Increased incidence of melanoma in children and adolescents in Finland in 1990-2014 : nationwide re-evaluation of histopathological characteristics

Background Changes in the incidence of melanoma in children and adolescents have been reported in Europe and in the USA in the recent decades. Aims The aim of this study was to examine the incidence of paediatric and adolescent melanomas in Finland in 1990-2014, and the associated clinical and histopathological characteristics to reveal temporal trends, such as changes in diagnostic sensitivity of Spitzoid melanomas. Methods Information on 122 patients diagnosed with cutaneous melanoma at 0-19 years of age in Finland in 1990-2014 were retrieved from the Finnish Cancer Registry. 73 primary melanoma archival samples were re-evaluated by two dermatopathologists to allow comparability over time. Results A 5.6% annual increase was observed in the incidence of melanoma among children and adolescents during the study period. Fifty-six tumours were confirmed as malignant melanomas in the re-evaluation. After correction for tumour misclassification in the Cancer Registry, the age-adjusted annual incidence was estimated to have increased from 1.4/1 000 000 in 1990-1994 to 5.8/1 000 000 in 2010-2014. The change in incidence was most prominent among adolescents and in Spitzoid melanoma subtype. Melanomas diagnosed 1990-2002 and 2003-2014 did not differ in terms of their clinicopathological characteristics or prognosis (hazard ratio for melanoma-related death 1.53, 95% CI 0.30 to 7.88). Spitzoid melanomas were diagnosed at a younger age, were of higher stage and had higher Clark level than other melanomas, yet the hazard ratio for death was 0.52 (95% CI 0.10 to 2.58) for Spitzoid versus other melanomas. Conclusions The incidence of cutaneous melanoma has clearly increased among the young in Finland, especially among adolescents. No evidence for overdiagnosis of Spitzoid melanomas as the underlying cause of the increased incidence was observed. Key message A nationwide retrospective re-evaluation of the cutaneous melanomas recorded in the Finnish Cancer Registry among patients aged 0-19 years in Finland in 1990-2014 revealed an approximately 4-fold increase in the incidence. The increase in the incidence was most prominent among adolescents and in the Spitzoid melanoma subtype. Our results contrast those reported in other countries, where the incidence of melanoma among adolescents has declined.Peer reviewe

Foundations of the B method

B is a method for specifying, designing and coding software systems. It is based on Zermelo-Fraenkel set theory with the axiom of choice, the concept of generalized substitution and on structuring mechanisms (machine, refinement, implementation). The concept of refinement is the key notion for developing B models of (software) systems in an incremental way. B models are accompanied by mathematical proofs that justify them. Proofs of B models convince the user (designer or specifier) that the (software) system is effectively correct. We provide a survey of the underlying logic of the B method and the semantic concepts related to the B method; we detail the B development process partially supported by the mechanical engine of the prover

Event Systems and Access Control

We consider the interpretations of notions of access control (permissions, interdictions, obligations, and user rights) as run-time properties of information systems specified as event systems with fairness. We give proof rules for verifying that an access control policy is enforced in a system, and consider preservation of access control by refinement of event systems. In particular, refinement of user rights is non-trivial; we propose to combine low-level user rights and system obligations to implement high-level user rights

Structural and transport properties of GaAs/delta<Mn>/GaAs/InxGa1-xAs/GaAs quantum wells

We report results of investigations of structural and transport properties of GaAs/Ga(1-x)In(x)As/GaAs quantum wells (QWs) having a 0.5-1.8 ML thick Mn layer, separated from the QW by a 3 nm thick spacer. The structure has hole mobility of about 2000 cm2/(V*s) being by several orders of magnitude higher than in known ferromagnetic two-dimensional structures. The analysis of the electro-physical properties of these systems is based on detailed study of their structure by means of high-resolution X-ray diffractometry and glancing-incidence reflection, which allow us to restore the depth profiles of structural characteristics of the QWs and thin Mn containing layers. These investigations show absence of Mn atoms inside the QWs. The quality of the structures was also characterized by photoluminescence spectra from the QWs. Transport properties reveal features inherent to ferromagnetic systems: a specific maximum in the temperature dependence of the resistance and the anomalous Hall effect (AHE) observed in samples with both "metallic" and activated types of conductivity up to ~100 K. AHE is most pronounced in the temperature range where the resistance maximum is observed, and decreases with decreasing temperature. The results are discussed in terms of interaction of 2D-holes and magnetic Mn ions in presence of large-scale potential fluctuations related to random distribution of Mn atoms. The AHE values are compared with calculations taking into account its "intrinsic" mechanism in ferromagnetic systems.Comment: 15 pages, 9 figure

Painleve equations from Darboux chains - Part 1: P3-P5

We show that the Painleve equations P3-P5 can be derived (in a unified way) from a periodic sequence of Darboux transformations for a Schrodinger problem with quadratic eigenvalue dependency. The general problem naturally divides into three different branches, each described by an infinite chain of equations. The Painleve equations are obtained by closing the chain periodically at the lowest nontrivial level(s). The chains provide ``symmetric forms'' for the Painleve equations, from which Hirota bilinear forms and Lax pairs are derived. In this paper (Part 1) we analyze in detail the cases P3-P5, while P6 will be studied in Part 2.Comment: 23 pages, 1 reference added + minor change

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF &lt;5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants