The Variegation of Human Brain Vulnerability to Rare Genetic Disorders and Convergence With Behaviorally Defined Disorders.

BACKGROUND: Diverse gene dosage disorders (GDDs) increase risk for psychiatric impairment, but characterization of GDD effects on the human brain has so far been piecemeal, with few simultaneous analyses of multiple brain features across different GDDs. METHODS: Here, through multimodal neuroimaging of 3 aneuploidy syndromes (XXY [total n = 191, 92 control participants], XYY [total n = 81, 47 control participants], and trisomy 21 [total n = 69, 41 control participants]), we systematically mapped the effects of supernumerary X, Y, and chromosome 21 dosage across a breadth of 15 different macrostructural, microstructural, and functional imaging-derived phenotypes (IDPs). RESULTS: The results revealed considerable diversity in cortical changes across GDDs and IDPs. This variegation of IDP change underlines the limitations of studying GDD effects unimodally. Integration across all IDP change maps revealed highly distinct architectures of cortical change in each GDD along with partial coalescence onto a common spatial axis of cortical vulnerability that is evident in all 3 GDDs. This common axis shows strong alignment with shared cortical changes in behaviorally defined psychiatric disorders and is enriched for specific molecular and cellular signatures. CONCLUSIONS: Use of multimodal neuroimaging data in 3 aneuploidies indicates that different GDDs impose unique fingerprints of change in the human brain that differ widely depending on the imaging modality that is being considered. Embedded in this variegation is a spatial axis of shared multimodal change that aligns with shared brain changes across psychiatric disorders and therefore represents a major high-priority target for future translational research in neuroscience.

Aneuploidy effects on human gene expression across three cell types.

Aneuploidy syndromes impact multiple organ systems but understanding of tissue-specific aneuploidy effects remains limited-especially for the comparison between peripheral tissues and relatively inaccessible tissues like brain. Here, we address this gap in knowledge by studying the transcriptomic effects of chromosome X, Y, and 21 aneuploidies in lymphoblastoid cell lines, fibroblasts and iPSC-derived neuronal cells (LCLs, FCL, and iNs, respectively). We root our analyses in sex chromosome aneuploidies, which offer a uniquely wide karyotype range for dosage effect analysis. We first harness a large LCL RNA-seq dataset from 197 individuals with one of 6 sex chromosome dosages (SCDs: XX, XXX, XY, XXY, XYY, and XXYY) to i) validate theoretical models of SCD sensitivity and ii) define an expanded set of 41 genes that show obligate dosage sensitivity to SCD and are all in cis (i.e., reside on the X or Y chromosome). We then use multiple complementary analyses to show that cis effects of SCD in LCLs are preserved in both FCLs (n = 32) and iNs (n = 24), whereas trans effects (i.e., those on autosomal gene expression) are mostly not preserved. Analysis of additional datasets confirms that the greater cross-cell type reproducibility of cis vs. trans effects is also seen in trisomy 21 cell lines. These findings i) expand our understanding of X, Y, and 21 chromosome dosage effects on human gene expression and ii) suggest that LCLs may provide a good model system for understanding cis effects of aneuploidy in harder-to-access cell types.

A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy.

