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Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
This study estimates agency’s impact on sugar plantation productivity using a unique early nineteenth-century panel data set from St. Vincent and the Grenadines. Results of fixed effects models, combined with a qualitative and quantitative analysis of potential endogeneity of the agency variable, provide no evidence that estates managed by agents were less productive than those managed by their owners. We discuss the results in the context of the historical and recent, revisionary, interpretations of agency, and the emergence of managerial hierarchies in the Atlantic economy.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
Introduction: Acute heart failure (AHF) is a common, serious condition that frequently results in morbidity and death and is a leading cause for hospital admissions. There is little evidence to guide ED physician disposition decisions for AHF patients. We sought to create a risk-stratification tool for use by ED physicians to determine which AHF patients are at high risk for poor outcomes. Methods: We conducted a prospective cohort study in 9 tertiary hospital EDs and enrolled adult patients presenting with shortness of breath due to AHF. Patients were assessed for standardized clinical and laboratory variables and then followed to determine short-term serious outcome (SSO), defined as death, intubation, myocardial infarction, or relapse requiring admission within 14 days. We identified predictors of SSO by stepwise logistic regression and then rounded beta coefficients to create a risk scale. Results: We enrolled 1,733 patients with mean age 77.1 years, male 54.5%, and initially admitted 50.1%. SSOs occurred in 202 (11.7%) cases (14.0% in those admitted and 9.3% in those discharged from the ED). We created the CHFRS consisting of:1. Initial Assessment a) History of valvular heart disease b) On anti-arrhythmic c) Arrival heart rate ≥ 110d) Treated with non-invasive ventilation2. Investigations a) Urea >12 mmol/L or Cr>150 µmol/L b) Serum CO2>35 mmol/L or pCO2 >60 mmHg (VBG or ABG) c) Troponin >5x Upper Reference Level 3. Fails reassessment after ED treatment:(i) Resting vital signs abnormal, (SaO2 <90% on room air or usual O2, or HR >110, or RR >28); OR(ii) Unable to complete 3-minute walk test. The risk of SSO varied from 5.0% for a score of 0, to 77.4% for a score of 9. Discrimination between SSO and no SSO cases was good with an area under the ROC curve of 0.70 (95% CI 0.66-0.74). There was good calibration between the observed and expected probability of SSO and internal validation showed the risk scores to be very accurate across 1,000 replications using the bootstrap method. Conclusion: We have created the CHFRS tool which consists of 8 simple variables and which estimates the short-term risk of SSOs in AHF patients. CHFRS should help improve and standardize admission practices, diminishing both unnecessary admissions for low-risk patients and unsafe discharge decisions for high-risk patients. This will ultimately lead to better safety for patients and more efficient use of hospital resources.
Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects.
In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained.
Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (rspearman = −0.48, p = 0.044), and by tendency also for the MED sample (rspearman = −0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample.
In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.
Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.
Introduction: Patients with acute exacerbations of heart failure (HF) or chronic obstructive pulmonary disease (COPD) may be at high risk for preventable adverse events (AEs). Preventable AEs are ED care-associated complications due to medical error. Our objective was to identify and characterize preventable AEs among ED patients over 50 presenting with dyspnea from an acute exacerbation of HF or COPD; who were subsequently admitted or discharged. Methods: We conducted a multicentre health records review from six academic centers in Ontario and Alberta. We analysed health records for all prospectively enrolled patients who experienced flagged outcomes: relapse to ED within 14 days requiring admission; admission to a monitored unit (AMU), cardiac care unit(CCU), or intensive care unit(ICU); intubation(ETI); non-invasive ventilation(NIV); diagnosis of acute myocardial infarction(AMI); or death within 30 days. Using a validated approach, an ED physician analyzed case summaries for flagged outcomes that were associated with ED care, designated as AEs. Preventable AEs had contributing errors in diagnosis, management, procedure, medications or unsafe disposition decisions. We analyzed these data using thematic coding and descriptive statistics. Results: Of 2,515 patients enrolled (1,100 HF and 1,415 COPD), 210 patients experienced flagged outcomes, 47.1% of which were female, 64.3% had HF and the remaining COPD. The majority (86.2%) of flagged outcomes were related to underlying disease, but 13.8% of cases met criteria for AE and all were deemed preventable. Of the identified AEs, 72.4% returned to the ED and required admission to hospital; 17.2% were admitted to ICU, CCU, or AMU; 6.9% of patients died; 3.4% were intubated; 3.4% had a diagnosis of AMI and 0% required NIV. We found 75.8% of preventable AEs resulted from a management error (eg. not prescribing steroids on discharge for moderate COPD exacerbation); 31.0% from an unsafe disposition decision and 10.3% of AEs resulted from diagnostic error. Conclusion: Patients with acute exacerbations of HF and COPD are at high risk of preventable AEs directly related to care provided in the ED. Management and disposition decisions were a concerning source of error and should compel and focus future quality improvement efforts.
