Frontotemporal Dementia in the Netherlands

__Abstract__ In 1892, Arnold Pick described the first patients with a clinical syndrome that is currently named frontotemporal dementia (FTD). He emphasised the focal aspect of cortical atrophy in his patients, to this day the hallmark of this disorder. Following a detailed description of the neuropathological changes by Alois Alzheimer in 1911, including the argyrophilic neuronal inclusions later known as Pick bodies, the term Pick’s disease was introduced in 1926. Over the years, many different names have been used to describe this clinical and pathological entity: frontal lobe dementia, dementia of non-Alzheimer type, dementia of frontal lobe type, Pick’s disease, and others. In 1994, the term FTD was introduced to describe the clinical syndrome associated with focal frontotemporal degeneration, with semantic dementia and primary progressive aphasia being recognised as clinical variants of FTD. Typical features of this syndrome, which often presents with a presenile onset, are progressive behavioural changes and language disturbances. FTD can be caused by a number of neuropathological substrates, including Pick’s disease, which is currently defined by the presence of argyrophilic Pick bodies. In 1994, a genetic-epidemiological study on FTD was started at the Erasmus MC of Rotterdam. The main research questions addressed in this study are the estimation of the prevalence of FTD in the Netherlands, the clinical aspects of the temporal variant of FTD, and further elucidation of the genetic and other risk factors involved in the aetiology of FTD

Two-parameter Quantum Affine Algebra Ur,s(sln^)U_{r,s}(\widehat{\frak {sl}_n}), Drinfel'd Realization and Quantum Affine Lyndon Basis

We further define two-parameter quantum affine algebra $U_{r,s}(\widehat{\frak {sl}_n})$ $(n>2)$ after the work on the finite cases (see [BW1], [BGH1], [HS] & [BH]), which turns out to be a Drinfel'd double. Of importance for the quantum {\it affine} cases is that we can work out the compatible two-parameter version of the Drinfel'd realization as a quantum affinization of $U_{r,s}(\frak{sl}_n)$ and establish the Drinfel'd isomorphism Theorem in the two-parameter setting, via developing a new combinatorial approach (quantum calculation) to the quantum {\it affine} Lyndon basis we present (with an explicit valid algorithm based on the use of Drinfel'd generators).Comment: 31 page

Coherent States for Quantum Compact Groups

Coherent states are introduced and their properties are discussed for all simple quantum compact groups. The multiplicative form of the canonical element for the quantum double is used to introduce the holomorphic coordinates on a general quantum dressing orbit and interpret the coherent state as a holomorphic function on this orbit with values in the carrier Hilbert space of an irreducible representation of the corresponding quantized enveloping algebra. Using Gauss decomposition, the commutation relations for the holomorphic coordinates on the dressing orbit are derived explicitly and given in a compact R--matrix formulation (generalizing this way the $q$--deformed Grassmann and flag manifolds). The antiholomorphic realization of the irreducible representations of a compact quantum group (the analogue of the Borel--Weil construction) are described using the concept of coherent state. The relation between representation theory and non--commutative differential geometry is suggested.}Comment: 25 page

Finite-dimensional representations of the quantum superalgebra Uq[gl(n/m)]U_q[gl(n/m)] and related q-identities

Explicit expressions for the generators of the quantum superalgebra $U_q[gl(n/m)]$ acting on a class of irreducible representations are given. The class under consideration consists of all essentially typical representations: for these a Gel'fand-Zetlin basis is known. The verification of the quantum superalgebra relations to be satisfied is shown to reduce to a set of $q$-number identities.Comment: 12 page

Epigenetic effects of chromatin remodeling agents on organotypic cultures

Background: Tumor epigenetic defects are of increasing relevance to clinical practice, because they are 'druggable' targets for cancer therapy using chromatin-remodeling agents (CRAs). New evidences highlight the importance of the microenvironment on the epigenome regulation and the need to use culture models able to preserve tissue morphology, to better understand the action of CRAs. Methods & methods: We studied the epigenetic response induced by culturing and CRAs in a preclinical model, preserving ex vivo the original tissue microenvironment and morphology, assessing different epigenetic signatures. Our overall findings suggest that culturing and CRAs cause heterogeneous effects on the genes methylation; CRAs affect the global DNA methylation and can trigger an active DNA demethylation; the culture induces alterations in the histone deacetylase expression. Conclusion: Despite the limited number of cases, these findings can be considered a proof of concept of the possibility to test CRAs epigenetic effects on ex vivo tissues maintained in their native tissue architecture

The foot (Fragmentation Of Target) experiment

Particle therapy uses proton or 12C beams for the treatment of deep-seated solid tumors. Due to the features of energy deposition of charged particles a small amount of dose is released to the healthy tissue in the beam entrance region, while the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However nuclear interactions between beam and patient tissues induce fragmentation both of projectile and target and must be carefully taken into account. In 12C treatments the main concern are long range fragments due to projectile fragmentation that release dose in the healthy tissue after the tumor, while in proton treatment the target fragmentation produces low energy, short range fragments along all the beam range. The FOOT experiment (FragmentatiOn Of Target) is designed to study these processes. Target nuclei (16O,12C) fragmentation induced by 150-250 AMeV proton beam will be studied via inverse kinematic approach. 16O,12C therapeutic beams, with the quoted kinetic energy, collide on graphite and hydrocarbons target to provide the cross section on Hydrogen. This configuration explores also the projectile fragmentation of these 16O,12C beams. The detector includes a magnetic spectrometer based on silicon pixel detectors and drift chamber, a scintillating crystal calorimeter with TOF capabilities, able to stop the heavier fragments produced, and a \u394E detector to achieve the needed energy resolution and particle identification. An alternative setup of the experiment will exploit the emulsion chamber capabilities. A specific emulsion chambers will be coupled with the interaction region of the FOOT setup to measure the production in target fragmentation of light charged fragments as protons, deuterons, tritons and Helium nuclei. The FOOT data taking is foreseen at the CNAO experimental room and will start during early 2018 with the emulsion setup, while the complete electronic detector will take data since 2019

Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems