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Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients.
We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients.
Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006.
Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology.
Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP.
This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses.
Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength.
Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
TAOS II is a next-generation occultation survey with the goal of measuring the size distribution of the small end of the Kuiper Belt (objects with diameters 0.5–30 km). Such objects have magnitudes r > 30, and are thus undetectable by direct imaging. The project will operate three telescopes at San Pedro Mártir Observatory in Baja California, México. Each telescope will be equipped with a custom-built camera comprised of a focal-plane array of CMOS imagers. The cameras will be capable of reading out image data from 10,000 stars at a cadence of 20 Hz. The telescopes will monitor the same set of stars simultaneously to search for coincident occultation detections, thus minimising the false-positive rate. This talk described the project, and reported on the progress of the development of the survey infrastructure.
Better understanding of the complex interplay among key determinants of functional outcome is crucial to promoting recovery in psychotic disorders. However, this is understudied in the early course of illness. We aimed to examine the relationships among negative symptoms, neurocognition, general self-efficacy and global functioning in first-episode psychosis (FEP) patients using structural equation modeling (SEM).
Three hundred and twenty-one Chinese patients aged 26–55 years presenting with FEP to an early intervention program in Hong Kong were recruited. Assessments encompassing symptom profiles, functioning, perceived general self-efficacy and a battery of neurocognitive tests were conducted. Negative symptom measurement was subdivided into amotivation and diminished expression (DE) domain scores based on the ratings in the Scale for the Assessment of Negative Symptoms.
An initial SEM model showed no significant association between functioning and DE which was removed from further analysis. A final trimmed model yielded very good model fit (χ2 = 15.48, p = 0.63; comparative fit index = 1.00; root mean square error of approximation <0.001) and demonstrated that amotivation, neurocognition and general self-efficacy had a direct effect on global functioning. Amotivation was also found to mediate a significant indirect effect of neurocognition and general self-efficacy on functioning. Neurocognition was not significantly related to general self-efficacy.
Our results indicate a critical intermediary role of amotivation in linking neurocognitive impairment to functioning in FEP. General self-efficacy may represent a promising treatment target for improvement of motivational deficits and functional outcome in the early illness stage.
The Universe is permeated by hot, turbulent, magnetized plasmas. Turbulent plasma is a major constituent of active galactic nuclei, supernova remnants, the intergalactic and interstellar medium, the solar corona, the solar wind and the Earth’s magnetosphere, just to mention a few examples. Energy dissipation of turbulent fluctuations plays a key role in plasma heating and energization, yet we still do not understand the underlying physical mechanisms involved. THOR is a mission designed to answer the questions of how turbulent plasma is heated and particles accelerated, how the dissipated energy is partitioned and how dissipation operates in different regimes of turbulence. THOR is a single-spacecraft mission with an orbit tuned to maximize data return from regions in near-Earth space – magnetosheath, shock, foreshock and pristine solar wind – featuring different kinds of turbulence. Here we summarize the THOR proposal submitted on 15 January 2015 to the ‘Call for a Medium-size mission opportunity in ESAs Science Programme for a launch in 2025 (M4)’. THOR has been selected by European Space Agency (ESA) for the study phase.
An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT–PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.
The effects of various parameters, such as thermal properties of substrates, thermal interface materials (TIMs) and heat sinks on the thermal performance of the light emitting diode (LED) light bars and backlight module are investigated experimentally and numerically in terms of junction temperature (Tj) and thermal resistances from junction to air (Rj-a). The results show that the measured Rj-a of the light bars by powering-on five LEDs in the test is different from one by powering-on only one LED, resulting from the extra heat coming from the adjacent LED packages affecting the Tj for the case of powering-on five LEDs. For the modules, Rj-a is significantly reduced by using the heat sinks for all backlight modules, and aluminum and iron heat sinks do not show any obvious difference in heat dissipation along with any substrates and TIMs. Furthermore, both experimental and simulation results show that the thermal conductivity of the substrates are more important and dominant than TIM and heat sink for the Rj-a of the backlight modules concerned, and also demonstrate that the thermal field for the local model can represent the one in full-scale backlight module.
Differences by ethnic group in STI diagnosis rates have long been recognized in England. We investigated whether these may be explained by ethnic disparities in socioeconomic deprivation (SED). Data on all diagnoses made in sexual health clinics in England in 2013 were obtained from the mandatory STI surveillance system. Poisson regression was used to calculate incidence rate ratios (IRRs) of STIs, by ethnicity, with and without adjustment for index of multiple deprivation (IMD) a measure of area-level deprivation. Unadjusted IRRs (95% confidence intervals) were highest for gonorrhoea [8·18 (7·77–8·61) and 5·76 (5·28–6·29)] and genital herpes [4·24 (3·99–4·51) and 3·58 (3·23–3·98)] for people of black Caribbean and non-Caribbean/non-African black ethnicity and IRRs were highest for syphilis [8·76 (7·97–9·63)] and genital warts [2·23 (2·17–2·29)] for people of non-British/non-Irish white ethnicity compared to white British ethnicity. After adjustment for IMD, IRRs for gonorrhoea [5·76 (5·47–6·07)] and genital herpes [3·73 (3·50–3·97)] declined but remained highest for black Caribbeans and IRRs for syphilis [7·35 (6·68–8·09)] and genital warts [2·10 (2·04–2·16)] declined but remained highest for non-British/non-Irish white compared to white British. In England, ethnic disparities in STI diagnosis rates are partially explained by SED, but behavioural and contextual factors likely contribute. Clinic and community-based interventions should involve social peer networks to ensure they are targeted and culturally sensitive.
Relapse is distressingly common after the first episode of psychosis, yet it is poorly understood and difficult to predict. Investigating changes in cognitive function preceding relapse may provide new insights into the underlying mechanism of relapse in psychosis. We hypothesized that relapse in fully remitted first-episode psychosis patients was preceded by working memory deterioration.
Visual memory and verbal working memory were monitored prospectively in a 1-year randomized controlled trial of remitted first-episode psychosis patients assigned to medication continuation (quetiapine 400 mg/day) or discontinuation (placebo). Relapse (recurrence of positive symptoms of psychosis), visual (Visual Patterns Test) and verbal (Letter–Number span test) working memory and stressful life events were assessed monthly.
Remitted first-episode patients (n = 102) participated in the study. Relapsers (n = 53) and non-relapsers (n = 49) had similar baseline demographic and clinical profiles. Logistic regression analyses indicated relapse was associated with visual working memory deterioration 2 months before relapse [odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19–7.92, P = 0.02], more stressful life events 1 month before relapse (OR 2.11, 95% CI 1.20–3.72, P = 0.01) and medication discontinuation (OR 5.52, 95% CI 2.08–14.62, P = 0.001).
Visual working memory deterioration beginning 2 months before relapse in remitted first-episode psychosis patients (not baseline predictor) may reflect early brain dysfunction that heralds a psychotic relapse. The deterioration was found to be unrelated to a worsening of psychotic symptoms preceding relapse. Testable predictors offer insight into the brain processes underlying relapse in psychosis.
Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.
Delusional disorder (DD) is thought to be distinct from schizophrenia (SZ). However, few systematic investigations have been conducted on DD because of the difficulty in ascertaining a representative sample size. Existing knowledge has been mostly generated from inpatient cohorts, which may be biased towards a more severe sample.
We compared the demographic, clinical and cognitive differences between 71 patients with first-episode DD and 71 age-matched patients with first-episode SZ. Participants were consecutively recruited from a population-based territory-wide study of early psychosis in Hong Kong targeting first-episode psychosis. Basic demographic information, premorbid functioning, duration of untreated psychosis, pathways to care, symptomatology, social, occupational, and cognitive functioning were comprehensively assessed using standardized measurements.
Patients with DD had less premorbid schizoid and schizotypal traits compared to patients with SZ. More patients with DD were married compared to patients with SZ. However, at first episode, there were no significant differences between the two groups in regards to the duration of untreated psychosis, pathways to care, symptom severity, neurocognitive performance, treatment, and functioning.
