A Three-Stage Search for Supermassive Black Hole Binaries in LISA Data

Gravitational waves from the inspiral and coalescence of supermassive black-hole (SMBH) binaries with masses ~10^6 Msun are likely to be among the strongest sources for the Laser Interferometer Space Antenna (LISA). We describe a three-stage data-analysis pipeline designed to search for and measure the parameters of SMBH binaries in LISA data. The first stage uses a time-frequency track-search method to search for inspiral signals and provide a coarse estimate of the black-hole masses m_1, m_2 and of the coalescence time of the binary t_c. The second stage uses a sequence of matched-filter template banks, seeded by the first stage, to improve the measurement accuracy of the masses and coalescence time. Finally, a Markov Chain Monte Carlo search is used to estimate all nine physical parameters of the binary. Using results from the second stage substantially shortens the Markov Chain burn-in time and allows us to determine the number of SMBH-binary signals in the data before starting parameter estimation. We demonstrate our analysis pipeline using simulated data from the first LISA Mock Data Challenge. We discuss our plan for improving this pipeline and the challenges that will be faced in real LISA data analysis.Comment: 12 pages, 3 figures, submitted to Proceedings of GWDAW-11 (Berlin, Dec. '06

Evaluation of an investigative model in dairy herds with high calf perinatal mortality rates in Switzerland

peer-reviewedThe objective of this study was to evaluate an investigative model which encompassed the risk factors, incidence, timing and causes of perinatal mortality (PM) (0–48 h) on high risk dairy farms (PM of >5% in the previous year) in Switzerland. This pilot-study was carried out on 47 predominantly Holstein PM calves from 21 dairy farms, between September 2016 and January 2018. Gross pathological examinations of calves and placentae as well as histopathological examinations of internal organs and placental tissue were performed. Further investigations included microbiological examinations: broad-spectrum bacterial and fungal culture, detection of Chlamydia abortus, Coxiella burnetii, pathogenic Leptospira spp. and Neospora caninum by real-time PCR (qPCR) and of bovine viral diarrhoea virus (BVDV) by Ag-ELISA. Maternal blood samples were used for serology of bovine herpesvirus 1 (BHV-1), Brucella abortus, Chlamydia abortus, Coxiella burnetii and nine pathogenic leptospiral serovars and the evaluation of trace element status. A questionnaire was completed with the farmer, which included general farm characteristics and case-related data. Inbreeding coefficients (IC) were calculated for pure-bred matings. At the farm-level, the PM rate was 10.0% (5.3–28.2%) and at the cow-level, 11.5%. These values, from high-risk farms, were approximately five-times higher than the contemporary national bovine PM rate (2.3%) in Switzerland. The risk factors associated with these high PM rates were the self-selection of high risk herds, the high proportion of primiparae in these herds (45%) and the evidence of widespread pathogenic infections on these farms (exposure: 67% of herds, 53% of dams; infection: 57% of herds, 45% of calves). The majority (68.1%) of calves died intrapartum. The most commonly diagnosed initiating/ultimate cause of death (UCOD) was infection (34%) of which Coxiella burnetii was the most frequently detected pathogen, by antigen. The most frequently diagnosed proximate cause of death (PCOD) was asphyxia (44.7%), though multiple PCOD was also common (21.3%). This study was the first detailed investigation of bovine PM in Switzerland. Infectious causes were diagnosed more frequently than expected. While the findings from these high PM Swiss herds may have limited external validity, the investigative model adopted and the detailed research methodologies employed can be replicated and re-evaluated, respectively, in future studies on PM internationally

The establishment of the GENEQOL consortium to investigate the genetic disposition of patient-reported quality-of-life outcomes

To our knowledge, no comprehensive, interdisciplinary initiatives have been taken to examine the role of genetic variants on patient-reported quality-of-life outcomes. The overall objective of this paper is to describe the establishment of an international and interdisciplinary consortium, the GENEQOL Consortium, which intends to investigate the genetic disposition of patient-reported quality-of-life outcomes. We have identified five primary patient-reported quality-of-life outcomes as initial targets: negative psychological affect, positive psychological affect, self-rated physical health, pain, and fatigue. The first tangible objective of the GENEQOL Consortium is to develop a list of potential biological pathways, genes and genetic variants involved in these quality-of-life outcomes, by reviewing current genetic knowledge. The second objective is to design a research agenda to investigate and validate those genes and genetic variants of patient-reported quality-of-life outcomes, by creating large datasets. During its first meeting, the Consortium has discussed draft summary documents addressing these questions for each patient-reported quality-of-life outcome. A summary of the primary pathways and robust findings of the genetic variants involved is presented here. The research agenda outlines possible research objectives and approaches to examine these and new quality-of-life domains. Intriguing questions arising from this endeavor are discussed. Insight into the genetic versus environmental components of patient-reported quality-of-life outcomes will ultimately allow us to explore new pathways for improving patient care. If we can identify patients who are susceptible to poor quality of life, we will be able to better target specific clinical interventions to enhance their quality of life and treatment outcome

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. FUNDING: Bill & Melinda Gates Foundation

Measuring the health-related Sustainable Development Goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015

Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.Peer reviewe

The development of an enzyme-linked immunosorbent assay for bovine lactoferrin : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry at Massey University

Methods were established for the estimation of bovine lactoferrin by enzyme-linked immunosorbent assay (ELISA) on microtitre plates and nitrocellulose (dot assay). Mfinity-puri:fied antibodies to bovine lactoferrin were prepared and conjugated to horseradish peroxidase by the periodate method. Conjugates with enzymatic and immunological activity had an apparent molecular weight of 65 or 95 kd. Four methods of ELISA on microtitre plates and three dot assays were developed. ii Differences between the seven assays could be attributed to the absorption capacity of the solid phase and the types of conjugates and substrates used. The range of the two successful quantitative assays were 3-lOOOng lactoferrin/ml (sandwich) and 60-8000ng lactoferrin/ml (competitive), while the qualitative dot assays had a range of 1-lOOJ.lg lactoferrin/ml. More replicates would be required to reduce variability. Results from these assays generally corresponded to results from ROCKET electrophoresis. Dot assay on nitrocellulose has a greater potential for reproducible and quantitative assays than assay on microtitre plates, because of the greater adsorption capacity of the nitrocellulose. In addition, the dot assays are faster and lend themselves to more applications than either ROCKET electrophoresis or ELISA on microtitre plates. The ELISA developed in this project appear to be the first alternatives to radial immunodiffusion and ROCKET electrophoresis for the measurement of bovine lactoferrin

Germination of Bacillus anthracis spores within alveolar macrophages

International audienceThe fatal character of the infection caused by inhalation of Bacillus anthracis spores results from a complex pathogenic cycle involving the synthesis of toxins by the bacterium. We have shown using immunofluorescent staining, confocal scanning laser microscopy and image cytometry analysis that the alveolar macrophage was the primary site of B. anthracis germination in a murine inhalation infection model. Bacillus anthracis germinated inside murine macrophage-like RAW264.7 cells and murine alveolar macrophages. Germination occurred in vesicles derived from the phagosomal compartment. We have also demonstrated that the toxin genes and their trans-activator, AtxA, were expressed within the macrophages after germination