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Membrane-glycogen arrays composed of double membranes in alternation with glycogen layers (Figs. 1,4) have been described in many kinds of tissue and were recently observed in extraocular muscle of apparently normal adult rabbits. These systematically organized glycogen bodies are often seen to be continuous with the intermyofibrillar sarcoplasmic reticulum, as well as with randomly disposed membrane-glycogen complexes which form extensive structures that are independent of the myofibrils. Often seen in close association with these complexes are groupings of 10-20 mu particles which are typically discriminable from the 30-40 mu β-glycogen particles. These small particles may appear at the periphery of arrays, either unbounded or enclosed within rounded cisternae; they may also occur between the cisternal lamellae well within the arrays, either as short layers or in small clusters (Figs. 1,4). Histochemical EM procedures were employed to test whether the 10-20 mu particles are polysaccharide entities such as have been proposed to be the structural subunits of particulate glycogen, and which may also occur as independent populations of small particles under certain conditions.
Introduction: Emergency care serves as an important health resource for First Nations (FN) persons. Previous reporting shows that FN persons visit emergency departments at almost double the rate of non-FN persons. Working collaboratively with FN partners, academic researchers and health authority staff, the objective of this study is to investigate FN emergency care patient visit statistics in Alberta over a five year period. Methods: Through a population-based retrospective cohort study for the period from April 1, 2012 to March 31, 2017, patient demographics and emergency care visit characteristics for status FN patients in Alberta were analyzed and compared to non-FN statistics. Frequencies and percentages (%) describe patients and visits by categorical variables (e.g., Canadian Triage Acuity Scale (CTAS)). Means and standard deviations (medians and interquartile ranges (IQR)) describe continuous variables (e.g., distances) as appropriate for the data distribution. These descriptions are repeated for the FN and non-FN populations, separately. Results: The data set contains 11,686,288 emergency facility visits by 3,024,491 unique persons. FN people make up 4.8% of unique patients and 9.4% of emergency care visits. FN persons live further from emergency facilities than their non-FN counterparts (FN median 6 km, IQR 1-24; vs. non-FN median 4 km, IQR 2-8). FN visits arrive more often by ground ambulance (15.3% vs. 10%). FN visits are more commonly triaged as less acute (59% CTAS levels 4 and 5, compared to non-FN 50.4%). More FN visits end in leaving without completing treatment (6.7% vs. 3.6%). FN visits are more often in the evening – 4:01pm to 12:00am (43.6% vs. 38.1%). Conclusion: In a collaborative validation session, FN Elders and health directors contextualized emergency care presentation in evenings and receiving less acute triage scores as related to difficulties accessing primary care. They explained presentation in evenings, arrival by ambulance, and leaving without completing treatment in terms of issues accessing transport to and from emergency facilities. Many factors interact to determine FN patients’ emergency care visit characteristics and outcomes. Further research needs to separate the impact of FN identity from factors such as reasons for visiting emergency facilities, distance traveled to care, and the size of facility where care is provided.
An interim analysis of 1 year outcomes in schizophrenia patients enrolled in e-STAR in Australia and treated with RLAI continuously for 12 months.
e-STAR is a secure web-based, international, long-term (1 year retrospective, 2 years prospective) observational study of schizophrenia patients who initiate a new antipsychotic drug during their routine clinical management.
Currently, 315 patients have received RLAI continuously for 12 months; mean age 39.6 years, 68.9% male, mean duration of illness at baseline 11.8 years. Mean Clinical Global Impression Severity (CGI-S) scores at baseline (4.6) decreased significantly at 3, 6 and 12 months (n=284) (4.0, 3.7, 3.7, respectively; all p<0.001 vs baseline) indicating a reduction in illness severity from moderately-marked to mildly-moderate at month 3 and maintained to 1 year. The proportion of patients with CGI-S scores of 1–3 (not ill to mild severity) increased from 12.7% at baseline to 40.8% at 12 months (p<0.0001). Mean Global Assessment of Functioning (GAF) scale scores improved from 41.7 at baseline (serious impairment) to 56.7 (moderate impairment) at 12 months with improvements evident from month 3 after the start of RLAI (p<0.001 for both timepoints). Other significant improvements included fewer hospital stays (p<0.001) and rehospitalisations (p<0.001), reduced suicidal ideation (p=0.008) and violent behaviour (p=0.03), and decreased use of concomitant psychiatric medication.
