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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.
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.
Estimates of test size (probability of Type I error) were obtained for several specific repeated measures designs. Estimates were presented for configurations where the underlying covariance matrices exhibited varying degrees of heterogeneity. Conventional variance ratios were employed as basic statistics in order to produce estimates of size for a conventional test, an ∊-adjusted test, and ∊-adjusted test and a conservative test. Indices for empirical distributions of two estimators of ∊j, a measure of covariance heterogeneity, were also provided.
The interaction of relativistically intense lasers with opaque targets represents a highly non-linear, multi-dimensional parameter space. This limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation, although to-date this has been the accepted methodology due to low data acquisition rates. High repetition-rate (HRR) lasers augmented by machine learning present a valuable opportunity for efficient source optimization. Here, an automated, HRR-compatible system produced high-fidelity parameter scans, revealing the influence of laser intensity on target pre-heating and proton generation. A closed-loop Bayesian optimization of maximum proton energy, through control of the laser wavefront and target position, produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60% of the laser energy. This demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.
Multi-messenger observations of the transient sky to detect cosmic explosions and counterparts of gravitational wave mergers critically rely on orbiting wide-FoV telescopes to cover the wide range of wavelengths where atmospheric absorption and emission limit the use of ground facilities. Thanks to continuing technological improvements, miniaturised space instruments operating as distributed-aperture constellations are offering new capabilities for the study of high-energy transients to complement ageing existing satellites. In this paper we characterise the performance of the upcoming joint SpIRIT and HERMES-TP/SP constellation for the localisation of high-energy transients through triangulation of signal arrival times. SpIRIT is an Australian technology and science demonstrator satellite designed to operate in a low-Earth Sun-synchronous Polar orbit that will augment the science operations for the equatorial HERMES-TP/SP constellation. In this work we simulate the improvement to the localisation capabilities of the HERMES-TP/SP constellation when SpIRIT is included in an orbital plane nearly perpendicular (inclination = 97.6°) to the HERMES-TP/SP orbits. For the fraction of GRBs detected by three of the HERMES satellites plus SpIRIT, we find that the combined constellation is capable of localising 60% of long GRBs to within ${\sim}30\,\textrm{deg}^{2}$ on the sky, and 60% of short GRBs within ${\sim}1850\,\textrm{deg}^{2}$ ($1\sigma$ confidence regions), though it is beyond the scope of this work to characterise or rule out systematic uncertainty of the same order of magnitude. Based purely on statistical GRB localisation capabilities (i.e., excluding systematic uncertainties and sky coverage), these figures for long GRBs are comparable to those reported by the Fermi Gamma Burst Monitor instrument. These localisation statistics represents a reduction of the uncertainty for the burst localisation region for both long and short GRBs by a factor of ${\sim}5$ compared to the HERMES-TP/SP alone. Further improvements by an additional factor of 2 (or 4) can be achieved by launching an additional 4 (or 6) SpIRIT-like satellites into a Polar orbit, respectively, which would both increase the fraction of sky covered by multiple satellite elements, and also enable localisation of ${\geq} 60\%$ of long GRBs to within a radius of ${\sim}1.5^{\circ}$ (statistical uncertainty) on the sky, clearly demonstrating the value of a distributed all-sky high-energy transient monitor composed of nano-satellites.
Early life trauma (ELT) refers to various types of adversity that occur during the early years (usually defined as the first 5 years) of a person’s life. It is a key determinant of mental health and well-being throughout the life course. A series of three workshops on early life trauma and mental health care were conducted in Belarus and Ukraine in 2018-2019 to support stakeholders and service providers to better understand and respond to ELT, and to support the development of a network of ELT specialists dedicated to finding common goals, pooling cross-disciplinary data and sharing experiences and good practice across countries. The workshops found that different attitudes, expectations and experiences amongst stakeholders and service providers could hinder the development of consistent, effective and empowering care in Belarus and Ukraine. However, opportunities for more protective and health-enhancing responses were also identified, including the need for: evidence-based education and training; clear roles and communication pathways across sectors; and inter-sectoral partnerships and networks to leverage resources, mitigate practitioner burnout, and build a continuum of support within communities. Findings have been disseminated through a directory of resources in Belarus, a project webpage (www.earlylifetrauma.info) and a report on ELT in Belarus and Ukraine published by WHO Europe.
