McMaster University

Aims: Magnetic resonance imaging (MRI) studies have identified brain structural predictors of treatment response in individuals with alcohol use disorder (AUD), but with varying findings and primarily in male veterans. The present study investigated cortical surface area and thickness (CT) as predictors of brief intervention response in community-based adults with AUD. Methods: Sixty-five non-treatment-seeking adults with AUD (44.6% male, aged 33.2±10.3 years) underwent an MRI and received a brief intervention comprising personalized feedback and motivational interviewing, with follow-up approximately 6-8 weeks later to quantify changes in drinks/week (DPW), the primary outcome. Eighteen bilateral a priori regions of interest (ROIs) were used to predict DPW at follow-up, adjusting for baseline drinking. Significant predictors were examined with secondary outcomes, percent drinking and heavy drinking days, and in relation to out-of-scanner measures of impulsivity and comorbidities. Results: Participants exhibited expected significant decreases in alcohol consumption in response to the brief intervention. Eight bilateral CT ROIs in the frontal, temporal, and occipital lobes, most notably medial orbitofrontal, middle temporal, and lateral occipital gyri, predicted DPW; however, only three predicted the secondary outcomes. Significant associations were observed between CT in frontal and occipital regions with impulsivity (delay discounting, lack of premeditation), executive functioning, anxiety, and stress. Conclusions: Thinner frontal, temporal, and occipital ROIs predicted poorer brief intervention response, with notable overlap with brain regions previously implicated in AUD. Clarifying whether these regions reflect premorbid or acquired differences and, if the latter, the potential for recovery of cortical gray matter following drinking reductions are future priorities.

While the aging population is well documented and understood, as is the fact that avoiding premature death is important in being able to age well, the concept of aging well is a more elusive idea. In general, the idea of successful aging in health terms means compression of the period of morbidity experienced by an individual (Fries et al. J Aging Res, 2011). Comments in the literature noting that there is not yet a consensus definition of aging well reflects the very individual and subjective nature of expectations, adaptation, and satisfaction with life that relate to this. A systematic analysis by Kim et al. of “successful aging” includes domains such as avoiding disease and disability, having high cognitive, mental, and physical function, being actively engaged in life, and being psychologically well adapted in later life (Kim and Park, Res Aging 39(5):657–677, 2017). Similarly, in the model of “Aging well” by Fernandez-Ballesteros et al., successful aging is defined by the domains of health and activities of daily living (ADL), physical and cognitive functioning, social participation and engagement, and also positive affect and control (Fernández-Ballesteros et al. J Am Geriatr Soc 56(5):950–952, 2008). For every individual a life worth living on their terms may be very different, as eloquently expressed by Sir Theodore Fox, an Editor of the Lancet for many years. “Not least do people differ in their attitude to life. Some cling to it as a miser to his money, and to as little purpose. Others wear it lightly—ready to risk it for a cause, a hope, a song, the wind on their face. When so many people think of it as a means, the doctor, surely, would be wrong to insist that it is always the first of ends. Life is not really the most important thing in life.” (Fox Lancet 286(7417):801–805, 1965)

Atrial fibrillation is a frequent cardiac arrhythmia and is associated with an increased risk of cardioembolic stroke. The left atrial appendage is a finger-like extension originating from the main body of the left atrium and the main location of thrombus formation in patients with atrial fibrillation. Surgical or percutaneous left atrial appendage occlusion (LAAO) aims at preventing clot formation in the left atrial appendage. Here, we describe available surgical and percutaneous approaches to achieve LAAO and discuss the available evidence for LAAO in patients with atrial fibrillation. We discuss the role of LAAO and its role in stroke prevention in frequent scenarios in cerebrovascular medicine: LAAO as a potential alternative to oral anticoagulation in patients with a history of intracranial hemorrhage, and LAAO as a promising add-on therapy to direct oral anticoagulant therapy in patients with breakthrough stroke despite anticoagulation. Finally, we provide an outlook on currently ongoing trials that will provide further evidence in the next years.

