We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure [email protected]
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.
The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.
Methods
We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.
Results
In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.
Conclusion
Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.
High cognitive activity possibly reduces the risk of cognitive decline and dementia.
Aims
To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.
Method
Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.
Results
Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.
Conclusions
A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.
The ASACUSA (atomic spectroscopy and collisions using slow antiprotons) Cusp experiment requires the production of dense positron plasmas with a high repetition rate to produce a beam of antihydrogen. In this work, details of the positron production apparatus used for the first observation of the antihydrogen beam, and subsequent measurements, are described in detail. This apparatus replaced the previous compact trap design resulting in an improvement in the positron accumulation rate by a factor of $52\pm 3$.
Methods for reducing the radius, temperature and space charge of a non-neutral plasma are usually reported for conditions which approximate an ideal Penning Malmberg trap. Here, we show that (i) similar methods are still effective under surprisingly adverse circumstances: we perform strong drive regime (SDR) compression and SDREVC in a strong magnetic mirror field using only 3 out of 4 rotating wall petals. In addition, we demonstrate (ii) an alternative to SDREVC, using e-kick instead of evaporative cooling (EVC) and (iii) an upper limit for how much plasma can be cooled to $T<20\ \mathrm {K}$ using EVC. This limit depends on the space charge, not on the number of particles or the plasma density.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
A terrestrial (lacustrine and fluvial) palaeoclimate record from Hoxne (Suffolk, UK) shows two temperate phases separated by a cold episode, correlated with MIS 11 subdivisions corresponding to isotopic events 11.3 (Hoxnian interglacial period), 11.24 (Stratum C cold interval), and 11.23 (warm interval with evidence of human presence). A robust, reproducible multiproxy consensus approach validates and combines quantitative palaeotemperature reconstructions from three invertebrate groups (beetles, chironomids, and ostracods) and plant indicator taxa with qualitative implications of molluscs and small vertebrates. Compared with the present, interglacial mean monthly air temperatures were similar or up to 4.0°C higher in summer, but similar or as much as 3.0°C lower in winter; the Stratum C cold interval, following prolonged nondeposition or erosion of the lake bed, experienced summers 2.5°C cooler and winters between 5°C and 10°C cooler than at present. Possible reworking of fossils into Stratum C from underlying interglacial assemblages is taken into account. Oxygen and carbon isotopes from ostracod shells indicate evaporatively enriched lake water during Stratum C deposition. Comparative evaluation shows that proxy-based palaeoclimate reconstruction methods are best tested against each other and, if validated, can be used to generate more refined and robust results through multiproxy consensus.
Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate access to care generally, the concept of “access to genomic medicine” is largely unexplored and a clear framework for studying and addressing major dimensions is lacking.
Methods:
Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them.
Results:
CSER’s enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies.
Conclusions:
Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.
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.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
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.
Results
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.
Conclusions
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.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias.
Methods
A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses.
Results
MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = −0.42) and underestimation (e.g. magical thinking, d = −0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition.
Conclusion
Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
The aim of the study is to validate an enlarged version of the Lie/Bet questionnaire for screening pathological gambling behaviour (Johnson, Hamer & Nora, 1998) in French. This version of the Lie/Bet has the following features: it was enlarged with one item derived from de CAGE screening for alcoholism (Ewing, 1984) and items were rated on a 4-points scale ranging from ‘All the time’ to ‘Never’ instead of being rated on a ‘Yes/No’ scale. The addition of the third item meets the need for a measure of social irritability about gambling. The use of 4-options responses scales is motivated by the necessity to measure severity of problem gambling and allow parametric epidemiological analysis. The study was conducted on three samples: one group of people concerned with gambling who participated to an online survey about gambling (N= 36), one group of out patients (N=33) and one group of respondents to the Swiss Health Survey 2007 (N=75). Analyses were conducted to measure internal consistency and convergent validity of the instrument. Results show good internal consistency of the enlarged Lie/Bet as well as good convergent validity.
Psychiatric patients tend to have severe metabolic alterations of multifactorial causes, lifestyle, diet, drug use and psychopharmacological treatment, especially antipsychotic drugs which act as risk factors for cardiovascular disease, strokes, infections and complications of diseases basal negatively influencing its evolution and prognosis.
Objectives
Rating the profile lipid and the prevalence of obesity in patients registered as disorder mental severe in treatment with antipsychotics.
Aims/methods
A descriptive study was performed taking as variables to take into account levels of cholesterol, triglycerides, weight and size.
Results
Of the 28 patients included in the study 7 refused to perform the corresponding measurements. Of the 21 remaining, 3 showed values higher than 150 mg/dl triglycerides and cholesterol figures higher than 200 mg/dl. Other 3 patients presented hypercholesterolemia without alteration of triglycerides and 2 hypertriglyceridemia without elevation of the cholesterol. Concerning the IMC, found that 7 patients presented overweight (BMI > 25 and < 30) and 5 patients obesity (BMI > 30). Of the 8 patients with lipid disorders, 2 had prescribed treatment with risperidone (oral or injectable) more quetiapine, 2 oral risperidone as monotherapy, risperidone1 more amisulpride, 1 quetiapine more aripiprazole, quetiapine 1 in monotherapyand 1 injection invega more oxcarbamacepina.
Conclusions
We found lipid alterations in a 38.1% of patients and a BMI greater than 25 in a 57.14% of 21 patients who agreed to the study. The most prescribed antipsychoticamong these patients were risperidone (5 patients) followed closely by quetiapine (4 patients).
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In recent years, the discovery of massive quasars at $z\sim7$ has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated.
Methods
Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms.
Results
All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86–96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47–82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly ‘very good’ (κ = 0.86–0.96).
Conclusions
The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.
Household surveys are one of the most commonly used tools for generating insight into rural communities. Despite their prevalence, few studies comprehensively evaluate the quality of data derived from farm household surveys. We critically evaluated a series of standard reported values and indicators that are captured in multiple farm household surveys, and then quantified their credibility, consistency and, thus, their reliability. Surprisingly, even variables which might be considered ‘easy to estimate’ had instances of non-credible observations. In addition, measurements of maize yields and land owned were found to be less reliable than other stationary variables. This lack of reliability has implications for monitoring food security status, poverty status and the land productivity of households. Despite this rather bleak picture, our analysis also shows that if the same farm households are followed over time, the sample sizes needed to detect substantial changes are in the order of hundreds of surveys, and not in the thousands. Our research highlights the value of targeted and systematised household surveys and the importance of ongoing efforts to improve data quality. Improvements must be based on the foundations of robust survey design, transparency of experimental design and effective training. The quality and usability of such data can be further enhanced by improving coordination between agencies, incorporating mixed modes of data collection and continuing systematic validation programmes.