Novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like macular dystrophy

Journal ArticlePURPOSE. To conduct clinical and genetic studies in a European family with autosomal dominant Stargardt-like macular dystrophy (adSTGD-like MD) and to investigate the functional consequences of a novel ELOVL4 mutatio

Effect of Ru susbstitution on atomic displacements in the layered SmFe_{1-x}Ru_xAsO_{0.85}F_{0.15} superconductor

The effect of Ru substitution on the local structure of layered SmFe$_{1-x}$Ru$_x$AsO$_{0.85}$F$_{0.15}$ superconductor has been studied by As $K$- and Sm $L_3$ - edges x-ray-absorption spectroscopy. The extended x-ray-absorption fine-structure measurements reveal distinct Fe-As and Ru-As bondlengths in the Ru substituted samples with the latter being $\sim$0.03 \AA\ longer. Local disorder induced by the Ru substitution is mainly confined to the FeAs layer while the SmO spacer layer sustains a relative order, consistent with the x-ray-absorption near-edge structure spectra. The results suggest that, in addition to the order/disorder in the active active iron-arsenide layer, its coupling to the rare-earth\textminus oxygen spacer layer needs to be considered for describing the electronic properties of these layered superconductors

DAPK1 Promoter Methylation and Cervical Cancer Risk: A Systematic Review and a Meta-Analysis.

Objective: The Death-Associated Protein Kinase 1 (DAPK1) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. Methods A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. Results: A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14–40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83–36.78). The association was also confirmed in all the subgroups analyses. Conclusions: A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus

Clinical and experimental evidences on the prothrombotic properties of neutrophils

Epidemiologic studies have shown that the neutrophil count correlates with the risk of myocardial infarction and stroke and identify patients more susceptible to reinfarction and in-hospital death. In particular, neutrophils action was initially associated to blood rheological changes, or to the effect of neutrophil-derived eicosanoids or proteases. Animal models indicate that platelet-leukocyte P-selectin dependent cross-talk contributes to fibrin deposition during in vivo thrombus formation. In fact, platelet P-selectin, through its leukocyte counter-receptor PSGL-1, determines the activation of leukocyte ?2 integrins, the binding of fibrinogen and the expression of tissue factor on leukocyte surface. Monocytes stimulated in vitro with LPS, PMA and P-selectin synthesize and express tissue factor. fMLP, P-selectin, TNFalpha and C5a are effective stimuli that trigger the synthesis and expression of biologically active tissue factor in neutrophils. The experimental evidence well agrees with clinical observations: patients with acute coronary syndromes, acute respiratory distress syndrome, antiphospholipid syndromes, giant cell arteritis and myeloproliferative syndromes have increased the expression of tissue factor on leukocyte surface. Moreover circulating neutrophils express mRNA codifying for fulllength and/or alternatively spliced tissue factor, suggesting a new important link between thrombosis and inflammation. All together, clinical and experimental evidence suggest that the leukocyte thrombogenic profile is a relevant player in patients with a high risk of thromboembolic events and possibly represents a suitable target for molecular intervention

Variability of orographic enhancement of precipitation in the Alpine region

Climate change impacts are non uniformly distributed over the globe. Mountains have a peculiar response to large scale variations, documented by elevation gradients of surface temperature increase observed over many mountain ranges in the last decades. Significant changes of precipitation are expected in the changing climate and orographic effects are important in determining the amount of rainfall at a given location. It thus becomes particularly important to understand how orographic precipitation responds to global warming and to anthropogenic forcing. Here, using a large rain gauge dataset over the European Alpine region, we show that the distribution of annual precipitation among the lowlands and the mountains has varied over time, with an increase of the precipitation at the high elevations compared to the low elevations starting in the mid 20 century and peaking in the 1980s. The simultaneous increase and peak of anthropogenic aerosol load is discussed as a possible source for this interdecadal change. These results provide new insights to further our understanding and improve predictions of anthropic effects on mountain precipitations, which are fundamental for water security and management

A multi-century meteo-hydrological analysis for the Adda river basin (Central Alps). Part I: Gridded monthly precipitation (1800–2016) records

The 1800–2016 monthly precipitation record for the upper Adda river basin is presented. It is computed by applying the anomaly method to a quality-checked and homogenized observation database. The reconstruction accuracy and its evolution over the study period is evaluated at both station and grid-cell levels. The anomaly-based interpolation provides rather robust estimates even for the early years of sparse station coverage with basin precipitation reconstruction errors around 10%. The Theil-Sen trend analysis on the basin precipitation series shows significant (Mann-Kendall p value <.05) long-term tendencies of −3.8 ± 1.9% and −9.3 ± 3.8% century−1 for annual and autumn precipitation, respectively, even though the annual trend is not significant by excluding the first decades from the evaluation. As the basin precipitation record is expected to be underestimated due to the rain-gauge snow undercatch, the monthly precipitation fields are subjected to a correction procedure which allows to derive the multiplicative correcting constant to be applied to the basin annual precipitation series. The comparison between 1845 and 2016 yearly corrected precipitation and runoff records highlights current annual water losses of about 400 mm while the annual runoff coefficients exhibit a long-term significant decrease of −6.4 ± 1.0% century−1. This change in the hydrological cycle is mostly to be ascribed to the strong long-term reduction in annual runoff values (−11.8 ± 3.2% century−1) driven by increasing evapotranspiration due to both temperature increase and, likely, land-use changes

