Removing exogenous information using pedigree data

Management of certain populations requires the preservation of its pure genetic background. When, for different reasons, undesired alleles are introduced, the original genetic conformation must be recovered. The present study tested, through computer simulations, the power of recovery (the ability for removing the foreign information) from genealogical data. Simulated scenarios comprised different numbers of exogenous individuals taking partofthe founder population anddifferent numbers of unmanaged generations before the removal program started. Strategies were based on variables arising from classical pedigree analyses such as founders? contribution and partial coancestry. The ef?ciency of the different strategies was measured as the proportion of native genetic information remaining in the population. Consequences on the inbreeding and coancestry levels of the population were also evaluated. Minimisation of the exogenous founders? contributions was the most powerful method, removing the largest amount of genetic information in just one generation.However, as a side effect, it led to the highest values of inbreeding. Scenarios with a large amount of initial exogenous alleles (i.e. high percentage of non native founders), or many generations of mixing became very dif?cult to recover, pointing out the importance of being careful about introgression events in populatio

Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice

<p>Managing Incidental Genomic Findings in Clinical Trials: Fulfillment of the Principle of Justice</p

Multi-Regge kinematics and the moduli space of Riemann spheres with marked points

We show that scattering amplitudes in planar N = 4 Super Yang-Mills in multi-Regge kinematics can naturally be expressed in terms of single-valued iterated integrals on the moduli space of Riemann spheres with marked points. As a consequence, scattering amplitudes in this limit can be expressed as convolutions that can easily be computed using Stokes' theorem. We apply this framework to MHV amplitudes to leading-logarithmic accuracy (LLA), and we prove that at L loops all MHV amplitudes are determined by amplitudes with up to L + 4 external legs. We also investigate non-MHV amplitudes, and we show that they can be obtained by convoluting the MHV results with a certain helicity flip kernel. We classify all leading singularities that appear at LLA in the Regge limit for arbitrary helicity configurations and any number of external legs. Finally, we use our new framework to obtain explicit analytic results at LLA for all MHV amplitudes up to five loops and all non-MHV amplitudes with up to eight external legs and four loops.Comment: 104 pages, six awesome figures and ancillary files containing the results in Mathematica forma

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

AIDS in adults 50 years of age and over: characteristics, trends and spatial distribution of the risk

OBJECTIVE: to analyze the sociodemographic characteristics, epidemic trend and spatial distribution of the risk of AIDS in adults 50 years of age and over.METHOD: population-based, ecological study, that used secondary data from the Notifiable Disease Information System (Sinan/AIDS) of Paraíba state from the period January 2000 to December 2010.RESULTS: during the study period, 307 cases of AIDS were reported among people 50 years of age or over. There was a predominance of males (205/66, 8%), mixed race, and low education levels. The municipalities with populations above 100 thousand inhabitants reported 58.5% of the cases. There was a progressive increase in cases among women; an increasing trend in the incidence (positive linear correlation); and an advance in the geographical spread of the disease, with expansion to the coastal region and to the interior of the state, reaching municipalities with populations below 30 thousand inhabitants. In some locations the risk of disease was 100 times greater than the relative risk for the state.CONCLUSION: aging, with the feminization and interiorization of the epidemic in adults 50 years of age and over, confirms the need for the induction of affirmative policies targeted toward this age group

Phylogeographic Analysis of HIV-1 Subtype C Dissemination in Southern Brazil

The HIV-1 subtype C has spread efficiently in the southern states of Brazil (Rio Grande do Sul, Santa Catarina and Paraná). Phylogeographic studies indicate that the subtype C epidemic in southern Brazil was initiated by the introduction of a single founder virus population at some time point between 1960 and 1980, but little is known about the spatial dynamics of viral spread. A total of 135 Brazilian HIV-1 subtype C pol sequences collected from 1992 to 2009 at the three southern state capitals (Porto Alegre, Florianópolis and Curitiba) were analyzed. Maximum-likelihood and Bayesian methods were used to explore the degree of phylogenetic mixing of subtype C sequences from different cities and to reconstruct the geographical pattern of viral spread in this country region. Phylogeographic analyses supported the monophyletic origin of the HIV-1 subtype C clade circulating in southern Brazil and placed the root of that clade in Curitiba (Paraná state). This analysis further suggested that Florianópolis (Santa Catarina state) is an important staging post in the subtype C dissemination displaying high viral migration rates from and to the other cities, while viral flux between Curitiba and Porto Alegre (Rio Grande do Sul state) is very low. We found a positive correlation (r2 = 0.64) between routine travel and viral migration rates among localities. Despite the intense viral movement, phylogenetic intermixing of subtype C sequences from different Brazilian cities is lower than expected by chance. Notably, a high proportion (67%) of subtype C sequences from Porto Alegre branched within a single local monophyletic sub-cluster. These results suggest that the HIV-1 subtype C epidemic in southern Brazil has been shaped by both frequent viral migration among states and in situ dissemination of local clades

