Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease.

Inherited pheochromocytomas are often part of familial syndromes, especially multiple endocrine neoplasia type 2 (MEN 2), retinal cerebellar hemangioblastomatosis [von Hippel-Lindau (vHL) disease] or neurofibromatosis type 1. It is not clear whether isolated familial pheochromocytoma exists as a separate clinical entity. In a family with pheochromocytomas in three generations and with at least seven affected members, we investigated by clinical and genetic analyses the presence or absence of associated conditions. The clinical investigations included ophthalmological and radiological studies for von Hippel-Lindau disease (magnetic resonance imaging of the brain, computed tomography of the abdomen, and direct ophthalmoscopy after mydriasis) and annual calcitonin stimulation tests for C cell disease in five members who agreed to regular follow-up. Besides the pheochromocytomas (so far, these have been multiple in five of seven individuals) no definite second associated condition was found. Genetic analysis did not identify any MEN 2-specific RET protooncogene point mutations (which are present in 97% of MEN 2a families). However, despite the complete absence of other clinical manifestations of the vHL disease (besides pheochromocytomas), a previously undescribed germline missense mutation in the vHL tumor suppressor gene was found (C775G transversion with a predicted substitution of a leucine by a valine at codon 259 in the putative vHL protein). We conclude that in this family the sole occurrence of pheochromocytoma is a variant of vHL disease

Investigating the Machinability of Al-Si-Cu cast alloy containing bismuth and antimony using coated carbide insert

Surface roughness and cutting force are two key measures that describe machined surface integrity and power requirement evaluation, respectively. This investigation presents the effect of melt treatment with addition of bismuth and antimony on machinability when turning Al-11 Si-2 Cu alloy. The experiments are carried out under oblique dry cutting conditions using a PVD TIN-coated insert at three cutting speeds of 70, 130 and 250 m/min, feed rates of 0.05, 0.1, 0.15 mm/rev, and 0.05 mm constant depth of cut. It was found that the Bi-containing workpiece possess the best surface roughness value and lowest cutting force due to formation of pure Bi which plays an important role as a lubricant in turning process, while Sb-containing workpiece produced the highest cutting force and highest surface roughness value. Additionally, change of silicon morphology from flake-like to lamellar structure changed value of cutting force and surface roughness during turning. (C) 2014 Elsevier Ltd. All rights reserved

The closest elastic tensor of arbitrary symmetry to an elasticity tensor of lower symmetry

The closest tensors of higher symmetry classes are derived in explicit form for a given elasticity tensor of arbitrary symmetry. The mathematical problem is to minimize the elastic length or distance between the given tensor and the closest elasticity tensor of the specified symmetry. Solutions are presented for three distance functions, with particular attention to the Riemannian and log-Euclidean distances. These yield solutions that are invariant under inversion, i.e., the same whether elastic stiffness or compliance are considered. The Frobenius distance function, which corresponds to common notions of Euclidean length, is not invariant although it is simple to apply using projection operators. A complete description of the Euclidean projection method is presented. The three metrics are considered at a level of detail far greater than heretofore, as we develop the general framework to best fit a given set of moduli onto higher elastic symmetries. The procedures for finding the closest elasticity tensor are illustrated by application to a set of 21 moduli with no underlying symmetry.Comment: 48 pages, 1 figur

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Increasing the productivity of the wire-cut electrical discharge machine associated with sustainable production

Wire-cut electric discharge machining is a nontraditional technique by which the required profile is acquired using sparks energy. Concerning wire-cut electric discharge machining, high cutting rates and precision machining is necessary to improve productivity and achieve high quality of machined workpieces. In this research work, an experimental investigation was introduced to achieve higher productivity of the wire electrode associated with sustainable production in terms of product quality and less heat-affected zone. For this purpose, the effects of machining parameters including peak current, pulse on time and wire preloading were investigated using adaptive neuro-fuzzy inference system along with the Taguchi method. From this study, the optimal setting of machining parameters to achieve higher productivity and sustainability was identified. Moreover, Neuro-fuzzy modeling was successfully used to build an empirical model for the selection of machining parameters to achieve higher productivity at highest possible surface quality and minimum cost for sustainable production. (C) 2015 Elsevier Ltd. All rights reserved