High&#8208;resolution monthly precipitation climatologies over Norway (1981&#8211;2010): Joining numerical model data sets and in situ observations

The 1981-2010 monthly precipitation climatologies for Norway at 1 km resolution are presented. They are computed by an interpolation procedure (HCLIM+RK) combining the output from a numerical model with the in situ observations. Specifically, the regional climate model data set HCLIM-AROME, based on the dynamical downscaling of the global ERA-Interim reanalysis onto 2.5 km resolution, is considered together with 2009 rain-gauges located within the model domain. The precipitation climatologies are defined by superimposing the grid of 1981-2010 monthly normals from the numerical model and the kriging interpolation of station residuals. The combined approach aims at improving the quality of gridded climatologies and at providing reliable precipitation gradients also over those remote Norwegian regions not covered by observations, especially over the northernmost mountainous areas. The integration of rain-gauge data greatly reduces the original HCLIM-AROME biases. The HCLIM+RK errors obtained from the leave-one-out station validation turn out to be lower than those provided by two considered interpolation schemes based on observations only: a multi-linear local regression kriging (MLRK) and a local weighted linear regression (LWLR). As average over all months, the mean absolute (percentage) error is 10.0 mm (11%) for HCLIM+RK, and 11.4 (12%) and 11.6 mm (12%) for MLRK and LWLR, respectively. In addition, by comparing the results at both station and grid cell level, the accuracy of MLRK and LWLR is more sensitive to the spatial variability of station distribution over the domain and their interpolated fields are more affected by discontinuities and outliers, especially over those areas not covered by the rain-gauge network. The obtained HCLIM+RK climatologies clearly depict the main west-to-east gradient occurring from the orographic precipitation regime of the coast to the more continental climate of the inland and it allows to point out the features of the climatic subzones of Norway

Impasse in the management of recurrent basal cell carcinoma of the skull with sagittal sinus erosion1

Abstract Basal cell carcinoma (BCC) is a non melanocytic skin cancer that arises from basal cells, affecting commonly fair-skinned human beings. Although the tumor is well known for local recurrences, extension into the intracranial space is reported. A case of a giant BCC of the scalp invading the middle and posterior third of the superior sagittal sinus (SSS) is reported. A 70-year-old male with a basal cell carcinoma history presented with a massive bleeding from the SSS invaded by the tumor. Since the patient refused surgery the bleeding was managed through direct compression by applying a thrombin-based hemostatic agents and sterile dressings. This procedure was performed daily in order to stimulate the spontaneous thrombosis of the dural sinus and development of collateral circle. BCC invading the SSS is rarely reported. A technical description of this case is provided. This case underscores the importance of early and appropriate treatment for high risk BCC, and whenever surgical procedure is not suitable appropriate conservative treatment may be efficacious

Learning to be literate in Aboriginal communities: The significance of text

In Australia the model of reading outlined in many syllabus documents and the Australian National Curriculum: English acknowledges that reading is a socio-cultural practice and that both the contexts of culture and situation define the meanings individual students will make when approaching a given text. The difficulty of any given text therefore varies for individual students, depending not only on their skills but their understandings about the cultural context and the situation in which they encounter the text. Many students might find school a “natural setting” in which to learn, and may therefore be acquiring knowledge at school because their understandings about language and education predispose them to learning in such an environment. Many Aboriginal children however, do not find their understandings of language and culture reflected in the school environment. The purpose of this multi-site case study was to better understand the significance of authentic local texts in the teaching of reading in four Aboriginal communities. The project that formed the basis of this case study, was the development of the One Mob books community writers kit, aimed at creating local books in these four communities and involving teachers, community workers and members of the local community. The role of story for Aboriginal children and the importance of the local community in becoming literate were central features of the research findings. Under achievement in literacy was identified as a barrier to educational success in each context. Sharing local stories and language provided the Aboriginal communities with a positive way to interact with the school community, to engage their own and other children in their history and culture and to support their children’s literacy learning

The mobility of Atlantic baric depressions leading to intense precipitation over Italy: a preliminary statistical analysis

International audienceThe speed of Atlantic surface depressions, occurred during the autumn and winter seasons and that lead to intense precipitation over Italy from 1951 to 2000, was investigated. Italy was divided into 5 regions as documented in previous climatological studies (based on Principal Component Analysis). Intense precipitation events were selected on the basis of in situ rain gauge data and clustered according to the region that they hit. For each intense precipitation event we tried to identify an associated surface depression and we tracked it, within a large domain covering the Mediterranean and Atlantic regions, from its formation to cyclolysis in order to estimate its speed. "Depression speeds" were estimated with 6-h resolution and clustered into slow and non-slow classes by means of a threshold, coinciding with the first quartile of speed distribution and depression centre speeds were associated with their positions. Slow speeds occurring over an area including Italy and the western Mediterranean basin showed frequencies higher than 25%, for all the Italian regions but one. The probability of obtaining by chance the observed more than 25% success rate was estimated by means of a binomial distribution. The statistical reliability of the result is confirmed for only one region. For Italy as a whole, results were confirmed at 95% confidence level. Stability of the statistical inference, with respect to errors in estimating depression speed and changes in the threshold of slow depressions, was analysed and essentially confirmed the previous results