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Individuals at Ultra High Risk (UHR) for psychosis typically present with attenuated psychotic symptoms. However it is difficult to predict which individuals will later develop frank psychosis when their mental state is rated in terms of individual symptoms.
The objective of the study was to examine the phenomenological structure of the UHR mental state and identify symptom profiles that predict later transition to psychosis.
Psychopathological data from a large sample of UHR subjects were analysed using latent class cluster analysis.
A total of 318 individuals with a UHR for psychosis. Data were collected from two specialised community mental health services for people at UHR for psychosis: OASIS in London and PACE, in Melbourne.
Latent class cluster analysis produced 4 classes: Class 1 - Mild was characterized by lower scores on all the CAARMS items. Subjects in Class 2 - Moderate scored moderately on all CAARMS items and was more likely to be in employment. Those in Class 3 - Moderate-Severe scored moderately-severe on negative symptoms, social isolation and impaired role functioning. Class 4 - Severe was the smallest group and was associated with the most impairment: subjects in this class scored highest on all items of the CAARMS, had the lowest GAF score and were more likely to be unemployed. This group was also characterized by the highest transition rate (41%).
Different constellations of symptomatology are associates with varying levels of risk to of transition to psychosis.
Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
Protocols for conducting in situ transmission electron microscopy (TEM) reactions using an environmental TEM with dry gases have been well established. However, many important reactions that are relevant to catalysis or high-temperature oxidation occur at atmospheric pressure and are influenced by the presence of water vapor. These experiments necessitate using a closed-cell gas reaction TEM holder. We have developed protocols for introducing and controlling water vapor concentrations in experimental gases from 2% at a full atmosphere to 100% at ~17 Torr, while measuring the gas composition using a residual gas analyzer (RGA) on the return side of the in situ gas reactor holder. Initially, as a model system, cube-shaped MgO crystals were used to help develop the protocols for handling the water vapor injection process and confirming that we could successfully inject water vapor into the gas cell. The interaction of water vapor with MgO triggered surface morphological and chemical changes as a result of the formation of Mg(OH)2, later validated with mass spectra obtained with our RGA system with and without water vapor. Integrating an RGA with an in situ scanning/TEM closed-cell gas reaction system can thus provide critical measurements correlating gas composition with dynamic surface restructuring of materials during reactions.
Adverse developmental outcomes for some children following institutional care are well established. Removal from institutional care and placement into families can promote recovery. However, little is known about how positive outcomes are sustained across adolescence among children with histories of severe deprivation. The present study examined the caregiving conditions that are associated with attaining and maintaining competent functioning (i.e., outcomes within typical levels) from middle childhood to adolescence following exposure to early institutional care. The participants included children with and without a history of institutional care who had competence assessed at ages 8, 12, and 16 years across seven domains: family relationships, peer relationships, academic performance, physical health, mental health, substance use (ages 12 and 16 years only), and risk-taking behavior. The participants were grouped based on whether they were always versus not always competent and never versus ever competent at ages 8 through 16 years. Adolescents with a history of institutional care were less likely to be consistently competent than those who were family reared. Among those who were exposed to early institutional rearing, maintaining competent functioning from 8 to 16 years was associated with spending less time in institutions and receiving higher-quality caregiving early in life. Ensuring high quality early caregiving may promote competent functioning following early deprivation.
Self-monitoring biases and overconfidence in incorrect judgments have been suggested as playing a role in schizophrenia spectrum disorders. Little is known about whether self-monitoring biases may contribute to early risk factors for psychosis. In this study, action self-monitoring (i.e., discrimination between imagined and performed actions) was investigated, along with confidence in judgments among ultra-high risk (UHR) for psychosis individuals and first-episode psychosis (FEP) patients.
Thirty-six UHR for psychosis individuals, 25 FEP patients and 33 healthy controls (CON) participated in the study. Participants were assessed with the Action memory task. Simple actions were presented to participants verbally or non-verbally. Some actions were required to be physically performed and others were imagined. Participants were asked whether the action was presented verbally or non-verbally (action presentation type discrimination), and whether the action was performed or imagined (self-monitoring). Confidence self-ratings related to self-monitoring responses were obtained.
The analysis of self-monitoring revealed that both UHR and FEP groups misattributed imagined actions as being performed (i.e., self-monitoring errors) significantly more often than the CON group. There were no differences regarding performed actions as being imagined. UHR and FEP groups made their false responses with higher confidence in their judgments than the CON group. There were no group differences regarding discrimination between the types of actions presented (verbal vs non-verbal).
A specific type of self-monitoring bias (i.e., misattributing imagined actions with performed actions), accompanied by high confidence in this judgment, may be a risk factor for the subsequent development of a psychotic disorder.
Language and communication are fundamental to the human experience, and, traditionally, spoken language is studied as an isolated skill. However, before propositional language (i.e., spontaneous, voluntary, novel speech) can be produced, propositional content or ‘ideas’ must be formulated.
This review highlights the role of broader cognitive processes, particularly ‘executive attention’, in the formulation of propositional content (i.e., ‘ideas’) for propositional language production.
Several key lines of evidence converge to suggest that the formulation of ideas for propositional language production draws on executive attentional processes. Larger-scale clinical research has demonstrated a link between attentional processes and language, while detailed case studies of neurological patients have elucidated specific idea formulation mechanisms relating to the generation, selection and sequencing of ideas for expression. Furthermore, executive attentional processes have been implicated in the generation of ideas for propositional language production. Finally, neuroimaging studies suggest that a widely distributed network of brain regions, including parts of the prefrontal and parietal cortices, supports propositional language production.
Theoretically driven experimental research studies investigating mechanisms involved in the formulation of ideas are lacking. We suggest that novel experimental approaches are needed to define the contribution of executive attentional processes to idea formulation, from which comprehensive models of spoken language production can be developed. Clinically, propositional language impairments should be considered in the context of broader executive attentional deficits.
Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease.
A literature search was performed using the keywords ‘nasopharyngeal neoplasm’, ‘cetuximab’ and ‘Erbitux’.
Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting.
There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Using quantitative and qualitative data from a large national sample of lawyers, we examine self-reports of perceived discrimination in the legal workplace. Across three waves of surveys, we find that persons of color, white women, and LGBTQ attorneys are far more likely to perceive they have been a target of discrimination than white men. These differences hold in multivariate models that control for social background, status in the profession and the work organization, and characteristics of the work organization. Qualitative comments describing these experiences reveal that lawyers of different races, genders, and sexual orientations are exposed to distinctive types of bias, that supervisors and clients are the most frequent sources of discriminatory treatment, and the often-overt character of perceived discrimination. These self-reports suggest that bias in the legal workplace is widespread and rooted in the same hierarchies of race, gender, and sexual orientation that pervade society.
The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case–control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014–February 2016. Case-patients were defined as children aged 1–5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P < 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18–17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.
To assess the extent of error present in self-reported weight data in the Women’s Health Initiative, variables that may be associated with error, and to develop methods to reduce any identified error.
Prospective cohort study.
Forty clinical centres in the USA.
Women (n 75 336) participating in the Women’s Health Initiative Observational Study (WHI-OS) and women (n 6236) participating in the WHI Long Life Study (LLS) with self-reported and measured weight collected about 20 years later (2013–2014).
The correlation between self-reported and measured weights was 0·97. On average, women under-reported their weight by about 2 lb (0·91 kg). The discrepancies varied by age, race/ethnicity, education and BMI. Compared with normal-weight women, underweight women over-reported their weight by 3·86 lb (1·75 kg) and obese women under-reported their weight by 4·18 lb (1·90 kg) on average. The higher the degree of excess weight, the greater the under-reporting of weight. Adjusting self-reported weight for an individual’s age, race/ethnicity and education yielded an identical average weight to that measured.
Correlations between self-reported and measured weights in the WHI are high. Discrepancies varied by different sociodemographic characteristics, especially an individual’s BMI. Correction of self-reported weight for individual characteristics could improve the accuracy of assessment of obesity status in postmenopausal women.
To evaluate whole-genome sequencing (WGS) as a molecular typing tool for MRSA outbreak investigation.
Investigation of MRSA colonization/infection in a neonatal intensive care unit (NICU) over 3 years (2014–2017).
Single-center level IV NICU.
NICU infants and healthcare workers (HCWs).
