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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Exercise has been found to be important in maintaining neurocognitive health. However, the effect of exercise intensity level remains relatively underexplored. Thus, to test the hypothesis that self-paced high-intensity exercise and cardiorespiratory fitness (peak aerobic capacity; VO2peak) increase grey matter (GM) volume, we examined the effect of a 6-month exercise intervention on frontal lobe GM regions that support the executive functions in older adults.
Ninety-eight cognitively normal participants (age = 69.06 ± 5.2 years; n = 54 female) were randomised into either a self-paced high- or moderate-intensity cycle-based exercise intervention group, or a no-intervention control group. Participants underwent magnetic resonance imaging and fitness assessment pre-intervention, immediately post-intervention, and 12-months post-intervention.
The intervention was found to increase fitness in the exercise groups, as compared with the control group (F = 9.88, p = <0.001). Changes in pre-to-post-intervention fitness were associated with increased volume in the right frontal lobe (β = 0.29, p = 0.036, r = 0.27), right supplementary motor area (β = 0.30, p = 0.031, r = 0.29), and both right (β = 0.32, p = 0.034, r = 0.30) and left gyrus rectus (β = 0.30, p = 0.037, r = 0.29) for intervention, but not control participants. No differences in volume were observed across groups.
At an aggregate level, six months of self-paced high- or moderate-intensity exercise did not increase frontal GM volume. However, experimentally-induced changes in individual cardiorespiratory fitness was positively associated with frontal GM volume in our sample of older adults. These results provide evidence of individual variability in exercise-induced fitness on brain structure.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19.
This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis.
In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9–59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1–11.4), an affective disorder (OR 4.1; CI 1.6–10.9), and severe respiratory symptoms (OR 4.6; CI 2.2–9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1–0.9) predicted a lower risk of a confusional state.
COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.
New Caledonia hosts a large part of the world’s breeding population of the Tahiti Petrel Pseudobulweria rostrata. This rare, cryptic and little-studied seabird nests locally in the mountains up to 1,200 m in altitude, particularly in ultramafic (i.e. nickel-rich) areas where mining activity is a major threat. The considerable development of mining activities in New Caledonia over the past decade raises concerns about its potential impacts on breeding populations through both direct habitat destruction and side effects such as pollution or repeated disturbances. This context calls for a dedicated assessment of the persistence of local populations to guide the design of an adapted conservation strategy and potential restoration programmes. We investigated the impact of mining activities on a Tahiti Petrel population when surveyed pre-mining (2004–2007) and following a period of full mining (2017–2018). The vocal activity was assessed at a total of 114 night-call count stations spread over the Koniambo massif. Areas with ground-originated vocal activity were then searched during daytime for nesting evidence. Finally, georeferenced aerial photos were used to estimate habitat degradation as the percentage of bare soil cover (PBSC) within a 400-m radius around each call count station. Our study revealed a dramatic decline in the Tahiti Petrel vocal activity and a desertion of breeding habitats during the full-mining period compared to the pre-mining period. In light of these results, we recommend designing safe breeding areas and combining restoration methods including social attraction, predation control and artificial burrows at mining sites.
Around 8150 BP, the Storegga tsunami struck North-west Europe. The size of this wave has led many to assume that it had a devastating impact upon contemporaneous Mesolithic communities, including the final inundation of Doggerland, the now submerged Mesolithic North Sea landscape. Here, the authors present the first evidence of the tsunami from the southern North Sea, and suggest that traditional notions of a catastrophically destructive event may need rethinking. In providing a more nuanced interpretation by incorporating the role of local topographic variation within the study of the Storegga event, we are better placed to understand the impact of such dramatic occurrences and their larger significance in settlement studies.
