Inference of population splits and mixtures from genome-wide allele frequency data

Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In this model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication, and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.comComment: 28 pages, 6 figures in main text. Attached supplement is 22 pages, 15 figures. This is an updated version of the preprint available at http://precedings.nature.com/documents/6956/version/

Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

The Dynamics of EBV Shedding Implicate a Central Role for Epithelial Cells in Amplifying Viral Output

To develop more detailed models of EBV persistence we have studied the dynamics of virus shedding in healthy carriers. We demonstrate that EBV shedding into saliva is continuous and rapid such that the virus level is replaced in ≤2 minutes, the average time that a normal individual swallows. Thus, the mouth is not a reservoir of virus but a conduit through which a continuous flow stream of virus passes in saliva. Consequently, virus is being shed at a much higher rate than previously thought, a level too high to be accounted for by replication in B cells in Waldeyer's ring alone. Virus shedding is relatively stable over short periods (hours-days) but varies through 3.5 to 5.5 logs over longer periods, a degree of variation that also cannot be accounted for solely by replication in B cells. This variation means, contrary to what is generally believed, that the definition of high and low shedder is not so much a function of variation between individuals but within individuals over time. The dynamics of shedding describe a process governing virus production that is occurring independently ≤3 times at any moment. This process grows exponentially and is then randomly terminated. We propose that these dynamics are best explained by a model where single B cells sporadically release virus that infects anywhere from 1 to 5 epithelial cells. This infection spreads at a constant exponential rate and is terminated randomly, resulting in infected plaques of epithelial cells ranging in size from 1 to 105 cells. At any one time there are a very small number (≤3) of plaques. We suggest that the final size of these plaques is a function of the rate of infectious spread within the lymphoepithelium which may be governed by the structural complexity of the tissue but is ultimately limited by the immune response

Chronic disease risk factors associated with health service use in the elderly

<p>Abstract</p> <p>Background</p> <p>To examine the association between number and combination of chronic disease risk factors on health service use.</p> <p>Methods</p> <p>Data from the 1995 Nova Scotia Health Survey (n = 2,653) was linked to provincial health services administrative databases. Multivariate regression models were developed that included important interactions between risk factors and were stratified by sex and at age 50. Negative-binomial regression models were estimated using generalized estimating equations assuming an autoregressive covariance structure.</p> <p>Results</p> <p>As the number of chronic disease risk factors increased so did the number of annual general practitioner visits, specialist visits and days spent in hospital in people aged 50 and older. This was not seen among individuals under age 50. Comparison of smokers, people with high blood pressure and people with high cholesterol showed no significantly different impact on health service use.</p> <p>Conclusion</p> <p>As the number of chronic disease risk factors increased so did health service use among individuals over age 50 but risk factor combination had no impact.</p

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Predicting Housekeeping Genes Based on Fourier Analysis

Housekeeping genes (HKGs) generally have fundamental functions in basic biochemical processes in organisms, and usually have relatively steady expression levels across various tissues. They play an important role in the normalization of microarray technology. Using Fourier analysis we transformed gene expression time-series from a Hela cell cycle gene expression dataset into Fourier spectra, and designed an effective computational method for discriminating between HKGs and non-HKGs using the support vector machine (SVM) supervised learning algorithm which can extract significant features of the spectra, providing a basis for identifying specific gene expression patterns. Using our method we identified 510 human HKGs, and then validated them by comparison with two independent sets of tissue expression profiles. Results showed that our predicted HKG set is more reliable than three previously identified sets of HKGs

Temporal Artery versus Bladder Thermometry during Adult Medical-Surgical Intensive Care Monitoring: An Observational Study

Abstract Background We sought to evaluate agreement between a new and widely implemented method of temperature measurement in critical care, temporal artery thermometry and an established method of core temperature measurement, bladder thermometry as performed in clinical practice. Methods Temperatures were simultaneously recorded hourly (n = 736 observations) using both devices as part of routine clinical monitoring in 14 critically ill adult patients with temperatures ranging ≥1°C prior to consent. Results The mean difference between temporal artery and bladder temperatures measured was -0.44°C (95% confidence interval, -0.47°C to -0.41°C), with temporal artery readings lower than bladder temperatures. Agreement between the two devices was greatest for normothermia (36.0°C to < 38.3°C) (mean difference -0.35°C [95% confidence interval, -0.37°C to -0.33°C]). The temporal artery thermometer recorded higher temperatures during hypothermia (< 36°C) (mean difference 0.66°C [95% confidence interval, 0.53°C to 0.79°C]) and lower temperatures during hyperthermia (≥38.3°C) (mean difference -0.90°C [95% confidence interval, -0.99°C to -0.81°C]). The sensitivity for detecting fever (core temperature ≥38.3°C) using the temporal artery thermometer was 0.26 (95% confidence interval, 0.20 to 0.33), and the specificity was 0.99 (95% confidence interval, 0.98 to 0.99). The positive likelihood ratio for fever was 24.6 (95% confidence interval, 10.7 to 56.8); the negative likelihood ratio was 0.75 (95% confidence interval, 0.68 to 0.82). Conclusions Temporal artery thermometry produces somewhat surprising disagreement with an established method of core temperature measurement and should not to be used in situations where body temperature needs to be measured with accuracy

'How to know what you need to do': a cross-country comparison of maternal health guidelines in Burkina Faso, Ghana and Tanzania

Initiatives to raise the quality of care provided to mothers need to be given priority in Sub Saharan Africa (SSA). The promotion of clinical practice guidelines (CPGs) is a common strategy, but their implementation is often challenging, limiting their potential impact. Through a cross-country perspective, this study explored CPGs for maternal health in Burkina Faso, Ghana, and Tanzania. The objectives were to compare factors related to CPG use including their content compared with World Health Organization (WHO) guidelines, their format, and their development processes. Perceptions of their availability and use in practice were also explored. The overall purpose was to further the understanding of how to increase CPGs' potential to improve quality of care for mothers in SSA. The study was a multiple case study design consisting of cross-country comparisons using document review and key informant interviews. A conceptual framework to aid analysis and discussion of results was developed, including selected domains related to guidelines' implementability and use by health workers in practice in terms of usability, applicability, and adaptability. The study revealed few significant differences in content between the national guidelines for maternal health and WHO recommendations. There were, however, marked variations in the format of CPGs between the three countries. Apart from the Ghanaian and one of the Tanzanian CPGs, the levels of both usability and applicability were assessed as low or medium. In all three countries, the use of CPGs by health workers in practice was perceived to be limited. Our cross-country study suggests that it is not poor quality of content or lack of evidence base that constitute the major barrier for CPGs to positively impact on quality improvement in maternal care in SSA. It rather emphasises the need to prioritise the format of guidelines to increase their usability and applicability and to consider these attributes together with implementation strategies as integral to their development processes

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Childhood leukaemia: long-term excess mortality and the proportion ‘cured'

Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion ‘cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971–2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11–14) to 19 years (95% CI: 14–26) for lymphoid leukaemia (average annual increase of 0.3 years; P<0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment