Search

Colorectal cancer is a leading cause of death and the third most common cancer in Canada. Evidence suggests that screening can reduce mortality rates and the cost effectiveness of a program compares favourably with initiatives for breast and cervical cancer. The objectives of the Association des gastro-entérologues du Québec Task Force were to determine the need for a policy on screening for colorectal cancer in Quebec, to evaluate the testing methods available and to propose one or more of these alternatives as part of a formal screening program, if indicated. Fecal occult blood testing (FOBT), endoscopy (including sigmoidoscopy and colonoscopy), barium enema and virtual colonoscopy were considered. Although most clinical efficacy data are available for FOBT and sigmoidoscopy, there are limitations to programs based on these strategies. FOBT has a high false positive rate and a low detection yield, and even a combination of these strategies will miss 24% of cancers. Colonoscopy is the best strategy to both detect and remove polyps and to diagnose colorectal cancer, with double contrast barium enema also being a sensitive detection method. The Task Force recommended the establishment, in Quebec, of a screening program with five- to 10-yearly double contrast barium enema or 10-yearly colonoscopy for individuals aged 50 years or older at low risk. The program should include outcome monitoring, public and professional education to increase awareness and promote compliance, and central coordination with other provincial programs. The program should be evaluated; specific billing codes for screening for colorectal cancer would help facilitate this. Formal feasibility, effectiveness and cost-effectiveness studies in Quebec are now warranted.

Summary: Background: Factors such as age, pre-injury health, and injury severity, account for less than 35% of outcome variability in traumatic brain injury (TBI). While some residual outcome variability may be attributable to genetic factors, published candidate gene association studies have often been underpowered and subject to publication bias. Methods: We performed the first genome- and transcriptome-wide association studies (GWAS, TWAS) of genetic effects on outcome in TBI. The study population consisted of 5268 patients from prospective European and US studies, who attended hospital within 24 h of TBI, and satisfied local protocols for computed tomography. Findings: The estimated heritability of TBI outcome was 0·26. GWAS revealed no genetic variants with genome-wide significance (p < 5 × 10−8), but identified 83 variants in 13 independent loci which met a lower pre-specified sub-genomic statistical threshold (p < 10−5). Similarly, none of the genes tested in TWAS met tissue-wide significance. An exploratory analysis of 75 published candidate variants associated with 28 genes revealed one replicable variant (rs1800450 in the MBL2 gene) which retained significance after correction for multiple comparison (p = 5·24 × 10−4). Interpretation: While multiple novel loci reached less stringent thresholds, none achieved genome-wide significance. The overall heritability estimate, however, is consistent with the hypothesis that common genetic variation substantially contributes to inter-individual variability in TBI outcome. The meta-analytic approach to the GWAS and the availability of summary data allows for a continuous extension with additional cohorts as data becomes available. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Background: Posttraumatic stress disorder (PTSD) is triggered by environmental stressors. Empathy may predispose an individual to respond to life events differently if high empathizers are emotionally more sensitive to trauma. For the first time, we test this hypothesis using genetic information. Methods: We applied polygenic scoring (PGS) to investigate the shared genetics linking empathy (measured using the Empathy Quotient (EQ), a self-report measure of empathy; N = 46,861) and PTSD symptom severity (measured using the 6-item PTSD Checklist 6-item (PCL-6)) in the UK Biobank (N = 126,219). Follow-up analyses were performed in the context of (1) experiencing any of 16 potential traumas, (2) the total number of traumas endorsed, and (3) the context of trauma. Autism, depression, generalized anxiety, and PCL-17 PGS were included as covariates to verify the specificity of the effect. Results: EQPGS associated with PCL-6 (R2 = 0.012%, P = 9.35 × 10−5). This effect remained significant after accounting for autism, depression, PTSD, and anxiety PGS but was observed only in those who endorsed experiencing at least one traumatic event. EQPGS showed the strongest effect on PCL-6 (β = 2.32, s.e. = 0.762, P = 0.002) among those who endorsed childhood neglect/abuse (felt hated as a child). With respect to case status, the highest probability of PTSD was 17.93% and 10.04% for those who endorsed “feeling hated as a child” and those who did not, respectively (Pdiff = 0.011; Cohen's d = 1.951, 95%CI 1.70–2.20). Conclusions: A genetic predisposition to higher empathy, which may index greater emotional sensitivity, predisposes an individual to more severe PTSD symptoms, especially after early-life adversity.

In the decades around the turn of the twentieth century, Buddhists in imperial Japan, the British Raj, and the American empire developed lay-oriented youth groups. These groups’ members developed intertwined ethnoreligious and national identities informed by Buddhists’ relative status in these three empires. This article describes the trans-imperial development of early Buddhist youth groups, examines how these groups developed nationalist politics that were often intertwined with ethnic identity, and considers how the concept of “Buddhist youth” flattened differences unite lay Buddhists across various divides.

Abstract Background Communication between health care provider and patients in oncology presents challenges. Communication skills training have been frequently developed to address those. Given the complexity of communication training, the choice of outcomes and outcome measures to assess its effectiveness is important. The aim of this paper is to 1) perform a systematic review on outcomes and outcome measures used in evaluations of communication training, 2) discuss specific challenges and 3) provide recommendations for the selection of outcomes in future studies. Methods To identify studies and reviews reporting on the evaluation of communication training for health care professionals in oncology, we searched seven databases (Ovid MEDLINE, CENTRAL, CINAHL, EMBASE, PsychINFO, PsychARTICLES and Web of Science). We extracted outcomes assessed and the respective assessment methods. We held a two-day workshop with experts (n = 16) in communication theory, development and evaluation of generic or cancer-specific communication training and/or outcome measure development to identify and address challenges in the evaluation of communication training in oncology. After the workshop, participants contributed to the development of recommendations addressing those challenges. Results Out of 2181 references, we included 96 publications (33 RCTs, 2 RCT protocols, 4 controlled trials, 36 uncontrolled studies, 21 reviews) in the review. Most frequently used outcomes were participants’ training evaluation, their communication confidence, observed communication skills and patients’ overall satisfaction and anxiety. Outcomes were assessed using questionnaires for participants (57.3%), patients (36.0%) and observations of real (34.7%) and simulated (30.7%) patient encounters. Outcomes and outcome measures varied widely across studies. Experts agreed that outcomes need to be precisely defined and linked with explicit learning objectives of the training. Furthermore, outcomes should be assessed as broadly as possible on different levels (health care professional, patient and interaction level). Conclusions Measuring the effects of training programmes aimed at improving health care professionals’ communication skills presents considerable challenges. Outcomes as well as outcome measures differ widely across studies. We recommended to link outcome assessment to specific learning objectives and to assess outcomes as broadly as possible.

Abstract Background Although the majority of active duty U.S. Army soldiers are full-time personnel in the Active Component (AC), a substantial minority of soldiers on active duty are in the Reserve Components (RCs). These “citizen-soldiers” (Army National Guard and Army Reserve) represent a force available for rapid activation in times of national need. RC soldiers experience many of the same stressors as AC soldiers as well as stressors that are unique to their intermittent service. Despite the important role of RC soldiers, the vast majority of military mental health research focuses on AC soldiers. One important goal of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is to address this gap. Here we examine predictors of suicide attempts among activated RC soldiers. Methods This longitudinal, retrospective cohort study used individual-level person-month records from Army and Department of Defense administrative data systems to examine socio-demographic, service-related, and mental health predictors of medically documented suicide attempts among activated RC soldiers during 2004–2009. Data from all 1103 activated RC suicide attempters and an equal-probability sample of 69,867 control person-months were analyzed using a discrete-time survival framework. Results Enlisted soldiers comprised 84.3% of activated RC soldiers and accounted for 95.7% of all activated RC suicide attempts (overall rate = 108/100,000 person-years, more than four times the rate among officers). Multivariable predictors of enlisted RC suicide attempts included being female, entering Army service at age ≥ 25, current age

The spindle shows remarkable diversity, and changes in an integrated fashion, as cells vary over evolution. Here, we provide a mechanistic explanation for variations in the first mitotic spindle in nematodes. We used a combination of quantitative genetics and biophysics to rule out broad classes of models of the regulation of spindle length and dynamics, and to establish the importance of a balance of cortical pulling forces acting in different directions. These experiments led us to construct a model of cortical pulling forces in which the stoichiometric interactions of microtubules and force generators (each force generator can bind only one microtubule), is key to explaining the dynamics of spindle positioning and elongation, and spindle final length and scaling with cell size. This model accounts for variations in all the spindle traits we studied here, both within species and across nematode species spanning over 100 million years of evolution.

Abstract Background High rates of mental disorders, suicidality, and interpersonal violence early in the military career have raised interest in implementing preventive interventions with high-risk new enlistees. The Army Study to Assess Risk and Resilience in Servicemembers (STARRS) developed risk-targeting systems for these outcomes based on machine learning methods using administrative data predictors. However, administrative data omit many risk factors, raising the question whether risk targeting could be improved by adding self-report survey data to prediction models. If so, the Army may gain from routinely administering surveys that assess additional risk factors. Methods The STARRS New Soldier Survey was administered to 21,790 Regular Army soldiers who agreed to have survey data linked to administrative records. As reported previously, machine learning models using administrative data as predictors found that small proportions of high-risk soldiers accounted for high proportions of negative outcomes. Other machine learning models using self-report survey data as predictors were developed previously for three of these outcomes: major physical violence and sexual violence perpetration among men and sexual violence victimization among women. Here we examined the extent to which this survey information increases prediction accuracy, over models based solely on administrative data, for those three outcomes. We used discrete-time survival analysis to estimate a series of models predicting first occurrence, assessing how model fit improved and concentration of risk increased when adding the predicted risk score based on survey data to the predicted risk score based on administrative data. Results The addition of survey data improved prediction significantly for all outcomes. In the most extreme case, the percentage of reported sexual violence victimization among the 5% of female soldiers with highest predicted risk increased from 17.5% using only administrative predictors to 29.4% adding survey predictors, a 67.9% proportional increase in prediction accuracy. Other proportional increases in concentration of risk ranged from 4.8% to 49.5% (median = 26.0%). Conclusions Data from an ongoing New Soldier Survey could substantially improve accuracy of risk models compared to models based exclusively on administrative predictors. Depending upon the characteristics of interventions used, the increase in targeting accuracy from survey data might offset survey administration costs.

Abstract Background The nature and underlying mechanisms of the observed increased vulnerability to posttraumatic stress disorder (PTSD) in women are unclear. Methods We investigated the genetic overlap of PTSD with anthropometric traits and reproductive behaviors and functions in women. The analysis was conducted using female-specific summary statistics from large genome-wide association studies (GWAS) and a cohort of 3577 European American women (966 PTSD cases and 2611 trauma-exposed controls). We applied a high-resolution polygenic score approach and Mendelian randomization analysis to investigate genetic correlations and causal relationships. Results We observed an inverse association of PTSD with genetically determined anthropometric traits related to body shape, independent of body mass index (BMI). The top association was related to BMI-adjusted waist circumference (WCadj; R = –0.079, P

Abstract Background The U.S. Army suicide attempt rate increased sharply during the wars in Iraq and Afghanistan. Risk may vary according to occupation, which significantly influences the stressors that soldiers experience. Methods Using administrative data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), we identified person-month records for all active duty Regular Army enlisted soldiers who had a medically documented suicide attempt from 2004 through 2009 (n = 9650) and an equal-probability sample of control person-months (n = 153,528). Logistic regression analyses examined the association of combat occupation (combat arms [CA], special forces [SF], combat medic [CM]) with suicide attempt, adjusting for socio-demographics, service-related characteristics, and prior mental health diagnosis. Results In adjusted models, the odds of attempting suicide were higher in CA (OR = 1.2 [95% CI: 1.1–1.2]) and CM (OR = 1.4 [95% CI: 1.3–1.5]), but lower in SF (OR = 0.3 [95% CI: 0.2–0.5]) compared to all other occupations. CA and CM had higher odds of suicide attempt than other occupations if never deployed (ORs = 1.1–1.5) or previously deployed (ORs = 1.2–1.3), but not when currently deployed. Occupation was associated with suicide attempt in the first ten years of service, but not beyond. In the first year of service, primarily a time of training, CM had higher odds of suicide attempt than both CA (OR = 1.4 [95% CI: 1.2–1.6]) and other occupations (OR = 1.5 [95% CI: 1.3–1.7]). Discrete-time hazard functions revealed that these occupations had distinct patterns of monthly risk during the first year of service. Conclusions Military occupation can inform the understanding suicide attempt risk among soldiers.

Adoptive T cell therapy using patient T cells redirected to recognize tumor-specific antigens by expressing genetically engineered high-affinity T-cell receptors (TCRs) has therapeutic potential for melanoma and other solid tumors. Clinical trials implementing genetically modified TCRs in melanoma patients have raised concerns regarding off-target toxicities resulting in lethal destruction of healthy tissue, highlighting the urgency of assessing which off-target peptides can be recognized by a TCR. As a model system we used the clinically efficacious NY-ESO-1-specific TCR C259, which recognizes the peptide epitope SLLMWITQC presented by HLA-A*02:01. We investigated which amino acids at each position enable a TCR interaction by sequentially replacing every amino acid position outside of anchor positions 2 and 9 with all 19 possible alternative amino acids, resulting in 134 peptides (133 altered peptides plus epitope peptide). Each peptide was individually evaluated using three different in vitro assays: binding of the NY-ESOc259 TCR to the peptide, peptide-dependent activation of TCR-expressing cells, and killing of peptide-presenting target cells. To represent the TCR recognition kernel, we defined Position Weight Matrices (PWMs) for each assay by assigning normalized measurements to each of the 20 amino acids in each position. To predict potential off-target peptides, we applied a novel algorithm projecting the PWM-defined kernel into the human proteome, scoring NY-ESOc259 TCR recognition of 336,921 predicted human HLA-A*02:01 binding 9-mer peptides. Of the 12 peptides with high predicted score, we confirmed 7 (including NY-ESO-1 antigen SLLMWITQC) strongly activate human primary NY-ESOc259-expressing T cells. These off-target peptides include peptides with up to 7 amino acid changes (of 9 possible), which could not be predicted using the recognition motif as determined by alanine scans. Thus, this replacement scan assay determines the “TCR fingerprint” and, when coupled with the algorithm applied to the database of human 9-mer peptides binding to HLA-A*02:01, enables the identification of potential off-target antigens and the tissues where they are expressed. This platform enables both screening of multiple TCRs to identify the best candidate for clinical development and identification of TCR-specific cross-reactive peptide recognition and constitutes an improved methodology for the identification of potential off-target peptides presented on MHC class I molecules.

Human-carnivore conflict is a leading cause of large carnivore declines and minimizing these conflicts is vital to maintaining viable carnivore populations. Often, however, conservation agencies and governments do not have a proper understanding of conflicts prior to establishing mitigation programs or are unable to collect the appropriate data to verify claims of livestock loss. We investigated livestock depredation events in the Eastern Panhandle of the Okavango Delta, Botswana between October 2014 and December 2016 and compared these investigations with concurrent Problem Animal Control (PAC) information from the Botswana Department of Wildlife and National Parks (DWNP) compensation program. Only animals killed in livestock enclosures or while being herded qualify for reimbursement through the compensation program, but DWNP is typically unable to verify claims. We identified wildlife sign at the depredation event location and collected information from the livestock owner to determine the species responsible for the attack, time of the attack, the livestock lost, and the husbandry methods employed. In total, 116 livestock were killed and 13 more injured in 102 confirmed wild carnivore attacks. Most (90%) attacks occurred while livestock were unattended and freely grazing in multi-use, communal areas. Cows, oxen (castrated male cows) and calves (Bos taurus and B. t. indicus) were killed most often and African lions (Panthera leo) were responsible for 74% of investigated attacks, while African wild dogs (Lycaon pictus) accounted for 13%, leopard (Panthera pardus) 8%, and spotted hyena (Crocuta crocuta) 5%. Valuation of verified losses totaled ∼$30,000 over the study period. There were 50% more events reported to DWNP for compensation than we confirmed through independent investigations. In its current form, the compensation program does not seem sustainable, nor does it enable the verification of claims. While compensation programs should not be abandoned, programs designed to provide monetary reimbursement for losses caused by predators should require timely reporting and in-depth investigation of depredation events. Additional conflict mitigation strategies should target increasing livestock husbandry methods in the area, with a specific focus on herding. Keywords: Livestock depredation, Conflict, Compensation, Panthera leo, Crocuta crocuta, Herding

Across Africa, lions (Panthera leo) are heavily persecuted in anthropogenic landscapes. Trans-disciplinary research and virtual boundaries (geofences) programmed into GPS-tracking transmitters offer new opportunities to improve coexistence. During a 24-month pilot study (2016–2018), we alerted communities about approaching lions, issuing 1,017 alerts to four villages and 19 cattle posts. Alerts reflected geofence breaches of nine lions (2,941 monitoring days) moving between Botswana's Okavango Delta and adjacent agro-pastoral communities. Daily alert system costs per lion were US$18.54, or $5,460.24 per GPS deployment (n = 13). Alert-responsive livestock owners mainly responded by night-kraaling of cattle (68.9%), significantly reducing their losses (by $124.61 annually), whereas losses of control group and non-responsive livestock owners remained high ($317.93 annually). Community satisfaction with alerts (91.8%) was higher than for compensation of losses (24.3%). Study lions spent 26.3% of time monitored in geofenced community areas, but accounted for 31.0% of conflict. Manual alert distribution proved challenging, static geofences did not appropriately reflect human safety or the environment's strong seasonality that influenced cattle predation risk, and tracking units with on-board alert functions often failed or under-recorded geofence breaches by 27.9%. These insufficiencies prompted the design of a versatile and autonomous lion alert platform with automated, dynamic geofencing. We co-designed this prototype platform with community input, thereby incorporating user feedback. We outline a flexible approach that recognizes conflict complexity and user community heterogeneity. Here, we describe the evolution of an innovative Information and Communication Technologies-based (ICT) alert system that enables instant data processing and community participation through interactive interfaces on different devices. We highlight the importance of a trans-disciplinary co-design and development process focussing on community engagement while synthesizing expertise from ethnography, ecology, and socio-informatics. We discuss the bio-geographic, social, and technological variables that influence alert system efficacy and outline opportunities for wider application in promoting coexistence and conservation.