Sex differences in muscle morphology of the knee flexors and knee extensors

Introduction Females experience higher risk of anterior cruciate ligament (ACL) injuries; males experience higher risk of hamstring strain injuries. Differences in injury may be partially due to sex differences in knee flexor (KF) to knee extensor (KE) muscle size ratio and the proportional size of constituent muscles. Purpose To compare the absolute and proportional size, and mass distribution, of individual KE and KF muscles, as well as overall size and balance (size ratio) of these muscle groups between the sexes. Methods T1-weighted axial plane MR images (1.5T) of healthy untrained young males and females (32 vs 34) were acquired to determine thigh muscle anatomical cross-sectional area(ACSA). Maximal ACSA (ACSAmax) ofconstituent muscles, summated for KF and KE muscle groups, and the KF:KE ratio were calculated. Results Females had 25.3% smaller KE ACSAmax (70.9±12.1 vs 93.6±10.3 cm2; P<0.001) and 29.6% smaller KF ACSAmax than males (38.8±7.3cm2 vs 55.1±7.3cm2; P<0.001).Consequently, females had lower KF:KE ACSA ratio (P = 0.031). There were sex differences in the proportional size of 2/4 KE and 5/6 KF. In females, vastus lateralis (VL), biceps femoris long-head (BFlh) and semimembranosus (SM) were a greater proportion and sartorius(SA), gracilis (GR) and biceps femoris short-head (BFsh) a smaller proportion of their respective muscle groups compared to males (All P<0.05). Conclusion Sex differences in KF:KE ACSAmax ratio may contribute to increased risk of ACL injury in females. Sex discrepancies in absolute and proportional size of SA, GR, VL and BFlh may contribute further anatomical explanations for sex differences in injury incidence

Big Data Needs Big Governance: Best Practices From Brain-CODE, the Ontario-Brain Institute’s Neuroinformatics Platform

The Ontario Brain Institute (OBI) has begun to catalyze scientific discovery in the field of neuroscience through its large-scale informatics platform, known as Brain-CODE. The platform supports the capture, storage, federation, sharing, and analysis of different data types across several brain disorders. Underlying the platform is a robust and scalable data governance structure which allows for the flexibility to advance scientific understanding, while protecting the privacy of research participants. Recognizing the value of an open science approach to enabling discovery, the governance structure was designed not only to support collaborative research programs, but also to support open science by making all data open and accessible in the future. OBI’s rigorous approach to data sharing maintains the accessibility of research data for big discoveries without compromising privacy and security. Taking a Privacy by Design approach to both data sharing and development of the platform has allowed OBI to establish some best practices related to large-scale data sharing within Canada. The aim of this report is to highlight these best practices and develop a key open resource which may be referenced during the development of similar open science initiatives

Validating a novel deterministic privacy-preserving record linkage between administrative & clinical data: applications in stroke research

Introduction Research data combined with administrative data provides a robust resource capable of answering unique research questions. However, in cases where personal health data are encrypted, due to ethics requirements or institutional restrictions, traditional methods of deterministic and probabilistic record linkages are not feasible. Instead, privacy-preserving record linkages must be used to protect patients' personal data during data linkage. Objectives To determine the feasibility and validity of a deterministic privacy preserving data linkage protocol using homomorphically encrypted data. Methods Feasibility was measured by the number of records that successfully matched via direct identifiers. Validity was measured by the number of records that matched with multiple indirect identifiers. The threshold for feasibility and validity were both set at 95%. The datasets shared a single, direct identifier (health card number) and multiple indirect identifiers (sex and date of birth). Direct identifiers were encrypted in both datasets and then transferred to a third-party server capable of linking the encrypted identifiers without decrypting individual records. Once linked, the study team used indirect identifiers to verify the accuracy of the linkage in the final dataset. Results With a combination of manual and automated data transfer in a sample of 8,128 individuals, the privacy-preserving data linkage took 36 days to match to a population sample of over 3.2 million records. 99.9% of the records were successfully matched with direct identifiers, and 99.8% successfully matched with multiple indirect identifiers. We deemed the linkage both feasible and valid. Conclusions As combining administrative and research data becomes increasingly common, it is imperative to understand options for linking data when direct linkage is not feasible. The current linkage process ensured the privacy and security of patient data and improved data quality. While the initial implementations required significant computational and human resources, increased automation keeps the requirements within feasible bounds

Designing and Implementing a Privacy Preserving Record Linkage Protocol

Introduction The Ontario Brain Institute has developed Brain-CODE, an informatics platform, to support the acquisition, storage, management and analysis of multi-modal data. The standardized research data within Brain-CODE spans several brain disorders, allowing for integrative analyses, while also providing the opportunity to leverage existing clinical administrative data holdings through external linkages. Objectives and Approach Within Ontario, the majority of individuals who access the healthcare system have a unique identifier, the Ontario Health Insurance Plan (OHIP) number. The OHIP number can facilitate linkages with administrative data holdings, such as those at the Institute for Clinical Evaluative Sciences (ICES). Given that OBI is not permitted under Ontario’s privacy legislation to hold OHIP numbers, identifiers for consented participants are encrypted using a public key mechanism upon entry into Brain-CODE, where the private key is inaccessible. To facilitate linkages involving OHIP numbers between Brain-CODE and ICES, Brain-CODE Link software was co-developed by members of the Indoc Consortium. Results Brain-CODE Link allows a deterministic linkage between encrypted identifiers (OHIP numbers), without revealing participant identity. The same homomorphic encryption algorithm applied to identifiers upon entry to Brain-CODE, is applied to relevant identifiers within ICES data holdings. Encrypted identifiers from Brain-CODE are securely transferred to ICES, where a comparison computation calculates differences between the encrypted sets. These differences are sent to a semi-trusted third party, who has no access to the original data, to decrypt the differences using the private key. A zero difference indicates a set of matching identifiers. One of the main challenges during testing and development of Brain-CODE Link was ensuring the software was capable of scaling to a population level, performing a large number of comparisons, in a computationally efficient manner. Conclusion/Implications Ongoing pilot projects within the areas of epilepsy, neurodevelopment disorders, and neurodegeneration will be the first examples of linkages between Brain-CODE and ICES. Brain-CODE Link has successfully performed several billion test comparisons, indicating its suitability to function as a scalable privacy preserving record linkage to support comprehensive analyses

General practitioner workforce planning: assessment of four policy directions

<p>Abstract</p> <p>Background</p> <p>Estimating the supply of GPs into the future is important in forecasting shortages. The lengthy training process for medicine means that adjusting supply to meet demand in a timely fashion is problematic. This study uses Ireland as a case study to determine the future demand and supply of GPs and to assess the potential impact of several possible interventions to address future shortages.</p> <p>Methods</p> <p>Demand was estimated by applying GP visit rates by age and sex to national population projections. Supply was modelled using a range of parameters derived from two national surveys of GPs. A stochastic modelling approach was adopted to determine the probable future supply of GPs. Four policy interventions were tested: increasing vocational training places; recruiting GPs from abroad; incentivising later retirement; increasing nurse substitution to enable practice nurses to deliver more services.</p> <p>Results</p> <p>Relative to most other European countries, Ireland has few GPs per capita. Ireland has an ageing population and demand is estimated to increase by 19% by 2021. Without intervention, the supply of GPs will be 5.7% less than required in 2021. Increasing training places will enable supply to meet demand but only after 2019. Recruiting GPs from overseas will enable supply to meet demand continuously if the number recruited is approximately 0.8 per cent of the current workforce per annum. Later retirement has only a short-term impact. Nurse substitution can enable supply to meet demand but only if large numbers of practice nurses are recruited and allowed to deliver a wide range of GP services.</p> <p>Conclusions</p> <p>A significant shortfall in GP supply is predicted for Ireland unless recruitment is increased. The shortfall will have numerous knock-on effects including price increases, longer waiting lists and an increased burden on hospitals. Increasing training places will not provide an adequate response to future shortages. Foreign recruitment has ethical considerations but may provide a rapid and effective response. Increased nurse substitution appears to offer the best long-term prospects of addressing GP shortages and presents the opportunity to reshape general practice to meet the demands of the future.</p

Mythical numbers and the proceeds of organised crime: estimating mafia proceeds in Italy

Organised crime is a field vulnerable to mythical numbers, i.e. exaggerated estimates lacking empirical support, but acquiring acceptance through repetition. The figures on mafia proceeds in Italy are a striking example of this problem. This study proposes an estimation of mafia proceeds in Italy from nine criminal activities (sexual exploitation of women, illicit firearms trafficking, drug trafficking, counterfeiting, the illicit cigarette trade, illicit gambling, illicit waste disposal, loan sharking, and extortion racketeering) by region and type of mafia (Cosa Nostra, Camorra,\u2018Ndrangheta, Apulian mafias, and other mafias). The results estimate yearly mafia proceeds at approximately \u20ac10.7 bn (0.7% of the Italian GDP), discussing the impact on the regional and national economies and the differences among the types of mafias as to their geographical sources of revenue

The CAMH Neuroinformatics Platform: A Hospital-Focused Brain-CODE Implementation

Investigations of mental illness have been enriched by the advent and maturation of neuroimaging technologies and the rapid pace and increased affordability of molecular sequencing techniques, however, the increased volume, variety and velocity of research data, presents a considerable technical and analytic challenge to curate, federate and interpret. Aggregation of high-dimensional datasets across brain disorders can increase sample sizes and may help identify underlying causes of brain dysfunction, however, additional barriers exist for effective data harmonization and integration for their combined use in research. To help realize the potential of multi-modal data integration for the study of mental illness, the Centre for Addiction and Mental Health (CAMH) constructed a centralized data capture, visualization and analytics environment—the CAMH Neuroinformatics Platform—based on the Ontario Brain Institute (OBI) Brain-CODE architecture, towards the curation of a standardized, consolidated psychiatric hospital-wide research dataset, directly coupled to high performance computing resources

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction: Prespecified analyses from the REVIVED-BCIS2 trial

BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82–1.30]; P =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920048