These interim data show that a significant degree of clinical improvement and reduction in hospitalisation occurs early at 3 months in patients treated with RLAI and is maintained with continued treatment over 12 months.
To evaluate changes in the use of non-antipsychotic concomitant medication related to schizophrenia in patients enrolled in e-STAR in Belgium (B), Spain (S) and Australia (A) who were initiated on RLAI.
e-STAR is a secure web-based, international, long-term (1 year retrospective and 2 year prospective) ongoing observational study of schizophrenia patients who initiate a new antipsychotic drug during their routine clinical management. Data reported here are for patients enrolled to date in B, S and A who had information available about the use of concomitant medication at baseline and at 6 months after the start of RLAI.
Of 1,605 evaluable patients (B, n=180; S, n=919; A, n=506), 73.7% received concomitant non-antipsychotic medication at baseline. This proportion had reduced to 60.3% at 6 months after the start of RLAI (82.2% to 71.7% for B, p<0.001; 72.8% to 54.8% for S, p<0.001; 72.3% to 66.2% for A, p=0.01). Reductions between baseline and 6 months were overall: for anticholinergics 29.4% to 17.0% and for antidepressants 22.9% to 19.3% (each p<0.05 for B; p<0.001 for S); for mood stabilisers 17.6% to 15.8% (p=0.01 for S); for benzodiazepines 48.9% to 39.0% (p<0.001 for S; p=0.002 for A); for somatic medication 16.9% to 16.0%. Conclusions. Following the start of RLAI, the use of concomitant non-antipsychotic medication for the management of symptoms associated with schizophrenia or its treatment declined significantly at 6 months compared to baseline.
Hypoxic ischemic encephalopathy (HIE) is a condition that occurs when the entire brain is deprived of an adequate oxygen supply, and is often a complication of cardiac arrest or profound hypotension. This can result in poor outcomes including significant impairments in memory, cognition, and attention.
In the context of sparse literature reports on chronic delirum following cardiac arrest related HIE, we report a case of a 59 year old male patient with normal premorbid functioning who developed chronic confusional state following a hypoxic insult to the brain subsequent to cardiac arrest and try to highlight the challenges encountered during his clinical course and management.
This case highlights the presence of chronic delirium following hypoxic ischaemic encephalopathy, an unfortunate consequence of cardiac arrest. It also highlights the problems encountered in managing such patients.
The German version of the Conners Adult ADHD Rating Scales (CAARS) has proven to show very high model fit in confirmative factor analyses with the established factors inattention/memory problems, hyperactivity/restlessness, impulsivity/emotional lability, and problems with self-concept in both large healthy control and ADHD patient samples. This study now presents data on the psychometric properties of the German CAARS-self-report (CAARS-S) and observer-report (CAARS-O) questionnaires.
CAARS-S/O and questions on sociodemographic variables were filled out by 466 patients with ADHD, 847 healthy control subjects that already participated in two prior studies, and a total of 896 observer data sets were available. Cronbach's-alpha was calculated to obtain internal reliability coefficients. Pearson correlations were performed to assess test-retest reliability, and concurrent, criterion, and discriminant validity. Receiver Operating Characteristics (ROC-analyses) were used to establish sensitivity and specificity for all subscales.
Coefficient alphas ranged from .74 to .95, and test-retest reliability from .85 to .92 for the CAARS-S, and from .65 to .85 for the CAARS-O. All CAARS subscales, except problems with self-concept correlated significantly with the Barrett Impulsiveness Scale (BIS), but not with the Wender Utah Rating Scale (WURS). Criterion validity was established with ADHD subtype and diagnosis based on DSM-IV criteria. Sensitivity and specificity were high for all four subscales.
The reported results confirm our previous study and show that the German CAARS-S/O do indeed represent a reliable and cross-culturally valid measure of current ADHD symptoms in adults.
Mechanistic models (MMs) have served as causal pathway analysis and ‘decision-support’ tools within animal production systems for decades. Such models quantitatively define how a biological system works based on causal relationships and use that cumulative biological knowledge to generate predictions and recommendations (in practice) and generate/evaluate hypotheses (in research). Their limitations revolve around obtaining sufficiently accurate inputs, user training and accuracy/precision of predictions on-farm. The new wave in digitalization technologies may negate some of these challenges. New data-driven (DD) modelling methods such as machine learning (ML) and deep learning (DL) examine patterns in data to produce accurate predictions (forecasting, classification of animals, etc.). The deluge of sensor data and new self-learning modelling techniques may address some of the limitations of traditional MM approaches – access to input data (e.g. sensors) and on-farm calibration. However, most of these new methods lack transparency in the reasoning behind predictions, in contrast to MM that have historically been used to translate knowledge into wisdom. The objective of this paper is to propose means to hybridize these two seemingly divergent methodologies to advance the models we use in animal production systems and support movement towards truly knowledge-based precision agriculture. In order to identify potential niches for models in animal production of the future, a cross-species (dairy, swine and poultry) examination of the current state of the art in MM and new DD methodologies (ML, DL analytics) is undertaken. We hypothesize that there are several ways via which synergy may be achieved to advance both our predictive capabilities and system understanding, being: (1) building and utilizing data streams (e.g. intake, rumination behaviour, rumen sensors, activity sensors, environmental sensors, cameras and near IR) to apply MM in real-time and/or with new resolution and capabilities; (2) hybridization of MM and DD approaches where, for example, a ML framework is augmented by MM-generated parameters or predicted outcomes and (3) hybridization of the MM and DD approaches, where biological bounds are placed on parameters within a MM framework, and the DD system parameterizes the MM for individual animals, farms or other such clusters of data. As animal systems modellers, we should expand our toolbox to explore new DD approaches and big data to find opportunities to increase understanding of biological systems, find new patterns in data and move the field towards intelligent, knowledge-based precision agriculture systems.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Neonates are at high risk of bleeding after open-heart surgery. We sought to determine pre-operative and intra-operative risk factors for increased bleeding after neonatal open-heart surgery with cardiopulmonary bypass.
We conducted a retrospective cohort study of neonates (0–30 days old) who underwent open-heart surgery with cardiopulmonary bypass from January, 2009, to March, 2013. Cardiac diagnosis; demographic and surgical data; and blood products, haemostatic agents, and anti-thrombotic agents administered before, during, and within 24 hours after surgery were abstracted from the electronic health record and anaesthesia records. The outcome of interest was chest tube output (in ml/kg body weight) within 24 hours. Relationships between chest tube output and putative associated factors were evaluated by unadjusted and adjusted linear regression.
The cohort consisted of 107 neonates, of whom 79% had a Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) Mortality Category of 4 or 5. Median chest tube output was 37 ml/kg (range 9–655 ml/kg). Age, African-American race, and longer durations of surgery and cardiopulmonary bypass each had statistically significant associations with increased chest tube output in unadjusted analyses. In multivariable analysis, African-American race retained an independent, statistically significant association with increased chest tube output; the geometric mean of chest tube output among African-American neonates was 71% higher than that of Caucasians (95% confidence interval, 29–125%; p = 0.001).
Among neonates with CHD undergoing open-heart surgery with cardiopulmonary bypass, African-American race is independently associated with greater chest tube output over the first 24 hours post-operatively.
Meta-analyses suggest that clinical psychopathology is preceded by dimensional behavioral and cognitive phenotypes such as psychotic experiences, executive functioning, working memory and affective dysregulation that are determined by the interplay between genetic and nongenetic factors contributing to the severity of psychopathology. The liability to mental ill health can be psychometrically measured using experimental paradigms that assess neurocognitive processes such as salience attribution, sensitivity to social defeat and reward sensitivity. Here, we describe the TwinssCan, a longitudinal general population twin cohort, which comprises 1202 individuals (796 adolescent/young adult twins, 43 siblings and 363 parents) at baseline. The TwinssCan is part of the European Network of National Networks studying Gene-Environment Interactions in Schizophrenia project and recruited from the East Flanders Prospective Twin Survey. The main objective of this project is to understand psychopathology by evaluating the contribution of genetic and nongenetic factors on subclinical expressions of dimensional phenotypes at a young age before the onset of disorder and their association with neurocognitive processes, such as salience attribution, sensitivity to social defeat and reward sensitivity.
