Single German centre experience with patient journey and care-relevant needs in amyloidosis: The German AMY-NEEDS research and care program.

BACKGROUND: Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress. METHODS: Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program. RESULTS: 118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need. CONCLUSION: The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.

Cardio-Hepatic Interaction in Cardiac Amyloidosis.

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

Vector autoregression: Useful in rare diseases?-Predicting organ response patterns in a rare case of secondary AA amyloidosis.

BACKGROUND: Statistical analyses of clinical data are a cornerstone in understanding pathomechanisms of disorders. In rare disorders, cross-sectional datasets of sufficient size are usually not available. Taking AA amyloidosis as an example of a life-threatening rare disorder resulting from of uncontrolled chronic inflammation, we propose techniques from time series analysis to predict organ response to treatment. The advantage of time-series analysis is that it solely relies on temporal variation and therefore allows analyzing organ response to treatment even when the cross-sectional dimension is small. METHODS: The joint temporal interdependence of inflammatory activity and organ response was modelled multivariately using vector autoregression (VAR) based on a unique 4.5 year spanning data set of routine laboratory, imaging data (e.g., 18F-Florbetaben-PET/CT) and functional investigations of a 68-year-old patient with multi-organ involvement of AA amyloidosis due to ongoing inflammatory activity of a malignant paraganglioma in stable disease for >20 years and excellent response to tocilizumab). RESULTS: VAR analysis showed that alterations in inflammatory activity forecasted alkaline phosphatase (AP). AP levels, but not inflammatory activity at the previous measurement time point predicted proteinuria. CONCLUSION: We demonstrate the feasibility and value of time series analysis for obtaining clinically reliable information when the rarity of a disease prevents conventional prognostic modelling approaches. We illustrate the comparative utility of blood, functional and imaging markers to monitor the development and regression of AA amyloidosis.

Can University Leaders Effectively Promote Research on Complex Societal Challenges? A Change-Agency Perspective.

In recent years, new expectations have been placed on universities, demanding academic contributions towards solving large-scale, interdisciplinary challenges. This is in conflict with existing insights from university governance research, which emphasises that scientific communities focus on reproducing disciplinary practices that are unsuitable in addressing societal challenges, because the problems associated with them are usually large-scale, complex and interdisciplinary. In light of this seeming paradox, we revisit the question of how-and on which theoretical grounds-universities may still be able to develop suitable internal governance mechanisms that allow them to address complex societal challenges effectively. Because university leaders are usually unable to coerce individual researchers to address such challenges in their research simply through their bureaucratic powers, we will argue that university leaders can, however, leverage individual researchers' agency to deviate from routine and disciplinary practice by developing novel or legitimising existing interdisciplinary scripts necessary to deal with such societal problems. Specifically, we outline that university managements can create a dual role consisting of the communication of legitimising interdisciplinary research on societal challenges, as well as providing for the necessary degree of interdisciplinary coordination by convening researchers around these topics.

Right Heart Failure in Mice Upon Pressure Overload Is Promoted by Mitochondrial Oxidative Stress.

We sought to unravel pathomechanisms of the transition of maladaptive right ventricular (RV) remodeling to right heart failure (RHF) upon pressure overload. Exposure of C57BL/6J and C57BL/6N mice to pulmonary artery banding disclosed a tight relation of structural remodeling with afterload, but a dissociation from RV systolic function. Reduced release of mitochondrial reactive oxygen species in C57BL/6J mice prevented the development of RHF. In patients with left heart failure, increased oxidative damage in RV sections was associated with severely impaired RV function. In conclusion, reactive oxygen species are involved in the transition of maladaptive RV remodeling to RHF.

Indicators on firm level innovation activities from web scraped data.

This article presents data on companies' innovative behavior measured at the firm-level based on web scraped firm-level data derived from medium-high and high-technology companies in the European Union and the United Kingdom. The data are retrieved from individual company websites and contains in total data on 96,921 companies. The data provide information on various aspects of innovation, most significantly the research and development orientation of the company at the company and product level, the company's collaborative activities, company's products, and use of standards. In addition to the web scraped data, the dataset aggregates a variety firm-level indicators including patenting activities. In total, the dataset includes 21 variables with unique identifiers which enables connecting to other databases such as financial data.

Connecting firm's web scraped textual content to body of science: Utilizing microsoft academic graph hierarchical topic modeling.

This paper demonstrates a method to transform and link textual information scraped from companies' websites to the scientific body of knowledge. The method illustrates the benefit of Natural Language Processing (NLP) in creating links between established economic classification systems with novel and agile constructs that new data sources enable. Therefore, we experimented on the European classification of economic activities (known as NACE) on sectoral and company levels. We established a connection with Microsoft Academic Graph hierarchical topic modeling based on companies' website content. Central to the operationalization of our method are a web scraping process, NLP and a data transformation/linkage procedure. The method contains three main steps: data source identification, raw data retrieval, and data preparation and transformation. These steps are applied to two distinct data sources.

Recruiting strategic human capital from MNCs-Does hiring MNC managers enable exporting in domestic firms?