Background Clinical practice guidelines provide important evidence-based recommendations to optimize patient care, but their development is labor-intensive and time-consuming. Large language models have shown promise in supporting academic writing and the development of systematic reviews, but their ability to assist with guideline development has not been explored. In this study, we tested the capacity of LLMs to support each stage of guideline development, using the latest SAGES guideline on the surgical management of appendicitis as a comparison. Methods Prompts were engineered to trigger LLMs to perform each task of guideline development, using key questions and PICOs derived from the SAGES guideline. ChatGPT-4, Google Gemini, Consensus, and Perplexity were queried on February 21, 2024. LLM performance was evaluated qualitatively, with narrative descriptions of each task’s output. The Appraisal of Guidelines for Research and Evaluation in Surgery (AGREE-S) instrument was used to quantitatively assess the quality of the LLM-derived guideline compared to the existing SAGES guideline. Results Popular LLMs were able to generate a search syntax, perform data analysis, and follow the GRADE approach and Evidence-to-Decision framework to produce guideline recommendations. These LLMs were unable to independently perform a systematic literature search or reliably perform screening, data extraction, or risk of bias assessment at the time of testing. AGREE-S appraisal produced a total score of 119 for the LLM-derived guideline and 156 for the SAGES guideline. In 19 of the 24 domains, the two guidelines scored within two points of each other. Conclusions LLMs demonstrate potential to assist with certain steps of guideline development, which may reduce time and resource burden associated with these tasks. As new models are developed, the role for LLMs in guideline development will continue to evolve. Ongoing research and multidisciplinary collaboration are needed to support the safe and effective integration of LLMs in each step of guideline development.

The dominant model of musical scales in academic theories is derived from instrument tunings. However, the study of vocal scales – most especially in indigenous cultures – has been all but ignored. The voice is almost certainly the original musical instrument, and so an analysis of vocal scales provides a more naturalistic means of understanding the evolution of music. In particular, we explore the idea that the structure of musical scales is a reflection of the vocal imprecision inherent in the way that people sing, regardless of culture. To investigate this issue globally, we carried out a large-scale computational analysis of 418 ethnographic field recordings of vocal songs from indigenous/traditional cultures, spanning the 10 principal musical-style regions of the world, analyzing the number of pitch-classes, the number of interval-classes, the pitch-class distribution, the scale intervals, and scale typology. The results revealed that vocal scales have reliably larger intervallic spacings between pitch-classes than do theory-based and instrumental scales in Western culture. In addition, the mean interval-size of the scales was significantly correlated with people’s imprecision in singing pitches across the world regions. These results lend support to a physiological model in which musical scales optimize pitch spacing in order to accommodate the imprecision inherent in vocal production and thereby maintain distinguishability between pitch-classes during musical communication.

Indoor positioning systems (IPS) can be used to measure mobility at home, which is an important indicator for health and wellbeing. In this work, we designed and developed a Bluetooth Low Energy (BLE) based IPS that identifies individual users; does not require floorplans; and allows the end-users to perform on-site install/setup. Additionally, a dynamic calibration process is implemented to learn room boundaries based on the distribution of the BLE signal strength. The functionality and performance of IPS system were validated in two residential home settings. Raw and filtered relative signal strength indicators (RSSI) and variability of RSSI were measured during testing. Room detection was determined by comparing a user input location (ground truth) with the IPS detected location for over 300 positions. The IPS produced a 96% accuracy of correctly detecting room location when using RSSI and the additional motion sensors. The use of PIR motion and ultrasonic sensors information provided improved validity when compared with existing indoor positioning systems. The ease of use and modular design of this IPS makes it a good choice for implementation in larger scale smart healthcare monitoring systems.

Different decision-making styles can be used to provide counselling for the multiple reasonable treatment options for patients with stress urinary incontinence (SUI). Shared decision-making (SDM) is currently advocated as the preferred style for preference sensitive decisions, as SDM takes patient preferences into account. This study aimed to map the current decision-making process for SUI in three Western countries. We included 124 patients and 18 physicians in a multicentre, prospective study in five hospitals in Canada, the United Kingdom and the Netherlands. We used patient and physician versions of the Control Preference Scale (CPS) questionnaires and examined audio-recordings of consultations with the OPTION-5 instrument to assess the degree of SDM. Most patients (63%) perceived the decision-making as informative, some (29%) as shared and only a few (8%) as paternalistic. Dutch patients more often perceived the decision-making as informative than UK or Canadian patients. Patients’ preferred and perceived decision-making styles matched in 70% of consultations. Patients’ and physicians’ perceptions of decision-making were the same in 60% of consultations, but their perceptions of SDM use did not match. This also did not match the OPTION-5 scores reflecting the use of SDM. Almost all patients were satisfied with the decision-making they perceived. Most patients and physicians prefer and perceive the current decision-making process as informative decision-making. However, patients and physicians have different perceptions of their mutual consultation. This highlights the imprecise concept of SDM for both patients and physicians.

Purpose An international working group (IWG) consisting of experts in X-linked hypophosphatemia (XLH) developed global guidelines providing a comprehensive, evidence-based approach to XLH diagnosis, management, and monitoring. Methods The IWG, consisting of 43 members as well as methodologists and a patient partner, conducted 2 systematic reviews (SRs) and narrative reviews to address key areas. The SRs addressed the impact of burosumab compared to conventional therapy (phosphate and active vitamin D) or no therapy on patient-important outcomes in adults. They also evaluated conventional therapy compared to no therapy. GRADE methodology was applied to evaluate the certainty of evidence. Non-GRADED recommendations were made in the presence of insufficient evidence to conduct SRs. These guidelines have been reviewed and endorsed by several medical and patient societies and organizations. Results The diagnosis of XLH is based on integrating clinical evaluation, laboratory findings confirming renal phosphate wasting (following exclusion of conditions mimicking XLH), and skeletal imaging. Fibroblast growth factor 23 measurement and DNA analysis are of value in the diagnosis, if available. Pathogenic or likely pathogenic variants in the PHEX gene are confirmatory but not necessary for the diagnosis. Management requires a multidisciplinary team knowledgeable and experienced in XLH. Effective medical therapy with burosumab can improve fracture and pseudofracture healing. Main Conclusion In adults with XLH and fractures or pseudofractures, burosumab is recommended over no therapy (strong recommendation, GRADEd). Additionally, burosumab is suggested as the preferred treatment compared to conventional therapy (conditional recommendation, GRADEd) in the absence of fractures or pseudofractures. If burosumab is not available, symptomatic adults should be treated with conventional therapy (Non-GRADEd recommendation).

We aimed to develop an Explanation & Elaboration document to provide explanations, rationales, and good examples of reporting for each item in the COSMIN Reporting Guideline 2.0. The development of the Explanation & Elaboration document was conducted in four phases. In phase 1, experts on measurement properties were invited as writers to draft explanations and examples for each item. The original COSMIN Reporting Guideline items into 22 clusters, each containing two to six items, which were self-assigned by writers based on expertise. In phase 2, a draft of the Explanation & Elaboration document was created. For each item, an ‘Explanation’, ‘Essential elements’, and ‘Item examples’ were written. The draft was reviewed by a team of reviewers for grammar, conciseness, and consistency with other COSMIN tools. In phase 3, the Explanation & Elaboration document was extensively revised considering the newly created COSMIN reporting guidelines 2.0. In phase 4, the final version incorporated feedback from all writers and final approval. Eighteen writers drafted the item explanations and provided examples of good reporting. The Explanation & Elaboration document contains explanations of the General and Specific items. We explain the reasons why reporting of the item is recommended and how to report the items with examples of good reporting. The Explanation & Elaboration document of the COSMIN Reporting Guideline 2.0 facilitates comprehensive reporting of studies on measurement properties of PROMs and should be used in conjunction with the COSMIN Reporting Guideline 2.0.

p class="ICST-abstracttext"> Hadoop is an open-source framework that enables the parallel processing of large data sets across a cluster of machines. It faces several challenges that can lead to poor performance, such as I/O operations, network data transmission, and high data access time. In recent years, researchers have explored prefetching techniques to reduce the data access time as a potential solution to these problems. Nevertheless, several issues must be considered to optimize the prefetching mechanism. These include launching the prefetch at an appropriate time to avoid conflicts with other operations and minimize waiting time, determining the amount of prefetched data to avoid overload and underload, and placing the prefetched data in locations that can be accessed efficiently when required. In this paper, we propose a smart prefetch mechanism that consists of three phases designed to address these issues. First, we enhance the task progress rate to calculate the optimal time for triggering prefetch operations. Next, we utilize K-Nearest Neighbor clustering to identify which data blocks should be prefetched in each round, employing the data locality feature to determine the placement of prefetched data. Our experimental results demonstrate that our proposed smart prefetch mechanism improves job execution time by an average of 28.33% by increasing the rate of local tasks. </p

The rapid advancements in big data and the Internet of Things (IoT) have significantly accelerated the digital transformation of medical institutions, leading to the widespread adoption of Digital Twin Healthcare (DTH). The Cloud DTH Platform (CDTH) serves as a cloud-based framework that integrates DTH models, healthcare resources, patient data, and medical services. By leveraging real-time data from medical devices, the CDTH platform enables intelligent healthcare services such as disease prediction and medical resource optimization. However, the platform functions as a system of systems (SoS), comprising interconnected yet independent healthcare services. This complexity is further compounded by the integration of both black-box AI models and domain-specific mechanistic models, which pose challenges in ensuring the interpretability and trustworthiness of DTH models. To address these challenges, we propose a Model-Based Systems Engineering (MBSE)-driven DTH modeling methodology derived from systematic requirement and functional analyses. To implement this methodology effectively, we introduce a DTH model development approach using the X language, along with a comprehensive toolchain designed to streamline the development process. Together, this methodology and toolchain form a robust framework that enables engineers to efficiently develop interpretable and trustworthy DTH models for the CDTH platform. By integrating domain-specific mechanistic models with AI algorithms, the framework enhances model transparency and reliability. Finally, we validate our approach through a case study involving elderly patient care, demonstrating its effectiveness in supporting the development of DTH models that meet healthcare and interpretability requirements.

In vitro selection methods are used to identify catalytic RNAs from pools of random sequences. We discuss the central concepts using experimental data and computational models. Experiments proceed in multiple rounds, each with a reaction step and a step in which reacted sequences are recovered. Sequences are enriched each round by a factor depending on combined reaction and recovery probability. In the first round, there are few functional sequences, and it is necessary to minimize the probability of losing these. In later rounds, the loss probability is negligible, and the procedure can be optimized to maximize the enrichment factor. Clusters of related sequences emerge which descend from separate sequences in the initial pool. The fitness of an RNA depends on how well it matches a structure with specified sequence and base-pair constraints. Sequences that exactly match the constraints may be rare, but sequences a few mutations away are much more common; hence it is likely that clusters descend from suboptimal sequences. There is a high probability that beneficial mutations arise during the experiment. This explains the experimental observation that there is little correlation between cluster frequencies and fitnesses, whereas correlation between enrichment factors and fitnesses is strong.

Periodic election is the hallmark of electoral democracy. In achieving this, continental groups such as the African Union (AU) have initiated interventions to allow nations to function and compare notes within a measurable framework. Tanzania is one of the signatories to the APRM document and has engaged several partners in recent presidential, parliamentary, and councillorship elections. The transitions were held despite the recurring socioeconomic challenges as well as the increased burden of the fight against the effects of insurgency, displacements, and the COVID-19 pandemic, which ravaged the resources of these countries. However, the country’s First-Past-the-Post electoral system was confronted by issues such as the adoption of technology, election management agencies, political participation, free press, independent candidacy, and election dispute resolution mechanisms. This study examines the role of partner institutions, especially the African Development Bank (AfDB), the United Nations Development Programme, and the United Nations Economic Commission for Africa (UNECA), in the democratization process of the member countries. The study relied on data from democratic partner agencies as well as existing data from relevant secondary sources and suggested ways to further strengthen democracy in these countries and other democracies across the world.