Our findings challenge previous thinking that patients with DD had better functioning than patients with SZ. This study not only provides an updated perspective into conceptualizing the clinical differences between DD and SZ, but also expands the descriptive account of the two disorders to include the neurocognitive dimension.
The rapid rise in syphilis cases has prompted a number of public health campaigns to assist men who have sex with men (MSM) recognize and present early with symptoms. This study aimed to investigate the temporal trend of the duration of self-report symptoms and titre of rapid plasma reagin (RPR) in MSM with infectious syphilis. Seven hundred and sixty-one syphilis cases in MSM diagnosed at the Melbourne Sexual Health Centre (MSHC) from 2007–2013 were reviewed. Median duration of symptoms and RPR titres in each year were calculated. The median durations of symptoms with primary and secondary syphilis were 9 [interquartile range (IQR) 6–14] days and 14 (IQR 7–30) days, respectively. The overall median titre of RPR in secondary syphilis (median 128, IQR 64–256) was higher than in primary syphilis (median 4, IQR 1–32) and in early latent syphilis (median 32, IQR 4–64). The median duration of symptoms for primary syphilis, secondary syphilis and titre of RPR level did not change over time. Public health campaigns were not associated with a significant shorter time from onset of symptoms to treatment. Alternative strategies such as more frequent testing of MSM should be promoted to control the syphilis epidemic in Australia.
Here we present a novel silicon nanopore planar patch clamp chip for single ion channel screening. We fabricate our devices using a combination of KOH and metal-assisted etching. Electrical characterization shows that the shunt capacitance and access resistance are within the accepted ranges for single channel recordings. In order to test our devices, we cultured and differentiated human neuroblastoma SH-SY5Y cells on chip. We reliably obtained a high resistance seal to the cell membrane and report single ion channel activity recordings.
The influence of the substrate temperature on the morphology and ordering of InGaAs quantum dots (QD), grown on GaAs (001) wafers by Molecular Beam Epitaxy (MBE) under As2 flux has been studied using Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and Photoluminescence (PL) measurements. The experimental results show that lateral and vertical orderings occur for temperatures greater than 520°C and that QDs self-organize in a 6-fold symmetry network on (001) surface for T=555°C. Vertical orderings of asymmetric QDs, along directions a few degrees off , are observed on a large scale and their formation is discussed.
Despite evidence on the short-term benefits of early intervention (EI) service for psychosis, long-term outcome studies are limited by inconsistent results. This study examined the 10-year outcomes of patients with first-episode psychosis who received 2-year territory-wide EI service compared to those who received standard care (SC) in Hong Kong using an historical control design.
Consecutive patients who received the EI service between 1 July 2001 and 30 June 2002, and with diagnosis of schizophrenia-spectrum disorders, were identified and matched with patients who received SC first presented to the public psychiatric service from 1 July 2000 to 30 June 2001. In total, 148 matched pairs of patients were identified. Cross-sectional information on symptomatology and functioning was obtained through semi-structured interview; longitudinal information on hospitalization, functioning, suicide attempts, mortality and relapse over 10 years was obtained from clinical database. There were 70.3% (N = 104) of SC and 74.3% (N = 110) of EI patients interviewed.
Results suggested that EI patients had reduced suicide rate (χ2(1) = 4.35, p = 0.037), fewer number [odds ratio (OR) 1.56, χ2 = 15.64, p < 0.0001] and shorter duration of hospitalization (OR 1.29, χ2 = 4.06, p = 0.04), longer employment periods (OR −0.28, χ2 = 14.64, p < 0.0001) and fewer suicide attempts (χ2 = 11.47, df = 1, p = 0.001) over 10 years. At 10 years, no difference was found in psychotic symptoms, symptomatic remission and functional recovery.
The short-term benefits of the EI service on number of hospitalizations and employment was sustained after service termination, but the differences narrowed down. This suggests the need to evaluate the optimal duration of the EI service.