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Executive function (EF) deficits are often associated with Autism Spectrum Disorder (ASD), even in the absence of Attention Deficit Hyperactivity Disorder (ADHD) diagnosis. To date, no approved medication treatments exist for EF deficits associated with ASD.
To assess the efficacy of transcranial photobiomodulation (tPBM) on EF in adults with ASD.
Adults (18-59) with high-functioning (HF)-ASD received twice a week tPBM for 8 weeks in an open-label single group design. ASD and EF deficits were assessed by clinician-rated Clinical Global Impression Scale and patient-rated scales of Behavior Rating Inventory of Executive Function-Adult (BRIEF-A).
Eleven participants were enrolled. Ten participants completed the study. Nine participants who completed the study had comorbid ADHD diagnosis. All 10 participants were included in efficacy analyses of EF deficits. Statistically significant improvements in executive function deficits were found in BRIEF-A total score and in subdomains of Inhibition, Emotional Control, Planning and Organization, Organization of Materials, Behavioral Regulation, Metacognitive Index and Global Executive Control. All participants were found to have mild to moderate improvement in their ADHD symptom severity per clinician rated CGIs. Statistically significant improvements in ADHD symptoms were noted in self-rated scales. No adverse events required changes in tPBM protocol.
tPBM is a safe and feasible treatment approach that has the potential to treat core features of ASD. Further research is necessary and warranted.
This work is funded by Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder and the MGH Pediatric Psychopharmacology Council Fund.
The catastrophic declines of three species of ‘Critically Endangered’ Gyps vultures in South Asia were caused by unintentional poisoning by the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Despite a ban on its veterinary use in 2006 (India, Nepal, Pakistan) and 2010 (Bangladesh), residues of diclofenac have continued to be found in cattle carcasses and in dead wild vultures. Another NSAID, meloxicam, has been shown to be safe to vultures. From 2012 to 2018, we undertook covert surveys of pharmacies in India, Nepal and Bangladesh to investigate the availability and prevalence of NSAIDs for the treatment of livestock. The purpose of the study was to establish whether diclofenac continued to be sold for veterinary use, whether the availability of meloxicam had increased and to determine which other veterinary NSAIDs were available. The availability of diclofenac declined in all three countries, virtually disappearing from pharmacies in Nepal and Bangladesh, highlighting the advances made in these two countries to reduce this threat to vultures. In India, diclofenac still accounted for 10–46% of all NSAIDs offered for sale for livestock treatment in 2017, suggesting weak enforcement of existing regulations and a continued high risk to vultures. Availability of meloxicam increased in all countries and was the most common veterinary NSAID in Nepal (89.9% in 2017). Although the most widely available NSAID in India in 2017, meloxicam accounted for only 32% of products offered for sale. In Bangladesh, meloxicam was less commonly available than the vulture-toxic NSAID ketoprofen (28% and 66%, respectively, in 2018), despite the partial government ban on ketoprofen in 2016. Eleven different NSAIDs were recorded, several of which are known or suspected to be toxic to vultures. Conservation priorities should include awareness raising, stricter implementation of current bans, bans on other vulture-toxic veterinary NSAIDs, especially aceclofenac and nimesulide, and safety-testing of other NSAIDs on Gyps vultures to identify safe and toxic drugs.
Introduction: Oxygen is commonly administered to prehospital patients presenting with acute myocardial infarction (AMI). We conducted a systematic review to determine if oxygen administration, in AMI, impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central, clinicaltrials.gov and ISRCTN for relevant randomized controlled trials and observational studies comparing oxygen administration and no oxygen administration. The outcomes of interest were: mortality (≤30 days, in-hospital, and intermediate 2-11 months), infarct size, and major adverse cardiac events (MACE). Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. A meta-analysis was performed using RevMan 5 software. Results: Our search yielded 1192 citations of which 48 studies were reviewed as full texts and a total of 8 studies were included in the analysis. All evidence was considered low or very low quality. Five studies reported on mortality finding low quality evidence of no benefit or harm. Low quality evidence demonstrated no benefit or harm from supplemental oxygen administration. Similarly, no benefit or harm was found in MACE or infarct size (very low quality). Normoxia was defined as oxygen saturation measured via pulse oximetry at ≥90% in one recent study and ≥94% in another. Conclusion: We found low and very low quality evidence that the administration of supplemental oxygen to normoxic patients experiencing AMI, provides no clear harm nor benefit for mortality or MACE. The evidence on infarct size was inconsistent and warrants further prospective examination.
Introduction: Opioids are routinely administered for analgesia to prehospital patients experiencing chest discomfort from acute myocardial infarction (AMI). We conducted a systematic review to determine if opioid administration impacts patient outcomes. Methods: We conducted a systematic search using MeSH terms and keywords in Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Central and Clinicaltrials.gov for relevant randomized controlled trials and observational studies comparing opioid administration in AMI patients from 1990 to 2017. The outcomes of interest were: all-cause short-term mortality (≤30 days), major adverse cardiac events (MACE), platelet activity and aggregation, immediate adverse events, infarct size, and analgesia. Included studies were hand searched for additional citations. Risk of Bias assessments were performed and GRADE methodology was employed to assess quality and overall confidence in the effect estimate. Results: Our search yielded 3001 citations of which 19 studies were reviewed as full texts and a total of 9 studies were included in the analysis. The studies predominantly reported on morphine as the opioid. Five studies reported on mortality (≤30 days), seven on MACE, four on platelet activity and aggregation, two on immediate adverse events, two on infarct size and none on analgesic effect. We found low quality evidence suggesting no benefit or harm in terms of mortality or MACE. However, low quality evidence indicates that opioids increase infarct size. Low-quality evidence also shows reduced serum P2Y12 (eg: clopidogrel and ticagrelor) active metabolite levels and increased platelet reactivity in the first several hours post administration following an increase in vomiting. Conclusion: We find low and very low quality evidence that the administration of opioids in STEMI may be adversely related to vomiting and some surrogate outcomes including increased infarct size, reduced serum P2Y12 levels, and increased platelet activity. We found no clear benefit or harm on patient-oriented clinical outcomes including mortality.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
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.
During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.
To integrate electronic clinical decision support tools into clinical practice and to evaluate the impact on indwelling urinary catheter (IUC) use and catheter-associated urinary tract infections (CAUTIs).
Design, Setting, and Participants
This 4-phase observational study included all inpatients at a multicampus, academic medical center between 2011 and 2015.
Phase 1 comprised best practices training and standardization of electronic documentation. Phase 2 comprised real-time electronic tracking of IUC duration. In phase 3, a triggered alert reminded clinicians of IUC duration. In phase 4, a new IUC order (1) introduced automated order expiration and (2) required consideration of alternatives and selection of an appropriate indication.
Overall, 2,121 CAUTIs, 179,070 new catheters, 643,055 catheter days, and 2,186 reinsertions occurred in 3·85 million hospitalized patient days during the study period. The CAUTI rate per 10,000 patient days decreased incrementally in each phase from 9·06 in phase 1 to 1·65 in phase 4 (relative risk [RR], 0·182; 95% confidence interval [CI], 0·153–0·216; P<·001). New catheters per 1,000 patient days declined from 53·4 in phase 1 to 39·5 in phase 4 (RR, 0·740; 95% CI, 0·730; P<·001), and catheter days per 1,000 patient days decreased from 194·5 in phase 1 to 140·7 in phase 4 (RR, 0·723; 95% CI, 0·719–0·728; P<·001). The reinsertion rate declined from 3·66% in phase 1 to 3·25% in phase 4 (RR, 0·894; 95% CI, 0·834–0·959; P=·0017).
The phased introduction of decision support tools was associated with progressive declines in new catheters, total catheter days, and CAUTIs. Clinical decision support tools offer a viable and scalable intervention to target hospital-wide IUC use and hold promise for other quality improvement initiatives.
Significant increases in excess all-cause mortality, particularly in the elderly, were observed during the winter of 2014/15 in England. With influenza A(H3N2) the dominant circulating influenza A subtype, this paper determines the contribution of influenza to this excess controlling for weather. A standardised multivariable Poisson regression model was employed with weekly all-cause deaths the dependent variable for the period 2008–2015. Adjusting for extreme temperature, a total of 26 542 (95% CI 25 301–27 804) deaths in 65+ and 1942 (95% CI 1834–2052) in 15–64-year-olds were associated with influenza from week 40, 2014 to week 20, 2015. This is compatible with the circulation of influenza A(H3N2). It is the largest estimated number of influenza-related deaths in England since prior to 2008/09. The findings highlight the potential health impact of influenza and the important role of the annual influenza vaccination programme that is required to protect the population including the elderly, who are vulnerable to a severe outcome.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (β2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β2-1 fructan as the sole carbohydrate source. β2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β2-1 fructans in healthy subjects.
We present polarimetric observations of the 4 ground-state transitions of OH, toward a sample of maser-emitting planetary nebulae (PNe) using the Australia Telescope Compact Array. This sample includes confirmed OH-emitting PNe, confirmed and candidate H2O-maser-emitting PNe. Polarimetric observations provide information related to the magnetic field of these sources. Maser-emitting PNe are very young PNe and magnetic fields are a key ingredient in the early evolution and shaping process of PNe. Our preliminary results suggest that magnetic field strengths may change very rapidly in young PNe.
Radio astrometric campaigns using VLBI have provided distances and proper motions for masers associated with young massive stars (BeSSeL survey). The ongoing BAaDE project plans to obtain astrometric information of SiO maser stars located in the inner Galaxy. These stars are associated with evolved, mass-losing stars. By overlapping optical (Gaia), infrared (2MASS, MSX and WISE) and radio (BAaDE) sources, we expect to obtain important clues on the intrinsic properties and population distribution of late-type stars. Moreover, a comparison of the Galactic parameters obtained with Gaia and VLBI can be done using radio observations on different targets: young massive stars (BeSSeL) and evolved stars (BAaDE).
Adolescence and young adulthood carry risk for suicidal thoughts and behaviours (STB). An increasing subpopulation of young people consists of college students. STB prevalence estimates among college students vary widely, precluding a validated point of reference. In addition, little is known on predictors for between-study heterogeneity in STB prevalence.
A systematic literature search identified 36 college student samples that were assessed for STB outcomes, representing a total of 634 662 students [median sample size = 2082 (IQR 353–5200); median response rate = 74% (IQR 37–89%)]. We used random-effects meta-analyses to obtain pooled STB prevalence estimates, and multivariate meta-regression models to identify predictors of between-study heterogeneity.
Pooled prevalence estimates of lifetime suicidal ideation, plans, and attempts were 22.3% [95% confidence interval (CI) 19.5–25.3%], 6.1% (95% CI 4.8–7.7%), and 3.2% (95% CI 2.2–4.5%), respectively. For 12-month prevalence, this was 10.6% (95% CI 9.1–12.3%), 3.0% (95% CI 2.1–4.0%), and 1.2% (95% CI 0.8–1.6%), respectively. Measures of heterogeneity were high for all outcomes (I2 = 93.2–99.9%), indicating substantial between-study heterogeneity not due to sampling error. Pooled estimates were generally higher for females, as compared with males (risk ratios in the range 1.12–1.67). Higher STB estimates were also found in samples with lower response rates, when using broad definitions of suicidality, and in samples from Asia.
Based on the currently available evidence, STB seem to be common among college students. Future studies should: (1) incorporate refusal conversion strategies to obtain adequate response rates, and (2) use more fine-grained measures to assess suicidal ideation.
Using the VLBA, the BeSSeL survey has provided distances and proper motions of young massive stars, allowing an accurate measure of the Galactic spiral structure. By the same technique, we are planning to map the inner Galaxy using positions and velocities of evolved stars (provided by the BAaDE survey). These radio astrometric measurements (BeSSeL and BAaDE) will be complementary to Gaia results and the overlap will provide important clues on the intrinsic properties and population distribution of the stars in the bulge.
Historical outbreaks can be an important source of information in the understanding of norovirus evolution and epidemiology. Here, we revisit an outbreak of undiagnosed gastroenteritis that occurred in Shippensburg, Pennsylvania in 1972. Nearly 5000 people fell ill over the course of 10 days. Symptoms included diarrhea, vomiting, stomach cramps, and fever, lasting for a median of 24 h. Using current techniques, including next-generation sequencing of full-length viral genomic amplicons, we identified an unusual norovirus recombinant (GII.Pg/GII.3) in nine of 15 available stool samples from the outbreak. This particular recombinant virus has not been reported in recent decades, although GII.3 and GII.Pg genotypes have been detected individually in current epidemic strains. The consensus nucleotide sequences were nearly identical among the four viral genomes analysed, although each strain had three to seven positions in the genome with heterogenous non-synonymous nucleotide subpopulations. Two of these resulting amino acid polymorphisms were conserved in frequency among all four cases, consistent with common source exposure and successful transmission of a mixed viral population. Continued investigation of variant nucleotide populations and recombination events among ancestral norovirus strains such as the Shippensburg virus may provide unique insight into the origin of contemporary strains.
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.
We sought to conduct a major objective of the CAEP Academic Section, an environmental scan of the academic emergency medicine programs across the 17 Canadian medical schools.
We developed an 84-question questionnaire, which was distributed to academic heads. The responses were validated by phone by the lead author to ensure that the questions were answered completely and consistently. Details of pediatric emergency medicine units were excluded from the scan.
At eight of 17 universities, emergency medicine has full departmental status and at two it has no official academic status. Canadian academic emergency medicine is practiced at 46 major teaching hospitals and 13 specialized pediatric hospitals. Another 69 Canadian hospital EDs regularly take clinical clerks and emergency medicine residents. There are 31 full professors of emergency medicine in Canada. Teaching programs are strong with clerkships offered at 16/17 universities, CCFP(EM) programs at 17/17, and RCPSC residency programs at 14/17. Fourteen sites have at least one physician with a Master’s degree in education. There are 55 clinical researchers with salary support at 13 universities. Sixteen sites have published peer-reviewed papers in the past five years, ranging from four to 235 per site. Annual budgets range from $200,000 to $5,900,000.
This comprehensive review of academic activities in emergency medicine across Canada identifies areas of strengths as well as opportunities for improvement. CAEP and the Academic Section hope we can ultimately improve ED patient care by sharing best academic practices and becoming better teachers, educators, and researchers.