Shaping pension reform in Poland : security through diversity

All over the world, pension systems have financing difficulties that need to be addressed. There are three ways of dealing with pension systems problems - finance it to a greater extent from general revenues, rationalize the system, or a full-fledged reform. After several years of political and professional discussions, Poland decided to follow the latter path and introduced a new defined contribution multipillar system, consisting of a public National Defined Contribution, pay-as-you-go first pillar, a funded private second pillar, and voluntary funded third pillar. The new framework covers only retirement savings, while other benefits still remain under the old defined-benefit pay-as-you-go regime. The reform was launched on January 1, 1999. This paper presents the current situation of the pension system, the struggle for pension reform in the 1990s, structure, the long-term outlook of the new pension system and the main aspects of the system design as well as first experiences from the implementation process. Long-term projection show that the new system allows for greater financial stability of the public pension scheme and increases the savings rate with a positive impact on economic growth.Pensions&Retirement Systems,Information Technology,Banks&Banking Reform,Gender and Law,Children and Youth

Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study

$\textbf{Background}$: Immune infiltration of breast tumours is associated with clinical outcome. However, past work has not accounted for the diversity of functionally distinct cell types that make up the immune response. The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in breast tumours influence survival and treatment response, and whether these effects differ by molecular subtype. $\textbf{Methods and Findings}$: We applied an established computational approach (CIBERSORT) to bulk gene expression profiles of almost 11,000 tumours to infer the proportions of 22 subsets of immune cells. We investigated associations between each cell type and survival and response to chemotherapy, modelling cellular proportions as quartiles. We found that tumours with little or no immune infiltration were associated with different survival patterns according to oestrogen receptor (ER) status. In ER-negative disease, tumours lacking immune infiltration were associated with the poorest prognosis, whereas in ER-positive disease, they were associated with intermediate prognosis. Of the cell subsets investigated, T regulatory cells and M0 and M2 macrophages emerged as the most strongly associated with poor outcome, regardless of ER status. Among ER-negative tumours, CD8+ T cells (hazard ratio [HR] = 0.89, 95% CI 0.80-0.98; $p$ = 0.02) and activated memory T cells (HR 0.88, 95% CI 0.80-0.97; $p$ = 0.01) were associated with favourable outcome. T follicular helper cells (odds ratio [OR] = 1.34, 95% CI 1.14-1.57; $p$ < 0.001) and memory B cells (OR = 1.18, 95% CI 1.0-1.39; $p$ = 0.04) were associated with pathological complete response to neoadjuvant chemotherapy in ER-negative disease, suggesting a role for humoral immunity in mediating response to cytotoxic therapy. Unsupervised clustering analysis using immune cell proportions revealed eight subgroups of tumours, largely defined by the balance between M0, M1, and M2 macrophages, with distinct survival patterns by ER status and associations with patient age at diagnosis. The main limitations of this study are the use of diverse platforms for measuring gene expression, including some not previously used with CIBERSORT, and the combined analysis of different forms of follow-up across studies. $\textbf{Conclusions}$: Large differences in the cellular composition of the immune infiltrate in breast tumours appear to exist, and these differences are likely to be important determinants of both prognosis and response to treatment. In particular, macrophages emerge as a possible target for novel therapies. Detailed analysis of the cellular immune response in tumours has the potential to enhance clinical prediction and to identify candidates for immunotherapy.HRA is an NIHR Academic Clinical Lecturer and was a recipient of a Career Development Fellowship from The Pathological Society of GB and N Ireland, and a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences. LC, CC, and FM received funding from the CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester (grant C197/A16465)

Pension reform and public information in Poland

The introduction of a new pension system in Poland in 1999 was the culmination of a long policy dialogue and years of debate. During this period, the role of public opinion shaped the reform and was, in turn, shaped by the reform process. Implementation of the reform was also affected by the quality of information available to the public and the public's financial literacy. In contrast to their passive role in the old public, defined-benefit schemes, People who chose to divert their contributions to individual, defined-contribution accounts must now take an active role in the new system. This paper documents the evolution of public opinion and its affects on the reform process as well as the early experiences of millions of people who, for the first time, are faced with the challenge of choice as consumers in the new market for pension services.Pensions&Retirement Systems,Economic Stabilization,Banks&Banking Reform,Health Monitoring&Evaluation,Children and Youth

Why the share of small amount pensions is so substantial in Latvia?