Belarus is undergoing legislative shifts towards community-based mental health care. Responding effectively to support this process requires an understanding of the experiences and challenges facing families caring for a relative affected by mental illness.
Objectives
To identify how caring for a person with severe mental illness impacts on family carers, and what carers identify as their support needs.
Methods
Semi-structured interviews were undertaken with 17 caregivers of people affected by severe mental illness (diagnosis of F06.8, F20, F25, F7, and/or F 84) in Belarus between March - June 2019.
Results
Care-giving for a family member was usually undertaken on a full time basis with no option for respite. Whilst caring did, in cases, strengthen family solidarity, it also resulted in intensive stress and burnout, financial pressures, and high levels of family tension, exacerbated when the person living with mental illness was perceived as a potential safety risk. High levels of societal stigma meant that care-givers commonly felt unable to discuss their circumstances, travel in public spaces, or participate in community activities. Stigma also deterred carers from seeking professional support. Priorities for support amongst carers included better information, public awareness raising and sensitization, advocacy to support patient integration into social and economic life, peer support and respite for family carers, and an increase in mental health specialists.
Conclusions
Caregiving affected family carers on multiple levels with predominantly negative consequences. Priorities identified by carers need to be considered and acted upon if community-based care is to become an effective option.
The Personal and Social Performance (PSP) scale is a reliable and valid instrument that utilizes objective parameters for assessment of social functioning in patients with schizophrenia. The aim of this study was to determine the validity and reliability of the French version of PSP in a population of French schizophrenic patients.
Methods
Patients with DSM-IV diagnoses of schizophrenia and schizoaffective disorder were recruited and assessed in a cross-sectional design using the PSP, GAF, SOFS, PANSS, CGI severity. Internal consistency for the PSP was obtained and convergent validity was assessed using correlations between PSP, GAF and PANSS factors. Inter-rater reliability was evaluated with intra class correlation coefficient (ICC).
Results
147 in and out patients, at 5 French sites participated in this study. The Cronbach's alpha coefficient of the PSP was good (alpha=0.77). The PSP showed very good inter rater reliability (ICC = 0.90). Pearson correlation coefficient for association between PSP and GAF (r=0.85) and PSP and SOFS (r=- 0.78).are high proving good convergent validity for PSP. Pearson correlation coefficients are moderate when PSP is correlated with 4 of the five PANSS sub factors (r from -0.43 to -0.48). The anxious and depression factor (r=-0.17) showed low correlation with PSP. Spearman Rank correlation coefficient between PSP and CGI severity was r=-0.72.
Conclusions
Our results demonstrate that the PSP scale is a reliable and valid instrument for assessing social functioning of patients with schizophrenia during the course of treatment as well as in acute state.
Body image disturbances are core symptoms of Anorexia Nervosa (AN). This study investigated self-face recognition in cases of AN, and the influence of others factors associated with AN, such as massive weight loss.
Method
Fifteen anorexic female patients and 15 matched Healthy Controls (HC) performed a self-face recognition task. Participants viewed digital morphs between their own face and a gender-matched, unfamiliar other face presented in a random sequence (Fig. 1). For each stimulus, subjects were asked if they recognized their own face, and respond by selectively pressing a button on a computer. Participants’ self-face recognition failures, cognitive flexibility, body concerns and eating habits were assessed, respectively, with the Self-Face Recognition Questionnaire (SFRQ), the Trail Marking Task (TMT), the Body Shape Questionnaire (BSQ) and the Eating Disorder Inventory-2 (EDI-2).
Fig. 1
Examples of stimulus. For each subject, a photograph of an unfamiliar face was digitally morphed into a photograph of the subject's face in 10% increments.
results
Anorexic patients showed a significantly greater difficulty than healthy control in identifying their own face (P = 0.028, Fig. 2). No significant difference was observed between the two groups for TMT (all P > 0.1). However, analysis did not reveal significant correlations between behavioral data and the EDI-2 or BSQ (all P > 0.1). A correlation analysis revealed a significant, negative correlation with BMI (P < 0.001) and the SFRQ “self-face recognition” subscale (P = 0.015).
Fig. 2
Self response rates per stimulus ranked in increasing order of familiarity (other to self) in both groups.
Discussion
We observed a decrease in self-face recognition, correlated with BMI, suggesting this disturbance could be linked to massive weight loss. It thus supports the theory of a lack of ability to update body image by the central nervous system, underlying self-images distortion in AN patients.
This chapter describes the current state of, and normative basis for, the law of reasonable royalties among the leading jurisdictions for patent infringement litigation, as well as the principal arguments for and against various practices relating to the calculation of reasonable royalties; and for each of the major issues discussed, the chapter provides one or more recommendations. The chapter’s principal recommendation is that, when applying a “bottom-up” approach to estimating reasonable royalties, courts should replace the Georgia-Pacific factors (and analogous factors used outside the United States) with a smaller list of considerations, specifically (1) calculating the incremental value of the invention and dividing it appropriately between the parties; (2) assessing market evidence, such as comparable licenses; and (3) where feasible and cost justified, using each of these first two considerations as a “check” on the accuracy of the other
Patent systems commonly empower courts to order accused or adjudged infringers to refrain from continuing infringing conduct in the future. Some patentees file suit for the primary purpose of obtaining and enforcing an injunction against infringement by a competitor, and even in cases in which the patentee is willing to license an invention to an accused infringer for an agreed price, the indirect monetary value of an injunction against future infringement can dwarf the amount a finder of fact is likely to award as compensation for past infringement. In some of these cases, an injunction, if granted, would impose costs on accused infringers or third parties that go well beyond the more intrinsic value of the patented technology. This chapter explores the theory behind injunctive relief in patent cases, surveys the availability of this remedy in major patent systems, and suggests a general framework for courts to use when deciding whether injunctive relief is appropriate in individual cases.
Childhood adversity is associated with poor mental and physical health outcomes across the life span. Alterations in the hypothalamic–pituitary–adrenal axis are considered a key mechanism underlying these associations, although findings have been mixed. These inconsistencies suggest that other aspects of stress processing may underlie variations in this these associations, and that differences in adversity type, sex, and age may be relevant. The current study investigated the relationship between childhood adversity, stress perception, and morning cortisol, and examined whether differences in adversity type (generalized vs. threat and deprivation), sex, and age had distinct effects on these associations. Salivary cortisol samples, daily hassle stress ratings, and retrospective measures of childhood adversity were collected from a large sample of youth at risk for serious mental illness including psychoses (n = 605, mean age = 19.3). Results indicated that childhood adversity was associated with increased stress perception, which subsequently predicted higher morning cortisol levels; however, these associations were specific to threat exposures in females. These findings highlight the role of stress perception in stress vulnerability following childhood adversity and highlight potential sex differences in the impact of threat exposures.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
Methods
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
Results
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
Conclusions
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
Ten montmorillonites of different origins with variable Fe contents were analysed using transmission IR spectroscopy. Special attention was devoted to the OH-bending region to obtain information about the distribution of octahedral cations. For low to medium Fe contents (≤0.56 per Si8 formula unit), a linear relationship between the position of the δAlFeOH band and Fe content was observed. Such correlation might be explained by changes in the cis-trans occupancy of Fe in the octahedral sheet. Deconvolution of the OH-bending domain allows us to discriminate three components (δAlAlOH, δAlMgOH and δAlFeOH) which are correlated with cation abundances derived from chemical analysis. The relative area of each band can then be compared with theoretical areas calculated assuming a fully random distribution of cations in the octahedral sheet. Using such treatment, eight of the 10 montmorillonites studied presented a nearly randomized octahedral distribution. The two samples from Wyoming were clearly different as they exhibited a strong ordering tendency.
Evidence suggests that skin picking disorder (SPD) could be a prevalent condition associated with comorbidity and psychosocial dysfunction. However, just a few studies have assessed the prevalence and correlates of SPD in samples from low- and middle-income countries. In addition, the impact of SPD on quality of life (QoL) dimension after multivariable adjustment to potential confounders remains unclear.
Methods
Data were obtained from a Brazilian anonymous Web-based research platform. Participants provided sociodemographic data and completed the modified Skin Picking–Stanford questionnaire, the Hypomania Checklist (HCL-32), the Patient Health Questionnaire-9 (PHQ-9), the Fagerström Test for Nicotine Dependence, Alcohol Use Disorder Identification Test (AUDIT), Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report–short form, and the World Health Organization quality of life abbreviated scale (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models.
Results
For our survey, 7639 participants took part (71.3% females; age: 27.2±7.9 years). The prevalence of SPD was 3.4% (95% CI: 3.0–3.8%), with a female preponderance (P<0.001). In addition, SPD was associated with a positive screen for a major depressive episode, nicotine dependence, and alcohol dependence, as well as suicidal ideation. Physical and psychological QoL was significantly more impaired in participants with SPD compared to those without SPD, even after adjustment for comorbidity.
Conclusions
In this large sample, SPD was a prevalent condition associated with co-occurring depression, nicotine, and alcohol dependence. In addition, SPD was independently associated with impaired physical and psychological QoL. Public health efforts toward the early recognition and treatment of SPD are warranted.
The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.
An experimental investigation of an unsteady adverse pressure gradient turbulent boundary layer is described. It is demonstrated that the local flow physics is largely dominated by an inflectional instability which gives rise to an embedded shear layer contained within the boundary layer. Experimental measurements are presented which are fully consistent with the presence of clockwise spanwise-oriented coherent vorticity within the embedded shear layer. Using embedded shear layer scaling parameters in the form of the shear layer vorticity thickness and the velocity defect at the upper inflection point, both the mean and the phase-averaged boundary layer velocity profiles exhibit similarity in both space and time over a large wall-normal extent. In a similar manner, the profiles of the streamwise-component turbulence intensity and Reynolds stress also exhibit similarity when scaled with the embedded shear layer parameters. The embedded shear layer scaling of previously published adverse pressure gradient turbulent boundary layer measurements confirms its generic applicability in a wide range of flow-field geometries and extending to high Reynolds numbers.
Glyphosate-resistant crop species have increased in number over the past decade as growers eagerly adopt this simple and effective weed management technology. Glyphosate-resistant wheat cultivars are being developed and may soon be available to growers. The objective of this paper is to discuss the pest management implications of glyphosate-resistant wheat in the western United States, a region stretching from the Great Plains to the Pacific Ocean that produces more than 80% of the nation's wheat crop. The benefits of glyphosate-resistant wheat include: (1) improved weed control, particularly of difficult-to-control weeds, such as winter annual grasses belonging to the Aegilops, Avena, Bromus, Lolium, Poa, Secale, and Setaria genera; (2) an ability to control weeds resistant to currently available wheat herbicides; (3) an extended application window for control of late-emerging weeds; and (4) improved crop safety. Although these benefits are not to be minimized, they need to be considered in the light of the concerns surrounding this new technology in wheat. These concerns are about (1) the lack of an equally effective and affordable herbicide to control glyphosate-resistant volunteer wheat, which may increase wheat diseases such as wheat streak mosaic and Rhizoctonia root rot; (2) the possibility that overreliance on glyphosate will lead to species shifts, with unknown consequences for weed management in wheat; and (3) the use of multiple glyphosate-resistant crops in rotation with glyphosate-resistant wheat, which could rapidly increase glyphosate-resistant weeds, thereby limiting the future utility of glyphosate. If, or when, glyphosate-resistant wheat becomes commercially available, it will require careful management to sustain its usefulness. We have proposed several areas of research that we feel are critical to help develop sound management guidelines for deployment and use of this new weed management technology in wheat. These include (1) developing effective “green bridge” management strategies, i.e., using cultural and chemical approaches to control plants that sustain insect vector populations between wheat crop periods; (2) predicting potential weed species shifts resulting from the use of glyphosate-resistant wheat; and (3) developing management systems that include herbicide-resistant wheat on a rotational basis and rotating the use of glyphosate with other weed management strategies in the fallow period to minimize the potential development of glyphosate-resistant weeds or weed communities.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.