Mathematical modelling for pandemic preparedness in Canada: Learning from COVID-19.

Background: The COVID-19 pandemic underlined the need for pandemic planning but also brought into focus the use of mathematical modelling to support public health decisions. The types of models needed (compartment, agent-based, importation) are described. Best practices regarding biological realism (including the need for multidisciplinary expert advisors to modellers), model complexity, consideration of uncertainty and communications to decision-makers and the public are outlined.

State-level association between income inequality and mortality in the USA, 1989-2019: ecological study.

Background: Prior studies have shown a positive relationship between income inequality and population-level mortality. This study investigates whether the relationship between US state-level income inequality and all-cause mortality persisted from 1989 to 2019 and whether changes in income inequality were correlated with changes in mortality rates.

Methods: We perform repeated cross-sectional regressions of mortality on state-level inequality measures (Gini coefficients) at 10-year intervals.

Extent and socioeconomic correlates of small area variations in life expectancy in Canada and the United States.

Background: An extensive literature documents substantial variations in life expectancy (LE) between countries and at various levels of subnational geography. These variations in LE are significantly correlated with socioeconomic covariates, though no analyses have been produced at the finest feasible census tract (CT) level of geographic disaggregation in Canada or designed to compare Canada with the United States.

Data And Methods: Abridged life tables for each CT where robust estimates were feasible were estimated comparably with U.

The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.

Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector.

Stem cell-derived extracellular vesicles as senotherapeutics.

Cellular senescence (CS) is recognized as one of the hallmarks of aging, and an important player in a variety of age-related pathologies. Accumulation of senescent cells can promote a pro-inflammatory and pro-cancerogenic microenvironment. Among potential senotherapeutics are extracellular vesicles (EVs) (40-1000 nm), including exosomes (40-150 nm), that play an important role in cell-cell communications.

The potential of phosphorylated α-synuclein as a biomarker for the diagnosis and monitoring of multiple system atrophy.

Introduction: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α-synuclein (p-syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring.

Endocannabinoid regulation in the cervix during pregnancy: insights into molecular mechanisms of premature labor.

In Brief: The cervix plays a crucial role not only in the maintenance of pregnancy but also during delivery, when it undergoes extensive changes. This study highlights the involvement of the endocannabinoidome in cervical remodeling, emphasizing its relevance in the shift from a nonpregnant to pregnant state and its potential contribution to preterm delivery in inflammatory contexts.

Abstract: During pregnancy, the main role of the cervix is to isolate the fetus from outside pathogens and maintain the relatively closed system of uterine gestation.

Pathways to opioid use and implications for prevention: voices of young adults in recovery.

Background: Opioid use remains a major public health issue, especially among young adults. Despite investment in harm reduction and supply-side strategies such as reducing overprescribing and safe medication disposal, little is known about demand-side issues, such as reasons for use and pathways to opioid use. Adolescents and young adults who struggle with opioid use disorder (OUD) are multifaceted individuals with varied individual histories, experiences, challenges, skills, relationships, and lives.

Treatment Referrals Post-prohibition of Alcohol Exclusion Laws: Evidence from Colorado and Illinois.

Background: Individuals with alcohol-related disorders often encounter barriers to accessing treatment. One potential barrier is the state alcohol exclusion laws (AELs) that allow insurers to deny coverage for injuries or illnesses caused by alcohol intoxication. Several states have repealed AELs by prohibiting them completely, including banning exclusions in health and accident insurance policies, limiting their scope, or creating exemptions.

The Development and Testing of a Point-of-Sale E-Cigarette Health Communication Campaign.

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1).

Survey of Resources in Behavioral Sleep Medicine Across the Department of Defense, Defense Health Agency.

Introduction: Insomnia affects approximately 40% of active duty service members and adversely affects health, readiness, and safety. The VA/DoD Clinical Practice Guideline for the management of insomnia recommends cognitive-behavioral treatment of insomnia (CBTI) or its abbreviated version (brief behavioral treatment of insomnia [BBTI]) as the first-line insomnia treatment. The goal of this study was to assess CBTI/BBTI resources at MTFs, perceived facilitators and barriers for CBTI/BBTI, and gaps in these treatments across the Defense Health Agency.

Digital CBTI hubs as a treatment augmentation strategy in military clinics: study protocol for a pragmatic randomized clinical trial.

Background: Chronic insomnia is the most prevalent sleep disorder among military service members, and it compromises readiness, performance, and physical and mental health. Cognitive behavioral treatment for insomnia (CBTI) is the standard of care for the treatment of insomnia recommended by the VA/DoD Clinical Practice Guideline, the American Academy of Sleep Medicine, and the American College of Physicians. CBTI is highly effective but has limited scalability.

