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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.
The digital twin approach has gained recognition as a promising solution to the challenges faced by the Architecture, Engineering, Construction, Operations, and Management (AECOM) industries. However, its broader application across some AECOM sectors remains limited. A significant obstacle is that traditional DTs rely on deterministic models, which require deterministic input parameters. This limits their accuracy, as they do not account for the substantial uncertainties that are inherent in AECOM projects. These uncertainties are particularly pronounced in geotechnical design and construction. To address this challenge, we propose a probabilistic digital twin (PDT) framework that extends traditional DT methodologies by incorporating uncertainties and is tailored to the requirements of geotechnical design and construction. The PDT framework provides a structured approach to integrating all sources of uncertainty, including aleatoric, data, model, and prediction uncertainties, and propagates them throughout the entire modeling process. To ensure that site-specific conditions are accurately reflected as additional information is obtained, the PDT leverages Bayesian methods for model updating. The effectiveness of the PDT framework is showcased through an application to a highway foundation construction project, demonstrating its potential to integrate existing probabilistic methods to improve decision-making and project outcomes in the face of significant uncertainties. By embedding these methods within the PDT framework, we lower the barriers to practical implementation, making probabilistic approaches more accessible and applicable in real-world engineering workflows.
Microbial mineral weathering has been predominantly investigated at shallow depths in humid and tropical environments. Much less is understood about its role in the deeper subsurface of arid and semi-arid environments where microbial weathering is limited by the availability of water and energy sources for microbial metabolism. However, the deep subsurface in these climate zones may host a microbial community that thrives on weathering of iron (Fe)-bearing minerals that serve as electron donors or acceptors.
To investigate the role of microorganisms in weathering of Fe-bearing minerals in a dry climate, we recovered a >80 m deep weathering profile in a semi-arid region of the Chilean Coastal Cordillera. The bedrock is rich in Fe-bearing minerals (hornblende, biotite, chlorite, magnetite and hematite) but lacks detectable organic carbon. We evaluated the bioavailability of Fe(III)-bearing minerals that may serve as an electron acceptor for Fe(III)-reducing microorganisms. Using geochemical, mineralogical and cultivation-based methods, we found enhanced Fe bioavailability and more in vitro microbial Fe(III) reduction at increased depth. We obtained an Fe(III)-reducing enrichment culture from the deepest weathered rock found at 77 m depth. This enrichment culture is capable of reducing ferrihydrite (up to 0.6 mM d–1) using lactate or dihydrogen as an electron donor and grows at circumneutral pH. The main organism in the enrichment culture is the spore-forming Desulfotomaculum ruminis (abundance of 98.5%) as revealed by 16S rRNA gene amplicon sequencing.
Our findings provide evidence for a microbial contribution to the weathering of Fe-bearing minerals in semi-arid environments. While microorganisms are probably not contributing to the weathering of Fe(II)-bearing silicate minerals, they are most likely of importance regarding reductive dissolution of secondary weathering products. The Fe(III) reduction quantified in this weathering profile by the in situ microbial community suggests that microorganisms are active weathering agents in semi-arid climates.
Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.
Methods
We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.
Results
Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.
Conclusions
Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.
The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.
Methods
Our approach involved a two-step procedure. First, we conducted a review of prior studies utilizing the PAI, evaluating each study using the Prediction model study Risk Of Bias Assessment Tool (PROBAST). We specifically assessed whether the studies adhered to two standards of predictive modeling: refraining from using leave-one-out cross-validation (LOO CV) and preventing data leakage. Second, we examined the impact of deviating from these methodological standards in real data. We employed both a traditional approach violating these standards and an advanced approach implementing them in two large-scale datasets, PANIC-net (n = 261) and Protect-AD (n = 614).
Results
The PROBAST-rating revealed a substantial risk of bias across studies, primarily due to inappropriate methodological choices. Most studies did not adhere to the examined prediction modeling standards, employing LOO CV and allowing data leakage. The comparison between the traditional and advanced approach revealed that ignoring these standards could systematically overestimate the utility of the PAI.
Conclusion
Our study cautions that violating standards in predictive modeling may strongly influence the evaluation of the PAI's utility, possibly leading to false positive results. To support an unbiased evaluation, crucial for potential clinical application, we provide a low-bias, openly accessible, and meticulously annotated script implementing the PAI.
The avoidance of asthma triggers, like tobacco smoke, facilitates asthma management. Reliance upon caregiver report of their child’s environmental tobacco smoke (ETS) exposure may result in information bias and impaired asthma management. This analysis aimed to characterize the chronicity of ETS exposure, assess the validity of caregiver report of ETS exposure, and investigate the relationship between ETS exposure and asthma attack.
