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IMPORTANCE: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown. OBJECTIVE: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain. DESIGN, SETTING, AND PARTICIPANTS: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023. INTERVENTIONS: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy. MAIN OUTCOMES AND MEASURES: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years. RESULTS: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients. CONCLUSIONS AND RELEVANCE: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02400229

Die Resektion des Radiuskopfes war in der Vergangenheit bei nicht rekonstruierbaren Radiuskopffrakturen häufig die einzige Therapieoption. Mit den modernen Prothesen steht nun eine weitere Behandlungsmethode zur Auswahl. Die vorliegende Arbeit befasst sich mit der Frage in welchen Fällen die ersatzlose Resektion noch vertretbar ist. In einem Studienkollektiv von 44 Patienten wurden 28 Patienten mit einer Radiuskopfprothese, 9 Patienten mit einer Radiuskopfresektion und 7 Patienten mit einer Radiuskopfteilresektion versorgt. Die mittlere Nachuntersuchungszeit betrug 29 Monate. Insgesamt wurden 13 Mason III- und 31 Mason IV-Frakturen versorgt. Der Score nach Morrey ergab bei den Radiuskopfprothesen im Mittel 79 (83; 47–98) Punkte; bei den Radiuskopfresektionen einen Durchschnittswert von 79 Punkten (74; 56–95) und bei den Teilresektionen des Kopfes einen Mittelwert von 74 Punkten (72; 48–93). Die Resektion des Radiuskopfes bei ansonsten stabiler ligamentärer Führung des Ellenbogens kann zu guten Ergebnissen führen. Bei ligamentären Begleitverletzungen ist jedoch die Radiuskopfprothese vorzuziehen, da durch sie der radiale Pfeiler und somit die Gelenkgeometrie wieder hergestellt werden kann, wodurch eine frühfunktionelle Beübung möglich ist. Unter Berücksichtigung dieser Tatsachen zeigen die RK-Resektion und die RK- Prothese bessere Ergebnisse als die Teilresektion des Radiuskopfes. Diese ist aufgrund verstärkter Schmerzen und Bewegungseinschränkungen nicht zu empfehlen. The resection of the radial head was previously the only therapy option for radial head fractures. Today, modern prosthetics present further alternatives for treatment. The following paper deals with answering the question of whether there are still instances in which resection is justifiable. The patient collective consisted of 44 patients: 28 received a radial head prosthetic implant, 9 a radial head resection, and 7 a partial radial head resection. The average follow up time was 29 months. Altogether, 13 Mason III and 31 Mason IV fractures were treated. The mean Morrey Score after implantation of a radial head prosthetic device was 79 points (83; 47–98); for radial head resections 79 points (74; 56–95), and for the partial resection of the head 74 points (72; 48–93). The resection of the radial head after fracture can yield good outcome in the short-term in a stable joint. If there is a ligamentous instability, the implantation of a radial head prosthetic device is recommended. It stabilizes the radial axis and reconstructs joint geometry, allowing for early functional use. Because of intensified pain and movement restriction partial resection of the radial head is not recommended.

Der prozessbasierte Therapieansatz stellt ein neues Konzept der Diagnostik, Therapieplanung und zum Therapieprozess dar. Im Zentrum des Verständnisses von psychischen Störungen steht die Auffassung, dass die „Ursache“ psychischer Störungen nicht etwa auf latente „Krankheiten“ zurückgeführt wird, sondern diese in dynamischen Netzwerken von psychischen Prozessen eines Individuums gesehen wird. Durch Erfassung von Variablen in Alltagssituationen, die im individuellen Fall relevant sind, sollen solche zentralen Faktoren („Knoten“), die maladaptive Netzwerke aus sich wechselseitig beeinflussenden Störungsprozessen aufrechterhalten, identifiziert werden. Aus der konkreten Erfassung von störungsrelevanten Prozessen im Problemkontext lassen sich individuell relevante Ansatzpunkte für evidenzbasierte Interventionen ableiten; diese verändern das maladaptive Muster des Störungsnetzwerkes und fördern adaptivere Erlebnis- und Verhaltensweisen. Zusätzlich sind die Interaktionsprozesse in der therapeutischen Beziehung zu berücksichtigen und auf die individuellen Bedürfnisse der Patient*innen anzupassen. Im vorliegenden Beitrag werden auch die gegenwärtig noch offenen Fragen bei der Anwendung prozessbasierter Therapie in der therapeutischen Praxis behandelt.

Individual responses to behavioral treatment of anxiety disorders vary considerably, which requires a better understanding of underlying processes. In this study, we examined the violation and change of threat beliefs during exposure. From 8,484 standardized exposure records of 605 patients with different anxiety disorders, learning indicators were derived: expectancy violation as mismatch between threat expectancy before exposure and threat occurrence, expectancy change as difference between original and adjusted expectancy after exposure, and prediction-error learning rate as extent to which expectancy violation transferred into change. Throughout sessions, high threat expectancy but low occurrence and adjusted expectancy indicated successful violation and change of threat beliefs by exposure. Expectancy violation, change, and learning rate substantially varied between patients. Not expectancy violation itself, but higher learning rate and expectancy change predicted better treatment outcome. Successful exposure thus requires expectancy violation to induce actual expectancy change, supporting learning from prediction error as transdiagnostic mechanism underlying successful exposure therapy.

Negative outcome expectations of psychological treatments predict unfavorable treatment outcomes. Therefore, therapists should approach negative outcome expectations and ideally transform them into more positive outcome expectations. In this study, we investigated the therapist’s interpersonal behavior to optimize the modification of negative outcome expectations. After inducing negative expectations in an online experiment, we presented different videos of therapist–patient interactions to violate the induced negative outcome expectations. We kept the expectation-violating information constant and manipulated the therapist’s warmth and competence. Results confirmed a significant influence of the therapist’s warmth and competence on expectation violation, which led to the most positive outcome expectations when the therapist was both warm and competent. In contrast to former correlational analyses, our experimental study confirms the causal role of the therapist’s interpersonal behavior and its impact on changing patients’ negative outcome expectations. On the basis of these findings, more powerful approaches to optimize critical outcome expectations can be developed.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive–behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which ‘downgraded’ the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Protein allostery requires a communication channel for functional regulation between distal sites within a protein. In the molecular chaperone Hsp70, a two-domain enzyme, the ATP/ADP status of an N-terminal nucleotide-binding domain regulates the substrate affinity of a C-terminal substrate-binding domain. Recently available three-dimensional structures of Hsp70 in ATP/ADP states have provided deep insights into molecular pathways of allosteric signals. However, direct mechanical probing of long-range allosteric coupling between the ATP hydrolysis step and domain states is missing. Using laser optical tweezers, we examined the mechanical properties of a truncated two-domain DnaK(1–552ye) in apo/ADP/ATP- and peptide-bound states. We find that in the apo and ADP states, DnaK domains are mechanically stable and rigid. However, in the ATP state, substrate-binding domain (SBD)∗ye is mechanically destabilized as the result of interdomain docking followed by the unfolding of the α-helical lid. By observing the folding state of the SBD, we could observe the continuous ATP/ADP cycling of the enzyme in real time with a single molecule. The SBD lid closure is strictly coupled to the chemical steps of the ATP hydrolysis cycle even in the presence of peptide substrate.

Childhood trauma is a common and potent risk factor for developing major depressive disorder in adulthood, associated with earlier onset, more chronic or recurrent symptoms, and greater probability of having comorbidities. Some studies indicate that evidence-based pharmacotherapies and psychotherapies for adult depression might be less efficacious in patients with a history of childhood trauma than patients without childhood trauma, but findings are inconsistent. Therefore, we examined whether individuals with major depressive disorder, including chronic forms of depression, and a reported history of childhood trauma, had more severe depressive symptoms before treatment, had more unfavourable treatment outcomes following active treatments, and were less likely to benefit from active treatments relative to a control condition, compared with individuals with depression without childhood trauma.

Currently applied manufacturing technologies for hollow composite structures impose design restrictions, such as limited integration potential, whereas differential designs are limited regarding lightweight design and load transfer due to the need of joints. This paper introduces the patented concept of structural carbon fibre-reinforced polymer (CFRP) cores, intending to overcome limitations allowing for integral, yet complex designs. The hollow cores are initially manufactured and partially cured via resin transfer moulding (RTM) with inflatable rubber core. These cores are then integrated in a dry textile-based preform which is impregnated in another RTM process. Here, the cores stabilize the preform during injection and afterwards remain in the component as load-carrying elements. Thereby the partial degree of cure of the cores before the second RTM process is optmised to balance dimensional stability and bonding strength. The process route using structural CFRP cores was successfully applied to a generic structure and proven by structural testing.

