Home is Where the Health Is: The Convergence of Environmental Justice, Affordable Housing, and Green Building

The issues this paper discusses–housing affordability, environmental equity, indoor and outdoor air quality, responsible use of natural resources, transportation and neighborhood character–are all connected. Green affordable housing is especially important in the context of the disproportionate effects that low-wealth households experience from environmental degradation, including air, water, and noise pollution. To frame this discussion, Part II of this paper discusses the concept of environmental justice, a relatively new topic in the arena of American environmental concerns. It looks at how the concept has evolved over time, to the point that it is no longer concerned only with disparate impacts of environmental hazards but also the equitable distribution of environmental benefits. Part III looks at what constitutes affordable housing, and how supplying it is a function of local governments’ land use authority. Part IV merges the concepts of affordable housing and environmental justice in the paradigm of green housing, demonstrating why both affordability and environmental justice are closely tied to issues of energy efficiency, transportation, indoor air quality, water conservation, and other attributes of green housing. Part V and VI conclude with observations about how law and policy can help establish comprehensive plans and legal mandates to insure that green features and affordability are incorporated in housing planning, as a matter of environmental justice

Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda

The potential use of ivermectin as an additional vector control tool is receiving increased attention from the malaria elimination community, driven by the increased importance of outdoor/residual malaria transmission and the threat of insecticide resistance where vector tools have been scaled-up. This report summarizes the emerging evidence presented at a side meeting on "Ivermectin for malaria elimination: current status and future directions" at the annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans on November 4, 2014. One outcome was the creation of the "Ivermectin Research for Malaria Elimination Network" whose main goal is to establish a common research agenda to generate the evidence base on whether ivermectin-based strategies should be added to the emerging arsenal to interrupt malaria transmission

Insulin-Like Growth Factor-1 Receptor Signaling Increases the Invasive Potential of Human Epidermal Growth Factor Receptor 2-Overexpressing Breast Cancer Cells via Src-Focal Adhesion Kinase and Forkhead Box Protein M1 s

ABSTRACT Resistance to the human epidermal growth factor receptor (HER2)-targeted antibody trastuzumab is a major clinical concern in the treatment of HER2-positive metastatic breast cancer. Increased expression or signaling from the insulin-like growth factor-1 receptor (IGF-1R) has been reported to be associated with trastuzumab resistance. However, the specific molecular and biologic mechanisms through which IGF-1R promotes resistance or disease progression remain poorly defined. In this study, we found that the major biologic effect promoted by IGF-1R was invasion, which was mediated by both Src-focal adhesion kinase (FAK) signaling and Forkhead box protein M1 (FoxM1). Cotargeting IGF-1R and HER2 using either IGF-1R antibodies or IGF-1R short hairpin RNA in combination with trastuzumab resulted in significant but modest growth inhibition. Reduced invasion was the most significant biologic effect achieved by cotargeting IGF-1R and HER2 in trastuzumab-resistant cells. Constitutively active Src blocked the anti-invasive effect of IGF-1R/HER2 cotargeted therapy. Furthermore, knockdown of FoxM1 blocked IGF-1-mediated invasion, and dual targeting of IGF-1R and HER2 reduced expression of FoxM1. Reexpression of FoxM1 restored the invasive potential of IGF-1R knockdown cells treated with trastuzumab. Overall, our results strongly indicate that therapeutic combinations that cotarget IGF-1R and HER2 may reduce the invasive potential of cancer cells that are resistant to trastuzumab through mechanisms that depend in part on Src and FoxM1

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study.

BACKGROUND: Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use. METHODS: We validated an existing population-level mathematical model of the effect of ivermectin mass drug administration (MDA) on the mosquito population and malaria transmission against two datasets: clinical data from a cluster- randomised trial done in Burkina Faso in 2015 wherein ivermectin was given to individuals taller than 90 cm and entomological data from a study of mosquito outcomes after ivermectin MDA for onchocerciasis or lymphatic filariasis in Burkina Faso, Senegal, and Liberia between 2008 and 2013. We extended the existing model to include a range of complementary malaria interventions (seasonal malaria chemoprevention and MDA with dihydroartemisinin-piperaquine) and to incorporate new data on higher doses of ivermectin with a longer mosquitocidal effect. We consider two ivermectin regimens: a single dose of 400 μg/kg (1 × 400 μg/kg) and three consecutive daily doses of 300 μg/kg per day (3 × 300 μg/kg). We simulated the effect of these two doses in a range of usage scenarios in different transmission settings (highly seasonal, seasonal, and perennial). We report percentage reductions in clinical incidence and slide prevalence. FINDINGS: We estimate that MDA with ivermectin will reduce prevalence and incidence and is most effective in areas with highly seasonal transmission. In a highly seasonal moderate transmission setting, three rounds of ivermectin only MDA at 3 × 300 μg/kg (rounds spaced 1 month apart) and 70% coverage is predicted to reduce clinical incidence by 71% and prevalence by 34%. We predict that adding ivermectin MDA to seasonal malaria chemoprevention in this setting would reduce clinical incidence by an additional 77% in children younger than 5 years compared with seasonal malaria chemoprevention alone; adding ivermectin MDA to MDA with dihydroartemisinin-piperaquine in this setting would reduce incidence by an additional 75% and prevalence by an additional 64% (all ages) compared with MDA with dihydroartemisinin-piperaquine alone. INTERPRETATION: Our modelling predictions suggest that ivermectin could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing interventions are insufficient and in areas approaching elimination to prevent resurgence. FUNDING: Imperial College Junior Research Fellowship

