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Psychiatric symptoms are typically highly inter-correlated at the group level. Collectively, these correlations define the architecture of psychopathology – informing taxonomic and mechanistic models in psychiatry. However, to date, it remains unclear if this architecture differs between etiologically distinct subgroups, despite the core relevance of this understanding for personalized medicine. Here, we introduce a new analytic pipeline to probe group differences in the psychopathology architecture – demonstrated through the comparison of two distinct neurogenetic disorders.
Methods
We use a large questionnaire battery in 300 individuals aged 5–25 years (n = 102 XXY/KS, n = 64 XYY, n = 134 age-matched XY) to characterize the structure of correlations among 53 diverse measures of psychopathology in XXY/KS and XYY syndrome – enabling us to compare the effects of X- versus Y-chromosome dosage on the architecture of psychopathology at multiple, distinctly informative levels.
Results
Behavior correlation matrices describe the architecture of psychopathology in each syndrome. A comparison of matrix rows reveals that social problems and externalizing symptoms are most differentially coupled to other aspects of psychopathology in XXY/KS versus XYY. Clustering the difference between matrices captures coordinated group differences in pairwise coupling between measures of psychopathology: XXY/KS shows greater coherence among externalizing, internalizing, and autism-related features, while XYY syndrome shows greater coherence in dissociality and early neurodevelopmental impairment.
Conclusions
These methods offer new insights into X- and Y-chromosome dosage effects on behavior, and our shared code can now be applied to other clinical groups of interest – helping to hone mechanistic models and inform the tailoring of care.
Adolescents with depression have distinct affective reactions to daily events, but current research is controversial. The emotional context insensitivity theory suggests blunted reactivity in depression, whereas the hypotheses of negative potentiation and mood brightening effect suggest otherwise. While nonlinear associations between depression severity and affective reactivity have been observed, studies with a separate subclinical group remain rare. Subthreshold depression (SD), defined by two to four symptoms lasting for two weeks or more, provides a dimensional view to the underpinnings of affective reactivity. In this study, we compared positive affect (PA) and negative affect (NA) reactivity to positive and negative daily events (uplifts and stress) among adolescents with Major Depressive Disorder (MDD), SD and healthy controls (HC) using experience sampling methods (ESM).
Objectives
We hypothesized a stepped difference in affective reactivity along the depression spectrum: the MDD group will have the strongest reactivity of PA and NA to uplifts and stress, followed by SD and HC.
Methods
Three groups (MDD, SD, and HC) of adolescents were recruited from an epidemiologic sample entitled ‘Hong Kong Child and Adolescent Psychiatric Epidemiologic Survey: Age 6 to 17’. Group status was determined by the Diagnostic Interview Schedule for Children Version 5. They completed an experience sampling diary on smartphone for 14 consecutive days, with 5-10 entries per day. Momentary levels of PA (happy, relaxed, contented), NA (irritated, low, nervous), uplifts and stress experienced before the entry were measured on a 1-7 Likert scale.
Results
The sample consisted of 19 adolescents with MDD, 30 with SD, and 59 HC. The M:F ratio was 17:19. The age range was 12-18 with a mean of 14.8. The overall ESM completion rate was 46%. The MDD group had the highest levels of stress and NA, and the lowest levels of uplifts and PA, followed by the SD and HC groups respectively (p<0.01). Across groups, levels of PA were positively associated with uplifts and negatively associated with stress, whereas levels of NA were positively associated with stress and negatively associated with uplifts. The Group x Uplift interaction effect on PA was significant, with greater PA reactivity in SD (p<0.01) and MDD (p=0.07) when compared with HC. The Group x Uplift interaction effect on NA was significant, with greater NA reactivity in SD than HC (p<0.01). The Group x Stress interaction effect on PA was significant, with greater PA reactivity in SD than HC (p<0.01) and MDD (p<0.01). The Group x Stress interaction effect with NA is non-significant.
Conclusions
Contrary to our hypothesis, adolescents with SD experienced strongest PA and NA reactivity in uplifts and PA reactivity in stress. It provides evidence towards a nonlinear relationship between severity of depression and affective reactivity.
Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.
Ultrafast optical probing is a widely used method of underdense plasma diagnostic. In relativistic plasma, the motion blur limits spatial resolution in the direction of motion. For many high-power lasers the initial pulse duration of 30–50 fs results in a 10–15 μm motion blur, which can be reduced by probe pulse post-compression. Here we used the compression after compressor approach [Phys.-Usp. 62, 1096 (2019); JINST 17 P07035 (2022)], where spectral broadening is performed in thin optical plates and is followed by reflections from negative-dispersion mirrors. Our initially low-intensity probe beam was down-collimated for a more efficient spectral broadening and higher probe-to-self-emission intensity ratio. The setup is compact, fits in a vacuum chamber and can be implemented within a short experimental time slot. We proved that the compressed pulse retained the high quality necessary for plasma probing.
Schistosoma species have traditionally been arranged in groups based on egg morphology, geographical origins, and the genus or family of snail intermediate host. One of these groups is the ‘S. indicum group’ comprising species from Asia that use pulmonate snails as intermediate hosts. DNA sequences were obtained from the four members of this group (S. indicum, S. spindale, S. nasale and S. incognitum) to provide information concerning their phylogenetic relationships with other Asian and African species and species groups. The sequences came from the second internal transcribed spacer (ITS2) of the ribosomal gene repeat, part of the 28S ribosomal RNA gene (28S), and part of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene. Tree analyses using both distance and parsimony methods showed the S. indicum group not to be monophyletic. Schistosoma indicum, S. spindale and S. nasale were clustered among African schistosomes, while S. incognitum was placed as sister to the African species (using ITS2 and 28S nucleotide sequences and CO1 amino acid sequences), or as sister to all other species of Schistosoma (CO1 nucleotide sequences). Based on the present molecular data, a scenario for the evolution of the S. indicum group is discussed.
The status of Schistosoma sinensium (samples from Thailand and from Sichuan, China) relative to other species of the genus Schistosoma was investigated using DNA sequences from the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene (partial) and the nuclear ribosomal DNA second internal transcribed spacer 2 (ITS2). Trees inferred from these sequences place S. sinensium as sister to the S. japonicum group and suggest a basal position in the clade utilizing snails of the family Pomatiopsidae. The sequence differences between specimens of S. sinensium from China and Thailand are at least as great as between S. malayensis and S. mekongi. Schistosoma sinensium is probably best regarded as a species complex.
Physically compliant actuator brings significant benefits to robots in terms of environmental adaptability, human–robot interaction, and energy efficiency as the introduction of the inherent compliance. However, this inherent compliance also limits the force and position control performance of the actuator system due to the induced oscillations and decreased mechanical bandwidth. To solve this problem, we first investigate the dynamic effects of implementing variable physical damping into a compliant actuator. Following this, we propose a structural scheme that integrates a variable damping element in parallel to a conventional series elastic actuator. A damping regulation algorithm is then developed for the parallel spring-damping actuator (PSDA) to tune the dynamic performance of the system while remaining sufficient compliance. Experimental results show that the PSDA offers better stability and dynamic capability in the force and position control by generating appropriate damping levels.
The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
Background: Neurosurgery is a high-risk specialty with a low margin of error. We aim to assess the risk of neurosurgeons being involved in medicolegal cases in Canada. Methods: This retrospective descriptive study evaluated ten years (2012-2021) of closed legal cases, college cases, and hospital complaints against neurosurgeons with data from the CMPA. Included cases were cranial cases, VP shunts, or cases where a catheter or wire was inserted into the brain. Cases excluded angiography, radiation, ultrasound, or percutaneous procedures. Results: We identified 77 cases (66 urgent or emergent). Neurosurgeons had a significantly higher medicolegal risk than the CMPA surgeon membership, however lower risk compared to all physician specialties. Legal cases accounted for 69% with favourable outcomes in 52%. Forty-one cases involved post-operative complications and 16 cases involved VP shunts. Multiple surgeons or residents could be involved spanning age groups and years in practice. Thirty-four cases had a harmful incident, 41% of these severe. The majority of cases occurred at urban centers. The average case duration was 41 months. Conclusions: This study provides a recent medicolegal analysis of cranial neurosurgery in Canada. We identified areas of common complaints and hope the data can be used to mitigate risk surgical risk in the future.
Accumulating evidence suggests that positive and negative emotions, as well as emotion regulation, play key roles in human health and disease. Recent work has shown the gut microbiome is important in modulating mental and physical health through the gut–brain axis. Yet, its association with emotions and emotion regulation are understudied. Here we examined whether positive and negative emotions, as well as two emotion regulation strategies (i.e. cognitive reappraisal and suppression), were associated with the gut microbiome composition and functional pathways in healthy women.
Methods
Participants were from the Mind-Body Study (N = 206, mean age = 61), a sub-study of the Nurses' Health Study II cohort. In 2013, participants completed measures of emotion-related factors. Two pairs of stool samples were collected, 6 months apart, 3 months after emotion-related factors measures were completed. Analyses examined associations of emotion-related factors with gut microbial diversity, overall microbiome structure, and specific species/pathways and adjusted for relevant covariates.
Results
Alpha diversity was negatively associated with suppression. In multivariate analysis, positive emotions were inversely associated with the relative abundance of Firmicutes bacterium CAG 94 and Ruminococcaceae bacterium D16, while negative emotions were directly correlated with the relative abundance of these same species. At the metabolic pathway level, negative emotions were inversely related to the biosynthesis of pantothenate, coenzyme A, and adenosine.
Conclusions
These findings offer human evidence supporting linkages of emotions and related regulatory processes with the gut microbiome and highlight the importance of incorporating the gut microbiome in our understanding of emotion-related factors and their associations with physical health.
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.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
Background: Despite a higher prevalence of traumatic spinal cord injury (TSCI) amongst Canadian Indigenous peoples, there is a paucity of studies focused on Indigenous TSCI. We present the first Canada-wide study comparing TSCI amongst Canadian Indigenous and non-Indigenous peoples. Methods: This study is a retrospective analysis of prospectively-collected TSCI data from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) from 2004-2019. We divided participants into Indigenous and non-Indigenous cohorts and compared them with respect to demographics, injury mechanism, level, severity, and outcomes. Results: Compared with non-Indigenous patients, Indigenous patients were younger, more female, less likely to have higher education, and less likely to be employed. The mechanism of injury was more likely due to assault or transportation-related trauma in the Indigenous group. The length of stay for Indigenous patients was longer. Indigenous patients were more likely to be discharged to a rural setting, less likely to be discharged home, and more likely to be unemployed following injury. Conclusions: Our results suggest that more resources need to be dedicated for transitioning Indigenous patients sustaining a TSCI to community living and for supporting these patients in their home communities. A focus on resources and infrastructure for Indigenous patients by engagement with Indigenous communities is needed.
Background: Chordomas are rare malignant skull-base/spine cancers with devastating neurological morbidities and mortality. Unfortunately, no reliable prognostic factors exist to guide treatment decisions. This work identifies DNA methylation-based prognostic chordoma subtypes that are detectable non-invasively in plasma. Methods: Sixty-eight tissue samples underwent DNA methylation profiling and plasma methylomes were obtained for available paired samples. Immunohistochemical staining and publicly available methylation and gene expression data were utilized for validation. Results: Unsupervised clustering identified two prognostic tissue clusters (log-rank p=0.0062) predicting disease-specific survival independent of clinical factors (Multivariable Cox: HR=16.5, 95%CI: 2.8-96, p=0.0018). The poorer-performing cluster showed immune-related pathway promoter hypermethylation and higher immune cell abundance within tumours, which was validated with external RNA-seq data and immunohistochemical staining. The better-performing cluster showed higher tumour cellularity. Similar clusters were seen in external DNA methylation data. Plasma methylome-based models distinguished chordomas from differential diagnoses in independent testing sets (AUROC=0.84, 95%CI: 0.52-1.00). Plasma methylomes were highly correlated with tissue-based signals for both clusters (r=0.69 & 0.67) and leave-one-out models identified the correct cluster in all plasma cases. Conclusions: Prognostic molecular chordoma subgroups are for the first time identified, characterized, and validated. Plasma methylomes can detect and subtype chordomas which may transform chordoma treatment with personalized approaches tailored to prognosis.
In this study, an active defence cooperative guidance (ADCG) law that enables cheap and low-speed airborne defence missiles with low manoeuverability to accurately intercept fast and expensive attack missiles with high manoeuverability was designed to enhance the capability of aircraft for active defence. This guidance law relies on the line-of-sight (LOS) guidance method, and it realises active defence by adjusting the geometric LOS relationship involving an attack missile, a defence missile and an aircraft. We use a nonlinear integral sliding surface and an improved second-order sliding mode reaching law to design the guidance law. This can not only reduce the chattering phenomenon in the guidance command, but it can also ensure that the system can reach the sliding surface from any initial position in a finite time. Simulations were carried out to verify the proposed law using four cases: different manoeuvering modes of the aircraft, different speed ratios of the attack and defence missiles, different reaching laws applied to the ADCG law and a robustness analysis. The results show that the proposed guidance law can enable a defence missile to intercept an attack missile by simultaneously using information about the relative motions of the attack missile and the aircraft. It is also highly robust in the presence of errors and noise.
