Impact of climate change on the domestic indoor environment and associated health risks in the UK.

There is growing evidence that projected climate change has the potential to significantly affect public health. In the UK, much of this impact is likely to arise by amplifying existing risks related to heat exposure, flooding, and chemical and biological contamination in buildings. Identifying the health effects of climate change on the indoor environment, and risks and opportunities related to climate change adaptation and mitigation, can help protect public health. We explored a range of health risks in the domestic indoor environment related to climate change, as well as the potential health benefits and unintended harmful effects of climate change mitigation and adaptation policies in the UK housing sector. We reviewed relevant scientific literature, focusing on housing-related health effects in the UK likely to arise through either direct or indirect mechanisms of climate change or mitigation and adaptation measures in the built environment. We considered the following categories of effect: (i) indoor temperatures, (ii) indoor air quality, (iii) indoor allergens and infections, and (iv) flood damage and water contamination. Climate change may exacerbate health risks and inequalities across these categories and in a variety of ways, if adequate adaptation measures are not taken. Certain changes to the indoor environment can affect indoor air quality or promote the growth and propagation of pathogenic organisms. Measures aimed at reducing greenhouse gas emissions have the potential for ancillary public health benefits including reductions in health burdens related heat and cold, indoor exposure to air pollution derived from outdoor sources, and mould growth. However, increasing airtightness of dwellings in pursuit of energy efficiency could also have negative effects by increasing concentrations of pollutants (such as PM2.5, CO and radon) derived from indoor or ground sources, and biological contamination. These effects can largely be ameliorated by mechanical ventilation with heat recovery (MVHR) and air filtration, where such solution is feasible and when the system is properly installed, operated and maintained. Groups at high risk of these adverse health effects include the elderly (especially those living on their own), individuals with pre-existing illnesses, people living in overcrowded accommodation, and the socioeconomically deprived. A better understanding of how current and emerging building infrastructure design, construction, and materials may affect health in the context of climate change and mitigation and adaptation measures is needed in the UK and other high income countries. Long-term, energy efficient building design interventions, ensuring adequate ventilation, need to be promoted

Seasonal variation in exploitative competition between honeybees and bumblebees.

Funder: University of SussexFunder: Charles Brian British Beekeepers Research TrustHoneybees (Apis mellifera) and bumblebees (Bombus spp.) often undergo exploitative competition for shared floral resources, which can alter their foraging behaviour and flower choice, even causing competitive exclusion. This may be strongest in summer, when foraging conditions are most challenging for bees, compared to other times of the year. However, the seasonal dynamics of competition between these major pollinator groups are not well understood. Here, we investigate whether the strength of exploitative competition for nectar between honeybees and bumblebees varies seasonally, and whether competitive pressure is greatest in summer months. We carried out experimental bee exclusion trials from May to late September, using experimental patches of lavender, variety Grosso, in full bloom. In each trial, we compared the numbers of honeybees (HB) foraging on patches from which bumblebees had been manually excluded (bumblebee excluded, BBE) versus control (CON) patches, HB(BBE-CON). This measure of exploitative competition varied significantly with season. As expected, mean HB(BBE-CON) was significantly greater in summer trials than in spring or autumn trials. This was despite high nectar standing crop volumes in BBE patch flowers in spring and autumn trials. Mean HB(BBE-CON) was not different between spring and autumn trials. Our results show that nectar competition between honeybees and bumblebees varies seasonally and is stronger in summer than spring or autumn, adding to current understanding of the seasonality of resource demand and competition between bee species. This information may also help to inform conservation programs aiming to increase floral resources for bees by showing when these resources are most needed

Seasonal variation in exploitative competition between honeybees and bumblebees

Funder: University of SussexFunder: Charles Brian British Beekeepers Research TrustAbstract: Honeybees (Apis mellifera) and bumblebees (Bombus spp.) often undergo exploitative competition for shared floral resources, which can alter their foraging behaviour and flower choice, even causing competitive exclusion. This may be strongest in summer, when foraging conditions are most challenging for bees, compared to other times of the year. However, the seasonal dynamics of competition between these major pollinator groups are not well understood. Here, we investigate whether the strength of exploitative competition for nectar between honeybees and bumblebees varies seasonally, and whether competitive pressure is greatest in summer months. We carried out experimental bee exclusion trials from May to late September, using experimental patches of lavender, variety Grosso, in full bloom. In each trial, we compared the numbers of honeybees (HB) foraging on patches from which bumblebees had been manually excluded (bumblebee excluded, BBE) versus control (CON) patches, HB(BBE-CON). This measure of exploitative competition varied significantly with season. As expected, mean HB(BBE-CON) was significantly greater in summer trials than in spring or autumn trials. This was despite high nectar standing crop volumes in BBE patch flowers in spring and autumn trials. Mean HB(BBE-CON) was not different between spring and autumn trials. Our results show that nectar competition between honeybees and bumblebees varies seasonally and is stronger in summer than spring or autumn, adding to current understanding of the seasonality of resource demand and competition between bee species. This information may also help to inform conservation programs aiming to increase floral resources for bees by showing when these resources are most needed

Feminist Reflections on the Scope of Labour Law: Domestic Work, Social Reproduction and Jurisdiction

Drawing on feminist labour law and political economy literature, I argue that it is crucial to interrogate the personal and territorial scope of labour. After discussing the “commodification” of care, global care chains, and body work, I claim that the territorial scope of labour law must be expanded beyond that nation state to include transnational processes. I use the idea of social reproduction both to illustrate and to examine some of the recurring regulatory dilemmas that plague labour markets. I argue that unpaid care and domestic work performed in the household, typically by women, troubles the personal scope of labour law. I use the example of this specific type of personal service relation to illustrate my claim that the jurisdiction of labour law is historical and contingent, rather than conceptual and universal. I conclude by identifying some of the implications of redrawing the territorial and personal scope of labour law in light of feminist understandings of social reproduction

Changes in Outcomes and Factors Associated With Survival in Melanoma Patients With Brain Metastases

BACKGROUND: Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. METHODS: Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). RESULTS: A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9-12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P \u3c .001). Elevated serum lactate dehydrogenase (LDH) was the only factor associated with worse OS in both PE and CE patients. Factors associated with survival in CE MBM patients included patient age, primary tumor Breslow thickness, prior immunotherapy, leptomeningeal disease, symptomatic MBMs, and whole brain radiation therapy. Several factors associated with OS in the PE were not significant in the CE. RPA demonstrated that elevated serum LDH and prior immunotherapy treatment are the most important determinants of survival in CE MBM patients. CONCLUSIONS: OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations

Melanoma central nervous system metastases: current approaches, challenges, and opportunities

Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area

Neoadjuvant Checkpoint Inhibitor Immunotherapy for Resectable Mucosal Melanoma

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM. METHOD: Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities. RESULTS: We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients. CONCLUSION: Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients

Melanoma Central Nervous System Metastases: An Update to Approaches, Challenges, and Opportunities

Brain metastases are the most common brain malignancy. This review discusses the studies presented at the third annual meeting of the Melanoma Research Foundation in the context of other recent reports on the biology and treatment of melanoma brain metastases (MBM). Although symptomatic MBM patients were historically excluded from immunotherapy trials, efforts from clinicians and patient advocates have resulted in more inclusive and even dedicated clinical trials for MBM patients. The results of checkpoint inhibitor trials were discussed in conversation with current standards of care for MBM patients, including steroids, radiotherapy, and targeted therapy. Advances in the basic scientific understanding of MBM, including the role of astrocytes and metabolic adaptations to the brain microenvironment, are exposing new vulnerabilities which could be exploited for therapeutic purposes. Technical advances including single-cell omics and multiplex imaging are expanding our understanding of the MBM ecosystem and its response to therapy. This unprecedented level of spatial and temporal resolution is expected to dramatically advance the field in the coming years and render novel treatment approaches that might improve MBM patient outcomes

Concurrent Intrathecal and Intravenous Nivolumab in Leptomeningeal Disease: Phase 1 Trial Interim Results

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256