Tandem-repeat proteins comprise small secondary structure motifs that stack to form one-dimensional arrays with distinctive mechanical properties that are proposed to direct their cellular functions. Here, we use single-molecule optical tweezers to study the folding of consensus-designed tetratricopeptide repeats (CTPRs), superhelical arrays of short helix-turn-helix motifs. We find that CTPRs display a spring-like mechanical response in which individual repeats undergo rapid equilibrium fluctuations between partially folded and unfolded conformations. We rationalize the force response using Ising models and dissect the folding pathway of CTPRs under mechanical load, revealing how the repeat arrays form from the center toward both termini simultaneously. Most strikingly, we also directly observe the protein’s superhelical tertiary structure in the force signal. Using protein engineering, crystallography, and single-molecule experiments, we show that the superhelical geometry can be altered by carefully placed amino acid substitutions, and we examine how these sequence changes affect intrinsic repeat stability and inter-repeat coupling. Our findings provide the means to dissect and modulate repeat-protein stability and dynamics, which will be essential for researchers to understand the function of natural repeat proteins and to exploit artificial repeats proteins in nanotechnology and biomedical applications.

In this study, thermoset-based carbon fiber-reinforced polymer structures manufactured by the so-called modified co-curing process are analyzed and compared to well-established co-curing and co-bonding. The modified co-curing process allows manufacturing geometrically complex parts without traditional core technologies by producing laminates from a un-cured half and a pre-cured half in contrast to using two un-cured halves (co-curing) or a fully cured half plus an un-cured half (co-bonding). The interlaminar fracture toughness under Mode I loading, GIC, was determined in double cantilever beam (DCB) tests. GICdisplays a correlation of the degree of cure and the joint properties, with the co-curing laminates having 11% and 33% higher fracture toughness than the modified co-curing configurations. However, modified co-curing in all cases results is superior or equal to co-bonding. To assess the influence of surface properties for the bonding quality, different peel plies were compared with respect to the resulting joint properties. The results with up to 50% loss in GICvalues indicate the high importance of appropriate surface preparation. Subsequent tests also show that the negative influence of the peel ply on the joint properties can be reversed by abrasive surface treatment. It was found that at higher degrees of partial curing before co-curing, crack growth increasingly occurs in the interface of the bonded laminates. Therefore, the properties of the surface before joining were analyzed and modified to assess its relevance for the bonding properties and the potential for improvement.

Prolyl isomerization is recognized as one of the key regulatory mechanisms, which plays a crucial role in cell signaling, ion channel gating, phage virus infection, and molecular timing. This isomerization is usually slow but often accelerated by an enzyme, called peptidyl–prolyl isomerase (PPIase). In the current project, we investigate using single-molecule force spectroscopy (SMFS) the impact of a bacterial PPIase, SlyD, on the cis–transisomerization of the proline 2225 (P2225) in an isolated 20th domain of a cytoskeletal mechanosensing protein filamin-A (FlnA20). To explore the FlnA20–PPIase interaction, we have used multiple SMFS modes, like constant velocity, constant distance, and jumping trap experiments. In our previous study, we reported the unique nature of the P2225, which is conserved in all naturally occurring filamins and can slowly (minutes) interconvert between cis–transisomers, in absence of any PPIase. Our current results show a staggering 25-fold acceleration of the trans-to-cisisomerization rate in the presence of saturating SlyD concentration (7.25 μM) compared to the unenzymatic condition. A SlyD concentration-dependent depletion of the transisomeric lifetime was also observed. Additionally, we observed that SlyD stabilizes the cis-isomer in the native state of FlnA20 by ∼2 kBT. This is the first single-molecule observation of the cis–transisomerization catalysis by a PPIase in a mechanosensing protein.

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p< 1 × 10−4were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10  × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p= 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Purpose: The purpose of the study was to examine the relationship between officer perceptions of fit in their organization and stress (organizational and operational), overall job satisfaction and turnover contemplation (within the last 6 months). Design/methodology/approach: The authors used cross-sectional survey data from a sample of 832 officers from two Midwest police departments to examine the relationships between fit, stress and work-related attitudes. Findings: Perceived stress and organizational fit were strong predictors of overall job satisfaction and turnover contemplation; organizational fit accounted for the most variation in stress, satisfaction and turnover contemplation. Organizational stress partially mediated the relationship between organizational fit and job satisfaction and organizational fit and turnover contemplation. Research Implications: More research is needed to identify predictors of organizational fit perceptions among police officers. Practical implications: Findings indicate that agencies should pay close attention to the organizational culture and structure when trying to address issues of officer well-being and retention. Further, the person−environment framework can be a useful tool in examining police occupational outcomes. Originality/value: The authors findings contribute to research on officer stress by exploring perceptions of organizational fit as a predictor of stress and unpacking howofficer stress matters to important work outcomes, including job satisfaction and thoughts of turnover, by considering stress as a mediator between organizational fit and these work outcomes.

Original reactive powder concrete (RPC) consists of a large amount of cement, fine sand, crushed quartz, and silica fume, with a very dense matrix achieved by optimizing the granular packaging of the materials. This study, therefore, applied the modified Andreasen & Andersen particle-packing model using Aceh quartzite powder to design a densely compacted matrix and low cement content RPC mixtures. The research involved the preparation of two series of the mixture with different percentages of silica fume and Aceh quartzite powder and the 70.7 mm cube specimens were treated with combined steam curing and normal curing after which their compressive strength was tested at the age of 7 days and 28 days. The result showed the use of 61% local quartzite powder by weight of cement through an optimized mix design and cured treatment improves the RPC strength at any variation of silica fume.

In participants with stable chest pain referred for invasive coronary angiography, those with a coronary artery calcium score of 0 at CT had very low, while higher scores had increasing occurrence of major adverse cardiovascular events.

When patients suspected of having coronary artery disease were stratified by body mass index category, no difference in clinical outcomes was observed between those who underwent initial management with CT and those who underwent invasive coronary angiography.

ABSTRACTWe studied abundance, diversity, and composition of soil invertebrates along snowmelt gradients to generally understand how soil animal communities are responding to life conditions across snowbeds along a west–east transect of the European Alps and to create a reference inventory for future investigations of climate change effects on snowbed habitats. We extracted microarthropods (collembolans, oribatid mites) and macroinvertebrates (spiders, beetles, insect larvae) from soil cores taken from three sections along the snowmelt gradient: high (early snowmelt), middle, and low (late snowmelt) sections. Linear models showed no correlations between either soil conditions or time of snowmelt and densities of soil animals. A small, though statistically significant, variation in the generally high soil organic matter and sand contents and high porosity of snowbed soils seems to have no effect on soil invertebrates. Species found along the snowmelt gradient were in similar shares generalist and specialist species. Microarthropod community composition in general was driven by soil porosity and soil organic matter content; for macroinvertebrate community composition we found no specific driver. We conclude that invertebrate species assemblages in snowbeds are rather similar in the European Alps.

Current education and training in psychological interventions is mostly based on different ‘schools’ (traditions such as cognitive–behavioural or psychodynamic therapy), and strong identification with these specific traditions continuously hinders a scientifically based development of psychotherapy. This review is selective rather than systematic and comprehensive. In addition to the consideration of other influential publications, we relied on a literature search in Web of Science using the following terms (update: 24 December 2020): (psychotherapy AND meta-analy* AND competence*). After summarising current problems, a pathway for solving these problems is presented. First, we have to recategorise psychological interventions according to the mechanisms and subgoals that are addressed. The interventions can be classified according to the foci: (1) skills acquisition (eg, communication, emotion regulation, mentalisation); (2) working with relationship patterns and using the therapeutic relationship to modify them; and (3) clarification of motives and goals. Afterwards, the training of psychotherapists can switch from focusing on one theoretical framework to learning the different competences for modification according to these new categories. The selection of topics to be addressed should follow best evidence-based mechanisms and processes of mental disorders and interventions. Psychology offers knowledge about these mechanisms that can be understood as a basic science for psychological treatments in general. This requires better connection with basic science, new research efforts that focus on treatment subgoals, theory-overarching optimisation of the selection and personalisation of treatments, and new types of training for psychotherapists that are designed to optimise therapists’ competences accordingly, instead of limiting training programmes to one single theoretical framework.

BackgroundCommunication about the end of life is especially important in the family context, as patients and their families are considered as the care unit in palliative care. Open end-of-life communication can positively affect medical, psychological and relational outcomes during the dying process for patient and family. Regardless of the benefits of end-of-life conversations, many patients and their family caregivers speak little about relevant end-of-life issues.AimTo identify barriers that hinder or influence the discussion of end-of-life issues in the family context.DesignA systematic mixed-method review according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.Data sourcesA systematic search of PsycInfo, CINAHL, PubMed and Web of Science was conducted and extended with a hand search. Peer-reviewed primary studies reporting on the barriers to or difficulties in end-of-life conversations experienced by terminally ill patients and/or family caregivers were included in this review.Results18 qualitative and two quantitative studies met the inclusion criteria. The experiences of n=205 patients and n=738 family caregivers were analysed qualitatively; n=293 patients and n=236 caregivers were surveyed in the questionnaire studies. Five overarching categories emerged from the extracted data: emotional, cognitive, communicative, relational and external processes can hinder end-of-life communication within the family. The most frequently reported barriers are emotional and cognitive processes such as protective buffering or belief in positive thinking.ConclusionsResearch on end-of-life communication barriers in the family context is scarce. Further research should enhance the development of appropriate assessment tools and interventions to support families with the challenges experienced regarding end-of-life conversations.

Single-molecule mechanical experiments have proven to be ideal tools for probing the energetics and mechanics of large proteins and domains. In this paper, we investigate the nucleotide-dependent unfolding mechanics of the nucleotide-binding domain (NBD) of the Hsp70 chaperone DnaK. The NBD binds ADP or ATP in the binding cleft formed by lobe I and lobe II, which consists of two subdomains each. When force is applied to the termini of the NBD, the observed unfolding forces are independent of the nucleotide state. In contrast, when force is applied across the nucleotide-binding pocket, the unfolding forces report specifically on the nucleotide–phosphate state. In this active, ligand-responsive pulling geometry, we observed a bifurcation of the unfolding pathway; the pathway proceeds either through a cooperative “coupled pathway” or through a noncooperative “uncoupled pathway”. The partitioning between individual unfolding pathways can be effectively tuned by mutation or by the nucleotide exchange factor GrpE, i.e., by the factors affecting the strength of the lobe I–lobe II interactions within the native NBD. These experiments provide important insight into the molecular origin of the internal signaling between the subdomains of the nucleotide-binding domain of Hsp70 proteins and how signals are efficiently transferred inside the protein molecule.

The Exposure Therapy Consortium (ETC) was established to advance the science and practice of exposure therapy. To encourage participation from researchers and clinicians, this article describes the organizational structure and activities of the ETC. Initial research working group experiences and a proof-of-principle study underscore the potential of team science and larger-scale collaborative research in this area. Clinical working groups have begun to identify opportunities to enhance access to helpful resources for implementing exposure therapy effectively. This article discusses directions for expanding the consortium’s activities and its impact on a global scale.

Anxiety and related disorders are a significant public-health burden with rising prevalence in the wake of the COVID-19 pandemic. As demand for effective anxiety treatment increases, so too does the need for strategies to bolster treatment outcomes. Research on the mechanisms of exposure therapy, the frontline behavioral treatment, will be critically important for optimizing clinical outcomes. We outline an initial agenda for future research on the mechanisms of change of exposure therapy, developed in collaboration with a large international team of researchers through the Exposure Therapy Consortium. Key questions and recommendations for future research focus on four priority areas: conceptualization, measurement, study design/analysis, and individual/contextual differences. Rising to the challenge of addressing these questions will require coordinated action and availability of centralized tools that can be used across trials, settings, and research groups.