The 2007–19 glaciological mass-balance series of Mera Glacier in the Everest Region, East Nepal, is reanalysed using the geodetic mass balance assessed by differencing two DEMs obtained from Pléiades stereo-images acquired in November 2012 and in October 2018. The glaciological glacier-wide annual mass balance of Mera Glacier has to be systematically decreased by 0.11 m w.e. a−1 to match the geodetic mass balance. We attribute part of the positive bias of the glaciological mass balance to an over-estimation of the accumulation above 5520 m a.s.l., likely due to a measurement network unable to capture its spatial variability. Over the period 2007–19, Mera Glacier has lost mass at a rate of −0.41 ± 0.20 m w.e. a−1, in general agreement with regional averages for the central Himalaya. We observe a succession of negative mass-balance years since 2013.
The DESCANT (Dementia Early Stage Cognitive Aids New Trial) intervention provided a personalised care package to improve the cognitive abilities, function and well -being of people with early-stage dementia and their carers by providing a range of memory aids, with training and support for use. This presentation will explore findings from a goal attainment scaling exercise undertaken within a multi-site pragmatic randomised trial, part of a NIHR-funded research programme ‘Effective Home Support in Dementia Care: Components, Impacts and Costs of Tertiary Prevention.’
The aim was to describe the Goal Attainment Scaling (GAS) approach developed; investigate the types of goals identified by people with dementia and their carers and subsequent attainment; and explore the role of Dementia Support Practitioners (DSPs) in the process. This GAS exercise was designed by researchers, a clinical psychologist, a clinician and a DSP. Goal setting and attainment were conducted with the person with dementia and their carer and recorded by DSPs. Data were obtained from 117 intervention records and semi-structured interviews with five DSPs delivering the intervention across seven NHS Trusts in England and Wales. The GAS exercise was conducted as planned with goals and extent of involvement in the exercise tailored to individual participants and engagement was high. Demographic characteristics from the trial baseline dataset were analysed. Measures were created from intervention records to permit quantification and descriptive analysis. Interviews were professionally transcribed and subject to thematic analysis to identify salient themes.
A total of 293 goals were identified across the 117 participants. From these 17 goal types were distinguished across six domains: self -care; household tasks; daily occupation; orientation; communication; and well-being and safety. A measure of goal attainment appropriate to both the client group and a modest intervention was obtained. On average participants had evidenced some improvement regarding goals set. Qualitative findings suggested overall DSPs were positive about their experience of goal setting. Although several challenges were identified, if these were overcome, measuring goal attainment was generally viewed as straightforward. GAS can be used in the context of a psychosocial intervention for people with early-stage dementia to identify and measure attainment of personalised care goals.
The Gaia satellite recently released parallax measurements for nearly 400,000 white dwarf stars, allowing for precise measurements of their physical parameters. By combining these parallaxes with Pan-STARRS and CFIS-u photometry, we measured the effective temperatures and surface gravities for all white dwarfs within 100 pc and identified a sample of ZZ Ceti white dwarf candidates within the instability strip. We report the results of a photometric follow-up, currently under way, aimed at identifying new ZZ Ceti stars among this sample using the PESTO camera attached to the 1.6-m telescope at the Mont Mégantic Observatory. Our goal is to verify that ZZ Ceti stars occupy a region in the logg-Teff plane where no nonvariable stars are found, supporting the idea that ZZ Ceti pulsators represent a phase through which all hydrogen-line (DA) white dwarfs must evolve.