In this paper, we present initial findings and analysis from an ongoing study on immigration detention in Canada. Participants who have been or are currently in immigration detention systems in Canada shared stories of dehumanizing torment and the abuse of their right to timely procedural fairness during their time in detention, in lockdown, and in transit. Drawing on critical disability studies and critical mental health literature using postcolonial theoretical framework, we show how participants resisted by caring for themselves and others in the present, and by imagining their freedom in the future. Through an analysis of interviews and focus groups, this paper discusses temporal torment as a manifestation of carceral violence in immigration detention in Canada. Immigration detainees experience time as static, where they are frozen in a state of paralysis, as though their time in detention does not matter or is not worthwhile. The frequency of Canada Border Services Agency consultations was experienced as restricted access to due process and the abuse of rights was lived as a method of indefinite carceral violence. The contributions from the participants highlight the complexities of carceral violence that are experienced through immigration detention in Canada, which functions as a denial of humanity, rights, and care, and highlights the need for urgent intervention.

Eosinophilia is a hallmark of allergic disorders, including asthma, allergic rhinitis, and atopic dermatitis. The onset and maintenance of allergic inflammation in atopic adults involves the activation of selective hemopoietic processes and the migration of mature and immature eosinophils to allergic tissue, where these cells release mediators of inflammation that participate in the regulation of inflammation. Eosinophils function in close cooperation with basophils and mast cells in allergic tissue, where crosstalk between these central effector cells regulates the inflammatory process. This chapter will review the cellular events leading to the accumulation of eosinophils and their progenitors in the airways in allergic asthma, with a particular focus on models of allergen‐induced allergic inflammation. Inhaled allergen challenges in allergic asthmatics have advanced understanding of the pathogenesis of allergen exposure leading to early and late asthmatic responses and the associated airway hyperresponsiveness and type 2 airway inflammation. This chapter will also discuss the mechanisms of commonly used asthma therapies on allergen‐induced eosinophilia and compare the effects of novel therapies targeting specific immune pathways for a better understanding of how to regulate airway eosinophil levels in patients with asthma.

Ventricular arrhythmias (VA), including ventricular tachycardia and fibrillation, are critical cardiac conditions that are often managed by catheter ablation among those unresponsive to pharmacologic therapy. The choice of anesthesia and sedation regimens for VA ablations may impact arrhythmia inducibility and hemodynamic stability, which can affect procedural success and complication rates. This systematic review and meta-analysis aimed to compare the efficacy and safety of sedation versus general anesthesia (GA) among patients undergoing VA ablation. The review was prospectively registered on PROSPERO (CRD42023441553). Database searches were conducted across five major databases from inception to March 9, 2024 to identify randomized trials or observational studies including adult patients undergoing ablations for VA. Screening and data extraction were completed in duplicate. Risk-of-bias assessments were conducted using ROBINS-I as all included studies were observational, and the quality of evidence was evaluated using the GRADE framework. Six observational studies (N = 16,435) were included. No significant differences were found between sedation and GA for total procedure time (MD: −14.16 minutes; 95%CI: −38.61 to 10.29 minutes), arrhythmia non-inducibility (RR: 0.73; 95% CI: 0.33–1.58), acute ablation success (RR: 1.06; 95% CI: 0.65–1.71), or procedural complications (RR: 0.72; 95% CI: 0.28–1.85). However, sedation was associated with significantly lower intraprocedural hemodynamic instability (RR: 0.28; 95% CI: 0.12–0.70). These findings indicate that while sedation and GA have comparable outcomes, sedation may be associated with less hemodynamic instability during VA ablation. However, more high-quality studies are needed to confirm these results.