McMaster University

Valid instrumental variables (IVs) must not directly impact the outcome variable and must also be uncorrelated with nonmeasured variables. However, in practice, IVs are likely to be invalid. The existing methods can lead to large bias relative to standard errors in situations with many weak and invalid instruments. In this paper, we derive a LASSO procedure for the k-class IV estimation methods in the linear IV model. In addition, we propose the jackknife IV method by using LASSO to address the problem of many weak invalid instruments in the case of heteroscedastic data. The proposed methods are robust for estimating causal effects in the presence of many invalid and valid instruments, with theoretical assurances of their execution. In addition, two-step numerical algorithms are developed for the estimation of causal effects. The performance of the proposed estimators is demonstrated via Monte Carlo simulations as well as an empirical application. We use Mendelian randomization as an application, wherein we estimate the causal effect of body mass index on the health-related quality of life index using single nucleotide polymorphisms as instruments for body mass index.

To better understand the link between formative assessments and progress difficulty, we conducted an analysis in the undergraduate MD program of the Michael G. DeGroote School of Medicine by comparing formative assessment scores on Short Answer Questions (SAQ) called Concept Application Exercises (CAE) with subsequent progress difficulty. CAE scores are designed to formatively assess knowledge translation. These scores are not formally incorporated into the progress decision at the end of each curricular unit, which is holistic in nature. Students are referred to a student progress remediation committee if they fail to meet the curricular objectives. We sought to investigate the following research question: Do short answer questions, in the form of CAEs, predict subsequent learner progress difficulty? Data from the last four student cohorts of 2022–2025 were included. To address the predictive power of CAE score characteristics, a binary logistic regression model was constructed with remediation committee referral as the dependent variable and CAE score characteristics as the independent variable. This study found that the average CAE score is the most powerful predictor of later progress difficulty, with each point drop in average score associated with a 37% increase in the odds of referral to the remediation committee. These findings illustrate the predictive value of the SAQ to identify later progress difficulty.

Physeal stress injuries of the shoulder include proximal humeral epiphysiolysis, also known as Little League shoulder (LLS), and acromial apophysiolysis, with LLS far more common. These stress injuries of the shoulder are most common in adolescent male baseball pitchers, presenting as pain, particularly with throwing. Radiographs may show widening of the physis, and magnetic resonance imaging, if needed, will show bone marrow edema. Conservative modalities including rest, physical therapy, and cessation from throwing for a period of approximately 3–4 months are the mainstay of treatment. Risk factors include pitching mechanics and the number of pitches thrown and prevention is arguably the most important aspect of treatment for physeal stress injuries of the shoulder. Most patients are able to return to sport and throwing following a period of rest and conservative management. However, in those that do return to pitching, recurrence of little league shoulder, and the development of os acromiale have been reported.

Background Very large sample sizes are often needed to capture heterogeneity in autism, necessitating data sharing across multiple studies with diverse assessment instruments. In these cases, data harmonization can be a critical tool for deriving a single dataset for analysis. This can be done through computational approaches that enable the conversion of scores across various instruments. To this end, our study examined the use of analytical approaches for mapping scores on two measures of adaptive functioning, namely predicting the scores on the vineland adaptive behavior scales II (VABS) from the scores on the adaptive behavior assessment system II (ABAS). Methods Data from the province of Ontario neurodevelopmental disorders network were used. The dataset included scores VABS and the ABAS for 720 participants (autism n = 547, 433 male, age: 11.31 ± 3.63 years; neurotypical n = 173, 95 male, age: 12.53 ± 4.05 years). Six regression approaches (ordinary least squares (OLS) linear regression, ridge regression, ElasticNet, LASSO, AdaBoost, random forest) were used to predict VABS total scores from the ABAS scores, demographic variables (age, sex), and phenotypic measures (diagnosis; core and co-occurring features; IQ; internalizing and externalizing symptoms). Results The VABS scores were significantly higher than the ABAS scores in the autism group, but not the neurotypical group (median difference: 8, 95% CI = (7,9)). The difference was negatively associated with age (beta = -1.2 ± 0.12, t = -10.6, p < 0.0001). All estimators demonstrated similar performance, with no statistically significant differences in mean absolute error (MAE) values across estimators (MAE range: 4.96–6.91). The highest contributing features to the prediction model were ABAS composite score, diagnosis, and age. Limitations This study has several strengths, including the large sample. We did not examine the conversion of domain scores across the two measures of adaptive functioning and suggest this as a future area of investigation. Conclusion Overall, our results supported the feasibility of harmonization. Our results suggest that a linear regression model trained on the ABAS composite score, the ABAS raw domain scores, and age, sex, and diagnosis would provide an acceptable trade-off between accuracy, parsimony, and data collection and processing complexity.

