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The processing of organic substances by vacuum deposition is opening new possibilities for the properties of optical surfaces. Organic small molecules can be evaporated and deposited like optical thin films. Plasma etching, which has been successfully applied to generate nanostructures on polymer substrates, is now used for obtaining antireflective nanostructures on top of interference stacks on glass. The latest results in achieving excellent antireflective properties for a wide range of light incidence angles were accomplished through multiple etching of polymer substrates and organic layers.

State-of-the-art Earth system models typically employ grid spacings of O(100 km), which is too coarse to explicitly resolve main drivers of the flow of energy and matter across the Earth system. In this paper, we present the new ICON-Sapphire model configuration, which targets a representation of the components of the Earth system and their interactions with a grid spacing of 10 km and finer. Through the use of selected simulation examples, we demonstrate that ICON-Sapphire can (i) be run coupled globally on seasonal timescales with a grid spacing of 5 km, on monthly timescales with a grid spacing of 2.5 km, and on daily timescales with a grid spacing of 1.25 km; (ii) resolve large eddies in the atmosphere using hectometer grid spacings on limited-area domains in atmosphere-only simulations; (iii) resolve submesoscale ocean eddies by using a global uniform grid of 1.25 km or a telescoping grid with the finest grid spacing at 530 m, the latter coupled to a uniform atmosphere; and (iv) simulate biogeochemistry in an ocean-only simulation integrated for 4 years at 10 km. Comparison of basic features of the climate system to observations reveals no obvious pitfalls, even though some observed aspects remain difficult to capture. The throughput of the coupled 5 km global simulation is 126 simulated days per day employing 21 % of the latest machine of the German Climate Computing Center. Extrapolating from these results, multi-decadal global simulations including interactive carbon are now possible, and short global simulations resolving large eddies in the atmosphere and submesoscale eddies in the ocean are within reach.

Classical numerical models for the global atmosphere, as used for numerical weather forecasting or climate research, have been developed for conventional central processing unit (CPU) architectures. This hinders the employment of such models on current top-performing supercomputers, which achieve their computing power with hybrid architectures, mostly using graphics processing units (GPUs). Thus also scientific applications of such models are restricted to the lesser computer power of CPUs. Here we present the development of a GPU-enabled version of the ICON atmosphere model (ICON-A), motivated by a research project on the quasi-biennial oscillation (QBO), a global-scale wind oscillation in the equatorial stratosphere that depends on a broad spectrum of atmospheric waves, which originates from tropical deep convection. Resolving the relevant scales, from a few kilometers to the size of the globe, is a formidable computational problem, which can only be realized now on top-performing supercomputers. This motivated porting ICON-A, in the specific configuration needed for the research project, in a first step to the GPU architecture of the Piz Daint computer at the Swiss National Supercomputing Centre and in a second step to the JUWELS Booster computer at the Forschungszentrum Jülich. On Piz Daint, the ported code achieves a single-node GPU vs. CPU speedup factor of 6.4 and allows for global experiments at a horizontal resolution of 5 km on 1024 computing nodes with 1 GPU per node with a turnover of 48 simulated days per day. On JUWELS Booster, the more modern hardware in combination with an upgraded code base allows for simulations at the same resolution on 128 computing nodes with 4 GPUs per node and a turnover of 133 simulated days per day. Additionally, the code still remains functional on CPUs, as is demonstrated by additional experiments on the Levante compute system at the German Climate Computing Center. While the application shows good weak scaling over the tested 16-fold increase in grid size and node count, making also higher resolved global simulations possible, the strong scaling on GPUs is relatively poor, which limits the options to increase turnover with more nodes. Initial experiments demonstrate that the ICON-A model can simulate downward-propagating QBO jets, which are driven by wave–mean flow interaction.

Diffusion weighted brain imaging (DWI) is used in acute stroke, but may also be useful in patients wits minor stroke or TIA when seen several days or weeks after symptom [...]

Abstract Background Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Abstract Background Transition from distinct Child and Adolescent Mental Health (CAMHS) to Adult Mental Health Services (AMHS) is beset with multitude of problems affecting continuity of care for young people with mental health needs. Transition-related discontinuity of care is a major health, socioeconomic and societal challenge globally. The overall aim of the Managing the Link and Strengthening Transition from Child to Adult Mental Health Care in Europe (MILESTONE) project (2014–19) is to improve transition from CAMHS to AMHS in diverse healthcare settings across Europe. MILESTONE focuses on current service provision in Europe, new transition-related measures, long term outcomes of young people leaving CAMHS, improving transitional care through ‘managed transition’, ethics of transitioning and the training of health care professionals. Methods Data will be collected via systematic literature reviews, pan-European surveys, and focus groups with service providers, users and carers, and members of youth advocacy and mental health advocacy groups. A prospective cohort study will be conducted with a nested cluster randomised controlled trial in eight European Union (EU) countries (Belgium, Croatia, France, Germany, Ireland, Italy, Netherlands, UK) involving over 1000 CAMHS users, their carers, and clinicians. Discussion Improving transitional care can facilitate not only recovery but also mental health promotion and mental illness prevention for young people. MILESTONE will provide evidence of the organisational structures and processes influencing transition at the service interface across differing healthcare models in Europe and longitudinal outcomes for young people leaving CAMHS, solutions for improving transitional care in a cost-effective manner, training modules for clinicians, and commissioning and policy guidelines for service providers and policy makers. Trial registration “MILESTONE study” registration: ISRCTN ISRCTN83240263 Registered 23 July 2015; ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

