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To evaluate the discriminative ability of hyperlactataemia for early morbidity and mortality in neonates with CHD following cardiac surgery.
Retrospective, observational study of neonates who underwent cardiac surgery on cardiopulmonary bypass at a tertiary care children’s hospital from June 2015 to June 2019. The primary predictor was lactate. The primary composite outcome was defined as ≥1 of the following: cardiac arrest or extracorporeal membrane oxygenation within 72 hours or 30-day mortality post-operatively. The secondary outcome was the presence of major residual lesions, according to the Technical Performance Score.
Of 432 neonates, 28 (6.5%) sustained the composite outcome. On univariate analysis, peak lactate within 48 hours, increase in lactate from ICU admission through 12 hours, and single ventricle physiology were significantly associated with the composite outcome. The peak lactate occurred at a median of 2.9 hours (interquartile range: 1, 35) before the event. Through multi-variable analysis, a multi-variable risk algorithm was created. Predicted probabilities demonstrated an increasing risk based on single ventricle status and delta lactate, ranging from 1.8% (95% CI: 0.9, 3.9) to 52.4% (95% CI: 32.4, 71.7). The model had good discriminative ability for the composite outcome on receiver operating characteristic analysis (area under the curve = 0.79; 95% CI: 0.75, 0.89). Moreover, a peak lactate of 7.3 mmol/l or greater was significantly associated with the presence of a major residual lesion (odds ratios: 5.16, 95% CI: 3.01, 8.87).
We present a simple, two-variable model, including delta lactate in the immediate post-operative period and single ventricle status, to prognosticate the risk of early morbidity and mortality in neonates undergoing cardiac surgery for potential intervention.
Elusive species are challenging to study and conserve because basic elements of their biology may be unknown. Specimens of opportunity provide a means of collecting information on these species and may be critical for elusive species’ conservation. We used snowball sampling to identify Sowerby’s beaked whale (Mesoplodon bidens) specimens in museums and research institutions. Snowball sampling proved highly effective: we located 180 specimens from 24 institutions in North America and Europe, 62 of which were not listed in online collections databases, resulting in the largest collated dataset for this species. Analysis of these data resulted in several new findings for this species, including significant morphological variation between specimens from different collection regions, suggesting the presence of previously unidentified population structuring in this species. These data provide critical information regarding this species and demonstrate the effectiveness of specimens of opportunity for elusive species research and conservation. We recommend other researchers consider snowball sampling when designing research projects utilizing specimens of opportunity. Our results demonstrate the usefulness of snowball sampling and specimens of opportunity to elusive species research and conservation, and the methods of our study can be readily adapted for other species.
We performed a prospective study of 501 patients, regardless of symptoms, admitted to the hospital, to estimate the predictive value of a negative nasopharyngeal swab for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). At a positivity rate of 10.2%, the estimated negative predictive value (NPV) was 97.2% and the NPV rose as prevalence decreased during the study.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Our objective was to examine the performance characteristics of a bladder stimulation technique for urine collection among infants presenting to the emergency department (ED).
This prospective cohort study enrolled a convenience sample of infants aged ≤ 90 days requiring urine testing in the ED. Infants were excluded if critically ill, moderately to severely dehydrated, or having significant feeding issues. Bladder stimulation consisted of finger tapping on the lower abdomen with or without lower back massage while holding the child upright. The primary outcome was successful midstream urine collection within 5 minutes of stimulation. Secondary outcomes included sample contamination, bladder stimulation time for successful urine collection, and perceived patient distress on a 100-mm visual analog scale (VAS).
We enrolled 151 infants and included 147 in the analysis. Median age was 53 days (interquartile range [IQR] 27–68 days). Midstream urine sample collection using bladder stimulation was successful in 78 infants (53.1%; 95% confidence interval [CI] 45–60.9). Thirty-nine samples (50%) were contaminated. Most contaminated samples (n = 31; 79.5%) were reported as “no significant growth” or “growth of 3 or more organisms”. Median bladder stimulation time required for midstream urine collection was 45 seconds (IQR 20–120 seconds). Mean VAS for infant distress was 22 mm (standard deviation 23 mm).
The success rate of this bladder stimulation technique was lower than previously reported. The contamination rate was high, however most contaminated specimens were easily identified and had no clinical impact.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Poor physical health in severe mental illness (SMI) remains a major issue for clinical practice.