We review a key subset of the experimental studies that have recently focused on cubic pyrochlore magnets whose pseudospin-1 / 2 degrees of freedom have mixed dipolar and octupolar character. We discuss how this comes about and how the character of the pseudospin-1 / 2 can be experimentally determined. The minimal spin Hamiltonian for such magnetic insulators is known to give rise to a rich phase diagram with both disordered U(1) quantum spin ice (QSI) states and all-in–all-out (AIAO) noncollinear ordered states, each with dipolar and octupolar character. We focus primarily on experimental studies on two such single crystal systems, the \TimesFont{J} = 5 / 2 Ce 2 Zr 2 O 7 and the \TimesFont{J} = 9 / 2 Nd 2 Zr 2 O 7 . We make the case that Ce 2 Zr 2 O 7 is an excellent QSI ground-state candidate material, close to the border between QSIs with dipolar and octupolar symmetry. Nd 2 Zr 2 O 7 exhibits an AIAO ordered phase, featuring an order parameter consisting of dipolar and octupolar magnetic moments. It is found to reside close to a QSI phase boundary and features dynamic fragmentation in its excitation spectrum.

The capacity to tune the degree of mucoadhesion and mucopenetration of nanoparticles is essential to improving drug bioavailability, transport, and efficacy at mucosal interfaces. Herein, self-assembled nanoparticles (NPs) fabricated from...

Introduction Patients with pancreatic ductal adenocarcinoma (PDAC) face challenging treatment decisions following their diagnosis. We developed and validated a survival prognostication model using routinely available clinical information, patient-reported symptoms, performance status, and initial cancer-directed treatment. Methods This retrospective cohort study included PDAC patients from 2007 to 2020 using linked administrative databases in Ontario, Canada. Patients were randomly selected for model development (75%) and validation (25%). Using the development cohort, a multivariable Cox proportional hazards regression with backward stepwise variable selection was used to predict the probability of survival. Model performance was assessed on the validation cohort using the concordance index and calibration plots. Results There were 17,450 patients (49% female) with a median age of 72 (IQR 63-81) and a mean survival time of nine months. In the derivation cohort, 1,469 (11%) patients had early stage, 4,202 (32%) had advanced stage disease, and 7,417 (57%) had unknown stage. The following factors were associated with an increased risk of death by more than 10%: tumour in the tail of the pancreas, advanced stage, hospitalization three months prior to diagnosis, congestive heart failure or dementia, low, moderate, or high pain score, moderate or high appetite score, high dyspnea and tiredness score, and a performance status score of 60-70 or lower. The calibration plot indicated good agreement with a C index of 0.76. Discussion This model accurately predicted one-year survival for PDAC using clinical factors, symptoms, and performance status. This model may foster shared decision making for patients and their providers.

The urbanization of Indigenous peoples in Canada has increased substantially during recent decades, with over 44% of Indigenous peoples now residing in urban centres. Despite the urban concentration of healthcare services, Indigenous health outcomes remain significantly worse than non-Indigenous health outcomes for people living in urban centres. The historical and subsisting impacts of colonialism have had a profound negative influence on social determinants of health for Indigenous peoples, resulting in higher rates of chronic disease and mortality. Mistrust of the healthcare system, racial discrimination, and medical paternalism remain barriers to accessing care and diminish the quality of care received. This commentary explores how Indigenous-led health services can improve Indigenous health outcomes and how urban reserves could be used to improve the health of urban Indigenous residents.

Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.

