Prognostic Value of Standard Heart Failure Medication in Patients with Cardiac Transthyretin Amyloidosis.

Introduction: Cardiac transthyretin amyloidosis (ATTR) is a progressive, fatal disease leading to heart failure due to accumulation of amyloid fibrils in the interstitial space and may occur as a hereditary (ATTRv) or wild-type (ATTRwt) form. Guidelines recommend the use of ACE inhibitors (ACEis) and beta-blockers (BBs) as heart failure therapy (HFT) in all patients with symptomatic heart failure and reduced ejection fraction, independent of the underlying etiology. However, the prognostic benefit of ACEis and BBs in ATTR has not been elucidated in detail yet. We thus sought to retrospectively investigate the outcome of patients with ATTRwt or ATTRv under HFT. Methods: Medical records of 403 patients with cardiac ATTR (ATTRwt: n = 268, ATTRv: n = 135) were screened for long-term medication as well as clinical, laboratory, electrocardiographic and echocardiographic data. Patients were assessed between 2005 and 2020 at the University Hospital Heidelberg. Kaplan-Meier analysis was used to analyze potential differences in survival among different subgroups. Results: The mean follow-up was 28 months. In total, 43 patients (32%) with ATTRv and 140 patients (52%) with ATTRwt received HFT. Survival was significantly shorter in patients receiving HFT in ATTRv (46 vs. 83 months, p = 0.0007) vs. non-HFT. A significantly better survival was observed in patients with comorbidities (coronary artery disease, arterial hypertension) and HFT among ATTRwt patients (p = 0.004). No significant differences in survival were observed in the other subgroups. Conclusions: Survival analysis revealed a potential benefit of HFT in patients with ATTRwt and cardiac comorbidities such as coronary artery disease and/or arterial hypertension. In contrast, HFT should be used with caution in patients with ATTRv.

Indirect bonding: an in-vitro comparison of a Polyjet printed versus a conventional silicone transfer tray.

OBJECTIVES: To investigate and compare transfer accuracy between a Polyjet printed indirect bonding (IDB) tray (SureSmile, Dentsply Sirona, Richardson, TX, USA) and a conventional two-layered silicone tray. MATERIALS AND METHODS: Plaster models of 24 patients were digitized with an intraoral scanner, and brackets and tubes were positioned virtually on the provider's homepage. IDB trays were designed over the planned attachments and Polyjet 3D-printed. For the conventional tray, brackets and tubes were bonded in their ideal positions manually before fabricating a two-layered silicone tray. For both trays, attachments were transferred indirectly to corresponding models. A second scan was performed of each bonded model to capture actual attachment positions, which were then compared to initial bracket positions using Geomagic Control (3D Systems Inc., Rock Hill, SC, USA). Linear and angular deviations were evaluated for each attachment within a clinically acceptable range of ≤0.2 mm and 1°. A descriptive statistical analysis and a mixed model were executed. RESULTS: Both trays showed highest accuracy in the orobuccal direction (99.5% for the 3D-printed tray and 100% for the conventional tray). For the 3D-printed tray, most frequent deviations were found for torque (15.4%) and, for the silicone tray, for rotation (1.9%). A significant difference was observed for angular measurements (P = .004) between the trays. CONCLUSIONS: Transfer accuracy of Polyjet printed IDB tray is not as high as transfer accuracy of the conventional silicone tray, though both trays show good results and are suitable for clinical application.

Comparison of Two 3D-Printed Indirect Bonding (IDB) Tray Design Versions and Their Influence on the Transfer Accuracy.

Objective: This study aims to investigate the transfer accuracy of two different design versions for 3D-printed indirect bonding (IDB) trays. Materials and Methods: Digital plaster models of 27 patients virtually received vestibular attachments on every tooth using OnyxCeph³™ (Image Instruments, Chemnitz, Germany). Based on these simulated bracket and tube positions, two versions of transfer trays were designed for each dental arch and patient, which differed in the mechanism of bracket retention: Variant one (V1) had arm-like structures protruding from the tray base and reaching into the horizontal and vertical bracket slots, and variant two (V2) had a pocket-shaped design enclosing the brackets from three sides. Both tray designs were 3D-printed with the same digital light processing (DLP) printer using a flexible resin-based material (IMPRIMO® LC IBT/Asiga MAX™, SCHEU-DENTAL, Iserlohn, Germany). Brackets and tubes (discovery® smart/pearl, Ortho-Cast M-Series, Dentaurum, Ispringen, Germany) were inserted into the respective retention mechanism of the trays and IDB was performed on corresponding plaster models. An intraoral scan (TRIOS® 3W, 3Shape, Copenhagen, Denmark) was performed to capture the actual attachment positions and compared to the virtually planned positions with Geomagic© Control (3D Systems Inc., Rock Hill, SC, USA) using a scripted calculation tool, which superimposed the respective tooth surfaces. The resulting attachment deviations were determined in three linear (mesiodistal, vertical and orovestibular) and three angular (torque, rotation and tip) directions and analyzed with a descriptive statistical analysis. A comparison between the two IDB tray designs was conducted using a mixed model analysis (IBM, SPSS® Statistics 27, Armonk, NY, USA). Results: Both design versions of the 3D-printed IDB trays did not differ significantly in their transfer accuracy (p > 0.05). In total, 98% (V1) and 98.5% (V2) of the linear deviations were within the clinically acceptable range of ±0.2 mm. For the angular deviations, 84.9% (V1) and 86.8% (V2) were within the range of ±1°. With V1, most deviations occurred in the mesiodistal direction (3.3%) and in rotation (18%). With V2, most deviations occurred in the vertical direction (3.8%) and in palatinal and lingual crown torque (16.3%). Conclusions: The transfer accuracies of the investigated design versions for 3D-printed IDB trays show good and comparable results albeit their different retention mechanisms for the attachments and are, therefore, both suitable for clinical practice.

Differences in the Treatment of Acute Coronary Syndrome in the Pre-COVID and COVID Era: An Analysis from Two German High-Volume Centers.

The COVID-19 pandemic is placing a heavy burden on healthcare systems worldwide with the risk that acute cardiovascular diseases are treated too late. The present study aims to analyze patients with acute coronary syndrome in the current pandemic. A total of 966 patients (2019 n = 463, 2020 n = 503) can be evaluated. A comparison of patient care during and before the COVID-19 pandemic was made in terms of patient characteristics and pre- and in-hospital processes. Another aim is to show how many patients seek clinical care at a late stage of the disease. After Lockdown in Germany at week 12, 2020, there was a significant decrease in patients with an acute coronary syndrome (ACS), significant for STEMI cases in the first weeks after Lockdown (calendar week 13-16 2019 n = 43, 2020 n = 30; p = 0.02). The time from pain to first medical contact (time to FMC) is significantly extended during Lockdown, while internal clinical processes are unchanged. The rate of subacute myocardial infarction is numerically, but not significantly increased in calendar weeks 15, 2020 (p = 0.40) and 16 (p = 0,19). In addition, elderly patients avoid treatment for multifactorial reasons, and the longer overall pain to FMC may impact long-term mortality.

Accurate Bracket Placement with an Indirect Bonding Method Using Digitally Designed Transfer Models Printed in Different Orientations-An In Vitro Study.

OBJECTIVE: A digital workflow opens up new possibilities for the indirect bonding (IDB) of brackets. We tested if the printing orientation for bracket transfer models on the build platform of a 3D printer influences the accuracy of the following IDB method. We also evaluated the clinical acceptability of the IDB method combining digitally planned and printed transfer models with the conventional fabrication of pressure-molded transfer trays. MATERIALS AND METHODS: In total, 27 digitally planned bracket transfer models were printed with both 15° and 75° angulation from horizontal plane on the build platform of a digital light processing (DLP) printer. Brackets were temporarily bonded to the transfer models and pressure-molded trays were produced on them. IDB was then performed using the trays on the respective plaster models. The plaster models were scanned with an optical scanner. Digitally planned pre-bonding and scanned post-bonding bracket positions were superimposed with a software and resulted in three linear and three angular deviations per bracket. RESULTS: No statistically significant differences of the transfer accuracy of printed transfer models angulated 15° or 75° on the 3D printer build platform were found. About 97% of the linear and 82% of the angular deviations were within the clinically acceptable range of ±0.2 mm and ±1°, respectively. The highest inaccuracies in the linear dimension occurred in the vertical towards the gingival direction and in the angular dimension in palatal crown torque. CONCLUSION: For the IDB method used, the printing orientation on the build platform did not have a significant impact on the transfer accuracy.

