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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.
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.
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.
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.
Research on prehistoric mainland Southeast Asia is dominated by mortuary contexts, leaving processes such as the transition to sedentism relatively understudied. Recent excavations in southern Vietnam, however, have recovered new evidence for settlement. The authors report on investigations at the neolithic site of Loc Giang (3980–3270 cal BP) in southern Vietnam, where excavation revealed a vertical sequence of more than 30 surfaces. Microarchaeological analyses indicate that these features are carefully prepared lime mortar floors; the lime was probably produced from burnt shell. The floors date to between 3510 and 3150 cal BP, providing the earliest-known evidence for the use of lime mortar, and for durable settlement construction, in this region.
Seabirds are declining globally and are one of the most threatened groups of birds. To halt or reverse this decline they need protection both on land and at sea, requiring site-based conservation initiatives based on seabird abundance and diversity. The Important Bird and Biodiversity Area (IBA) programme is a method of identifying the most important places for birds based on globally agreed standardised criteria and thresholds. However, while great strides have been made identifying terrestrial sites, at-sea identification is lacking. The Chagos Archipelago, central Indian Ocean, supports four terrestrial IBAs (tIBAs) and two proposed marine IBAs (mIBAs). The mIBAs are seaward extensions to breeding colonies based on outdated information and, other types of mIBA have not been explored. Here, we review the proposed seaward extension mIBAs using up-to-date seabird status and distribution information and, use global positioning system (GPS) tracking from Red-footed Booby Sula sula – one of the most widely distributed breeding seabirds on the archipelago – to identify any pelagic mIBAs. We demonstrate that due to overlapping boundaries of seaward extension to breeding colony and pelagic areas of importance there is a single mIBA in the central Indian Ocean that lays entirely within the Chagos Archipelago Marine Protected Area (MPA). Covering 62,379 km2 it constitutes ~10% of the MPA and if designated, would become the 11th largest mIBA in the world and 4th largest in the Indian Ocean. Our research strengthens the evidence of the benefits of large-scale MPAs for the protection of marine predators and provides a scientific foundation stone for marine biodiversity hotspot research in the central Indian Ocean.
The response of garnet and zircon to prograde amphibolite-facies metamorphism in late Proterozoic mica schists from the Scottish Highlands has been investigated. Spatial analysis of zircon populations using scanning electron microscopy was undertaken in Dalradian Schists that have undergone a sequence of prograde garnet growth and localised breakdown reactions involving coupled dissolution–reprecipitation. Fluid availability and matrix permeability strongly control this metamorphic response and different generations of garnet contain radically different populations of metamorphic micro-zircon and associated changes in the detrital zircon population. Micro-zircon abundance increases during garnet growth, whereas that of detrital zircon decreases. The mineralogy of the matrix influences zircon abundance in porphyroblast phases, where garnet overgrows a micaceous matrix zircon-rich garnet forms and where it overgrows a quartzofeldspathic matrix the result is zircon-poor garnet. Following garnet growth, micro-zircon abundance decreases at each stage of the prograde reaction history, with sillimanite-zone schists containing the lowest abundance, suggesting micro-zircons are texturally less stable at staurolite- and sillimanite-grade metamorphism. Micro-zircons are distributed evenly across host minerals in the matrix, with the exception of retrograde chlorite where micro-zircons are absent due to fluids removing Zr before new zircon can precipitate. There is an overall decrease in the mode of zircon at each stage of the reaction history, indicating that zircon is a highly reactive phase during amphibolite-facies metamorphism and is very sensitive to individual prograde and retrograde reactions.
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.
Wavelength-dispersive X-ray (WDX) spectroscopy was used to measure silicon atom concentrations in the range 35–100 ppm [corresponding to (3–9) × 1018 cm−3] in doped AlxGa1–xN films using an electron probe microanalyser also equipped with a cathodoluminescence (CL) spectrometer. Doping with Si is the usual way to produce the n-type conducting layers that are critical in GaN- and AlxGa1–xN-based devices such as LEDs and laser diodes. Previously, we have shown excellent agreement for Mg dopant concentrations in p-GaN measured by WDX with values from the more widely used technique of secondary ion mass spectrometry (SIMS). However, a discrepancy between these methods has been reported when quantifying the n-type dopant, silicon. We identify the cause of discrepancy as inherent sample contamination and propose a way to correct this using a calibration relation. This new approach, using a method combining data derived from SIMS measurements on both GaN and AlxGa1–xN samples, provides the means to measure the Si content in these samples with account taken of variations in the ZAF corrections. This method presents a cost-effective and time-saving way to measure the Si doping and can also benefit from simultaneously measuring other signals, such as CL and electron channeling contrast imaging.
The timing and duration of the coldest period in the last glacial stage, often referred to as the last glacial maximum (LGM), has been observed to vary spatially and temporally. In Australia, this period is characterised by colder, and in some places more arid, climates than today. We applied Monte-Carlo change point analysis to all available continuous proxy records covering this period, primarily pollen records, from across Australia (n = 37) to assess this change. We find a significant change point occurred (within uncertainty) at 28.6 ± 2.8 ka in 25 records. We interpret this change as a shift to cooler climates, associated with a widespread decline in biological productivity. An additional change point occurred at 17.7 ± 2.2 ka in 24 records. We interpret this change as a shift towards warmer climates, associated with increased biological productivity. We broadly characterise the period between 28.6 (± 2.8) – 17.7 (± 2.2) ka as an extended period of maximum cooling, with low productivity vegetation that may have occurred as a combined response to reduced temperatures, lower moisture availability and atmospheric CO2. These results have implications for how the spatial and temporal coherence of climate change, in this case during the LGM, can be best interrogated and interpreted.
We have found a class of circular radio objects in the Evolutionary Map of the Universe Pilot Survey, using the Australian Square Kilometre Array Pathfinder telescope. The objects appear in radio images as circular edge-brightened discs, about one arcmin diameter, that are unlike other objects previously reported in the literature. We explore several possible mechanisms that might cause these objects, but none seems to be a compelling explanation.
The Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory (BDI-II) and the Generalised Anxiety Disorder Assessment (GAD-7) are widely used in the evaluation of interventions for depression and anxiety. The smallest reduction in depressive symptoms that matter to patients is known as the Minimum Clinically Important Difference (MCID). Little empirical study of the MCID for these scales exists.
A prospective cohort of 400 patients in UK primary care were interviewed on four occasions, 2 weeks apart. At each time point, participants completed all three questionnaires and a ‘global rating of change’ scale (GRS). MCID estimation relied on estimated changes in symptoms according to reported improvement on the GRS scale, stratified by baseline severity on the Clinical Interview Schedule (CIS-R).
For moderate baseline severity, those who reported improvement on the GRS had a reduction of 21% (95% confidence interval (CI) −26.7 to −14.9) on the PHQ-9; 23% (95% CI −27.8 to −18.0) on the BDI-II and 26.8% (95% CI −33.5 to −20.1) on the GAD-7. The corresponding threshold scores below which participants were more likely to report improvement were −1.7, −3.5 and −1.5 points on the PHQ-9, BDI-II and GAD-7, respectively. Patients with milder symptoms require much larger reductions as percentage of their baseline to endorse improvement.
An MCID representing 20% reduction of scores in these scales, is a useful guide for patients with moderately severe symptoms. If treatment had the same effect on patients irrespective of baseline severity, those with low symptoms are unlikely to notice a benefit.
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.
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.
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.
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.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Self-administered questionnaires are widely used in primary care and other clinical settings to assess the severity of depressive symptoms and monitor treatment outcomes. Qualitative studies have found that changes in questionnaire scores might not fully capture patients' experience of changes in their mood but there are no quantitative studies of this issue. We examined the extent to which changes in scores from depression questionnaires disagreed with primary care patients' perceptions of changes in their mood and investigated factors influencing this relationship.
Prospective cohort study assessing patients on four occasions, 2 weeks apart. Patients (N = 554) were recruited from primary care surgeries in three UK sites (Bristol, Liverpool and York) and had reported depressive symptoms or low mood in the past year [68% female, mean age 48.3 (s.d. 12.6)]. Main outcome measures were changes in scores on patient health questionnaire (PHQ-9) and beck depression inventory (BDI-II) and the patients' own ratings of change.