All eutherian mammals show chromosomal sex determination with contrasting sex chromosome dosages (SCDs) between males (XY) and females (XX). Studies in transgenic mice and humans with sex chromosome trisomy (SCT) have revealed direct SCD effects on regional mammalian brain anatomy, but we lack a formal test for cross-species conservation of these effects. Here, we develop a harmonized framework for comparative structural neuroimaging and apply this to systematically profile SCD effects on regional brain anatomy in both humans and mice by contrasting groups with SCT (XXY and XYY) versus XY controls. Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences. However, mice do show subtle effects of XXY and XYY on regional volume, although there is not a general spatial convergence in these effects within mice or between species. Notwithstanding this general lack of conservation in SCT effects, we detect several brain regions that show overlapping effects of XXY and XYY both within and between species (cerebellar, parietal, and orbitofrontal cortex), thereby nominating high priority targets for future translational dissection of SCD effects on the mammalian brain. Our study introduces a generalizable framework for comparative neuroimaging in humans and mice and applies this to achieve a cross-species comparison of SCD effects on the mammalian brain through the lens of SCT.SIGNIFICANCE STATEMENT Sex chromosome dosage (SCD) affects neuroanatomy and risk for psychopathology in humans. Performing mechanistic studies in the human brain is challenging but possible in mouse models. Here, we develop a framework for cross-species neuroimaging analysis and use this to show that an added X- or Y-chromosome significantly alters human brain anatomy but has muted effects in the mouse brain. However, we do find evidence for conserved cross-species impact of an added chromosome in the fronto-parietal cortices and cerebellum, which point to regions for future mechanistic dissection of sex chromosome dosage effects on brain development.

Cardiac remodeling in amateur triathletes after 24 weeks of exercise training for a half-Ironman event: a brief report.

BACKGROUND: Triathletes' physiological adaptations to exercise training can have a different impact on cardiac remodeling based on the extreme exercise preparation. Moreover, cardiac remodeling might be different depending on whether triathletes have trained for many years or if they just decided to be more active. Nevertheless, data are limited in amateur endurance athletes and studies about them are key for their safety. Therefore, we investigated the effects of exercise training for a half-ironman on cardiac remodeling. METHODS: A total of 24 amateur athletes underwent a 24-week exercise program and were followed by three-dimensional echocardiography to assess its global impact on cardiac remodeling. Subanalyses were performed based on participants past-training experience (low versus high). RESULTS: We found significant group effects on the right and left ventricle, significant time effect on the right ventricle. No significant interaction effects were observed. We observed significant correlations between the right ventricle, clinical and performance characteristics where the peak power output explained 38% of the variance, while the body surface area, weight and power at the second ventilatory threshold explained 34%, 31% and 30%, respectively. CONCLUSIONS: Changes in cardiac remodeling in response to an exercise program for a half-ironman are not homogeneous across the ventricles and are influenced by participants' past-training experience. This study strengthens our knowledge of extreme exercise training for a half-ironman to further develop better training programs and medical follow-up in amateur triathletes.

IQ Modulates Coupling Between Diverse Dimensions of Psychopathology in Children and Adolescents.

OBJECTIVE: Correlations between cognitive ability and psychopathology are well recognized, but prior research has been limited by focusing on individuals with intellectual disability, single-diagnosis psychiatric populations, or few measures of psychopathology. Here, we quantify relationships between full-scale IQ and multiple dimensions of psychopathology in a diverse care-seeking population, with a novel focus on differential coupling between psychopathology dimensions as a function of IQ. METHOD: A total of 70 dimensional measures of psychopathology, plus IQ and demographic data, were collated for 2,752 children and adolescents from the Healthy Brain Network dataset. We first examined univariate associations between IQ and psychopathology, and then characterized how the correlational architecture of psychopathology differs between groups at extremes of the IQ distribution. RESULTS: Associations with IQ vary in magnitude between different domains of psychopathology: IQ shows the strongest negative correlations with attentional and social impairments, but is largely unrelated to affective symptoms and psychopathy. Lower IQ is associated with stronger coupling between internalizing problems and aggression, repetitive behaviors, and hyperactivity/inattentiveness. CONCLUSION: Our analyses reveal that variation in general cognitive ability is associated not only with significant and selective shifts in severity of psychopathology, but also in the coupling between different dimensions of psychopathology. These findings have relevance for the clinical assessment of mental health in populations with varying IQ, and may also inform ongoing efforts to improve the measurement of psychopathology and to understand how relationships between cognition and behavior are reflected in brain organization. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science.

Physiological Demands of Basic Fire Management Tasks in Members of the Canadian Armed Forces: A Pilot Study.