Weapon target allocation (WTA) is an effective method to solve the battlefield fire optimisation problem, which plays an important role in intelligent automated decision-making. We researched the multitarget allocation problem to maximise the attack effectiveness when multiple interceptors cooperatively attack multiple ground targets. Firstly, an effective and reasonable fitness function is established, based on the situation between the interceptors and targets, by comprehensively considering the relative range, relative angle, speed, capture probability and radiation source matching performance and thoroughly evaluating them based on the advantage of the attack effectiveness. Secondly, the optimisation performance of the particle swarm optimisation (PSO) algorithm is adaptively improved. We propose an adaptive simulated annealing-particle swarm optimisation (SA-PSO) algorithm by introducing the simulated annealing algorithm into the adaptive PSO algorithm. The proposed algorithm can enhance the convergence speed and overcome the disadvantage of the PSO algorithm easily falling into a local extreme point. Finally, a simulation example is performed in a scenario where ten interceptors cooperate to attack eight ground targets; comparative experiments are conducted between the adaptive SA-PSO algorithm and PSO algorithm. The simulation results indicate that the proposed adaptive SA-PSO algorithm demonstrates great performance in convergence speed and global optimisation capabilities, and a maximised attack effectiveness can be guaranteed.
High-energy and high-intensity lasers are essential for pushing the boundaries of science. Their development has allowed leaps forward in basic research areas, including laser–plasma interaction, high-energy density science, metrology, biology and medical technology. The Helmholtz International Beamline for Extreme Fields user consortium contributes and operates two high-peak-power optical lasers using the high energy density instrument at the European X-ray free electron laser (EuXFEL) facility. These lasers will be used to generate transient extreme states of density and temperature to be probed by the X-ray beam. This paper introduces the ReLaX laser, a short-pulse high-intensity Ti:Sa laser system, and discusses its characteristics as available for user experiments. It will also present the first experimental commissioning results validating its successful integration into the EuXFEL infrastructure and viability as a relativistic-intensity laser driver.
This chapter uses evidence from the Parenting across Cultures (PAC) project to illustrate ways in which longitudinal data can help achieve the Sustainable Development Goals (SDGs; https://sustainabledevelopment.un.org/). The chapter begins by providing an overview of the research questions that have guided PAC as well as a description of the participants, procedures and measures. Next, empirical findings from PAC are summarized to illustrate implications for six specific SDGs. Then the chapter describes how longitudinal data offer advantages over cross-sectional data in operationalizing SDG targets and implementing the SDGs. Finally, limitations, future research directions and conclusions are provided.
PAC was developed in response to concerns that understanding of parenting and child development was biased by the predominant focus in the literature on studying families in Western, educated, industrialized, rich and democratic (WEIRD) societies and that findings in such countries may not generalize well to more diverse populations around the world (Henrich et al, 2010). In an analysis of the sample characteristics in the most influential journals in six subdisciplines of psychology from 2003 to 2007, 96% of research participants were from Western industrialized countries, and 68% were from the United States alone (Arnett, 2008), which means that 96% of research participants in these psychological studies were from countries with only 12% of the world's population (Henrich et al, 2010). When basic science research is limited to WEIRD countries, knowledge of human development becomes defined by a set of experiences that may not be widely shared in different cultural contexts, so studying parenting and child development in a wide range of diverse cultural contexts is important to understand development more fully.
PAC has been conceptualized and funded as a consecutive series of three five-year grants, each covering a different developmental period and guided by different research questions. In the first project period, participants were aged 8 to 12. The main research questions focused on cultural differences in links between discipline and child adjustment, warmth as a moderator of links between harsh discipline and child outcomes, and cognitive and emotional mediators of effects of harsh discipline on children's aggression and anxiety. In the second period, target participants were 13 to 17 years old.
This study was a retrospective multicentre cohort study of patients with coronavirus disease 2019 (COVID-19) diagnosed at 24 hospitals in Jiangsu province, China as of 15 March 2020. The primary outcome was the occurrence of acute respiratory failure during hospital stay. Of 625 patients, 56 (9%) had respiratory failure. Some selected demographic, epidemiologic, clinical and laboratory features as well as radiologic features at admission and treatment during hospitalisation were significantly different in patients with and without respiratory failure. The multivariate logistic analysis indicated that age (in years) (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.03–1.10; P = 0.0002), respiratory rate (breaths/minute) (OR, 1.23; 95% CI: 1.08–1.40; P = 0.0020), lymphocyte count (109/l) (OR, 0.18; 95% CI: 0.05–0.69; P = 0.0157) and pulmonary opacity score (per 5%) (OR, 1.38; 95% CI: 1.19–1.61; P < 0.0001) at admission were associated with the occurrence of respiratory failure. Older age, increased respiratory rate, decreased lymphocyte count and greater pulmonary opacity score at admission were independent risk factors of respiratory failure in patients with COVID-19. Patients having these risk factors need to be intensively managed during hospitalisation.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.