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Objective: Remission from problem gambling (PG) continues to be a priority of clinicians and researchers. Data from cross-sectional studies indicate that some correlates are more predictive of PG, and existing longitudinal studies have exclusively examined risk factors that predict emergence of PG. This study's objective is to fill in the remaining pieces of the puzzle by identifying factors that might facilitate remission from PG. Method: A stratified sample of 10,199 Canadian adult gamblers were recruited from an online panel. Respondents who screened positively for PG at baseline and completed a follow-up assessment 1 year later (n = 468) were assessed on a series of modifiable gambling, psychosocial, mental health, and substance use variables. A forward stepwise logistic regression was conducted to identify the strongest predictors of remission from PG at follow-up. A Least Absolute Shrinkage and Selection Operator regression was also conducted to confirm the most relevant predictors. Results: Out of 75 candidate variables, 10 were retained by the regression model. Two were related to cessation of specific gambling activities, two were related to gambling motivations, two were psychosocial in nature, two were related to substance use while gambling, and one was related to remission from a mental health disorder. The final and strongest predictor was PG severity at baseline. Conclusions: Although PG remission predictors were mostly gambling-related, psychosocial aspects may also be targeted by stakeholders aiming to reduce PG. Ceasing to use tobacco while gambling and diversifying leisure activities may be promising targets. Other mental health and substance use predictors may still possibly be relevant, but only for a subset of people with PG. Public Health Significance Statement: Gambling-related, psychosocial, and mental health variables predict remission from problem gambling 1 year later. Initial problem gambling severity is the strongest predictor of remission. Cessation of electronic gaming machine gambling and decreasing the frequency of tobacco use while gambling is associated with a higher likelihood of remission. Different predictors of remission may be identified when separating people who gamble into subgroups based on their biopsychosocial profiles. [ABSTRACT FROM AUTHOR]

Objective: The current research aimed to examine the biopsychosocial characteristic profile of online gamblers, relative to land-based exclusive gamblers, both concurrently and prospectively in a large national cohort of Canadian adults. Method: This cohort was recruited from Leger Opinion's registered panel of online participants. In addition to demographic information, the survey battery included assessment of comorbidities of disordered gambling (substance use disorder and other behavioral addictions), level of stress, past year life events, presence of mental health disorders, impulsivity, gambling engagement, gambling fallacies, family history of problem gambling, past year problem gambling and gambling-related harm. The 1-year follow-up survey was completed by 55.9% of this cohort. Results: Significant differences between online and land-based exclusive gamblers were detected on all gambling engagement measures at baseline. For example, those who gamble via online platforms spend more time gambling than land-based exclusive gamblers (M = 58.86 versus M = 20.13 hours respectively), engage in more types of gambling (M = 4.10 versus M = 2.46) and incur greater gambling losses (M = $-960.56 versus M = $-382.84). Both the concurrent and prospective predictive analyses indicate that access to legal online gambling, increased frequency of engagement, higher impulsivity, younger age, and being male are variables that robustly and significantly predict gambling engagement via an online platform. Conclusions: The results of this study indicate while there are some robust factors that distinguish online from land-based exclusive gamblers, online gamblers are psychosocially a heterogenous group that does tend to engage in gambling to a greater extent than land-based exclusive gamblers. Additional longitudinal research is required examining the individual characteristics of online gamblers as this sub-population does appear to differ from that of land-based exclusive gamblers. [ABSTRACT FROM AUTHOR]

Objective: Sports betting accounts for the greatest proportion of online gambling behavior globally and has been linked to various harms. Few studies have examined the average sports bettor profile using stratified samples of adults who gamble regularly. The present study builds upon existing research on the demographic variables of sports bettors and provides an in-depth examination of the clinical and gambling-related factors associated with sports betting. Method: Participants (N = 10,039; 53.6% female) consisted of a stratified sample of Canadian adults who endorsed participating in gambling at least once per month in the past year. Participants completed standardized measures assessing demographics, gambling behavior, problem gambling severity, gambling-related harms, gambling motives, and psychological characteristics (e.g., substance use, mental health). Results: About 1,816 participants (18.1%) reported engaging in sports betting in the past year. Sports bettors tended to be younger, male, and employed full-time compared to nonsports bettors. Sports bettors endorsed different patterns of clinical comorbidities and greater substance use. Sports betting was also associated with unique gambling motives and greater time and money spent on gambling. Among participants who endorsed problem gambling, sports betting was associated with greater impulsivity and likelihood of using illicit substances while gambling. Conclusions: The results highlight the characteristics of individuals who bet on sports, as well as the characteristics of sports bettors with problem gambling which may help to inform the development of targeted prevention and intervention efforts to mitigate the potential harms of sports betting. [ABSTRACT FROM AUTHOR]