INTRODUCTION: Members of the Canadian Armed Forces (CAF) are required to meet the minimum standards of the Fitness for Operational Requirements of CAF Employment (FORCE) job-based simulation test (JBST) and must possess the capacity to perform other common essential tasks. One of those tasks is to perform basic fire management tasks during fire emergencies to mitigate damage and reduce the risk of injuries and/or death until professional firefighters arrive at the scene. To date however, the physiological demands of common firefighting tasks have mostly been performed on professional firefighters, thus rendering the transferability of the demands to the general military population unclear. This pilot study aimed to quantify, for the first time, the physiological demands of basic fire management tasks in the military, to determine if they are reflected in the FORCE JBST minimum standard. We hypothesized that the physiological demands of basic fire management tasks within the CAF are below the physiological demands of the FORCE JBST minimum standard, and as such, be lower than the demands of professional firefighting. MATERIALS AND METHODS: To achieve this, 21 CAF members (8 females; 13 males; mean [SD] age: 33 [10] years; height: 174.5 [10.5] cm; weight: 85.4 [22.1] kg, estimated maximal oxygen uptake [$\dot V$O2peak]: 44.4 (7.4) mL kg-1 min-1) participated in a realistic, but physically demanding, JBST developed by CAF professional firefighting subject matter experts. The actions included lifting, carrying, and manipulating a 13-kg powder fire extinguisher and connecting, coupling, and dragging a 38-mm fire hose over 30 m. The rate of oxygen uptake ($\dot V$O2), heart rate, and percentage of heart rate reserve were measured continuously during two task simulation trials, which were interspersed by a recovery period. Rating of perceived exertion (6-no exertion; 20-maximal exertion) was measured upon completion of both task simulations. Peak $\dot V$O2 ($\dot V$O2peak) was estimated based on the results of the FORCE JBST. RESULTS: The mean (SD) duration of both task simulation trials was 3:39 (0:19) min:s, whereas the rest period in between both trials was 62 (19) minutes. The mean O2 was 21.1 (4.7) mL kg-1 min-1 across trials, which represented 52.1 (12.2) %$\dot V$O2peak and ∼81% of the FORCE JBST. This was paralleled by a mean heart rate of 136 (18) beats min-1, mean percentage of heart rate reserve of 61.2 (10.8), and mean rating of perceived exertion of 11 ± 2. Other physical components of the JBST consisted of lifting, carrying, and manipulating a 13-kg load for ∼59 seconds, which represents 65% of the load of the FORCE JBST. The external resistance of the fire hose drag portion increased up to 316 N, translating to a total of 6205 N over 30 m, which represents 96% of the drag force measured during the FORCE JBST. CONCLUSIONS: Our findings demonstrate that the physiological demands of basic fire management tasks in the CAF are of moderate intensity, which are reflected in the CAF physical fitness standard. As such, CAF members who achieve the minimum standard on the FORCE JBST are deemed capable of physically performing basic fire management tasks during fire emergencies.

Assessment of Training Load, Sleep, Injuries, and Operational Physical Performance During Basic Military Qualification.

INTRODUCTION: Optimizing training load (TL) and sleep is essential to maximize physical performance and prevent musculoskeletal injuries (MSKIs) for Canadian forces recruits during the 10-week basic military qualification (BMQ) course. The purpose of this study was to assess the TL, sleep duration, the occurrence of MSKIs during the BMQ, and the operation fitness performance during the BMQ. MATERIALS AND METHODS: Forty Canadian recruits, eight females and 32 males, (age 24 ± 5 years; height 176.4 ± 10.4 cm), were monitored with an accelerometer (GENEActiv) on their wrist between weeks 1 and 9 to evaluate the TL and sleep duration. During weeks 2 and 10, the recruits completed an operational fitness evaluation. Injury surveillance was performed over 10 weeks. RESULTS: TL intensity was significantly different (P = 0.0001) from week to week. The weekly average total time of moderate and vigorous physical activity was 189.7 ± 48.1 min and 44.7 ± 15.2 min, respectively. The average sleep duration was 5.4 ± 0.4 h per night and decreased to 4.2 h ± 0.4 during field exercises. A significant difference in sleep duration was observed between recruits with and without a MSKI. The recruits accumulated a total of 95 days under medical restrictions with an average of 3.8 consecutive days. The VO2peak estimated from the Fitness for Operational Requirements of Canadian Armed Forces Employment job-based simulation test significantly improved from weeks 2 to 10 (pre, 47.1 ± 6.3; post: 50.2 ± 5.8; P = 0.001). CONCLUSIONS: TL is of high magnitude and varies from week to week. The reported mean sleep duration per week may perhaps negatively impact the occurrence of MSKI. No significant improvement was detected in operational fitness by the end of the BMQ.

