CAG Repeat Variants in the POLG1 Gene Encoding mtDNA Polymerase-Gamma and Risk of Breast Cancer in African-American Women

The DNA polymerase-gamma (POLG) gene, which encodes the catalytic subunit of enzyme responsible for directing mitochondrial DNA replication in humans, contains a polyglutamine tract encoded by CAG repeats of varying length. The length of the CAG repeat has been associated with the risk of testicular cancer, and other genomic variants that impact mitochondrial function have been linked to breast cancer risk in African-American (AA) women. We evaluated the potential role of germline POLG-CAG repeat variants in breast cancer risk in a sample of AA women (100 cases and 100 age-matched controls) who participated in the Women's Circle of Health Study, an ongoing multi-institutional, case-control study of breast cancer. Genotyping was done by fragment analysis in a blinded manner. Results from this small study suggest the possibility of an increased risk of breast cancer in women with minor CAG repeat variants of POLG, but no statistically significant differences in CAG repeat length were observed between cases and controls (multivariate-adjusted odds ratio 1.74; 95% CI, 0.49–6.21). Our study suggests that POLG-CAG repeat length is a potential risk factor for breast cancer that needs to be explored in larger population-based studies

Variants in the vitamin D pathway, serum levels of vitamin D, and estrogen receptor negative breast cancer among African-American women: A case-control study

Introduction: American women of African ancestry (AA) are more likely than European Americans (EA) to have estrogen receptor (ER)-negative breast cancer. 25-hydroxyvitamin D (25OHD) is low in AAs, and was associated with ER-negative tumors in EAs. We hypothesized that racial differences in 25OHD levels, as well as in inherited genetic variations, may contribute, in part, to the differences in tumor characteristics.Methods: In a case (n = 928)-control (n = 843) study of breast cancer in AA and EA women, we measured serum 25OHD levels in controls and tested associations between risk and tag single nucleotide polymorphisms (SNPs) in VDR, CYP24A1 and CYP27B1, particularly by ER status.Results: More AAs had severe vitamin D deficiency ( twofold increased risk of ER-negative breast cancer among AAs (OR = 2.62, 95% CI = 1.38-4.98), but had no effect in EAs. rs2209314 decreased risk among EAs (OR = 0.38, 95% CI = 0.20-0.73), with no associations in AAs. The increased risk of ER-negative breast cancer in AAs compared to EAs was reduced and became non-significant (OR = 1.20, 95% CI = 0.80-1.79) after adjusting for these two CYP24A1 SNPs.Conclusions: These data suggest that genetic variants in the vitamin D pathway may be related to the higher prevalence of ER-negative breast cancer in AA women. © 2012 Yao et al.; licensee BioMed Central Ltd

Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X

The prevalence of obesity (body mass index (BMI) ≥30 kg/m2) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (ρ = −0.042, P = 1.6×10−7). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = −3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = −4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI

Supplement use during an intergroup clinical trial for breast cancer (S0221)

The use of supplements during chemotherapy is controversial, partly due to the potential effect of antioxidants on reduced efficacy of chemotherapy-related cytotoxicity. We examined supplement use among breast cancer patients registered to a clinical trial (SWOG 0221) before diagnosis and during treatment. Patients (n = 1,467) completed questionnaires regarding multivitamin and supplement use at trial registration (baseline) to capture use before diagnosis. Of these patients, 1,249 completed a 6-month followup questionnaire to capture use during treatment. We examined the use of vitamins C, D, E, B6, B12, folic acid, and calcium at these timepoints, as well as physician recommendations regarding supplement use. The use of vitamins C, E, folic acid, and calcium decreased during treatment, while the use of vitamin B6 increased. Five hundred seventy four patients (51 %) received no physician recommendations regarding supplement use. Among the remaining 49, 10 % were advised not to take multivitamins and/or supplements, 7 % were advised to use only multivitamins, and 32 % received recommendations to use multivitamins and/or supplements. Among patients who took vitamin C before diagnosis, those who were advised not to take supplements were >5 times more likely not to use of vitamin C during treatment than those not advised to stop use (OR = 5.27, 95 % CI 1.13–24.6). Previous non-users who were advised to take a multivitamin were nearly 5 times more likely to use multivitamins during treatment compared to those who received no recommendation (OR = 4.66, 95 % CI 2.10–10.3). In this clinical trial for high-risk breast cancer, supplement use generally decreased during treatment. Upon followup from the clinical trial, findings regarding supplement use and survival outcomes will better inform physician recommendations for patients on adjuvant chemotherapy

Determining the Bivariate Design Characteristics of the Storm-Snowmelt Floods in an Urban Area of a Seaport in Ustka – Selected Problems

W artykule poruszono problematykę interpretacji wyników analizy dwuwymiarowej w odniesieniu do: 1) zasadności wyboru stochastycznego modelu w warunkach stacjonarności i niestacjonarności wezbrania sztormowo-roztopowego, 2) porównywania okresów powtarzalności i prawdopodobieństw przewyższenia zdefiniowanych w różnych zbiorach, oraz 3) porównywania jednowymiarowych prawdopodobieństw przewyższenia z ich dwuwymiarowymi odpowiednikami. Zmienną 2D utworzyły najwyższy poziom morza zaobserwowany w czasie wezbrań sztormowych w profilu wodowskazowym Ustka HUST (cm) i korespondujący z tym zdarzeniem przepływ w ujściowym odcinku rzeki w profilu wodowskazowym Charnowo QCHA (m3s-1). Parametry łącznej dystrybuanty oszacowano za pomocą 2-wymiarowej 2-parametrowej kopuli archimedesowskiej BB1. Do obliczania charakterystyk projektowych użyto 7 funkcji łącznego i warunkowego prawdopodobieństwa zmiennej 2D (HUST, QCHA). Wykonana analiza wykazała, ze porównywanie prawdopodobieństw zdefiniowanych w różnych dziedzinach i zbiorach oraz jednowymiarowych z dwuwymiarowymi powinno być wykonywane tylko w celu zbadania błędu wynikającego z nieprawidłowego wyboru modelu probabilistycznego. Każde zjawisko może być opisane za pomocą zmiennej wielowymiarowej, natomiast często własności losowej tylko jednej zmiennej są istotne z punktu widzenia celów projektowych.The article discusses the problem of determining the bivariate design characteristics of storm-snowmelt floods. For analysis the section of estuary Slupia basin in the area which is positioned a seaport in Ustka was used. The main natural hazard that determine the functioning of the seaport are: (i) storm surges in conjunction with backwater, (ii) uncontrolled increase in water level due to ice jam on the River Slupia and ice cover of the Baltic sea, (iii) snowmelt and rainy floods, (iv) destruction of sea coasts as results of waves, wind, sea currents, and (v) the movement of sediment. Seven functions for frequency analysis of storm and snowmelt floods were compared. The copula-based 2D probability distribution was applied to statistically describe floods with two parameters: maximum water level observed in the coastal area at Ustka in the period 1967-2005 HUST [cm] and correspondent of the event the peak of discharge observed in outlet of Slupia River at Charnowo QCHA [m3s-1]. The scope of this article is focused mainly on determine the bivariate characteristics and interpretation of different the joint and conditional probabilities. This article is an attempt to answer the question whether in the nonstationary conditions of phenomena can be used relatively simple stochastic model as it has a significant impact on the practice of planning and design of water sources. The article highlighted the need to properly define the various probabilities, especially in biand multivariate analyses. Comparing the probabilities defined in different domains and in different sets comparing the univariate probability with bivariate should only be carried out to examine the error resulting from improper selection of a probabilistic model. Analyzing the frequency of extreme events such floods, droughts is best considered in terms of the joint and the conditional probability, reasoning in terms of return period can lead to an erroneous understanding of the probability of events and incorrect description of the mechanism of this event

Application of copula method in twodimensional storm surges analysis at Świnoujście and at Kołobrzeg

W artykule zastosowano metod. kopuli do dwuwymiarowej analizy wezbra. sztormowych. Wezbrania sztormowe scharakteryzowano dwuwymiarow. zmienn. losow.: maksymalnym poziomem morza ponad nape.nienie w profilach wodowskazowych .winouj.cie PM.WI i Ko.obrzeg PMKOL. Proba losowa zosta.a wyznaczona na podstawie zidentyfikowanych wezbra. sztormowych wzd.u. po.udniowych wybrze.y Ba.tyku w latach 1976.2000. Celem artyku.u by.o znalezienie najlepszego dwuwymiarowego rozk.adu prawdopodobie.stwa badanej zmiennej losowej (PM.WI, PMKOL). Badaniu poddano eliptyczn. kopul. gaussowsk. i archimedesowsk. jednoparametrow. Gumela-Hougaarda. Do badania zgodno.ci kopuli z zaobserwowanymi realizacjami zmiennej losowej (PM.WI, PMKOL) u.yto wspo.czynnika korelacji rang Spearmana. Najlepsz. zgodno.. uzyskano dla kopuli Gumbela-Hougaarda �Ďs = 0,9871.The copula method was applied to analyze 2D storm surges. Storm surges were described with 2D variable: the maximum water level above the filling level at Świnoujście PMŚWI and at Kołobrzeg PMKOL. The identified storm surges along of southern Baltic coasts in the period 1976–2000 were used to set the random sample. The aim of this paper is to find the best fit 2D probability distribution of the variable (PMŚWI, PMKOL). Two copula functions: elliptical Gaussian and Archimedean Gumbel-Hougaard copula were investigated. To verify copula conformity with the data observed the non-parametric dependence measure such as Spearman’s ńs was used. The best conformity was recorded for Gumbel-Hougaard copula ńs = 0,9871

Logistics in collective transport of emergency medical services

W artykule został omówiony temat logistyki w transporcie karetek na przykładzie pogotowia ratunkowego. Poruszając ten temat warto zauważyć, że ważnym zagadnieniem związanym z jego funkcjonowaniem jest to odnoszące się do jego związków z logistyką w transporcie, a dotyczące czasu dojazdu do pacjenta i segregacji poszkodowanych. Omówienie tego tematu będzie przedmiotem tego artykułu. Przedstawiony zostanie proces logistyczny na przykładzie logistyki w transporcie karetek pogotowia ratunkowego.The paper discusses the subject of logistics in ambulance transport based on the example of an ambulance service. When discussing this subject, it is worth noting that an interesting issue related to its functioning is that relating to its relationship with transport logistics regarding travel time to the patient. Discussing this topic will be the subject of this paper. A logistics process will be presented on the example of logistics in the transport of ambulances