The impact of framing and anchoring on postponing labour market exit - evidence from Polish NDC+FDC pension scheme

Purpose: The article examines whether the level of effective retirement age can be shifted upwards by increasing awareness of the consequences of premature retirement. Design/Methodology/Approach: The study uses multinomial logistic regression on the representative survey data for Polish working population. Special interest is given to the questionnaire with framing and anchoring effects included. Findings: The findings reveal strong retirement preferences of a minimum retirement age being the reference point and the natural anchor. However, these might change once framing is provided. Pension awareness is a significant predictor of postponing retirement. There can be distinguished a segment of working population with extremely low pension literacy. Practical Implications: Increasing effective retirement age is among most important factors reducing labour supply deficits and improving long-term sustainability of public finance. Special interest should be given to rational individuals with wrong assumptions on the mechanics of the pension scheme and individuals with extremely low pension knowledge in order to avoid severe old-age poverty. Originality/value: The study confirms that use of framing in increasing financial literacy leads to significant postponement of the labour market exit declared. Furthermore, there is a segment of the Polish working population with extremely low pension knowledge which should be educated.peer-reviewe

Extending pension coverage: Tax versus non-tax incentives

This paper compares the design, cost and e?ectiveness of three voluntary approaches for increasing pension coverage. The frst facilitates plan features designed to attract workers. The second provides tax and other fnancial incentives. The third mandates autoenrollment of workers with opt out. The non-tax incentives of plan features in the United States have had little e?ect on increasing coverage. Generous tax incentives in Germany and Czechia have raised coverage but are costly. Mandatory autoenrollment with opt out in the United Kingdom has achieved the highest coverage rate of the three approaches

Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection.

Current knowledge on the role of microRNAs (miRNAs) in rabbit hemorrhagic disease virus (RHDV) infection and the pathogenesis of rabbit hemorrhagic disease (RHD) is still limited. RHDV replicates in the liver, causing hepatic necrosis and liver failure. MiRNAs are a class of short RNA molecules, and their expression profiles vary over the course of diseases, both in the tissue environment and in the bloodstream. This paper evaluates the expression of miRNAs in the liver tissue (ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p) and serum (ocu-miR-122-5p) of rabbits experimentally infected with RHDV. The expression levels of ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p in liver tissue were determined using reverse transcription quantitative real-time PCR (RT-qPCR), and the expression level of circulating ocu-miR-122-5p was established using droplet digital PCR (ddPCR). The expression levels of ocu-miR-155-5p and ocu-miR-16b-5p were significantly higher in the infected rabbits compared to the healthy rabbits (a fold-change of 5.8 and 2.5, respectively). The expression of ocu-miR-122-5p was not significantly di�erent in the liver tissue from the infected rabbits compared to the healthy rabbits (p = 0.990), while the absolute expression level of the circulating ocu-miR-122-5p was significantly higher in the infected rabbits than in the healthy rabbits (p < 0.0001). Furthermore, a functional analysis showed that ocu-miR-155-5p, ocu-miR-16b-5p, and ocu-miR-122-5p can regulate the expression of genes involved in processes correlated with acute liver failure (ALF) in rabbits. Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that the potential target genes of the three selected miRNAs may interact with each other in di�erent pathways. The results indicate the roles of these miRNAs in RHDV infection and over the course of RHD and may reflect hepatic inflammation and impairment/dysfunction in RHD

Interindividual variability of atorvastatin treatment influence on the MPO gene expression in patients after acute myocardial infarction

Myeloperoxidase (MPO) and C-reactive protein (CRP) may play critical roles in generation of oxidative stress and the development of the systemic inflammatory response. The aim of the study was to determine the effect of atorvastatin therapy on the MPO gene expression and its plasma level in relation to lipids level lowering and an anti-inflammatory response in patients after acute myocardial infarction. The research material was represented by 112 samples. Thirty-eight patients with first AMI receiving atorvastatin therapy (40 mg/day) and followed up for one month were involved in the study. The relative MPO gene expression in peripheral blood mononuclear cells (PBMCs) was examined using RT-qPCR in 38 patients before-, 38 patients after-therapy and in 36 patients as the control group. The plasma concentrations of MPO and serum concentrations of biochemical parameters were determined using commercially available diagnostic tests. After one month of atorvastatin therapy, in 60.5% patients a decrease of MPO gene expression, whereas in 39.5% patients an increase, was observed. The plasma MPO levels behaved in the same way as the MPO gene expression. However, the serum lipids and CRP concentrations were significantly lower after one month of atorvastatin therapy in both groups of patients - with decreased and increased MPO gene expression. Atorvastatin exhibited a different effect on MPO gene expression and its plasma level. Short-term atorvastatin therapy resulted in lipid lowering and anti-inflammatory activity in patients after AMI, independently of its effect on MPO gene expression. The molecular mechanisms of this phenomenon are not yet defined and require further research