AbstractProblems in the area of text and document processing can often be described as text rewriting tasks: given an input text, produce a new text by applying some fixed set of rewriting rules. In its simplest form, a rewriting rule is given by a pair of strings, representing a source string (the ?original?) and its substitute. By a rewriting dictionary, we mean a finite list of such pairs; dictionary-based text rewriting means to replace in an input text occurrences of originals by their substitutes. We present an efficient method for constructing, given a rewriting dictionary D, a subsequential transducer that accepts any text tas input and outputs the intended rewriting result under the so-called ?leftmost-longest match? replacement with skips, t'. The time needed to compute the transducer is linear in the size of the input dictionary. Given the transducer, any text tof length |t| is rewritten in a deterministic manner in time O(|t|+|t'|), where t' denotes the resulting output text. Hence the resulting rewriting mechanism is very efficient. As a second advantage, using standard tools, the transducer can be directly composed with other transducers to efficiently solve more complex rewriting tasks in a single processing step. [ABSTRACT FROM AUTHOR]

Wachkraniotomien in der Tumor- und Epilepsiechirurgie oder bei der stereotaktischen Elektrodenimplantation für die tiefe Hirnstimulation erfordern spezifische anästhesiologische Strategien. Mit Propofol werden kurze Aufwachzeiten sichergestellt, und die respiratorische Funktion des üblicherweise spontan atmenden Patienten wird nur wenig beeinträchtigt. Die Schmerzausschaltung sollte primär durch einen Hemiskalpblock bei großflächiger Trepanation oder eine lokale Anästhetikainfiltration bei der Tiefenelektrodenimplantation erfolgen. Zusätzlich kann bei einer Trepanation (Tumor- oder Epilepsiechirurgie) Remifentanil in niedriger Dosierung empfohlen werden. Durch einen transnasal eingeführten Tubus, dessen Spitze unter der Epiglottis platziert wird, kann der Atemweg frei gehalten werden. Zum Schutz vor Erbrechen ist eine ausreichende antiemetische Prophylaxe erforderlich. [ABSTRACT FROM AUTHOR]

The coracoacromial arch is a static anterior-superior stabilizer of the humeral head. Thus coracoacromial arch inclination, which varies depending on coracoid tip position, may be related to shoulder pathologies. Therefore, we retrospectively analysed coracoid tip positions in the true anterior posterior view of different shoulder pathologies: reference shoulders (n=27), shoulders with rotator cuff tear (supraspinatus tear n=29; subscapularis tear n=21) and shoulders with anterior glenohumeral instability (traumatic n=17; atraumatic n=14). In supraspinatus tear shoulders, the coracoid tip projected onto inferior glenoid half in 86% of cases (type I coracoid), extending more inferiorly compared with reference group (p=0.0002) or subscapularis tear shoulders (p<0.0001). In contrast, 78% of cases with subscapularis tear show the coracoid tip projected onto the superior glenoid half (type II coracoid). Atraumatic glenohumeral instabilities had a more superior coracoid tip position than traumatic instabilities (p=0.04), but no differences were observed on basis of coracoid type or in comparison with normal controls. We conclude that coracoid tip position is highly variable. Since type I coracoids are predominant in shoulders with supraspinatus tears and type II coracoids in shoulders with subscapularis tears, coracoid tip position may thus provide a simple diagnostic complement for a probable site of rotator cuff tears. [ABSTRACT FROM AUTHOR]

Power dissipation besides chip area is still one main optimization issue in high performance CMOS design. Regarding high throughput building blocks for digital signal processing architectures which are optimized down to the physical level a complementary two-phase clocking scheme (CTPC) is often advantageous concerning ATE-efficiency. The clock system dissipates a significant part of overall power up to more than 50% in some applications. One efficient power saving strategy for CTPC signal generation is the charge balancing technique. To achieve high efficiency with this approach a careful optimization of timing relations within the control is inevitable. However, as in modern CMOS processes device variations increase, timing relations between sensitive control signals can be affected seriously. In order to compensate for the influence of global and local variations in this work, an adaptive control system for charge balancing in a CTPC generator is presented. An adjustment for the degree of charge recycling is performed in each clock cycle. In the case of insufficient recycling the delay elements which define duration and timing position of the recycling pulse are corrected by switchable timing units. In a benchmark with the conventional clock generation system, a power reduction gain of up to 24.7% could be achieved. This means saving in power of more than 12% for a complete number-crunching building block.

Following publication of the original article [1], the authors reported they wanted to reinstate a co-author, who previously declined his authorship due to a misinterpretation of authorship limitations per research center.

INTRODUCTION: The explanation for the prognostic value of the ABCD2-score remains uncertain. If it genuinely measures cerebral susceptibility to ischaemia, it should correlate with other markers of susceptibility, such as leukoaraiosis (LA). We studied the association of the ABCD2-score with the severity of LA in a large cohort of patients with TIA or minor stroke. METHODS: Consecutive patients attending a TIA-clinic were recruited and underwent routine MR-imaging (T2/DWI). Detailed clinical data were obtained and the ABCD2 score calculated. Two independent observers assessed the presence and severity of LA with standard rating scales. RESULTS: 671 patients (56% men; mean age=71 (SD=11) years) with TIA (45%) or minor stroke attended the clinic. LA was more prevalent (p=0.015) and more severe (p=0.007) in patients with stroke vs TIA. LA was associated with lesion presence on DWI (p<0.0001) and history of prior stroke (p=0.026). LA and the ABCD2-score were strongly associated (p<0.0001), due mainly to association of LA with age (p<0.0001), with motor symptoms at presentation (p<0.0001) and with hypertension (p=0.001). Associations were similar in analyses stratified by diagnosis and adjusted for age. CONCLUSION: The associations of LA with prior stroke, presenting stroke and with lesion presence on DWI confirm it as a marker of cerebral susceptibility to ischaemia. The strong association of the ABCD2-score with LA may therefore at least partly explain its prognostic value. [ABSTRACT FROM AUTHOR]

BACKGROUND: Leukoaraiosis (LA) may reflect chronic small vessel ischaemia, but its underlying aetiology is uncertain. Possibilities include atheroma more proximally in the small cerebral vessels. In this case, LA would be expected to be associated with other risk factors for, and markers of, atherosclerosis. In light of conflicting results from previous studies, we investigated this association in a large cohort of well phenotyped patients with transient ischaemic attack (TIA) or minor stroke. METHODS: Consecutive patients with TIA or minor stroke attending a TIA clinic were recruited and underwent routine MR-imaging and MR-angiography. LA was assessed by two independent observers using standard rating scales. A standardised clinical questionnaire was used to record data on major vascular risk factors. RESULTS: 671 patients (mean (SD) age 71 (11), 56% men) with TIA (N=301) or minor stroke (N=370) attended the clinic. LA was independently associated with older age (p<0.0001), hypertension (p=0.001) and female sex (p<0.0001). The latter associations were still present after adjusting the analysis for age. However, LA was not associated with smoking, hypercholesterolaemia, ischaemic heart disease, peripheral vascular disease or diabetes, and it was unrelated to the severity of carotid disease. CONCLUSION: Leukoaraiosis was not associated with either carotid stenosis or risk factors for atherosclerosis, suggesting that its aetiology is independent of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

This dataset contains demographic, clinical, and health-related quality of life (HRQoL) data from 2905 patients including 200 cancer patients after immune checkpoint inhibitor (ICI) cessation and 2705 patients with a wide variety of autoimmune diseases.Within this multicenter, cross-sectional survey study data were collected questionnaire-based in cancer patients (ICI-patients) ≥ 18 years of age who had received at least one dose of ICI with ≥ 12 weeks since ICI discontinuation. Patients with autoimmune diseases (AI-patients) were ≥ 18 years, had at least one autoimmune disease and had never received ICI. ICI-patients were recruited in three skin cancer centers and via support groups. AI-patients were recruited in an outpatient clinic for internal medicine and via support groups.Specific questionnaires for ICI-patients/AI-patients were provided paper-based for patients from outpatient clinics and online for patients from support groups. Both questionnaires contained sections with demographic information, clinical data, and the standardized patient-reported outcome measure EuroQol 5D-5L (EQ-5D-5L) to assess HRQoL. Clinical data focused on autoimmunity and therapy of autoimmunity in (1) ICI-patients referring to particularly persistent immune-related adverse events (persistent irAEs) and in (2) AI-patients referring to respective autoimmune diseases. Additionally, specific items on cancer and cancer therapy were included in ICI-patients, and AI-patients were asked about the presence of acute exacerbations of autoimmune diseases.This dataset contains the raw data for ICI-patients and AI-patients, analyzed data on patient demographics, clinical characteristics and HRQoL scores among ICI-patients with/without persistent irAEs and among AI-patients.The data provide a basis for further investigations within the cohort of ICI-patients after ICI cessation and/or for AI-patients with different autoimmune diseases with regard to HRQoL, autoimmunity and therapy of autoimmunity.

Objectives Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.Design In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.Setting UK stroke services.Participants 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.Results Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.Conclusion It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration number ISRCTN83290762; Post-results.