Prototyping Apps for the Management of Sleep, Fatigue, and Behavioral Health in Austere Far-Forward Environments: Development Study.

Background: Military service inherently includes frequent periods of high-stress training, operational tempo, and sustained deployments to austere far-forward environments. These occupational requirements can contribute to acute and chronic sleep disruption, fatigue, and behavioral health challenges related to acute and chronic stress and disruption of team dynamics. To date, there is no centralized mobile health platform that supports self- and supervised detection, monitoring, and management of sleep and behavioral health issues in garrison and during and after deployments.

CB1 receptor expression and signaling are required for dexamethasone-induced aversive memory consolidation.

The molecular processes that underlie long-term memory formation involve signaling pathway activation by neurotransmitter release, which induces the expression of immediate early genes, such as Zif268, having a key role in memory formation. In this work, we show that the cannabinoid CB1 receptor signaling is necessary for the effects of dexamethasone on the behavioral response in an inhibitory avoidance task, on dexamethasone-induced ERK phosphorylation, and on dexamethasone-dependent Zif268 expression. Furthermore, we provide primary evidence for the mechanism responsible for this crosstalk between cannabinoid and glucocorticoid-mediated signaling pathways, showing that dexamethasone regulates endocannabinoid metabolism by inhibiting the activity of the Fatty acid amide hydrolase (FAAH), an integral membrane enzyme that hydrolyzes endocannabinoids and related amidated signaling lipids.

Managing unit human capital resources: Integrating insights from human resource management and unit leadership literatures.

Unit human capital resources (HCR) are vital to performance across organizational levels. Crucially, the benefits of unit HCR often hinge on resource access and effective resource management. Yet, how units manage HCR remains unclear.

Regulating cancer risk prediction: legal considerations and stakeholder perspectives on the Canadian context.

Risk prediction models hold great promise to reduce the impact of cancer in society through advanced warning of risk and improved preventative modalities. These models are evolving and becoming more complex, increasingly integrating genetic screening data and polygenic risk scores as well as calculating risk for multiple types of a disease. However, unclear regulatory compliance requirements applicable to these models raise significant legal uncertainty and new questions about the regulation of medical devices.

Development of Training to Prepare Army Medics to Address Behavioral Health Needs of Soldiers in Far-Forward Environments Utilizing Mobile App Technology.

Introduction: Multi-domain operational combat environments will likely restrict key components of current behavioral health (BH) service delivery models. Combat teams in far-forward outposts or extended missions may need to rely on their own internal assets to manage combat and operational stress reactions for extended periods of time. As such, combat medics are expected to take on additional responsibilities as providers of BH support for isolated teams.

Non-Redundant Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN-101).

Objective: CD28 and inducible T cell costimulator (ICOS) appear to have nonredundant roles in T cell activation and adaptive immunity. We undertook this study to characterize in vitro and in vivo the therapeutic potential of acazicolcept (ALPN-101), an Fc fusion protein of a human variant ICOS ligand (ICOSL) domain designed to inhibit both CD28 and ICOS costimulation, in inflammatory arthritis.

Methods: Acazicolcept was compared in vitro with inhibitors of either the CD28 or ICOS pathways (abatacept and belatacept [CTLA-4Ig], prezalumab [anti-ICOSL monoclonal antibody]) in receptor binding and signaling assays, and in a collagen-induced arthritis (CIA) model.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

Objective: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors.

Methods: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303).

Development and validation of an electronic health records-based opioid use disorder algorithm by expert clinical adjudication among patients with prescribed opioids.

Background: In the US, over 200 lives are lost from opioid overdoses each day. Accurate and prompt diagnosis of opioid use disorders (OUD) may help prevent overdose deaths. However, international classification of disease (ICD) codes for OUD are known to underestimate prevalence, and their specificity and sensitivity are unknown.

Does state repeal of alcohol exclusion laws increase problem drinking?

Background: For decades, alcohol exclusion laws (AELs) have allowed insurance companies to reject claims for physical injuries caused by alcohol consumption, including injuries from impaired driving. A central premise of AELs is that they function as a deterrent to risk-taking behaviors, such as excessive drinking. If this assumption is correct, state repeal of these laws should result in increased drinking.

Using Real-World Data to Determine Health System Costs of Ontario Women Screened for Breast Cancer.

Our study was to determine breast cancer screening costs in Ontario, Canada for screenings conducted through a formal (Ontario Breast Screening Program, OBSP) and informal (non-OBSP) screening program using administrative databases. Included women were 49-74 years of age when receiving screening mammograms between 1 January 2013 to 31 December 2019. Each woman was followed for a screening episode with screening and diagnostic components, and costs were calculated as an average cost per woman per month in 2021 Canadian dollars.