As open science principles continue to gain traction, striking a balance between patient privacy and data accessibility has become more crucial in medical research than ever before. Encryption-based pseudonymization is a powerful tool to ensure compliance with data protection regulations from both local institutional guidelines and broader regional regulations, such as the General Data Protection Regulation of the European Union. Employing this type of pseudonymization protects the privacy and security of research participants, and allows researchers to effortlessly comply with data security regulations. The pseudonymization workflow however, can vary significantly across research projects, limiting the usability of supporting software tools. Here we present ALIIAS, a customizable pseudonymization framework that allows easy and flexible deployment of custom pseudonymization software, dedicated to the specific ethical and experimental requirements of individual research projects. Features include compatibility with hardware security tokens paired with two-factor authentication, integration to the survey web application LimeSurvey, as well as custom-format pseudonyms and automatic barcode generation. Collectively, these features make ALIIAS suitable for integration into various research infrastructures and lower the initial barrier to incorporating cutting-edge encryption-based pseudonymization in translational and clinical research practices.

With the increasing utilization of fiber-reinforced polymers in various areas of application such as aviation and automotive, the need for efficient production methods appropriate for these materials also gains importance. The widespread use of metallic fasteners in conjunction with differential design leads to stress concentrations when applied to FRPs and prevents the full utilization of their mechanical properties. In an effort to develop an appropriate joining technology that also contributes to reducing tooling costs, co-curing of thermoset FRP laminates is analyzed in the present work. To gain insight into the feasibility of the use of pre-cured laminates in co-curing processes, laminates of varying degree of cure are joined with uncured laminates in a co-curing process and the mechanical properties of the resulting laminates are investigated experimentally. Based on these experimental results, an interdependence between bonding properties and the degree of cure of the pre-cured laminate can be shown.

In a multicenter prospective study, patients had a two- to threefold preference for coronary CT angiography with stress perfusion over SPECT and invasive coronary angiography for evaluation of coronary artery disease.

Herein, the synthesis and pharmacological characterization of an extended library of differently substituted N-methyl-14-O-methylmorphinans with natural and unnatural amino acids and three dipeptides at position 6 that emerged as potent μ/δ opioid receptor (MOR/DOR) agonists with peripheral antinociceptive efficacy is reported. The current study adds significant value to our initial structure–activity relationships on a series of zwitterionic analogues of 1(14-O-methyloxymorphone) by targeting additional amino acid residues. The new derivatives showed high binding and potent agonism at MOR and DOR in vitro. In vivo, the new 6-amino acid- and 6-dipeptide-substituted derivatives of 1were highly effective in inducing antinociception in the writhing test in mice after subcutaneous administration, which was antagonized by naloxone methiodide demonstrating activation of peripheral opioid receptors. Such peripheral opioid analgesics may represent alternatives to presently available drugs for a safer pain therapy.

Hsp90 is an essential molecular chaperone, which has to be in a dimeric form for its correct function. While the affinity of the dimer has previously been measured, little is known about how it associates and dissociates and the factors that influence this. We perform an in-depth single molecule characterization of the C-terminal association and dissociation of Hsp90. We find more than one dissociation rate, indicating that the dimer has a stable and an unstable state. Furthermore, we find that the stability of the C-terminal association is dependent on the presence of ATP, despite the C-terminal dimerization interface being distal to the catalytic site.

This multicenter study showed that the diagnostic performance of myocardial CT perfusion was similar to that of MR perfusion imaging in the detection of coronary artery disease.

Abstract.Background:Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. Patients and methods:In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). Results:There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128–236] meters to 345 [95 % CI 227–463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109–210] meters to 268 [95 % CI 182–366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. Conclusions:Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Förster resonance energy transfer (FRET)-based tension sensor modules (TSMs) are available for investigating how distinct proteins bear mechanical forces in cells. Yet, forces in the single piconewton (pN) regime remain difficult to resolve, and tools for multiplexed tension sensing are lacking. Here, we report the generation and calibration of a genetically encoded, FRET-based biosensor called FL-TSM, which is characterized by a near-digital force response and increased sensitivity at 3–5 pN. In addition, we present a method allowing the simultaneous evaluation of coexpressed tension sensor constructs using two-color fluorescence lifetime microscopy. Finally, we introduce a procedure to calculate the fraction of mechanically engaged molecules within cells. Application of these techniques to new talin biosensors reveals an intramolecular tension gradient across talin-1 that is established upon integrin-mediated cell adhesion. The tension gradient is actomyosin- and vinculin-dependent and sensitive to the rigidity of the extracellular environment.