Predictors and Prognostic Implications of Cardiac Arrhythmias in Patients Hospitalized for COVID-19.

BACKGROUND: Cardiac manifestation of COVID-19 has been reported during the COVID pandemic. The role of cardiac arrhythmias in COVID-19 is insufficiently understood. This study assesses the incidence of cardiac arrhythmias and their prognostic implications in hospitalized COVID-19-patients. METHODS: A total of 166 patients from eight centers who were hospitalized for COVID-19 from 03/2020-06/2020 were included. Medical records were systematically analyzed for baseline characteristics, biomarkers, cardiac arrhythmias and clinical outcome parameters related to the index hospitalization. Predisposing risk factors for arrhythmias were identified. Furthermore, the influence of arrhythmia on the course of disease and related outcomes was assessed using univariate and multiple regression analyses. RESULTS: Arrhythmias were detected in 20.5% of patients. Atrial fibrillation was the most common arrhythmia. Age and cardiovascular disease were predictors for new-onset arrhythmia. Arrhythmia was associated with a pronounced increase in cardiac biomarkers, prolonged hospitalization, and admission to intensive- or intermediate-care-units, mechanical ventilation and in-hospital mortality. In multiple regression analyses, incident arrhythmia was strongly associated with duration of hospitalization and mechanical ventilation. Cardiovascular disease was associated with increased mortality. CONCLUSIONS: Arrhythmia was the most common cardiac event in association with hospitalization for COVID-19. Older age and cardiovascular disease predisposed for arrhythmia during hospitalization. Whereas in-hospital mortality is affected by underlying cardiovascular conditions, arrhythmia during hospitalization for COVID-19 is independently associated with prolonged hospitalization and mechanical ventilation. Thus, incident arrhythmia may indicate a patient subgroup at risk for a severe course of disease.

Novel ß-Glucocerebrosidase Activators That Bind to a New Pocket at a Dimer Interface and Induce Dimerization.

Genetic, preclinical and clinical data link Parkinson's disease and Gaucher's disease and provide a rational entry point to disease modification therapy via enhancement of ß-Glucocerebrosidase (GCase) activity. We discovered a new class of pyrrolo[2,3-b]pyrazine activators effecting both Vmax and Km. They bind to human GCase and increase substrate metabolism in the lysosome in a cellular assay. We obtained the first crystal structure for an activator and identified a novel non-inhibitory binding mode at the interface of a dimer, rationalizing the observed structure-activity relationship (SAR). The compound binds GCase inducing formation of a dimeric state at both endoplasmic reticulum (ER) and lysosomal pHs, as confirmed by analytical ultracentrifugation. Importantly, the pyrrolo[2,3-b]pyrazines have central nervous system (CNS) drug-like properties. Our findings are important for future drug discovery efforts in the field of GCase activation and provide a deeper mechanistic understanding of the requirements for enzymatic activation, pointing to the relevance of dimerization.

The Influence of Regulation on Trust and Risk Preference in Sharing Communities.

Sharing within communities has gained popularity in recent years. However, taking part in a community also comes with a certain amount of risk. This perceived amount of risk can be contained by regulations within a community as well as by potential participants' trust in the community and the other members. We argue for a relation between regulation and the willingness to take the risk of joining a sharing community with trust as a mediator. Thereby, we distinguish between two kinds of regulation (soft and harsh regulation) and two kinds of trust (implicit and reason-based trust) on two different levels (vertical and horizontal trust). In one laboratory and one online experiment with 432 participants overall, we found that the compound of high soft and low harsh regulation increases participants' willingness to take the risk of participation and that the effect of soft regulation is mediated mainly by vertical and horizontal reason-based trust. Based on our results, we encourage sharing communities to count on soft regulation in order to increase potential members' trust in the community and therefore take the risk to participate.

The impact of powerful authorities and trustful taxpayers: evidence for the extended slippery slope framework from Austria, Finland, and Hungary.

Tax authorities utilize a wide range of instruments to motivate honest taxpaying ranging from strict audits to fair procedures or personalized support, differing from country to country. However, little is known about how these different instruments and taxpayers' trust influence the generation of interaction climates between tax authorities and taxpayers, motivations to comply, and particularly, tax compliance. The present research examines the extended slippery slope framework (eSSF), which distinguishes tax authorities' instruments into different qualities of power of authority (coercive and legitimate) and trust in authorities (reason-based and implicit), to shed light on the effect of differences between power and trust. We test eSSF assumptions with survey data from taxpayers from three culturally different countries (N = 700) who also vary concerning their perceptions of power, trust, interaction climates, and tax motivations. Results support assumptions of the eSSF. Across all countries, the relation of coercive power and tax compliance was mediated by implicit trust. The connection from legitimate power to tax compliance is partially mediated by reason-based trust. The relationship between implicit trust and tax compliance is mediated by a confidence climate and committed cooperation. Theoretical and practical implications are discussed.

The Relationship Between Austrian Tax Auditors and Self-Employed Taxpayers: Evidence From a Qualitative Study.

A constructive, highly professional relationship between tax authorities and taxpayers is essential for tax compliance. The aim of the present paper was to explore systematically the determinants of this relationship and related tax compliance behaviors based on the extended slippery slope framework. We used in-depth qualitative interviews with 33 self-employed taxpayers and 30 tax auditors. Interviewees described the relationship along the extended slippery slope framework concepts of power and trust. However, also novel sub-categories of power (e.g., setting deadlines) and trust (e.g., personal assistance) were mentioned. Furthermore, also little-studied categories of tax behavior emerged, such as accepting tax behavior, e.g., being available to the tax authorities, or stalling tax behavior, e.g., the intentional creation of complexity. The results comprehensively summarize the determinants of the tax relationship and tax compliance behaviors. Additionally, results highlight future research topics and provide insights for policy strategies.

Cultural Collectivism and Tightness Moderate Responses to Norm Violators: Effects on Power Perception, Moral Emotions, and Leader Support.

Responses to norm violators are poorly understood. On one hand, norm violators are perceived as powerful, which may help them to get ahead. On the other hand, norm violators evoke moral outrage, which may frustrate their upward social mobility. We addressed this paradox by considering the role of culture. Collectivistic cultures value group harmony and tight cultures value social order. We therefore hypothesized that collectivism and tightness moderate reactions to norm violators. We presented 2,369 participants in 19 countries with a norm violation or a norm adherence scenario. In individualistic cultures, norm violators were considered more powerful than norm abiders and evoked less moral outrage, whereas in collectivistic cultures, norm violators were considered less powerful and evoked more moral outrage. Moreover, respondents in tighter cultures expressed a stronger preference for norm followers as leaders. Cultural values thus influence responses to norm violators, which may have downstream consequences for violators' hierarchical positions.

Coercive and legitimate authority impact tax honesty: evidence from behavioral and ERP experiments.

Cooperation in social systems such as tax honesty is of central importance in our modern societies. However, we know little about cognitive and neural processes driving decisions to evade or pay taxes. This study focuses on the impact of perceived tax authority and examines the mental chronometry mirrored in ERP data allowing a deeper understanding about why humans cooperate in tax systems. We experimentally manipulated coercive and legitimate authority and studied its impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal (experiment 2) processes. Experiment 1 showed that in a condition of coercive authority, tax payments are lower, decisions are faster and participants report more rational reasoning and enforced compliance, however, less voluntary cooperation than in a condition of legitimate authority. Experiment 2 confirmed most results, but did not find a difference in payments or self-reported rational reasoning. Moreover, legitimate authority led to heightened cognitive control (expressed by increased MFN amplitudes) and disrupted attention processing (expressed by decreased P300 amplitudes) compared to coercive authority. To conclude, the neuronal data surprisingly revealed that legitimate authority may led to higher decision conflict and thus to higher cognitive demands in tax decisions than coercive authority.