Psychotic experiences (PEs) may be associated with injuries, but studies focusing specifically on low- and middle-income countries (LAMICs) are scarce. Thus, the current study examined the link between injuries and PEs in a large number of LAMICs.
Cross-sectional data were used from 242 952 individuals in 48 LAMICs that were collected during the World Health Survey in 2002–2004 to examine the association between traffic-related and other (non-traffic-related) forms of injury and PEs. Multivariable logistic regression analysis and meta-analysis were used to examine associations while controlling for a variety of covariates including depression.
In fully adjusted analyses, any injury [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.85–2.31], traffic injury (OR 1.84, 95% CI 1.53–2.21) and other injury (OR 2.09, 95% CI 1.84–2.37) were associated with higher odds for PEs. Results from a country-wise analysis showed that any injury was associated with significantly increased odds for PEs in 39 countries with the overall pooled OR estimated by meta-analysis being 2.46 (95% CI 2.22–2.74) with a moderate level of between-country heterogeneity (I2 = 56.3%). Similar results were observed across all country income levels (low, lower-middle and upper-middle).
Different types of injury are associated with PEs in LAMICs. Improving mental health systems and trauma capacity in LAMICs may be important for preventing injury-related negative mental health outcomes.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.
Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011–2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world’s most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
The interfacial behaviour of surfactant-laden drops squeezing through tight constrictions in a uniform far-field flow is modelled with respect to capillary number, drop-to-medium viscosity ratio and surfactant contamination. The surfactant is treated as insoluble and non-diffusive, and drop surface tension is related to surfactant concentration by a linear equation of state. The constriction is formed by three solid spheres held rigidly in space. A characteristic aspect of this confined and contaminated multiphase system is the rapid development of steep surfactant-concentration gradients during the onset of drop squeezing. The interplay between two physical effects of surfactant, namely the greater interface deformability due to decreased surface tension and interface immobilization due to Marangoni stresses, results in particularly rich drop-squeezing dynamics. A three-dimensional boundary-integral algorithm is used to describe drop hydrodynamics, and accurate treatment of close squeezing and trapped states is enabled by advanced singularity subtraction techniques. Surfactant transport and hydrodynamics are coupled via the surface convection equation (or convection–diffusion equation, if artificial diffusion is included), the interfacial stress balance and a solid-particle contribution based on the Hebeker representation. For extreme conditions, such as drop-to-medium viscosity ratios significantly less than unity, it is found that upwind-biased methods are the only stable approaches for modelling surfactant transport. Two distinct schemes, upwind finite volume and flow-biased least squares, are found to provide results in close agreement, indicating negligible numerical diffusion. Surfactant transport is enhanced by low drop-to-medium viscosity ratios, at which extremely sharp concentration gradients form during various stages of the squeezing process. The presence of surfactant, even at low degrees of contamination, significantly decreases the critical capillary number for droplet trapping, due to the accumulation of surfactant at the downwind pole of the drop and its subsequent elongation. Increasing the degree of contamination significantly affects surface mobility and further decreases the critical capillary number as well as drop squeezing times, up to a threshold above which the addition of surfactant negligibly affects squeezing dynamics.
On many Australian commercial pig farms, groups of growing pigs are mass-medicated through their drinking water with selected antimicrobials for short periods to manage herd health. However, delivery of medication in drinking water cannot be assumed to deliver an equal dose to all animals in a group. There is substantial between-animal variability in systemic exposure to an antimicrobial (i.e. the antimicrobial concentration in plasma), resulting in under-dosing or over-dosing of many pigs. Three sources of this between-animal variability during a water medication dosing event are differences in: (1) concentration of the active constituent of the antimicrobial product in water available to pigs at drinking appliances in each pen over time, (2) medicated water consumption patterns of pigs in each pen over time, and (3) pharmacokinetics (i.e. oral bioavailability, volume of distribution and clearance between pigs and within pigs over time). It is essential that factors operating on each farm that influence the range of systemic exposures of pigs to an antimicrobial are factored into antimicrobial administration regimens to reduce under-dosing and over-dosing.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.