Methods:
A secondary data analysis was performed on data from a longitudinal study of 162 children aged 7–12 years with asthma living in federally subsidized housing in three US cities (Boston, Cincinnati, and New Orleans). Data were collected at three time points over 1 year.
Results:
Over 90% of children were exposed to ETS (≥0.25 ng/ml of urine cotinine (UC)). Exposure was consistent over 1 year. Questionnaire data had a sensitivity of 28–34% using UC ≥0.25 ng/ml as the gold standard. High ETS exposure (UC ≥ 30 ng/ml) was significantly associated with asthma attack (aOR 2.97, 0.93–9.52, p = 0.07). Lower levels (UC 0.25–30 ng/ml) were not statistically significant (aOR 1.76, 0.71– 4.38, p = 0.22). No association was found using caregiver-reported ETS exposure.
Conclusion:
Relying on questionnaire data to assess children’s exposure to tobacco smoke may lead to substantial information bias. For children with asthma, incorrect characterization may substantially impact asthma morbidity.
To maximize its value, the design, development and implementation of structural health monitoring (SHM) should focus on its role in facilitating decision support. In this position paper, we offer perspectives on the synergy between SHM and decision-making. We propose a classification of SHM use cases aligning with various dimensions that are closely linked to the respective decision contexts. The types of decisions that have to be supported by the SHM system within these settings are discussed along with the corresponding challenges. We provide an overview of different classes of models that are required for integrating SHM in the decision-making process to support the operation and maintenance of structures and infrastructure systems. Fundamental decision-theoretic principles and state-of-the-art methods for optimizing maintenance and operational decision-making under uncertainty are briefly discussed. Finally, we offer a viewpoint on the appropriate course of action for quantifying, validating, and maximizing the added value generated by SHM. This work aspires to synthesize the different perspectives of the SHM, Prognostic Health Management, and reliability communities, and provide directions to researchers and practitioners working towards more pervasive monitoring-based decision-support.
Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations.
Methods:
In 410 male and female participants aged 17–35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites.
Results:
Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake.
Conclusions:
Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.
Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.
Methods
We addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.
Results
A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.
Conclusions
These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Christopher Smart’s drag orations as Mary Midnight were enabled by burgeoning British social policy legislation combined with widespread cultural aspirations for creating an educated British public through public oratory. Ironically, the state censorship enacted in the 1752 Public Entertainments Act, which sought to limit public performances outside the licensed London theatres, created conditions that enabled Smart’s innovative attempts at entertaining—and therefore creating—a public unified across class and gender differences through a mixture of humor, erudition, dance, and music, among other forms of performances (including trained dog and monkey acts). The case of Smart’s Mary Midnight is key to understanding the achievements and limits of a British urban entertainment industry in the mid eighteenth century that was dedicated to creating a civil public sphere, as well as making money.
Data-informed predictive maintenance planning largely relies on stochastic deterioration models. Monitoring information can be utilized to update sequentially the knowledge on model parameters. In this context, on-line (recursive) Bayesian filtering algorithms typically fail to properly quantify the full posterior uncertainty of time-invariant model parameters. Off-line (batch) algorithms are—in principle—better suited for the uncertainty quantification task, yet they are computationally prohibitive in sequential settings. In this work, we adapt and investigate selected Bayesian filters for parameter estimation: an on-line particle filter, an on-line iterated batch importance sampling filter, which performs Markov Chain Monte Carlo (MCMC) move steps, and an off-line MCMC-based sequential Monte Carlo filter. A Gaussian mixture model approximates the posterior distribution within the resampling process in all three filters. Two numerical examples provide the basis for a comparative assessment. The first example considers a low-dimensional, nonlinear, non-Gaussian probabilistic fatigue crack growth model that is updated with sequential monitoring measurements. The second high-dimensional, linear, Gaussian example employs a random field to model corrosion deterioration across a beam, which is updated with sequential sensor measurements. The numerical investigations provide insights into the performance of off-line and on-line filters in terms of the accuracy of posterior estimates and the computational cost, when applied to problems of different nature, increasing dimensionality and varying sensor information amount. Importantly, they show that a tailored implementation of the on-line particle filter proves competitive with the computationally demanding MCMC-based filters. Suggestions on the choice of the appropriate method in function of problem characteristics are provided.
Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme
Stigma resistance (SR) is defined as one's ability to deflect or challenge stigmatizing beliefs. SR is positively associated with patient's outcomes in serious mental illness (SMI). SR appears as a promising target for psychiatric rehabilitation as it might facilitate personal recovery.
Objectives
The objectives of the present study are: (i) to assess the frequency of SR in a multicentric non-selected psychiatric rehabilitation SMI sample; (ii) to investigate the correlates of high SR
Methods
A total of 693 outpatients with SMI were recruited from the French National Centers of Reference for Psychiatric Rehabilitation cohort (REHABase). Evaluation included standardized scales for clinical severity, quality of life, satisfaction with life, wellbeing, and personal recovery and a large cognitive battery. SR was measured using internalized stigma of mental illness – SR subscale.
Results
Elevated SR was associated with a preserved executive functioning, a lower insight into illness and all recovery-related outcomes in the univariate analyses. In the multivariate analysis adjusted by age, gender and self-stigma, elevated SR was best predicted by the later stages of personal recovery [rebuilding; p = 0.004, OR = 2.89 (1.36–4.88); growth; p = 0.005, OR = 2.79 (1.30–4.43)). No moderating effects of age and education were found.
Conclusion
The present study has indicated the importance of addressing SR in patients enrolled in psychiatric rehabilitation. Recovery-oriented psychoeducation, metacognitive therapies and family interventions might improve SR and protect against insight-related depression. The effectiveness of psychiatric rehabilitation on SR and the potential mediating effects of changes in SR on treatment outcomes should be further investigated in longitudinal studies.
This paper examines the velocity distribution function and cyclotron resonance conditions for a beam of electrons moving in a magnetic field which gradually changes with time. A spatial gradient of magnetic field is known to result in an unstable horseshoe distribution of electrons. The field gradient in time adds additional effects due to an induced electric field. The resultant anisotropic velocity distribution function, which we call a Luvdisk distribution, has some distinctive properties when compared to the horseshoe. Fitting the cyclotron resonance condition circle shows that the frequency of the resultant emission is under the local cyclotron frequency. While the spatial gradient results in the emission coming almost perpendicularly to the field, the direction of the radiation under a time-changing field has more variability. The Luvdisk distribution also arises when the magnetic field has a gradient both in space and time. The beam can be unstable if those gradients are added or subtracted from each other (if the gradients are of equal or different sign), which occurs even when the total change of magnetic field is negative. While the frequency of the emission is related to the final magnetic field value, its direction is indicative of the field’s history which produced the instability.
Recent studies by Cloninger suggest that the temperament dimension of harm avoidance might be related to serotonergic activity. Since serotonergic mechanisms equally play a major role in sleep regulation, we decided to use Cloninger’s psychobiological model of temperament and character to assess whether there is a link between psychophysiologic insomnia and specific personality traits. Chronic insomnia is a common complaint in modern society, and it is still controversial whether insomniacs share specific personality traits. Thirty-two chronic insomniacs (<50 years) were studied. They underwent polysomnography for two consecutive nights and filled out the 226-item self-questionnaire of Temperament and Character Inventory as well as the Hospital Anxiety and Depression scale. (1) Harm avoidance for all subscores was significantly higher in insomniac patients when compared with controls; (2) self-directedness scores were lower in insomniacs; (3) sleep latency was positively correlated to harm avoidance; (4) HA1 (anticipatory worry) was negatively correlated to REM latency. Temperament and Character Inventory is a useful tool in the investigation of chronic insomnia. Serotonergic mechanisms might explain the high incidence of harm avoidance as personality trait in psychophysiologic insomniac patients. Further studies are needed to see whether harm avoidance could be a psychological vulnerability marker for primary insomnia and be used as predictor of SSRI treatment responders.
The main symptoms of Gilles de la Tourette syndrome (GTS) are motor and vocal tics, but there are also several psychiatric disturbances such as obsessive compulsive symptoms (OCD) and mutilations. The etiology and pathophysiology of this basal ganglia disorder are unknown. Though many patients benefit from therapy with dopamine antagonists, the effect is often insufficient. Therapeutic efficacy of the opiate antagonist naltrexone has been described in recent years. Ten patients (three f, seven m) with GTS were invesitgated in a seven-week, open dose-response trial, using naltrexone in doses ranging from 12.5 mg to 200 mg/day. The severity of the GTS symptoms were rated with the Yale Global Tic Severity Scale (YGTSS) and the Tourette Syndrome Global Scale (TSGS); OCD was estimated by the Maudsley Obsessive Compulsive Inventory (MOCI). The course of tics and psychopathology was assessed by three self-report scales, and two scales rated by clinicians (Clinical Global Impression, CGI; Brief Psychiatric Rating Scale, BPRS). Only two patients showed improvement of the GTS. In four patients, no effect was observed, whereas the other four patients exhibited deterioration. One patient finished the complete trial, three patients dropped out because of lack of improvement, and four because of deterioration of the symptoms. Considering the mean values, no improvement of GTS could therefore be observed, and because of the unpredictable effect, the study was stopped after ten patients. Nevertheless, the effects were quite controversial. The opiate system seems to be affected only in some of the GTS patients in a clinically relevant manner, and opiate antogonists can either improve or provoke GTS symptoms. Pathophysiologically different subgroups of GTS may contribute to the controversal results.