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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
We undertake a comprehensive investigation into the distribution of in situ stars within Milky Way-like galaxies, leveraging TNG50 simulations and comparing their predictions with data from the H3 survey. Our analysis reveals that 28% of galaxies demonstrate reasonable agreement with H3, while only 12% exhibit excellent alignment in their profiles, regardless of the specific spatial cut employed to define in situ stars. To uncover the underlying factors contributing to deviations between TNG50 and H3 distributions, we scrutinise correlation coefficients among internal drivers (e.g. virial radius, star formation rate [SFR]) and merger-related parameters (such as the effective mass-ratio, mean distance, average redshift, total number of mergers, average spin-ratio, and maximum spin alignment between merging galaxies). Notably, we identify significant correlations between deviations from observational data and key parameters such as the median slope of virial radius, mean SFR values, and the rate of SFR change across different redshift scans. Furthermore, positive correlations emerge between deviations from observational data and parameters related to galaxy mergers. We validate these correlations using the Random Forest Regression method. Our findings underscore the invaluable insights provided by the H3 survey in unravelling the cosmic history of galaxies akin to the Milky Way, thereby advancing our understanding of galactic evolution and shedding light on the formation and evolution of Milky Way-like galaxies in cosmological simulations.
During the COVID-19 pandemic, virtual physician visits rapidly increased among community-dwelling older persons living with dementia (PLWD) in Ontario. Rural residents often have less access to medical care compared to their urban counterparts, and it is unclear whether access to virtual care was equitable between PLWD in urban versus rural locations.
Methods:
Using population-based health administrative data and a repeated cross-sectional study design, we identified and described community-dwelling PLWD between March 2020 and August 2022 in Ontario, Canada. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals comparing rates of virtual visits between rural and urban PLWD by key physician specialties: family physicians, neurologists and psychiatrists/geriatricians.
Results:
Of 122,751 PLWD in our cohort, 9.2% (n = 11,304) resided in rural areas. Rural PLWD were slightly younger compared to their urban counterparts (mean age = 81 vs. 82 years; standardized difference = 0.16). There were no differences across areas by sex or income quintile. In adjusted models, rates of virtual visits were significantly lower for rural compared to urban PLWD across all specialties: family physicians (RR = 0.71 [0.69–0.73]), neurologists (RR = 0.79 [0.75–0.83]) and psychiatrists/geriatricians (RR = 0.72 [0.68–0.76]).
Conclusions:
PLWD in rural areas had significantly lower rates of virtual family physician, neurologist and psychiatrist/geriatrician visits compared to urban dwellers during the study period. This finding raises important issues regarding access to primary and specialist healthcare services for rural PLWD. Future work should explore barriers to care to improve health care access among PLWD in rural communities.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
The poor environmental stability of natural anthocyanin hinders its usefulness in various functional applications. The objectives of the present study were to enhance the environmental stability of anthocyanin extracted from Lycium ruthenicum by mixing it with montmorillonite to form an organic/inorganic hybrid pigment, and then to synthesize allochroic biodegradable composite films by incorporating the hybrid pigment into sodium alginate and test them for potential applications in food testing and packaging. The results of X-ray diffraction, Fourier-transform infrared spectroscopy, and use of the Brunauer–Emmett–Teller method and zeta potential demonstrated that anthocyanin was both adsorbed on the surface and intercalated into the interlayer of montmorillonite via host–guest interaction, and the hybrid pigments obtained allowed good, reversible, acid/base behavior after exposure to HCl and NH3 atmospheres. The composite films containing hybrid pigments had good mechanical properties due to the uniform dispersion of the pigments in a sodium alginate substrate and the formation of hydrogen bonds between them. Interestingly, the composite films also exhibited reversible acidichromism. The as-prepared hybrid pigments in composite films could, therefore, serve simultaneously as a reinforced material and as a smart coloring agent for a polymer substrate.
Physician parents encounter unique challenges in balancing new parenthood with work responsibilities, especially upon their return from parental leave. We designed a pilot program that incorporated 1:1 parental coaching to expectant and new physician parents and provided stipends for lactation support and help at home. Additional initiatives included launching a virtual new parent group during the COVID-19 pandemic and starting an emergency backup pump supplies program. There was positive feedback for our Parental Wellness Program (PWP), which was used to secure expanded funding. Pilot results showed that our program had a meaningful impact on parental wellness, morale, productivity, and lactation efforts.
We examine the association between high ambient temperature and acute mental health-related healthcare encounters in New York City for children, adolescents and young adults.
Methods
This case-crossover study included emergency department (ED) visits and hospital encounters with a primary diagnosis of any mental health disorder during warm-season months (June–August) in New York City from 2005 to 2011 from patients of three age groups (6–11, 12–17 and 18–25 years). Using a distributed lag non-linear model over 0–5 lag days, by fitting a conditional logistic regression for each age group, we calculated the cumulative odds ratios of mental health encounters associated with an elevated temperature. Analyses were stratified by race/ethnicity, payment source and mental health categories to elucidate vulnerable subpopulations.
Results
In New York City, there were 82,982 mental health–related encounters for young people aged 6 to 25 years during our study period months. Elevated temperature days were associated with higher risk of mental health–related ED and hospital encounters for the 6- to 11-year-olds (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.13–1.46), for the 12- to 17-year-olds (OR: 1.17, 95% CI: 1.09–1.25) and for the 18- to 25-year-olds (OR: 1.09, 95% CI: 1.04–1.15). Children with reaction disorders, adolescents with anxiety and bipolar disorders, young adults with psychosis and reaction disorders and Black and non-Hispanic children and adolescents showed vulnerability to elevated temperature.
Conclusions
We found that elevated ambient temperatures were associated with acute mental health ED or hospital encounters across childhood, adolescence and young adulthood.
The great demographic pressure brings tremendous volume of beef demand. The key to solve this problem is the growth and development of Chinese cattle. In order to find molecular markers conducive to the growth and development of Chinese cattle, sequencing was used to determine the position of copy number variations (CNVs), bioinformatics analysis was used to predict the function of ZNF146 gene, real-time fluorescent quantitative polymerase chain reaction (qPCR) was used for CNV genotyping and one-way analysis of variance was used for association analysis. The results showed that there exists CNV in Chr 18: 47225201-47229600 (5.0.1 version) of ZNF146 gene through the early sequencing results in the laboratory and predicted ZNF146 gene was expressed in liver, skeletal muscle and breast cells, and was amplified or overexpressed in pancreatic cancer, which promoted the development of tumour through bioinformatics. Therefore, it is predicted that ZNF146 gene affects the proliferation of muscle cells, and then affects the growth and development of cattle. Furthermore, CNV genotyping of ZNF146 gene was three types (deletion type, normal type and duplication type) by Real-time fluorescent quantitative PCR (qPCR). The association analysis results showed that ZNF146-CNV was significantly correlated with rump length of Qinchuan cattle, hucklebone width of Jiaxian red cattle and heart girth of Yunling cattle. From the above results, ZNF146-CNV had a significant effect on growth traits, which provided an important candidate molecular marker for growth and development of Chinese cattle.
The cosmic evolution of the chemical elements from the Big Bang to the present time is driven by nuclear fusion reactions inside stars and stellar explosions. A cycle of matter recurrently re-processes metal-enriched stellar ejecta into the next generation of stars. The study of cosmic nucleosynthesis and this matter cycle requires the understanding of the physics of nuclear reactions, of the conditions at which the nuclear reactions are activated inside the stars and stellar explosions, of the stellar ejection mechanisms through winds and explosions, and of the transport of the ejecta towards the next cycle, from hot plasma to cold, star-forming gas. Due to the long timescales of stellar evolution, and because of the infrequent occurrence of stellar explosions, observational studies are challenging, as they have biases in time and space as well as different sensitivities related to the various astronomical methods. Here, we describe in detail the astrophysical and nuclear-physical processes involved in creating two radioactive isotopes useful in such studies, $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$. Due to their radioactive lifetime of the order of a million years, these isotopes are suitable to characterise simultaneously the processes of nuclear fusion reactions and of interstellar transport. We describe and discuss the nuclear reactions involved in the production and destruction of $^{26}\mathrm{Al}$ and $^{60}\mathrm{Fe}$, the key characteristics of the stellar sites of their nucleosynthesis and their interstellar journey after ejection from the nucleosynthesis sites. This allows us to connect the theoretical astrophysical aspects to the variety of astronomical messengers presented here, from stardust and cosmic-ray composition measurements, through observation of $\gamma$ rays produced by radioactivity, to material deposited in deep-sea ocean crusts and to the inferred composition of the first solids that have formed in the Solar System. We show that considering measurements of the isotopic ratio of $^{26}\mathrm{Al}$ to $^{60}\mathrm{Fe}$ eliminate some of the unknowns when interpreting astronomical results, and discuss the lessons learned from these two isotopes on cosmic chemical evolution. This review paper has emerged from an ISSI-BJ Team project in 2017–2019, bringing together nuclear physicists, astronomers, and astrophysicists in this inter-disciplinary discussion.
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.
Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.
Methods:
This is a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. 210 treatment-seekers with DSM-IV diagnosis of cocaine dependence consented and enrolled. 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants attended the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy once per week. The primary outcome was the increase in weekly percentage of non-use days. Secondary outcomes included: decrease in the weekly median log of urine benzoylecgonine, subgroup analyses of balancing factors and co-morbid conditions, self-report of alcohol use, addiction severity, craving, and risk behaviors for HIV.
Results:
125 participants completed 12 weeks of treatment (60%). The GEE regression analysis showed that for the total sample, the difference between modafinil groups and placebo in the weekly percentage of cocaine non-use days over the 12-week treatment period was not statistically significant (p=0.95). A post-hoc analysis showed a significant effect for modafinil, only in the subgroup of cocaine patients without alcohol dependence. Modafinil 200mg also showed significant effects of an increase in the total number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04).
Conclusions:
These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing craving.
We report a significant advance in thermally insulating transparent materials: silica-based monoliths with controlled porosity which exhibit the transparency of windows in combination with a thermal conductivity comparable to aerogels.
The lack of transparent, thermally insulating windows leads to substantial heat loss in commercial and residential buildings, which accounts for ~4.2% of primary US energy consumption annually. The present study provides a potential solution to this problem by demonstrating that ambiently dried silica aerogel monoliths, i.e., ambigels, can simultaneously achieve high optical transparency and low thermal conductivity without supercritical drying. A combination of tetraethoxysilane, methyltriethoxysilane, and post-gelation surface modification precursors were used to synthesize ambiently dried materials with varying pore fractions and pore sizes. By controlling the synthesis and processing conditions, 0.5–3 mm thick mesoporous monoliths with transmittance >95% and a thermal conductivity of 0.04 W/(m K) were produced. A narrow pore size distribution, <15 nm, led to the excellent transparency and low haze, while porosity in excess of 80% resulted in low thermal conductivity. A thermal transport model considering fractal dimension and phonon-boundary scattering is proposed to explain the low effective thermal conductivity measured. This work offers new insights into the design of transparent, energy saving windows.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together $60+$ programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350 $\mu$m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200 $\mu$m images will also have a factor $\sim $30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.