More than 70% of all old-age pensions in Latvia are smaller than 300 euro, which is close to the monetary value of the at-risk-of-poverty threshold. There is a number of reasons for it: the lack of non-contributory component and inadequately low minimum pensions, the absence of redistribution mechanisms in the mandatory notional defined contribution (pillar I) and funded (pillar II) schemes, an unfair conversion of pre-reform employment record into pension formula, and a high tax burden on pensioners. The authors proposed a package of measures to improve the situation: an introduction of basis pensions, linking minimum pensions to the country average wages, increasing income tax exempt for pensions, restoration of the supplements for pre-reform employment and their regular indexation, removal of the threshold in initial notional pension capital calculation or its reduction from 30 to 20 years

Machine Learning Methods for Cancer Immunology

Tumours are highly heterogeneous collections of tissues characterised by a repertoire of heavily mutated and rapidly proliferating cells. Evading immune destruction is a fundamental hallmark of cancer, and elucidating the contextual basis of tumour-infiltrating leukocytes is pivotal for improving immunotherapy initiatives. However, progress in this domain is hindered by an incomplete characterisation of the regulatory mechanisms involved in cancer immunity. Addressing this challenge, this thesis is formulated around a fundamental line of inquiry: how do we quantitatively describe the immune system with respect to tumour heterogeneity? Describing the molecular interactions between cancer cells and the immune system is a fundamental goal of cancer immunology. The first part of this thesis describes a three-stage association study to address this challenge in pancreatic ductal adenocarcinoma (PDAC). Firstly, network-based approaches are used to characterise PDAC on the basis of transcription factor regulators of an oncogenic KRAS signature. Next, gene expression tools are used to resolve the leukocyte subset mixing proportions, stromal contamination, immune checkpoint expression and immune pathway dysregulation from the data. Finally, partial correlations are used to characterise immune features in terms of KRAS master regulator activity. The results are compared across two independent cohorts for consistency. Moving beyond associations, the second part of the dissertation introduces a causal modelling approach to infer directed interactions between signaling pathway activity and immune agency. This is achieved by anchoring the analysis on somatic genomic changes. In particular, copy number profiles, transcriptomic data, image data and a protein-protein interaction network are integrated using graphical modelling approaches to infer directed relationships. Generated models are compared between independent cohorts and orthogonal datasets to evaluate consistency. Finally, proposed mechanisms are cross-referenced against literature examples to test for legitimacy. In summary, this dissertation provides methodological contributions, at the levels of associative and causal inference, for inferring the contextual basis for tumour-specific immune agency.This PhD was supported by the Cancer Research UK and Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester (C197/A16465

The minimum pension as an instrument of poverty protection in the defined contribution pension system – an example of Poland

Pension systems’ reforms are often related to a shift towards (fully or partially) defined contribution systems, in which the pension distribution reflects to a larger extent the wage distribution. Additionally, relatively shorter working lives of those that have lower earnings, increase the risk of receiving lower benefits. The aim of the paper is to present the changing role of minimum pension as a tool of redistribution in Poland after the pension reform. The new mandatory pension system covers workers born after 1948 and is based on two components – notional and funded defined contribution (NDC and FDC). It replaced the old defined-benefit PAYG system, which had a significant redistribution through the pension formula. The formula itself served as a tool of low income protection, that was additionally strengthened by the minimum pension guarantee. The new system aims at actuarial fairness, which means that the only mechanism of redistribution is the minimum pension, financed from general taxes. As a result of this change, grater income inequalities of pensioners following those of people in working age are expected. This means a change of the role of the minimum pension from one of the tools supporting redistributive policy to the main tool of social policy preventing poverty among elderly persons. The minimum pension is expected to fall compared to average wage. The decision on its level and evolution becomes one of the most important policy questions. It will have crucial importance in preventing poverty in the old-age. Simulations are used to present the impact of changes in the pension distribution on the number of pensioners covered by minimum pension

The minimum pension as an instrument of poverty protection in the defined contribution pension system – an example of Poland

Pension systems’ reforms are often related to a shift towards (fully or partially) defined contribution systems, in which the pension distribution reflects to a larger extent the wage distribution. Additionally, relatively shorter working lives of those that have lower earnings, increase the risk of receiving lower benefits. The aim of the paper is to present the changing role of minimum pension as a tool of redistribution in Poland after the pension reform. The new mandatory pension system covers workers born after 1948 and is based on two components – notional and funded defined contribution (NDC and FDC). It replaced the old defined-benefit PAYG system, which had a significant redistribution through the pension formula. The formula itself served as a tool of low income protection, that was additionally strengthened by the minimum pension guarantee. The new system aims at actuarial fairness, which means that the only mechanism of redistribution is the minimum pension, financed from general taxes. As a result of this change, grater income inequalities of pensioners following those of people in working age are expected. This means a change of the role of the minimum pension from one of the tools supporting redistributive policy to the main tool of social policy preventing poverty among elderly persons. The minimum pension is expected to fall compared to average wage. The decision on its level and evolution becomes one of the most important policy questions. It will have crucial importance in preventing poverty in the old-age. Simulations are used to present the impact of changes in the pension distribution on the number of pensioners covered by minimum pension

Master Regulators of Oncogenic KRAS Response in Pancreatic Cancer: An Integrative Network Biology Analysis.

BACKGROUND: KRAS is the most frequently mutated gene in pancreatic ductal adenocarcinoma (PDAC), but the mechanisms underlying the transcriptional response to oncogenic KRAS are still not fully understood. We aimed to uncover transcription factors that regulate the transcriptional response of oncogenic KRAS in pancreatic cancer and to understand their clinical relevance. METHODS AND FINDINGS: We applied a well-established network biology approach (master regulator analysis) to combine a transcriptional signature for oncogenic KRAS derived from a murine isogenic cell line with a coexpression network derived by integrating 560 human pancreatic cancer cases across seven studies. The datasets included the ICGC cohort (n = 242), the TCGA cohort (n = 178), and five smaller studies (n = 17, 25, 26, 36, and 36). 55 transcription factors were coexpressed with a significant number of genes in the transcriptional signature (gene set enrichment analysis [GSEA] p < 0.01). Community detection in the coexpression network identified 27 of the 55 transcription factors contributing to three major biological processes: Notch pathway, down-regulated Hedgehog/Wnt pathway, and cell cycle. The activities of these processes define three distinct subtypes of PDAC, which demonstrate differences in survival and mutational load as well as stromal and immune cell composition. The Hedgehog subgroup showed worst survival (hazard ratio 1.73, 95% CI 1.1 to 2.72, coxPH test p = 0.018) and the Notch subgroup the best (hazard ratio 0.62, 95% CI 0.42 to 0.93, coxPH test p = 0.019). The cell cycle subtype showed highest mutational burden (ANOVA p < 0.01) and the smallest amount of stromal admixture (ANOVA p < 2.2e-16). This study is limited by the information provided in published datasets, not all of which provide mutational profiles, survival data, or the specifics of treatment history. CONCLUSIONS: Our results characterize the regulatory mechanisms underlying the transcriptional response to oncogenic KRAS and provide a framework to develop strategies for specific subtypes of this disease using current therapeutics and by identifying targets for new groups.IdS and FM were funded by Cancer Research UK core grant C14303/A17197 and A19274 (to FM). LC was supported by the Cancer Research UK and Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester (C197/A16465)