How Mistimed and Unwanted Pregnancies Affect Timing of Antenatal Care Initiation in three Districts in Tanzania

Early antenatal care (ANC) initiation is a doorway to early detection and management of potential complications associated with pregnancy. Although the literature reports various factors associated with ANC initiation such as parity and age, pregnancy intentions is yet to be recognized as a possible predictor of timing of ANC initiation. Data originate from a cross-sectional household survey on health behaviour and service utilization patterns. The survey was conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania on 910 women of reproductive age who had given birth in the past two years. ANC initiation was considered to be early only if it occurred in the first trimester of pregnancy gestation. A recently completed pregnancy was defined as mistimed if a woman wanted it later, and if she did not want it at all the pregnancy was termed as unwanted. Chisquare was used to test for associations and multinomial logistic regression was conducted to examine how mistimed and unwanted pregnancies affect timing of ANC initiation. Although 49.3% of the women intended to become pregnant, 50.7% (34.9% mistimed and 15.8% unwanted) became pregnant unintentionally. While ANC initiation in the 1st trimester was 18.5%, so was 71.7% and 9.9% in the 2nd and 3rd trimesters respectively. Multivariate analysis revealed that ANC initiation in the 2nd trimester was 1.68 (95% CI 1.10‒2.58) and 2.00 (95% CI 1.05‒3.82) times more likely for mistimed and unwanted pregnancies respectively compared to intended pregnancies. These estimates rose to 2.81 (95% CI 1.41‒5.59) and 4.10 (95% CI 1.68‒10.00) respectively in the 3rd trimester. We controlled for gravidity, age, education, household wealth, marital status, religion, district of residence and travel time to a health facility. Late ANC initiation is a significant maternal and child health consequence of mistimed and unwanted pregnancies in Tanzania. Women should be empowered to delay or avoid pregnancies whenever they need to do so. Appropriate counseling to women, especially those who happen to conceive unintentionally is needed to minimize the possibility of delaying ANC initiation.\u

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Experimental Evolution of an Oncolytic Vesicular Stomatitis Virus with Increased Selectivity for p53-Deficient Cells

Experimental evolution has been used for various biotechnological applications including protein and microbial cell engineering, but less commonly in the field of oncolytic virotherapy. Here, we sought to adapt a rapidly evolving RNA virus to cells deficient for the tumor suppressor gene p53, a hallmark of cancer cells. To achieve this goal, we established four independent evolution lines of the vesicular stomatitis virus (VSV) in p53-knockout mouse embryonic fibroblasts (p53−/− MEFs) under conditions favoring the action of natural selection. We found that some evolved viruses showed increased fitness and cytotoxicity in p53−/− cells but not in isogenic p53+/+ cells, indicating gene-specific adaptation. However, full-length sequencing revealed no obvious or previously described genetic changes associated with oncolytic activity. Half-maximal effective dose (EC50) assays in mouse p53-positive colon cancer (CT26) and p53-deficient breast cancer (4T1) cells indicated that the evolved viruses were more effective against 4T1 cells than the parental virus or a reference oncolytic VSV (MΔ51), but showed no increased efficacy against CT26 cells. In vivo assays using 4T1 syngeneic tumor models showed that one of the evolved lines significantly delayed tumor growth compared to mice treated with the parental virus or untreated controls, and was able to induce transient tumor suppression. Our results show that RNA viruses can be specifically adapted typical cancer features such as p53 inactivation, and illustrate the usefulness of experimental evolution for oncolytic virotherapy

Maternal educational level and risk of gestational hypertension: the Generation R Study.

We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrolment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrolment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrolment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrolment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy

Estimating Dengue Transmission Intensity from Sero-Prevalence Surveys in Multiple Countries

BACKGROUND:Estimates of dengue transmission intensity remain ambiguous. Since the majority of infections are asymptomatic, surveillance systems substantially underestimate true rates of infection. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing both the burden of disease from dengue and the likely impact of interventions. METHODOLOGY/PRINCIPAL FINDINGS:The force of infection (λ) and corresponding basic reproduction numbers (R0) for dengue were estimated from non-serotype (IgG) and serotype-specific (PRNT) age-stratified seroprevalence surveys identified from the literature. The majority of R0 estimates ranged from 1-4. Assuming that two heterologous infections result in complete immunity produced up to two-fold higher estimates of R0 than when tertiary and quaternary infections were included. λ estimated from IgG data were comparable to the sum of serotype-specific forces of infection derived from PRNT data, particularly when inter-serotype interactions were allowed for. CONCLUSIONS/SIGNIFICANCE:Our analysis highlights the highly heterogeneous nature of dengue transmission. How underlying assumptions about serotype interactions and immunity affect the relationship between the force of infection and R0 will have implications for control planning. While PRNT data provides the maximum information, our study shows that even the much cheaper ELISA-based assays would provide comparable baseline estimates of overall transmission intensity which will be an important consideration in resource-constrained settings