlete health 4.59), to least (performance potential 2.83) important cluster, when compared to the other four socioecological levels. There were statistically significant differences between the ratings between genders (Men/Women) for two clusters for each rating scale: Importance: 'athlete health' (M3.33:W3.84 [p 0.012]); 'performance potential' (M3.35:W2.57; [p 0.001]), Feasibility: 'abuse and mismanagement of health' (M2.97:W3.68; [p 0.000]) and 'athlete health' (M2.54:W3.33; [p 0.000]). CONCLUSIONS: This study highlights the need to implement more robust athlete attrition monitoring protocols. It also highlights the importance of listening to youth athletes' voices, and enabling equal gender representation to ensure holistically tailored environments are created to retain talented athletes in high-performance pathway programmes.

Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints include the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) was associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

A T cell receptor ß chain-directed antibody fusion molecule activates and expands subsets of T cells to promote antitumor activity.

Despite the success of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) inhibitors in treating solid tumors, only a proportion of patients respond. Here, we describe a first-in-class bifunctional therapeutic molecule, STAR0602, that comprises an antibody targeting germline Vß6 and Vß10 T cell receptors (TCRs) fused to human interleukin-2 (IL-2) and simultaneously engages a nonclonal mode of TCR activation with costimulation to promote activation and expansion of αß T cell subsets expressing distinct variable ß (Vß) TCR chains. In solution, STAR0602 binds IL-2 receptors in cis with Vß6/Vß10 TCRs on the same T cell, promoting expansion of human Vß6 and Vß10 CD4+ and CD8+ T cells that acquire an atypical central memory phenotype. Monotherapy with a mouse surrogate molecule induced durable tumor regression across six murine solid tumor models, including several refractory to anti-PD-1. Analysis of murine tumor-infiltrating lymphocyte (TIL) transcriptomes revealed that expanded Vß T cells acquired a distinct effector memory phenotype with suppression of genes associated with T cell exhaustion and TCR signaling repression. Sequencing of TIL TCRs also revealed an increased T cell repertoire diversity within targeted Vß T cell subsets, suggesting clonal revival of tumor T cell responses. These immunological and antitumor effects in mice were recapitulated in studies of STAR0602 in nonhuman primates and human ex vivo models, wherein STAR0602 boosted human antigen-specific T cell responses and killing of tumor organoids. Thus, STAR0602 represents a distinct class of T cell-activating molecules with the potential to deliver enhanced antitumor activity in checkpoint inhibitor-refractory settings.

Neurolysin Knockout Mice in a Diet-Induced Obesity Model.

Neurolysin oligopeptidase (E.C.3.4.24.16; Nln), a member of the zinc metallopeptidase M3 family, was first identified in rat brain synaptic membranes hydrolyzing neurotensin at the Pro-Tyr peptide bond. The previous development of C57BL6/N mice with suppression of Nln gene expression (Nln-/-), demonstrated the biological relevance of this oligopeptidase for insulin signaling and glucose uptake. Here, several metabolic parameters were investigated in Nln-/- and wild-type C57BL6/N animals (WT; n = 5-8), male and female, fed either a standard (SD) or a hypercaloric diet (HD), for seven weeks. Higher food intake and body mass gain was observed for Nln-/- animals fed HD, compared to both male and female WT control animals fed HD. Leptin gene expression was higher in Nln-/- male and female animals fed HD, compared to WT controls. Both WT and Nln-/- females fed HD showed similar gene expression increase of dipeptidyl peptidase 4 (DPP4), a peptidase related to glucagon-like peptide-1 (GLP-1) metabolism. The present data suggest that Nln participates in the physiological mechanisms related to diet-induced obesity. Further studies will be necessary to better understand the molecular mechanism responsible for the higher body mass gain observed in Nln-/- animals fed HD.

Extramural US Federal Research Grants For Health Outcomes Associated With Climate Change Inadequate, Too Narrow In Focus.

Climate change causes and exacerbates disease, creates and worsens health disparities, disrupts health care delivery, and imposes a significant disease burden in the US and globally. Critical knowledge gaps hinder an evidence-based response and are perpetuated by scarce federal research funds. We identified and described extramural US federal research funding (that is, grants provided to organizations and institutions outside of federal agencies) that both addressed health outcomes associated with climate change and was awarded between 2010 and 2020. During this eleven-year period, 102 grants met our criteria, totaling approximately $58.7 million, or approximately $5.3 million per year (2020 adjusted US dollars). Federal investments in climate change and health research during this period failed to address the breadth of climate-sensitive exposures, health outcomes, and impacts on vulnerable populations. Moving forward, in addition to increasing investment in climate and health research across all known hazards, critical attention should be placed on vulnerable populations and health equity. To achieve this, increased federal research coordination and cooperation are needed, as well as a mechanism to track this funding.