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Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.
To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.
We used regression analyses to compare cortical thickness and surface area (total and across gyri) between 120 unaffected carriers of rare CNVs associated with schizophrenia and 16 670 participants without any pathogenic CNV. A measure of cortical thickness and surface area covariance across gyri was also compared between groups.
Carrier status was associated with reduced surface area (β = −0.020 mm2, P < 0.001) and less robustly with increased cortical thickness (β = 0.015 mm, P = 0.035), and with increased covariance in thickness (carriers z = 0.31 v. non-carriers z = 0.22, P < 0.0005). Associations were mainly present in frontal and parietal areas and driven by a limited number of rare risk alleles included in our analyses (mainly 15q11.2 deletion for surface area and 16p13.11 duplication for thickness covariance).
Results for surface area conformed with previous clinical findings, supporting surface area reductions as an indicator of genetic liability for schizophrenia. Results for cortical thickness, though, argued against its validity as a potential risk marker. Increased structural thickness covariance across gyri also appears related to risk for schizophrenia. The heterogeneity found across the effects of rare risk alleles suggests potential different neurobiological gateways into schizophrenia's phenotype.
In this overview we discuss the role of psychiatry in managing delirium in acute hospital admissions. We briefly discuss the role psychiatry can offer in four main domains: (a) assessment; (b) management; (c) recovery; and (d) paradigm, education and research. In the assessment section we discuss accurately detecting delirium in the context of comorbid mixed neuropsychiatric syndromes, including depression and dementia, and the clinical importance of delirium subtyping. The management section briefly outlines pharmacological and non-pharmacological approaches to delirium and their evidence-based rationale. The recovery section focuses on the effect delirium can have on cognitive decline, mental health and long-term health, including functional outcome and need for institutional care after hospital discharge. Finally, we outline the role of psychiatry in delirium research and education. We hope that this article will encourage clinicians to reflect on their current practice and consider holistic and evidence-based care for this vulnerable population in the acute hospital setting.
Hearing loss affects over 1.3 billion individuals worldwide, with the greatest burden among adults. Little is known regarding the association between adult-onset hearing loss and employment.
Seven databases (PubMed, Embase, Cochrane Library, ABI/Inform Collection, Business Source Ultimate, Web of Science and Scopus) were searched through to October 2018. The key word terms used related to hearing loss and employment, excluding paediatric or congenital hearing loss and deaf or culturally deaf populations.
The initial search resulted in 13 144 articles. A total of 7494 articles underwent title and abstract screening, and 243 underwent full-text review. Twenty-five articles met the inclusion criteria. Studies were set in 10 predominantly high-income countries. Seven of the 25 studies analysed regionally or nationally representative datasets and controlled for key variables. Six of these seven studies reported associations between hearing loss and employment.
The highest quality studies currently available indicate that adult-onset hearing loss is associated with unemployment. However, considerable heterogeneity exists, and more rigorous studies that include low- and middle-income countries are needed.
Introduction: Prehospital field trauma triage (FTT) standards were reviewed and revised in 2014 based on the recommendations of the Centers for Disease Control and Prevention. The FTT standard allows a hospital bypass and direct transport, within 30 min, to a lead trauma hospital (LTH). Our objectives were to assess the impact of the newly introduced prehospital FTT standard and to describe the emergency department (ED) management and outcomes of patients that had bypassed closer hospitals. Methods: We conducted a 12-month multi-centred health record review of paramedic and ED records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness (physiologic), step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as urgent that met FTT standard, regardless of transport time. We developed and piloted a data collection tool and obtained consensus on all definitions. The primary outcome was the rate of appropriate triage to a LTH which was defined as: ISS ≥12, admitted to intensive care unit (ICU), non-orthopedic surgery, or death. We have reported descriptive statistics. Results: 570 patients were included: mean age 48.8, male 68.9%, falls 29.6%, motor vehicle collisions 20.2%, stab wounds 10.5%, transported to a LTH 76.5% (n = 436). 72.2% (n = 315) of patients transported to a LTH had bypassed a closer hospital and 126/306 (41.2%) of those were determined to be an appropriate triage to LTH (9 patients had missing outcomes). ED management included: CT head/cervical spine 69.9%, ultrasound 53.6%, xray 51.6%, intubation 15.0%, sedation 11.1%, tranexamic acid 9.8%, blood transfusion 8.2%, fracture reduction 6.9%, tube thoracostomy 5.9%. Outcomes included: ISS ≥ 12 32.7%, admitted to ICU 15.0%, non-orthopedic surgery 11.1%, death 8.8%. Others included: admission to hospital 57.5%, mean LOS 12.8 days, orthopedic surgery 16.3% and discharged from ED 37.3%. Conclusion: Despite a high number of admissions, the majority of trauma patients bypassed to a LTH were considered over-triaged, with a low number of ED procedures and non-orthopedic surgeries. Continued work is needed to appropriately identify patients requiring transport to a LTH.
Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction.
Methods and Results:
Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate.
In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.
Red meat is an important dietary source of protein and many other essential nutrients including omega(n)-3 polyunsaturated fatty acids (PUFA) which provide numerous benefits to human health. It is well known that grass-fed meat contains a more favourable fatty acid profile, compared to other feeding regimes, but the feasibility of grass finishing is in decline for many farmers/producers. Therefore, alternative methods to enhance the fatty acid profile of red meats, such as beef, are needed to meet increasing consumer demands for ‘healthier’ products. This study compared plasma PUFA concentrations across cattle finished on three different feeding regimes. Three farms supplied livestock to the current study, where cattle were fed three different feeding regimes for a minimum of 15-weeks prior to slaughter. Feeding regimes were ad lib concentrate (negative control), n3-enriched ad lib concentrate (treatment) or grass-fed only (positive control). Blood was collected at slaughter into EDTA tubes and plasma aliquots were stored at -80°C until analysis. A validated gas chromatography–mass spectrometry (GC-MS) method was used to quantify individual PUFA concentrations in mg/ml [linoleic acid (LA); arachidonic acid (AA); alpha-linolenic acid (ALA); eicosapentaenoic acid (EPA); docosapentaenoic acid (DPA); docosahexaenoic acid (DHA)]. Samples from 23, 49 and 40 animals (in control, treatment & grass groups, respectively) were available for the current analysis. One-way ANOVA tests revealed significant differences between groups in all PUFA concentrations quantified (all P < 0.026). Post-hoc (LSD) tests showed mean ± SD n3 PUFA concentrations were significantly different within all three groups (all P < 0.04), increasing from negative control (0.049 ± 0.013 mg/ml), to treatment (0.095 ± 0.034 mg/ml) and grass-fed groups (0.461 ± 0.132 mg/ml). The opposite was observed for mean ± SD n6 PUFA concentrations (1.060 ± 0.297 vs. 0.918 ± 0.267 vs. 0.355 ± 0.085 mg/ml, respectively; all P < 0.02). Cattle finished on either treatment or grass regimes had a more favourable n6:n3 PUFA ratio, compared to negative control (11.98 and 0.79 vs. 22.65, respectively). This study demonstrates that the finishing diet can impact plasma PUFA concentrations of beef cattle. Animals finished on the n3-enriched concentrate had, on average, double the total n3 PUFA concentrations, as well as an improved n6:n3 ratio, compared to control cattle. These results provide preliminary data on an alternative n3-enriched feeding regime for beef cattle to improve PUFA concentrations. Further research, however, is required to confirm if such beneficial changes are also observed in bovine muscle, which would have direct benefits for consumers.
A new carbon isotope record for two high-latitude sedimentary successions that span the Jurassic–Cretaceous boundary interval in the Sverdrup Basin of Arctic Canada is presented. This study, combined with other published Arctic data, shows a large negative isotopic excursion of organic carbon (δ13Corg) of 4‰ (V-PDB) and to a minimum of −30.7‰ in the probable middle Volgian Stage. This is followed by a return to less negative values of c. −27‰. A smaller positive excursion in the Valanginian Stage of c. 2‰, reaching maximum values of −24.6‰, is related to the Weissert Event. The Volgian isotopic trends are consistent with other high-latitude records but do not appear in δ13Ccarb records of Tethyan Tithonian strata. In the absence of any obvious definitive cause for the depleted δ13Corg anomaly, we suggest several possible contributing factors. The Sverdrup Basin and other Arctic areas may have experienced compositional evolution away from open-marine δ13C values during the Volgian Age due to low global or large-scale regional sea levels, and later become effectively coupled to global oceans by Valanginian time when sea level rose. A geologically sudden increase in volcanism may have caused the large negative δ13Corg values seen in the Arctic Volgian records but the lack of precise geochronological age control for the Jurassic–Cretaceous boundary precludes direct comparison with potentially coincident events, such as the Shatsky Rise. This study offers improved correlation constraints and a refined C-isotope curve for the Boreal region throughout latest Jurassic and earliest Cretaceous time.
The 1891–92, final issue of Leaves of Grass (commonly called the “deathbed” edition) has declined in the opinion of critics who see it as a negative benchmark within Whitman’s production for its heightened conservative poetics, both thematically and stylistically. The first three editions of Leaves of Grass have instead been championed, beginning in the 1950s and continuing to today. Our chapter investigates the question of what is still radical, experimental, and inspiring in the final edition, especially considering that it remains the most widely read version across the world, and that it was the one with which American and international modernist writers were most familiar. Particular attention is given to the edition’s juxtaposition of traditional and innovative poems, shifting styles, obsession with sound, and with what remains unutterable, especially as seen in the annexes to the edition.
Optimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.
To estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.
Surveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.
Questionnaire response was 79% at baseline and 82% at follow-up. For those aged 17–19, incident rate (range adjusted for non-response) of transition need was 202–511 per 100 000 people aged 17–19 per year, with successful transition of 38–96 per 100 000 people aged 17–19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.
As inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.
The archaeological site of Saruq al-Hadid, Dubai, United Arab Emirates, presents a long sequence of persistent temporary human occupation on the northern edge of the Rub’ al-Khali desert. The site is located in active dune fields, and evidence for human activity is stratified within a deep sequence of natural dune deposits that reflect complex taphonomic processes of deposition, erosion and reworking. This study presents the results of a program of radiocarbon (14C) and thermoluminescence dating on deposits from Saruq al-Hadid, allied with studies of material remains, which are amalgamated with the results of earlier absolute dating studies provide a robust chronology for the use of the site from the Bronze Age to the Islamic period. The results of the dating program allow the various expressions of human activity at the site—ranging from subsistence activities such as hunting and herding, to multi-community ritual activities and large scale metallurgical extraction—to be better situated chronologically, and thus in relation to current debates regarding the development of late prehistoric and early historic societies in southeastern Arabia.
Introduction: Depending on the time and day of initial Emergency Department (ED) presentation, some patients may require a return to the ED the following day for ultrasound examination. Return visits for ultrasound may be time and resource intensive for both patients and the ED. Qualitative experience suggests that a percentage of return ultrasounds could be performed at a non-ED facility. Our objective was to undertake a retrospective audit of return for ultrasound usage, patterns and outcomes at 2 academic EDs. Methods: A retrospective review of all adult patients returning to the ED for ultrasound at both LHSC ED sites in 2016 was undertaken. Each chart was independently reviewed by two emergency medicine consultants. Charts were assessed for day and time of initial presentation and return, type of ultrasound ordered, and length of ED stay on initial presentation and return visit. Opinion based questions were considered by reviewers, including urgency of diagnosis clarification required, if symptoms were still present on return, and if any medical or surgical treatment or follow up was arranged based on ultrasound results. Agreement between reviewers was assessed. Results: After eliminating charts for which the return visit was not for a scheduled ultrasound examination, 328 patient charts were reviewed. 63% of patients were female and median [IQR] age was 40 years [27-56]. Abdomen/pelvis represented 50% of the ultrasounds; renal 24%; venous Doppler 15.9%. Symptoms were still present and documented in 79% of cases. 22% of cases required a medical intervention and 9% an immediate surgical intervention. 11% of patients were admitted to hospital on their return visit. Outpatient follow-up based on US results was initiated in 29% of cases. Median [IQR] combined LOS was 479.5 minutes [358.5-621.75]. Agreement between reviewers for opinion based questions was poor (63%-96%). Conclusion: Ideally, formal ultrasound should be available on a 24 hour basis for ED patients in order to avoid return visits. A percentage of return for ultrasound examinations do not result in any significant change in treatment. Emergency departments should consider the development of pathways to avoid return visits for follow up ultrasound when possible. The low incidence of surgical treatment in those returning for US suggests that this population could be served in a non-hospital setting. Further research is required to support this conclusion.
