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A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.
Aims
To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.
Method
We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model.
Results
We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723–0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism.
Conclusions
We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.
The Porters Creek Formation is mined as an absorbent clay in Illinois, Mississippi, Missouri, and Tennessee. The absorptive properties of the Porters Creek Formation are due to the high content of smectite which constitutes >50% of the minerals present. Analyses of 220 samples of the Porters Creek collected in Illinois, Missouri, and Tennessee indicate that the smectite content is highest on the western side of the Mississippi embayment and that the kaolinite content is highest on the northeastern side. The major influx of detritral clays appears to have entered the embayment from a large river on the northeast side. A major control of the distribution of clay minerals during the time of Porters Creek deposition was differential flocculation of kaolinite, illite, and smectite, as evidenced by the numerous syneresis cracks on bedding planes in the area of greatest kaolinite content. Estimates of the smectite, illite, and kaolinite contents suggest both horizontal and vertical variations among these clay minerals. In certain localities the oxidation of pyrite has created acid conditions, which apparently were conducive to the formation of authigenic halloysite.
Edited by
Richard Williams, University of South Wales,Verity Kemp, Independent Health Emergency Planning Consultant,Keith Porter, University of Birmingham,Tim Healing, Worshipful Society of Apothecaries of London,John Drury, University of Sussex
This chapter explores the moral dimensions of work in emergency and pre-hospital medicine, with an emphasis on protecting the workforce and maintaining optimal functioning of teams. It explores the concepts of moral distress and moral injury from the literature and as they apply to emergency and pre-hospital medicine, but also in the light of the COVID-19 pandemic. It includes reference to the experience of one helicopter emergency medical service (HEMS) organisation attempting to make changes to its culture.
The eastern Great Lakes Late Quaternary timescale is based on older thermoluminescence dates and on uncalibrated radiocarbon dates from extensive sections along the north shores of Lakes Erie and Ontario. New optically stimulated luminescence dates from Late Quaternary delta sediments from the north shores of Lake Erie at Sand Hills Park give consistent ages of 23.5 to 20.5 ka. This is 4 to 7 ka older than previously assigned based on lithologic correlation with 16.5 ka calibrated radiocarbon dated sediments 5 km to the west at Vanderven. On the existing eastern Great Lakes stratigraphy, it puts deposition of these Sand Hills Park sediments in the Erie interstadial and not in the fluctuating postglacial glacial retreat of the Mackinaw phase to which the Vanderven sediments belong. The Sand Hills delta and underlying diamicts must have been overridden by the Porty Bruce advance at 18 ka. IntCal20 calibration of existing radiocarbon ages suggests that the physical stratigraphic relations of the various Wisconsin units are accurate and that the existing timescale is simply too young.
The chapter describes the main nature conservation challenges in Ireland, its main policy responses and actions, and their achievements and lessons, primarily over the last 40 years. This covers the country’s natural characteristics, habitats and species of particular importance; the status of nature and main pressures affecting it; nature conservation policies (including biodiversity strategies), legislation, governance and key actors; species measures; protected areas and networks; general conservation measures (e.g. development planning, species-rich grasslands and agri-environment schemes, and peatland management and restoration); nature conservation costs, economic benefits and funding sources; and biodiversity monitoring. Likely future developments are also identified. Conclusions are drawn on what measures have been most effective and why, and what is needed to improve the implementation of existing measures and achieve future nature conservation goals.
Risk of suicide-related behaviors is elevated among military personnel transitioning to civilian life. An earlier report showed that high-risk U.S. Army soldiers could be identified shortly before this transition with a machine learning model that included predictors from administrative systems, self-report surveys, and geospatial data. Based on this result, a Veterans Affairs and Army initiative was launched to evaluate a suicide-prevention intervention for high-risk transitioning soldiers. To make targeting practical, though, a streamlined model and risk calculator were needed that used only a short series of self-report survey questions.
Methods
We revised the original model in a sample of n = 8335 observations from the Study to Assess Risk and Resilience in Servicemembers-Longitudinal Study (STARRS-LS) who participated in one of three Army STARRS 2011–2014 baseline surveys while in service and in one or more subsequent panel surveys (LS1: 2016–2018, LS2: 2018–2019) after leaving service. We trained ensemble machine learning models with constrained numbers of item-level survey predictors in a 70% training sample. The outcome was self-reported post-transition suicide attempts (SA). The models were validated in the 30% test sample.
Results
Twelve-month post-transition SA prevalence was 1.0% (s.e. = 0.1). The best constrained model, with only 17 predictors, had a test sample ROC-AUC of 0.85 (s.e. = 0.03). The 10–30% of respondents with the highest predicted risk included 44.9–92.5% of 12-month SAs.
Conclusions
An accurate SA risk calculator based on a short self-report survey can target transitioning soldiers shortly before leaving service for intervention to prevent post-transition SA.
This study uses luminescence and 14C accelerator mass spectrometry procedures to date relevant glaciofluvial and glacial deposits from the south-central and southeastern Pyrenees (Andorra–France–Spain). We distinguish two types of end-moraine complexes: (1) those in which at least a far-flung moraine exists beyond a frequently nested end-moraine complex (the most common) and (2) those in which a close-nested end moraine encompasses at least two glacial cycles. Both types formed within six distinctive glacial intervals: (1) A penultimate glacial cycle during Marine Oxygen Isotope Stage (MIS) 6 and older glaciofluvial terraces occurred beyond the range of the luminescence dating method. (2) An early glacial advance in MIS 5d (~97 −15/+19 ka) was followed by glacial retreat during MIS 5c (< 91 ± 9 ka). (3) The last maximum ice extent (LMIE) was in early MIS 4 (~74 ± 4.5 ka). (4) Unexpectedly, glaciers thinned during the second half of MIS 3 (~39 −6/+11 ka). (5) During the MIS 3–2 transition, glaciers subsequently fluctuated behind the LMIE limits. (6) The global last glacial maximum (LGM) started as early as ~26.6 ± 0.365 ka b2k, and the corresponding end moraines were built behind the LMIE limits or merged with it, forming close-nested moraines.
Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.
Methods
The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.
Results
Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.
Discussion
Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.
Lake settlements, particularly crannogs, pose several contradictions—visible yet inaccessible, widespread yet geographically restricted, persistent yet vulnerable. To further our understanding, we developed the integrated use of palaeolimnological (scanning XRF, pollen, spores, diatoms, chironomids, Cladocera, microcharcoal, biogenic silica, SEM-EDS, stable-isotopes) and biomolecular (faecal stanols, bile acids, sedaDNA) analyses of crannog cores in south-west Scotland and Ireland. Both can be effective methods sets for revealing occupation chronologies and identifying on-crannog activities and practices. Strong results from sedaDNA and lipid biomarker analyses demonstrate probable on-site animal slaughter, food storage and possible feasting, suggesting multi-period, elite site associations, and the storage and protection of valuable resources.
Major depressive disorder (MDD) was previously associated with negative affective biases. Evidence from larger population-based studies, however, is lacking, including whether biases normalise with remission. We investigated associations between affective bias measures and depressive symptom severity across a large community-based sample, followed by examining differences between remitted individuals and controls.
Methods
Participants from Generation Scotland (N = 1109) completed the: (i) Bristol Emotion Recognition Task (BERT), (ii) Face Affective Go/No-go (FAGN), and (iii) Cambridge Gambling Task (CGT). Individuals were classified as MDD-current (n = 43), MDD-remitted (n = 282), or controls (n = 784). Analyses included using affective bias summary measures (primary analyses), followed by detailed emotion/condition analyses of BERT and FAGN (secondary analyses).
Results
For summary measures, the only significant finding was an association between greater symptoms and lower risk adjustment for CGT across the sample (individuals with greater symptoms were less likely to bet more, despite increasingly favourable conditions). This was no longer significant when controlling for non-affective cognition. No differences were found for remitted-MDD v. controls. Detailed analysis of BERT and FAGN indicated subtle negative biases across multiple measures of affective cognition with increasing symptom severity, that were independent of non-effective cognition [e.g. greater tendency to rate faces as angry (BERT), and lower accuracy for happy/neutral conditions (FAGN)]. Results for remitted-MDD were inconsistent.
Conclusions
This suggests the presence of subtle negative affective biases at the level of emotion/condition in association with depressive symptoms across the sample, over and above those accounted for by non-affective cognition, with no evidence for affective biases in remitted individuals.
Prenatal glucocorticoid overexposure causes adult metabolic dysfunction in several species but its effects on adult mitochondrial function remain largely unknown. Using respirometry, this study examined mitochondrial substrate metabolism of fetal and adult ovine biceps femoris (BF) and semitendinosus (ST) muscles after cortisol infusion before birth. Physiological increases in fetal cortisol concentrations pre-term induced muscle- and substrate-specific changes in mitochondrial oxidative phosphorylation capacity in adulthood. These changes were accompanied by muscle-specific alterations in protein content, fibre composition and abundance of the mitochondrial electron transfer system (ETS) complexes. In adult ST, respiration using palmitoyl-carnitine and malate was increased after fetal cortisol treatment but not with other substrate combinations. There were also significant increases in protein content and reductions in the abundance of all four ETS complexes, but not ATP synthase, in the ST of adults receiving cortisol prenatally. In adult BF, intrauterine cortisol treatment had no effect on protein content, respiratory rates, ETS complex abundances or ATP synthase. Activity of citrate synthase, a marker of mitochondrial content, was unaffected by intrauterine treatment in both adult muscles. In the ST but not BF, respiratory rates using all substrate combinations were significantly lower in the adults than fetuses, predominantly in the saline-infused controls. The ontogenic and cortisol-induced changes in mitochondrial function were, therefore, more pronounced in the ST than BF muscle. Collectively, the results show that fetal cortisol overexposure programmes mitochondrial substrate metabolism in specific adult muscles with potential consequences for adult metabolism and energetics.
The transition from military service to civilian life is a high-risk period for suicide attempts (SAs). Although stressful life events (SLEs) faced by transitioning soldiers are thought to be implicated, systematic prospective evidence is lacking.
Methods
Participants in the Army Study to Assess Risk and Resilience in Servicemembers (STARRS) completed baseline self-report surveys while on active duty in 2011–2014. Two self-report follow-up Longitudinal Surveys (LS1: 2016–2018; LS2: 2018–2019) were subsequently administered to probability subsamples of these baseline respondents. As detailed in a previous report, a SA risk index based on survey, administrative, and geospatial data collected before separation/deactivation identified 15% of the LS respondents who had separated/deactivated as being high-risk for self-reported post-separation/deactivation SAs. The current report presents an investigation of the extent to which self-reported SLEs occurring in the 12 months before each LS survey might have mediated/modified the association between this SA risk index and post-separation/deactivation SAs.
Results
The 15% of respondents identified as high-risk had a significantly elevated prevalence of some post-separation/deactivation SLEs. In addition, the associations of some SLEs with SAs were significantly stronger among predicted high-risk than lower-risk respondents. Demographic rate decomposition showed that 59.5% (s.e. = 10.2) of the overall association between the predicted high-risk index and subsequent SAs was linked to these SLEs.
Conclusions
It might be possible to prevent a substantial proportion of post-separation/deactivation SAs by providing high-risk soldiers with targeted preventive interventions for exposure/vulnerability to commonly occurring SLEs.
The aim of this review was to examine: (1) the ability of cholecystokinin (CCK) or analogues of CCK to influence satiation and changes in body weight generally and (2) the efficacy of CCK in influencing satiation and eating behaviour specifically at physiological levels of dosing. A systematic review of the literature was performed following the PRISMA 2020 guidelines in five electronic databases investigating the effect of exogenous CCK or analogues on satiation and body weight. A meta-analysis of studies that infused CCK and measured satiation via changes in food/energy intake was also conducted. A total of 1054 studies were found using the search terms which were reduced to fifteen studies suitable for inclusion. Of the twelve studies measuring the effect on the weight of food ingested or energy intake, eleven showed a decrease. An analogue of CCK which can be administered orally failed to produce any weight loss at 24 weeks. The meta-analysis found the effect of CCK on satiation dosed at physiological levels was significant with a standardised mean difference of 0·57 (95 % CI 0·30, 0·85, P < 0·0001). By comparison, CCK dosed at higher, pharmacological levels also had a significant effect with a standardised mean difference of 0·91 (95 % CI 0·46, 1·36, P < 0·0001). Eight of the ten studies in the meta-analysis combined CCK infusion with some means to facilitate stomach distension. The present review found evidence that at both physiological and pharmacological levels of dosing CCK has a significant effect on satiation but no evidence for weight loss over the long term.
As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age.
Methods
Using a population representative sample of 5088 adults aged •50 years from the English Longitudinal Study of Ageing, we investigated relationships of polygenic predisposition to general cognition with a rate of change in cognition during a 10-year follow-up period. Polygenic predisposition was measured with polygenic scores for general cognition (GC-PGS). Cognition was measured employing tests for verbal memory and semantic fluency.
Results
The average baseline memory score was 11.1 (s.d. = 2.9) and executive function score was 21.5 (s.d. = 5.8). An increase in GC-PGS by one standard deviation (1-s.d.) was associated with a higher baseline verbal memory by an average 0.27 points (95% CI 0.19–0.34, p < 0.001). Similarly, 1-s.d. increase in GC-PGS was associated with a higher semantic fluency score at baseline in the entire sample (β = 0.45, 95% CI 0.27–0.64, p < 0.001). These associations were significant for women and men, and all age groups. Nonetheless, 1-s.d. increase in GC-PGS was not associated with decreases in verbal memory nor semantic fluency during follow-up in the entire sample, as well stratified models by sex and age.
Conclusion
Although common genetic variants associated with general cognition additively are associated with a stable surplus to cognition in adults, a polygenic predisposition to general cognition is not associated with age-related cognitive decline during a 10-year follow-up.
Recently the NHS has expanded the provision of liaison mental health services (LMHS) to ensure that every acute hospital with an emergency department in England has a liaison psychiatry service. Little work has been undertaken to explore first-hand experiences of these services. The aim of this study was to capture service users’ experiences of LMHS in both emergency departments and acute inpatient wards in the UK, with a view to adapt services to better meet the needs of its users.
Method
This cross-sectional internet survey was initially advertised from May-July 2017 using the social media platform Facebook. Due to a paucity of male respondents, it was re-run from November 2017-February 2018, specifically targeting this demographic group. 184 people responded to the survey, of which 147 were service users and 37 were service users’ accompanying partners, friends or family members. The survey featured a structured questionnaire divided into three categories: the profile of the respondent, perceived professionalism of LMHS, and overall opinion of the service. Space was available for free-text comments in each section. Descriptive analysis of quantitative data was undertaken with R statistical software V.3.2.2. Qualitative data from free-text comments were transcribed and interpreted independently by three researchers using framework analysis; familiarisation with the data was followed by identification of a thematic framework, indexing, charting, mapping and interpretation.
Result
Opinions of the service were mixed but predominantly negative. 31% of service users and 27% of their loved ones found their overall contact with LMHS useful. Features most frequently identified as important were the provision of a 24/7 service, assessment by a variety of healthcare professionals and national standardisation of services. Respondents indicated that the least important feature was the provision of a separate service for older people. They also expressed that a desirable LMHS would include faster assessments following referral from the parent team, clearer communication about next steps and greater knowledge of local services and third sector organisations.
Conclusion
Our survey identified mixed responses, however service users and their loved ones perceived LMHS more frequently as negative than positive. This may be attributed to the recent governmental drive to assess, treat and discharge 95% of all patients seen in emergency departments within four hours of initial attendance. Additionally, dissatisfied service users are more likely to volunteer their opinions. The evaluation and adaptation of LMHS should be prioritised to enhance their inherent therapeutic value and improve engagement with treatment and future psychiatric care.
The reputation of the Normans is rooted in warfare, faith and mobility. They were simultaneously famed as warriors, noted for their religious devotion, and celebrated as fearless travellers. In the Middle Ages few activities offered a better conduit to combine warfare, religiosity, and movement than crusading and pilgrimage. However, while scholarship is abundant on many facets of the Norman world, it is a surprise that the Norman relationship with crusading and pilgrimage, so central in many ways to Norman identity, has hitherto not received extensive treatment. The collection here seeks to fill this gap. It aims to identify what was unique or different about the Normans and their relationship with crusading and pilgrimage, as well as how and why crusade and pilgrimage were important to the Normans. Particular focus is given to Norman participation in the First Crusade, to Norman interaction in later crusading initiatives, to the significance of pilgrimage in diverse parts of the Norman world, and finally to the ways in which crusading and pilgrimage were recorded in Norman narrative. Ultimately, this volume aims to assess, in some cases to confirm, and in others to revise the established paradigm of the Normans as crusaders par excellence and as opportunists who used religion to serve other agendas.
Dr Kathryn Hurlock is Senior Lecturer in Medieval History at Manchester Metropolitan University; Dr Paul Oldfield is Lecturer in Medieval History at the University of Manchester.
Contributors: Andrew Abram, William M. Aird, Emily Albu, Joanna Drell, Leonie Hicks, Natasha Hodgson, Kathryn Hurlock, Alan V. Murray, Paul Oldfield, David S. Spear, Lucas Villegas-Aristizábal.
We assessed long-term incidence and prevalence trends of dementia and parkinsonism across major ethnic and immigrant groups in Ontario.
Methods:
Linking administrative databases, we established two cohorts (dementia 2001–2014 and parkinsonism 2001–2015) of all residents aged 20 to 100 years with incident diagnosis of dementia (N = 387,937) or parkinsonism (N = 59,617). We calculated age- and sex-standardized incidence and prevalence of dementia and parkinsonism by immigrant status and ethnic groups (Chinese, South Asian, and the General Population). We assessed incidence and prevalence trends using Poisson regression and Cochran–Armitage trend tests.
Results:
Across selected ethnic groups, dementia incidence and prevalence were higher in long-term residents than recent or longer-term immigrants from 2001 to 2014. During this period, age- and sex-standardized incidence of dementia in Chinese, South Asian, and the General Population increased, respectively, among longer-term immigrants (by 41%, 58%, and 42%) and long-term residents (28%, 7%, and 4%), and to a lesser degree among recent immigrants. The small number of cases precluded us from assessing parkinsonism incidence trends. For Chinese, South Asian, and the General Population, respectively, prevalence of dementia and parkinsonism modestly increased over time among recent immigrants but significantly increased among longer-term immigrants (dementia: 134%, 217%, and 117%; parkinsonism: 55%, 54%, and 43%) and long-term residents (dementia: 97%, 132%, and 71%; parkinsonism: 18%, 30%, and 29%). Adjustment for pre-existing conditions did not appear to explain incidence trends, except for stroke and coronary artery disease as potential drivers of dementia incidence.
Conclusion:
Recent immigrants across major ethnic groups in Ontario had considerably lower rates of dementia and parkinsonism than long-term residents, but this difference diminished with longer-term immigrants.
SR is a 50-year-old, former professional golfer. Five years ago, he had a lower back injury, which required extensive physiotherapy. He never fully recovered and subsequently retired from the professional golfers’ tour. During this time, he had become increasingly worried about the future, about whether he could even play golf socially and became concerned about his financial security. S’s sleep became disrupted and his alcohol consumption increased, drinking bourbon (whisky) most evenings. Also, he was going through divorce proceedings initiated by his wife, following frequent arguments and a breakdown in their marriage.
The timing of the Neanderthal-associated Middle Palaeolithic demise and a possible overlap with anatomically modern humans (AMH) in some regions of Eurasia continues to be debated. The Iberian Peninsula is considered a possible refuge zone for the last Neanderthals, but the chronology of the later Middle Palaeolithic record has undergone revision and has increased the debate on the timing of Neanderthal extinction. Here we report on a study of the 5-m-thick archaeological stratigraphy of the Cardina-Salto do Boi, an open-air site located in inland Iberia, from which optically stimulated luminescence (OSL) ages were obtained for Middle and Upper Palaeolithic occupations preserved in overbank alluvial deposits. Geomorphology, archaeostratigraphy, stone-tool evolution, and OSL dating support the persistence of Neanderthals after 41 ka in central Iberia; the transition between the Middle Palaeolithic material culture and the AMH-associated Aurignacian blade and bladelet production is estimated to lie between 34.0 ± 2.0 ka and 38.4 ± 1.9 ka. Our results demonstrate that investigations focusing on different geomorphological situations are necessary to overcome the current limitations of the evidence and to establish more consistent models for Neanderthal disappearance and AMH expansion in the Iberian Peninsula.