A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse

Adaptively Transforming Graph Matching

Recently, many graph matching methods that incorporate pairwise constraint and that can be formulated as a quadratic assignment problem (QAP) have been proposed. Although these methods demonstrate promising results for the graph matching problem, they have high complexity in space or time. In this paper, we introduce an adaptively transforming graph matching (ATGM) method from the perspective of functional representation. More precisely, under a transformation formulation, we aim to match two graphs by minimizing the discrepancy between the original graph and the transformed graph. With a linear representation map of the transformation, the pairwise edge attributes of graphs are explicitly represented by unary node attributes, which enables us to reduce the space and time complexity significantly. Due to an efficient Frank-Wolfe method-based optimization strategy, we can handle graphs with hundreds and thousands of nodes within an acceptable amount of time. Meanwhile, because transformation map can preserve graph structures, a domain adaptation-based strategy is proposed to remove the outliers. The experimental results demonstrate that our proposed method outperforms the state-of-the-art graph matching algorithms

Best Practices in Dengue Surveillance: A Report from the Asia-Pacific and Americas Dengue Prevention Boards

The Pediatric Dengue Vaccine Initiative organized Dengue Prevention Boards in the Asia-Pacific and the Americas regions consisting of dengue experts from endemic countries. Both Boards convened meetings to review issues in surveillance. Through presentations, facilitated discussions, and surveys, the Boards identified best practices in dengue surveillance including: (1) Dengue should be a notifiable disease in endemic countries; (2) World Health Organization regional case definitions should be consistently applied; (3) electronic reporting systems should be developed and used broadly to speed delivery of data to stakeholders; (4) minimum reporting should include incidence rates of dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and dengue deaths, and hospitalization and mortality rates should be reported by age group; (5) periodic additional studies (e.g., capture/recapture) should be conducted to assess under-detection, under-reporting, and the quality of surveillance; (6) laboratory methods and protocols should be standardized; (7) national authorities should encourage laboratories to develop networks to share expertise and data; and (8) RT-PCR and virus isolation (and possibly detection of the NS1 protein) are the recommended methods for confirmation of an acute dengue infection, but are recommended only for the four days after onset of fever—after day 4, IgM-capture enzyme-linked immunosorbent assay is recommended

Evaluation of several adjuvants in avian influenza vaccine to chickens and ducks

The effects of three different adjuvants, mineral oil, Montanide™ ISA 70M VG, and Montanide™ ISA 206 VG, were evaluated on reverse genetics H5N3 avian influenza virus cell cultured vaccine. The immune results of SPF chickens after challenging with highly pathogenic avian influenza (HPAI) virus demonstrated that mineral oil adjuvant group and 70M adjuvant group provided 100% protection efficiency, but 206 adjuvant group provided only 40%. Statistical analysis indicated that the protection effects of mineral oil adjuvant group and the 70M adjuvant showed no significant difference to each other, but with significant difference to 206 adjuvant group. All three groups could induce high titres of antibody after immunizing SPF ducks, but there was no significant difference among them. The immunization effect of 70M adjuvant group on SPF chickens were the best and showed significant difference compared with optimized 70Mi Montanide™ eight series adjuvants groups. These results suggest that 70M adjuvant could be a novel adjuvant for preparing avian influenza vaccine

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

A new method for determining physician decision thresholds using empiric, uncertain recommendations

<p>Abstract</p> <p>Background</p> <p>The concept of risk thresholds has been studied in medical decision making for over 30 years. During that time, physicians have been shown to be poor at estimating the probabilities required to use this method. To better assess physician risk thresholds and to more closely model medical decision making, we set out to design and test a method that derives thresholds from actual physician treatment recommendations. Such an approach would avoid the need to ask physicians for estimates of patient risk when trying to determine individual thresholds for treatment. Assessments of physician decision making are increasingly relevant as new data are generated from clinical research. For example, recommendations made in the setting of ocular hypertension are of interest as a large clinical trial has identified new risk factors that should be considered by physicians. Precisely how physicians use this new information when making treatment recommendations has not yet been determined.</p> <p>Results</p> <p>We derived a new method for estimating treatment thresholds using ordinal logistic regression and tested it by asking ophthalmologists to review cases of ocular hypertension before expressing how likely they would be to recommend treatment. Fifty-eight physicians were recruited from the American Glaucoma Society. Demographic information was collected from the participating physicians and the treatment threshold for each physician was estimated. The method was validated by showing that while treatment thresholds varied over a wide range, the most common values were consistent with the 10-15% 5-year risk of glaucoma suggested by expert opinion and decision analysis.</p> <p>Conclusions</p> <p>This method has advantages over prior means of assessing treatment thresholds. It does not require physicians to explicitly estimate patient risk and it allows for uncertainty in the recommendations. These advantages will make it possible to use this method when assessing interventions intended to alter clinical decision making.</p

The Diabetes Pearl: Diabetes biobanking in The Netherlands

Contains fulltext : 109720.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. METHODS/DESIGN: Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG), retina photographs, ankle-brachial index, peripheral vibration perception), self-report questionnaire (socio-economic status, lifestyle, (family) history of disease, and psychosocial well-being), laboratory measurements (glucose, A1c, lipid profile, kidney function), biobank material (storage of urine and blood samples and isolated DNA). All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. DISCUSSION: The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with an interest in diabetes related research

Cognitive and psychological science insights to improve climate change data visualization

Visualization of climate data plays an integral role in the communication of climate change findings to both expert and non-expert audiences. The cognitive and psychological sciences can provide valuable insights into how to improve visualization of climate data based on knowledge of how the human brain processes visual and linguistic information. We review four key research areas to demonstrate their potential to make data more accessible to diverse audiences: directing visual attention, visual complexity, making inferences from visuals, and the mapping between visuals and language. We present evidence-informed guidelines to help climate scientists increase the accessibility of graphics to non-experts, and illustrate how the guidelines can work in practice in the context of Intergovernmental Panel on Climate Change graphics

Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4

BACKGROUND: Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. CONCLUSIONS/SIGNIFICANCE: This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas

Association between maternal depression symptoms across the first eleven years of their child’s life and subsequent offspring suicidal ideation

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19,4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis