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Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.
Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.
In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.
An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.
CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.
One view of major Solar Energetic Particle (SEP) events is that these (proton-dominated) fluxes are accelerated in heliospheric shock sources created by Interplanetary Coronal Mass Ejections (ICMEs), and then travel mainly along interplanetary magnetic field lines connecting the shock(s) to the observer(s). This places a particular emphasis on the role of the heliospheric conditions during the event, requiring a realistic description of the latter to interpret and/or model SEP events. The well-known ENLIL heliospheric simulation with cone model generated ICME shocks is used together with the SEPMOD particle event modeling scheme to demonstrate the value of applying these concepts at multiple inner heliosphere sites.
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
Environmental enteropathy (EE) is a syndrome of altered small intestine structure and function hypothesized to be common among individuals lacking access to improved water and sanitation. There are plausible biological mechanisms, both inflammatory and non-inflammatory, by which EE may alter the cardiometabolic profile. Here, we test the hypothesis that EE is associated with the cardiometabolic profile among young children living in an environment of intense enteropathogen exposure. In total, 156 children participating in the Peruvian cohort of a multicenter study on childhood infectious diseases, growth and development were contacted at 3–5 years of age. The urinary lactulose:mannitol ratio, and plasma antibody to endotoxin core were determined in order to assess intestinal permeability and bacterial translocation. Blood pressure, anthropometry, fasting plasma glucose, insulin, and cholesterol and apolipoprotein profiles were also assessed. Extant cohort data were also used to relate biomarkers of EE during the first 18 months of life to early child cardiometabolic profile. Lower intestinal surface area, as assessed by percent mannitol excretion, was associated with lower apolipoprotein-AI and lower high-density lipoprotein concentrations. Lower intestinal surface area was also associated with greater blood pressure. Inflammation at 7 months of age was associated with higher blood pressure in later childhood. This study supports the potential for a relationship between EE and the cardiometabolic profile.
Although mental disorders are significant predictors of educational attainment throughout the entire educational career, most research on mental disorders among students has focused on the primary and secondary school years.
The World Health Organization World Mental Health Surveys were used to examine the associations of mental disorders with college entry and attrition by comparing college students (n = 1572) and non-students in the same age range (18–22 years; n = 4178), including non-students who recently left college without graduating (n = 702) based on surveys in 21 countries (four low/lower-middle income, five upper-middle-income, one lower-middle or upper-middle at the times of two different surveys, and 11 high income). Lifetime and 12-month prevalence and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were assessed with the Composite International Diagnostic Interview (CIDI).
One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1% of these cases had pre-matriculation onsets. Disorders with pre-matriculation onsets were more important than those with post-matriculation onsets in predicting subsequent college attrition, with substance disorders and, among women, major depression the most important such disorders. Only 16.4% of students with 12-month disorders received any 12-month healthcare treatment for their mental disorders.
Mental disorders are common among college students, have onsets that mostly occur prior to college entry, in the case of pre-matriculation disorders are associated with college attrition, and are typically untreated. Detection and effective treatment of these disorders early in the college career might reduce attrition and improve educational and psychosocial functioning.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining.
Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design.
A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2).
The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (β = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%.
Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.
We present 3 representative cases from a sample of 16 local Brightest Cluster Galaxies observed using integral field spectroscopy. The observations extend to nearby neighbours and into the Intracluster Light (ICL). Population synthesis modeling shows that the ICL is younger and more metal poor compared to the BCG core and outskirts. This is consistent with a scenario in which the ICL grows by cluster processes, and alongside the growth of the BCG.
The decomposition of the 21 cm rotation curve of galaxies into contribution from the disk and dark halo depends on the adopted mass to light ratio (M/L) of the disk. Given the vertical velocity dispersion (σz) of stars in the disk and its scale height (h), the disk surface density and hence the M/L can be estimated. Earlier works have used this technique to conclude that galaxy disks are submaximal. Here we address an important conceptual problem: σz and h must pertain to the same population. Our analysis concludes that previous studies underestimate the disk surface mass density by ~ 2, sufficient to make a maximal disk for M74 appear like a submaximal disk.
Peer volunteers can be key to delivering effective social cognitive interventions due to increased potential for social modeling. We consulted peer volunteers who had just taken part in an 8-week social and nutritional mealtime intervention with older adults living alone, to seek their evaluation of the intervention.
Semi-structured focus groups were used with a total of 21 volunteers (17 female) and two facilitators. Thematic analysis was used to interrogate the data.
Six themes (16 sub-themes) are discussed. Peer volunteers described the importance of the socializing aspect of the intervention, of pairing considerations and compatibility in peer interventions, of considering the needs of the participant, of benefits to the volunteers, and of the practical considerations of conducting an intervention. Volunteers also discussed considerations for future research and services for older adults living alone.
Volunteers found their involvement in the intervention to be personally beneficial, and revealed some valuable considerations for the researchers to take forward to future research. Results are pertinent to intervention design and could inform future social cognitive and other peer-oriented interventions for older adults living alone.
The use of underground geological repositories, such as in radioactive waste disposal (RWD) and in carbon capture (widely known as Carbon Capture and Storage; CCS), constitutes a key environmental priority for the 21st century. Based on the identification of key scientific questions relating to the geophysics, geochemistry and geobiology of geodisposal of wastes, this paper describes the possibility of technology transfer from high-technology areas of the space exploration sector, including astrobiology, planetary sciences, astronomy, and also particle and nuclear physics, into geodisposal. Synergies exist between high technology used in the space sector and in the characterization of underground environments such as repositories, because of common objectives with respect to instrument miniaturization, low power requirements, durability under extreme conditions (in temperature and mechanical loads) and operation in remote or otherwise difficult to access environments.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.