Identification of BRCA1/2 Founder Mutations in Southern Chinese Breast Cancer Patients Using Gene Sequencing and High Resolution DNA Melting Analysis

Background: Ethnic variations in breast cancer epidemiology and genetics have necessitated investigation of the spectra of BRCA1 and BRCA2 mutations in different populations. Knowledge of BRCA mutations in Chinese populations is still largely unknown. We conducted a multi-center study to characterize the spectra of BRCA mutations in Chinese breast and ovarian cancer patients from Southern China. Methodology/Principal Findings: A total of 651 clinically high-risk breast and/or ovarian cancer patients were recruited from the Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2011. Comprehensive BRCA1 and BRCA2 mutation screening was performed using bi-directional sequencing of all coding exons of BRCA1 and BRCA2. Sequencing results were confirmed by in-house developed full high resolution DNA melting (HRM) analysis. Among the 451 probands analyzed, 69 (15.3%) deleterious BRCA mutations were identified, comprising 29 in BRCA1 and 40 in BRCA2. The four recurrent BRCA1 mutations (c.470_471delCT, c.3342_3345delAGAA, c.5406+1_5406+3delGTA and c.981_982delAT) accounted for 34.5% (10/29) of all BRCA1 mutations in this cohort. The four recurrent BRCA2 mutations (c.2808_2811delACAA, c.3109C>T, c.7436_7805del370 and c.9097_9098insA) accounted for 40% (16/40) of all BRCA2 mutations. Haplotype analysis was performed to confirm 1 BRCA1 and 3 BRCA2 mutations are putative founder mutations. Rapid HRM mutation screening for a panel of the founder mutations were developed and validated. Conclusion: In this study, our findings suggest that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Southern Chinese population. Knowing the spectrum and frequency of the founder mutations in this population will assist in the development of a cost-effective rapid screening assay, which in turn facilitates genetic counseling and testing for the purpose of cancer risk assessment. © 2012 Kwong et al.published_or_final_versio

Hypoxia causes transgenerational impairments in reproduction of fish

published_or_final_versio

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

A longitudinal survey of African animal trypanosomiasis in domestic cattle on the Jos Plateau, Nigeria:prevalence, distribution and risk factors

BACKGROUND: Trypanosomiasis is a widespread disease of livestock in Nigeria and a major constraint to the rural economy. The Jos Plateau, Nigeria was free from tsetse flies and the trypanosomes they transmit due to its high altitude and the absence of animal trypanosomiasis attracted large numbers of cattle-keeping pastoralists to inhabit the plateau. The Jos Plateau now plays a significant role in the national cattle industry, accommodating approximately 7% of the national herd and supporting 300,000 pastoralists and over one million cattle. However, during the past two decades tsetse flies have invaded the Jos Plateau and animal trypanosomiasis has become a significant problem for livestock keepers. METHODS: In 2008 a longitudinal two-stage cluster survey on the Jos Plateau. Cattle were sampled in the dry, early wet and late wet seasons. Parasite identification was undertaken using species-specific polymerase chain reactions to determine the prevalence and distribution bovine trypanosomiasis. Logistic regression was performed to determine risk factors for disease. RESULTS: The prevalence of bovine trypanosomiasis (Trypanosoma brucei brucei, Trypanosoma congolense savannah, Trypanosoma vivax) across the Jos Plateau was found to be high at 46.8% (39.0 – 54.5%) and significant, seasonal variation was observed between the dry season and the end of the wet season. T. b. brucei was observed at a prevalence of 3.2% (1% – 5.5%); T. congolense at 27.7% (21.8% - 33.6%) and T. vivax at 26.7% (18.2% - 35.3%). High individual variation was observed in trypanosomiasis prevalence between individual villages on the Plateau, ranging from 8.8% to 95.6%. Altitude was found to be a significant risk factor for trypanosomiasis whilst migration also influenced risk for animal trypanosomiasis. CONCLUSIONS: Trypanosomiasis is now endemic on the Jos Plateau showing high prevalence in cattle and is influenced by seasonality, altitude and migration practices. Attempts to successfully control animal trypanosomiasis on the Plateau will need to take into account the large variability in trypanosomiasis infection rates between villages, the influence of land use, and husbandry and management practices of the pastoralists, all of which affect the epidemiology of the disease

Auditory temporal resolution of a wild white-beaked dolphin (Lagenorhynchus albirostris)

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 195 (2009): 375-384, doi:10.1007/s00359-009-0415-x.Adequate temporal resolution is required across taxa to properly utilize amplitude modulated acoustic signals. Among mammals, odontocete marine mammals are considered to have relatively high temporal resolution, which is a selective advantage when processing fast traveling underwater sound. However, multiple methods used to estimate auditory temporal resolution have left comparisons among odontocetes and other mammals somewhat vague. Here we present the estimated auditory temporal resolution of an adult male white-beaked dolphin, (Lagenorhynchus albirostris), using auditory evoked potentials and click stimuli. Ours is the first of such studies performed on a wild dolphin in a capture-and-release scenario. The white-beaked dolphin followed rhythmic clicks up to a rate of approximately 1125-1250 Hz, after which the modulation rate transfer function (MRTF) cut-off steeply. However, 10% of the maximum response was still found at 1450 Hz indicating high temporal resolution. The MRTF was similar in shape and bandwidth to that of other odontocetes. The estimated maximal temporal resolution of white-beaked dolphins and other odontocetes was approximately twice that of pinnipeds and manatees, and more than ten-times faster than humans and gerbils. The exceptionally high temporal resolution abilities of odontocetes are likely due primarily to echolocation capabilities that require rapid processing of acoustic cues.We wish to thank the Danish Natural Science Research Council for major financial support (grant no. 272-05-0395)

Methods to study splicing from high-throughput RNA Sequencing data

The development of novel high-throughput sequencing (HTS) methods for RNA (RNA-Seq) has provided a very powerful mean to study splicing under multiple conditions at unprecedented depth. However, the complexity of the information to be analyzed has turned this into a challenging task. In the last few years, a plethora of tools have been developed, allowing researchers to process RNA-Seq data to study the expression of isoforms and splicing events, and their relative changes under different conditions. We provide an overview of the methods available to study splicing from short RNA-Seq data. We group the methods according to the different questions they address: 1) Assignment of the sequencing reads to their likely gene of origin. This is addressed by methods that map reads to the genome and/or to the available gene annotations. 2) Recovering the sequence of splicing events and isoforms. This is addressed by transcript reconstruction and de novo assembly methods. 3) Quantification of events and isoforms. Either after reconstructing transcripts or using an annotation, many methods estimate the expression level or the relative usage of isoforms and/or events. 4) Providing an isoform or event view of differential splicing or expression. These include methods that compare relative event/isoform abundance or isoform expression across two or more conditions. 5) Visualizing splicing regulation. Various tools facilitate the visualization of the RNA-Seq data in the context of alternative splicing. In this review, we do not describe the specific mathematical models behind each method. Our aim is rather to provide an overview that could serve as an entry point for users who need to decide on a suitable tool for a specific analysis. We also attempt to propose a classification of the tools according to the operations they do, to facilitate the comparison and choice of methods.Comment: 31 pages, 1 figure, 9 tables. Small corrections adde

Bus accident severity and passenger injury: evidence from Denmark

Purpose Bus safety is a concern not only in developing countries, but also in the U.S. and Europe. In Denmark, disentangling risk factors that are positively or negatively related to bus accident severity and injury occurrence to bus passengers can contribute to promote safety as an essential principle of sustainable transit and advance the vision “every accident is one too many”. Methods Bus accident data were retrieved from the national accident database for the period 2002–2011. A generalized ordered logit model allows analyzing bus accident severity and a logistic regression enables examining occurrence of injury to bus passengers. Results Bus accident severity is positively related to (i) the involvement of vulnerable road users, (ii) high speed limits, (iii) night hours, (iv) elderly drivers of the third party involved, and (v) bus drivers and other drivers crossing in yellow or red light. Occurrence of injury to bus passengers is positively related to (i) the involvement of heavy vehicles, (ii) crossing intersections in yellow or red light, (iii) open areas, (iv) high speed limits, and (v) slippery road surface. Conclusions The findings of the current study provide a comprehensive picture of the bus safety situation in Denmark and suggest the necessity of further research into bus drivers’ attitudes and perceptions of risks and road users’ perceptions of bus operations. Moreover, these findings suggest the need for further training into bus drivers’ hazard recognition skills and infrastructural solutions to forgive possible driving errors

From the Eye of the Albatrosses: A Bird-Borne Camera Shows an Association between Albatrosses and a Killer Whale in the Southern Ocean

Albatrosses fly many hundreds of kilometers across the open ocean to find and feed upon their prey. Despite the growing number of studies concerning their foraging behaviour, relatively little is known about how albatrosses actually locate their prey. Here, we present our results from the first deployments of a combined animal-borne camera and depth data logger on free-ranging black-browed albatrosses (Thalassarche melanophrys). The still images recorded from these cameras showed that some albatrosses actively followed a killer whale (Orcinus orca), possibly to feed on food scraps left by this diving predator. The camera images together with the depth profiles showed that the birds dived only occasionally, but that they actively dived when other birds or the killer whale were present. This association with diving predators or other birds may partially explain how albatrosses find their prey more efficiently in the apparently ‘featureless’ ocean, with a minimal requirement for energetically costly diving or landing activities

Differential Effects of Bartonella henselae on Human and Feline Macro- and Micro-Vascular Endothelial Cells

Bartonella henselae, a zoonotic agent, induces tumors of endothelial cells (ECs), namely bacillary angiomatosis and peliosis in immunosuppressed humans but not in cats. In vitro studies on ECs represent to date the only way to explore the interactions between Bartonella henselae and vascular endothelium. However, no comparative study of the interactions between Bartonella henselae and human (incidental host) ECs vs feline (reservoir host) ECs has been carried out because of the absence of any available feline endothelial cell lines