The mean, trend and variability of net snow accumulation in firn cores are often used to validate model output, develop remote-sensing algorithms and quantify ice-sheet surface mass balance. Thus, accurately defining uncertainties associated with these in situ measurements is critical. In this study, we apply statistical simulation methods to quantify the uncertainty in firn-core accumulation data due to the uncertainty in depth–age scales. The methods are applied to a suite of firn cores from central West Antarctica. The results show that uncertainty in depth–age scales can give rise to spurious trends in accumulation that are the same order of magnitude as accumulation trends reported in West Antarctica. The depth–age scale uncertainties also significantly increase the apparent interannual accumulation variability, so these uncertainties must first be accounted for before using firn-core data to assess such processes as small-spatial-scale variability. Better quantification of error in accumulation will improve our ability to meaningfully compare firn-core data across different regions of the ice sheet, and provide appropriate targets for calibration and/or validation of model output and remote-sensing data.
We present the KMOS (K-band Multi-Object Spectrograph) Cluster and VIRIAL (VLT IRIFU Absorption Line) Guaranteed Time Observation (GTO) programs. KMOS provides 24 arms each feeding an integral field unit (14×14 spaxels of 0.2″ pixels) for IZ, YJ, H and K band near infrared (NIR) medium resolution spectroscopy (R ∼ 3500). Targets are selected from a 7.2′ diameter patrol field. Ultra-deep spectroscopy of ∼ 80 early-type cluster galaxies (∼ 20hr on source) and ∼ 200 (∼ 10hr on source) early-type field galaxies at 1 < z < 2 will dramatically improve the situation at z > 1 for which measurements of stellar velocity dispersions and absorption indices are limited to a few, often relatively young passively evolving galaxies (e.g. Bezanson 2013). In ESO Periods P92 and P93, 15 nights worth of data has been collected for KMOS-Clusters and 6 nights for VIRIAL: this will be supplemented with more data in upcoming semesters. All galaxies have multiband HST imaging including existing or upcoming WFC3 IR imaging, providing stellar mass maps and sizes. Combined with our dispersion measurements, this will allow us to examine the fundamental plane and the dynamical mass of a large sample of z > 1 galaxies for the first time, for both cluster and field galaxies.
The Wind River Range in Wyoming, USA, contains the largest concentration of glacial mass in the Rocky Mountains of the contiguous USA. Despite this distinction, only a few field or remotely sensed studies providing glacier volume changes have been published. The current study focuses on Continental Glacier located on the northern end of the range and uses two field datasets (high-accuracy GPS surface elevation points and ice-penetrating radar transects of the glacier bed) to create a three-dimensional model of glacier volume. Current surface elevations are compared with historical elevation data to calculate surface elevation change over time. An average thinning rate of 13.8 ± 7.8 m (0.30 ± 0.17 m a–1) between 1966 and 2012 was found. Surface elevation change rates varied across the glacier, ranging from +0.30 to –0.98 m a–1. Taking into account variable melt rates across the glacier, along with a glacial volume of 72.1 × 106 ± 10.8 × 106 m3, we estimate that Continental Glacier will be reduced in volume by 43% over the next 100 years and will disappear completely over the next 300–400 years, if current climatic conditions persist.
We report on experiments aimed at the generation and characterization of solid density plasmas at the free-electron laser FLASH in Hamburg. Aluminum samples were irradiated with XUV pulses at 13.5 nm wavelength (92 eV photon energy). The pulses with duration of a few tens of femtoseconds and pulse energy up to 100 µJ are focused to intensities ranging between 1013 and 1017 W/cm2. We investigate the absorption and temporal evolution of the sample under irradiation by use of XUV and optical spectroscopy. We discuss the origin of saturable absorption, radiative decay, bremsstrahlung and atomic and ionic line emission. Our experimental results are in good agreement with simulations.
Surface scratches in a series of controlled epoxy networks (CEN) were measured using a combination of instrumented indentation protocols and laser scanning confocal microscopy. Identical epoxy chemistry with increasing molecular weight between crosslinks provided different viscoelastic relaxation behaviors with the same modulus at ambient conditions. The glass transition temperatures (Tg)ranged between 70°C and 117°C. The high Tg CEN exhibited the lowest penetration depth and the highest elastic recovery. The results are analyzed with respect to the macroscale bulk properties and underlying molecular architecture of the CEN materials.