Distance to health services influences insecticide-treated net possession and use among six to 59 month-old children in Malawi

<p>Abstract</p> <p>Background</p> <p>Health ministries and providers are rapidly scaling up insecticide-treated nets (ITN) distribution to control malaria, yet possession and proper use typically remain below targeted levels. In Malawi, health facilities (HFs) are currently the principal points of ITN distribution, making it important to understand how access to these ITN sources affects ownership, possession, and use. The authors evaluated the association between proximity to HFs and ITN possession or use among Malawian children six to 59 months of age.</p> <p>Methods</p> <p>A household malaria survey undertaken in eight districts of Malawi during 2007 was used to characterize ITN possession and use. The location of each respondent's household was geocoded as was those of Ministry of Health (MoH) HFs and other health centres. Euclidean distance from each household to the nearest HF was calculated. Patterns of net possession and use were determined through descriptive methods. The authors then analysed the significance of distance and ITN possession/use through standard statistical tests, including logistic regression.</p> <p>Results</p> <p>Median distance to HFs was greater among households that did not possess ITNs and did not use an ITN the previous evening. Descriptive statistical methods confirmed a pattern of decreasing ITN possession and use with increasing distance from HFs. Logistic regression showed the same statistically significant association of distance to HFs, even when controlling for age and gender of the child, ratio of nets to children in household, community net possession and use, and household material wealth.</p> <p>Conclusions</p> <p>Strategies that exclusively distribute ITNs through HFs are likely to be less effective in increasing possession and use in communities that are more distant from those health services. Health providers should look towards community-based distribution services that take ITNs directly to community members to more effectively scale up ITN possession and regular use aimed at protecting children from malaria.</p

Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells

Phenoxodiol is a novel isoflav-3-ene, currently undergoing clinical trials, that has a broad in vitro activity against a number of human cancer cell lines. Phenoxodiol alone inhibited DU145 and PC3 in a dose- and time-dependent manner with IC50 values of 8±1 and 38±9 μM, respectively. The combination of phenoxodiol and cisplatin was synergistic in DU145, and additive in PC3, as assessed by the Chou–Talalay method. Carboplatin was also synergistic in combination with phenoxodiol in DU145 cells. The activity of the phenoxodiol and cisplatin combination was confirmed in vivo using a DU145 xenograft model in nude mice. Pharmacokinetic data from these mice suggest that the mechanism of synergy may occur through a pharmacodynamic mechanism. An intracellular cisplatin accumulation assay showed a 35% (P<0.05) increase in the uptake of cisplatin when it was combined in a ratio of 1 μM: 5 μM phenoxodiol, resulting in a 300% (P<0.05) increase in DNA adducts. Taken together, our results suggest that phenoxodiol has interesting properties that make combination therapy with cisplatin or carboplatin appealing

Decreasing Burden of Malaria in Pregnancy in Malawian Women and Its Relationship to Use of Intermittent Preventive Therapy or Bed Nets

The World Health Organization recommends insecticidal bednets and intermittent preventive treatment to reduce malaria in pregnancy. Longitudinal data of malaria prevalence and pregnancy outcomes are valuable in gauging the impact of these antimalarial interventions.We recruited 8,131 women delivering in a single Malawian hospital over 9 years. We recorded demographic data, antenatal prescription of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine and bed net use, and examined finger-prick blood for malaria parasites and hemoglobin concentration. In 4,712 women, we examined placental blood for malaria parasites and recorded the infant's birth weight. Peripheral and placental parasitemia prevalence declined from 23.5% to 5.0% and from 25.2% to 6.8% respectively. Smaller declines in prevalence of low birth weight and anemia were observed. Coverage of intermittent preventive treatment and bednets increased. Number of sulfadoxine-pyrimethamine doses received correlated inversely with placental parasitemia (Odds Ratio (95% CI): 0.79 (0.68, 0.91)), maternal anemia (0.81, (0.73, 0.90)) and low birth weight from 1997-2001 (0.63 (0.53, 0.75)), but not from 2002-2006. Bednet use protected from peripheral parasitemia (0.47, (0.37, 0.60)) and placental parasitemia (0.41, (0.31, 0.54)) and low birth weight (0.75 (0.59, 0.95)) but not anemia throughout the study. Compared to women without nets who did not receive 2-dose sulfadoxine-pyrimethamine, women using nets and receiving 2-dose sulfadoxine-pyrimethamine were less likely to have parasitemia or low birth weight babies. Women receiving 2-dose sulfadoxine-pyrimethamine alone had little evidence of protection whereas bednets alone gave intermediate protection.Increased bednet coverage explains changes in parasitemia and birth weight among pregnant women better than sulfadoxine-pyrimethamine use. High bed net coverage, and sulfadoxine-pyrimethamine resistance, may be contributing to its apparent loss of effectiveness

Who attends antenatal care and expanded programme on immunization services in Chad, Mali and Niger? the implications for insecticide-treated net delivery

