It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4+ lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposed mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.

The purpose of this study was to explore whether repeated exposure to aerosolized ovalbumin (OVA) in the context of local expression of GM-CSF can initiate a Th2-driven, eosinophilic inflammation in the airways. On day Ϫ 1, Balb/c mice were infected intranasally with an adenovirus construct expressing GM-CSF (Ad/GM-CSF). From day 0 to day 9 mice were exposed daily to an OVA aerosol. Mice exposed to OVA alone did not show any evidence of airway inflammation. Mice receiving both Ad/GM-CSF and aerosolized OVA exhibited marked airway inflammation characterized by eosinophilia and goblet cell hyperplasia. Migration of eosinophils into the airway was preceded by a rise in IL-5 and IL-4. Both IL-5 and class II MHC were critically required to generate airway eosinophilia. After resolution, airway eosinophilia was reconstituted after a single OVA exposure. Flow cytometric analysis of dispersed lung cells revealed an increase in macrophages and dendritic cells expressing B7.1 and B7.2, and expansion of activated (CD69-expressing) CD4 and CD8 T cells in mice exposed to OVA and Ad/GM-CSF. Our data indicate that expression of GM-CSF in the airway compartment increases local antigen presentation capacity, and concomitantly facilitates the development of an antigen-specific, eosinophilic inflammatory response to an otherwise innocuous antigen. ( J. Clin. Invest.

the president of the World Bank noted that "'Human capital'-the potential of individuals-is going to be the most important long-term investment any country can make for its people's future prosperity and quality of life". Nevertheless, leaders and practitioners in academic science and medicine continue to be unaware of and poorly educated about the nature, extent, and impact of barriers to full participation of women and minorities in science and medicine around the world. This lack of awareness and education results in failures to fully mobilise the human capital of half the population and limits global technological and medical advancements. The chronic lack of recruitment, promotion, and retention of women in science and medicine is due to systemic, structural, organisational, institutional, cultural, and societal barriers to equity and inclusion. These barriers must be identified and removed through increased awareness of the challenges combined with evidence-based, data-driven approaches leading to measurable targets and outcomes. In this Review, we discuss these issues and highlight actions that could achieve gender equality in science and medicine. We survey approaches and insights that have helped to identify and remove systemic bias and barriers in science and medicine, and propose tools that will help organisational change toward gender equality. We describe tools that include formal legislation and mandated quotas at national or large-scale levels (eg, gender parity), techniques that increase fairness (eg, gender equity) through facilitated organisational cultural change at institutional levels, and professional development of core competencies at individual levels. This Review is not intended to be an extensive analysis of all the literature currently available on achieving gender equality in academic medicine and science, but rather, a reflection on finding multifactorial solutions.

While it is generally understood that Alzheimer's disease (AD) and related dementias (ADRD) is one of the costliest diseases to society, there is widespread concern that researchers and policymakers are not comprehensively capturing and describing the full scope and magnitude of the socioeconomic burden of ADRD. This review aimed to 1) catalogue the different types of AD-related socioeconomic costs described in the literature; 2) assess the challenges and gaps of existing approaches to measuring these costs; and 3) analyze and discuss the implications for stakeholders including policymakers, healthcare systems, associations, advocacy groups, clinicians, and researchers looking to improve the ability to generate reliable data that can guide evidence-based decision making. A centrally emergent theme from this review is that it is challenging to gauge the true value of policies, programs, or interventions in the ADRD arena given the long-term, progressive nature of the disease, its insidious socioeconomic impact beyond the patient and the formal healthcare system, and the complexities and current deficiencies (in measures and real-world data) in accurately calculating the full costs to society. There is therefore an urgent need for all stakeholders to establish a common understanding of the challenges in evaluating the full cost of ADRD and define approaches that allow us to measure these costs more accurately, with a view to prioritizing evidence-based solutions to mitigate this looming public health crisis.

