Evaluation of E-Learning Lessons for Strengthening Early Childhood Practitioner Use of Family Capacity-Building Practices

Findings from a case study field-test evaluation of e-learning lessons for promoting early childhood intervention practitioners’ understanding and use of family capacity-building practices are described. Participants were two early childhood program directors, two early childhood technical assistance providers, and two early childhood intervention practitioners. Pattern matching was used to evaluate whether or not participants with different roles and responsibilities judged the instructional design, interactivity, video illustrations, and usefulness of the e-learning lessons similarly or differently. Results indicated that the different features of the e-learning lessons were rated highly by all but one participant and that the patterns of responses were much the same regardless of participants’ professional roles or responsibilities. Participant feedback and suggestions were used to revise the e-learning lessons and correct technical problems

Adult height and risk of 50 diseases : a combined epidemiological and genetic analysis

Funding FYL and SEH are funded by the National Institute for Health Research Leicester Biomedical Research Centre. CPN and NJS are funded by the British Heart Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Availability of data and materials The data reported in this paper are available via application directly to the UK Biobank.Peer reviewedPublisher PD

Remotely acting SMCHD1 gene regulatory elements: in silico prediction and identification of potential regulatory variants in patients with FSHD

Background: Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of the D4Z4 macro-satellite repeat on chromosome 4q35 (FSHD1) or mutations in the SMCHD1 gene (FSHD2). Recent studies have shown that the clinical manifestation of FSHD1 can be modified by mutations in the SMCHD1 gene within a given family. The absence of either D4Z4 contraction or SMCHD1 mutations in a small cohort of patients suggests that the disease could also be due to disruption of gene regulation. In this study, we postulated that mutations responsible for exerting a modifier effect on FSHD might reside within remotely acting regulatory elements that have the potential to interact at a distance with their cognate gene promoter via chromatin looping. To explore this postulate, genome-wide Hi-C data were used to identify genomic fragments displaying the strongest interaction with the SMCHD1 gene. These fragments were then narrowed down to shorter regions using ENCODE and FANTOM data on transcription factor binding sites and epigenetic marks characteristic of promoters, enhancers and silencers

Synthesis of ZnO nanocrystals by subsequent implantation of Zn and O species

We report the preparation of ZnO nanocrystals embedded in a SiO2 matrix formed using sequential zinc and oxygen ion implantations. The optical absorption spectra and photoemission spectra of zinc implanted and zinc/oxygen coimplanted silica show that the first zinc implantation produces zinc clusters and that the subsequent oxygen implantation following the zinc implantation rearranges the distribution of zinc and oxygen ions at an atomic level. While thermal annealing of Zn only implanted silica leads to the formation of Zn nanocrystals, thermal annealing of zinc/oxygen coimplanted silica promotes the growth of ZnO nanocrystals. The absorption and photoluminescence spectra show that ZnO nanocrystals form in an amorphous SiO2 matrix and that their systematic change as a function of annealing temperature corresponds to the typical correlation between the increase of particle size and a redshift in near-band-edge emission.Peer reviewedMechanical and Aerospace Engineerin

Parameter uncertainty and sensitivity in a liquid-effluent dose model

Radioactive materials which are released into streams on the Savannah River Site (SRS) eventually flow into the Savannah River. Tritium, 90 Sr, 137 Cs, and 239 Pu account for the majority of the radiation dose received by users of the Savannah River. This paper focuses on the dose uncertainties originating from variability in parameters describing the transport and uptake of these nuclides. Parameter sensitivity has also been determined for each liquid pathway exposure model. The models used here to estimate radiation dose to an exposed individual provide a range of possible dose estimates that span approximately one order of magnitude. A pathway analysis reveals that aquatic food and water consumption account for more than 95% of the total dose to an individual.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42692/1/10661_2004_Article_BF00547126.pd

Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions

INTRODUCTION: Bicuspid aortic valve (BAV) affects 1% of the general population. NOTCH1 was the first gene associated with BAV. The proportion of familial and sporadic BAV disease attributed to NOTCH1 mutations has not been estimated. AIM: The aim of our study was to provide an estimate of familial and sporadic BAV disease attributable to NOTCH1 mutations. METHODS: The population of our study consisted of participants of the University of Leicester Bicuspid aoRtic vAlVe gEnetic research-8 pedigrees with multiple affected family members and 381 sporadic patients. All subjects underwent NOTCH1 sequencing. A systematic literature search was performed in the NCBI PubMed database to identify publications reporting NOTCH1 sequencing in context of congenital heart disease. RESULTS: NOTCH1 sequencing in 36 subjects from 8 pedigrees identified one variant c.873C>G/p.Tyr291* meeting the American College of Medical Genetics and Genomics criteria for pathogenicity. No pathogenic or likely pathogenic NOTCH1 variants were identified in 381 sporadic patients. Literature review identified 64 relevant publication reporting NOTCH1 sequencing in 528 pedigrees and 9449 sporadic subjects. After excluding families with syndromic disease pathogenic and likely pathogenic NOTCH1 variants were detected in 9/435 (2.1%; 95% CI: 0.7% to 3.4%) of pedigrees and between 0.05% (95% CI: 0.005% to 0.10%) and 0.08% (95% CI: 0.02% to 0.13%) of sporadic patients. Incomplete penetrance of definitely pathogenic NOTCH1 mutations was observed in almost half of reported pedigrees. CONCLUSIONS: Pathogenic and likely pathogenic NOTCH1 genetic variants explain 2% of familial and <0.1% of sporadic BAV disease and are more likely to associate with tetralogy of Fallot and hypoplastic left heart

Variational methods

International audienceThis contribution presents derivative-based methods for local sensitivity analysis, called Variational Sensitivity Analysis (VSA). If one defines an output called the response function, its sensitivity to inputs variations around a nominal value can be studied using derivative (gradient) information. The main issue of VSA is then to provide an efficient way of computing gradients. This contribution first presents the theoretical grounds of VSA: framework and problem statement, tangent and adjoint methods. Then it covers pratical means to compute derivatives, from naive to more sophisticated approaches, discussing their various 2 merits. Finally, applications of VSA are reviewed and some examples are presented, covering various applications fields: oceanography, glaciology, meteorology

AMS 3.0: prediction of post-translational modifications

<p>Abstract</p> <p>Background</p> <p>We present here the recent update of AMS algorithm for identification of post-translational modification (PTM) sites in proteins based only on sequence information, using artificial neural network (ANN) method. The query protein sequence is dissected into overlapping short sequence segments. Ten different physicochemical features describe each amino acid; therefore nine residues long segment is represented as a point in a 90 dimensional space. The database of sequence segments with confirmed by experiments post-translational modification sites are used for training a set of ANNs.</p> <p>Results</p> <p>The efficiency of the classification for each type of modification and the prediction power of the method is estimated here using recall (sensitivity), precision values, the area under receiver operating characteristic (ROC) curves and leave-one-out tests (LOOCV). The significant differences in the performance for differently optimized neural networks are observed, yet the AMS 3.0 tool integrates those heterogeneous classification schemes into the single consensus scheme, and it is able to boost the precision and recall values independent of a PTM type in comparison with the currently available state-of-the art methods.</p> <p>Conclusions</p> <p>The standalone version of AMS 3.0 presents an efficient way to indentify post-translational modifications for whole proteomes. The training datasets, precompiled binaries for AMS 3.0 tool and the source code are available at <url>http://code.google.com/p/automotifserver</url> under the Apache 2.0 license scheme.</p

Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS

BRCA2 gene mutations in families with aggregations of breast and stomach cancers

Stomach cancer ranks second to lung cancer in the global cancer burden. It is estimated that 25% of families meeting the criteria for hereditary diffuse gastric carcinoma (HDCG) will have germline mutations in the E-cadherin gene. Evidence suggests that stomach cancer might also be a malignant manifestation of other inherited predispositions to disease. Recently, it has been reported that the incidence of stomach cancer is significantly increased in BRCA2 gene mutation carriers. We analysed by direct sequencing the BRCA2 gene in 29 breast cancer patients derived from 29 families with an aggregation of at least one female breast cancer diagnosed before the age of 50 years and one male stomach cancer diagnosed before the age of 55 years. In all but one of these families at least one additional relative was also affected by a malignant tumour. We identified three frameshift mutations and three sequence variants – potentially missense mutations, in six unrelated patients representing 20.7% (six out of 29) of the families investigated. Our results confirm that BRCA2 gene mutations are also associated with familial aggregations of not only breast but also of stomach cancer. In comparison to the number of cancers expected in the study population compared to the general population there is an over-representation of several cancers with significant confidence intervals to suggest that the associations are real and not a selection artefact