There was marked disagreement between clinically important changes in questionnaire scores and patient-rated change, with disagreement of 51% (95% CI 46–55%) on PHQ-9 and 55% (95% CI 51–60%) on BDI-II. Patients with more severe anxiety were less likely, and those with better mental and physical health-related quality of life were more likely, to report feeling better, having controlled for depression scores.
Our results illustrate the limitations of self-reported depression scales to assess clinical change. Clinicians should be cautious in interpreting changes in questionnaire scores without further clinical assessment.
Cognitive-behavioural therapy (CBT) is an effective treatment for depressed adults. CBT interventions are complex, as they include multiple content components and can be delivered in different ways. We compared the effectiveness of different types of therapy, different components and combinations of components and aspects of delivery used in CBT interventions for adult depression. We conducted a systematic review of randomised controlled trials in adults with a primary diagnosis of depression, which included a CBT intervention. Outcomes were pooled using a component-level network meta-analysis. Our primary analysis classified interventions according to the type of therapy and delivery mode. We also fitted more advanced models to examine the effectiveness of each content component or combination of components. We included 91 studies and found strong evidence that CBT interventions yielded a larger short-term decrease in depression scores compared to treatment-as-usual, with a standardised difference in mean change of −1.11 (95% credible interval −1.62 to −0.60) for face-to-face CBT, −1.06 (−2.05 to −0.08) for hybrid CBT, and −0.59 (−1.20 to 0.02) for multimedia CBT, whereas wait list control showed a detrimental effect of 0.72 (0.09 to 1.35). We found no evidence of specific effects of any content components or combinations of components. Technology is increasingly used in the context of CBT interventions for depression. Multimedia and hybrid CBT might be as effective as face-to-face CBT, although results need to be interpreted cautiously. The effectiveness of specific combinations of content components and delivery formats remain unclear. Wait list controls should be avoided if possible.
To assess the effect of rural-to-urban migration on nutrition transition and overweight/obesity risk among women in Kenya.
Secondary analysis of data from nationally representative cross-sectional samples. Outcome variables were women’s BMI and nutrition transition. Nutrition transition was based on fifteen different household food groups and was adjusted for socio-economic and demographic characteristics. Stepwise backward multiple ordinal regression analysis was applied.
Kenya Demographic and Health Survey 2014.
Rural non-migrant, rural-to-urban migrant and urban non-migrant women aged 15–49 years (n 6171).
Crude data analysis showed rural-to-urban migration to be associated with overweight/obesity risk and nutrition transition. After adjustment for household wealth, no significant differences between rural non-migrants and rural-to-urban migrants for overweight/obesity risk and household consumption of several food groups characteristic of nutrition transition (animal-source, fats and sweets) were observed. Regardless of wealth, migrants were less likely to consume main staples and legumes, and more likely to consume fruits and vegetables. Identified predictive factors of overweight/obesity among migrant women were age, duration of residence in urban area, marital status and household wealth.
Our analysis showed that nutrition transition and overweight/obesity risk among rural-to-urban migrants is apparent with increasing wealth in urban areas. Several predictive factors were identified characterising migrant women being at risk for overweight/obesity. Future research is needed which investigates in depth the association between rural-to-urban migration and wealth to address inequalities in diet and overweight/obesity in Kenya.
The nomenclature of CaZrTi2O7 minerals has become very confused, such that zirconolite, zirkelite and polymignite each have acquired multiple meanings and represent five different crystal structures. To resolve these inconsistencies, the IMA approved resolutions as follows. Zirconolite is the non- crystalline (metamict) mineral or mineral with undetermined polytypoid of CaZrTi2O7. Zirconolite-3O is the three-layered orthorhombic polytypoid of CaZrTi2O7. Zirconolite-3T is the three-layered trigonal polytypoid of CaZrTi2O7. Zirconolite-2M is the two-layered monoclinic polytypoid of CaZrTi2O7. Polymignite (metamict) is discarded as equivalent to zirconolite. Zirkelite is the cubic mineral with formula (Ti,Ca,Zr)O2−x.
Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent.
To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980).
Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up.
No variants passed a genome-wide significance threshold (P=5×10–8) in either analysis. Four variants met criteria for suggestive significance (P<5×10–6) in association with response post-treatment, and three variants in the 6-month follow-up analysis.
This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.