This study examined the perceptions of administrators and teachers to determine how the lack of broadband access has impacted decisions on virtual learning and the subsequent impact on student learning. The participants in the study were administrators and teachers from school districts that serve a low-income population (as determined by USDA Free/Reduced Lunch Program Statistics). The study utilized a quantitative methodology. Surveys were developed and sent to school district administrators and teachers in order to determine their perceptions on broadband access in rural areas and the impact on student learning. The study sought to answer the following research questions: 1. Is efficient broadband Internet readily accessible to all students? 2. In areas where broadband is accessible, do all students have access to Internet? 3. Based on the perceptions of teachers and administrators, how many students do not have Internet? 4. Based on the perceptions of teachers and administrators, how has the lack of Internet impacted student learning? [ABSTRACT FROM AUTHOR]

Objective: To conduct a large-scale national cohort study to identify the current etiological risk factors for problem gambling in Canada. Method: A cohort of 10,119 Canadian gamblers completed a comprehensive self-administered online questionnaire in 2018 and were reassessed in 2019. At baseline, the sample contained 1,388 at-risk gamblers, 1,346 problem gamblers, and 2,710 with a major DSM-5 mental health disorder. A total of 108 independent variables (IVs) were available for analysis, as well as the self-report of perceived causes of gambling-related problems for 1,261 individuals. Results: The strongest multivariate predictors of current and future problem gambling were "gambling-related" variables (i.e., current and past problem gambling, intensive gambling involvement, playing electronic gambling machines (EGMs), gambling fallacies, socializing with other people having gambling-related problems, and family history of having gambling-related problems). Beyond gambling-related variables, greater impulsivity and lower household income were robustly predictive. Thirteen additional variables were either concurrently or prospectively predictive, but not both. In contrast to the many different quantitative predictors, self-reported causes tended to be singular and psychologically oriented (i.e., desire to win money, boredom, stress, poor self-control). Conclusions: The predictors of problematic gambling in the present study are very similar to the predictors identified in prior international longitudinal and cross-sectional research. This implies core cross-cultural risk factors, with gambling-related variables and impulsivity being most important, and comorbidities and demographic variables having more modest contributions. The additional value of the present results is that they comprehensively identify the relative importance of all known etiologically relevant variables within a current Canadian context. [ABSTRACT FROM AUTHOR]

Background: The study of how extracellular Aβ‐amyloid (Aβ) drives intracellular, heterogeneous tau accumulation in Alzheimer's disease has been approached using linear models under an implicit assumption of regionally independent tau accumulation (Lockhart et al, 2017; Iaccarino et al, 2017). Multivariate, non‐linear models which enable relaxation of this assumption can be used; we employed a convolutional neural network (CNN) to identify critical tau topographic changes associated with Aβ‐burden in a cohort with a range of Aβ values, and compared results with linear analyses. Method: 134 subjects with [NAV4694 (Aβ) and [MK6240 (tau) scans were considered. A CNN was trained to map normalised tau (input) to Aβ Centiloid values (CL). CNN models were interpreted using saliency maps, denoting the importance of corresponding voxels to the output. The CNN approach was compared with linear analysis by testing the following voxel‐wise models: estimating tau SUVR from Aβ CL, and saliency from Aβ CL. All models were tested with minimum cluster extent of 200 after controlling for age and sex. Occlusion analysis was used to assess the importance of CNN‐identified salient clusters, which quantified the change in output after removing salient clusters from the input tau images. Result: The Aβ CL values were well predicted by tau topography using the CNN (training R2 = 0.86, validation R2 = 0.75, testing R2 = 0.72). Linear analysis identified widespread correlation between Aβ CL and tau‐SUVR in the brain, while CNN analysis demonstrated focal clusters in frontal lobes, middle cingulate, precuneus, postcentral gyrus and bilateral medial temporal lobes. At low Aβ levels, information from the frontal lobe, middle cingulate and precuneus regions was more predictive of Aβ CL while the information from medial temporal lobes was more predictive of high Aβ levels. Conclusion: The nonlinear data‐driven CNN approach, relaxing the assumption of independent regional tau accumulation, has revealed new associations between tau topography and Aβ burden. [ABSTRACT FROM AUTHOR]

