Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera

Background: Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. Results: We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients. The 12 shared variants (maximum allowed minor allele frequency G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1, and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients. Somatic mutations in BCORL1 have been reported in myeloid malignancies. We further screened the variants in eight PV patients in six other Finnish families, but no other carriers were found. Conclusions: Exome sequencing provides a powerful tool for the identification of novel variants, and understanding the familial predisposition of diseases. This is the first report on Finnish familial PV cases, and we identified three novel candidate variants that may predispose to the disease.Peer reviewe

Efficient Heralding of Photonic Qubits with Apllications to Device Independent Quantum Key Distribution

We present an efficient way of heralding photonic qubit signals using linear optics devices. First we show that one can obtain asymptotically perfect heralding and unit success probability with growing resources. Second, we show that even using finite resources, we can improve qualitatively and quantitatively over earlier heralding results. In the latte r scenario, we can obtain perfect heralded photonic qubits while maintaining a finite success probability. We demonstrate the advantage of our heralding scheme by predicting key rates for device independent quantum key distribution, taking imperfections of sources and detectors into account

Регіональні й глобальні наслідки незалежності Косово

У статті розглянуто регіональні й міжнародні аспекти проголошення незалежності Косово. Проаналізовано конфліктні аспекти косовської проблеми у регіональному й глобальному контекстах.В статье рассматриваются региональные и международные аспекты провозглашения независимости Косово. Проанализировано конфликтные аспекты косовской проблемы в региональном и глобальном контекстах.The article presents the regional and international aspects of Kosovo Independents. Special attention is to the conflict of Kosovo in the regional and global context

Surface Water Intrusion, Land Use Impacts, and Bacterial Community Composition in Shallow Groundwater Wells Supplying Potable Water in Sparsely Populated Areas of a Boreal Region

Rural communities often rely on groundwater for potable water supply. In this study, untreated groundwater samples from 28 shallow groundwater wells in Finland ( IMPORTANCE Standard physicochemical water quality analyses and microbial indicator analyses leave much of the (largely uncultured) complexity of groundwater microbial communities unexplored. This study combined these standard methods with additional analyses of stable water isotopes, bacterial community data, and environmental data about the surrounding areas to investigate the associations between physicochemical and microbial properties of 28 shallow groundwater wells in Finland. We detected impaired groundwater quality in some wells, identified potential land use impacts, and revealed indications of surface water intrusion which were negatively correlated with bacterial alpha diversity. The potential influence of surface water intrusion on groundwater wells and their bacterial communities is of particular interest and warrants further investigation because surface water intrusion has previously been linked to groundwater contamination, which is the primary cause of waterborne outbreaks in the Nordic region and one of the major causes in the United States and Canada.Peer reviewe

Ab initio study of the surface properties of austenitic stainless steel alloys

Using ab initio calculations we investigated the surface energies of paramagnetic Fe1-c-nCrcNin random alloys within the concentration range of 0.12 <= c <= 032 and 0.04 <= n <= 0.32. These alloys crystallize mainly in the face centred cubic (fcc) structure and constitute the main building blocks of austenitic stainless steels. It is shown that all alloys have the lowest surface energies along the most close packed crystal orientation, namely the fcc (111) surfaces. The amount of Ni seems to have little effect on the surface energy, while almost all composition-driven change may be attributed to the changes in the Cr content. Within the studied compositional range, the change of the surface energy with the composition is of the order of 10%. Trends of the surface energy can be related to the magnetic structure of surfaces. Using the total energy as a function of the concentration, we determine the effective chemical potentials in bulk and at the surface, which can be used to estimate the surface segregation energies. (C) 2012 Elsevier B.V. All rights reserved

Long-term outcome after treatment of pulmonary atresia with ventricular septal defect : nationwide study of 109 patients born in 1970-2007

OBJECTIVES: Treatment of pulmonary atresia with ventricular septal defect (PA + VSD) has evolved during recent decades, but it still remains challenging. This study evaluated 41-year experience of outcome, survival and treatment of PA + VSD patients. METHODS: Patient records and angiograms of 109 patients with PA + VSD born in Finland between 1970 and 2007, and treated at the Children's Hospital, Helsinki University Central Hospital, were retrospectively analysed in this nationwide study. RESULTS: Of the 109 patients, 66 (61%) had simple PA + VSD without major aortopulmonary collateral arteries (MAPCAs). Although we observed no difference in overall survival between those with or without MAPCAs, the patients without MAPCAs had better probability to achieve repair (64 vs 28%, P <0.0003). Only 3 patients were treated by compassionate care. Overall survival was affected by the size of true central pulmonary arteries on the first angiogram (P = 0.001) and whether repair was achieved (P <0.0001). After successful repair, the survival rate was 93% at 1 year, 91% from the second year, and functional capacity as assessed by New York Heart Association (NYHA) I-II remained in 85% of patients alive at the end of follow-up. Palliated patients at 1, 5, 10 and 20 years of age had Kaplan-Meier estimated survival rates of 55, 42, 34 and 20%, respectively. Patients who underwent repair attempts but were left palliated with right ventricle (RV)-pulmonary artery connection and septal fenestration had better survival than the rest of the palliated patients (P = 0.001). Further, the McGoon index improved after implementation of a systemic-pulmonary artery shunt in the overall PA + VSD population (P <0.0001). CONCLUSIONS: These findings show that achievement of repair and initial size of true central pulmonary arteries affect survival of patients with PA + VSD. Although the overall survival of patients with MAPCAs showed no difference compared with simple PA + VSD patients, they had a higher risk of remaining palliated. However, palliative surgery may have a role in treatment of PA + VSD because the size of pulmonary arteries increased after placement of systemic-pulmonary artery shunt. In addition, subtotal repair by a RV-pulmonary artery connection and septal fenestration improved survival over extracardiac palliation.Peer reviewe

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations