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Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.
Introduction: For rhythm control of acute atrial fibrillation (AAF) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAF, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an apriori-specified modified intention-to-treat (MITT) basis excluding patients who never received the study infusion (e.g. spontaneous conversion). Data were analyzed using chi-squared tests and logistic regression. Our target sample size was 374 evaluable patients. Results: Of 395 randomized patients, 18 were excluded from the MITT analysis; none were lost to follow-up. The Drug-Shock (N = 198) and Shock Only (N = 180) groups (total = 378) were similar for all characteristics including mean age (60.0 vs 59.5 yrs), duration of AAF (10.1 vs 10.8 hrs), previous AF (67.2% vs 68.3%), median CHADS2 score (0 vs 0), and mean initial heart rate (119.9 vs 118.0 bpm). More patients converted to normal sinus rhythm in the Drug-Shock group (97.0% vs 92.2%; absolute difference 4.8%, 95% CI 0.2-9.9; P = 0.04). The multivariable analyses confirmed the Drug-Shock strategy superiority (P = 0.04). There were no statistically significant differences for time to conversion (91.4 vs 85.4 minutes), total ED length of stay (7.1 vs 7.7 hours), disposition home (97.0% vs 96.1%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion was more common in the Drug-Shock group (8.1% vs 0.6%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAF patients to go home in sinus rhythm. A strategy of initial cardioversion with procainamide was superior to a strategy of immediate ECV.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
The SPICA mid- and far-infrared telescope will address fundamental issues in our understanding of star formation and ISM physics in galaxies. A particular hallmark of SPICA is the outstanding sensitivity enabled by the cold telescope, optimised detectors, and wide instantaneous bandwidth throughout the mid- and far-infrared. The spectroscopic, imaging, and polarimetric observations that SPICA will be able to collect will help in clarifying the complex physical mechanisms which underlie the baryon cycle of galaxies. In particular, (i) the access to a large suite of atomic and ionic fine-structure lines for large samples of galaxies will shed light on the origin of the observed spread in star-formation rates within and between galaxies, (ii) observations of HD rotational lines (out to ~10 Mpc) and fine structure lines such as [C ii] 158 μm (out to ~100 Mpc) will clarify the main reservoirs of interstellar matter in galaxies, including phases where CO does not emit, (iii) far-infrared spectroscopy of dust and ice features will address uncertainties in the mass and composition of dust in galaxies, and the contributions of supernovae to the interstellar dust budget will be quantified by photometry and monitoring of supernova remnants in nearby galaxies, (iv) observations of far-infrared cooling lines such as [O i] 63 μm from star-forming molecular clouds in our Galaxy will evaluate the importance of shocks to dissipate turbulent energy. The paper concludes with requirements for the telescope and instruments, and recommendations for the observing strategy.
IR spectroscopy in the range 12–230 μm with the SPace IR telescope for Cosmology and Astrophysics (SPICA) will reveal the physical processes governing the formation and evolution of galaxies and black holes through cosmic time, bridging the gap between the James Webb Space Telescope and the upcoming Extremely Large Telescopes at shorter wavelengths and the Atacama Large Millimeter Array at longer wavelengths. The SPICA, with its 2.5-m telescope actively cooled to below 8 K, will obtain the first spectroscopic determination, in the mid-IR rest-frame, of both the star-formation rate and black hole accretion rate histories of galaxies, reaching lookback times of 12 Gyr, for large statistically significant samples. Densities, temperatures, radiation fields, and gas-phase metallicities will be measured in dust-obscured galaxies and active galactic nuclei, sampling a large range in mass and luminosity, from faint local dwarf galaxies to luminous quasars in the distant Universe. Active galactic nuclei and starburst feedback and feeding mechanisms in distant galaxies will be uncovered through detailed measurements of molecular and atomic line profiles. The SPICA’s large-area deep spectrophotometric surveys will provide mid-IR spectra and continuum fluxes for unbiased samples of tens of thousands of galaxies, out to redshifts of z ~ 6.
Glacier surface mass-balance measurements on Greenland started more than a century ago, but no compilation exists of the observations from the ablation area of the ice sheet and local glaciers. Such data could be used in the evaluation of modelled surface mass balance, or to document changes in glacier melt independently from model output. Here, we present a comprehensive database of Greenland glacier surface mass-balance observations from the ablation area of the ice sheet and local glaciers. The database spans the 123 a from 1892 to 2015, contains a total of ~3000 measurements from 46 sites, and is openly accessible through the PROMICE web portal (http://www.promice.dk). For each measurement we provide X, Y and Z coordinates, starting and ending dates as well as quality flags. We give sources for each entry and for all metadata. Two thirds of the data were collected from grey literature and unpublished archive documents. Roughly 60% of the measurements were performed by the Geological Survey of Denmark and Greenland (GEUS, previously GGU). The data cover all regions of Greenland except for the southernmost part of the east coast, but also emphasize the importance of long-term time series of which there are only two exceeding 20 a. We use the data to analyse uncertainties in point measurements of surface mass balance, as well as to estimate surface mass-balance profiles for most regions of Greenland.
Most research on interventions to counter stigma and discrimination has
focused on short-term outcomes and has been conducted in high-income
To synthesise what is known globally about effective interventions to
reduce mental illness-based stigma and discrimination, in relation first
to effectiveness in the medium and long term (minimum 4 weeks), and
second to interventions in low- and middle-income countries (LMICs).
We searched six databases from 1980 to 2013 and conducted a
multi-language Google search for quantitative studies addressing the
research questions. Effect sizes were calculated from eligible studies
where possible, and narrative syntheses conducted. Subgroup analysis
compared interventions with and without social contact.
Eighty studies (n = 422 653) were included in the
review. For studies with medium or long-term follow-up (72, of which 21
had calculable effect sizes) median standardised mean differences were
0.54 for knowledge and −0.26 for stigmatising attitudes. Those containing
social contact (direct or indirect) were not more effective than those
without. The 11 LMIC studies were all from middle-income countries.
Effect sizes were rarely calculable for behavioural outcomes or in LMIC
There is modest evidence for the effectiveness of anti-stigma
interventions beyond 4 weeks follow-up in terms of increasing knowledge
and reducing stigmatising attitudes. Evidence does not support the view
that social contact is the more effective type of intervention for
improving attitudes in the medium to long term. Methodologically strong
research is needed on which to base decisions on investment in
Congenital airway obstruction is rare but potentially fatal. We developed a complex airways interventional delivery team to manage such cases. Antenatal imaging detects airway compromise at an early stage and facilitates the planning of delivery procedures (‘ex utero intrapartum treatment’ and ‘operation on placental support’) which maintain feto-placental circulation whilst an airway is secured.
A retrospective review was performed of cases in which ENT input was required at birth for airway obstruction.
Four neonates were delivered before implementation of the service: two were intubated and another two underwent tracheostomy but died in the peri-natal period. Seven neonates were delivered after implementation of the service: six were intubated and one underwent immediate tracheostomy. Five subsequently underwent tracheostomy (three have since been decannulated). One child with multiple congenital anomalies died due to respiratory failure. Airway obstruction was caused by lymphatic malformation, teratoma, costo-craniomandibular syndrome and choristoma.
In the absence of other anomalies, interventional airway delivery led to reduced mortality and improved outcomes.
Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI.
A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted.
Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80–10.04) and corticosteroid (1.81; 1.15–2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52–9.12), renal failure (2.64; 1.23–5.68), hematologic cancer (1.75; 1.02–5.68), and diabetes mellitus (1.15; 1.05–1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years.
Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.
To explore the role of psychiatric admission, diagnosis and reported unfair treatment in the relationship between ethnicity and mistrust of mental health services.
The Mental Illness-Related Investigations on Discrimination (MIRIAD) study was a cross-sectional study of 202 individuals using secondary mental health services in South London. Two structural equation models were estimated, one using Admission (whether admitted to hospital for psychiatric treatment in the past 5 years) and one using involuntary admission to hospital in the past 5 years.
Increased mistrust was directly associated with the latent variable ‘unfair treatment by mental health services and staff’ and with Black or mixed ethnicity in both models. Those with a diagnosis of schizophrenia spectrum (as compared to depression and bipolar disorder) had a lower average score on the latent variable, suggesting that on average they reported less unfair treatment. We found evidence of increased reporting of unfair treatment by those who had an admission in the past 5 years, had experienced involuntary admission, and for people of Black of mixed Black and White ethnicity.
Neither prevalence of schizophrenia spectrum nor rates of hospital admission explained the greater mistrust of mental health services found among people of Black and mixed Black and White ethnicity compared with White ethnicity. Rather, people of Black and mixed Black and white ethnicity may be more likely to experience unfair treatment, generating mistrust; furthermore, this group is more likely to express mistrust even after accounting for reporting of unfair treatment by mental health services and staff.