Sex-specific associations between subcortical morphometry in childhood and adult alcohol consumption: A 17-year follow-up study.

Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.

Sex Chromosome Dosage Effects on White Matter Structure in the Human Brain.

Sex chromosome aneuploidies, a group of neurogenetic conditions characterized by aberrant sex chromosome dosage (SCD), are associated with increased risks for psychopathology as well as alterations in gray matter structure. However, we still lack a comprehensive understanding of potential SCD-associated changes in white matter structure, or knowledge of how these changes might relate to known alterations in gray matter anatomy. Thus, here, we use voxel-based morphometry on structural neuroimaging data to provide the first comprehensive maps of regional white matter volume (WMV) changes across individuals with varying SCD (n = 306). We show that mounting X- and Y-chromosome dosage are both associated with widespread WMV decreases, including in cortical, subcortical, and cerebellar tracts, as well as WMV increases in the genu of the corpus callosum and posterior thalamic radiation. We also correlate X- and Y-chromosome-linked WMV changes in certain regions to measures of internalizing and externalizing psychopathology. Finally, we demonstrate that SCD-driven WMV changes show a coordinated coupling with SCD-driven gray matter volume changes. These findings represent the most complete maps of X- and Y-chromosome effects on human white matter to date, and show how such changes connect to psychopathological symptoms and gray matter anatomy.

Psychological Status During and After the Preparation of a Long-distance Triathlon Event in Amateur Athletes.

Preparation for an endurance event among amateur athletes requires a major commitment on their part. Knowing amateur athletes' psychological characteristics during a training period should be a priority for coaches and athletes. The aim of our longitudinal study was to characterize the psychological profile of amateur athletes over a training period of six months prior to and after a long-distance triathlon. Thirty-two amateur athletes (13 females; 19 males; 1.5±1.3 years of experience) were recruited for this observational study. All participants (39±9.9 years old; weighs 73±12.9 kg; measure 172±10.2 cm) underwent a physical fitness assessment pre- and post 6-months of training, a monthly psychological questionnaire battery assessing mood, positive and negative affect, passion and motivation and, for some participants (n=5), an interview post event. Positive emotions increased until the sixth month, from 38.1±22.0 to 54.3±7.2 (Z=3.49, p<0.001, r=0.80). Participants were more harmonious (29.0±3.0) than obsessive (13.0±1.0) with their triathlon's passion (Z=4.91, p<0.001, r=0.85). Participants felt a high level of intrinsic motivation (15.9±1.76) and a low level of external motivation (4.9±1.08) about their triathlon training (p<0.05). The vigor score is the only sub scale that significantly changed from the 1st to the 6th month of training, and ranged between 21.4±10.6 and 28.1±4.1 (Z=2.0, p=0.046, r=0.46). This longitudinal observational study is the first to have explored athletes' psychological and emotional parameters over a training period of six months prior to a long-distance triathlon event and one month after. Thus, specific interventions and mental training can be structured around these important milestones.

Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY).

Klinefelter syndrome (47, XXY; henceforth: XXY syndrome) is a high-impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first study to map alterations of functional brain connectivity in XXY syndrome and relate these changes to brain anatomy and psychopathology. We used resting-state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males to 1) implement a brain-wide screen for altered global resting-state functional connectivity (rsFC) in XXY versus XY males and 2) decompose these alterations through seed-based analysis. We then compared these rsFC findings with measures of regional brain anatomy, psychopathology, and cognition. XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC)-reflecting DLPFC overconnectivity with diverse rsFC networks. Functional overconnectivity was partly coupled to co-occurring regional volumetric changes in XXY syndrome, and variation in DLPFC-precuneus rsFC was correlated with the severity of psychopathology. By providing the first view of altered rsFC in XXY syndrome and contextualizing observed changes relative to neuroanatomy and behavior, our study helps to advance biological understanding of XXY syndrome-both as a disorder in its own right and more broadly as a model of genetic risk for psychopathology.

Measuring the Acetabular Index: An Accurate and Reliable Alternative Method of Measurement.

OBJECTIVE. In children (4 months to 8 years old), radiographic measurements of the acetabular index are the preferred method to assess developmental hip dysplasia. However, the acetabular index has been criticized as having variable reliability owing to difficulty identifying the correct anatomic landmarks. An alternative method of measuring the acetabular index using the ischium is being proposed to avoid the variability of the triradiate cartilage line as a reference point. With the alternative method, the acetabular index is derived by measuring the angle between a line connecting the ischial tuberosi-ties and a line connecting the inferomedial and superolateral edges of the acetabulum. The purpose of this study was to evaluate the accuracy and reliability of this alternative method of measuring the acetabular index compared with the traditional method. MATERIALS AND METHODS. Children 4 months to 8 years old who presented for evaluation of developmental dysplasia of the hip were included. Two physicians, each using both the traditional and the alternative method, measured acetabular indexes on all radiographs. Accuracy was defined as mean absolute error less than 6°. Reliability was calculated by means of intraclass correlation coefficient (ICC). RESULTS. Pelvic radiographs of 40 children (324 hips) were included. The mean age was 23.7 months (range, 4-96 months) and mean acetabular index was 24.2° (range, 8-50°). The alternative method was associated with mean absolute error of 2.50°, which is significantly below the threshold of 6° (t < 0.001). Intrarater reliability for the traditional method was high (ICC, 0.81) and for the alternative method was very high (ICC, 0.92). Interrater reliability for the traditional method was high (ICC, 0.89) and for the alternative method was very high (ICC, 0.91). CONCLUSION. Measuring the acetabular index using the alternative method has very high accuracy and intrarater and interrater reliability.

Morphological integration of the human brain across adolescence and adulthood.

Brain structural covariance norms capture the coordination of neurodevelopmental programs between different brain regions. We develop and apply anatomical imbalance mapping (AIM), a method to measure and model individual deviations from these norms, to provide a lifespan map of morphological integration in the human cortex. In cross-sectional and longitudinal data, analysis of whole-brain average anatomical imbalance reveals a reproducible tightening of structural covariance by age 25 y, which loosens after the seventh decade of life. Anatomical imbalance change in development and in aging is greatest in the association cortex and least in the sensorimotor cortex. Finally, we show that interindividual variation in whole-brain average anatomical imbalance is positively correlated with a marker of human prenatal stress (birthweight disparity between monozygotic twins) and negatively correlated with general cognitive ability. This work provides methods and empirical insights to advance our understanding of coordinated anatomical organization of the human brain and its interindividual variation.

Remote Ischemic Preconditioning Does Not Improve the Six Minutes Walk Test Performance in Chronic Heart Failure Patients: a Randomised Pilot Trial.

Cycles of ischemia and reperfusion induced with a pressure cuff on a skeletal muscle, also know as remote ischemic preconditioning (RIPC), appears to improve performance in different time-trial events in healthy individuals. Our primary goal was to assess the effect of RIPC in heart failure (HF) patients' functional capacity using the six-minute walk test (6MWT). A randomized crossover design comparing RIPC (4 × five-minutes of upper arm ischemia) to the SHAM procedure was done in 15 patients prior to a 6MWT. The primary outcome measure was the total distance walked in a standardized 6MWT (20m corridor). Metabolic and hemodynamic responses were measured using gas exchange analysis with a portable metabolic analyzer and peripheral skeletal muscle oxygen saturation (smO2) with near-infrared spectroscopy. The total distance travelled during 6MWT was not significantly different between the RIPC (347 ± 63 m) and the SHAM procedure (352 ± 65 m; p = 0.514). Relative oxygen uptake did not change when comparing interventions: 10.26 ± 2.01 ml/kg/min vs 10.69 ± 2.51 ml/kg/min (RIPC vs SHAM, respectively, p = 0.278). As well, no significant differences were observed for heart rate, respiratory exchange ratio, smO2, and ventilation. Even though HF patients tolerated well the RIPC intervention, it did not provide any significant improvement in functional capacity and other physiological parameters in our sample of patients.

Author Correction: Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Case Report of a Remote Ischemic Preconditioning Intervention during Aerobic Exercise in a 44-year-old Amateur Triathlete Male with a History of Acute Myocardial Infarction.

Over the years, exercise has become increasingly important in patients with acute myocardial infarction (AMI). However, AMI patients need to be closely monitored since they maintain cardiovascular disease risks, such as ventricular repolarization abnormalities in electrocardiograms during exercise and rest. A recent study showed the need to focus on the different potential mechanisms and the applicability of remote ischemic preconditioning (RIPC) for cardiac patients engaged in exercise rehabilitation. This is the first case report that explores the effectiveness of an RIPC intervention in a 44-year-old amateur triathlete male with a history of AMI during a moderate (75% of gas exchange threshold) and high (115% of gas exchange threshold) intensity steady-state cycling aerobic exercise. Prior to aerobic exercise, the participant was allocated to either RIPC intervention or CTL (control) with four cycles of five minutes of ischemia followed by five minutes of reperfusion. ECG was continuously recorded during the protocol. These findings showed that RIPC improved participant's oxygen uptake response and shortened his ventricular repolarization during steady-state aerobic exercises. By measuring the physiological and electrophysical parameters, this case report adds new evidence for the benefits of RIPC. This study also demonstrates the safety of the intervention for cardiac patients in addition to showing that the intervention is not dangerous or harmful. This provides a new approach to cardiac rehabilitation programs. Future studies with cardiac patients are needed to provide a safe, standardized exercise intervention in cardiac rehabilitation.

Transcriptomic and cellular decoding of regional brain vulnerability to neurogenetic disorders.

Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.

Preparation for an Half-Ironmantm Triathlon amongst Amateur Athletes: Finishing Rate and Physiological Adaptation.

Long distance triathlon has gained in popularity amongst the general population. Coaches establish training programs based upon their knowledge, personal experience and on current training principles. The goal was to observe the effect of a triathlon training program for a half Ironman event in neophyte amateur athletes. A specific triathlon training program was followed from February to June 2016 by a group preparing for their first half ironman. Out of the 32 participants (19 Males and 13 Females; mean age of 39 ± 9.9 years old; body weight of 72.7 ± 13.4 kg and a height of 171.5 ± 10.2 cm), only one did not complete the event. A mean training volume of 410 ± 201 min per week led to a mean finishing time of 6 hours 28 minutes. The training program significantly increased the maximal oxygen consumption (45.9 ± 8.2 to 48.6 ± 7.5 ml/kg/min, p =0.002) and the maximal power output (293.1 ± 63.7 to 307.8 ± 58.7 W, p < 0.001). The absolute oxygen consumption and power output at both ventilatory thresholds also significantly increased (VT1: 2.2 ± 0.4 to 2.5 ± 0.5 L, p = 0.001; 157.8 ± 41.8 to 176.7 ± 41.1 W p = 0.009 and VT2: 2.9 ± 0.4 to 3.0 ± 0.4 L, p = 0.017; 229.3 ± 62.0 to 244.8± 55.2 W, p = 0.022 ). A significant diminution of waist circumference was observed (83.2 ± 10.0 to 81.8 ± 9.5 cm, p = 0.032) with no significant changes in body weight. Thus, a 24-week specific training program appears to be safe and efficient for amateur athletes aiming to finish their first half- Ironman event.