Genetic engineering and molecular characterization of yeast strain expressing hybrid human-yeast squalene synthase as a tool for anti-cholesterol drug assessment

AIMS: The main objective of the study is molecular and biological characterization of the human-yeast hybrid squalene synthase (SQS), as a promising target for treatment of hypercholesterolaemia. METHODS AND RESULTS: The human-yeast hybrid SQS, with 67% amino acids, including the catalytic site derived from human enzyme, was expressed in Saccharomyces cerevisiae strain deleted of its own SQS gene. The constructed strain has a decreased level of sterols compared to the control strain. The mevalonate pathway and sterol biosynthesis genes are induced and the level of triacylglycerols is increased. Treatment of the strain with rosuvastatin or zaragozic acid, two mevalonate pathway inhibitors, decreased the amounts of squalene, lanosterol and ergosterol, and up-regulated expression of several genes encoding enzymes responsible for biosynthesis of ergosterol precursors. Conversely, expression of the majority genes implicated in the biosynthesis of other mevalonate pathway end products, ubiquinone and dolichol, was down-regulated. CONCLUSIONS: The S. cerevisiae strain constructed in this study enables to investigate the physiological and molecular effects of inhibitors on cell functioning. SIGNIFICANCE AND IMPACT OF THE STUDY: The yeast strain expressing hybrid SQS with the catalytic core of human enzyme is a convenient tool for efficient screening for novel inhibitors of cholesterol-lowering properties

POTENTIAL GENETIC AGENT BFL1 FOR TARGETED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA

Background: Many prognostic factors have been identified in chronic lymphocytic leukemia (CLL) but new ones are still desired. The biological characterization of CLL is now being translated into novel treatment strategies. One new prognostic factor, and therapeutic target, may be BFL1. It is both a serum and a molecular marker that contributes to the progression of CLL and its resistance to chemotherapy. The aim of this study was to evaluate the prognostic value of BFL1 and to assess its correlation with other known prognostic markers in CLL for the cladribine and cyclophosphamide regimen (CC). Methods: qPCR TaqMan® Low Density Array was used for gene expression measurements. Assessment of CD38, ZAP70 and BFL-1 proteins expression was done by means of flow cytometry. Serum TK activity was measured by immunoassay. Results: Protein BFL1 expression was found to be significantly higher in CLL patients than healthy volunteers (p=0.001). Moreover its level was significantly higher in patients with no response (NR) to CC therapy (p=0.009). The expression of BFL1 was considerably down regulated during CC treatment and BFL1 mRNA levels were inversely correlated with apoptotic response. In addition, protein BFL1 expression was found to be similar to thymidine kinase (TK) concentration regarding treatment response. As far as other markers are concerned, a positive correlation was identified between BFL1 and TK (r=0.52, p=0.01). Conclusions: Our findings suggest that BFL1 contributes to chemoresistance and may be a co-existing prognostic factor in CLL in the future

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy

Purpose: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. Material and methods: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. Results: An inter-centre variation in SPR prediction (2 sigma) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2 sigma) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung-and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. Conclusion: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion. (C) 2021 The Authors. Published by Elsevier B.V