Infants were screened for MRSA using a swab of the anterior nares, axilla, and groin, initially by targeted (ring) screening, and later by universal weekly screening. Clinical cultures were collected as indicated. HCWs were screened once using swabs of the anterior nares. MRSA isolates were typed using WGS with core-genome multilocus sequence typing (cgMLST) analysis and by pulsed-field gel electrophoresis (PFGE). Colonized and infected infants and HCWs were decolonized. Control strategies included reinforcement of hand hygiene, use of contact precautions, cohorting, enhanced environmental cleaning, and remodeling of the NICU.
We identified 64 MRSA-positive infants: 53 (83%) by screening and 11 (17%) by clinical cultures. Of 85 screened HCWs, 5 (6%) were MRSA positive. WGS of MRSA isolates identified 2 large clusters (WGS groups 1 and 2), 1 small cluster (WGS group 3), and 8 unrelated isolates. PFGE failed to distinguish WGS group 2 and 3 isolates. WGS groups 1 and 2 were codistributed over time. HCW MRSA isolates were primarily in WGS group 1. New infant MRSA cases declined after implementation of the control interventions.
We identified 2 contemporaneous MRSA outbreaks alongside sporadic cases in a NICU. WGS was used to determine strain relatedness at a higher resolution than PFGE and was useful in guiding efforts to control MRSA transmission.
Post-translocation monitoring is fundamental for assessing translocation success and identifying potential threats. We measured outcomes for four cohorts of tuatara Sphenodon punctatus translocated to warmer climates outside of their ecological region, to understand effects of climate warming. Translocation sites were on average 2–4 °C warmer than the source site. We used three short-term measures of success: survival, growth and reproduction. Data on recaptures, morphometric measurements, and reproduction were gathered over 2.5 years following release. Although decades of monitoring will be required to determine long-term translocation success in this species, we provide an interim measure of population progress and translocation site suitability. We found favourable recapture numbers, growth of founders and evidence of reproduction at most sites, with greater increases in body mass observed at warmer, less densely populated sites. Variable growth in the adult population at one translocation site suggested that higher population density, intraspecific competition, and lower water availability could be responsible for substantial weight loss in multiple individuals, and we make management recommendations to reduce population density. Overall, we found that sites with warmer climates and lower population densities were potentially beneficial to translocated tuatara, probably because of enhanced temperature-dependent and density-dependent growth rates. We conclude that tuatara could benefit from translocations to warmer sites in the short term, but further monitoring of this long-lived species is required to determine longer-term population viability following translocation. Future vulnerability to rising air temperatures, associated water availability, and community and ecosystem changes beyond the scope of this study must be considered.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
Depression and post-traumatic stress disorder (PTSD) are significant risks for suicide and other adverse events among US military personnel, but prevalence data among ship-assigned personnel at the onset of deployment are unknown.
To determine the prevalence of shipboard personnel who screen positive for PTSD and/or major depressive disorder (MDD) at the onset of deployment, and also those who reported these diagnoses made by a physician or healthcare professional in the year prior to deployment.
Active-duty ship-assigned personnel (N = 2078) completed anonymous assessments at the beginning of deployment. Depression was measured using the Center for Epidemiologic Studies Depression Scale (CES-D; score of ≥22), and PTSD was assessed using the PTSD Checklist–Civilian Version (PCL-C; both score and symptom criteria were used).
In total, 7.3% (n = 151 of 2076) screened positive for PTSD and 22% (n = 461 of 2078) for MDD at deployment onset. Only 6% and 15% of those who screened positive for PTSD or MDD, respectively, had been diagnosed by a healthcare professional in the past year.
Missed opportunities for mental healthcare among screen-positive shipboard personnel reduce the benefits associated with early identification and linkage to care. Improved methods of mental health screening that promote early recognition and referral to care may mitigate psychiatric events in theatre.
We provide a qualitative analysis of a system of nonlinear differential equations that model the spread of alcoholism through a population. Alcoholism is viewed as an infectious disease and the model treats it within a sir framework. The model exhibits two generic types of steady-state diagram. The first of these is qualitatively the same as the steady-state diagram in the standard sir model. The second exhibits a backwards transcritical bifurcation. As a consequence of this, there is a region of bistability in which a population of problem drinkers can be sustained, even when the reproduction number is less than one. We obtain a succinct formula for this scenario when the transition between these two cases occurs.