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When characterizing beam-sensitive materials in the scanning transmission electron microscope (STEM), low-dose techniques are essential for the reliable observation of samples in their true state. A simple route to minimize both the total electron-dose and the dose-rate is to reduce the electron beam-current and/or raster the probe at higher speeds. At the limit of these settings, and with current detectors, the resulting images suffer from unacceptable artifacts, including signal-streaking, detector-afterglow, and poor signal-to-noise ratios (SNRs). In this article, we present an alternative approach to capture dark-field STEM images by pulse-counting individual electrons as they are scattered to the annular dark-field (ADF) detector. Digital images formed in this way are immune from analog artifacts of streaking or afterglow and allow clean, high-SNR images to be obtained even at low beam-currents. We present results from both a ThermoFisher FEI Titan G2 operated at 300 kV and a Nion UltraSTEM200 operated at 200 kV, and compare the images to conventional analog recordings. ADF data are compared with analog counterparts for each instrument, a digital detector-response scan is performed on the Titan, and the overall rastering efficiency is evaluated for various scanning parameters.
Background: Accurate identification of Clostridioides difficile infections (CDIs) from electronic data sources is important for surveillance. We evaluated how frequently laboratory findings were supported by diagnostic coding and treatment data in the electronic health record. Methods: We analyzed a retrospective cohort of patients in the Veterans’ Affairs Health System from 2006 through 2016. A CDI event was defined as a positive laboratory test for C. difficile toxin or toxin genes in the inpatient, outpatient, or long-term care setting with no prior positive test in the preceding 14 days. Events were classified as incident (no CDI in the prior 56 days), or recurrent (CDI in the prior 56 days) and were evaluated for evidence of clinical diagnosis based on International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10-CM codes and at least 1 dose of an anti-CDI agent (intravenous or oral metronidazole, fidaxomicin, or oral vancomycin). We further assessed the possibility of treatment without testing by quantifying positive laboratory tests and diagnostic codes among inpatients receiving an anti-CDI agent. A course of anti-CDI therapy was defined as continuous treatment with the same drug. Results: Among 119,063 incident and recurrent CDI events, 70,114 (58.9%) had a diagnosis code and 15,850 (13.3%) had no accompanying treatment. The proportion of patients with ICD codes was highest among patients treated with fidaxomicin (82.6% of 906) or oral vancomycin (74.3% of 30,777) and was lower among patients receiving metronidazole (63.3% of 103,231) and those without treatment (29.9% of 15,850). The proportion of events with ICD codes and treatment was similar between incident and recurrent episodes. During the study period, there were ~470,000 inpatient courses of metronidazole, fidaxomicin, and oral vancomycin. Table 1 shows the presence of ICD codes and positive laboratory tests by anti-CDI agents. Among 51,100 courses of oral vancomycin, 51% had an ICD code and 44% had a positive test for C. difficile within 7 days of treatment initiation. Among 1,013 courses of fidaxomicin, 79% had an ICD code and 56% had a positive laboratory test. Conclusions: In this large cohort, there was evidence of substantial CDI treatment without confirmatory C. difficile testing and, to a lesser extent, some positive tests without accompanying treatment or coding. A combination of data sources may be needed to more accurately identify CDI from electronic health records for surveillance purposes.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis.
Subjects and methods
We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points.
Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up.
The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results.
It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.
Increasing evidence suggests psychosis may be more meaningfully viewed in dimensional terms rather than as discrete categorical states and that specific symptom clusters may be identified. If so, particular risk factors and premorbid factors may predict these symptom clusters.
(i) To explore, using principal component analysis, whether specific factors for psychotic symptoms can be isolated. (ii) To establish the predictors of the different symptom factors using multiple regression techniques.
One hundred and eighty-nine inpatients with psychotic illness were recruited and information on family history, premorbid factors and current symptoms obtained from them and their mothers.
Seven distinct symptom components were identified. Regression analysis failed to identify any developmental predictors of depression or mania. Delusions/hallucinations were predicted by a family history of schizophrenia and by poor school functioning in spite of normal premorbid IQ (F = 6.5; P < 0.001); negative symptoms by early onset of illness, developmental delay and a family history of psychosis (F = 4.1; P = 0.04). Interestingly disorganisation was predicted by the combination of family history of bipolar disorder and low premorbid IQ (F = 4.9; P = 0.003), and paranoia by obstetric complications (OCs) and poor school functioning (F = 4.2; P = 0.01).
Delusions and hallucinations, negative symptoms and paranoia all appeared to have a developmental origin though they were associated with different childhood problems. On the other hand, neither mania nor depression was associated with childhood dysfunction. Our most striking finding was that disorganisation appeared to arise when a familial predisposition to mania was compounded by low premorbid IQ.
Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT.
Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial.
Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before.
Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.
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.
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.
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.
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.
Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.
We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).
After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21–34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22–1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47–69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18–1.82).
About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.
One of the founding concepts of the high-entropy alloy (HEA) field was that the lattice structures of multicomponent solid solution phases are highly distorted. The displacement of the constituent atoms, away from their ideal locations (local lattice strain), has been widely cited as the reason for a number of the observed physical and mechanical properties. However, very little data directly characterizing these lattice distortions exist and, thus, the validity of this hypothesis remains an open question. Here, the concept is reviewed by considering the underlying principles of the lattice distortions, the suitability of different assessment methods, and the direct experimental data currently available. It is found that, at present, there is no clear evidence that the lattice distortions in HEAs are significantly greater than those of conventional alloys. However, so few alloys have been appropriately characterized that this conclusion cannot be considered overarching and further research is required.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.