Gender and respiratory factors associated with dyspnea in chronic obstructive pulmonary disease

RATIONALE: We had shown that COPD women expressed more dyspnea than men for the same degree of airway obstruction. OBJECTIVES: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. METHODS: In a FEV(1 )% matched population of 100 men and women with COPD we measured: age, MMRC, FEV(1), FVC, TLC, IC/TLC, PaO(2), PaCO(2), D(LCO), P(imax), P(0.1), Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. RESULTS: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:-0.39, p = 0.01), FEV(1 )% (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO(2 )(men:-0.59, p < 0.001), PaCO(2 )(men:0.27, p = 0.05), D(LCO )(men:-0.54, p < 0.001), P(0.1)/P(imax )(men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P(0.1)/P(imax )in women (r(2 )= 0.30) and BMI, DL(CO), PaO(2 )and P(0.1)/P(imax )in men (r(2 )= 0.81) were the strongest predictors of MMRC scores. CONCLUSION: In mild to severe COPD patients attending a pulmonary clinic, P(0.1)/P(imax )was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD

Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby

Background: The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies. Results: Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped ‘dipping’ sequences near the ground, which have been mentioned in the literature, but never before quantified. Conclusions: Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour

"They don't care what happens to us." The situation of double orphans heading households in Rakai District, Uganda

<p>Abstract</p> <p>Background</p> <p>This article is based on information collected about the situation of double orphans who are heading households in Rakai District, Uganda. The information will be used as justification and guidance for planning actions to improve the situation of these and similar children. This research is thus the first step in an Action Research approach leading to specific interventions. The aim of this article is to describe the situation of these orphaned children, with an emphasis on the psychosocial challenges they face.</p> <p>Methods</p> <p>The study involved interviews, focus group discussions, observations and narratives. Forty-three heads of sibling-headed households participated. Information derived from informal discussions with local leaders is also included. The responses were analyzed using a modified version of Giorgi's psychological phenomenological method as described by Malterud <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p> <p>Results</p> <p>Factors such as lack of material resources, including food and clothes, limited possibilities to attend school on a regular basis, vast responsibilities and reduced possibilities for social interaction all contribute to causing worries and challenges for the child heads of households. Most of the children claimed that they were stigmatized and, to a great extent, ignored and excluded from their community. The Local Council Secretary ("Chairman") seemed to be the person in the community most responsible and helpful, but some chairmen seemed not to care at all. The children requested counseling for themselves as well as for community members because they experienced lack of understanding from other children and from adult community members.</p> <p>Conclusion</p> <p>The children experienced their situation as a huge and complex problem for themselves as well as for people in their villages. However, the situation might improve if actions focused on practical and psychological issues as well as on sensitization about the children's situation could be initiated. In addition to the fact that these children need adult guidance to become citizens who act in accordance with the expectations in their communities, material aid is important in order to reduce the children's experiences of being "different" and constantly experiencing survival anxieties.</p> <p indent="1"><it>Before my parents died, I was schooling without facing any problems and my heart was at rest. When they died I went to live with Jjajja [grandmother]. She fell very sick and I came out of school for a full term to look after her. I was treating Jjajja but she was not getting better. She died...so...I got my schoolmates' books and copied notes that they had taken while I was away from school...I face the problem of not having good friends. Some see me as a disease...other people are not bad. Some call me names and say that I am stupid, that I probably inherited the stupidity from my mother or father...Ever since my parents died, I have not had peace. I spend most of the time thinking, crying and struggling within myself asking God why He really had to do such a thing and saying to myself that: "God, help me overcome these problems!"</it></p> <p indent="1"><it>Girl, 15</it>.</p