The Lunenfeld-Tanenbaum Research Institute is a medical research institute in Toronto, Ontario and part of the Sinai Health System. It was originally established in 1985 as the Samuel Lunenfeld Research Institute, the research arm of Mount Sinai Hospital, by an endowment from the Lunenfeld and Kunin families. It was renamed to the current name on June 24, 2013, after a $35 million donation from Larry and Judy Tanenbaum.It comprises 36 principal investigators, has a budget of C$90 million (2005/6), has over 200 trainees and approximately 600 staff. The institute conducts research into various forms of cancer (colon, breast, pancreatic, prostate, lung, etc.), neurological disorders and brain illnesses, women's and infants' health, diabetes, developmental biology, stem cell biology and tissue regeneration, mouse models of human disease, genomic medicine and systems biology. The institute has 100,000 sq ft (9,300 m2) of space and is split between the main hospital and the Joseph and Wolf Lebovic Health Complex.The Lunenfeld-Tanenbaum Research Institute is a world pioneer in the fields of Systems Biology, Diabetes, and Infectious Bowel Disease. Its Systems Biology team consistently ranked Top 5 worldwide. Researchers at the Lunenfeld have the highest per capita funding and citations in Canada.The founding director was Louis Siminovitch (1984–1994), followed by Alan Bernstein (1995–2000), Janet Rossant and Anthony Pawson (2001–2002), Anthony Pawson (2002–2005) and James Woodgett (2005–). Researchers are supported by the Mount Sinai Hospital Foundation, donors and external funding sources including the Canadian Institutes of Health Research, Canadian Cancer Society, Terry Fox Foundation, National Institutes of Health and Genome Canada.
We consider parameter inference for linear quantile regression with non-stationary predictors and errors, where the regression parameters are subject to inequality constraints. We show that the constrained quantile coefficient estimators are asymptotically equivalent to the metric projections of the unconstrained estimator onto the constrained parameter space. Utilizing a geometry-invariant property of this projection operation, we propose inference procedures - the Wald, likelihood ratio, and rank-based methods - that are consistent regardless of whether the true parameters lie on the boundary of the constrained parameter space. We also illustrate the advantages of considering the inequality constraints in analyses through simulations and an application to an electricity demand dataset.
Executive function (EF) is a core aspect of development, however, the current body of EF research is disproportionately influenced by studies conducted in Western, high-income countries, with limited representation from low- and middle-income countries (LMICs) such as India. This imbalance raises concerns about the generalizability and cultural relevance of EF constructs and assessment tools. To address this gap, this scoping review examined the tools used to assess EFs in preschool-aged children (birth to six years) in India. The review also explored which EF domains were most frequently assessed and identified disciplinary patterns in EF research within India. The search process yielded 3,540 articles, 210 were selected for full-text review, 28 met the inclusion criteria and were retained for data extraction. Findings revealed that emerging culturally responsive instruments developed by local researchers show promise. However, there is a persisting reliance on Western-developed instruments. Only six studies utilized locally developed tools, few measures included standardized translations into Indian languages, and only two studies in this review focused on instrument validation or design. Furthermore, EF was often examined as an auxiliary construct as few studies were designed with EF as a core developmental construct deserving of targeted investigation. Addressing these gaps require a shift toward EF specific research that prioritize culturally grounded measures, linguistic inclusivity, and ecological validity.
The aim of this paper was to report on fidelity in the preconception phase of the Healthy Life Trajectories Initiative Bukhali randomised controlled trial with young women in Soweto, South Africa, covering fidelity of content, dose and delivery, as well as barriers to fidelity, and opportunities and solutions to overcome these barriers. This mixed methods, descriptive study collected qualitative data from sessions with staff delivering the intervention component of the trial (referred to as ‘Health Helpers’) to report on content and delivery, and an open-ended survey about a key component of intervention delivery, Healthy Conversation Skills. Quantitative data on dose were collected from dosage data, structured observations (also providing data on delivery), and staff records. Health Helpers were generally positive about the relevance and relatability of the intervention materials, and highlighted the importance of simplifying, translating, contextualising and tailoring the content for participants. Adaptations to the dose and delivery of the intervention included shifting to individual sessions (versus groups), and increasing the number of telephonic compared to in-person sessions at the research site. Dosage data indicated a high level of fidelity in terms of sessions delivered for intervention and control arms, and regarding the delivery of multi-micronutrient supplements to intervention participants. Results from the structured observations also evidenced good fidelity, although challenges were noted with some aspects of the delivery of Healthy Conversation Skills. These findings provide actionable strategies for designing, delivering, and scaling complex interventions that remain both rigorous and responsive to local realities.
The ability to reduce the risk of developing diabetic ketoacidosis (DKA) remains a major care gap for people with diabetes, particularly those on intensive insulin therapy. The anticipated availability of continuous ketone monitoring (CKM) has the potential to reduce the risk of developing DKA, one of the most life-threatening acute complications of type 1 and type 2 diabetes. International clinical guidelines have established ketone thresholds for suspected and confirmed diagnoses of DKA, based on use of point-of-care testing, as part of a triad of markers with allied thresholds for hyperglycaemia and acidosis. The increasing occurrence of euglycemic DKA, with glucose concentrations below established diagnostic thresholds, makes the availability and use of CKM technology an important addition to the diabetes management toolkit. CKM data could alert the user when the risk of acute DKA is high on sick days in addition to signalling that individuals might be predicted to be at greater overall risk of future DKA on the basis of the distribution and degree of ketone measures in daily life. If widespread use of CKM devices is to be safe and effective in reducing the occurrence of DKA, it is important to establish clear ketone thresholds which notify CKM users when action on their part is required. In defining these thresholds and actions, it was important to ensure that the CKM user is not exposed to avoidable anxiety or suffers alarm fatigue, thus adding to the burden of living with diabetes. In the absence of substantial evidence that can identify appropriate ketone thresholds for CKM use, a panel of international experts in the management of DKA was convened with the aim of developing a number of objective, practical recommendations on how this novel diabetes technology could improve outcomes for individuals at risk of DKA, the results of which we report in this Personal View. These recommendations have been endorsed by the International Society for Pediatric and Adolescent Diabetes (ISPAD).
Glucagon-like peptide-1 (GLP-1) medicines improve metabolic liver disease through weight-loss-dependent and -independent actions. Here, we interrogated semaglutide's action in mice with metabolic dysfunction-associated steatohepatitis (MASH). In Glp1rWnt1-/- mice resistant to GLP-1RA-induced weight loss, semaglutide improved steatosis, fibrosis, and immune remodeling. GEM-X Flex-seq localized Glp1r expression to pericentral liver sinusoidal endothelial cells (ECs) (LSECs) and CD8+ T cells. EC Glp1r deletion in Glp1rTie2-/- mice or AAV8-Cre-mediated hepatic EC Glp1r knockdown substantially abrogated semaglutide's hepatic benefits despite preserved weight loss. Transcriptomic profiling revealed that Glp1r+ LSECs adopt a stress-responsive phenotype in MASH that is reversed by semaglutide. Glp1r+ LSECs function as dominant contributors to semaglutide-regulated circuits linked to injury and repair involving VWF, SELE, CEACAM, and BMP. Molecular profiling revealed semaglutide-coordinated transcriptional and protein-level reversal of disease signatures. Together, the data using mouse models of MASH reveal an EC-specific, weight-loss-independent, semaglutide-regulated, GLP-1R-dependent intrahepatic network for improving liver health.