From theory to practice: improving the impact of health services research

BACKGROUND: While significant strides have been made in health research, the incorporation of research evidence into healthcare decision-making has been marginal. The purpose of this paper is to provide an overview of how the utility of health services research can be improved through the use of theory. Integrating theory into health services research can improve research methodology and encourage stronger collaboration with decision-makers. DISCUSSION: Recognizing the importance of theory calls for new expectations in the practice of health services research. These include: the formation of interdisciplinary research teams; broadening the training for those who will practice health services research; and supportive organizational conditions that promote collaboration between researchers and decision makers. Further, funding bodies can provide a significant role in guiding and supporting the use of theory in the practice of health services research. SUMMARY: Institutions and researchers should incorporate the use of theory if health services research is to fulfill its potential for improving the delivery of health care

This work was supported by The Department of the Interior Alaska Climate Adaptation Science Center, which is managed by the USGS National Climate Adaptation Science Center.

53 pages : color illustrations, color maps ; 28 cmThis report is designed as a living document to inform the community, decision makers, and academics and to serve as a learning and teaching tool. The nine key messages summarized on pages 6 and 7 are intended for use as a quick reference. Unique for this type of report, these key messages highlight actions by Juneau's civil society, including local nonprofit organizations.We thank the City and Borough of Juneau (CBJ) for its support in bringing this vital information on climate change to the Juneau community and to others. Thanks especially to all the co-authors and other contributors. The inclusion of such a diverse array of material, including local knowledge, was made possible by the many elders, scientists, and local experts who contributed their time and expertise. The report is online at acrc.alaska.edu/ juneau-climate-report. It is an honor to be the lead editor and project manager for this critical effort. We have a chance to save our world from the most extreme effects of climate change. Let us take it. Gunalchéesh, sincerely, James E. Powell (Jim), PhD, Alaska Coastal Rainforest Center, UASWelcome / Thomas F. Thornton -- Juneau's climate report: History and background / Bruce Botelho -- Using this report -- Acknowledgements / James E. Powell -- A regional Indigenous perspective on adaptation: The Central Council of Tlingit & Haida Indian Tribes of Alaska's Climate Change Adaptation Plan / Raymond Paddock -- Nine key messages -- What we're experiencing: Atmospheric, marine, terrestrial, and ecological effects. Climate. Setting and seasons / Tom Ainsworth -- More precipitation / Rick Thoman -- Higher temperatures / Rich Thoman -- Less snowfall / Eran Hood -- Ocean. Surface uplift and sea level rise / Eran Hood -- Extensive effects of a warming ocean / Heidi Pearson -- Increasing ocean acidification / Robert Foy -- Land. More landslides / Sonia Nagorski & Aaron Jacobs -- Mendenhall Glacier continues to retreat / Jason Amundson -- Tongass Forest impacts and carbon / Dave D'Amore -- Animals. Terrestrial vertebrates in A¿¿ak'w & T'aak¿łu Aani¿¿ / Richard Carstensen -- Three animals as indicators of change / Richard Carstensen -- Insects / Bob Armstrong -- What we're doing: Community response. Upgrading ifrastructure and mitigation / Katie Koester -- Upgrading utilities and other energy consumers / Alec Mesdag -- Growing demand for hydropower / Duff Mitchell -- Leading a shift in transportation / Duff Mitchell -- Maintaining mental health through community and recreation / Linda Kruger & Kevin Maier -- Food security / Darren Snyder & Jim Powell -- Large cruise ship air emissions / Jim Powell -- Tourists' views on climate change mitigation / Jim Powell -- Lowering greenhouse gas emissions / Jim Powell & Peggy Wilcox -- Residents taking action / Andy Romanoff & Jim Powell -- Summary and Recommendations -- References -- Graphics and data sources -- Appendix: Juneau nonprofit climate change organization

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation