Mid-term Evaluation of NGO Programmes Under EEA Grants 2009-2014

The EEA Financial Mechanism (2009-2014) have committed 160,4 million to support seventeen NGO Programmes in sixteen countries: Bulgaria, Croatia, Cyprus, the Czech Republic, Estonia, Greece, Hungary, Latvia, Lithuania, Malta, Poland, Portugal, Romania, the Slovak Republic, Slovenia and Spain. The overall objective of the EEA Grants NGO Programmes is strengthened civil society development and enhanced contribution to social justice, democracy and sustainable development in each of the beneficiary countries. As of 30 of June 2014, 957 projects in total of 53,793,561 have been supported mainly in the fields of democracy, citizen participation, human rights, social justice and empowerment, sustainable development and provision of basic welfare services. The mid-term evaluation of the NGO Programmes funded by the EEA Financial Mechanism (2009- 2014) is an independent formative evaluation. Its objective was two-fold: 1) to assess the progress and needs for improvement of the current Programmes, and 2) to inform policies for the next financial period. The main purpose of this evaluation was to provide an expert independent mid-term assessment of the contribution of the EEA Grants 2009-2014 to the NGO sectors in the beneficiary states operating NGO Programmes. The evaluation was of dual nature: (1) of a formative evaluation to identify progress and needs for improvement of the current Programmes and (2) of a forward oriented strategic review to inform policies for the next financial period

Mineralization Potential of Polarized Dental Enamel

Background: Management of human teeth has moved from a surgical to a more conservative approach of inhibiting or preventing lesion progression. Increasing enamel mineralization is crucial in this regard. A potential difficulty is the preferential mineralization of the outermost portion of the enamel that can prevent overall mineralization. We describe a strategy for increasing the mineralization potential of dental enamel. Methodology/Principal Findings: Extracted human premolar teeth enamel (n = 5) were exposed to a high concentration of hydrogen peroxide with an energizing source. Samples were stored in artificial saliva at 37uC for 1 wk. A desktop X-ray micro-CT system was used to evaluate the mineral density of samples. Mineral distribution was polarized between the lower and the higher mineralized portion of enamel by charged oxygen free radicals due to activation of permeated hydrogen peroxide. The kinetics of energy absorption in the deeper enamel region demonstrated improvement of preferential mineralization into the region without restricting overall mineralization of the enamel. Subsequent increasing mineralization, even in the dense mineralized outer portion of enamel, was also achieved. Conclusions/Significance: This increased mineralization may promote resistance to acidic deterioration of the structure. The present study is one of the primary steps towards the development of novel application in reparative and restorativ

Spectroscopy and 2.1 µm laser operation of Czochralski-grown Tm3+:YScO3 crystals

We report on growth, temperature-dependent spectroscopy, and laser experiments of Tm3+-doped YScO3 mixed sesquioxide crystals. For the first time, cm3-scale laser quality Tm3+:YScO3 crystals with 2.2 at.% and 3.1 at.% doping levels were grown by the Czochralski method from iridium crucibles. We reveal that the structural disorder in the mixed crystals allows for broad and smooth spectral features even at cryogenic temperatures. We obtained the first continuous wave laser operation in this material at wavelengths around 2100 nm using a laser diode emitting at 780 nm as a pump source. A maximum slope efficiency of 45% was achieved using a Tm3 + (3.1 at.%):YScO3 crystal. Our findings demonstrate the high potential of Tm3+-doped mixed sesquioxides for efficient ultrafast pulse generation in the 2.1 µm range

A plasma telomeric cell-free DNA level in unaffected women with BRCA1 or/and BRCA2 mutations: a pilot study

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls of 28 healthy women. The results showed that the plasma telomeric cfDNA level was lower in unaffected BRCA1&2 mutation carriers than in age-matched controls from non-obese women (BMI 30). Moreover, the plasma telomeric cfDNA level applied aptly to the Tyrer-Cuzick model in non-obese women. These findings suggest that circulating cfDNA may detect dysfunctional telomeres derived from cells with BRCA1&2 mutations and, therefore, its level is associated with breast cancer susceptibility. This pilot study warrants further investigation to elucidate the implication of plasma telomeric cfDNA levels in relation to cancer and obesity

Association Between Hypocholesterolemia and Mortality in Critically Ill Patients With Sepsis: A Systematic Review and Meta-Analysis

OBJECTIVE: To ascertain the association between cholesterol and triglyceride levels on ICU admission and mortality in patients with sepsis. DATA SOURCES: Systematic review and meta-analysis of published studies on PubMed and Embase. STUDY SELECTION: All observational studies reporting ICU admission cholesterol and triglyceride levels in critically ill patients with sepsis were included. Authors were contacted for further data. DATA EXTRACTION: Eighteen observational studies were identified, including 1,283 patients with a crude overall mortality of 33.3%. Data were assessed using Revman (Version 5.1, Cochrane Collaboration, Oxford, United Kingdom) and presented as mean difference (MD) with 95% CIs, p values, and I2 values. DATA SYNTHESIS: Admission levels of total cholesterol (17 studies, 1,204 patients; MD = 0.52 mmol/L [0.27–0.77 mmol/L]; p < 0.001; I2 = 91%), high-density lipoprotein (HDL)-cholesterol (14 studies, 991 patients; MD = 0.08 mmol/L [0.01–0.15 mmol/L]; p = 0.02; I2 = 61%), and low-density lipoprotein (LDL) cholesterol (15 studies, 1,017 patients; MD = 0.18 mmol/L [0.04–0.32 mmol/L]; p = 0.01; I2 = 71%) were significantly lower in eventual nonsurvivors compared with survivors. No association was seen between admission triglyceride levels and mortality (15 studies, 1,070 patients; MD = 0.00 mmol/L [–0.16 to 0.15 mmol/L]; p = –0.95; I2 = 79%). CONCLUSIONS: Mortality was associated with lower levels of total cholesterol, HDL-cholesterol, and LDL-cholesterol, but not triglyceride levels, in patients admitted to ICU with sepsis. The impact of cholesterol replacement on patient outcomes in sepsis, particularly in at-risk groups, merits investigation. KEYWORDS: cholesterol levels; intensive care unit; lipids; sepsis; triglyceride

Effects of the stellar wind on X-ray spectra of Cygnus X-3

We study X-ray spectra of Cyg X-3 from BeppoSAX, taking into account absorption and emission in the strong stellar wind of its companion. We find the intrinsic X-ray spectra are well modelled by disc blackbody emission, its upscattering by hot electrons with a hybrid distribution, and by Compton reflection. These spectra are strongly modified by absorption and reprocessing in the stellar wind, which we model using the photoionization code cloudy. The form of the observed spectra implies the wind is composed of two phases. A hot tenuous plasma containing most of the wind mass is required to account for the observed features of very strongly ionized Fe. Small dense cool clumps filling <0.01 of the volume are required to absorb the soft X-ray excess, which is emitted by the hot phase but not present in the data. The total mass-loss rate is found to be (0.6--1.6) x 10^-5 solar masses per year. We also discuss the feasibility of the continuum model dominated by Compton reflection, which we find to best describe our data. The intrinsic luminosities of our models suggest that the compact object is a black hole.Comment: MNRAS, in pres

Racial differences in cumulative disadvantage among women and its relation to health: Development and preliminary validation of the CSI-WE

Background: Cumulative disadvantage (CD) is a measure of accumulated social, economic, and person-related stressors due to unequal access to resources and opportunities, which increases a person's biological risk for disease. The purpose of this research was to develop an instrument tailored to women's experiences that had intervention and translational potential. In addition, we explored whether CD contributed to racial health disparities among black and white women. Methods: In-depth life course interviews were used to assess stressful experiences of 15 black and 15 white women. Using information from the interviews, we developed the Cumulative Stress Inventory of Women's Experiences (CSI-WE) as a quantitative instrument to measure stressful life experiences from childhood to adulthood. The CSI-WE was then administered to the original 30 women for validation and feedback. Results: Qualitative and quantitative assessments were highly correlated, which suggested that the CSI-WE reliably captured the experiences of the interviewed women. Black participants reported significantly higher numbers of childhood and adult stressors, more acute adulthood and lifetime stressors, and worse adult physical self-rated health. Conclusions: This study supports the preliminary validity of an instrument that once fully validated may be used in future studies to elucidate the experiences of CD among black and white women and examines how these experiences relate to perceived and objective health status

Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy

Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy. Using proteomic and cellular approaches, we show that upon translocation to mitochondria, Parkin activates the ubiquitin–proteasome system (UPS) for widespread degradation of outer membrane proteins. This is evidenced by an increase in K48-linked polyubiquitin on mitochondria, recruitment of the 26S proteasome and rapid degradation of multiple outer membrane proteins. The degradation of proteins by the UPS occurs independently of the autophagy pathway, and inhibition of the 26S proteasome completely abrogates Parkin-mediated mitophagy in HeLa, SH-SY5Y and mouse cells. Although the mitofusins Mfn1 and Mfn2 are rapid degradation targets of Parkin, we find that degradation of additional targets is essential for mitophagy. These results indicate that remodeling of the mitochondrial outer membrane proteome is important for mitophagy, and reveal a causal link between the UPS and autophagy, the major pathways for degradation of intracellular substrates

Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster

A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (&lt;5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (&lt;5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P &lt; 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P &lt; 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect