Physical Activity Policy for Older Adults in the Northwest Territories, Canada: Gaps and Opportunities for Gains

In the Northwest Territories (NWT), Canada, the population of older adults is increasing, and this population reports much poorer health than other age cohorts. Given the number of benefits that physical activity (PA) can have for older adults, we analyzed policies concerning older adults and PA of both the NWT government and non-governmental organizations in the health, recreation, and sports sectors. Our findings indicate that although the majority of the organizations had no PA policies specific to older adults or Aboriginal older adults, some organizations completed all five stages of the policy cycle (agenda setting, policy formulation, decision making, implementation, and evaluation). Our analysis suggests that PA for older adults is not on the agenda for many organizations in the NWT and that often the policy process does not continue past the decision-making stage. To address the need for connections between all stages of the policy cycle, we suggest that organizations collaborate across multiple sectors and with older adults to develop a territory-wide, age-friendly rural and remote community strategy that is applicable to the NWT. Prioritizing age-friendly communities would, in turn, facilitate appropriate PA opportunities for older adults in the NWT and thus contribute to a healthier aging population.Dans les Territoires du Nord-Ouest (T.N.-O.), au Canada, la population de personnes âgées augmente, et la santé de ce segment de population est bien inférieure à celle des autres segments. Étant donné les bienfaits que peut comporter l’activité physique (AP) chez les personnes âgées, nous avons analysé les politiques concernant les personnes âgées et l’AP au sein des organismes gouvernementaux et non gouvernementaux des Territoires du Nord-Ouest en matière de santé, de loisirs et de sports. Nos constatations indiquent que même si la majorité des organismes n’étaient pas dotés de politiques d’AP visant particulièrement les personnes âgées ou les Autochtones âgés, certains organismes avaient déjà fait les cinq étapes du cycle stratégique (détermination de l’ordre du jour, formulation de politiques, prise de décisions, mise en oeuvre et évaluation). Notre analyse suggère que pour bien des organismes des T.N.-O., l’AP chez les personnes âgées ne figure pas au programme et que souvent, le processus d’élaboration de politiques ne se poursuit pas après l’étape de la prise de décisions. Afin de relier toutes les étapes du cycle, nous suggérons que les organismes des divers secteurs collaborent entre eux ainsi qu’avec les personnes âgées afin de parvenir à une stratégie qui correspond bien aux gens plus âgés des localités rurales et éloignées, à l’échelle des T.N.-O. En accordant une priorité à la création de collectivités qui tiennent compte des personnes âgées, on pourrait aboutir à des activités physiques convenant aux personnes âgées des T.N.-O., ce qui contribuerait à une population vieillissante en meilleure santé

Editors\u27 Notes

Editors\u27 Note

Age-dependent maintenance of motor control and corticostriatal innervation by death receptor 3

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3(ko)) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3(ko) mice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3(ko) mice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV):an open-label randomised controlled phase 3 trial

Background The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. Methods We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1: 1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m(2) on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m(2) loading dose followed by seven weekly infusions of 250 mg/m(2)). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. Findings Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4.8 [95% CI 4.2-5.4] with cisplatin vs 4.8 [4.2-5.4] with cetuximab; p=0.98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29.2 [95% CI 27.3-31.0] with cisplatin vs 30.1 [28.3-31.9] with cetuximab; p=0.49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97.5% vs 89.4%, hazard ratio 5.0 [95% CI 1.7-14.7]; p=0.001) and 2-year recurrence (6.0% vs 16.1%, 3.4 [1.6-7.2]; p=0.0007). Interpretation Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. Funding Cancer Research UK. Copyright (c) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Planning and Development Strategies for Holy Trinity, Alabama

This report was written at the behest of and with the support of the Missionary Servants of the Most Holy Trinity for the School of City and Regional Planning course, CP 6052 second-year masters studio. The course is comprised of 16 Masters in City and Regional Planning candidates (MCRP) at the Georgia Institute of Technology in Atlanta, Ga.The Missionary Servants of the Most Holy Trinity (MSMHT) own and oversee parcels of rural land in Russell County, Alabama. The Missionary Servants are currently exploring and assessing how best to develop and utilize these major land holdings. By developing the land, members hope to provide services to their constituents, meet and help the needs of the larger community, and ensure a reliable source of income to fund Mission activities, all while promoting the principles of the Catholic Church as enunciated by MSMHT founder Father Thomas Judge, “Be good, do good, and be a power for good.” Towards this goal, the Missionary Servants have sought out the services and expertise of the School of City and Regional Planning Department of the Georgia Institute of Technology. MSMHT looked to Professor Michael Dobbins and professional planner Ray White for advice and guidance on how to best develop the land. The School subsequently formed a graduate level studio planning course around the project. Over the course of the Fall 2011 academic term, graduate students in the studio con­ducted site visits, interviewed stakeholders, solicited advice and guidance from subject-matter experts, examined the underlying data, engaged in quantitative analysis, created projections, generated maps and spatial analyses, and assessed various ideas and project proposals. Hundreds of hours were devoted to this project, with Professor Dobbins and Mr. White providing overall coordination, management, and expert guidance. The final report is presented here. It takes the form of a land management evaluation and pro­posal. The report is broken down into four major sections. The first section, “Description of Holy Trin­ity and Environs,” provides the background and context for the property located at the Holy Trinity site. Items in this section include a discussion of pertinent economic, housing, and demographic issues. This section addresses the composition of the land and environment, examines the social, cultural and busi­ness forces in the surrounding community and region, and provides an overview of the Church’s activi­ties in the area. The second section focuses on “Land Management.” This part of the report assesses current and potential revenue streams and amounts for the Mission. It also identifies and explores opportunities for Holy Trinity to partner with various businesses, investors, community and nonprofit organizations, and local and regional government offices and consortiums in furthering the goals of development, commu­nity service, and environmental preservation. The third section is devoted to “Development.” This portion analyzes and assesses various de­velopment possibilities for the property. It focuses on four potential scenarios for the land, consisting of agriculture industry, service provision, a town center concept, and/or environmental preservation. It also addresses land development from a functions perspective, examining how certain projects and pro­grams could realize the interests and meet some of the goals of the Mission and the larger community. Issues of infrastructure, design, policy and legal mechanisms, and recommendations are also contained in this section. A timeline for project planning and implementation accompanies these three sections. The re­port concludes with final land management recommendations, addresses long-term planning efforts, and furnishes contact and resource information.Michael Dobbins and Raymond Whit

Age-dependent maintenance of motor controland corticostriatal innervation by death receptor 3

Death receptor 3 is a proinflammatory member of the immunomodulatory tumor necrosis factor receptor superfamily, which has been implicated in several inflammatory diseases such as arthritis and inflammatory bowel disease. Intriguingly however, constitutive DR3 expression has been detected in the brains of mice, rats, and humans, although its neurological function remains unknown. By mapping the normal brain expression pattern of DR3, we found that DR3 is expressed specifically by cells of the neuron lineage in a developmentally regulated and region-specific pattern. Behavioral studies on DR3-deficient (DR3ko) mice showed that constitutive neuronal DR3 expression was required for stable motor control function in the aging adult. DR3ko mice progressively developed behavioral defects characterized by altered gait, dyskinesia, and hyperactivity, which were associated with elevated dopamine and lower serotonin levels in the striatum. Importantly, retrograde tracing showed that absence of DR3 expression led to the loss of corticostriatal innervation without significant neuronal loss in aged DR3ko mice. These studies indicate that DR3 plays a key nonredundant role in the retention of normal motor control function during aging in mice and implicate DR3 in progressive neurological disease

Recent Progress and Next Steps for the MATHUSLA LLP Detector

We report on recent progress and next steps in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC as part of the Snowmass 2021 process. Our understanding of backgrounds has greatly improved, aided by detailed simulation studies, and significant R&D has been performed on designing the scintillator detectors and understanding their performance. The collaboration is on track to complete a Technical Design Report, and there are many opportunities for interested new members to contribute towards the goal of designing and constructing MATHUSLA in time for HL-LHC collisions, which would increase the sensitivity to a large variety of highly motivated LLP signals by orders of magnitude.Comment: Contribution to Snowmass 2021 (EF09, EF10, IF6, IF9), 18 pages, 12 figures. v2: included additional endorser

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease