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• In 2022, a case of paralytic polio in an unvaccinated adult resident of Rockland County was confirmed. • In the US, detection of a single case of polio represents a public health emergency. • We assessed the cost of provider outreach and immunization record assessments of licensed childcare and Head Start facilities aimed at preventing future outbreaks of VPDs. • Total public health labor cost incurred of activities was approximately $139,000. In 1994, the World Health Organization Region of the Americas was declared polio-free. In July 2022, a confirmed case of paralytic polio in an unvaccinated adult resident of Rockland County, New York was reported by the New York State Department of Health (NYSDOH) and Rockland County Department of Health (RCDOH). While only one case was identified, a single case of paralytic polio represents a public health emergency in the United States. The patient's county of residence was identified to have low vaccination coverage indicating that the community was at risk for additional cases. Disease outbreaks are resource-intensive and incur high costs to the patient, local health departments, and to society. These costs are potentially avoidable for vaccine-preventable diseases and thus, highlight the urgency to not only interrupt transmission but to prevent future vaccine-preventable disease outbreaks by improving vaccination coverage. Following case confirmation, an investigation and response was initiated by NYSDOH, along with local health departments and the Centers for Disease Control and Prevention (CDC). After the initial investigation and response, collaborative efforts to mitigate risk and strengthen routine immunization continued, which included provider outreach and immunization record assessments of Head Start and licensed childcare facilities (primarily those with missing or incomplete required vaccination coverage reports from the previous year) in Rockland County. We estimated the costs of (1) provider outreach and (2) childcare and pre-kindergarten immunization record assessments of select licensed childcare and Head Start facilities in Rockland County. The total labor cost incurred for these activities was $138,514 with a total of 2,555 h incurred. Often there are unique opportunities in the midst of an outbreak for public health to implement activities to proactively address low vaccination and strengthen vaccination coverage and possibly prevent future outbreaks. Understanding the cost of these activities might help inform future outbreak planning. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is an arrhythmic cardiac disorder with a high and increasing prevalence in aging societies, which is associated with a risk for stroke and heart failure. However, early detection of onset AF can become cumbersome since it often manifests in an asymptomatic and paroxysmal nature, also known as silent AF. Large-scale screenings can help identifying silent AF and allow for early treatment to prevent more severe implications. In this work, we present a machine learning-based algorithm for assessing signal quality of hand-held diagnostic ECG devices to prevent misclassification due to insufficient signal quality. A large-scale community pharmacy-based screening study was conducted on 7295 older subjects to investigate the performance of a single-lead ECG device to detect silent AF. Classification (normal sinus rhythm or AF) of the ECG recordings was initially performed automatically by an internal on-chip algorithm. The signal quality of each recording was assessed by clinical experts and used as a reference for the training process. Signal processing stages were explicitly adapted to the individual electrode characteristics of the ECG device since its recordings differ from conventional ECG tracings. With respect to the clinical expert ratings, the artificial intelligence-based signal quality assessment (AISQA) index yielded strong correlation of 0.75 during validation and high correlation of 0.60 during testing. Our results suggest that large-scale screenings of older subjects would greatly benefit from an automated signal quality assessment to repeat measurements if applicable, suggest additional human overread and reduce automated misclassifications. [ABSTRACT FROM AUTHOR]

Education savings accounts (ESAs) are education funding mechanisms that allow families to receive a deposit of public funds to a government-authorized savings account for accessing approved educational services. Using student-level longitudinal data, this paper examines how families participating in the Florida Gardiner Scholarship Program use education savings account funds. Results indicate that families use an increasing proportion of ESA funds when students remain in the program for multiple years. The longer students remain in the program, the share of ESA funds devoted to private school tuition decreases while expenditure shares increase for curriculum, instruction, tutoring, and specialized services. Although students in rural areas use a lower portion of their ESA funds than families in urban and suburban areas, they spend smaller portions of their funds on tuition and appear to customize more. [ABSTRACT FROM AUTHOR]

Predicting treatment outcome in internalizing mental disorders prior to treatment initiation is pivotal for precision mental healthcare. In this regard, resting-state functional connectivity (rs-FC) and machine learning have often shown promising prediction accuracies. This systematic review and meta-analysis evaluates these studies, considering their risk of bias through the Prediction Model Study Risk of Bias Assessment Tool (PROBAST). We examined the predictive performance of features derived from rs-FC, identified features with the highest predictive value, and assessed the employed machine learning pipelines. We searched the electronic databases Scopus, PubMed and PsycINFO on the 12th of December 2022, which resulted in 13 included studies. The mean balanced accuracy for predicting treatment outcome was 77% (95% CI: [72%- 83%]). rs-FC of the dorsolateral prefrontal cortex had high predictive value in most studies. However, a high risk of bias was identified in all studies, compromising interpretability. Methodological recommendations are provided based on a comprehensive exploration of the studies' machine learning pipelines, and potential fruitful developments are discussed. • The mean balanced accuracy of predicting treatment outcome was estimated at 77%. • The dorsolateral prefrontal cortex may hold particularly high predictive value. • All studies had a high risk of bias, mitigating the results´ interpretability. • Further studies applying state-of-the-art-machine learning methods are needed. [ABSTRACT FROM AUTHOR]

Background: Alongside depression, anxiety disorders are the most frequent reason for consulting a psychotherapist. Objective: This article describes the recent progress in understanding basic learning processes in anxiety treatment, the resulting therapeutic procedures, the current state of knowledge on the efficacy of the various psychotherapeutic procedures and on the moderators of the success of treatment. Material and methods: The English and German language literature was reviewed and compiled, with an emphasis on the last 10 years. Results: Cognitive-behavioral therapy (CBT) achieves the best and broadest level of evidence across all anxiety disorders. Initial studies have also provided emerging evidence for the efficacy of manualized short-term psychodynamic treatment. The most discussed mechanism of action is that of inhibitory learning. Augmentation strategies and personalized treatment approaches are gaining in relevance. Conclusion: Current models of inhibitory learning are rooted in basic research and foster a deeper understanding of the underlying neurobiological mechanisms. In order to optimize success of exposure treatment in vulnerable subgroups of patients, many procedural, device-based and pharmacological augmentation strategies are currently under investigation, whereby the latter are mostly still in the stage of (pre)clinical testing. [ABSTRACT FROM AUTHOR]