UNLABELLED: ABSTRACT: BACKGROUND: Malaria remains one of the largest public health problems facing the developing world. Insecticide-treated nets (ITNs) are an effective intervention against malaria. ITN delivery through routine health services, such as antenatal care (ANC) and childhood vaccination (EPI), is a promising channel of delivery to reach individuals with the highest risk (pregnant women and children under five years old). Decisions on whether to deliver ITNs through both channels depends upon the reach of each of these systems, whether these are independent and the effectiveness and cost effectiveness of each. Predictors of women attending ANC and EPI separately have been studied, but the predictors of those who attend neither service have not been identified. METHODS: Data from Chad, Mali and Niger demographic and health surveys (DHS) were analyzed to determine risk factors for attending neither service. A conceptual framework for preventative health care-seeking behaviour was created to illustrate the hierarchical relationships between the potential risk factors. The independence of attending both ANC and EPI was investigated. A multivariate model of predictors for non-attendance was developed using logistic regression. RESULTS: ANC and EPI attendance were found to be strongly associated in all three countries. However, 47% of mothers in Chad, 12% in Mali and 36% in Niger did not attend either ANC or EPI. Region, mother's education and partner's education were predictors of non-attendance in all three countries. Wealth index, ethnicity, and occupation were associated with non-attendance in Mali and Niger. Other predictors included religion, healthcare autonomy, household size and number of children under five. CONCLUSIONS: Attendance of ANC and EPI are not independent and therefore the majority of pregnant women in these countries will have the opportunity to receive ITNs through both services. Although attendance at ANC and EPI are not independent, delivery through both systems may still add incrementally to delivery through one alone. Therefore, there is potential to increase the proportion of women and children receiving ITNs by delivering through both of these channels. However, modelling is required to determine the level of attendance and incremental potential at which it's cost effective to deliver through both services

Both Geography and Ecology Contribute to Mating Isolation in Guppies

Local adaptation to different environments can promote mating isolation – either as an incidental by-product of trait divergence, or as a result of selection to avoid maladaptive mating. Numerous recent empirical examples point to the common influence of divergent natural selection on speciation based largely on evidence of strong pre-mating isolation between populations from different habitat types. Accumulating evidence for natural selection's influence on speciation is therefore no longer a challenge. The difficulty, rather, is in determining the mechanisms involved in the progress of adaptive divergence to speciation once barriers to gene flow are already present. Here, we present results of both laboratory and field experiments with Trinidadian guppies (Poecilia reticulata) from different environments, who do not show complete reproductive isolation despite adaptive divergence. We investigate patterns of mating isolation between populations that do and do not exchange migrants and show evidence for both by-product and reinforcement mechanisms depending on female ecology. Specifically, low-predation females discriminate against all high-predation males thus implying a by-product mechanism, whereas high-predation females only discriminate against low-predation males from further upstream in the same river, implying selection to avoid maladaptive mating. Our study thus confirms that mechanisms of adaptive speciation are not necessarily mutually exclusive and uncovers the complex ecology-geography interactions that underlie the evolution of mating isolation in nature

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Background: Previous studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women.Methods: A total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p=0.05.Results: The diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77).Conclusions: On line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

A combined functional and structural genomics approach identified an EST-SSR marker with complete linkage to the Ligon lintless-2 genetic locus in cotton (Gossypium hirsutum L.)

<p>Abstract</p> <p>Background</p> <p>Cotton fiber length is an important quality attribute to the textile industry and longer fibers can be more efficiently spun into yarns to produce superior fabrics. There is typically a negative correlation between yield and fiber quality traits such as length. An understanding of the regulatory mechanisms controlling fiber length can potentially provide a valuable tool for cotton breeders to improve fiber length while maintaining high yields. The cotton (<it>Gossypium hirsutum </it>L.) fiber mutation Ligon lintless-2 is controlled by a single dominant gene (<it>Li₂</it>) that results in significantly shorter fibers than a wild-type. In a near-isogenic state with a wild-type cotton line, <it>Li₂</it>is a model system with which to study fiber elongation.</p> <p>Results</p> <p>Two near-isogenic lines of Ligon lintless-2 (<it>Li₂</it>) cotton, one mutant and one wild-type, were developed through five generations of backcrosses (BC₅). An F₂population was developed from a cross between the two <it>Li₂</it>near-isogenic lines and used to develop a linkage map of the <it>Li₂</it>locus on chromosome 18. Five simple sequence repeat (SSR) markers were closely mapped around the <it>Li₂</it>locus region with two of the markers flanking the <it>Li₂</it>locus at 0.87 and 0.52 centimorgan. No apparent differences in fiber initiation and early fiber elongation were observed between the mutant ovules and the wild-type ones. Gene expression profiling using microarrays suggested roles of reactive oxygen species (ROS) homeostasis and cytokinin regulation in the <it>Li₂</it>mutant phenotype. Microarray gene expression data led to successful identification of an EST-SSR marker (NAU3991) that displayed complete linkage to the <it>Li₂</it>locus.</p> <p>Conclusions</p> <p>In the field of cotton genomics, we report the first successful conversion of gene expression data into an SSR marker that is associated with a genomic region harboring a gene responsible for a fiber trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the <it>Li₂</it>locus on chromosome 18 and resided in a gene with similarity to a putative plectin-related protein. The complete linkage suggests that this expressed sequence may be the <it>Li₂</it>gene.</p

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases

Using State Space Exploration to Determine How Gene Regulatory Networks Constrain Mutation Order in Cancer Evolution

Cancer develops via the progressive accumulation of somatic mutations, which subvert the normal operation of the gene regulatory network of the cell. However, little is known about the order in which mutations are acquired in successful clones. A particular sequence of mutations may confer an early selective advantage to a clone by increasing survival or proliferation, or lead to negative selection by triggering cell death. The space of allowed sequences of mutations is therefore constrained by the gene regulatory network. Here, we introduce a methodology for the systematic exploration of the effect of every possible sequence of oncogenic mutations in a cancer cell modelled as a qualitative network. Our method uses attractor identification using binary decision diagrams and can be applied to both synchronous and asynchronous systems. We demonstrate our method using a recently developed model of ER-negative breast cancer. We show that there are differing levels of constraint in the order of mutations for different combinations of oncogenes, and that the effects of ErbB2/HER2 over-expression depend on the preceding mutations