Combining genomics and epidemiology to investigate a zoonotic outbreak of rabies in Romblon Province, Philippines.

Rabies is a viral zoonosis that kills thousands of people annually in low- and middle-income countries across Africa and Asia where domestic dogs are the reservoir. 'Zero by 30', the global strategy to end dog-mediated human rabies, promotes a One Health approach underpinned by mass dog vaccination, post-exposure vaccination of bite victims, robust surveillance and community engagement. Using Integrated Bite Case Management (IBCM) and whole genome sequencing (WGS), we enhanced rabies surveillance to detect an outbreak in a formerly rabies-free island province in the Philippines.

Seroepidemiology of human leptospirosis in the Dominican Republic: A multistage cluster survey, 2021.

Little is known about the epidemiology of leptospirosis in the Dominican Republic, the second most populous country in the Caribbean. We report on findings from a multi-stage household survey across two regions in the country that reveals a previously under-estimated burden of human Leptospira infection. Our findings, based on the reference-standard microscopic agglutination test, indicate a complex picture of serogroup diversity, spatial heterogeneity in infection and risk, and a marked discrepancy between reported cases and serologically estimated infections.

Social media quality in undergraduate medical education: A reconceptualisation and taxonomy.

Background: Social Media (SoMe) as a learning tool, though ubiquitous in society and popular within medical education, is often criticised as superficial. Its limitless output has been blamed for encouraging shorter attention spans and shirking in-depth reflection. The evidence base is itself superficial and lacking rigour or meaning.

Mathematical modelling for pandemic preparedness in Canada: Learning from COVID-19.

Background: The COVID-19 pandemic underlined the need for pandemic planning but also brought into focus the use of mathematical modelling to support public health decisions. The types of models needed (compartment, agent-based, importation) are described. Best practices regarding biological realism (including the need for multidisciplinary expert advisors to modellers), model complexity, consideration of uncertainty and communications to decision-makers and the public are outlined.

Biallelic Loss-of-Function Variants in UBAP1L and Nonsyndromic Retinal Dystrophies.

Importance: Inherited retinal dystrophies (IRDs) present a challenge in clinical diagnostics due to their pronounced genetic heterogeneity. Despite advances in next-generation sequencing (NGS) technologies, a substantial portion of the genetic basis underlying IRDs remains elusive. Addressing this gap seems important for gaining insights into the genetic landscape of IRDs, which may help improve diagnosis and prognosis and develop targeted therapies in the future.

Risk factors associated with the intensity of COVID-19 outbreaks in Canadian community settings: a retrospective analysis of outbreak-level surveillance data.

Background: The severity of COVID-19 outbreaks is disproportionate across settings (e.g., long-term care facilities (LTCF), schools) across Canada.

Genetic Implication of Specific Glutamatergic Neurons of the Prefrontal Cortex in the Pathophysiology of Schizophrenia.

Background: The prefrontal cortex (PFC) has been strongly implicated in the pathophysiology of schizophrenia. Here, we combined high-resolution single-nuclei RNA sequencing data from the human PFC with large-scale genomic data for schizophrenia to identify constituent cell populations likely to mediate genetic liability to the disorder.

Methods: Gene expression specificity values were calculated from a single-nuclei RNA sequencing dataset comprising 84 cell populations from the human PFC, spanning gestation to adulthood.

Sensitivity and specificity of International Classification of Diseases algorithms (ICD-9 and ICD-10) used to identify opioid-related overdose cases: A systematic review and an example of estimation using Bayesian latent class models in the absence of gold standards.

Objectives: This study aimed to summarize validity estimates of International Classification of Diseases (ICD) codes in identifying opioid overdose (OOD) among patient data from emergency rooms, emergency medical services, inpatient, outpatient, administrative, medical claims, and mortality, and estimate the sensitivity and specificity of the algorithms in the absence of a perfect reference standard.

Methods: We systematically reviewed studies published before December 8, 2023, and identified with Medline and Embase. Studies reporting sufficient details to recreate a 2 × 2 table comparing the ICD algorithms to a reference standard in diagnosing OOD-related events were included.

MicroRNAs as Bile-based biomarkers in pancreaticobiliary cancers (MIRABILE): a cohort study.

Background: Biliary obstruction can be due to both malignant and benign pancreaticobiliary disease. Currently, there are no biomarkers that can accurately help make this distinction. MicroRNAs (miRNAs) are stable molecules in tissue and biofluids that are commonly deregulated in cancer.

Unlocking the diagnostic power of plasma extracellular vesicle miR-200 family in pancreatic ductal adenocarcinoma.

Background: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers.

GP workforce sustainability to maximise effective and equitable patient care: a realist review of what works, for whom and in what circumstances?

Background: UK general practice has been described as being in crisis. A shortage and exodus of GPs is an urgent and challenging problem, attracting significant media attention, widespread public debate, and policy action.

Aim: Our review aims to examine which aspects of the healthcare system affect GP workforce sustainability, how, why, and for whom.

Spatiotemporal epidemiology of substance-related accidental acute toxicity deaths in Canada from 2016 to 2017.

Objectives: In Canada, substance-related accidental acute toxicity deaths (AATDs) continue to rise at the national and sub-national levels. However, it is unknown if, where, when, and to what degree AATDs cluster in space, time, and space-time across the country. The objectives of this study were to 1) assess for clusters of AATDs that occurred in Canada during 2016 and 2017 at the national and provincial/territorial (P/T) levels, and 2) examine the substance types detected in AATD cases within each cluster.

General practitioner workforce sustainability to maximise effective and equitable patient care: a realist review protocol.