Enhanced insulation and superior thermal characteristics are crucial in advanced packaging for medium voltage (MV) silicon carbide (SiC) power modules. Nonetheless, the reduction in thermal resistance typically compromises insulation level due to the decreased number of insulation layers. In this paper, the forced fluorinated liquid cooling methodology is proposed, whereby fluorinated liquid (3M FC-40) is directed into the power module, substituting silicone gel and diminishing thermal resistance. Through the utilization of forced fluorinated liquid cooling, a reduction of 21°C in junction temperature at full load is demonstrated in the experiment, compared to traditional power modules cooled with water. Furthermore, there is a 35.6% reduction observed in the maximum temperature rise ΔTj, thereby enhancing the lifespan of the power module. Enhanced cooling efficiency with lower flow rates of forced fluorinated liquid cooling offers greater energy savings than water cooling. As dissipation power is transferred from the topside of the chip to the fluorinated liquid, the possibility of unlimited stacking of direct bonded copper (DBC) is enabled to lower the electrical field, thereby facilitating insulation at the bottom side of the chip without any worries regarding heightened thermal resistance. Forced fluorinated liquid cooling resulted in a 39°C reduction in the junction temperature of the double-stacked DBC power module. Moreover, partial discharge (PD) detection under square wave excitation revealed that the DBC immersed in the fluorinated liquid remains free from PD at 10 kV, a significantly higher threshold than observed with silicone gel. A higher partial discharge inception voltage (PDIV) is anticipated for double-stacked DBC when immersed in 3M FC-40. Thus, the forced fluorinated liquid cooling, which simultaneously enhances thermal and insulation performance, can be considered a promising solution for the next generation of MV SiC power modules.

The development of current sensors for wide-bandgap (WBG) applications consistently emphasizes high bandwidth, minimal invasiveness, and integration. Despite the meticulous design that enables current shunts to achieve excellent performance with high bandwidth and low parasitics, their inherent bulkiness remains a significant challenge for their integration into high-integrated applications that depend on the high switching speeds of WBG power devices. This study thoroughly investigates and uncovers the trade-off faced by traditional current shunts in balancing miniaturization and high bandwidth. Building upon this understanding, the miniaturized current shunt (MiniShunt) concept is introduced to overcome inherent limitations and achieve both high performance and compact size. To realize this concept, a physical implementation that involves the high-density stacking of multiple coupled transmission lines is presented. Additionally, a thermal network model specifically for the proposed MiniShunt configuration is developed and a comprehensive thermal analysis methodology for the current shunts is established. By applying this methodology to finite element analysis (FEA), the thermal safe operating area (SOA) for the MiniShunt can be determined, further providing valuable insights into its maximum static power dissipation and maximum energy loss. These findings contribute to the development of a highly compact 9×9-mm, 100-mΩ current shunt with an ultrahigh bandwidth of 3 GHz, near-zero parasitic inductance, and a maximum energy loss of 2.0 J at a reference temperature rise limit of 20°C. Extensive experiments conducted in both the frequency and time domains serve to further validate the advantages of the MiniShunt in terms of its miniaturization, integration, ultrafast response, and low invasiveness for future high-integrated power electronics applications.

This paper studies the rate-distortion-perception (RDP) tradeoff for a memoryless source model in the asymptotic limit of large block-lengths. The perception measure is based on a divergence between the distributions of the source and reconstruction sequences conditioned on the encoder output, first proposed by Mentzer et al. We consider the case when there is no shared randomness between the encoder and the decoder and derive, for the case of discrete memoryless sources, a single-letter characterization of the RDP function. This is in contrast to the marginal-distribution metric case (introduced by Blau and Michaeli), whose RDP characterization remains open when there is no shared randomness. The achievability scheme is based on lossy source coding with a posterior reference map. For the case of continuous valued sources under the squared error distortion measure and the squared quadratic Wasserstein perception measure, we also derive a single-letter characterization and show that the decoder can be restricted to a noise-adding mechanism. Interestingly, the RDP function characterized for the case of zero perception loss coincides with that of the marginal metric and further zero perception loss can be achieved with a 3-dB penalty in minimum distortion. Finally we specialize to the case of Gaussian sources, and derive the RDP function for Gaussian vector case and propose a reverse water-filling type solution. We also partially characterize the RDP function for a mixture of Gaussian vector sources.