The optimal surgical approach in patients with pectus excavatum (PEx) who need cardiac surgery remains uncertain. The challenge is even greater, if it is already foreseeable that the patient will be needed further procedure in the next future. We describe a novel sternotomy-sparing approach for minimal-invasive biventricular assist device (BiVAD) implantation in a patient with an acute heart failure (HF) due to dilated cardiomyopathy and severe PEx. Moreover, alternative approaches for ventricular assist device (VAD) implantation and timing of the repair of PEx will be discussed., (© 2022. The Japanese Society for Artificial Organs.)

Objectives: Several studies have shown the potential advantage of less-invasive surgery (LIS) for left ventricular assist device (LVAD) implantation. This study aims to determine the impact of LIS on stroke and pump thrombosis events after LVAD implantation., Methods: Between January 2015 and March 2021, 335 consecutive patients underwent LVAD implantation using either conventional sternotomy (CS) or the LIS technique. Patient characteristics was prospectively collected. All patients were followed up until October 2021. Logistic multivariate regression and propensity-matched analyses were performed to account for confounding factors., Results: A total of 242 patients ( F  = 32; 13.0%) underwent LVAD implantation with CS and 93 patients ( F  = 8; 8.6%) with the LIS approach. Propensity matching generated two groups, including 98 patients in the CS group and 67 in the LIS group. Intensive care unit stay for the LIS group patients was significantly shorter than that for the CS group patients [2 (IQR: 2-5) days vs. 4 (IQR: 2-12) days, p  < 0.01]. There were no significant differences in the incidence of stroke events (14% in CS vs. 16% in the LIS group; p  = 0.6) or in pump thrombosis (6.1% in CS vs. 7.5% in the LIS group; p  = 0.8) between the groups. The hospital mortality rate in the matched cohort was significantly lower in the LIS group (7.5% vs. 19%; p  = 0.03). However, the 1-year mortality rate showed no significant difference between both groups (24.5% in CS and 17.9% in LIS; p  = 0.35)., Conclusions: The LIS approach for LVAD implantation is a safe procedure with potential advantage in the early postoperative period. However, the LIS approach remains comparable to the sternotomy approach in terms of postoperative stroke, pump thrombosis, and outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nozdrzykowski, Bauer, Schulz, Jawad, Bireta, Eifert, Sandri, Jozwiak-Nozdrzykowska, Borger and Saeed.)

A major problem for optical systems is the polarization splitting occurring at any interface in the event of oblique light. Low-index nanostructured silica layers were produced by overcoating an initial organic structure with silica and subsequent removal of the organic constituents. The nanostructured layers can be tailored to achieve defined low effective refractive indices down to 1.05. They can also be stacked together with homogeneous layers to produce broadband antireflective coatings with very low polarization splitting. Especially thin interlayers that separate the low-index structured layers turned out to be useful to optimize the polarization properties.

To increase the performance of optical systems, a good antireflective coating is required to ensure low reflectance and high transmittance of optical surfaces. Further problems, such as fogging that causes light scattering, negatively affect the image quality. This implies that other functional properties are also required. Presented here is a highly promising combination of an antireflective double nanostructure on top of an antifog coating with long-term stable properties, generated in a commercial plasma-ion-assisted coating chamber. It is demonstrated that the nanostructures do not affect the antifog properties and can be successfully used for many applications.

Objective:  Atherosclerosis is a common disease in older psittacines living in captivity with inadequate housing conditions. However, diagnosis in the living bird remains difficult and the disease is often only recognized during post mortem examination. In this context, we aimed at investigating the diagnostic value of currently reported methods in African grey parrots ( Psittacus erithacus )., Material and Methods:  7 clinically healthy African grey parrots and 32 African grey parrots with suspected atherosclerosis were evaluated in this study. An overall scoring system was implemented based on clinical signs, measurement of blood cholesterol and triglyceride levels, a radiographic exam, and an echocardiogram in B-mode. Furthermore, measurements of the blood flow velocity in the aortic root, heart rate and velocity time integral were performed using the spectral Doppler ultrasonographic function., Results:  Measurements of the blood flow velocity in the aortic root showed highly significant differences between the clinically healthy group and a subset of the patient group. Significant differences between the groups also were evident concerning the results of the overall scoring and of the initial examinations., Conclusion:  The results support that combining spectral Doppler ultrasonographic examination with other diagnostic options may be used to substantiate suspected atherosclerosis and provide additional information regarding the cardiovascular status of the patient., Clinical Relevance:  The presented findings indicate that employing the described diagnostic methods allows for an intra vitam diagnosis of atherosclerosis and therefore an earlier initiation of treatment., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by left or biventricular systolic impairment. Historically, most of the clinical attention has been devoted to the evaluation of left ventricular function and morphology, while right ventricle (RV) has been for many years the forgotten chamber. Recently, progresses in cardiac imaging gave clinicians precious tools for the evaluation of RV, raising the awareness of the importance of biventricular assessment in DCM. Indeed, RV involvement is far from being uncommon in DCM, and the presence of right ventricular dysfunction (RVD) is one of the major negative prognostic determinants in DCM patients. However, some aspects such as the possible role of specific genetic mutations in determining the biventricular phenotype in DCM, or the lack of specific treatments able to primarily counteract RVD, still need research. In this review, we summarized the current knowledge on RV involvement in DCM, giving an overview on the epidemiology and pathogenetic mechanisms implicated in determining RVD. Furthermore, we discussed the imaging techniques to evaluate RV function and the role of RV failure in advanced heart failure., (© 2022. The Author(s).)

