Differences in both prevalence and titre of specific immunoglobulin E among children with asthma in affluent and poor communities within a large town in Ghana.

Background Reports from several African countries have noted an increasing prevalence of asthma in areas of extensive urbanization. Objective To investigate the relevance of allergen-specific sensitization and body mass index (BMI) to asthma/wheezing and exercise-induced bronchospasm (EIB) among children from affluent and poorer communities within a large town in Ghana. Methods Children with physician-diagnosed asthma and/or current wheezing aged 9-16 years (n=99; cases) from three schools with differing socio-economic backgrounds [urban affluent (UA), urban poor (UP) or suburban/rural (SR)] were recruited from a cross-sectional study (n=1848) in Kumasi, Ghana, and matched according to age, sex and area of residence with non-asthmatic/non-wheezy controls. We assayed sera for IgE antibodies to mite, cat, dog, cockroach, Ascaris and galactose-α-1,3-galactose. Results Children from the UA school had the lowest total serum IgE. However, cases from the UA school had a higher prevalence and mean titre of sIgE to mite (71.4%, 21.2IU/mL) when compared with controls (14.3%, 0.8IU/mL) or cases from UP (30%, 0.8IU/mL) and SR community (47.8%, 1.6IU/mL). While similar findings were observed with EIB in the whole population, among cases there was no difference in IgE antibody prevalence or titre between children with or without EIB. BMI was higher among UA children with and without asthma; in UP and SR communities, children with EIB (n=14) had a significantly higher BMI compared with children with asthma/wheezing without EIB (n=38) (18.2 vs. 16.4, respectively, P<0.01). Conclusions and Clinical Relevance In the relatively affluent school, asthma/wheezing and EIB were associated with high titre IgE antibodies to mite, decreased total IgE, and increased BMI. This contrasted with children in the urban poor school and suggests that changes relevant to a Western model of childhood asthma can occur within a short geographical distance within a large city in Africa. © 2011 Blackwell Publishing Ltd

X-Ray fluorescence analysis of feldspars and silicate glass: effects of melting time on fused bead consistency and volatilisation

Reproducible preparation of lithium tetraborate fused beads for XRF analysis of glass and mineral samples is of paramount importance for analytical repeatability. However, as with all glass melting processes, losses due to volatilization must be taken into account and their effects are not negligible. Here the effects of fused bead melting time have been studied for four Certified Reference Materials (CRM’s-three feldspars, one silicate glass), in terms of their effects on analytical variability and volatilization losses arising from fused bead preparation. At melting temperatures of 1065 °C, and for feldspar samples, fused bead melting times shorter than approximately 25 minutes generally gave rise to greater deviation of XRF-analyzed composition from certified composition. This variation might be due to incomplete fusion and / or fused bead inhomogeneity but further research is needed. In contrast, the shortest fused bead melting time for the silicate glass CRM gave an XRF-analyzed composition closer to the certified values than longer melting times. This may suggest a faster rate of glass-in-glass dissolution and homogenization during fused bead preparation. For all samples, longer melting times gave rise to greater volatilization losses (including sulphates and halides) during fusion. This was demonstrated by a linear relationship between SO3 mass loss and time1/2, as predicted by a simple diffusion-based model. Iodine volatilization displays a more complex relationship, suggestive of diffusion plus additional mechanisms. This conclusion may have implications for vitrification of iodine-bearing radioactive wastes. Our research demonstrates that the nature of the sample material impacts on the most appropriate fusion times. For feldspars no less than ~25 min and no more than ~60 min of fusion at 1065 °C, using Li2B4O7 as the fusion medium and in the context of feldspar samples and the automatic fusion equipment used here, strikes an acceptable (albeit non-ideal) balance between the competing factors of fused bead quality, analytical consistency and mitigating volatilization losses. Conversely, for the silicate glass sample, shorter fusion times of less than ~30 minutes under the same conditions provided more accurate analyses whilst limiting volatile losses

X-ray Fluorescence Analysis of Feldspars and Silicate Glass: Effects of Melting Time on Fused Bead Consistency and Volatilisation

Reproducible preparation of lithium tetraborate fused beads for XRF analysis of glass and mineral samples is of paramount importance for analytical repeatability. However, as with all glass melting processes, losses due to volatilisation must be taken into account and their effects are not negligible. Here the effects of fused bead melting time have been studied for four Certified Reference Materials (CRM’s: three feldspars, one silicate glass), in terms of their effects on analytical variability and volatilisation losses arising from fused bead preparation. At melting temperatures of 1065 °C, and for feldspar samples, fused bead melting times shorter than approximately 25 min generally gave rise to a greater deviation of the XRF-analysed composition from the certified composition. This variation might be due to incomplete fusion and/or fused bead inhomogeneity but further research is needed. In contrast, the shortest fused bead melting time for the silicate glass CRM gave an XRF-analysed composition closer to the certified values than longer melting times. This may suggest a faster rate of glass-in-glass dissolution and homogenization during fused bead preparation. For all samples, longer melting times gave rise to greater volatilisation losses (including sulphates and halides) during fusion. This was demonstrated by a linear relationship between SO3 mass loss and time1/2, as predicted by a simple diffusion-based model. Iodine volatilisation displays a more complex relationship, suggestive of diffusion plus additional mechanisms. This conclusion may have implications for vitrification of iodine-bearing radioactive wastes. Our research demonstrates that the nature of the sample material impacts on the most appropriate fusion times. For feldspars no less than ~25 min and no more than ~60 min of fusion at 1065 °C, using Li2B4O7 as the fusion medium and in the context of feldspar samples and the automatic fusion equipment used here, strikes an acceptable (albeit non-ideal) balance between the competing factors of fused bead quality, analytical consistency and mitigating volatilisation losses. Conversely, for the silicate glass sample, shorter fusion times of less than ~30 min under the same conditions provided more accurate analyses whilst limiting volatile losses

Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts.Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6-59 mo) by country and infection-burden category.Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration &lt;110 g/L) and severe anemia (hemoglobin concentration &lt;70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration &lt;12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group.Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in &gt;50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high-infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high-infection categories, respectively.Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs

Evaluation of the effect of urbanization on urban thermal behaviour using urban heat island indicators: the case of the CBD of Accra.

Various studies have shown that urban heat island (UHI) can significantly affect the local climate of the built environment. Extreme air temperatures and heat waves adversely affect people's health, their overall well-being and productivity. Tropical urban sites are constantly under the threats of the harsh urban heat island (UHI) effects – a situation which is aggravated by climate change. Several urban morphological factors can potentially modify urban climate and, consequently, the potential energy demand and supply in cities. Since independence, Ghana has experienced a significant rise in population growth, which has culminated in the urbanisation of many of its towns. The rapid growth of Accra is attributed to rural-urban migration, natural population increase, booming economic activities, political factors among others. The influx of people into urban areas has led to a high demand for more housing, commercial and other infrastructural developments. For Accra however, this drive has resulted in a sharp reduction in urban greenery. Despite the obviously warm-humid climate that is prevalent in Ghana, no UHI study had previously been carried out in the country. Due to its compactness, the central business district (CBD) of Accra was chosen for the study. Through the quantification of UHI, this study aims at evaluating the effect of urbanization on the urban thermal behaviour in the CBD of Accra, with the view to developing suitable proposals that can influence current and future strategic urban design decisions meant to mitigate the negative impacts of UHI in the city. This study employs an explanatory mixed-methods research approach. By ascertaining the presence of UHI in the city through a pilot study, the proposed research method is further improved. The quantitative study involves the collection of weather data from selected monitoring points in the city's CBD. To gain an in-depth understanding of the underlying causes of the morphological transformation the city has undergone, face-to-face semi-structured interviews with some experienced Ghanaian built environment professionals are carried out. Using a clear temperature-morphology mapping, UHI intensity dynamics within identified local climate zones are analysed. The quantitative and qualitative data sets are analysed separately and sequentially and later triangulated. This study has shown that areas in the CBD of Accra that have large expanses of hardscapes and significantly reduced greeneries have been experiencing high UHI intensities. It is also evident that areas within deep canyons experience lower daytime temperatures compared to areas within shallow canyons; for night-time temperatures however, the opposite is the case. Upon analysing the qualitative data, other major causes of the morphological transformations that have emerged include poor enforcement of development control, non-adherence to building regulations; inadequacies in the existing building regulations; architects and building designers lacking the motivation for sustainable design etc. To adequately address the identified challenges and cushion the adverse effects of urban heat in the study area, this research ultimately recommends a holistic strategic plan that encompasses suitable environmental cooling measures and policy interventions

Investigating the major causes of morphological transformations in the CBD of Accra and the impact on urban heat island intensity.

Tropical urban sites are constantly under the threats of the adverse effects of urban heat island (UHI) - a situation which is aggravated by climate change. Urban morphology comprises a large set of factors that play an important role in modifying urban climate and, consequently, the potential energy demand and supply in cities. Ghana has since independence, experienced a rapid population growth, which has resulted in the urbanisation of many of its towns. The influx of people into the urban areas means there is a high demand for more housing, commercial and other infrastructural developments. For Accra however, this drive has resulted in drastic reduction in urban greenery. The aim of this study is to investigate the main causes of morphological transformations that have occurred in Accra over the past few decades, with the view to identifying possible measures for UHI mitigation. This study employs a mixed-methods research approach. First, to gain an in-depth understanding of the underlying causes of the morphological transformation the city has undergone, qualitative data are gathered through desktop studies and face-to-face semi-structured interviews with some experienced Ghanaian built environment professionals. The quantitative study involves the collection of weather data from selected monitoring points in the city. Upon analysing the qualitative data, other major causes of the morphological transformations that have emerged include poor enforcement of development control, non-adherence to building regulations; inadequacies in the existing building regulations; architects and building designers lacking the motivation for sustainable design etc. It is evident that areas with large expanse of hardscapes and significantly reduced greenery are experiencing high UHI intensities. Recommendations include measures which address the identified challenges as well as urban regeneration

Contract Package as an Antecedent of Value for Money: The Mediating Role of Competitive Procurement.

