Optimizing human pulmonary perfusion measurement using an in silico model of arterial spin labeling magnetic resonance imaging.

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) is an imaging methodology that uses blood as an endogenous contrast agent to quantify flow. One limitation of this method of capillary blood quantification when applied in the lung is the contribution of signals from non-capillary blood. Intensity thresholding is one approach that has been proposed for minimizing the non-capillary blood signal. This method has been tested in previous in silico modeling studies; however, it has only been tested under a restricted set of physiological conditions (supine posture and a cardiac output of 5 L/min). This study presents an in silico approach that extends previous intensity thresholding analysis to estimate the optimal "per-slice" intensity threshold value using the individual components of the simulated ASL signal (signal arising independently from capillary blood as well as pulmonary arterial and pulmonary venous blood). The aim of this study was to assess whether the threshold value should vary with slice location, posture, or cardiac output. We applied an in silico modeling approach to predict the blood flow distribution and the corresponding ASL quantification of pulmonary perfusion in multiple sagittal imaging slices. There was a significant increase in ASL signal and heterogeneity (COV = 0.90 to COV = 1.65) of ASL signals when slice location changed from lateral to medial. Heterogeneity of the ASL signal within a slice was significantly lower (P = 0.03) in prone (COV = 1.08) compared to in the supine posture (COV = 1.17). Increasing stroke volume resulted in an increase in ASL signal and conversely an increase in heart rate resulted in a decrease in ASL signal. However, when cardiac output was increased via an increase in both stroke volume and heart rate, ASL signal remained relatively constant. Despite these differences, we conclude that a threshold value of 35% provides optimal removal of large vessel signal independent of slice location, posture, and cardiac output

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 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

Rapid assessment methods for small farm storage surveys

Farm surveys are often the first step taken in identifying storage problems. As time and money for such work are generally scarce, it is important to be able to make the best use of them to get the information needed. This paper describes some of the specific techniques and experience developed by the Ghana MoFA/UK ODA Larger Grain Borer Project for rapid storage surveys on small-scale farms. It is argued that the following factors can critically contribute to producing more timely and relevant results: • formulation of specific survey objectives which focus on gathering data needed for decision-making. • use of a range of techniques to meet these objectives, including secondary data and key informants, informal surveys, case studies and participatory meetings. • avoidance of unwitting sampling bias, using rapid techniques such as transect village walks to select farmers, along with careful timing of field visits. • methods of sample analysis which can be used in the field, rather than the lab. Field analysis has many benefits including cost, speed, potential for increased sampling, and most importantly the greater participation of farmers and field staff in the analysis and interpretation of results. • use of rapid and flexible techniques of analysis and presentation, in particular mapping. Practical examples of each of these are given

Reduced prevalence of placental malaria in primiparae with blood group O

Background Blood group O protects African children against severe malaria and has reached high prevalence in malarious regions. However, its role in malaria in pregnancy is ambiguous. In 839 delivering Ghanaian women, associations of ABO blood groups with Plasmodium falciparum infection were examined. Methods Plasmodium falciparum infection was diagnosed in placental blood samples by microscopy and PCR assays. Present or past infection was defined as the detection of parasitaemia or haemozoin by microscopy, or a positive PCR result. Blood groups were inferred from genotyping rs8176719 (indicating the O allele) and rs8176746/rs8176747 (distinguishing the B allele from the A allele). Results The majority of women had blood group O (55.4%); present or past P. falciparum infection was seen in 62.3% of all women. Among multiparae, the blood groups had no influence on P. falciparum infection. In contrast, primiparae with blood group O had significantly less present or past infection than women with non-O blood groups (61.5 vs 76.2%, P = 0.007). In multivariate analysis, the odds of present or past placental P. falciparum infection were reduced by 45% in blood group O primiparae (aOR, 0.55 [95% CI, 0.33–0.94]). Conclusions The present study shows a clear protective effect of blood group O against malaria in primiparae. This accords with findings in severe malaria and in vitro results. The data underline the relevance of host genetic protection among primiparae, i.e. the high-risk group for malaria in pregnancy, and contribute to the understanding of high O allele frequencies in Africa

Dose-dependent T-cell Dynamics and Cytokine Cascade Following rVSV-ZEBOV Immunization.

BACKGROUND: The recent West African Ebola epidemic led to accelerated efforts to test Ebola vaccine candidates. As part of the World Health Organisation-led VSV Ebola Consortium (VEBCON), we performed a phase I clinical trial investigating rVSV-ZEBOV (a recombinant vesicular stomatitis virus-vectored Ebola vaccine), which has recently demonstrated protection from Ebola virus disease (EVD) in phase III clinical trials and is currently in advanced stages of licensing. So far, correlates of immune protection are incompletely understood and the role of cell-mediated immune responses has not been comprehensively investigated to date. METHODS: We recruited 30 healthy subjects aged 18-55 into an open-label, dose-escalation phase I trial testing three doses of rVSV-ZEBOV (3×105 plaque-forming units (PFU), 3×106 PFU, 2×107 PFU) (ClinicalTrials.gov; NCT02283099). Main study objectives were safety and immunogenicity, while exploratory objectives included lymphocyte dynamics, cell-mediated immunity and cytokine networks, which were assessed using flow cytometry, ELISpot and LUMINEX assay. FINDINGS: Immunization with rVSV-ZEBOV was well tolerated without serious vaccine-related adverse events. Ebola virus-specific neutralizing antibodies were induced in nearly all individuals. Additionally, vaccinees, particularly within the highest dose cohort, generated Ebola glycoprotein (GP)-specific T cells and initiated a cascade of signaling molecules following stimulation of peripheral blood mononuclear cells with Ebola GP peptides. INTERPRETATION: In addition to a benign safety and robust humoral immunogenicity profile, subjects immunized with 2×107 PFU elicited higher cellular immune responses and stronger interlocked cytokine networks compared to lower dose groups. To our knowledge these data represent the first detailed cell-mediated immuneprofile of a clinical trial testing rVSV-ZEBOV, which is of particular interest in light of its potential upcoming licensure as the first Ebola vaccine. VEBCON trial Hamburg, Germany (NCT02283099)

In utero exposure to cigarette smoking, environmental tobacco smoke and reproductive hormones in US girls approaching puberty

BACKGROUND/AIMS: Evidence is unclear whether prenatal smoking affects age at menarche and pubertal development, and its impact upon hormones has not been well studied. We aim to identify potential pathways through which prenatal smoking and environmental tobacco smoke (ETS) affect reproductive hormones in girls approaching puberty. METHODS: We examined the association between prenatal smoking, current ETS and luteinizing hormone (LH) and inhibin B (InB) in 6- to 11-year-old girls in the 3rd National Health and Nutrition Examination Survey, 1988-1994. Parents/guardians completed interviewer-assisted questionnaires on health and demographics at the time of physical examination. Residual blood samples were analyzed for reproductive hormones in 2008. RESULTS: Of 660 girls, 19 and 39% were exposed to prenatal smoke and current ETS, respectively. Accounting for multiple pathways in structural equation models, prenatally exposed girls had significantly lower LH (β = -0.205 log-mIU/ml, p < 0.0001) and InB (β = -0.162, log-pg/ml, p < 0.0001). Prenatal smoking also influenced LH positively and InB negatively indirectly through BMI-for-age. ETS was positively associated with LH, but not with InB. CONCLUSION: Exposure to maternal smoking may disrupt reproductive development manifesting in altered hormone levels near puberty