Adaptive radiotherapy and treatment planning strategies for ion beam therapy

At present there are around 30 ion beam therapy facilities operating all over the world. With several more being built and becoming operational during the next years, it is essential to focus research on the field of ion beam therapy. There are many challenges on the way to utilize ion beam therapy in its whole potential. One of the challenging areas is organ motion management, therefore advances in IGRT and ART are of particular interest. During fractionated radiotherapy, which usually takes several weeks, a patient is treated according to a treatment plan generated at the beginning of the treatment. However, the actual delivered dose to the patient can be different to the one originally planned, because of many factors (anatomical changes, positioning uncertainties, etc.), which may influence the delivered dose distribution. Adaptation of the treatment during the course of radiotherapy or choosing an appropriate planning approach is essential in order to successfully treat patients with ion beam therapy. However, the implementation of such methods needs further research and continuous development. This thesis is dedicated to adaptive radiotherapy strategies for ion beam therapy, which were assessed with treatment planning studies. It consists of 3 independent studies, each dealing with different areas of particle treatment, i.e. PTV margin definition, combined modality treatments and influence of the anatomical variations on dose distribution. Anatomical variations in the pelvic area can affect the delivered dose distribution in scanned proton beam therapy. The purpose of the first study was to investigate the most robust margin strategy to account for inter-fractional motion in low risk prostate cancer. With the use of one planning CT and 7 weekly repeated CBCTs, the following PTV approaches were investigated: conventional margin approach (PTV10mm), reduced margin recipe (PTVRed) and a patient specific margin (PTVHull). The dosimetric impact of organ motion on targets and OARs for all three approaches was evaluated. Results of the study showed that the patient specific margin is the most robust approach among all three compared, but also proved that repeated imaging is an useful tool to estimate inter-fractional motion and its impact on the dose distribution. The second study was conducted to compare particle treatment modalities (IMPT and IMIT) as boost options with advanced photon beam therapy (VMAT). This study was performed for two indications: locally advanced head-and-neck cancer (H&N) and patients diagnosed with high-risk prostate cancer (PC). For both, using VMAT, fast and effi cient treatments can be delivered. However, combining particles and photons spare OARs more beneficially compared to sole photon treatments. In this study, for H&N cases, not only main OARs (i.e. brainstem, spinal cord, parotid glands) were assessed, but we also evaluated various OAR (e.g. cochlea, middle ear, masticator space) that are currently discussed with respect to side effects after treatment, but usually not taken into consideration while optimizing the plan. Results showed that with advances in dose delivery techniques (especially a combination of VMAT+IMIT), nowadays, we are able to spare many more organs than it was possible with the conventional techniques. Consequently, modern radiotherapy is able to improve cancer treatment and can potentially increase the quality of life after radiation. For high precision dose deliveries such as scanned beam ion therapy, any inhomogeneities along the particles' path may change the outcome of the treatment. In respect to that conventional photon treatment is less sensitive and is expected to have more robust dose delivery. In the last study, a special focus was given to the impact of organ motion on the delivered dose and differences between VMAT and IMPT were studied. Moreover, the deformable registration of repeated CTs and dose accumulation was performed for H&N patients to assess the total dose delivered to the patient in two different scenarios: (1) when new plans were created and the dose was adapted to the current anatomy and (2) when no adaptation was performed. The assessment of the dose changes influenced by anatomical variations showed benefits of adaptive strategies for both modalities. However, those benefits were more apparent for individual patients, whereas for the averaged representation some of the information might have been smeared out. Moreover, the same anatomical variations within a patient resulted in very different dose distributions between IMPT and VMAT. Therefore, for successful implementation of ART into the clinic, among others, the adaptation strategy should be adjusted to needs of the chosen modality. The