Introduction: There are not enough general practitioners (GPs) in the UK National Health Service. This problem is worse in areas of the country where poverty and underinvestment in health and social care mean patients experience poorer health compared with wealthier regions. Encouraging more doctors to choose and continue in a GP career is a government priority.

Impact of the COVID-19 pandemic on inbound air travel to Canada.

Background: Commercial air travel can result in global dispersal of infectious diseases. During the coronavirus disease 2019 (COVID-19) pandemic, many countries implemented border measures, including restrictions on air travel, to reduce the importation risk of COVID-19. In the context of inbound air travel to Canada, this study aimed to: 1) characterize travel trends before and during the pandemic, and 2) statistically assess the association between travel volumes and travel restrictions during the pandemic.

A methodology for estimating SARS-CoV-2 importation risk by air travel into Canada between July and November 2021.

Background: Estimating rates of disease importation by travellers is a key activity to assess both the risk to a country from an infectious disease emerging elsewhere in the world and the effectiveness of border measures. We describe a model used to estimate the number of travellers infected with SARS-CoV-2 into Canadian airports in 2021, and assess the impact of pre-departure testing requirements on importation risk.

Methods: A mathematical model estimated the number of essential and non-essential air travellers infected with SARS-CoV-2, with the latter requiring a negative pre-departure test result.

Surveillance system integration: reporting the results of a global multicountry survey.

Objectives: Currently, there is no comprehensive picture of the global surveillance landscape. This survey examines the current state of surveillance systems, levels of integration, barriers and opportunities for the integration of surveillance systems at the country level, and the role of national public health institutes (NPHIs).

Study Design: This was a cross-sectional survey of NPHIs.

One Health communication channels: a qualitative case study of swine influenza in Canada in 2020.

Background: With increased attention to the importance of integrating the One Health approach into zoonotic disease surveillance and response, a greater understanding of the mechanisms to support effective communication and information sharing across animal and human health sectors is needed. The objectives of this qualitative case study were to describe the communication channels used between human and animal health stakeholders and to identify the elements that have enabled the integration of the One Health approach.

Methods: We combined documentary research with interviews with fifteen stakeholders to map the communication channels used in human and swine influenza surveillance in Alberta, Canada, as well as in the response to a human case of H1N2v in 2020.

Genetic and Phenotypic Features of Schizophrenia in the UK Biobank.

Importance: Large-scale biobanks provide important opportunities for mental health research, but selection biases raise questions regarding the comparability of individuals with those in clinical research settings.

Objective: To compare the genetic liability to psychiatric disorders in individuals with schizophrenia in the UK Biobank with individuals in the Psychiatric Genomics Consortium (PGC) and to compare genetic liability and phenotypic features with participants recruited from clinical settings.

Design, Setting, And Participants: This cross-sectional study included participants from the population-based UK Biobank and schizophrenia samples recruited from clinical settings (CLOZUK, CardiffCOGS, Cardiff F-Series, and Cardiff Affected Sib-Pairs).

Forecasting seasonal influenza activity in Canada-Comparing seasonal Auto-Regressive integrated moving average and artificial neural network approaches for public health preparedness.

Introduction: Public health preparedness is based on timely and accurate information. Time series forecasting using disease surveillance data is an important aspect of preparedness. This study compared two approaches of time series forecasting: seasonal auto-regressive integrated moving average (SARIMA) modelling and the artificial neural network (ANN) algorithm.

Rare variants in pharmacogenes influence clozapine metabolism in individuals with schizophrenia.

Clozapine is the only licensed medication for treatment-resistant schizophrenia (TRS). Few predictors for variation in response to clozapine have been identified, but clozapine metabolism is known to influence therapeutic response and adverse side effects. Here, we expand on genome-wide studies of clozapine metabolism, previously focused on common genetic variation, by analysing whole-exome sequencing data from 2062 individuals with schizophrenia taking clozapine in the UK.

The Association of Hippocampal Long-Term Potentiation-Induced Gene Expression with Genetic Risk for Psychosis.

Genomic studies focusing on the contribution of common and rare genetic variants of schizophrenia and bipolar disorder support the view that substantial risk is conferred through molecular pathways involved in synaptic plasticity in the neurons of cortical and subcortical brain regions, including the hippocampus. Synaptic long-term potentiation (LTP) is central to associative learning and memory and depends on a pattern of gene expression in response to neuronal stimulation. Genes related to the induction of LTP have been associated with psychiatric genetic risk, but the specific cell types and timepoints responsible for the association are unknown.

A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease.

Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis. As bile flows in close proximity to these lesions, we aimed to establish a bile-based microRNA (miRNA) signature to discriminate between malignant and benign pancreaticobiliary diseases.

Subfemtowatt Laser Phase Tracking.

Low power optical phase tracking is an enabling capability for intersatellite laser interferometry, as minimum trackable power places significant constraints on mission design. Through the combination of laser stabilization and control-loop parameter optimization, we have demonstrated continuous tracking of a subfemtowatt optical field with a mean time between slips of more than 1000 s. Comparison with analytical models and numerical simulations verified that the observed experimental performance was limited by photon shot noise and unsuppressed laser frequency fluctuations.

Genomic findings in schizophrenia and their implications.

There has been substantial progress in understanding the genetics of schizophrenia over the past 15 years. This has revealed a highly polygenic condition with the majority of the currently explained heritability coming from common alleles of small effect but with additional contributions from rare copy number and coding variants. Many specific genes and loci have been implicated that provide a firm basis upon which mechanistic research can proceed.