Identification of potentially pathogenic variants in candidate breast and ovarian cancer susceptibility genes in BRCAX patients

Mutations within the BRCA1 and BRCA2 genes account for approximately 20% of hereditary breast cancers, with a further 10%–15% being attributable to rare mutations in moderate-risk genes and common variants in low-risk genes. The genes harbouring mutations in the remaining ∼65% of hereditary breast cancers are unknown. The identification of mutation carriers in hereditary breast and ovarian cancer (hboc) families is critical for determining who is most at risk of developing the disease and therefore who should be offered risk-reducing procedures or more intensive screening, or both.

Many of the high- and moderate-risk genes for hereditary breast cancers encode proteins that work in concert to maintain genomic stability and in dna damage signalling and repair. A novel BRCA1 protein complex identified within the research group whose target genes are involved in dna repair provided novel candidates for hboc susceptibility genes. These 12 candidate genes were sequenced in a cohort of 675 affected individuals from the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) with hereditary breast or ovarian cancer, but with no mutations in known susceptibility genes (BRCAx patients). This analysis identified 20 individuals (each from a different BRCAx family) with different potentially pathogenic variants across 6 of the candidate hboc susceptibility genes. The family members of each BRCAx index case were tested for the presence of the specific mutation identified in the proband to examine segregation with disease. To further expand on the potential role of the novel candidate hboc susceptibility genes identified in this study, the genetic variation of a second cohort of 520 Northern Irish BRCAx patients is being characterized using a 61-gene panel.

Network analysis approach to find new candidate genes and pathways involved in the pathophysiology of familial hypercholesterolemia

Still a big gap exists between clinical and genetic diagnosis of dyslipidemic disorders. Almost the 60% of the patients with a clinical diagnosis of Familial hypercholesterolemia (FH) still lack of a genetic diagnosis. Here we present the preliminary results of an integrative approach intended to identify new candidate genes and to dissect pathways that can be dysregulated in the disease. Interesting hits will be subsequently knocked down in vitro in order to evaluate their functional role in the uptake of fluorescently-labeled LDL and free cell cholesterol using automated microscopy.

Redundancy gain : manifestations, causes and predictions

Les temps de réponse dans une tache de reconnaissance d’objets visuels diminuent de façon significative lorsque les cibles peuvent être distinguées à partir de deux attributs redondants. Le gain de redondance pour deux attributs est un résultat commun dans la littérature, mais un gain causé par trois attributs redondants n’a été observé que lorsque ces trois attributs venaient de trois modalités différentes (tactile, auditive et visuelle). La présente étude démontre que le gain de redondance pour trois attributs de la même modalité est effectivement possible. Elle inclut aussi une investigation plus détaillée des caractéristiques du gain de redondance. Celles-ci incluent, outre la diminution des temps de réponse, une diminution des temps de réponses minimaux particulièrement et une augmentation de la symétrie de la distribution des temps de réponse. Cette étude présente des indices que ni les modèles de course, ni les modèles de coactivation ne sont en mesure d’expliquer l’ensemble des caractéristiques du gain de redondance. Dans ce contexte, nous introduisons une nouvelle méthode pour évaluer le triple gain de redondance basée sur la performance des cibles doublement redondantes. Le modèle de cascade est présenté afin d’expliquer les résultats de cette étude. Ce modèle comporte plusieurs voies de traitement qui sont déclenchées par une cascade d’activations avant de satisfaire un seul critère de décision. Il offre une approche homogène aux recherches antérieures sur le gain de redondance. L’analyse des caractéristiques des distributions de temps de réponse, soit leur moyenne, leur symétrie, leur décalage ou leur étendue, est un outil essentiel pour cette étude. Il était important de trouver un test statistique capable de refléter les différences au niveau de toutes ces caractéristiques. Nous abordons la problématique d’analyser les temps de réponse sans perte d’information, ainsi que l’insuffisance des méthodes d’analyse communes dans ce contexte, comme grouper les temps de réponses de plusieurs participants (e. g. Vincentizing). Les tests de distributions, le plus connu étant le test de Kolmogorov- Smirnoff, constituent une meilleure alternative pour comparer des distributions, celles des temps de réponse en particulier. Un test encore inconnu en psychologie est introduit : le test d’Anderson-Darling à deux échantillons. Les deux tests sont comparés, et puis nous présentons des indices concluants démontrant la puissance du test d’Anderson-Darling : en comparant des distributions qui varient seulement au niveau de (1) leur décalage, (2) leur étendue, (3) leur symétrie, ou (4) leurs extrémités, nous pouvons affirmer que le test d’Anderson-Darling reconnait mieux les différences. De plus, le test d’Anderson-Darling a un taux d’erreur de type I qui correspond exactement à l’alpha tandis que le test de Kolmogorov-Smirnoff est trop conservateur. En conséquence, le test d’Anderson-Darling nécessite moins de données pour atteindre une puissance statistique suffisante.