presented PhD thesis underlined different issues concerning ion beam therapy. Starting from the most robust margin strategy for low risk prostate cancer, advantages of the combined modality treatments for both prostate and head and neck cancer and finally consideration of adaptive RT strategies for particle treatments. Each of the studies highlighted the advantages of ion beam therapy as well as its limitations, but above all they proved that the experience taken from conventional photon therapy cannot be directly translated into the particle field. Regardless of the tumor itself, which remains the same, for ion beam therapy much more factors must be taken into the account, in comparison to photon beam therapy, as they are less significant and could be neglected. This thesis answers only few questions and much more research in this field needs to be conducted.Die Strahlentherapie mit Ionen ist eine rasant wachsende Krebsbehandlungsmethode. Gegenwärtig gibt es um die 30 Teilchentherapiezentren auf der Welt. Mehr und mehr Zentren sind in Planung wodurch die Notwendigkeit für Forschung im Bereich der Teilchentherapie immer bedeutender wird. Gewöhnlich wird ein Patient im Laufe der fraktionierten Strahlentherapie über mehrere Wochen hinweg mit einem Bestrahlungsplan behandelt, welcher am Anfang der Bestrahlung erstellt wurde. Die verabreichte Dosis kann hierbei aber essentiell von der geplanten Dosis abweichen. Unterschiedlichste Faktoren wie anatomische angedrungen, Positionierungsungenauigkeiten usw. können die verabreichte Dosisverteilung beeinflussen. Die Anpassung der Bestrahlung während eines Strahlentherapiezyklus oder die Verwendung eines angepassten Bestrahlungsplanes kann dabei entscheidend zu einer erfolgreichen Behandlung beitragen und ermöglicht neue, effizientere Behandlungskonzepte. Diese Doktorarbeit beschäftigt sich mit die vergleichenden Bestrahlungsplanung, wobei unterschiedliche adaptive Bestrahlungsstrategien für Ionentherapie untersucht werden. Die Arbeit besteht aus drei unabhängigen Studien. Jede dieser Studien deckt komplementäre Aspekte der adaptiven Teilchentherapie ab, wie PTV-Marginkonzepte, kombinierte Bestrahlungsmodalitäten sowie dem Einfluss von Anatomieveränderungen auf die Dosisverteilung. Das Ziel der ersten Planungsstudie war das robusteste Marginkonzept zu definieren, um die interfraktionelle Bewegung bei Niedrigrisikoprostatapatienten zu kompensieren. Unter der Verwendung eines Planungs-CTs und 7 wiederholten wöchentlichen CBCT wurden die folgenden PTV Ansätze untersucht: das konventionelle Marginkonzept, die Verwendung eines reduzierten Margins und ein patientenspezifischer Ansatz. Die Resultate der Studie zeigten nicht nur, dass ein patientenspezifisches Marginkonzept das robusteste ist sondern auch, dass wöchentliche Bildgebung sehr gut geeignet ist, um interfraktionelle Bewegung und deren Einfluss auf die Dosisverteilung abzuschätzen. Die zweite Studie wurde durchgeführt, um verschiedene Teilchenbestrahlungsmodalitäten (IMPT) und (IMIT) als Boostoption mit einer Hochpräzisionsphotonentherapie (VMAT) zu vergleichen. Zwei Indikationen wurden in diese Studie eingeschlossen, H&N und Prostata Patienten. Resultate dieser Studie belegen, dass die Fortschritte hochentwickelter Bestrahlungstechniken (insbesondere die Kombination von VMAT + IMIT) es ermöglichen, mehr Risikoorgane zu schonen als die Verwendung von konventioneller Strahlentherapie allein. Somit kann moderne Strahlentherapie nicht nur ausreichende Tumorkontrolle ermöglichen sondern auch die Lebensqualität nach der Bestrahlung verbessern. In der dritten Studie wurde besonderes Augenmerk auf den Einfluss von Organbewegungen auf die verabreichte Dosisverteilung gelegt und die Unterschiede zwischen VMAT und IMPT dargestellt. Darüberhinaus wurde deformierbare Registrierung der wöchentlichen CTs und Dosisakkumulierung für H&N Patienten untersucht, wobei die verabreichte Dosis für 2 Szenarien berechnet wurde: (1) neue Pläne wurden erstellt und die Dosis wurde an die aktuelle Anatomie angepasst (2) Verwendung der Originalpläne ohne Anpassung an die aktuelle Anatomie. Die Untersuchung der Dosisveänderungen welche durch anatomische Veränderungen verursacht wurden zeigte, dass adaptive Bestrahlungsplanungsstrategien für beide Modalitäten von Vorteil sind. Zudem zeigte sich, dass dieselben anatomischen Veränderungen für einen individuellen Patienten sehr unterschiedliche Veränderungen der Dosisverteilungen für IMPT und VMAT verursachen. Daraus lässt sich schließen, dass eine erfolgreiche Implementierung von ART in den klinischen Betrieb an die jeweilige Bestrahlungsmodalität angepasst werden muss.by Joanna GoraAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZusammenfassung in deutscher SpracheMedizinische Universität Wien, Dissertation, 2015OeBB(VLID)171367