There are few epidemiological data on the dietary risk factors of Barrett's oesophagus, a precursor of oesophageal adenocarcinoma. The present study investigated the association between vegetable, fruit and nitrate intake and Barrett's oesophagus risk in a large prospective cohort. The Netherlands Cohort Study recruited 120 852 individuals aged 55–69 years in 1986. Vegetable and fruit intake was assessed using a 150-item FFQ, and nitrate intake from dietary sources and drinking water was determined. After 16·3 years of follow-up, 433 cases (241 men and 192 women) of Barrett's oesophagus with specialised intestinal metaplasia and 3717 subcohort members were analysed in a case–cohort design using Cox proportional hazards models while adjusting for potential confounders. Men exhibited a lower risk of Barrett's oesophagus in the highest v. the lowest quintile of total (multivariable-adjusted hazard ratio (HR): 0·66, 95 % CI 0·43, 1·01), raw (HR 0·63, 95 % CI 0·40, 0·99), raw leafy (HR 0·55, 95 % CI 0·36, 0·86) and Brassica (HR 0·64, 95 % CI 0·41, 1·00) vegetable intake. No association was found for other vegetable groups and fruits. No significant associations were found between vegetable and fruit intake and Barrett's oesophagus risk among women. Total nitrate intake was inversely associated with Barrett's disease risk in men (HR 0·50, 95 % CI 0·25, 0·99) and positively associated with it in women (HR 3·77, 95 % CI 1·68, 8·45) (P for interaction = 0·04). These results suggest that vegetable intake may contribute to the prevention of Barrett's oesophagus. The possible differential effect in men and women should be evaluated further.
Bipolar disorder (BD) has been reported to be associated with high risk of suicide. We aimed to investigate the frequency and characteristics of suicide in people with BD in a national sample.
Suicide in BD in England from 1996 to 2009 was explored using descriptive statistics on data collected by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI). Suicide cases with a primary diagnosis of BD were compared to suicide cases with any other primary diagnosis.
During the study period 1489 individuals with BD died by suicide, an average of 116 cases/year. Compared to other primary diagnosis suicides, those with BD were more likely to be female, more than 5 years post-diagnosis, current/recent in-patients, to have more than five in-patient admissions, and to have depressive symptoms. In BD suicides the most common co-morbid diagnoses were personality disorder and alcohol dependence. Approximately 40% were not prescribed mood stabilizers at the time of death. More than 60% of BD suicides were in contact with services the week prior to suicide but were assessed as low risk.
Given the high rate of suicide in BD and the low estimates of risk, it is important that health professionals can accurately identify patients most likely to experience poor outcomes. Factors such as alcohol dependence/misuse, personality disorder, depressive illness and current/recent in-patient admission could characterize a high-risk group. Future studies need to operationalize clinically useful indicators of suicide risk in BD.
TO investigate and describe the relationship between indigenous Australian populations, residential aged care services, and community-onset Staphylococcus aureus bacteremia (SAB) among patients admitted to public hospitals in Queensland, Australia.
We used administrative healthcare data linked to microbiology results from patients with SAB admitted to Queensland public hospitals from 2005 through 2010 to identify community-onset infections. Data about indigenous Australian population and residential aged care services at the local government area level were obtained from the Queensland Office of Economic and Statistical Research. Associations between community-onset SAB and indigenous Australian population and residential aged care services were calculated using Poisson regression models in a Bayesian framework. Choropleth maps were used to describe the spatial patterns of SAB risk.
We observed a 21% increase in relative risk (RR) of bacteremia with methicillin-susceptible S. aureus (MSSA; RR, 1.21 [95% credible interval, 1.15–1.26]) and a 24% increase in RR with nonmultiresistant methicillin-resistant S. aureus (nmMRSA; RR, 1.24 [95% credible interval, 1.13–1.34]) with a 10% increase in the indigenous Australian population proportion. There was no significant association between RR of SAB and the number of residential aged care services. Areas with the highest RR for nmMRSA and MSSA bacteremia were identified in the northern and western regions of Queensland.
The RR of community-onset SAB varied spatially across Queensland. There was increased RR of community-onset SAB with nmMRSA and MSSA in areas of Queensland with increased indigenous population proportions. Additional research should be undertaken to understand other factors that increase the risk of infection due to this organism.