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To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Design:
Prospective observational study.
Setting:
Neonatal intensive care unit (NICU).
Methods:
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
Results:
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
Conclusions:
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
We present the most sensitive and detailed view of the neutral hydrogen (
${\rm H\small I}$
) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal
${\rm H\small I}$
in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K (
$1.6\,\mathrm{mJy\ beam}^{-1}$
)
$\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$
spectral channel with an angular resolution of
$30^{\prime\prime}$
(
${\sim}10\,\mathrm{pc}$
). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire
${\sim}25\,\mathrm{deg}^2$
field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes
${\rm H\small I}$
test observations.
Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Methods
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
Results
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Conclusions
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.
Methods
We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case−control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.
Results
Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91–1.59) for any discrimination and 1.79 (95% CI 1.19–1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12–2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65–3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).
Conclusions
Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
In this chapter the major conservation issues bears face is reviewed and management actions that can address these conservation issues are highlighted. The future of bears across the world is bright for some species but dark for others. In some areas such as North America and in parts of Europe and Asia, bear populations have increased and stabilized because of increased management effort and increasing support for bears and their needs by the humans who share habitat with them. However, for most bear species, the future is uncertain. Andean bears continue to be threatened by habitat loss and human encroachment. In much of Asia outside Japan, Asiatic black bear, sloth bear, and sun bear populations are increasingly threatened by unmanaged excessive mortality combined with habitat loss to timber harvest, plantation agriculture, and human encroachment. The long-term future for polar bears is threatened by the unmanageable threat of climate change. Giant pandas are fragmented into small populations despite intense conservation efforts. Improving public and political support for bears is the most important need if we are to realize successful bear conservation and management.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
Methods
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
Results
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Conclusions
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
Objective
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
Aim
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
Methods
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
Results
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Conclusions
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
We sought to explore whether obstetric complications (OCs) are more likely to occur in the presence of familial/genetic susceptibility for schizophrenia or whether they themselves represent an independent environmental risk factor for schizophrenia.
Methods
The presence of OCs was assessed through maternal interview on 216 subjects, comprising 36 patients with schizophrenia from multiply affected families, 38 of their unaffected siblings, 31 schizophrenic patients with no family history of psychosis, 51 of their unaffected siblings and 60 normal comparison subjects. We examined the familiality of OCs and whether OCs were commoner in the patient and sibling groups than in the control group.
Results
OCs tended to cluster within families, especially in multiply affected families. Patients with schizophrenia, especially those from multiply affected families, had a significantly higher rate of OCs compared to normal comparison subjects, but there was no evidence for an elevated rate of OCs in unaffected siblings.
Conclusion
Our data provides little evidence for a link between OCs and genetic susceptibility to schizophrenia. If high rates of OCs are related to schizophrenia genes, this relationship is weak and will only be detected by very large sample sizes.
P300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Method:
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
Results:
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Conclusion:
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.
The increased prevalence of metabolic syndrome in people with severe mental illness (SMI) is well documented. The International Diabetes Federation (IDF) criteria for metabolic syndrome are three or more of the following: waist circumference ( 80 cm (females), (94 cm (males) OR BMI (30, triglycerides >1.7 mmol/l or on treatment, raised blood pressure (systolic >130 mg Hg or diastolic >85 mm Hg, OR on treatment for hypertension), raised fasting blood glucose (.5.6 mmol/l) OR diagnosed type II diabetes) and reduced HDL cholesterol (< 1.03 mmol/l) OR on treatment.
The IMPACT RCT is a Department of Health funded trial of a health promotion intervention (HPI) delivered by care co-ordinators to people with SMI across South London, Kent and Sussex. The intervention is focussed on improving health by addressing modifiable lifestyle factors such as diet, physical activity, obesity, cigarette smoking, alcohol and substance use.
Objectives/aims
We investigated the prevalence of metabolic syndrome in a sample of 212 patients for whom we had relevant baseline measures.
Methods
Data (weight, BMI, waist circumference, blood pressure, fasting HDL cholesterol, triglycerides and glucose levels) were analysed on 212 patients.
Results
45% of the sample met IDF criteria for metabolic syndrome. Mean BMI was 30.6, glucose 6.4 mmol/L, triglycerides 2.0 mmol/L, HDL 1.2 (mmol/L), waist circumference 105.8 cm, and BP 122/82 mm Hg.
Conclusions
Metabolic syndrome was highly prevalent in this sample, significantly increasing the risk of physical morbidity and potentially lowering life expectancy. There is an unmet need for health promotion interventions in order to lower morbidity and mortality risk in these populations.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
Method
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
Results
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Conclusions
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
There is a need for accurate and efficient assessment tools that cover a range of mental health and psychosocial problems. Existing, lengthy self-report assessments may reduce accuracy due to respondent fatigue. Using data from a sample of adults enrolled in a psychotherapy randomized trial in Thailand and a cross-sectional sample of adolescents in Zambia, we leveraged Item Response Theory (IRT) methods to create brief, psychometrically sound, mental health measures.
Methods
We used graded-response models to refine scales by identifying and removing poor performing items that were not well correlated with the underlying trait, and by identifying well-performing items at varying levels of a latent trait to assist in screening or monitoring purposes.
Results
In Thailand, the original 17-item depression scale was shortened to seven items and the 30-item Posttraumatic Stress Scale (PTS) was shortened to 10. In Zambia, the Child Posttraumatic Stress Scale (CPSS) was shortened from 17 items to six. Shortened scales in both settings retained the strength of their psychometric properties. When examining longitudinal intervention effects in Thailand, effect sizes were comparable in magnitude for the shortened and standard versions.
Conclusions
Using Item Response Theory (IRT) we created shortened valid measures that can be used to help guide clinical decisions and function as longitudinal research tools. The results of this analysis demonstrate the reliability and validity of shortened scales in each of the two settings and an approach that can be generalized more broadly to help improve screening, monitoring, and evaluation of mental health and psychosocial programs globally.
Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA.
Methods
We conducted a scoping review (Medline and EMBASE, 2000–2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters.
Results
Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters.
Conclusions
This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.