To use electronic health records of routinely collected clinical data to determine levels of screening for cardiometabolic disease and adverse health outcomes in a large sample (n = 7718) of patients with SMI, predominantly schizophrenia and bipolar disorder.
We linked data from the Glasgow Psychosis Clinical Information System (PsyCIS) to morbidity records, routine blood results and prescribing data.
There was no record of routine blood monitoring during the preceding 2 years for 16.9% of the cohort. However, monitoring was poorer for male patients, younger patients aged 16–44, those with schizophrenia, and for tests of cholesterol, triglyceride and glycosylated haemoglobin. We estimated that 8.0% of participants had diabetes and that lipids levels, and use of lipid-lowering medication, was generally high.
Electronic record linkage identified poor health screening and adverse health outcomes in this vulnerable patient group. This approach can inform the design of future interventions and health policy.
Consumption of certain berries appears to slow postprandial glucose absorption, attributable to polyphenols, which may benefit exercise and cognition, reduce appetite and/or oxidative stress. This randomised, crossover, placebo-controlled study determined whether polyphenol-rich fruits added to carbohydrate-based foods produce a dose-dependent moderation of postprandial glycaemic, glucoregulatory hormone, appetite and ex vivo oxidative stress responses. Twenty participants (eighteen males/two females; 24 (sd 5) years; BMI: 27 (sd 3) kg/m2) consumed one of five cereal bars (approximately 88 % carbohydrate) containing no fruit ingredients (reference), freeze-dried black raspberries (10 or 20 % total weight; LOW-Rasp and HIGH-Rasp, respectively) and cranberry extract (0·5 or 1 % total weight; LOW-Cran and HIGH-Cran), on trials separated by ≥5 d. Postprandial peak/nadir from baseline (Δmax) and incremental postprandial AUC over 60 and 180 min for glucose and other biochemistries were measured to examine the dose-dependent effects. Glucose AUC0–180 min trended towards being higher (43 %) after HIGH-Rasp v. LOW-Rasp (P=0·06), with no glucose differences between the raspberry and reference bars. Relative to reference, HIGH-Rasp resulted in a 17 % lower Δmax insulin, 3 % lower C-peptide (AUC0–60 min and 3 % lower glucose-dependent insulinotropic polypeptide (AUC0–180 min) P<0·05. No treatment effects were observed for the cranberry bars regarding glucose and glucoregulatory hormones, nor were there any treatment effects for either berry type regarding ex vivo oxidation, appetite-mediating hormones or appetite. Fortification with freeze-dried black raspberries (approximately 25 g, containing 1·2 g of polyphenols) seems to slightly improve the glucoregulatory hormone and glycaemic responses to a high-carbohydrate food item in young adults but did not affect appetite or oxidative stress responses at doses or with methods studied herein.
Cognitive behavioural therapy (CBT) for panic disorder encourages patients to learn about and make changes to thoughts and behaviour patterns that maintain symptoms of the disorder. Instruments to assess whether or not patients understand therapy content do not currently exist.
The aim of this study was to examine if increases within specific knowledge domains of panic disorder were related to improvement in panic symptoms following an intensive 2-day panic treatment.
Thirty-nine Veterans enrolled in an intensive weekend panic disorder treatment completed knowledge measures immediately before the first session of therapy and at the end of the last day of therapy. Four panic disorder experts evaluated items and reached consensus on subscales. Subscales were reduced further to create psychometrically sound subscales of catastrophic misinterpretation (CM), behaviours (BE), and self-efficacy (SE). A simple regression analysis was conducted to determine whether increased knowledge predicted symptom change at a 3-month follow-up assessment.
The overall knowledge scale was reduced to three subscales BE (n = 7), CM (n = 13) and SE (n = 8) with good internal consistency. Veterans’ knowledge of panic disorder improved from pre- to post-treatment. Greater increase in scores on the knowledge assessment predicted lower panic severity scores at a 3-month follow-up. A follow-up analysis using the three subscales as predictors showed that only changes in CM significantly contributed to the prediction.
In an intensive therapy format, reduction in panic severity was related to improved knowledge overall, but particularly as a result of fewer catastrophic misinterpretations.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
Breakthrough Listen is a 10-yr initiative to search for signatures of technologies created by extraterrestrial civilisations at radio and optical wavelengths. Here, we detail the digital data recording system deployed for Breakthrough Listen observations at the 64-m aperture CSIRO Parkes Telescope in New South Wales, Australia. The recording system currently implements two modes: a dual-polarisation, 1.125-GHz bandwidth mode for single-beam observations, and a 26-input, 308-MHz bandwidth mode for the 21-cm multibeam receiver. The system is also designed to support a 3-GHz single-beam mode for the forthcoming Parkes ultra-wideband feed. In this paper, we present details of the system architecture, provide an overview of hardware and software, and present initial performance results.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.
Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.
Neither genetic measure was associated with season or month of birth within the UKBB sample.
As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.
Fine resolution topographic data derived from methods such as Structure from Motion (SfM) and Multi-View Stereo (MVS) have the potential to provide detailed observations of geomorphological change, but have thus far been limited by the logistical constraints of conducting repeat surveys in the field. Here, we present the results from an automated time-lapse camera array, deployed around an ice-marginal lake on the western margin of the Greenland ice sheet. Fifteen cameras acquired imagery three-times per day over a 426 day period, yielding a dataset of ~19 000 images. From these data we derived 18 point clouds of the ice-margin across a range of seasons and successfully identified calving events (ranging from 234 to 1475 m2 in area and 815–8725 m3 in volume) induced by ice cliff undercutting at the waterline and the collapse of spalling flakes. Low ambient light levels, locally reflective surfaces and the large survey range hindered analysis of smaller scale ice-margin dynamics. Nevertheless, this study demonstrates that an integrated SfM-MVS and time-lapse approach can be employed to generate long-term 3-D topographic datasets and thus quantify ice-margin dynamics at a fine spatio-temporal scale. This approach provides a template for future studies of geomorphological change.
Measurements of glacier ice cliff evolution are sparse, but where they do exist, they indicate that such areas of exposed ice contribute a disproportionate amount of melt to the glacier ablation budget. We used Structure from Motion photogrammetry with Multi-View Stereo to derive 3-D point clouds for nine ice cliffs on Khumbu Glacier, Nepal (in November 2015, May 2016 and October 2016). By differencing these clouds, we could quantify the magnitude, seasonality and spatial variability of ice cliff retreat. Mean retreat rates of 0.30–1.49 cm d−1 were observed during the winter interval (November 2015–May 2016) and 0.74–5.18 cm d−1 were observed during the summer (May 2016–October 2016). Four ice cliffs, which all featured supraglacial ponds, persisted over the full study period. In contrast, ice cliffs without a pond or with a steep back-slope degraded over the same period. The rate of thermo-erosional undercutting was over double that of subaerial retreat. Overall, 3-D topographic differencing allowed an improved process-based understanding of cliff evolution and cliff-pond coupling, which will become increasingly important for monitoring and modelling the evolution of thinning debris-covered glaciers.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
We aimed to evaluate emergency medical services (EMS) data as disaster metrics and to assess stress in surrounding hospitals and a municipal network after the closure of Bellevue Hospital during Hurricane Sandy in 2012.
We retrospectively reviewed EMS activity and call types within New York City’s 911 computer-assisted dispatch database from January 1, 2011, to December 31, 2013. We evaluated EMS ambulance transports to individual hospitals during Bellevue’s closure and incremental recovery from urgent care capacity, to freestanding emergency department (ED) capability, freestanding ED with 911-receiving designation, and return of inpatient services.
A total of 2,877,087 patient transports were available for analysis; a total of 707,593 involved Manhattan hospitals. The 911 ambulance transports disproportionately increased at the 3 closest hospitals by 63.6%, 60.7%, and 37.2%. When Bellevue closed, transports to specific hospitals increased by 45% or more for the following call types: blunt traumatic injury, drugs and alcohol, cardiac conditions, difficulty breathing, “pedestrian struck,” unconsciousness, altered mental status, and emotionally disturbed persons.
EMS data identified hospitals with disproportionately increased patient loads after Hurricane Sandy. Loss of Bellevue, a public, safety net medical center, produced statistically significant increases in specific types of medical and trauma transports at surrounding hospitals. Focused redeployment of human, economic, and social capital across hospital systems may be required to expedite regional health care systems recovery. (Disaster Med Public Health Preparedness. 2016;10:333–343)