OBJECTIVES/SPECIFIC AIMS: Alcohol consumption perturbs the normal intestinal microbial communities (alcohol dysbiosis). To begin to investigate the relationship between alcohol-mediated dysbiosis and host defense we developed an alcohol dysbiosis fecal adoptive transfer model, which allows us to isolate the host immune response to a pathogenic challenge at a distal organ (ie, the lung). This model system allowed us to determine whether the host immune responses to Klebsiella pneumoniae are altered by ethanol-associated dysbiosis, independent of alcohol use. We hypothesized that alcohol-induced changes in intestinal microbial communities would impair pulmonary host defenses against K. pneumoniae. METHODS/STUDY POPULATION: Mice were treated with a cocktail of antibiotics daily for 2 weeks. Microbiota-depleted mice were then recolonized by gavage for 3-days with intestinal microbiota from ethanol-fed or pair-fed animals. Following recolonization groups of mice were sacrificed prior to and 48 hours post respiratory infection with K. pneumoniae. We then assessed susceptibility to Klebsiella infection by determining colony counts for pathogen burden in the lungs. We also determined lung and intestinal immunology, intestinal permeability, as well as, liver damage and inflammation. RESULTS/ANTICIPATED RESULTS: We found that increased susceptibility to K. pneumoniae is, in part, mediated by the intestinal microbiota, as animals recolonized with an alcohol-induced dysbiotic intestinal microbial community have significantly higher lung burdens of K. pneumoniae (5×104 CFU vs. 1×103 CFU) independent of EtOH. We also found that increased susceptibility in alcohol-dysbiosis recolonized animals was associated with a decrease in the recruitment and/or proliferation of CD4+ and CD8+ T-cells (1.5×109 cells vs. 2.5×109 cells) in the lung following Klebsiella infection. However, there were increased numbers of T-cells in the intestinal tract following Klebsiella infection, which may suggest that T cells are being sequestered in the intestinal tract to the detriment of host defense in the lung. Interestingly, mice recolonized with an alcohol-dysbiotic microbiota had increased intestinal permeability as measured by increased levels of serum intestinal fatty acid binding protein (55 vs. 30 ng/mL). Alcohol-dysbiotic microbiota also increased liver steatosis (Oil Red-O staining) and liver inflammation (>2-fold expression of IL-17 and IL-23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that the commensal intestinal microbiota support mucosal host defenses against infectious agents by facilitating normal immune responses to pulmonary pathogens. Our data also suggest that increased intestinal permeability coupled with increased liver inflammation may impair the recruitment/proliferation of immune cells in the respiratory tract following infection. The role of the microbiota during host defense will be important areas of future research directed at understanding the effects of microbial dysbiosis in patients with AUDs.
Attention Deficit Hyperactivity Disorder (ADHD) arising from a Western health model has generated much global debate about its relevance in Indigenous communities. More importantly, it has raised questions concerning acceptance of its diagnosis and intervention, hence affecting early identification and treatment compliance. The current study explored an Aboriginal perspective of diagnosis and treatment compliance of ADHD in an Australian Aboriginal community. Using a qualitative approach, 27 participants aged between 22 and 52 years from a Western Australian metropolitan Aboriginal community comprising community members, Aboriginal mental health and education professionals, and Aboriginal parents of children with ADHD, were interviewed either individually or in groups. Participants identified differences in child rearing practices, expectation of child behaviour in school, higher tolerance of hyperactive behaviour within the Aboriginal community and lack of information about ADHD as the main reasons for parents not seeking medical help for the child. Participants also saw the changes in a child's behaviour after medication as a loss of identity/self and this was reported to be the main contributor to treatment non-compliance. Overall, most participants recognised the detrimental effect of having ADHD. However, the current diagnostic process and treatment are not culturally appropriate to assist the Aboriginal community to effectively manage this disorder in their children.
Based on a single right cheliped from the Cape de Naze Formation (middle–upper Maastrichtian), Senegal, a new genus and species of hermit crab with capsulated setae is described. Paracapsulapagurus poponguinensis n. gen. n. sp. is characterized by platy, scale-like, non-spinose tubercles with setae arranged in curved rows. This is only the third record of a fossil hermit crab with capsulated setae. These are documented in detail using SEM-imaging. For the first time, capsulated setae are also figured for the Early Jurassic hermit crab Schobertella.
Atrazine has been the most widely used herbicide in North American
processing sweet corn for decades; however, increased restrictions in recent
years have reduced or eliminated atrazine use in certain production areas.
The objective of this study was to identify the best stakeholder-derived
weed management alternatives to atrazine in processing sweet corn. In field
trials throughout the major production areas of processing sweet corn,
including three states over 4 yr, 12 atrazine-free weed management
treatments were compared to three standard atrazine-containing treatments
and a weed-free check. Treatments varied with respect to herbicide mode of
action, herbicide application timing, and interrow cultivation. All
treatments included a PRE application of dimethenamid. No single weed
species occurred across all sites; however, weeds observed in two or more
sites included common lambsquarters, giant ragweed, morningglory species,
velvetleaf, and wild-proso millet. Standard treatments containing both
atrazine and mesotrione POST provided the most efficacious weed control
among treatments and resulted in crop yields comparable to the weed-free
check, thus demonstrating the value of atrazine in sweet corn production
systems. Timely interrow cultivation in atrazine-free treatments did not
consistently improve weed control. Only two atrazine-free treatments
consistently resulted in weed control and crop yield comparable to standard
treatments with atrazine POST: treatments with tembotrione POST either with
or without interrow cultivation. Additional atrazine-free treatments with
topramezone applied POST worked well in Oregon where small-seeded weed
species were prevalent. This work demonstrates that certain atrazine-free
weed management systems, based on input from the sweet corn growers and
processors who would adopt this technology, are comparable in performance to
standard atrazine-containing weed management systems.
Thalattosuchians are crocodylomorphs mainly known from marine strata of Early Jurassic to Early Cretaceous age. They represent the earliest crocodylomorph radiation to an aquatic habitat and their evolutionary history offers very few records from freshwater settings. Here, we report several exquisitely preserved thalattosuchian skulls attributed to a derived teleosaurid from a pedogenic horizon located at the base of a fluvial series of alternating silts and sandstones of the Phu Kradung Formation (Upper Jurassic) of northeastern Thailand. Using laser ablation multicollector inductively coupled mass spectrometry (MC-ICP-MS) on tooth enamel and dentine, we measured isotopic ratios of strontium (87Sr/86Sr) to test the habitat of these teleosaurids. In addition, Sr concentrations of the dental tissues were estimated from the calibrated signal intensities of the Sr isotope measurements. The dataset includes bioapatite (teeth or scales) of eight terrestrial and five aquatic vertebrates. Theropods exhibit lower Sr concentrations both in enamel and dentine compared to others groups, a pattern in accordance with the calcium biopurification process, which predicts that Sr concentrations in the body of vertebrates decrease up the trophic chain. It also excludes the possibility that diagenesis has completely overprinted the Sr isotope compositions of the fossil assemblage, which exhibits a homogeneous 87Sr/86Sr signature above the Late Jurassic seawater value. Values for teleosaurid teeth are in the range of other values for vertebrates in the continental assemblage and imply that these crocodylomorphs did not migrate between freshwater and marine habitats at least in the time constraint of the mineralizing tooth. This result represents the first demonstration that a population of teleosaurids was established for a prolonged time in a freshwater environment. Whether the ability of teleosaurids to inhabit freshwater habitats is a secondary adaptation or whether it is plesiomorphic and inherited from freshwater ancestors is discussed.
The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry.
The IMproving Paediatric and Adult Congenital Treatment– registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the ‘core’ IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis.
During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types – isolated or in combination with other procedures – were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory.
The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.
To report procedural characteristics and adverse events on data collected in the registry.
The IMPACT – IMproving Paediatric and Adult Congenital Treatment – Registry is a catheterisation registry of paediatric and adult patients with CHD undergoing diagnostic and interventional cardiac catheterisation. We are reporting the procedural characteristics and adverse events of patients undergoing diagnostic and interventional catheterisation procedures from January, 2011 to March, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at the participating centres and entered via either a web-based platform or software provided by American College of Cardiology-certified vendors, and were collected in a secure, centralised database. Centre participation was voluntary.
During the time frame of data collection, 19,797 procedures were entered into the IMPACT Registry. Procedures were classified as diagnostic only (35.4%); one of six specific interventions (23.8%); other or multiple interventions (40.7%); and were further broken down into four age groups. Anaesthesia was used in 84.1% of diagnostic procedures and 87.8% of interventional ones. Adverse events occurred in 10.0% of diagnostic and 11.1% of interventional procedures.
The IMPACT Registry is gathering data to set national benchmarks for diagnostic and certain specific interventional procedures. We are seeing little differences in procedural characteristics or adverse events in diagnostic procedures compared with interventional procedures overall, but there is significant variation in adverse events amongst age categories. Risk stratification and patient acuity scores will be required for further analysis of these differences.