Sex chromosome aneuploidy alters the relationship between neuroanatomy and cognition.

Sex chromosome aneuploidy (SCA) increases the risk for cognitive deficits, and confers changes in regional cortical thickness (CT) and surface area (SA). Neuroanatomical correlates of inter-individual variation in cognitive ability have been described in health, but are not well-characterized in SCA. Here, we modeled relationships between general cognitive ability (estimated using full-scale IQ [FSIQ] from Wechsler scales) and regional estimates of SA and CT (from structural MRI scans) in both aneuploid (28 XXX, 55 XXY, 22 XYY, 19 XXYY) and typically-developing euploid (79 XX, 85 XY) individuals. Results indicated widespread decoupling of normative anatomical-cognitive relationships in SCA: we found five regions where SCA significantly altered SA-FSIQ relationships, and five regions where SCA significantly altered CT-FSIQ relationships. The majority of areas were characterized by the presence of positive anatomy-IQ relationships in health, but no or slightly negative anatomy-IQ relationships in SCA. Disrupted anatomical-cognitive relationships generalized from the full cohort to karyotypically defined subcohorts (i.e., XX-XXX; XY-XYY; XY-XXY), demonstrating continuity across multiple supernumerary SCA conditions. As the first direct evidence of altered regional neuroanatomical-cognitive relationships in supernumerary SCA, our findings shed light on potential genetic and structural correlates of the cognitive phenotype in SCA, and may have implications for other neurogenetic disorders.

Association Between Musculoskeletal Injuries and the Canadian Armed Forces Physical Employment Standard Proxy in Canadian Military Recruits.

INTRODUCTION: Musculoskeletal injuries (MSKIs) and recruitment are major challenges faced by modern military forces. The Canadian Armed Forces uses a physical employment standard (PES) proxy to determine occupational fitness and job suitability. It is unknown whether the performance on the PES proxy can be also used as predictor of MSKIs. The purpose of this study was to investigate for relationships between age, sex, body composition, aerobic fitness, performance on the Canadian Armed Forces PES proxy (FORCE evaluation), and risk of sustaining a MSKI requiring intervention in the Training Rehabilitation Program (MSKI-TRP1) during Canadian Basic Military Qualification. MATERIALS AND METHODS: This was a retrospective analysis of MSKIs in recruits introduced in the Training Rehabilitation Program (TRP1) in 2016 and 2017. A two-tailed t-test and a multivariate stepwise logistic regression were completed to investigate the interrelationships of sex, age, FORCE performance (20 m rushes, sandbag lift, intermittent loaded shuttles, sandbag drag) and health-related characteristics (waist circumference, predicted peak oxygen consumption [$\dot{V}$O2peak]), and odds for sustaining a MSKI-TRP. RESULTS: The MSKI-TRP1 intervention rate observed was 4.3%. Rehabilitation duration was an average (SD) of 87 (76) days; nearly 80% of MSKI-TRP were lower body injuries. MSKI-TRP recruits were older, had a lower score on FORCE, and had a larger mean waist circumference and lower $\dot{V}$O2peak than non-TRP1 recruits (all P < 0.01). Recruits with performance lower than 1 SD below mean on the 20 m rushes, intermittent loaded shuttle, or sandbag drag were 2.69 (1.89-3.83), 2.74 (1.91-3.95), and 2.26 (1.52-3.37) times more likely to sustain a MSKI-TRP1, respectively (all P < 0.01). Recruits with $\dot{V}$O2peak lower than 1 SD below mean were also 2.19 (1.30-3.70) times more likely to sustain a MSKI-TRP. Neither sex, age, nor waist circumference impacted the risk of MSKI-TRP1 when controlling for FORCE performance. CONCLUSIONS: The Canadian Armed Forces PES proxy performance can be used to assess the odds of sustaining a MSKI-TRP1 in Canadian military recruit training.