The rate of students switching from public schools to private schools because they received a scholarship and would not have switched without the subsidy ("switcher rate") is an integral factor for reliably estimating the net fiscal impact of private school choice programs. Switcher rates observed among students in control groups in random assignment studies can provide useful information for inferring switcher rates among program participants when conducting fiscal analyses. This paper identifies 27 estimates of switcher rates from eight lottery-based evaluations of six private school choice programs in the United States that report information about which types of school students enroll in after they apply to a choice program and do not win a lottery. Switcher rates for both full samples and subgroups of students range from 52 percent to 98 percent. Lower bound weighted average and median switcher rates from these studies are 84 percent. Upper bound weighted average and median switcher rates are 90 percent and 89 percent, respectively. Switcher rates are slightly higher for African American students participating in three privately funded school choice programs, where the average switcher rate for these students is 93 percent and the median is 94 percent. Switcher rates observed in these studies are remarkably stable across time and states, and they can provide useful information for inferring switcher rates in fiscal analyses. [ABSTRACT FROM AUTHOR]

Although cognitive behavioral therapy (CBT) is an established and efficient treatment for a variety of common mental disorders, a considerable number of patients do not respond to treatment or relapse after successful CBT. Recent findings and approaches from neuroscience could pave the way for clinical developments to enhance the outcome of CBT. Herein, we will present how neuroscience can offer novel perspectives to better understand (a) the biological underpinnings of CBT, (b) how we can enrich CBT with neuroscience-informed techniques (augmentation of CBT), and (c) why some patients may respond better to CBT than others (predictors of therapy outcomes), thus paving the way for more personalized and effective treatments. We will introduce some key topics and describe a selection of findings from CBT-related research using tools from neuroscience, with the hope that this will provide clinicians and clinical researchers with a brief and comprehensible overview of the field. [ABSTRACT FROM AUTHOR]

Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder. An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment. At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs. The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: We evaluate differences in school‐safety‐related practices and problems between school sectors (private, public charter, and traditional public) in Indiana in 2018. Methods: Using survey data collected from 618 school leaders in the state, we empirically examine the relationship between school sector and the reported presence of school‐safety‐related practices and problems occurring at school. Subgroup analyses based on voucher program participation status, school level, and location are also performed. Results: After controlling for factors such as school type, enrollment, number of students eligible for the federal free and reduced‐price lunch, the number of minority students and teachers, and urbanicity, we find evidence to suggest that private and charter schools tend to report fewer discipline problems while employing fewer disciplinary practices than traditional public schools. Conclusion: Our descriptive results suggest that school sector may play a role in producing positive school environments. Further research is needed to better understand short‐ and long‐run consequences of school safety problems and how school safety and school sector might affect students' academic and life trajectories. [ABSTRACT FROM AUTHOR]

Während in der somatischen Medizin mittlerweile eine Vielzahl von biologischen Markern für die Diagnostik und Therapieplanung vorliegen, gibt es keine vergleichbaren bio-logischen oder psychologischen Marker für psychische Störungen. Hier sind die Pathogenese und Wirkung psychotherapeutischer Interventionen durch eine Vielzahl mitei-nander interagierender Faktoren determiniert. Die prädiktive Analytik verfügt mit dem maschinellen Lernen über eine aussichtsreiche Methode, komplexe Muster und Interaktionen zwischen verschiedenen Variablen in Aussagen für den individuellen Patienten zu übersetzen. Diese Methoden bestimmen ("lernen") aus bereits vorhandenen Daten die Beziehung zwischen Prädiktoren und Ergebnissen und können anschließend das entwickelte Modell auf neue Daten, bei denen das Ergebnis noch offen ist, anwenden. Zuvor muss aber zwingend geprüft werden, ob das Gelernte tatsächlich bedeutungsvoll ist. Zur Illustration des Ansatzes stellen wir eine Reihe von Studien vor, die das Paradigma der prädiktiven Analytik für diagnostische Fragestellungen, Vorhersage von Risikoverläufen sowie zur Prognose von Psychotherapieergebnissen genutzt haben. Die Ergebnisse sind vielversprechend; vor einem Einsatz in der klinischen Praxis muss die Vorhersagegenauigkeit jedoch weiter gesteigert und in verschiedenen Settings und Populationen überprüft werden. Zur Verbesserung der Vorhersagegüte scheinen insbesondere die Berücksichtigung unterschiedlicher Datenmodalitäten wie klinische Maße, (f)MRT-Daten und genetische Daten sowie der Fokus auf Variablen, die Mechanismen von Psychopathologie und Veränderungsmechanismen gut abbilden, sinnvoll. Darüber hinaus sollte eine enge Zusammenarbeit mit Vertretern von Praktikern und Betroffenen stattfinden, um die Akzeptanz solcher Marker zu gewährleisten. Wenn dies gelingt, bieten derartige Marker das Potenzial, die Diagnosesicherheit insbesondere in -schwierigen Fällen deutlich zu erhöhen, mögliche Risikoverläufe früh zu identifizieren und die Zuweisung von Patienten zu den für sie bestmöglichen Behandlungen zu unterstützen. [ABSTRACT FROM AUTHOR]

This article conducts a fiscal analysis of 10 tax-credit programs in seven states. In total, the 10 programs in the present study represent 90% of all scholarships awarded in tax-credit scholarship programs today. The analysis employs a set of cautious assumptions about switcher rates and students who receive multiple scholarships to generate a range of estimates of the net fiscal impact of these tax-credit scholarship programs on state and local taxpayers. Tax-credit scholarship programs up to fiscal year (FY) 2014 generated positive fiscal impacts worth between $1,650 and $3,000 per scholarship student. In FY 2014 alone, tax-credit scholarship programs generated between about $2 million and $223 million for their states. Break-even switcher rates for fiscal neutrality are reported for all programs. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) frequently entails non-motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well-evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with ( n = 582) or without dementia/depression ( n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS-15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients. [ABSTRACT FROM AUTHOR]

The advent of low-cost solar photovoltaics (PV) and battery electricity storage has the potential to bring about fundamental shifts in the structure of the power sector in the United States. We analyze how PV-battery systems of various sizes could reduce the dependence of residential customers on the central grid and their impact on CO 2 emissions. We further analyze how the costs of such systems change as customers attempt to decrease their dependence on the grid, considering the installed cost of PV-battery systems and the cost of electricity under a net-energy metered rate structure. We analyze these relationships for residential customers in five locations across the U.S. We find that fully disconnecting from the grid with a PV-battery system is impractical for most residential customers without also having dispatchable backup generation. Finally, we estimate how the economics of behind-the-meter PV-battery systems may change if the costs of PV systems continue to fall. [ABSTRACT FROM AUTHOR]

In the past couple of years, research on display content for helicopter operations headed in a new direction. The already reached goals could evolve into a paradigm change for information visualization. Technology advancements allow implementing three-dimensional and conformal content on a helmet-mounted see-through device. This superimposed imagery inherits the same optical flow as the environment. It is supposed to ease switching between display information and environmental cues. The concept is neither pathbreaking nor new, but it has not been successfully established in aviation yet. Nevertheless, there are certainly some advantages to expect—at least from perspective of a human-centered system design. Within the following pages, the next generation displays will be presented and discussed with a focus on human factors. Beginning with recalling some human factor related research facts, an experiment comparing the former two-dimensional research displays will be presented. Before introducing the DLR conformal symbol set and the three experiments about an innovative drift, indication related research activities toward conformal symbol sets will be addressed. [ABSTRACT FROM AUTHOR]

Background Generalized anxiety disorder ( GAD) is difficult to recognize and hard to separate from major depression ( MD) in clinical settings. Biomarkers might support diagnostic decisions. This study used machine learning on multimodal biobehavioral data from a sample of GAD, MD and healthy subjects to differentiate subjects with a disorder from healthy subjects (case-classification) and to differentiate GAD from MD (disorder-classification). Methods Subjects with GAD ( n = 19), MD without GAD ( n = 14), and healthy comparison subjects ( n = 24) were included. The sample was matched regarding age, sex, handedness and education and free of psychopharmacological medication. Binary support vector machines were used within a nested leave-one-out cross-validation framework. Clinical questionnaires, cortisol release, gray matter ( GM), and white matter ( WM) volumes were used as input data separately and in combination. Results Questionnaire data were well-suited for case-classification but not disorder-classification (accuracies: 96.40%, p < .001; 56.58%, p > .22). The opposite pattern was found for imaging data (case-classification GM/ WM: 58.71%, p = .09/43.18%, p > .66; disorder-classification GM/ WM: 68.05%, p = .034/58.27%, p > .15) and for cortisol data (38.02%, p = .84; 74.60%, p = .009). All data combined achieved 90.10% accuracy ( p < .001) for case-classification and 67.46% accuracy ( p = .0268) for disorder-classification. Conclusions In line with previous evidence, classification of GAD was difficult using clinical questionnaire data alone. Particularly cortisol and GM volume data were able to provide incremental value for the classification of GAD. Findings suggest that neurobiological biomarkers are a useful target for further research to delineate their potential contribution to diagnostic processes. [ABSTRACT FROM AUTHOR]

Abundant natural gas at low prices has prompted industry and politicians to welcome gas as a ‘bridge fuel’ between today's coal-intensive electric power generation and a future low-carbon grid. We used existing national datasets and publicly available models to investigate the upper limit to the emission benefits of natural gas in the USA power sector. As a limiting case, we analyzed a switch of all USA coal plants to natural gas plants, occurring in 2016. The human health benefits of such a switch are substantial: SO 2 emissions are reduced from the baseline (MATS (Mercury and Air Toxics Standard) retrofits by 2016) by more than 90%, and NO X emissions by more than 60%, reducing total national annual health damages by $20 – $50 billion annually. While the effect on global temperatures is small out to 2040, the USA power plant fleet's contribution could be changed by as much as −50% to +5% depending on the rate of fugitive CH 4 emissions and efficiency of replacement gas plants. [ABSTRACT FROM AUTHOR]

Individuals with high anxiety sensitivity (AS) have an increased risk of developing anxiety disorders and are more biased in how they process fear-related stimuli. This study investigates the neural correlates of fear-related words and word associations in high- and low-AS individuals. We used a semantic priming paradigm during functional magnetic resonance imaging in which three types of target words (fear symptoms, e.g. 'dizziness'; neutral, e.g. 'drink'; and pseudowords, e.g. 'salkom') were preceded by two types of prime words (fear-triggers, e.g. 'elevator'; and neutral, e.g. 'bottle'). Subjects with high AS rated fear-symptom words (vs neutral words) as more unpleasant than low-AS individuals; they also related these words more strongly to fear-triggers and showed prolonged reaction times. During the processing of fear-symptom words, greater activation in the left anterior insula was observed in high-AS subjects than in low-AS subjects. Lower activation in the left inferior frontal gyrus, angular gyrus, fusiform gyrus and bilateral amygdalae was found in high-AS subjects when fear-symptom words were preceded by fear-trigger words. The findings suggest that cognitive biases and the anterior insula play a crucial role in high-AS individuals. Furthermore, semantic processes may contribute to high AS and the risk of developing anxiety disorders. [ABSTRACT FROM AUTHOR]

Anxiety disorders constitute the largest group of mental disorders with a high individual and societal burden. Neurobiological markers of treatment response bear potential to improve response rates by informing stratified medicine approaches. A systematic review was performed on the current evidence of the predictive value of genetic, neuroimaging and other physiological markers for treatment response (pharmacological and/or psychotherapeutic treatment) in anxiety disorders. Studies published until March 2015 were selected through search in PubMed, Web of Science, PsycINFO, Embase, and CENTRAL. Sixty studies were included, among them 27 on genetic, 17 on neuroimaging and 16 on other markers. Preliminary evidence was found for the functional 5-HTT LPR/rs25531 genotypes, anterior cingulate cortex function and cardiovascular flexibility to modulate treatment outcome. Studies varied considerably in methodological quality. Application of more stringent study methodology, predictions on the individual patient level and cross-validation in independent samples are recommended to set the next stage of biomarker research and to avoid flawed conclusions in the emerging field of “Mental Health Predictomics”. [ABSTRACT FROM AUTHOR]

Background/objectives: The reimbursement of inpatient psychiatric psychotherapeutic/psychosomatic hospital treatment in Germany is regulated by the German personnel ordinance for psychiatric hospitals (Psych-PV), which has remained unchanged since 1991. The aim of this article was to estimate the personnel requirements for guideline-adherent psychiatric psychotherapeutic hospital treatment. Methods: A normative concept for the required psychotherapeutic 'dose' for anxiety disorders was determined based on a literature review. The required staffing contingent was compared to the resources provided by the Psych-PV based on category A1. Results: According to the German policy guidelines for outpatient psychotherapy, a quota of 25 sessions of 50 min each (as a rule plus 5 probatory sessions) is reimbursed. This approach is supported by studies on dose-response relationships. As patients undergoing inpatient treatment for anxiety disorders are usually more severely ill than outpatients, a contingent of 30 sessions for the average treatment duration of 5 weeks seems appropriate in order to fully exploit the costly inpatient treatment time (300 min per patient and week). In contrast, only 70 min are reimbursed according to the Psych-PV. The total personnel requirement for the normative concept is 624 min per patient and week. The Psych-PV only covers 488 min (78 %). Conclusion: Currently, the time contingents for evidence-based psychiatric psychotherapeutic/psychosomatic hospital care are nowhere near sufficient. In the development of future reimbursement systems this needs to be corrected. [ABSTRACT FROM AUTHOR]

Background Depression is frequent in panic disorder (PD); yet, little is known about its influence on the neural substrates of PD. Difficulties in fear inhibition during safety signal processing have been reported as a pathophysiological feature of PD that is attenuated by depression. We investigated the impact of comorbid depression in PD with agoraphobia (AG) on the neural correlates of fear conditioning and the potential of machine learning to predict comorbidity status on the individual patient level based on neural characteristics. Methods Fifty-nine PD/AG patients including 26 (44%) with a comorbid depressive disorder (PD/AG+DEP) underwent functional magnetic resonance imaging (fMRI). Comorbidity status was predicted using a random undersampling tree ensemble in a leave-one-out cross-validation framework. Results PD/AG−DEP patients showed altered neural activation during safety signal processing, while +DEP patients exhibited generally decreased dorsolateral prefrontal and insular activation. Comorbidity status was correctly predicted in 79% of patients (sensitivity: 73%; specificity: 85%) based on brain activation during fear conditioning (corrected for potential confounders: accuracy: 73%; sensitivity: 77%; specificity: 70%). Limitations No primary depressed patients were available; only medication-free patients were included. Major depression and dysthymia were collapsed (power considerations). Conclusions Neurofunctional activation during safety signal processing differed between patients with or without comorbid depression, a finding which may explain heterogeneous results across previous studies. These findings demonstrate the relevance of comorbidity when investigating neurofunctional substrates of anxiety disorders. Predicting individual comorbidity status may translate neurofunctional data into clinically relevant information which might aid in planning individualized treatment. The study was registered with the ISRCTN: ISRCTN80046034. [ABSTRACT FROM AUTHOR]

While neuroimaging research has advanced our knowledge about fear circuitry dysfunctions in anxiety disorders, findings based on diagnostic groups do not translate into diagnostic value for the individual patient. Machine-learning generates predictive information that can be used for single subject classification. We applied Gaussian process classifiers to a sample of patients with specific phobia as a model disorder for pathological forms of anxiety to test for classification based on structural MRI data. Gray (GM) and white matter (WM) volumetric data were analyzed in 33 snake phobics (SP; animal subtype), 26 dental phobics (DP; blood-injection-injury subtype) and 37 healthy controls (HC). Results showed good accuracy rates for GM and WM data in predicting phobia subtypes (GM: 62 % phobics vs. HC, 86 % DP vs. HC, 89 % SP vs. HC, 89 % DP vs. SP; WM: 88 % phobics vs. HC, 89 % DP vs. HC, 79 % SP vs. HC, 79 % DP vs. HC). Regarding GM, classification improved when considering the subtype compared to overall phobia status. The discriminatory brain pattern was not solely based on fear circuitry structures but included widespread cortico-subcortical networks. Results demonstrate that multivariate pattern recognition represents a promising approach for the development of neuroimaging-based diagnostic markers that could support clinical decisions. Regarding the increasing number of fMRI studies on anxiety disorders, researchers are encouraged to use functional and structural data not only for studying phenotype characteristics on a group level, but also to evaluate their incremental value for diagnostic or prognostic purposes. [ABSTRACT FROM AUTHOR]

Variation in the 5′-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT. [ABSTRACT FROM AUTHOR]

Depending on threat proximity, different defensive behaviours are mediated by a descending neural network involving forebrain (distal threat) vs midbrain areas (proximal threat). Compared to healthy subjects, it can be assumed that phobics are characterized by shortened defensive distances on a behavioural and neural level. This study aimed at characterizing defensive reactivity in two subtypes of specific phobia [snake (SP) and dental phobics (DP)]. Using functional magnetic resonance imaging (fMRI), n = 39 subjects (13 healthy controls, HC; 13 SP; 13 DP) underwent an event-related fMRI task employing an anticipation (5-10 s) and immediate perception phase (phobic pictures and matched neutral stimuli; 1250 ms) to modulate defensive distance. Although no differential brain activity in any comparisons was observed in DP, areas associated with defensive behaviours (e.g. amygdala, hippocampus, midbrain) were activated in SP. Decreasing defensive distance in SP was characterized by a shift to midbrain activity. Present findings substantiate differences between phobia types in their physiological and neural organization that can be expanded to early stages of defensive behaviours. Findings may contribute to a better understanding of the dynamic organization of defensive reactivity in different types of phobic fear. [ABSTRACT FROM AUTHOR]

The personality trait of sensation seeking (SS) has been traditionally linked to the construct of exteroception, that is, sensing of the outside world. Little is known about the relationship between SS and interoception, that is, sensing originating in the body. Interoceptive sensations have strong affective and motivational components that may influence behaviours such as risk taking in SS. This investigation examined whether interoceptive differences contribute to different behavioural characteristics in SS. Using an inspiratory resistive load breathing task, the response to an aversive interoceptive stimulus as a basic homeostatic process was studied in 112 subjects (n = 74 women and 38 men). A linear mixed-model approach was used to examine the influence of thrill and adventure seeking (TAS) on the interoceptive response across three levels of breathing resistances (10, 20, and 40 cm H2O/L/second). High-TAS relative to low-TAS individuals were less responsive in evaluating intensities of perceived choking with increasing inspiratory resistive loads. This effect was driven by male, but not female, high-TAS individuals and was particularly associated with reduced interoceptive sensitivity in men. The conceptualization of SS as primarily driven by exteroceptive stimuli can be expanded to a view of an altered homeostasis in SS, specifically in men. Copyright © 2013 European Association of Personality Psychology [ABSTRACT FROM AUTHOR]

Background: Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder with agoraphobia (PD/AG). It is unknown, how variants of CBT differentially modulate brain networks involved in PD/AG. This study was aimed to evaluate the effects of therapist-guided (T+) versus self-guided (T-) exposure on the neural correlates of fear conditioning in PD/AG. Method: In a randomized, controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before (t1) and after CBT (t2). Quality-controlled fMRI data from 42 patients and 42 healthy subjects (HS) were obtained. Patients were randomized to two variants of CBT (T+, n = 22, and T-, n = 20). Results: The interaction of diagnosis (PD/AG, HS), treatment group (T+, T-), time point (t1, t2) and stimulus type (conditioned stimulus: yes, no) revealed activation in the left hippocampus and the occipitotemporal cortex. The T+ group demonstrated increased activation of the hippocampus at t2 (t2 > t1), which was positively correlated with treatment outcome, and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time (t1 > t2). Conclusion: After T+ exposure, contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus, previously shown to be dysfunctionally activated in PD/AG. Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Research on the neurobiological basis of Generalized Anxiety Disorder (GAD) has considerably expanded in recent years. However, many studies investigated different domains and used different methods and paradigms. Therefore, this review aims to integrate the findings to date and to identify the core correlates of neurobiological underpinnings of GAD discovered so far. Methods: We conducted a systematic review of original papers investigating neural correlates, connectivity, or structural changes as well as reporting changes in the serotonergic system, noradrenergic system and cortisol levels in DSM-IV-defined GAD samples until December 2013. Results: Studies have identified abnormal amygdala and prefrontal cortex activation in patients and decreased functional connectivity between these areas. Furthermore, studies showed increased gray matter volume and decreased structural connectivity between these structures. Neuroendocrine findings are less consistent, but increased reactivity of the noradrenergic system and perpetuations in the cortisol secretion have been reported. Limitations: Only studies on DSM-IV defined Generalized Anxiety Disorder which employed a group comparison were included. Conclusions: Current research suggests a distinct set of neurobiological alterations in Generalized Anxiety Disorder. However, future research on the interaction between these structures and systems and on the specificity of these findings in relation to other mental disorders is urgently needed. [Copyright &y& Elsevier]

BackgroundAlthough several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.MethodThe blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.ResultsDifferential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.ConclusionsThe results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder. [ABSTRACT FROM PUBLISHER]

Background: By understanding specific differences between responders to a treatment and non-responders, treatment modalities may be fitted to the individual in order to increase effectiveness, a concept known as "precision medicine". This systematic review and meta-analysis investigated which pretreatment patient and family characteristics may predict the outcome of cognitive-behavioral therapy (CBT) in clinically anxious and/or depressed youth. In particular, higher symptom severity, more severe co-occurring anxiety or depression and more severe parental psychopathology were hypothesized to predict a worse CBT outcome.Methods: The databases PubMed, PsycINFO and Cochrane Library were searched; 73 publications were included in the review from which 23 studies were used for the meta-analysis.Results: Higher symptom severity represented a clinically relevant predictor of a worse CBT outcome, with large effects estimated by meta-analysis. Further, parental psychopathology was significant and detrimental for CBT outcome in anxious but not depressed youth, while the effects for co-occurring anxiety and depression remained unclear. The additional results of the review show that only few characteristics seemed to be clearly associated with a worse CBT outcome, namely worse coping skills and, restricted to depressed patients, more non-suicidal self-injury.Limitations: The available evidence was of only moderate quality in general, further high-quality research with more transparent reporting is needed.Conclusions: The patient characteristics identified as being relevant for CBT outcome may represent important candidates for use in single patient prediction models for precision medicine in the field of child and adolescent psychotherapy. The review was preregistered on PROSPERO (ID: CRD42018116881). [ABSTRACT FROM AUTHOR]

Objective: Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Method: Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. Results: At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. Conclusions: This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated. [ABSTRACT FROM AUTHOR]

It has been repeatedly shown that functional magnetic resonance imaging (fMRI) triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA), as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID) in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults. [ABSTRACT FROM AUTHOR]

We compare the power output from a year of electricity generation data from one solar thermal plant, two solar photovoltaic (PV) arrays, and twenty Electric Reliability Council of Texas (ERCOT) wind farms. The analysis shows that solar PV electricity generation is approximately one hundred times more variable at frequencies on the order of 10-3 Hz than solar thermal electricity generation, and the variability of wind generation lies between that of solar PV and solar thermal. We calculate the cost of variability of the different solar power sources and wind by using the costs of ancillary services and the energy required to compensate for its variability and intermittency, and the cost of variability per unit of displaced CO2 emissions. We show the costs of variability are highly dependent on both technology type and capacity factor. California emissions data were used to calculate the cost of variability per unit of displaced CO2 emissions. Variability cost is greatest for solar PV generation at $8-11 per MWh. The cost of variability for solar thermal generation is $5 per MWh, while that of wind generation in ERCOT was found to be on average $4 per MWh. Variability adds $15/tonne CO2 to the cost of abatement for solar thermal power, $25 for wind, and $33-$40 for PV. [ABSTRACT FROM AUTHOR]

Summary: Accumulating evidence suggests that the magnetic resonance imaging (MRI) scanner can act as a stressor, eliciting subjective and neuroendocrine stress responses. Approaches to familiarize subjects with the scanner could help minimizing unintended effects on neural activation patterns of interest. Controlled studies on the effects of a scanner training are however missing. Using a comparative design, we analyzed within- and between session changes in subjective and neuroendocrine stress parameters in 63 healthy, scanner-naïve adults who participated in a two-day training protocol in an MRI, mock, or lab environment. A habituation task was used to assess within-session changes in subjective and neuroendocrine (cortisol) stress parameters; between-session changes were indicated by differences between days. MRI and mock, but not lab training were successful in reducing subjective distress towards the scanner. In contrast, cortisol reactivity towards the training environment generally increased during day 2, and the percentage of cortisol responders particularly rose in the mock and MRI groups. Within-session habituation of subjective arousal and anxiety was observed during both days and irrespective of training condition. Present findings demonstrate that training in a scanner environment successfully reduces subjective distress, but may also induce sensitization of endocrine stress levels during repeated scanning. Subjective distress can further be stabilized by acclimating subjects to the environment prior to the MRI assessment, including a short habituation phase into the assessment protocol. If replicated, present findings should be considered by researchers employing repeated measurement designs where subjects are exposed to a scanner more than once. [Copyright &y& Elsevier]

Autobiographical memory comprises memories of one's own past that are characterized by a sense of subjective time and autonoetic awareness. Although autobiographical memory deficits are among the major complaints of patients with dementia, they have rarely been systematically assessed in mild cognitive impairment and Alzheimer's disease. We therefore investigated semantic and episodic aspects of autobiographical memory for remote and recent life periods in a sample of 239 nursing home residents (165 in different stages of Alzheimer's disease, 33 with mild cognitive impairment, and 41 cognitively unimpaired) with respect to potential confounders. Episodic autobiographical memories, especially the richness of details, were impaired early in the course of Alzheimer's disease or even in the preclinical phase, while semantic memories were spared until moderate stages, indicating a dissociation between both memory systems. The examination of autobiographic memory loss can facilitate the clinical diagnosis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Abstract: Although functional magnetic resonance imaging (fMRI) has gained increasing importance in investigating neural substrates of anxiety disorders, less is known about the stress eliciting properties of the scanner environment itself. The aim of the study was to investigate feasibility, self-reported distress and anxiety management strategies during an fMRI experiment in a comprehensive sample of patients with panic disorder and agoraphobia (PD/AG). Within the national research network PANIC-NET, n=89 patients and n=90 controls participated in a multicenter fMRI study. Subjects completed a retrospective questionnaire on self-reported distress, including a habituation profile and exploratory questions about helpful strategies. Drop-out rates and fMRI quality parameters were employed as markers of study feasibility. Different anxiety measures were used to identify patients particularly vulnerable to increased scanner anxiety and impaired data quality. Three (3.5%) patients terminated the session prematurely. While drop-out rates were comparable for patients and controls, data quality was moderately impaired in patients. Distress was significantly elevated in patients compared to controls; claustrophobic anxiety was furthermore associated with pronounced distress and lower fMRI data quality in patients. Patients reported helpful strategies, including motivational factors and cognitive coping strategies. The feasibility of large-scale fMRI studies on PD/AG patients could be proved. Study designs should nevertheless acknowledge that the MRI setting may enhance stress reactions. Future studies are needed to investigate the relationship between self-reported distress and fMRI data in patient groups that are subject to neuroimaging research. [Copyright &y& Elsevier]

Abstract: Specific phobia of the animal subtype has been employed as a model disorder exploring the neurocircuitry of anxiety disorders, but evidence is lacking whether the detected neural response pattern accounts for all animal subtypes, nor across other phobia subtypes. The present study aimed at directly comparing two subtypes of specific phobia: snake phobia (SP) representing the animal, and dental phobia (DP) representing the blood-injection-injury subtype. Using functional magnetic resonance imaging (fMRI), brain activation and skin conductance was measured during phobogenic video stimulation in 12 DP, 12 SP, and 17 healthy controls. For SP, the previously described activation of fear circuitry structures encompassing the insula, anterior cingulate cortex and thalamus could be replicated and was furthermore associated with autonomic arousal. In contrast, DP showed circumscribed activation of the prefrontal and orbitofrontal cortex (PFC/OFC) when directly compared to SP, being dissociated from autonomic arousal. Results provide preliminary evidence for the idea that snake and dental phobia are characterized by distinct underlying neural systems during sustained emotional processing with evaluation processes in DP being controlled by orbitofrontal areas, whereas phobogenic reactions in SP are primarily guided by limbic and paralimbic structures. Findings support the current diagnostic classification conventions, separating distinct subtypes in DSM-IV-TR. They highlight that caution might be warranted though for generalizing findings derived from animal phobia to other phobic and anxiety disorders. If replicated, results could contribute to a better understanding of underlying neurobiological mechanisms of specific phobia and their respective classification. [Copyright &y& Elsevier]