A more comprehensive understanding of how cells respond to drug intervention, the likely immediate signalling responses and how resistance may develop within different microenvironments will help inform treatment regimes. The nonreceptor tyrosine kinase SRC regulates many cellular signalling processes, and pharmacological inhibition has long been a target of cancer drug discovery projects. Here, we describe the in vitro and in vivo characterisation of the small‐molecule SRC inhibitor AZD0424. We show that AZD0424 potently inhibits the phosphorylation of tyrosine‐419 of SRC (IC50 ~ 100 nm) in many cancer cell lines; however, inhibition of cell viability, via a G1 cell cycle arrest, was observed only in a subset of cancer cell lines in the low (on target) micromolar range. We profiled the changes in intracellular pathway signalling in cancer cells following exposure to AZD0424 and other targeted therapies using reverse‐phase protein array (RPPA) analysis. We demonstrate that SRC is activated in response to treatment of KRAS‐mutant colorectal cell lines with MEK inhibitors (trametinib or AZD6244) and that AZD0424 abrogates this. Cell lines treated with trametinib or AZD6244 in combination with AZD0424 had reduced EGFR, FAK and SRC compensatory activation, and cell viability was synergistically inhibited. In vivo, trametinib treatment of mice‐bearing HCT116 tumours increased phosphorylation of SRC on Tyr419, and, when combined with AZD0424, inhibition of tumour growth was greater than with trametinib alone. We also demonstrate that drug‐induced resistance to trametinib is not re‐sensitised by AZD0424 treatment in vitro, likely as a result of multiple compensatory signalling mechanisms; however, inhibition of SRC remains an effective way to block invasion of trametinib‐resistant tumour cells. These data imply that SRC inhibition may offer a useful addition to MEK inhibitor combination strategies. [ABSTRACT FROM AUTHOR]

Objective: The relationship between the level of gambling fallacy endorsement and type of gambler (nongambler, recreational gambler, at-risk gambler, and problem/pathological gambler) was assessed both concurrently and prospectively in a large national cohort of Canadian adults. Method: This cohort (n = 10,199 at baseline; 18-24 years, n = 481, 43% female; 25-34 years, n = 1,335, 62% female; 35-44 years, n = 1,543, 55% female, 45-54 years, n = 1,985, 58% female; 55-64 years, n = 2,459, 55% female; 65-74 years, n = 1,865, 44% female, 75+ years, n = 531, 43% female) was recruited from LEO, Leger Opinion's registered online panelists. The follow-up survey was completed by 55.9% of the cohort, 1 year after baseline. The full survey can be viewed at https://www.ucalgary.ca/research/national-gambling-study/. For the current study, scores on the Gambling Fallacies Measure, the Problem and Pathological Gambling Measure, Gambling Participation Instrument, and Impulsivity were analyzed. Results: There were three main findings. The first is that gambling fallacies are common in all categories of gamblers but somewhat more prevalent in problem and pathological gamblers. Second, the multivariate analysis determined that gambling fallacies are significant concurrent and prospective predictors of the problem/pathological gambling category, but not strong predictors relative to other variables. Third, problem gambling and heavier gambling involvement are also predictors of a future higher level of gambling fallacies. Conclusions: Collectively, these results show that gambling fallacies have some etiological relationship to problem gambling but are not the main cause of problem gambling and should not be the exclusive focus of problem gambling treatment. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by tau deposition in the depths of the sulci associated with exposure to repetitive head impacts (RHI). It is a post‐mortem diagnosis. We previously reported a frontotemporal predominant tau 18F‐MK6240 PET pattern resembling the distribution of CTE in a retired Australian Rules Football player in the context of a moderate amyloid‐beta plaque burden.1 This study aimed to investigate the utility of 18F‐MK6240 PET as a potential biomarker for CTE in contact sports players with exposure to RHI (sRHI). Method: sRHI (n = 33) and age‐matched healthy controls (HC) (n = 32) completed amyloid (18F‐NAV4694) and tau (18F‐MK6240) PET scans. Amyloid PET was quantified in Centiloids. 18F‐MK240 standardized uptake value ratios (SUVRs) were generated for the dorsolateral prefrontal cortex and composite regions of interest (ROI) (frontal; mesial temporal; temporoparietal). Result: For sRHI, the primary contact sport was Australian Rules Football (n = 17), boxing/kickboxing/martial arts (n = 11), rugby (n = 4) and soccer (n = 1), with 36.4% participating at a professional level. sRHI had a mean age of 54.2 (±9.2) (vs HC 53.0±9.5, p = 0.61), and 94% were male (vs HC 78%, p = 0.08). sRHI did not differ from HC in years of education (p = 0.46) but had more impaired MMSE (28.1±1.9 vs 29.3±0.8, p = 0.006, d = ‐0.80) and Clinical Dementia Rating scores (0.21±0.3 vs 0±0, p<0.001, d = 1.25). sRHI and HC did not differ in mean Centiloid values (2.9±8.4 vs 3.0±8.2). sRHI and HC did not differ in 18F‐MK6240 SUVR in the regions examined, and no differences were observed between professional and amateur sRHI. Conclusion: Contact sports players with exposure to repetitive head impacts did not differ from age‐matched healthy controls on 18F‐MK6240 SUVR in frontal, mesial temporal, and temporoparietal brain regions. Study limitations include the small sample size, heterogeneity in sports type and highest level of participation, and participants with relatively mild cognitive and functional impairments. Additionally, while 18F‐MK6240 has high affinity for 3R/4R tau in Alzheimer's disease, its affinity in CTE, particularly important at early stages, remains unclear. References : 1 Krishnadas N et al. Case report: 18F‐MK6240 tau positron emission tomography pattern resembling chronic traumatic encephalopathy in a retired Australian Rules Football player. https://doi.org/10.3389/fneu.2020.598980. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by tau deposition in the depths of the sulci associated with exposure to repetitive head impacts (RHI). It is a post‐mortem diagnosis. We previously reported a frontotemporal predominant tau 18F‐MK6240 PET pattern resembling the distribution of CTE in a retired Australian Rules Football player in the context of a moderate amyloid‐beta plaque burden.1 This study aimed to investigate the utility of 18F‐MK6240 PET as a potential biomarker for CTE in contact sports players with exposure to RHI (sRHI). Method: sRHI (n = 33) and age‐matched healthy controls (HC) (n = 32) completed amyloid (18F‐NAV4694) and tau (18F‐MK6240) PET scans. Amyloid PET was quantified in Centiloids. 18F‐MK240 standardized uptake value ratios (SUVRs) were generated for the dorsolateral prefrontal cortex and composite regions of interest (ROI) (frontal; mesial temporal; temporoparietal). Result: For sRHI, the primary contact sport was Australian Rules Football (n = 17), boxing/kickboxing/martial arts (n = 11), rugby (n = 4) and soccer (n = 1), with 36.4% participating at a professional level. sRHI had a mean age of 54.2 (±9.2) (vs HC 53.0±9.5, p = 0.61), and 94% were male (vs HC 78%, p = 0.08). sRHI did not differ from HC in years of education (p = 0.46) but had more impaired MMSE (28.1±1.9 vs 29.3±0.8, p = 0.006, d = ‐0.80) and Clinical Dementia Rating scores (0.21±0.3 vs 0±0, p<0.001, d = 1.25). sRHI and HC did not differ in mean Centiloid values (2.9±8.4 vs 3.0±8.2). sRHI and HC did not differ in 18F‐MK6240 SUVR in the regions examined, and no differences were observed between professional and amateur sRHI. Conclusion: Contact sports players with exposure to repetitive head impacts did not differ from age‐matched healthy controls on 18F‐MK6240 SUVR in frontal, mesial temporal, and temporoparietal brain regions. Study limitations include the small sample size, heterogeneity in sports type and highest level of participation, and participants with relatively mild cognitive and functional impairments. Additionally, while 18F‐MK6240 has high affinity for 3R/4R tau in Alzheimer's disease, its affinity in CTE, particularly important at early stages, remains unclear. References: 1 Krishnadas N et al. Case report: 18F‐MK6240 tau positron emission tomography pattern resembling chronic traumatic encephalopathy in a retired Australian Rules Football player. https://doi.org/10.3389/fneu.2020.598980. [ABSTRACT FROM AUTHOR]

We analyze multimethod shear (SH)-wave velocity (VS) site characterization data acquired at three permanent and 25 temporary seismograph stations in Oklahoma that recorded M 4+ earthquakes within a 50 km hypocentral distance of at least one of the 2016 M 5.1 Fairview, M 5.8 Pawnee, or M 5.0 Cushing earthquakes to better constrain earthquake ground-motion modeling in the region. We acquired active-source seismic data for time-averaged VS to 30 m depth (VS30) at 28 seismograph stations near the Fairview, Pawnee, and Cushing epicentral areas. The SH-wave refraction travel times coupled with Rayleigh- and Love-wave phase velocity dispersion were extracted and modeled in a nonlinear least-squares (L2) joint inversion to obtain a best-fit 1D VS versus depth profile for each site. At a subset of sites where the preferred L2 inverse model did not optimally fit each of the Love, Rayleigh, and SH travel-time datasets, we explore application of simulated annealing in a joint inversion to find a more global solution. VS30 values range from 262 to 807 m/s for the preferred measured (in situ) VS profiles, or National Earthquake Hazards Reduction Program (NEHRP) site class D to B, and are broadly comparable with estimates from previous data reports in the region. Site amplification estimates were calculated next from 1D SH transfer functions of the preferred VS profiles and then compared against observed horizontal-to-vertical spectral ratios (HVSRs) from nearby seismograph stations. We generally see good agreement between the predicted in situ model and the observed HVSR resonant frequencies, with nominal amplifications between 2 and 10 within the 2-15 Hz frequency band. Next, using 40 known in situ VS30 measurements in the region, we demonstrate that the in situ VS30 values improve the fit for selected suites of ground-motion models (GMMs) for M 4+ earthquakes within a 50 km hypocentral distance when compared with proxy methods, arguing for future development of GMMs implementing in situ VS profiles. [ABSTRACT FROM AUTHOR]

Despite being prioritized during initial COVID-19 vaccine rollout, vulnerable individuals at high risk of severe COVID-19 (hospitalization, intensive care unit admission, or death) remain underrepresented in vaccine effectiveness (VE) studies. The RAVEN cohort study (NCT05047822) assessed AZD1222 (ChAdOx1 nCov-19) two-dose primary series VE in vulnerable populations. Using the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub, linked to secondary care, death registration, and COVID-19 datasets in England, COVID-19 outcomes in 2021 were compared in vaccinated and unvaccinated individuals matched on age, sex, region, and multimorbidity. Over 4.5 million AZD1222 recipients were matched (mean follow-up ∼5 months); 68% were ≥50 years, 57% had high multimorbidity. Overall, high VE against severe COVID-19 was demonstrated, with lower VE observed in vulnerable populations. VE against hospitalization was higher in the lowest multimorbidity quartile (91.1%; 95% CI: 90.1, 92.0) than the highest quartile (80.4%; 79.7, 81.1), and among individuals ≥65 years, higher in the 'fit' (86.2%; 84.5, 87.6) than the frailest (71.8%; 69.3, 74.2). VE against hospitalization was lowest in immunosuppressed individuals (64.6%; 60.7, 68.1). Based on integrated and comprehensive UK health data, overall population-level VE with AZD1222 was high. VEs were notably lower in vulnerable groups, particularly the immunosuppressed. [Display omitted] • AZD1222 (ChAdOx1 nCoV-19) real-world vaccine effectiveness (VE) in 2021 was studied. • Over 4.5 million vaccinated individuals were assessed with ∼5 months mean follow-up. • VE was 84.1%/90.7%/85.9% for hospitalization/intensive care admission/death. • People with higher comorbidity burden or more severe frailty had lower VE. • Immunosuppressed individuals had the lowest VE from primary series vaccination. [ABSTRACT FROM AUTHOR]

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The Latarjet procedure traditionally has been performed with 2 screws in an open manner. Recently, cortical suture button fixation for coracoid transfer has been used in hopes of mitigating complications seen with screw placement. The aim of this study was to evaluate a cortical suture button and technique currently available in the United States compared with screw fixation in the Latarjet procedure in a cadaveric model. We randomly assigned 9 matched pairs of fresh-frozen cadaveric shoulders (N = 18) to undergo the Latarjet procedure with either screw fixation or cortical suture button fixation. After fixation, all shoulders underwent biomechanical testing with direct loading on the graft vas a material testing system. Cyclic testing was performed for 100 cycles to determine axial displacement with time; each graft was then monotonically loaded to failure. The maximum cycle displacement was significantly less for screw fixation vs. cortical suture button fixation (3.1 ± 1.3 mm vs. 8.9 ± 2.1 mm, P <.0001). The total load at failure was 481.1 ± 88.8 N for screws and 175.5 ± 95.8 N for cortical suture buttons (P <.0001). Bony damage to the surrounding anatomy was more extensive at failure in the screw-fixation group. At time zero, the cortical button fixation and technique did not resist direct loads to the graft as much as traditional screw fixation, although bony damage to the surrounding anatomy was more extensive in screw fixation than button fixation. In the event of unanticipated loading, this could place a patient at higher risk of graft migration, which could lead to unintended early outcomes. These results support the need for implants and techniques specifically tailored to the Latarjet procedure and should bring into question the adoption of a cortical button and technique not specific to the procedure. [ABSTRACT FROM AUTHOR]