An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Effects of antiparasitic treatment on dynamically and statically tested cognitive skills over time.

The main objective of this work was to investigate two testing procedures, repeated static tests and dynamic testing, that can more clearly demonstrate the impact of treatment for parasites in children. Rural Tanzanian children were assessed for the presence/absence and burden of helminth parasites and assigned to one of three groups—infected/treated with anthelmintic medication, infected/not treated, and uninfected/not treated. All three groups were assessed with dynamically administered cognitive tests (on three separate occasions, with each session including pretest, instruction, and posttest), conventionally (statically) administered cognitive tests, and traditionally administered educational achievement tests. The data demonstrated that the children in the infected/treated and uninfected groups showed higher cognitive gains on two out of three dynamically administered and one out of eight statically administered tasks than did the children in the infected/not treated group. Thus, anthelmintic medications for parasitic illnesses appear to contribute to the improvement in cognitive functioning and this improvement is captured more clearly in dynamic than static tasks. The pathways of this improvement are still not understood and require further investigation

Achievable Hierarchies In Voting Games

Previous work by Diffo Lambo and Moulen [Theory and Decision 53, 313–325 (2002)] and Felsenthal and Machover [The Measurement of Voting Power, Edward Elgar Publishing Limited (1998)], shows that all swap preserving measures of voting power are ordinally equivalent on any swap robust simple voting game. Swap preserving measures include the Banzhaf, the Shapley–Shubik and other commonly used measures of a priori voting power. In this paper, we completely characterize the achievable hierarchies for any such measure on a swap robust simple voting game. Each possible hierarchy can be induced by a weighted voting game and we provide a constructive proof of this result. In particular, the strict hierarchy is always achievable as long as there are at least five players. Copyright Springer 2006desirability relation, ordinal equivalence, power indices, swap robust, voting games,

Anaemia in schoolchildren in eight countries in Africa and Asia.

OBJECTIVE: To report on the haemoglobin concentrations and prevalence of anaemia in schoolchildren in eight countries in Africa and Asia. DESIGN: Blood samples were collected during surveys of the health of schoolchildren as a part of programmes to develop school-based health services. SETTING: Rural schools in Ghana, Indonesia, Kenya, Malawi, Mali, Mozambique, Tanzania and Vietnam. SUBJECTS: Nearly 14 000 children enrolled in basic education in three age ranges (7-11 years, 12-14 years and > or =15 years) which reflect the new UNICEF/WHO thresholds to define anaemia. RESULTS: Anaemia was found to be a severe public health problem (defined as >40% anaemic) in five African countries for children aged 7-11 years and in four of the same countries for children aged 12-14 years. Anaemia was not a public health problem in the children studied in the two Asian countries. More boys than girls were anaemic, and children who enrolled late in school were more likely to be anaemic than children who enrolled closer to the correct age. The implications of the four new thresholds defining anaemia for school-age children are examined. CONCLUSIONS: Anaemia is a significant problem in schoolchildren in sub-Saharan Africa. School-based health services which provide treatments for simple conditions that cause blood loss, such as worms, followed by multiple micronutrient supplements including iron, have the potential to provide relief from a large burden of anaemia