MODELING THE MORTALITY TREND UNDER MODERN SOLVENCY REGIMES

Stochastic modeling of mortality/longevity risks is necessary for internal models of (re)insurers under the new solvency regimes, such as Solvency II and the Swiss Solvency Test. In this paper, we propose a mortality model which fulfills all requirements imposed by these regimes. We show how the model can be calibrated and applied to the simultaneous modeling of both mortality and longevity risk for several populations. The main contribution of this paper is a stochastic trend component which explicitly models changes in the long-term mortality trend assumption over time. This allows to quantify mortality and longevity risk over the one-year time horizon prescribed by the solvency regimes without relying on nested simulations. We illustrate the practical ability of our model by calculating solvency capital requirements for some example portfolios, and we compare these capital requirements with those from the Solvency II standard formul

Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales

Extracellular vesicles (EVs) provide a complex means of intercellular signalling between cells at local and distant sites, both within and between different organs. According to their cell-type specific signatures, EVs can function as a novel class of biomarkers for a variety of diseases, and can be used as drug-delivery vehicles. Furthermore, EVs from certain cell types exert beneficial effects in regenerative medicine and for immune modulation. Several techniques are available to harvest EVs from various body fluids or cell culture supernatants. Classically, differential centrifugation, density gradient centrifugation, size-exclusion chromatography and immunocapturing-based methods are used to harvest EVs from EV-containing liquids. Owing to limitations in the scalability of any of these methods, we designed and optimised a polyethylene glycol (PEG)based precipitation method to enrich EVs from cell culture supernatants. We demonstrate the reproducibility and scalability of this method and compared its efficacy with more classical EV-harvesting methods. We show that washing of the PEG pellet and the re-precipitation by ultracentrifugation remove a huge proportion of PEG co-precipitated molecules such as bovine serum albumine (BSA). However, supported by the results of the size exclusion chromatography, which revealed a higher purity in terms of particles per milligram protein of the obtained EV samples, PEG-prepared EV samples most likely still contain a certain percentage of other non-EV associated molecules. Since PEG-enriched EVs revealed the same therapeutic activity in an ischemic stroke model than corresponding cells, it is unlikely that such co-purified molecules negatively affect the functional properties of obtained EV samples. In summary, maybe not being the purification method of choice if molecular profiling of pure EV samples is intended, the optimised PEG protocol is a scalable and reproducible method, which can easily be adopted by laboratories equipped with an ultracentrifuge to enrich for functional active EVs

Time travelling with Triticum: An Ecotron experiment to study the wheat of the future

2. Zero hunger3. Good health and well-being12. Responsible consumption and production13. Climate action15. Life on land17. Partnerships for the goal

Tränenflüssigkeit als mögliche Quelle für Biomarker bei Patienten mit einem idiopathischem Parkinson-Syndrom

Idiopathic Parkinson's disease is the second most common neurodegenerative disorder worldwide with a growing prevalence in the continuously aging population. Until today, the diagnosis of Parkinson's disease is mainly based on the evaluation of distinctive clinical features and the differentiation from atypical parkinsonian syndromes and Parkinson's disease mimics. Despite remarkable developments in the field of diagnostics, the evaluation of Parkinson's disease patients can be challenging, particularly in oligosymptomatic early stages when distinctive clinical features are not that obvious. Therefore, biomarkers could contribute to an improved diagnostic accuracy. Tear fluid is an easily accessible body fluid reflecting pathophysiological changes in systemic and ocular diseases and is already used as a biomarker source for several ophthalmological disorders. Here, we analyzed the tear fluid of patients with Parkinson's disease and age-matched controls to describe disease-related changes in tear fluid and identify putative biomarkers for the diagnosis of Parkinson's disease. Therefore, unstimulated tear fluid samples of a pilot cohort with 36 Parkinson's disease patients and 18 controls were collected via Schirmer tear test strips and then analyzed via a Bottom-up liquid chromatography electrospray ionization tandem mass spectrometry workflow, followed by functional analysis encompassing protein-protein interaction as well as cellular component and pathway analysis. This mass spectrometric analysis lead to the identification of 571 tear proteins, whereby 31 proteins were exclusively detected in the Parkinson's disease group and 7 only in the control group. Whereas 21 proteins were significantly increased in the Parkinson's disease versus control group, 19 proteins were significantly decreased. Core networks of proteins involved in immune response, lipid metabolism and oxidative stress were distinctly altered in Parkinson's disease patients. Several proteins that are already well known in neurodegenerative disorders were identified. To our best knowledge, this is the first description of tear fluid proteome in Parkinson's disease patients. Tear protein level alterations suggest the contribution of different disease-related mechanisms in ocular pathology in Parkinson's disease and propose candidate proteins to be validated as potential biomarkers in larger cohorts.2022-03-3

On the pricing of longevity-linked securities

For annuity providers, longevity risk, i.e. the risk that future mortality trends differ from those anticipated, constitutes an important risk factor. In order to manage this risk, new financial products, so-called longevity derivatives, may be needed, even though a first attempt to issue a longevity bond in 2004 was not successful. While different methods of how to price such securities have been proposed in recent literature, no consensus has been reached. This paper reviews, compares and comments on these different approaches. In particular, we use data from the United Kingdom to derive prices for the proposed first longevity bond and an alternative security design based on the different methods.Longevity risk Stochastic mortality Longevity derivatives

Analysis of the Ion Channel Gating Mechanism in Solution by Nuclear Magnetic Resonance (NMR) Spectroscopy

Ion channels activated by cyclic nucleotides play crucial roles in signal transduction pathways. Upon binding of cyclic nucleotides to the intracellular cyclic nucleotide-binding domain (CNBD) of HCN or CNG channels (hyperpolarization-activated and cyclic nucleotide-gated channels or cyclic nucleotide-gated channels) an opening of the membrane pore occurs.To analyze the underlying gating mechanism highly resolved structures of the cyclic nucleotide-binding domains are necessary. Until now, structures of CNBDs from eukaryotic HCN channels as well as prokaryotic CNG channels are known. However, CNBD crystal structures of the HCN channels reveal no significant differences between apo and holo state1,2. In contrast, CNBD structures of the prokaryotic Mesorhizobium loti K1 channel, solved by liquid state NMR spectroscopy, show substantial rearrangements upon binding of a cyclic nucleotide3,4.Further elucidation of the gating mechanism will be done by structural analysis of an eukaryotic CNBD using liquid state NMR spectroscopy

The Volatility of Mortality

The use of forward models for the future development of mortality has been proposed by several authors. In this article, we specify adequate volatility structures for such models. We derive a Heath-Jarrow-Morton drift condition under different measures. Based on demographic and epidemiological insights, we then propose two different models with a Gaussian and a non-Gaussian volatility structure, respectively. We present a Maximum Likelihood approach for the calibration of the Gaussian model and develop a Monte Carlo Pseudo Maximum Likelihood approach that can be used in the non-Gaussian case. We calibrate our models to historic mortality data and analyze and value certain longevity-dependent payoffs within the models.

Der Kriterienkatalog der DEGAM für die Befugnis zur Facharztweiterbildung Allgemeinmedizin − ein Vorschlag zur Einschätzung der Strukturqualität in Weiterbildungspraxen

[english] Background: Whilst the structure of primary care vocational training in Germany is being increasingly formalized there remains an abundance of disparate locally defined criteria for the training practices. Advanced medical training in the ambulatory setting has also been identified as an area of need by other specialties. Goal: In contrast to the current practice of a unregulated authorization by regional medical associations this catalogue provide transparent, clearly defined criteria for the assignment of training practice status.Methods: The first draft of the criteria catalogue integrates feedback from 30 academic general practitioners. The feasibility of the catalogue was tested by a further 30 surgeries. Analysis included an assessment of the sociodemographic characteristics of the trainers and their practices as well as satisfaction of the participants with the approved authorization period.Results: The criteria catalogue comprises 19 items within the domains of trainer qualification, practice infrastructure and patient specific factors as well as mandatory criteria. The points scored through this system confer a variable period of authorization. Of the 30 participants 17 were satisfied with the period of authorization they received, 10 were dissatisfied, and one was indifferent.Satisfaction showed no correlation with sex, experience as a trainer, or with the score achieved through the criteria catalogue. It correlated little with the length of time practicing as a doctor.Conclusion: The criteria catalogue reflects both the breadth of general practice as well as the skills of the trainers. Satisfaction of participants in the test group was good, and infers a basis for applying the catalogue through regional medical associations to assign teaching practice status. It may also be used as a blue-print for other medical specialties

Exploring the chemical space of ureidothiophene-2-carboxylic acids as inhibitors of the quorum sensing enzyme PqsD from Pseudomonas aeruginosa.

Pseudomonas aeruginosa employs a quorum sensing (QS) communication system that makes use of small diffusible molecules. Among other effects, the QS system coordinates the formation of biofilm which decisively contributes to difficulties in the therapy of Pseudomonas infections. The present work deals with the structure-activity exploration of ureidothiophene-2-carboxylic acids as inhibitors of PqsD, a key enzyme in the biosynthetic pathway of signal molecules in the Pseudomonas QS system. We describe an improvement of the inhibitory activity by successfully combining features from two different PqsD inhibitor classes. Furthermore the functional groups, which are responsible for the inhibitory potency, were identified. Moreover, the inability of the new inhibitors, to prevent signal molecule formation in whole cell assays, is discussed