Exporting is a central growth strategy for most firms and managers with international experience are instrumental for export decisions. We suggest that such managers can be hired from Multinational Corporations (MNCs). We integrate theory from strategic human capital research into models explaining export decisions. We theorize that hiring managers from MNCs increases the odds of domestic firms to start exporting and this effect depends on the similarities between hiring firms and MNCs. We hypothesize that young firms will benefit comparatively less from hiring MNC managers. In contrast, firms with internationally diverse workforces and with high degrees of hierarchical specialization will benefit the most from hiring MNC managers. We test and support these hypotheses for 474,926 domestic firms in Sweden, which we observe between 2007 and 2015.

Emerging therapies for right ventricular dysfunction and failure.

Therapeutic options for right ventricular (RV) dysfunction and failure are strongly limited. Right heart failure (RHF) has been mostly addressed in the context of pulmonary arterial hypertension (PAH), where it is not possible to discern pulmonary vascular- and RV-directed effects of therapeutic approaches. In part, opposing pathomechanisms in RV and pulmonary vasculature, i.e., regarding apoptosis, angiogenesis and proliferation, complicate addressing RHF in PAH. Therapy effective for left heart failure is not applicable to RHF, e.g., inhibition of adrenoceptor signaling and of the renin-angiotensin system had no or only limited success. A number of experimental studies employing animal models for PAH or RV dysfunction or failure have identified beneficial effects of novel pharmacological agents, with most promising results obtained with modulators of metabolism and reactive oxygen species or inflammation, respectively. In addition, established PAH agents, in particular phosphodiesterase-5 inhibitors and soluble guanylate cyclase stimulators, may directly address RV integrity. Promising results are furthermore derived with microRNA (miRNA) and long non-coding RNA (lncRNA) blocking or mimetic strategies, which can target microvascular rarefaction, inflammation, metabolism or fibrotic and hypertrophic remodeling in the dysfunctional RV. Likewise, pre-clinical data demonstrate that cell-based therapies using stem or progenitor cells have beneficial effects on the RV, mainly by improving the microvascular system, however clinical success will largely depend on delivery routes. A particular option for PAH is targeted denervation of the pulmonary vasculature, given the sympathetic overdrive in PAH patients. Finally, acute and durable mechanical circulatory support are available for the right heart, which however has been tested mostly in RHF with concomitant left heart disease. Here, we aim to review current pharmacological, RNA- and cell-based therapeutic options and their potential to directly target the RV and to review available data for pulmonary artery denervation and mechanical circulatory support.

How imagining personal future scenarios influences affect: Systematic review and meta-analysis.

Imagining the future is a fundamental human capacity that occupies a large part of people's waking time and impacts their affective well-being. In this meta-analysis, we examined the effect of (1) positive future imagination and (2) negative future imagination on affect, and (3) compared the affective responses between imagining the future and remembering the past; lastly, we (4) examined potential moderating variables in this regard. We identified 63 experimental studies (N = 6813) from different research areas and combined studies that applied the best possible self imagination task, future worry induction, and episodic future simulation, respectively. Findings yielded that imagining the future has a moderate to strong impact on affect, and it has a stronger influence on affect compared to remembering the past. Relevant moderator variables in each research area were also identified. We discuss the findings for the field of psychology in general and clinical psychology in particular. More elaborate research on personal future imagination seems crucial for the further advancement of clinical applications for mental health complaints. We conclude with recommendations for future research on the impact of future imagination on affective well-being.

[Unreported Intentional Life-Ending Acts in Physicians and Nurses]. / Das Dunkelfeld intentional lebensbeendender Handlungen durch Ärzte und Pflegekräfte.

Introduction Intentional life-ending acts (LA) including euthanasia and termination of life without explicit request are illegal in Germany and have not been extensively studied. In a pilot study, unreported LA administered by physicians and nurses in German health care were explored. Methods All hospitals and nursing homes registered in 2015 (n = 13 393) were contacted via mail or e-mail and physician and nursing staff were asked to complete an anonymous online-survey or the identical attached paper-pencil questionnaire. 4629 participants, including physicians (n = 356), nurses (n = 3121) und geriatric nurses (n = 1152) from a predominant in-patient working area responded to questions about LA at their workplace, requests for euthanasia and performance of LA. Results 2.25 - 4.01 % (172 participants) of all physicians and nurses indicated to have heard of euthanasia at their workplace in the last 12 months and 1.42 - 3.39 % (77 participants) indicated to have performed LA themselves. LA was more frequently administered by male participants, physicians and on intensive care units. More than one third of all participants who had administered LA (38.10 - 41.67 %) were never asked for it. Discussion This pilot study indicates that beside legal forms of passive and indirect euthanasia, illegal intentional life-ending acts are administered by physicians and nurses in all health-care areas under investigation.

The effect of subjective social status on depressive thinking: An experimental examination.

Subjective social status (SSS) predicts health outcomes above and beyond objective measures of social status. Both objective and subjective measures of social status are strongly related with depression. Cognitive mechanisms such as depressive cognitions, rumination, and a negative cognitive style are seen as both concomitant and antecedent to depression. This experiment examined the causal role of SSS in developing depressive thinking. Participants were randomly assigned to a low and a high status group and followed a manipulation procedure targeting their SSS. Depressive thinking was subsequently assessed by depressive cognitions, stress-reactive state rumination and negative cognitive style. Low status participants exhibited higher levels of depressive cognitions and rumination compared to their high status counterparts, but both groups did not differ regarding their cognitive style. Findings support the causal nature of the relationship between SSS and depressive thinking. Several mechanisms of how low SSS may lead to depression are discussed.