Fukutin encoded by FKTN is a ribitol 5-phosphate transferase involved in glycosylation of α-dystroglycan. It is known that mutations in FKTN affect the glycosylation of α-dystroglycan, leading to a dystroglycanopathy. Dystroglycanopathies are a group of syndromes with a broad clinical spectrum including dilated cardiomyopathy and muscular dystrophy. In this study, we reported the case of a patient with muscular dystrophy, early onset dilated cardiomyopathy, and elevated creatine kinase levels who was a carrier of the compound heterozygous variants p.Ser299Arg and p.Asn442Ser in FKTN . Our work showed that compound heterozygous mutations in FKTN lead to a loss of fully glycosylated α-dystroglycan and result in cardiomyopathy and end-stage heart failure at a young age.

Background: Early hypoattenuated leaflet thickening (HALT) occurs in at least 10% of all transcatheter aortic valve replacement (TAVR) patients. The long-term prognostic impact of HALT is uncertain., Objectives: The aim of this study was to assess the long-term risk of early HALT post-TAVR., Methods: We report outcome data from our prospective observational registry with post-TAVR computed tomography angiography performed between May 2012 and December 2017. The outcomes were survival, cardiovascular mortality, ischemic cerebrovascular events, and symptomatic hemodynamic valve deterioration., Results: Early HALT was diagnosed in 115 (16.0%) of 804 patients. During a median follow-up of 3.25 years, survival rates did not differ significantly between patients with and without HALT (Kaplan-Meier 3-year estimates for survival 70.1% vs 74.0%, P = 0.597). The 3-year cardiovascular mortality rate was 13.2% versus 11.3% (with vs without HALT, P = 0.733). The 3-year event rate for cerebrovascular events was 2.0% versus 4.4% (with vs without HALT, P = 0.246), and the 3-year event rate of symptomatic hemodynamic valve deterioration was 9.4% versus 1.5% (with vs without HALT, P < 0.001). Multivariable analysis revealed the following predictors of symptomatic hemodynamic valve deterioration: HALT (HR: 6.10; 95% CI: 2.59-14.29; P < 0.001), the mixed valve-type group (HR: 6.51; 95% CI: 2.38-17.81; P < 0.001), and prosthesis diameter (HR valve size per 3 mm [HR: 0.37; 95% CI: 0.17-0.79]; P = 0.011)., Conclusions: During a median follow-up of more than 3 years, HALT was not associated with mortality or cerebrovascular events. However, we observed an association of HALT with symptomatic hemodynamic valve deterioration., Competing Interests: Funding Support and Author Disclosures Prof Neumann reports that his institution has received research grants, consultancy fees, and speaker honoraria to form Daiichi-Sankyo, AstraZeneca, Sanofi, Bayer, The Medicines Company, Bristol Myers Squibb, Novartis, Roche, Boston Scientific, Biotronik, Medtronic, Edwards, and Ferrer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

(1) Background: The aim of this study was to systematically compare TEM sections of mineralized human enamel and dentine prepared by focused ion beam (in situ lift-out) technique and ultramicrotomy through a combination of microscopic examination methods (scanning electron microscopy and transmission electron microscopy). In contrast with published studies, we compared the TEM preparation methods using the same specimen blocks as those for the ultramicrotomy and FIB technique. (2) Methods: A further evaluation of TEM sample preparation was obtained by confocal laser scanning microscopy and atomic force microscopy. In addition, ultramicrotome- and focused ion beam-induced artefacts are illustrated. (3) Results: The FIB technique exposed a major difference between non-decalcified enamel and dentine concerning the ultrastructural morphology compared to ultramicrotome-prepared sections. We found that ultramicrotomy was useful for cutting mineralized dentine, with the possibility of mechanical artefacts, but offers limited options for the preparation of mineralized enamel. FIB preparation produced high-quality TEM sections, showing the anisotropic ultrastructural morphology in detail, with minor structural artefacts. Our results show that the solution of artificial saliva and glutardialdehyde (2.5% by volume) is a very suitable fixative for human mineralized tissue. (4) Conclusions: The protocol that we developed has strong potential for the preparation of mineralized biomaterials for TEM imaging and analysis.

