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Background Ideally, medical research provides crucial data about disease processes, diagnoses, prognoses, treatment targets and outcomes, and systems of care. However, medical research is costly, and funding is difficult to receive because the processes are highly competitive. There is a paucity of data on the perspectives of researchers, funders, patients and the public about current funding paradigms. This study sought to understand the priorities and opinions of each group to better guide meaningful innovation in research funding processes.Method In this Priorities & Expectations of Researchers, Funders, Patients and the Public Regarding the Funding & Conduct of Stroke Research study, we conducted in-depth interviews with medical researchers, funders, patients and members of the general public to learn their opinions of the current funding process and thoughts about alternative approaches. We used both purposive and snowball sampling to recruit participants and conducted semistructured interviews. The study ended when thematic saturation was attained. Qualitative analysis followed inductive grounded theory methodology.Results 41 interviews were completed (11 researchers, 10 funders, 10 patients, 10 members of the general public; 61% female). Interviewees expressed a high interest in supporting a comprehensive evaluation of the research grant funding process while integrating funding mechanisms that are more inclusive and reduce bias in topic selection and researchers who receive funds. Participants acknowledged a gap in patient and public involvement in setting a research agenda, choosing topics to be studied and focusing on specific outcomes. Crowdfunding was identified as an alternative strategy that could facilitate research democratisation; however, participants emphasised the importance of expert review of research proposals, as in current processes to continue to support rigour and trust in research proposal quality.Conclusion Our research revealed stakeholder concerns about the transparency and equity of current research funding paradigms. Suggestions to democratize research and explore alternative fundraising platforms necessitate a fundamental shift in traditional research funding processes.

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate

Whether average sex differences in cardiorespiratory fitness can be mainly explained by blood inequalities in the healthy circulatory system remains unresolved. This study evaluated the contribution of blood volume (BV) and oxygen (O2) carrying capacity to the sex gap in cardiac and aerobic capacities in healthy young individuals. Healthy young women and men (n = 28, age range = 20–43 years) were matched by age and physical activity. Echocardiography, blood pressures, and O2 uptake were measured during incremental exercise. Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), peak O2 uptake (VO2peak), and BV were assessed with precise methods. The test was repeated in men after blood withdrawal and reduction of O2 carrying capacity, reaching women’s levels. Before blood normalization, exercise cardiac volumes and output (LVEDV, SV, Q) adjusted by body size and VO2peak (42 ± 9 vs. 50 ± 11 ml⋅min–1⋅kg–1, P < 0.05) were lower in women relative to men. Blood normalization abolished sex differences in cardiac volumes and output during exercise (P ≥ 0.100). Likewise, VO2peak was similar between women and men after blood normalization (42 ± 9 vs. 40 ± 8 ml⋅min–1⋅kg–1, P = 0.416). In conclusion, sex differences in cardiac output and aerobic capacity are not present in experimental conditions matching BV and O2 carrying capacity between healthy young women and men.

OBJECTIVES:. The reduced orthostatic tolerance (OT) that is characteristic of the female sex may be explained by multiple phenotypic differences between sexes. This study aimed to elucidate the mechanistic role of blood volume (BV) and oxygen carrying capacity on sex differences in OT. DESIGN:. Experimental intervention. SETTING:. University of Calgary, Main Campus, Calgary, AB, Canada. SUBJECTS:. Healthy women and men (n = 90) throughout the adult lifespan (20–89 yr) matched by age and physical activity. INTERVENTIONS:. Incremental lower body negative pressure (LBNP) in all individuals. Blood withdrawal and oxygen carrying capacity reduction in men to match with women’s levels. MEASUREMENTS AND MAIN RESULTS:. Transthoracic echocardiography and central blood pressures were assessed throughout incremental LBNP for 1 hour or until presyncope. Blood uniformization resulted in a precise sex match of BV and oxygen carrying capacity (p ≥ 0.598). A third of women (14/45) and two thirds of men (31/45) prior to blood uniformization completed the orthostatic test without presyncopal symptoms (p-for-sex < 0.001). After blood uniformization, seven out of 45 men completed the test (p-for-sex = 0.081). Left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) were progressively reduced with LBNP in both sexes, with women showing markedly lower volumes than men (p < 0.001). Blood uniformization did not eliminate sex differences in LVEDV and SV. CONCLUSIONS:. Sex differences in OT are not present when BV and oxygen carrying capacity are experimentally matched between sexes throughout the adult lifespan.