Background Hospitalized older adults have unique physical, emotional, and psychosocial needs. We sought to understand older patients’ and care partners’ experiences with multicomponent interventions that support age-friendly care and identify areas for improvement. Methods We conducted a mixed methods study using surveys and interviews to explore older adult patients’ (65 years or older) and their care partners’ experiences with hospital-delivered multicomponent initiatives. We recruited participants from the Geriatric Rehabilitation (GRU) and Musculoskeletal (MSK) Rehabilitation units in a Canadian academic hospital from October 2021 to April 2022 until we reached data saturation and no new themes emerged. Results We recruited 18 participants, 10 patients (mean age 78 years, 80.0% female) and 8 care partners (mean age 61, 87.5% female). Surveys revealed overall positive experiences with multicomponent interventions. Interviews revealed five themes: 1) various forms of companionship for patients, 2) recreation and entertainment, 3) physical activity, 4) communication, and 5) pleasant physical environment. Having forms of companionship and proper communication with the care team were highlighted as areas of importance. Physical activity was highly valued, but participants expressed hesitation around safety of mobilizing without physiotherapists. Recreational activities helped distract from social isolation during a hospital stay and participants had diverse preferences for activities. Participants had strong memories of the physical environment, including the lack of natural light, institutionallike décor, and smells. Conclusion Companionship, recreation and entertainment, physical activity, communication, and the physical environment were important to hospitalized patients and their care partners. Hospital administrators and policy makers should consider these when targeting areas to improve care for the aging population.

This study examined the change in weight at 6 months of naltrexone/bupropion (NB), a combination pharmacological therapy for weight management, in real‐world practice in Canada. The study was conducted through an observational, retrospective, single‐arm chart review of adult patients who attended the Wharton Medical Clinic in Ontario, Canada, between 2018 and 2021. The patients had a body mass index ≥30 or ≥27 kg/m ² with at least one weight‐related comorbidity. They were prescribed NB, titrated from 1 (8 mg/90 mg) to 4 tablets daily, along with lifestyle modification. Approximately 52% of 468 participants completed 6 months of treatment and 48.7% titrated to the maximum dose of 4 tablets daily. Participants were mainly female, with mean age of 49.5 years and BMI 38.4 kg/m ² . After 6 months, participants lost a mean of 4.23 kg (95% confidence interval [CI] −4.99, −3.47) or 4.05% (CI −4.77, −3.34) of body weight, with 42.5% losing at least 5% of their body weight and 15.5% losing at least 10%. The most frequent adverse events were nausea (5.7%), constipation (5.7%), and headache (2.5%). Participants also experienced decreased appetite (14.7%), decreased cravings (13.9%), decreased hunger (9.4%) and felt full sooner (2.5%), which are changes likely to result in sustained healthy food choices and improved quality of life. The 6‐month NB treatment adjunct to lifestyle modification in a real‐world population resulted in clinically significant weight loss.

In everyday conversation, bilingual individuals switch between their languages not only in reaction to monolinguals with different language profiles but also voluntarily and naturally. However, whether and how various switching contexts dynamically modulate domain-general cognitive control is still unclear. Using a cross-task paradigm in which a flanker task was interleaved with a language-switching task trial-by-trial, the present study examined the performance of unbalanced Chinese-English bilinguals on a flanker task in forced, voluntary, and natural switching contexts. The cross-domain interaction on the P3 component revealed an atypical flanker effect in forced switching contexts only, and the P3 amplitude of incongruent trials in forced switching contexts was smaller than in both natural and voluntary switching contexts. Furthermore, robust brain–brain and brain-behavior relationships between language control and domain-general control emerged in the forced switching context only. Altogether, our findings support the dynamic adaptation of language control to cognitive control and highlight the importance of different types of switching contexts.

Vanadium oxides are widely used for microsupercapacitors (MSCs) due to their multiple‐valence and high theoretical capacitance. A conceptually new approach of electric discharge machining (EDM) with computer‐aided control is developed to one‐step fabricate Mo‐doped VO0.2‐based electrodes and devices with designable geometry. The results demonstrate that the Mo@VO0.2 integrated interdigital MSCs (IIMSCs) with the narrowest electrode distance of 300 μm show the best capacitive performance, which is furtherly manifested by the electric field simulation. Moreover, this work concentrates on expounding the relationships between the EDM machining current, surface morphology of Mo@VO0.2, and the capacitive behavior of Mo@VO0.2 IIMSCs. Compared to the machining current of 2 and 3 A, the machining current of 1 A facilitates synthesizing smaller Mo@VO0.2 particles with more porosity and higher surface area and thus achieving a larger capacitance value for Mo@VO0.2 IIMSCs device, which is achieving 32 mF cm⁻² at 1 mV s⁻¹, working well up to an ultrahigh scan rate of 30 V s⁻¹, and obtaining a good cyclic stability of 88.61% after 5000 cycles. Moreover, this innovative EDM approach opens a new avenue for one‐step synthesis of various ceramic metal oxides for various microdevices such as microbatteries and microsensors.