Introduction: Trauma and injury play a significant role in the population's burden of disease. Limited research exists evaluating the role of trauma bypass protocols. The objective of this study was to assess the impact and effectiveness of a newly introduced prehospital field trauma triage (FTT) standard, allowing paramedics to bypass a closer hospital and directly transport to a trauma centre (TC) provided transport times were within 30 minutes. Methods: We conducted a 12-month multi-centred health record review of paramedic call reports and emergency department health records following the implementation of the 4 step FTT standard (step 1: vital signs and level of consciousness, step 2: anatomical injury, step 3: mechanism and step 4: special considerations) in nine paramedic services across Eastern Ontario. We included adult trauma patients transported as an urgent transport to hospital, that met one of the 4 steps of the FTT standard and would allow for a bypass consideration. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions. The primary outcome was the rate of appropriate triage to a TC, defined as any of the following: injury severity score ≥12, admitted to an intensive care unit, underwent non-orthopedic operation, or death. We report descriptive and univariate analysis where appropriate. Results: 570 adult patients were included with the following characteristics: mean age 48.8, male 68.9%, attended by Advanced Care Paramedic 71.8%, mechanisms of injury: MVC 20.2%, falls 29.6%, stab wounds 10.5%, median initial GCS 14, mean initial BP 132, prehospital fluid administered 26.8%, prehospital intubation 3.5%, transported to a TC 74.6%. Of those transported to a TC, 308 (72.5%) had bypassed a closer hospital prior to TC arrival. Of those that bypassed a closer hospital, 136 (44.2%) were determined to be “appropriate triage to TC”. Bypassed patients more often met the step 1 or step 2 of the standard (186, 66.9%) compared to the step 3 or step 4 (122, 39.6%). An appropriate triage to TC occurred in 104 (55.9%) patients who had met step 1 or 2 and 32 (26.2%) patients meeting step 3 or 4 of the FTT standard. Conclusion: The FTT standard can identify patients who should be bypassed and transported to a TC. However, this is at a cost of potentially burdening the system with poor sensitivity. More work is needed to develop a FTT standard that will assist paramedics in appropriately identifying patients who require a trauma centre.
Age at sexual debut is known to have implications for future sexual behaviours and health outcomes, including HIV infection, early pregnancy and maternal mortality, but may also influence educational outcomes. Longitudinal data on schooling and sexual behaviour from a demographic surveillance site in Karonga district, northern Malawi, were analysed for 3153 respondents between the ages of 12 and 25 years to examine the association between sexual debut and primary school dropout, and the role of prior school performance. Time to dropout was modelled using the Fine and Gray survival model to account for the competing event of primary school completion. To deal with the time-varying nature of age at sexual debut and school performance, models were fitted using landmark analyses. Sexual debut was found to be associated with a five-fold increase in rate of subsequent dropout for girls and a two-fold increase in dropout rate for boys (adjusted hazard ratio [aHR] of 5.27, CI 4.22–6.57, and 2.19, CI 1.77–2.7, respectively). For girls who were sexually active by age 16, only 16% ultimately completed primary schooling, compared with 70% aged 18 or older at sexual debut. Prior to sexual debut, girls had primary completion levels similar to those of boys. The association between sexual debut and school dropout could not be explained by prior poor school performance: the effect of sexual debut on dropout was as strong among those who were not behind in school as among those who were overage for their school grade. Girls who were sexually active were more likely to repeat a grade, with no effect being seen for boys. Pathways to dropout are complex and may differ for boys and girls. Interventions are needed to improve school progression so children complete primary school before sexual debut, and to improve sex education and contraception provision.
Recommending nitrofurantoin to treat uncomplicated cystitis was associated with increased nitrofurantoin use from 3.53 to 4.01 prescriptions per 1,000 outpatient visits, but nitrofurantoin resistance in E. coli isolates remained stable at 2%. Concomitant levofloxacin resistance was a significant risk for nitrofurantoin resistance in E. coli isolates (odds ratio [OR], 2.72; 95% confidence interval [CI], 1.04–7.17).
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.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to examine if stable health insurance coverage is associated with improved type 2 diabetes (DM) control and with reduced racial/ethnic health disparities. METHODS/STUDY POPULATION: We utilized EMR data (2005–2013) from 2 large, urban academic health centers with a racially/ethnically diverse patient population to longitudinally examine insurance coverage, and diabetes outcomes (A1C, LDL cholesterol, BP) and management measures (e.g., A1C and BP monitoring). We categorized insurance stability status during each 6-month interval as 6 separate categories based upon type (private, public, uninsured) and continuity of insurance (continuous, switches, or gaps in coverage). We will examine the association between insurance stability status and DM outcomes adjusting for time, age, sex, comorbidities, site of care, education, and income. Additional analysis will examine if insurance stability moderates the impact of race/ethnicity on DM outcomes. RESULTS/ANTICIPATED RESULTS: Overall, we anticipate that stable health insurance coverage will improve measures for DM care, particularly for racially/ethnically diverse patients. DISCUSSION/SIGNIFICANCE OF IMPACT: The finding of an interaction between insurance stability status and race/ethnicity in improved diabetes management and control would inform the national health care policy debate on the impact of stable health insurance.