Most individuals with autism spectrum disorder (ASD)-a complex, life-long developmental disorder-do not have access to the care required to address their diverse health needs. Here, we review: (1) common barriers to healthcare access (shortage/cost of services; physician awareness; stigma); (2) barriers encountered primarily during childhood (limited screening/diagnosis; unclear referral pathways), transition to adulthood (insufficient healthcare transition services; suboptimal physician awareness of healthcare needs) and adulthood (shortage of services/limited insurance; communication difficulties with physicians; limited awareness of healthcare needs of aging adults); and (3) advances in research/program development for better healthcare access. A robust understanding of barriers to accessing healthcare across the lifespan of autistic individuals is critical to ensuring the best use of healthcare resources to improve social, physical, and mental health outcomes. Stakeholders must strengthen healthcare service provision by coming together to: better understand healthcare needs of underserved populations; strengthen medical training on care of autistic individuals; increase public awareness of ASD; promote research into/uptake of tools for ASD screening, diagnosis, and treatment; understand specific healthcare needs of autistic individuals in lower resource countries; and conduct longitudinal studies to understand the lifetime health, social, and economic impacts of ASD and enable the evaluation of novel approaches to increasing healthcare access.

IntroductionHaemophilia A is a chronic disease requiring frequent intravenous infusions of recombinant factor VIII. Previous studies have shown that challenges associated with current treatments may have significant impacts on quality of life (QoL) that are as important as the health outcomes conferred by the therapy. Emerging therapeutic innovations offer the potential to mitigate treatment‐related challenges, and it is therefore important to develop a better understanding of patient and caregiver experiences with existing haemophilia A treatments in order to characterize the full value of new treatments.AimTo gather firsthand perspectives from people with haemophilia A (PWHA) and caregivers on the challenges with current treatment, their impact on QoL and desired improvements in future therapies.MethodsQualitative insights were gathered from 20 non‐inhibitor PWHA or caregivers of PWHA across Canada through one‐on‐one interviews; insights were further explored through focus group sessions to uncover overarching themes and prioritize issues with current treatments.ResultsPWHA and caregivers identified several challenges, including administration of intravenous infusions, coordination of treatment schedules and ensuring adequate medication and supplies. Participants described how these challenges impact psychosocial well‐being, physical health, personal/social life and work. Alternate modes of administration and longer‐lasting treatment effects were identified as desired improvements over current treatments.ConclusionThis study emphasizes the impact that existing haemophilia A treatments have on psychological well‐being, employment opportunities and adherence to treatment regimens. These considerations may help to inform decision‐making for policymakers and health systems around the true value of new therapies entering the haemophilia market.

Although the preliminary characterization of chemokines and their receptors has been prolific, comparatively little is known about the role of chemokines in the evolution of immune responses. We speculate that the preferential recruitment of a particular immune cell population has implications for the short- and long-term features of an adaptive response. To test this hypothesis, we employed adenovirus-mediated gene transfer to express the Th1-affiliated, CXC chemokine IFN-γ-inducible protein (IP) 10 in the airways of mice undergoing a mucosal sensitization regimen known to result in a Th2-polarized allergic response. This resulted in a ∼60–75% inhibition of eosinophils in the bronchoalveolar lavage (BAL); these inflammatory changes were accompanied by enhanced IFN-γ, ablated IL-4, and, peculiarly, unaltered IL-5 and eotaxin levels in the BAL. The effect of IP-10 expression was shown to be dependent on IFN-γ, as there was no statistically significant reduction in BAL eosinophilia in IFN-γ knockout mice subjected to the IP-10 intervention. Flow cytometric analysis of mononuclear cells in the lung revealed a ∼60% reduction in the fraction of CD4+ cells expressing T1/ST2, a putative Th2 marker, and a parallel increase in the proportion expressing intracellular IFN-γ following IP-10 treatment. The effect of IP-10 expression at the time of initial Ag encounter is persistent, as mice rechallenged with OVA following the resolution of acute inflammation exhibited reduced eosinophilia and IL-4 in the BAL. Collectively, these data illustrate that local expression of the chemokine IP-10 can introduce Th1 phenomena to a Th2-predisposed context and subvert the development of a Th2 response.

An awakening to systemic anti-black racism, anti-Indigenous racism, and harmful colonial structures in the context of a pandemic that has made health inequities and injustices impossible to ignore, is driving healthcare organizations to establish and strengthen approaches to inclusion, diversity, equity, and accessibility (IDEA). Health research and care organizations, which are shaping the future of healthcare, have a responsibility to make IDEA central to their missions. Many organizations are taking concrete action critically important to embedding IDEA principles, but durable change will not be achieved until IDEA becomes a core leadership competency. Drawing from the literature and consultation with individuals recognized for excellence in IDEA-informed leadership, this study will help Canadian healthcare and health research leaders—particularly those without lived experience—understand what it means to embed IDEA within traditional leadership competencies and propose opportunities to achieve durable change by rethinking governance, mentorship, and performance management through an IDEA lens.