Objectives: We sought to assess the impact of echocardiographic and hemodynamic grading of paravalvular leakage (PVL) after transcatheter aortic valve implantation (TAVI) on the prediction of 5-year mortality. PVL after TAVI is known to influence outcome after TAVI. Yet, present available data of long-term outcomes and especially the comparison of different modalities for measurement of PVL is little., Methods: We performed a retrospective single-center cohort study and compared the prognostic value of echocardiographic PVL grading as well as the aortic regurgitation index (ARI) pre- and post-TAVI. Univariable and multivariable Cox proportional regression analysis generated hazard ratios for mortality., Results: A total of 464 patients underwent TAVI at our center between August 2012 and Decemebr 2014, with self-expandable CoreValve (11%) or balloon-expandable Sapien XT (47.4%) and Sapien 3 (41.6) valves. Overall 5-year mortality was 52.4% (243/464). Echocardiographic classes of PVL at discharge showed a significant (p = 0.002) association with 5-year mortality, mild PVL remained as an independent predictor for 5-year mortality in multivariable analysis (hazard ratio: 1.642 [95% confidence interval: 1.235-2.182]; p = 0.001). Grades of PVL as assessed during the procedure by ARI (below the previously defined cut-off of 25) did not show a significant association with 5-year mortality (p = 0.417 and p = 0.995, respectively)., Conclusions: Even mild PVL assessed by echocardiography was an independent predictor for 5-year survival, whereas hemodynamic measurements did not help to identify PVLs that are relevant to 5-year survival., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Circulating graft-derived cell-free DNA (dd-cfDNA) is a new marker of cardiac allograft damage that is used for noninvasive rejection diagnostics. We performed dd-cfDNA (%) in heart transplant recipients during the first posttransplant year., Methods: In 87 patients, serial dd-cfDNA determination at predefined time-points was performed in 770 single samples. dd-cfDNA fraction (%) was measured using an established universal droplet digital polymerase chain reaction method, providing same-day turn-around. Rejection was diagnosed according to clinical parameters and biopsies., Results: Median dd-cfDNA (%) was high (5.36%) immediately after reperfusion and decreased to a median (interquartile range) of 0.10% (0.05%-0.24%) in clinically stable patients by postoperative day 10. Compared to dd-cfDNA (%) samples in clinically stable patients, values were higher (P < 0.001) in biopsy-proven rejection ISHLT 1R (0.42% [0.15%-0.53%]) and 2R rejection (0.84% [0.39%-0.97%]). Moreover, dd-cfDNA (%) was already significantly increased 9-30 days before biopsy-proven rejection (0.36% [0.20%-0.61%]). An as yet unknown finding was a slightly, but significantly (P < 0.0001) higher dd-cfDNA (%) value in samples of stable patients with pericardial effusions (PEs) (n = 94; 0.18% [0.07%-0.30%]) compared to samples of non-PE patients (n = 132; 0.07% [0.04%-0.17%]). Using a cutoff of 0.35%, sensitivity and specificity of dd-cfDNA for cardiac rejection were 0.76 and 0.83 (area under the curve [AUC] ROC-curve: 0.81 [95% confidence interval, 0.73-0.89]). Omitting PE samples from the control group yielded an AUC of 0.86 [95% confidence interval, 0.76-0.95]. Samples drawn <12 hours after endomyocardial biopsy showed high (0.40% [0.15%-1.21%]) dd-cfDNA values, also in ISHLT0R (0.36% [0.10%-0.60%])., Conclusions: dd-cfDNA plasma values were significantly associated with cardiac rejection. However, PE or improper sampling (eg, shortly after biopsy) should be considered as confounders for rejection diagnoses using dd-cfDNA., Competing Interests: J.B. reports personal fees from Chronix Biomedical GmbH, during the conduct of the study; in addition, J.B. has patent EP3004388 pending and patent EP3201361 pending. M.O. reports grants from Krankenhausbetriebsgesellschaft Bad Oeynhausen mbH (Herz- und Diabeteszentrum Nordrhein-Westfalen), during the conduction of the study; personal fees from Chronix Biomedical Inc., San José, CA, and personal fees from Liquid Biopsy Center (LBC) GmbH, Göttingen, Germany, outside the submitted work. U.S. reports grants from Novartis during the conduction of the study, personal fees from Novartis, personal fees from Astellas, personal fees from Sanofi, and grants from Actelion outside the submitted work. U.F. reports grants from Novartis during the conduction of the study. E.S. reports grants from the German Ministry for Education and Research and others from Chronix Biomedical during the conduct of the study; in addition, E.S. has patents EP3004388 and EP3201361 issued. I.B. received speaker’s honoraria from Aspen Germany GmbH, Bristol-Myers Squibb/Pfizer, Siemens Healthcare, and CSL Behring; reimbursement for congress traveling and accommodation from Aspen, and performed contract research for Siemens Healthcare; I.B. is a member of the advisory board of LFB Biomedicaments, Siemens Healthcare, and CSL Behring. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Peripartum cardiomyopathy (PPCM) is a rare, life-threatening form of heart disease, frequently associated with gene alterations and, in some cases, presenting with advanced heart failure. Little is known about ventricular assist device (VAD) implantation in severe PPCM cases. We describe long-term follow-up of PPCM patients who were resistant to medical therapy and received mechanical circulatory support or heart transplant., Methods and Results: A total of 13 patients were included with mean follow-up of eight years. Mean age of PPCM onset was 33.7 ± 7.7 years. All patients were initially treated with angiotensin-converting enzyme inhibitors and beta-blockers, and four received bromocriptine. Overall, five patients received VADs (three biventricular, two isolated left ventricular) at median 27 days (range: 3 to 150) following childbirth. Two patients developed drive line infection. Due to the short support time, none of those patients had a stroke or VAD thrombosis. In total, five patients underwent heart transplantation, of which four previously had implanted VADs. Median time to transplantation from PPCM onset was 140 days (range: 43 to 776), and time to transplantation from VAD implantation were 7, 40, 132, and 735 days, respectively. All patients survived until most recent follow up, with the exception of one patient who died following unrelated abdominal surgery two years after PPCM recovery., Conclusions: In patients with severe, life-threatening PPCM refractory to medical management, mechanical circulatory support with or without heart transplantation is a safe therapeutic option.