A genomewide association mapping study using ultrasound-scanned information identifies potential genomic regions and candidate genes affecting carcass traits in Nellore cattle

The aim of this study was to identify candidate genes and genomic regions associated with ultrasound-derived measurements of the rib-eye area (REA), backfat thickness (BFT) and rumpfat thickness (RFT) in Nellore cattle. Data from 640 Nellore steers and young bulls with genotypes for 290 863 single nucleotide polymorphisms (SNPs) were used for genomewide association mapping. Significant SNP associations were explored to find possible candidate genes related to physiological processes. Several of the significant markers detected were mapped onto functional candidate genes including ARFGAP3, CLSTN2 and DPYD for REA; OSBPL3 and SUDS3 for BFT; and RARRES1 and VEPH1 for RFT. The physiological pathway related to lipid metabolism (CLSTN2, OSBPL3, RARRES1 and VEPH1) was identified. The significant markers within previously reported QTLs reinforce the importance of the genomic regions, and the other loci offer candidate genes that have not been related to carcass traits in previous investigations.

Reliability, construct and criterion validity of the KIDSCREEN-10 score: a short measure for children and adolescents' well-being and health-related quality of life

Background To assess the criterion and construct validity of the KIDSCREEN-10 well-being and health-related quality of life (HRQoL) score, a short version of the KIDSCREEN-52 and KIDSCREEN-27 instruments. Methods The child self-report and parent report versions of the KIDSCREEN-10 were tested in a sample of 22,830 European children and adolescents aged 8–18 and their parents (n = 16,237). Correlation with the KIDSCREEN-52 and associations with other generic HRQoL measures, physical and mental health, and socioeconomic status were examined. Score differences by age, gender, and country were investigated. Results Correlations between the 10-item KIDSCREEN score and KIDSCREEN-52 scales ranged from r = 0.24 to 0.72 (r = 0.27–0.72) for the self-report version (proxy-report version). Coefficients below r = 0.5 were observed for the KIDSCREEN-52 dimensions Financial Resources and Being Bullied only. Cronbach alpha was 0.82 (0.78), test–retest reliability was ICC = 0.70 (0.67) for the self- (proxy-)report version. Correlations between other children self-completed HRQoL questionnaires and KIDSCREEN-10 ranged from r = 0.43 to r = 0.63 for the KIDSCREEN children self-report and r = 0.22–0.40 for the KIDSCREEN parent proxy report. Known group differences in HRQoL between physically/mentally healthy and ill children were observed in the KIDSCREEN-10 self and proxy scores. Associations with self-reported psychosomatic complaints were r = −0.52 (−0.36) for the KIDSCREEN-10 self-report (proxy-report). Statistically significant differences in KIDSCREEN-10 self and proxy scores were found by socioeconomic status, age, and gender. Conclusions Our results indicate that the KIDSCREEN-10 provides a valid measure of a general HRQoL factor in children and adolescents, but the instrument does not represent well most of the single dimensions of the original KIDSCREEN-52. Test–retest reliability was slightly below a priori defined thresholds.

Optimizing the creation of base populations for aquaculture breeding programs using phenotypic and genomic data and its consequences on genetic progress

The success of an aquaculture breeding program critically depends on the way in which the base population of breeders is constructed since all the genetic variability for the traits included originally in the breeding goal as well as those to be included in the future is contained in the initial founders. Traditionally, base populations were created from a number of wild strains by sampling equal numbers from each strain. However, for some aquaculture species improved strains are already available and, therefore, mean phenotypic values for economically important traits can be used as a criterion to optimize the sampling when creating base populations. Also, the increasing availability of genome-wide genotype information in aquaculture species could help to refine the estimation of relationships within and between candidate strains and, thus, to optimize the percentage of individuals to be sampled from each strain. This study explores the advantages of using phenotypic and genome-wide information when constructing base populations for aquaculture breeding programs in terms of initial and subsequent trait performance and genetic diversity level. Results show that a compromise solution between diversity and performance can be found when creating base populations. Up to 6% higher levels of phenotypic performance can be achieved at the same level of global diversity in the base population by optimizing the selection of breeders instead of sampling equal numbers from each strain. The higher performance observed in the base population persisted during 10 generations of phenotypic selection applied in the subsequent breeding program.

Search for associations containing young stars (SACY). VII. New stellar and substellar candidate members in the young associations

Context. The young associations offer us one of the best opportunities to study the properties of young stellar and substellar objects and to directly image planets thanks to their proximity (<200 pc) and age (≈5−150 Myr). However, many previous works have been limited to identifying the brighter, more active members (≈1 M_⊙) owing to photometric survey sensitivities limiting the detections of lower mass objects. Aims. We search the field of view of 542 previously identified members of the young associations to identify wide or extremely wide (1000−100 000 au in physical separation) companions. Methods. We combined 2MASS near-infrared photometry (J, H, K) with proper motion values (from UCAC4, PPMXL, NOMAD) to identify companions in the field of view of known members. We collated further photometry and spectroscopy from the literature and conducted our own high-resolution spectroscopic observations for a subsample of candidate members. This complementary information allowed us to assess the efficiency of our method. Results. We identified 84 targets (45: 0.2−1.3 M_⊙, 17: 0.08−0.2 M_⊙, 22: <0.08 M_⊙) in our analysis, ten of which have been identified from spectroscopic analysis in previous young association works. For 33 of these 84, we were able to further assess their membership using a variety of properties (X-ray emission, UV excess, Hα, lithium and K I equivalent widths, radial velocities, and CaH indices). We derive a success rate of 76–88% for this technique based on the consistency of these properties. Conclusions. Once confirmed, the targets identified in this work would significantly improve our knowledge of the lower mass end of the young associations. Additionally, these targets would make an ideal new sample for the identification and study of planets around nearby young stars. Given the predicted substellar mass of the majority of these new candidate members and their proximity, high-contrast imaging techniques would facilitate the search for new low-mass planets.

Evaluating Water Temperature, Habitat and Fish Communities in Candidate Coolwater Streams in Illinois Annual Project Report 2010

Work during this reporting period focused on characterizing temperature, habitat, and biological communities at candidate coolwater sites. During the past year we have collected additional temperature data from 57 candidate streams and other locations and now have records from 232 stream reaches. Eighty-two sites in Illinois have been identified as cool- or coldwater based on these records. Physical habitat surveys have been conducted at 79 sites where temperature data were available. Fish and macroinvertebrate data were obtained from the cooperative basin survey program data managers for candidate sites whenever possible and added to collections made during previous project years. This report summarizes progress for the period beginning 1 October 2009 and ending 30 September 2010. Additional analyses are ongoing and will be presented in the final report upon completion of this project.

Assessing caries status according to the CAST instrument and WHO criterion in epidemiological studies

ABSTRACT: Background: The Caries Assessment Spectrum and Treatment (CAST) is a new epidemiological instrument for detection and treatment of dental caries. Worldwide, the WHO criterion constitutes the epidemiological tool most commonly used for caries detection. The objective of the present study is to determine the levels of similarity and difference between the CAST instrument and WHO criterion on the basis of caries prevalence, dmf/DMF counts, examination time and reporting of results. Methods: An epidemiological survey was carried out in Brazil among 6-11-year-old schoolchildren. Time of examinations was recorded. dmft, dmfs, DMFT and DMFS counts and dental caries prevalence were obtained according to the WHO criterion and the CAST instrument, as well the correlation coefficient between the two instruments. Results: Four hundred nineteen children were examined. dmft and dmfs counts were 1.92 and 5.31 (CAST), 1.99 and 5.34 (WHO) with correlation coefficients (r) of 0.95 and 0.93, respectively. DMFT and DMFS counts were 0.20 and 0.33 (CAST), 0.19 and 0.30 (WHO), with r = 0.78 and r=0.72, respectively. Kappa coefficient values for intra-examiner consistency were CAST = 0.91-0.92; WHO = 0.95-0.96 and those for inter-examiner consistency were CAST = 0.90-0.96; WHO = 0.94-1.00. Mean time spent on applying CAST and WHO were 66.3 and 64.7 sec, respectively p = 0.26. The prevalence of dental caries using CAST (codes 2, 5-8) and the WHO criterion for the primary dentition were 63.0% and 65.9%, respectively, and for the permanent dentition they were 12.7% and 12.8%, respectively. Conclusions: The CAST instrument provided similar prevalence of dental caries values and dmf/DMF counts as the WHO criterion in this age group. Time spent on examining children was identical for both caries assessment methods. Presentation of results from use of the CAST instrument, in comparison to WHO criterion, allowed a more detailed reporting of stages of dental caries, which will be useful for oral health planners.

An investigation into the barriers to the implementation of automation and robotics technologies in the construction industry

The rising problems associated with construction such as decreasing quality and productivity, labour shortages, occupational safety, and inferior working conditions have opened the possibility of more revolutionary solutions within the industry. One prospective option is in the implementation of innovative technologies such as automation and robotics, which has the potential to improve the industry in terms of productivity, safety and quality. The construction work site could, theoretically, be contained in a safer environment, with more efficient execution of the work, greater consistency of the outcome and higher level of control over the production process. By identifying the barriers to construction automation and robotics implementation in construction, and investigating ways in which to overcome them, contributions could be made in terms of better understanding and facilitating, where relevant, greater use of these technologies in the construction industry so as to promote its efficiency. This research aims to ascertain and explain the barriers to construction automation and robotics implementation by exploring and establishing the relationship between characteristics of the construction industry and attributes of existing construction automation and robotics technologies to level of usage and implementation in three selected countries; Japan, Australia and Malaysia. These three countries were chosen as their construction industry characteristics provide contrast in terms of culture, gross domestic product, technology application, organisational structure and labour policies. This research uses a mixed method approach of gathering data, both quantitative and qualitative, by employing a questionnaire survey and an interview schedule; using a wide range of sample from management through to on-site users, working in a range of small (less than AUD0.2million) to large companies (more than AUD500million), and involved in a broad range of business types and construction sectors. Detailed quantitative (statistical) and qualitative (content) data analysis is performed to provide a set of descriptions, relationships, and differences. The statistical tests selected for use include cross-tabulations, bivariate and multivariate analysis for investigating possible relationships between variables; and Kruskal-Wallis and Mann Whitney U test of independent samples for hypothesis testing and inferring the research sample to the construction industry population. Findings and conclusions arising from the research work which include the ranking schemes produced for four key areas of, the construction attributes on level of usage; barrier variables; differing levels of usage between countries; and future trends, have established a number of potential areas that could impact the level of implementation both globally and for individual countries.

Facilities management action agenda : the Australian government and industry working together for improvement

This paper provides an overview of the Australian Government’s Facilities Management (FM) Action Agenda as announced in 2004 as a key policy plank designed to facilitate growth of the FM industry. The resulting consultation with industry leaders has seen the criterion and release in April 2005 of the FM Action Agenda’s strategic plan entitled ‘Managing the Built Environment’. This framework, representing a collaboration between the Australian Government, public and private sector stakeholders and Facility Management Association of Australia (FMA Australia) and other allied bodies, sets out to achieve the vision of a more “…productive and sustainable built environment…” through improved innovation, education and standards. The 36 month implementation phase is now underway and will take a multi-pronged approach to enhancing the recognition of the FM industry and removing impediments to its growth with a 20 point action plan across the following platforms: • Innovation – Improved appreciation of facility life cycles, and greater understanding of the key drivers of workplace productivity, and the improved application of information technology. • Education and Training – Improved access to dedicated FM education and training opportunities and creation clear career pathways into the profession. • Regulatory Reform – Explore opportunities to harmonise cross jurisdictional regulatory compliance requirements that have an efficiency impact on FM. • Sustainability – Improved utilization of existing knowledge and the development of tools and opportunities to improve the environmental performance of facilities. Additional information is available at www.fma.com.au

Development of the benefit finding in multiple sclerosis (MS) caregiving scale: A longitudinal study of relations between benefit finding and adjustment

Benefit finding is a meaning making construct that has been shown to be related to adjustment in people with MS and their carers. This study investigated the dimensions, stability and potency of benefit finding in predicting adjustment over a 12 month interval using a newly developed Benefit Finding in Multiple Sclerosis Scale (BFiMSS). Usable data from 388 persons with MS and 232 carers was obtained from questionnaires completed at Time 1 and 12 months later (Time 2). Factor analysis of the BFiMSS revealed seven psychometrically sound factors: Compassion/Empathy, Spiritual Growth, Mindfulness, Family Relations Growth, Life Style Gains, Personal Growth, New Opportunities. BFiMSS total and factors showed satisfactory internal and retest reliability coefficients, and convergent, criterion and external validity. Results of regression analyses indicated that the Time 1 BFiMSS factors accounted for significant amounts of variance in each of the Time 2 adjustment outcomes (positive states of mind, positive affect, anxiety, depression) after controlling for Time 1 adjustment, and relevant demographic and illness variables. Findings delineate the dimensional structure of benefit finding in MS, the differential links between benefit finding dimensions and adjustment and the temporal unfolding of benefit finding in chronic illness.

Estimation and compensation of clipping noise in OFDMA systems

We propose an efficient and low-complexity scheme for estimating and compensating clipping noise in OFDMA systems. Conventional clipping noise estimation schemes, which need all demodulated data symbols, may become infeasible in OFDMA systems where a specific user may only know his own modulation scheme. The proposed scheme first uses equalized output to identify a limited number of candidate clips, and then exploits the information on known subcarriers to reconstruct clipped signal. Simulation results show that the proposed scheme can significantly improve the system performance.

Diagnosing postpartum depression in mothers and fathers : Whatever happened to anxiety?

Although anxiety disorders are documented in the literature for new mothers (but less so for fathers), rates of postpartum caseness tend to include only those with depression when diagnostic interviews or self-report measures validated on such interviews are used. This methodology therefore underestimates the true percentage of women and men who experience significant psychological difficulties postpartum. This has implications for assessment, treatment and screening for postnatal mood disorders. Two studies were conducted on a total of 408 women and 356 men expecting their first child. They were recruited antenatally, and interviewed at 6 weeks postpartum using the Diagnostic Interview Schedule. DSM-IV criteria were applied to determine the presence since birth of depression (major or minor), panic disorder, acute adjustment disorder with anxiety (meeting the criteria for generalised anxiety disorder except for the duration criterion), and phobia. The inclusion of diagnostic assessment for panic disorder and acute adjustment disorder with anxiety increased the rates of caseness by between 57 and 100% for mothers, and 31-130% for fathers, over the rates for major or minor depression. Inclusion of assessment for phobia further increased the rates of disorder in both samples.