Lueken U, Hoyer J, Siegert J, Gloster AT, Wittchen H-U. Symptom provocation in dental anxiety using cross-phobic video stimulation. Eur J Oral Sci 2011; 119: 61-68. © 2011 Eur J Oral Sci Although video stimulation has been successfully employed in dental phobia, conclusions regarding the specificity of reactions are limited. A novel, video-based paradigm using cross-phobic video stimulation was validated based on subjective and autonomic responses. Forty subjects were stratified according to dental anxiety as measured by the Dental Fear Survey (DFS) using a median-split procedure (high-DFS and low-DFS groups). Anxiety stimuli comprised dental-anxiety scenes and non-dental-anxiety control scenes (snake stimuli). Neutral scenes were tailored to each anxiety stimulus. Dental, but not snake, stimuli were rated as more anxiety provoking only in the high-DFS group. Elevated skin-conductance amplitudes were observed in the high-DFS group for dental anxiety vs. neutral videos, but not for snake anxiety vs. neutral videos. State and trait anxiety and autonomic reactivity were correlated according to expectations. Using cross-phobic video stimulation, it was demonstrated that phobogenic reactions in dental anxiety are specific to the respective stimulus material and do not generalize to other non-dental-anxiety control conditions. The validation of the paradigm may support and stimulate future research on the characterization of dental anxiety on different response systems, including its underlying neural substrates. [ABSTRACT FROM AUTHOR]

Abstract: Subjects participating in magnetic resonance imaging (MRI) examinations regularly report anxiety and stress related reactions. This may result in impaired data quality and premature termination of scans. Moreover, cognitive functions and neural substrates can be altered by stress. While prior studies investigated pre–post scan differences in stress reactions only, the present study provides an in-depth analysis of mood changes and hormonal fluctuations during the time course of a typical fMRI session. Thirty-nine subjects participated in the study. Subjective mood, salivary alpha-amylase (sAA) and cortisol were assessed at six time points during the lab visit. Associations between hormonal data and neural correlates of a visual detection task were observed using a region of interest approach applied to the thalamic region. Mood and hormonal levels changed significantly during the experiment. Subjects were most nervous immediately after entering the scanner. SAA was significantly elevated after MRI preparation. A subgroup of n =5 (12.8%) subjects showed pronounced cortisol responses exceeding 2.5nmol/l. Preliminary fMRI data revealed an association between sAA levels and left thalamic activity during the first half of the experiment that disappeared during the second half. No significant correlation between cortisol and thalamic activity was observed. Results indicate that an fMRI experiment may elicit subjective and neuroendocrine stress reactions that can influence functional activation patterns. [Copyright &y& Elsevier]

Summary: Evidence is accumulating that cerebral laterality appears to be an important feature in the regulation of the stress response with the right hemisphere being closely linked to stress-regulatory systems, including the hypothalamic–pituitary–adrenal (HPA) axis. Although some animal and human data support this hypothesis, studies on brain damaged patients yet failed to substantiate laterality effects on cortisol secretion. The aim of this study was to examine whether unilateral stroke differentially affects tonic and phasic response characteristics of the HPA axis, and to evaluate the impact of intrahemispheric lesion location. Basal morning cortisol levels and phasic responses towards a mentally challenging task were examined in 32 stroke patients with left-sided (LH; n =18) or right-sided (RH; n =14) infarctions and 30 healthy controls matched for age and gender. Only LH, but not RH patients displayed increased morning cortisol levels when compared to controls. In contrast, phasic reactions were blunted in the combined patient group with RH patients showing the most distinct decline. More anterior located lesions were associated with reduced phasic, but not tonic cortisol measures. This relationship appeared to be particularly pronounced in RH patients. Results support the conclusion that the central regulation of cortisol secretion is under excitatory control of the right hemisphere and can be interpreted within a framework of asymmetrical regulation of the stress response. Left- and right-sided strokes may differentially affect response patterns of the HPA axis, a stress-regulatory system that is associated with effective protection against disease and external challenges. [Copyright &y& Elsevier]

Over the past decade, deep brain stimulation (DBS) has become an effective treatment option for managing severe Parkinson’s disease (PD). However, evidence is accumulating that DBS of target sites like the subthalamic nucleus (STN) can result in unintended cognitive effects that lie beyond motor control. The aim of the present study was to evaluate whether changes in executive task performance after chronic DBS might be predominantly associated with the stimulation of only one hemisphere. Eight patients with PD who had undergone DBS treatment of the STN were selected to participate in the study. Using a repeated measurements design, they underwent a neuropsychological examination under unilateral left- and right-sided stimulation in order to investigate laterality effects in their performance on the Wisconsin Card Sorting Test. All patients showed a significant improvement in motor symptoms postoperatively. Selected aspects of executive task performance were compromised under left- when compared to right-sided stimulation. Performance measures were unrelated to demographic, neurological, and behavioral characteristics of the patients. Findings are consistent with the emerging evidence that the STN is not only involved in motor control, but also participates in functions of the cognitive domain. Moreover, results raise the possibility that the left and right hemisphere might differ in their vulnerability to tolerate side effects on executive functions of DBS treatment. Potential consequences for future research questions and the management of cognitive side effects are discussed. [ABSTRACT FROM AUTHOR]

A computer program is introduced which analyses the magnetic susceptibility of mononuclear and exchange-coupled homodinuclear dN–dN and fN–fN systems as well as heterodinuclear dN–S and fN–S complexes (S standing for a pure spin centre with S=1/2,1,7/2) taking into consideration interelectronic repulsion, spin-orbit coupling, ligand field effect, isotropic exchange interactions, and applied magnetic field. The program is applied to interpret the paramagnetism of K6Cu12U2S15 (with magnetically active mononuclear uranium) and to predict the field-dependent magnetic susceptibility of the heterodinuclear complex 3d2–4f7. [Copyright &y& Elsevier]

Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF- and ARL-family member whose mRNA-expression is induced by liver X-receptor/retinoid X-receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7-enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over-expression on the cholesterol secretory pathway. We found that expression of wild type and dominant active ARL7-EGFP stimulated the rate of apolipoprotein AI-specific cholesterol efflux 1.7- and 2.8-fold. In contrast, expression of the dominant negative form of ARL7-EGFP led to ∼50% inhibition of cholesterol efflux. This data is consistent with a model in which ARL7 is involved in transport between a perinuclear compartment and the plasma membrane apparently linked to the ABCA1-mediated cholesterol secretion pathway. [Copyright &y& Elsevier]

Genotoxic combination effects of oxidative stress (induced by H2O2) and eight nongenotoxic environmental chemicals (4-chloroaniline, 2,3,4,6-tetrachlorophenol, lindane, 2,4-dichloroacetic acid (2,4-D), m-xylene, glyphosate, nitrilotriacetic acid and n-hexanol) were determined in human fibroblasts. Genotoxicity was measured quantitatively by the single cell gel electrophoresis assay. The nongenotoxic chemicals were used in non cytotoxic concentrations. H2O2 was used in concentrations producing low (50 μM) and no cytotoxicity (40 μM). All environmental chemicals acted in a synergistic way with H2O2 except DMSO which effectively inhibited H2O2-induced DNA damage. The most effective enhancers were 4-chloroaniline, 2,3,4,6-tetrachlorophenol, m-xylene, and n-hexanol. Synergistic effects of hexanol/H2O2 were still evident at a concentration of 0.09 noec (no observed effect concentration). In contrast to synergistic DNA damage in the cell antagonism was found measuring DNA breakage in isolated PM2 DNA. From the results we concluded that synergisms between H2O2 and nongenotoxic chemicals may be a general phenomenon which is not observed on the level of isolated DNA. [Copyright &y& Elsevier]

Background: The COVID‐19 pandemic exposed a substantial portion of society to multiple stressors, while access to mental health care was limited. To address this, we introduced a digital stepped‐care program rooted in cognitive–behavioral therapy (CBT) principles, aiming to alleviate mental health distress among the general public seeking help. Methods: The program comprises a 4‐week digital application using "Aury" the chatbot, followed by an optional 6‐week online group session for those still symptomatic. A 4‐week waiting period separated these steps. Participants entered based on self‐identified mental health concerns. Interventions addressed prevalent pandemic mental health issues: sleep disturbances, anxiety, depression, worry/rumination, interpersonal issues, and resource mobilization. Outcomes focused on depressive, anxiety, and somatic symptoms, assessed by the Patient Health Questionnaire (PHQ). Results: Of the 1261 initial participants, postchatbot results (N = 142) indicated small to medium effects (d = 0.412 to d = 0.523). Those finishing the entire program (N = 41) saw substantial symptom decline with medium to large effects (d = 0.757 to d = 0.818). No shifts were seen in the waiting phase. At follow‐up 6 months after baseline, both groups—those who only used the chatbot (N = 60; d = 0.284 to d = 0.416) and those who completed the entire program (N = 27; d = 0.854 to d = 0.926)—showed sustained symptom reduction. Comparing groups that received no intervention, used the chatbot only, and completed the entire program, we observed a dose–response effect. Conclusions: This resource‐efficient and adaptable digital approach effectively reduced pandemic‐induced mental health issues, indicating its potential in crisis periods with limited health resources. Randomized controlled trials are recommended for further validation. Trial Registration: Clinical Trial Registry identifier: DRKS00023220. [ABSTRACT FROM AUTHOR]

Studies the magnetism and electronic structure of the (pentamethylcyclopentadienyl)dichlororuthenium dimers. Magnetic susceptibility measurements; EPR measurements; Electronic structure.

Body sensor networks (BSNs) represent an important research tool for exploring novel diagnostic or therapeutic approaches. They allow for integrating different measurement techniques into body-worn sensors organized in a network structure. In 2011, the first Integrated Posture and Activity Network by MedIT Aachen (IPANEMA) was introduced. In this work, we present a recently developed platform for a wireless body sensor network with customizable applications based on a proprietary 868 MHz communication interface. In particular, we present a sensor setup for gait analysis during everyday life monitoring. The arrangement consists of three identical inertial measurement sensors attached at the wrist, thigh, and chest. We additionally introduce a force-sensitive resistor integrated insole for measurement of ground reaction forces (GRFs), to enhance the assessment possibilities and generate ground truth data for inertial measurement sensors. Since the 868 MHz is not strongly represented in existing BSN implementations, we validate the proposed system concerning an application in gait analysis and use this as a representative demonstration of realizability. Hence, there are three key aspects of this project. The system is evaluated with respect to (I) accurate timing, (II) received signal quality, and (III) measurement capabilities of the insole pressure nodes. In addition to the demonstration of feasibility, we achieved promising results regarding the extractions of gait parameters (stride detection accuracy: 99.6 ± 0.8 % , Root-Mean-Square Deviation (RMSE) of mean stride time: 5 ms , RMSE of percentage stance time: 2.3 % ). Conclusion: With the satisfactory technical performance in laboratory and application environment and the convincing accuracy of the gait parameter extraction, the presented system offers a solid basis for a gait monitoring system in everyday life. [ABSTRACT FROM AUTHOR]

Cabotegravir/rilpivirine (CAB/RPV) was recently approved by the US Food and Drug Administration (FDA) as the first complete parenteral antiretroviral (ART) regimen for treatment of people living with HIV (PLWH). As a monthly intramuscular (IM) injection, this therapy constitutes a major departure from the traditional paradigm of oral therapy requiring (at least) daily administration that has defined HIV treatment for decades. Composed of a second-generation integrase inhibitor (INSTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI), CAB/RPV has achieved high rates of sustained virologic suppression with a favorable safety profile for treatment-experienced PLWH following oral lead-in (OLI) during several clinical trials. In addition to the clinical benefits of this agent, patient-reported outcomes associated with convenience, confidentiality, and the tolerability of the injections have consistently reflected positive perceptions of CAB/RPV. The novel nature of this therapy in the field of HIV presents logistical challenges. Clinics will need to address barriers related to management of clinic workflow, procurement, reimbursement, and nonadherence. The aim of this review was to summarize the available safety, efficacy, and pharmacokinetic/pharmacodynamic (PK/PD) data of this long-acting (LA) injectable regimen as well as discuss some potential considerations for prescribing and operationalization. [ABSTRACT FROM AUTHOR]