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Barrett’s oesophagus (BE) is the precursor of oesophageal adenocarcinoma, which has become the most common type of oesophageal cancer in many Western populations. Existing evidence on diet and risk of BE predominantly comes from case–control studies, which are subject to recall bias in measurement of diet. We aimed to investigate the potential effect of diet, including macronutrients, carotenoids, food groups, specific food items, beverages and dietary scores, on risk of BE in over 20 000 participants of the Melbourne Collaborative Cohort Study. Diet at baseline (1990–1994) was measured using a food frequency questionnaire. The outcome was BE diagnosed between baseline and follow-up (2007–2010). Logistic regression models were used to estimate OR and 95 % CI for diet in relation to risk of BE. Intakes of leafy vegetables and fruit were inversely associated with risk of BE (highest v. lowest quartile: OR = 0·59; CI: 0·38, 0·94; P-trend = 0·02 and OR = 0·58; CI: 0·37, 0·93; P-trend = 0·02 respectively), as were dietary fibre and carotenoids. Stronger associations were observed for food than the nutrients found in them. Positive associations were observed for discretionary food (OR = 1·54; CI: 0·97, 2·44; P-trend = 0·04) and total fat intake (OR per 10 g/d = 1·11; CI: 1·00, 1·23), the association for fat was less robust in sensitivity analyses. No association was observed for meat, protein, dairy products or diet scores. Diet is a potential modifiable risk factor for BE. Public health and clinical guidelines that incorporate dietary recommendations could contribute to reduction in risk of BE and, thereby, oesophageal adenocarcinoma.
OBJECTIVES/GOALS: Recent research has attempted to identify diagnostic, prognostic, and predictive biomarkers, however, currently, no biomarkers can accurately diagnose GBC and predict patients prognosis. Using machine learning, we can utilize high-throughput RNA sequencing with clinicopathologic data to develop a predictive tool for GBC prognosis. METHODS/STUDY POPULATION: Current predictive models for GBC outcomes often utilize clinical data only. We aim to build a superior algorithm to predict overall survival in GBC patients with advanced disease, using machine learning approaches to prioritize biomarkers for GBC prognosis. We have identified over 80 fresh frozen GBC tissue samples from Rochester, Minnesota, Daegu, Korea, Vilnius, Lithuania, and Calgary, Canada. We will perform next-generation RNA sequencing on these tissue samples. The patients clinical, pathologic and survival data will be abstracted from the medical record. Random forests, support vector machines, and gradient boosting machines will be applied to train the data. Standard 5-fold cross validation will be used to assess performance of each ML algorithm. RESULTS/ANTICIPATED RESULTS: Our preliminary analysis of next generation RNA sequencing from 18 GBC tissue samples identified recurrent mutations in genes enriched in pathways in cytoskeletal signaling, cell organization, cell movement, extracellular matrix interaction, growth, and proliferation. The top three most significantly altered pathways, actin cytoskeleton signaling, hepatic fibrosis/hepatic stellate cell activation, and epithelial adherens junction signaling, emphasized a molecular metastatic and invasive fingerprint in our patient cohort. This molecular fingerprint is consistent with the previous knowledge of the highly metastatic nature of gallbladder tumors and is also manifested physiologically in the patient cohort. DISCUSSION/SIGNIFICANCE: Integrative analysis of molecular and clinical characterization of GBC has not been fully established, and minimal improvement has been made to the survival of these patients. If overall survival can be better predicted, we can gain a greater understanding of key biomarkers driving the tumor phenotype.
Relapse and recurrence of depression are common, contributing to the overall burden of depression globally. Accurate prediction of relapse or recurrence while patients are well would allow the identification of high-risk individuals and may effectively guide the allocation of interventions to prevent relapse and recurrence.
To review prognostic models developed to predict the risk of relapse, recurrence, sustained remission, or recovery in adults with remitted major depressive disorder.
We searched the Cochrane Library (current issue); Ovid MEDLINE (1946 onwards); Ovid Embase (1980 onwards); Ovid PsycINFO (1806 onwards); and Web of Science (1900 onwards) up to May 2021. We included development and external validation studies of multivariable prognostic models. We assessed risk of bias of included studies using the Prediction model risk of bias assessment tool (PROBAST).
We identified 12 eligible prognostic model studies (11 unique prognostic models): 8 model development-only studies, 3 model development and external validation studies and 1 external validation-only study. Multiple estimates of performance measures were not available and meta-analysis was therefore not necessary. Eleven out of the 12 included studies were assessed as being at high overall risk of bias and none examined clinical utility.
Due to high risk of bias of the included studies, poor predictive performance and limited external validation of the models identified, presently available clinical prediction models for relapse and recurrence of depression are not yet sufficiently developed for deploying in clinical settings. There is a need for improved prognosis research in this clinical area and future studies should conform to best practice methodological and reporting guidelines.
Mental illness amongst prison inmates is a prevailing issue across the world, as mental illnesses are overrepresented in correctional facilities when compared to community populations. Despite this, correctional officers receive little to no training on how to respond to inmates with mental illness. Implementing mental health training could improve officer knowledge, skills, and attitudes toward inmates with mental illness. This could lead to improvements in risk management, humane treatment of inmates, and interprofessional collaboration with healthcare providers. There is limited research on the educational value of inmate mental health training programs for correctional officers. As far as we are aware, there have been no prior reviews of this literature. The goal of the present study is to review this literature to explore the nature and effectiveness of correctional officer mental health training programs.
Medical and criminal justice databases were searched for scientific articles describing correctional officer mental health training programs. All studies that included a measurable outcome on either correctional officer knowledge or inmate mental health were included in a final analysis. The review adhered to PRISMA guidelines for systematic reviews.
Of 1492 articles identified using search terms, 11 were included in the analysis. 6 articles described mental health education programs, 2 articles described skill-specific programs, and 3 articles described suicide prevention programs. Training programs reviewed content about mental illness, practical skills, and included didactic and experiential teaching modalities. The programs led to improvements in knowledge, skills, and attitudes amongst officers. Prior mental health attitudes, knowledge, and work experience did not correlate with improvements following training. Officers were more receptive to program facilitators with correctional or lived mental health experience. Experiential teaching was preferred to didactic teaching. A decline in training improvements occurred several months after training.
There is limited but positive literature suggesting that structured training programs, particularly involving persons with lived experience and experiential components are beneficial. The decline in training improvements suggests need for ongoing education and systems change within correctional institutions to ensure sustainability of gains. In terms of limitations of this review, it is possible articles pertaining to correctional officer mental health training were not available on the databases searched or some programs may not be published. Studies were also limited in their outcome measurement, with no consistent tools, and no control groups. This review can guide the development, delivery, and contribute toward best practice guidelines for future inmate mental health training programs and studies.
The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.
To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).
Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.
A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994.
For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.
Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Rapid detection and isolation of coronavirus disease 2019 (COVID-19) patients is the only means of reducing hospital transmission. We describe the impact of implementation of on-site severe acute respiratory coronavirus virus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) testing on reducing turnaround time, isolation duration, pathology test ordering, and antibiotic use in patients who do not have COVID-19.
Across international contexts, people with serious mental illnesses (SMI) experience marked reductions in life expectancy at birth. The intersection of ethnicity and social deprivation on life expectancy in SMI is unclear. The aim of this study was to assess the impact of ethnicity and area-level deprivation on life expectancy at birth in SMI, defined as schizophrenia-spectrum disorders, bipolar disorders and depression, using data from London, UK.
Abridged life tables to calculate life expectancy at birth, in a cohort with clinician-ascribed ICD-10 schizophrenia-spectrum disorders, bipolar disorders or depression, managed in secondary mental healthcare. Life expectancy in the study population with SMI was compared with life expectancy in the general population and with those residing in the most deprived areas in England.
Irrespective of ethnicity, people with SMI experienced marked reductions in life expectancy at birth compared with the general population; from 14.5 years loss in men with schizophrenia-spectrum and bipolar disorders, to 13.2 years in women. Similar reductions were noted for people with depression. Across all diagnoses, life expectancy at birth in people with SMI was lower than the general population residing in the most deprived areas in England.
Irrespective of ethnicity, reductions in life expectancy at birth among people with SMI are worse than the general population residing in the most deprived areas in England. This trend in people with SMI is similar to groups who experience extreme social exclusion and marginalisation. Evidence-based interventions to tackle this mortality gap need to take this into account.
The General Medical Council has introduced a generic professional capabilities framework. It includes the need to develop the professional values, actions and aspirations fundamental to becoming a ‘dedicated doctor’. The history of psychiatry has potential to facilitate this learning, both by an understanding of content and the ability to think historically.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.