Given the limited resources available to the government institutions, value for money in procurement is crucial to ensuring the optimal use of finite budgetary resources. This study delves into contract package as an antecedent of value for money; competitive procurement as a mediating role. Fifty-three (53) pre-university educational institutions in the Eastern region of Ghana were selected for the study. Two research objectives were examined whilst two research hypotheses were tested. This study is a quantitative one, which employed purposive and simple random sampling techniques. Using the Confirmatory Factor Analysis (CFA) and Structural Equation Model (SEM) for data analysis, the study found no relationship between contract package and value for money. Again, the study revealed that competitive procurement failed to exert significant effect or influence on contract package and value for money linkages. The study recommended that appropriate procurement process at the public sector is highly required to generate wealth, enhance transparency and accountability, encourage consistent procurement procedures and lessen corruption. Through this, value for money can be achieved

Transcription control by the ENL YEATS domain in acute leukaemia

Recurrent chromosomal translocations producing a chimaeric MLL oncogene give rise to a highly aggressive acute leukaemia associated with poor clinical outcome. The preferential involvement of chromatin-associated factors as MLL fusion partners belies a dependency on transcription control. Despite recent progress made in targeting chromatin regulators in cancer, available therapies for this well-characterized disease remain inadequate, prompting the need to identify new targets for therapeutic intervention. Here, using unbiased CRISPR-Cas9 technology to perform a genome-scale loss-of-function screen in an MLL-AF4-positive acute leukaemia cell line, we identify ENL as an unrecognized gene that is specifically required for proliferation in vitro and in vivo. To explain the mechanistic role of ENL in leukaemia pathogenesis and dynamic transcription control, a chemical genetic strategy was developed to achieve targeted protein degradation. Acute loss of ENL suppressed the initiation and elongation of RNA polymerase II at active genes genome-wide, with pronounced effects at genes featuring a disproportionate ENL load. Notably, an intact YEATS chromatin-reader domain was essential for ENL-dependent leukaemic growth. Overall, these findings identify a dependency factor in acute leukaemia and suggest a mechanistic rationale for disrupting the YEATS domain in disease.K. LubinE. Wood

Low birth weight among adolescents at Cape Coast Metropolitan Hospital of Ghana

Background: Few studies have focused on low birth weight among adolescents. This study determines the incidence and factors associated with low birth weight (LBW) (weight at birth of less than 2,500 grams) among adolescents (aged <20 years) and how they differ from those in adult mothers (aged ≥20 years).Methods: The records of 768 deliveries at a hospital in Ghana from August 2014 to March 2015 were analyzed. Frequencies and percentages were generated. Bivariate relationships between maternal and neonatal characteristics and LBW were assessed using Chi-squared test. Multivariate logistic regression was used to evaluate the association between maternal age (being adolescent) and LBW. Odds ratios with 95% confidence interval were generated, and p < 0.05 was considered significant.Results: The incidence of LBW among adolescents was 14.3% and this was higher than the one among babies born to adult mothers (14.3 % vs. 7.4 %, p <0.013). Adolescent mothers were twice as likely to give birth to babies with LBW compared to adult mothers (OR 2.22; 95% CI: 1.16 - 4.25). Preterm birth was significantly associated with LBW among adolescent and adult mothers.Conclusions: Adolescents are at a higher risk of giving birth to babies of LBW than adults. Factors predicting LBW may not be different for adolescent and adult mothers. Interventions for prevention of negative sexual health outcomes should focus on adolescents

Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains

Bromodomains have been pursued intensively over the past several years as emerging targets for the development of anticancer and anti-inflammatory agents. It has recently been shown that some kinase inhibitors are able to potently inhibit the bromodomains of BRD4. The clinical activities of PLK inhibitor BI-2536 and JAK2-FLT3 inhibitor TG101348 have been attributed to this unexpected polypharmacology, indicating that dual-kinase/bromodomain activity may be advantageous in a therapeutic context. However, for target validation and biological investigation, a more selective target profile is desired. Here, we report that benzo[e]pyrimido-[5,4- b]diazepine-6(11H)-ones, versatile ATP-site directed kinase pharmacophores utilized in the development of inhibitors of multiple kinases, including several previously reported kinase chemical probes, are also capable of exhibiting potent BRD4-dependent pharmacology. Using a dual kinase-bromodomain inhibitor of the kinase domains of ERK5 and LRRK2, and the bromodomain of BRD4 as a case study, we define the structure-activity relationships required to achieve dual kinase/BRD4 activity, as well as how to direct selectivity toward inhibition of either ERK5 or BRD4. This effort resulted in identification of one of the first reported kinase-selective chemical probes for ERK5 (JWG-071), a BET selective inhibitor with 1 μM BRD4 IC50 (JWG-115), and additional inhibitors with rationally designed polypharmacology (JWG-047, JWG-069). Co-crystallography of seven representative inhibitors with the first bromodomain of BRD4 demonstrate that distinct atropisomeric conformers recognize the kinase ATP-site and the BRD4 acetyl lysine binding site, conformational preferences supported by rigid docking studies.</p