Background: Conduction disturbances after transcatheter aortic valve implantation (TAVI) are common, heterogeneous, and frequently result in permanent pacemaker implantation (PPI). Pacemaker therapy with a high rate of right ventricular pacing is associated with heart failure, hospitalizations, and reduced quality of life., Objective: The purpose of this study was to compare medium-term outcomes between PPI implantation strategies, as choosing the right indication for PPI is still an area of uncertainty and information on outcomes of PPI regimens beyond 1 year is rare., Methods: We compared outcomes after 3 years between a restrictive PPI strategy, in which the lowest threshold for PPI was left bundle branch block (LBBB) (QRS >120 ms) with the presence of new atrioventricular block (PQ >200 ms), and a liberal PPI regimen, in which PPI already was performed in patients with new-onset LBBB., Results: Between January 2014 and December 2016, TAVI was performed in 884 patients at our center. Of these, 383 consecutive, pacemaker-naive patients underwent TAVI with the liberal PPI strategy and subsequently 384 with the restrictive strategy. The restrictive strategy significantly reduced the percentage of patients undergoing PPI before discharge (17.2% vs 38.1%; P <.001). The incidence of the primary endpoint (all-cause-mortality and hospitalization for heart failure) after 3 years was similar in both groups (30.7% vs 35.2%; P = .242), as was all-cause-mortality (26.6% vs 29.2%; P = .718). Overall, patients who required PPI post-TAVI had significantly more hospitalizations due to heart failure (14.8% vs 7.8%; P = .004)., Conclusion: A restrictive PPI strategy after TAVI reduces PPI significantly and is safe in medium-term follow-up over 3 years., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Constant elevations of the serum concentration of cardiac troponin T (TnT) indicate a myocardial injury that may affect the long-term outcome of transcatheter aortic valve replacement (TAVR)., Objectives: We sought to investigate the impact of pre-TAVR TnT on outcomes after TAVR during long-term follow-up., Methods: In a retrospective, observational study we compared long term outcomes after TAVR between tertiles of preinterventional high-sensitivity TnT. Systematic follow-up was performed annually for 5 years. The primary endpoint was a composite of all-cause death and any rehospitalization., Results: Between 2010 and 2018, 2,129 patients with severe aortic valve stenosis underwent TAVR at our institution (mean age 82.6 years, 57.2% female, logistic EuroSCORE 20.5 ± 15.8). Boundaries for TnT tertiles were <21 ng/L and >42 ng/L. The median follow-up was 895 days. Three-year incidences for the primary endpoint were 70.9%, 76.6%, and 81.7% in the low, middle, and high tertile (log rank p < .001). Compared with the first tertile, the corresponding adjusted hazard ratios were 1.23 (95%-CI 1.08-1.40, p < .001) and 1.50 (95%-CI 1.32-1.70, p < .001) for the second and third tertile. We found consistent differences between TnT strata for all-cause death (3-year incidences 23.3%, 33.3%, and 47.1%; adjusted p < .001) and rehospitalization (3-year incidences 64.7%, 68.7% and 72.0%; adjusted p < .001), including significant differences in deaths (p < .001). The association between TnT and outcome was independent of coronary artery disease or low aortic valve gradient., Conclusions: TnT before TAVR is strongly associated with all-cause death and rehospitalization during 3-year follow-up., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

High-transparent polymers exhibiting a refractive index beyond 1.6 enhance the available range of optical plastics. The aim of this study is to evaluate optical polyesters (OKP-1 and OKP-4) and special new polycarbonates (PCs) (EP-6000 and EP-8000) in comparison with the widely used poly-bisphenol-A-based PC. The work is focused on optical properties as well as other properties that are important for the deposition of optical coatings. Plasma ion-assisted deposition is used for the deposition of an abrasion resistant antireflective coating (AR-hard).

A major cause of heart failure is cardiomyopathies, with dilated cardiomyopathy (DCM) as the most common form. Over 40 genes are linked to DCM, among them TTN and RBM20 . Next Generation Sequencing in clinical DCM cohorts revealed truncating variants in TTN ( TTN tv), accounting for up to 25% of familial DCM cases. Mutations in the cardiac splicing factor RNA binding motif protein 20 ( RBM20 ) are also known to be associated with severe cardiomyopathies. TTN is one of the major RBM20 splicing targets. Most of the pathogenic RBM20 mutations are localized in the highly conserved arginine serine rich domain (RS), leading to a cytoplasmic mislocalization of mutant RBM20 . Here, we present a patient with an early onset DCM carrying a combination of (likely) pathogenic TTN and RBM20 mutations. We show that the splicing of RBM20 target genes is affected in the mutation carrier. Furthermore, we reveal RBM20 haploinsufficiency presumably caused by the frameshift mutation in RBM20 .

Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Single-port access systems (SPASs) are currently used in human and veterinary surgeries. However, they pose technical challenges, such as instrument crowding, intra- and extracorporeal instrument collision, and reduced maneuverability. Studies comparing the maneuverability of the scopes and instruments in different SPASs are lacking. This study aimed to compare the maneuverability of three different SPASs: the Covidien SILS-port, Storz Endocone, and glove port. A clear acrylic box with artificial skin placed at the bottom was used to mimic the abdominal wall and cavity. The three SPASs were placed from below, and a 10-mm endoscope and 5-mm instrument were introduced. A motion analysis system consisting of 18 cameras and motion analysis software were used to track the movement of the endoscope and instrument, to determine the volume of the cone-shaped, three-dimensional figures over which movement was possible, with higher values indicating greater maneuverability. The Mann-Whitney U test was used for the analysis. The maneuverability of the endoscope alone was significantly higher in the glove port system than in the other two SPASs. When inserting an additional instrument, the maneuverability significantly decreased in the SILS-port and Endocone, but not in the glove port. The highest maneuverability overall was found in the glove port.

Durable mechanical circulatory support (MCS) systems are established therapy option in patients with end-stage heart failure, with increasing importance during the last years due to donor organ shortage. Left ventricular assist devices (LVADs) are traditionally implanted through median sternotomy (MS). However, improvement in the pump designs during the last years led to evolvement of new surgical approaches that aim to reduce the invasiveness of the procedure. Numerous reports and studies have shown the viability and possible advantages of less-invasive approach compared to the sternotomy approach. The less invasive implant strategies for LVADs, while vague in definition, are characterized by minimizing surgical trauma and if possible, cardio-pulmonary bypass related complications. Usually it involves minimizing or completely avoiding sternal trauma, avoiding heart luxation while simultaneously leaving the major part of pericardium intact. There is no consensus between the centers regarding the ideal approach for LVAD implantation. Some centers, like our center, perform by default VAD implantation using less invasive approach in almost all patients and some centers use only sternotomy approach. The aim of this review article is to shed light on the currently available less invasive options of LVAD implantation, with particular focus on the centrifugal pumps, and their possible advantages compared to traditional sternotomy approach., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1492). The series “Minimally Invasive Cardiac Surgery” was commissioned by the editorial office without any funding or sponsorship. Michael Borger serves as an unpaid editorial board member of Journal of Thoracic Disease from Sep 2018 to Aug 2020 and reports that his hospital receives modest (< $10,000 per annum) speakers‘ honoraria and/or consulting fees on his behalf from Edwards Lifesciences, Medtronic, Abbott, CryoLife, and Ascyrus. However, these are all related to heart valve therapy and not to LVAD therapy. The authors have no other conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Mutations in RBM20 encoding the RNA-binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine-rich domain (RS domain). Here, we investigated in several cardiomyopathy patients, the previously described RBM20-mutation p.Pro638Leu localized within the RS domain. In addition, we identified in a patient the novel mutation p.Val914Ala localized in the (glutamate-rich) Glu-rich domain of RBM20 encoded by exon 11. Its impact on the disease was investigated with a novel TTN- and RYR2-splicing assay based on the patients' cardiac messenger RNA. Furthermore, we showed in cell culture and in human cardiac tissue that mutant RBM20-p.Pro638Leu is not localized in the nuclei but causes an abnormal cytoplasmic localization of the protein. In contrast the splicing deficient RBM20-p.Val914Ala has no influence on the intracellular localization. These results indicate that disease-associated variants in RBM20 lead to aberrant splicing through different pathomechanisms dependent on the localization of the mutation. This might have an impact on the future development of therapeutic strategies for the treatment of RBM20-induced cardiomyopathies., (© 2020 The Authors. Human Mutation published by Wiley Periodicals LLC.)