Supplemental digital content is available in the text.

Supplemental digital content is available in the text.

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In scope of the investigation of residual stresses the hole drilling method is an accepted method. The method is though not applicable for materials with high anisotropic behavior. Therefore a new algorithm is derived which allows the calculation of residual stresses in laminates made of unidirectional layers. Also the strain gauges deliver only strains on the areas where the strain gauges are applied. With the use of a high resolution imaging system and digital image correlation this area and the informational output can be widely improved. First, the derivation of the residual stress analysis algorithm is presented. For this an adequate finite element model, which is modeling the cooldown process as well as the drilling process, is set up and the surface strains are extracted. Based on this information an algorithm is derived and presented. Within the derivation a change of the layup, a possible change of the cooldown process and a variation of the drilling steps can be investigated. In consequence the input parameters of the algorithm can vary dependent on these factors. Second, the new optical testing setup with refinements to be able to measure the small deformations within micro-strains on the specimen’s surface is prepared and the concept presented. To solve the problem of casting shadows of the drill a special camera setup is being used.

Zusammenfassung.In der psychotherapeutischen Versorgung in Deutschland wächst der Anteil an Patient/innen aus anderen Kulturen 1und damit auch die Bedeutsamkeit transkultureller Kompetenzen bei Psychotherapeut/innen. Aktuell mangelt es an evaluierten Schulungsprogrammen, um solche Kompetenzen gezielt zu fördern. Besonders webbasierte Programme, die eine zeitlich und örtlich flexible Bearbeitung ermöglichen, fehlen bisher gänzlich. Basierend auf dem theoretischen Konzept zu transkulturellen Kompetenzen von Sue und Kollegen (1992) wurde ein webbasiertes Programm zur Förderung transkultureller Kompetenzen bei Psychotherapeut/innen entwickelt. Es besteht aus sechs Modulen, die sich aus Texten und praktischen Übungen zusammensetzen. Es sollen Wissen und Fertigkeiten im Umgang mit Patient/innen aus anderen Kulturen geschult sowie Teilnehmenden die Bedeutung ihrer kulturellen Konzepte für die therapeutische Arbeit bewusst gemacht werden. Neben dem Programm wird das Design einer geplanten randomisiert-kontrollierten Studie (RCT) zu dessen Wirksamkeitsprüfung vorgestellt. Die Trainingsgruppe soll mit zwei Gruppen (Edukationsgruppe/Warteliste) hinsichtlich transkultureller Kompetenzen (u.a. erfasst mit dem Inventar zur Erfassung transkultureller Kompetenzen bei Psychotherapeuten) sowie assoziierter Variablen (z.B. Anteil an Patient/innen aus anderen Kulturen in Behandlung) verglichen werden. Daten sollen vor und nach dem Training sowie zwei und sechs Monate nach Abschluss des Trainings erhoben werden.

Es wird ein Ultraschallmikroskop zur zerstörungsfreien Untersuchung gekrümmter Prüflinge vorgestellt. Kommerziell erhältliche Ultraschallmikroskope sind lediglich für die Untersuchung an ebenen Oberflächen konzipiert. Sie verfügen über ein Verfahrsystem aus zwei Linearachsen, das den Ultraschallprüfkopf während der Messung lateral über den Prüfling bewegt. Um bei Prüflingen mit gekrümmter Oberfläche eine optimale Bildqualität zu erzielen, muss der Prüfkopf so justiert werden, dass er an jedem Messpunkt orthogonal auf deren Oberfläche schallt. Im vorgestellten Messaufbau wurde dazu ein hochpräziser Roboter integriert, der über sechs Bewegungsfreiheitsgrade verfügt. Dadurch ist es möglich, neben der mäanderförmigen Abtastung durch den Ultraschallprüfkopf eine zusätzliche Winkelnachführung des Prüflings durchzuführen. In diesem Beitrag wird das entwickelte Ultraschallmikroskop in Aufbau und Funktion beschrieben. Die Auflösungsgrenzen im resultierenden Bild sowie die erreichbare Positioniergenauigkeit des Verfahrsystems werden beleuchtet. Zudem wird das Potential des Systems anhand einiger Messungen an exemplarischen Prüflingen aufgezeigt.