Authorities' Coercive and Legitimate Power: The Impact on Cognitions Underlying Cooperation.

The execution of coercive and legitimate power by an authority assures cooperation and prohibits free-riding. While coercive power can be comprised of severe punishment and strict monitoring, legitimate power covers expert, and informative procedures. The perception of these powers wielded by authorities stimulates specific cognitions: trust, relational climates, and motives. With four experiments, the single and combined impact of coercive and legitimate power on these processes and on intended cooperation of n1 = 120, n2 = 130, n3 = 368, and n4 = 102 student participants is investigated within two exemplary contexts (tax contributions, insurance claims). Findings reveal that coercive power increases an antagonistic climate and enforced compliance, whereas legitimate power increases reason-based trust, a service climate, and voluntary cooperation. Unexpectedly, legitimate power is additionally having a negative effect on an antagonistic climate and a positive effect on enforced compliance; these findings lead to a modification of theoretical assumptions. However, solely reason-based trust, but not climate perceptions and motives, mediates the relationship between power and intended cooperation. Implications for theory and practice are discussed.

Motivation, values, and work design as drivers of participation in the R open source project for statistical computing.

One of the cornerstones of the R system for statistical computing is the multitude of packages contributed by numerous package authors. This amount of packages makes an extremely broad range of statistical techniques and other quantitative methods freely available. Thus far, no empirical study has investigated psychological factors that drive authors to participate in the R project. This article presents a study of R package authors, collecting data on different types of participation (number of packages, participation in mailing lists, participation in conferences), three psychological scales (types of motivation, psychological values, and work design characteristics), and various socio-demographic factors. The data are analyzed using item response models and subsequent generalized linear models, showing that the most important determinants for participation are a hybrid form of motivation and the social characteristics of the work design. Other factors are found to have less impact or influence only specific aspects of participation.

Does the sole description of a tax authority affect tax evasion?--the impact of described coercive and legitimate power.

Following the classic economic model of tax evasion, taxpayers base their tax decisions on economic determinants, like fine rate and audit probability. Empirical findings on the relationship between economic key determinants and tax evasion are inconsistent and suggest that taxpayers may rather rely on their beliefs about tax authority's power. Descriptions of the tax authority's power may affect taxpayers' beliefs and as such tax evasion. Experiment 1 investigates the impact of fines and beliefs regarding tax authority's power on tax evasion. Experiments 2-4 are conducted to examine the effect of varying descriptions about a tax authority's power on participants' beliefs and respective tax evasion. It is investigated whether tax evasion is influenced by the description of an authority wielding coercive power (Experiment 2), legitimate power (Experiment 3), and coercive and legitimate power combined (Experiment 4). Further, it is examined whether a contrast of the description of power (low to high power; high to low power) impacts tax evasion (Experiments 2-4). Results show that the amount of fine does not impact tax payments, whereas participants' beliefs regarding tax authority's power significantly shape compliance decisions. Descriptions of high coercive power as well as high legitimate power affect beliefs about tax authority's power and positively impact tax honesty. This effect still holds if both qualities of power are applied simultaneously. The contrast of descriptions has little impact on tax evasion. The current study indicates that descriptions of the tax authority, e.g., in information brochures and media reports, have more influence on beliefs and tax payments than information on fine rates. Methodically, these considerations become particularly important when descriptions or vignettes are used besides objective information.

Tax authorities' interaction with taxpayers: A conception of compliance in social dilemmas by power and trust.

Tax compliance represents a social dilemma in which the short-term self-interest to minimize tax payments is at odds with the collective long-term interest to provide sufficient tax funds for public goods. According to the Slippery Slope Framework, the social dilemma can be solved and tax compliance can be guaranteed by power of tax authorities and trust in tax authorities. The framework, however, remains silent on the dynamics between power and trust. The aim of the present theoretical paper is to conceptualize the dynamics between power and trust by differentiating coercive and legitimate power and reason-based and implicit trust. Insights into this dynamic are derived from an integration of a wide range of literature such as on organizational behavior and social influence. Conclusions on the effect of the dynamics between power and trust on the interaction climate between authorities and individuals and subsequent individual motivation of cooperation in social dilemmas such as tax contributions are drawn. Practically, the assumptions on the dynamics can be utilized by authorities to increase cooperation and to change the interaction climate from an antagonistic climate to a service and confidence climate.

Effects of supervision on tax compliance: Evidence from a field experiment in Austria.

We conduct a field experiment on tax compliance, focusing on newly founded firms. As a novelty the effect of tax authorities' supervision on timely tax payments is examined. Interestingly, results show no positive overall effect of close supervision on tax compliance.

Enhancing Tax Compliance through Coercive and Legitimate Power of Tax Authorities by Concurrently Diminishing or Facilitating Trust in Tax Authorities.

Both coercion, such as strict auditing and the use of fines, and legitimate procedures, such as assistance by tax authorities, are often discussed as means of enhancing tax compliance. However, the psychological mechanisms that determine the effectiveness of each strategy are not clear. Although highly relevant, there is rare empirical literature examining the effects of both strategies applied in combination. It is assumed that coercion decreases implicit trust in tax authorities, leading to the perception of a hostile antagonistic tax climate and enforced tax compliance. Conversely, it is suggested that legitimate power increases reason-based trust in the tax authorities, leading to the perception of a service climate and eventually to voluntary cooperation. The combination of both strategies is assumed to cause greater levels of intended compliance than each strategy alone. We conducted two experimental studies with convenience samples of 261 taxpayers overall. The studies describe tax authorities as having low or high coercive power (e.g., imposing lenient or severe sanctions) and/or low or high legitimate power (e.g., having nontransparent or transparent procedures). Data analyses provide supportive evidence for the assumptions regarding the impact on intended tax compliance. Coercive power did not reduce implicit trust in tax authorities; however, it had an effect on reason-based trust, interaction climate, and intended tax compliance if applied solely. When wielded in combination with legitimate power, it had no effect.

Preoperative botulinum toxin test injections before muscle lengthening in cerebral palsy.

BACKGROUND: Muscle weakening is a well-known side effect of muscle-tendon lengthening. Botulinum toxin A (BTX-A) weakens the muscle temporarily by blocking the neuromuscular junction. Hence application of the drug is a logical step to test whether weakness deteriorates function prior to an operation. In the present study, BTX-A application is used to test preoperatively whether the gait pattern depends on the strength of the tested muscle. Since 1999, instrumented gait analysis, including kinematic, kinetic, and dynamic electromyographic data, is routinely used to define the individual surgical program. METHODS: In our series of 110 consecutive patients with cerebral palsy (CP) considered for surgical muscle lengthening from 1999 to 2008, BTX-A was applied to identify patients at risk for functional deterioration. Gait analysis was repeated 6 weeks (maximum effect of BTX-A) and 12 weeks (follow-up) after the test injection to check for loss of joint control (excessive ankle dorsiflexion, knee flexion, increased anterior pelvic tilt). RESULTS: In all, 20.9% (n = 23) showed deterioration in gait after preoperative BTX-A test injections (n = 112, two patients had two test trials) in all muscles considered for lengthening. As a consequence, their lengthening surgery was canceled. A total of 68 patients underwent surgery as planned, and in none of them did gait function deteriorate. These clinical data were compared to those of a historical group (n = 105) before this test, where 18% showed functional deterioration after surgery. The similar percentage of patients filtered out by the test suggests that there could be a context to the number of poor results in the historical group. CONCLUSIONS: We conclude that preoperative BTX-A test injection is a reliable tool for filtering out patients with risk of deterioration after muscle lengthening surgery in patients with CP and can be helpful to avoid poor outcomes.