Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries

Background: As malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. However, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-Saharan Africa. Methods: A quantitative survey of human movement patterns was conducted in four countries in sub-Saharan Africa: Mali, Burkina Faso, Zambia, and Tanzania, with three to five survey locations chosen in each country. Questions were included on demographic and trip details, malaria risk behaviour, children accompanying travellers, and mobile phone usage to enable phone signal data to be better correlated with movement. A total of 4352 individuals were interviewed and 6411 trips recorded. Results: A cluster analysis of trips highlighted two distinct traveller groups of relevance to malaria transmission: women travelling with children (in all four countries) and youth workers (in Mali). Women travelling with children were more likely to travel to areas of relatively high malaria prevalence in Mali (OR = 4.46, 95 % CI = 3.42–5.83), Burkina Faso (OR = 1.58, 95 % CI = 1.23–1.58), Zambia (OR = 1.50, 95 % CI = 1.20–1.89), and Tanzania (OR = 2.28, 95 % CI = 1.71–3.05) compared to other travellers. They were also more likely to own bed nets in Burkina Faso (OR = 1.77, 95 % CI = 1.25–2.53) and Zambia (OR = 1.74, 95 % CI = 1.34 2.27), and less likely to own a mobile phone in Mali (OR = 0.50, 95 % CI = 0.39–0.65), Burkina Faso (OR = 0.39, 95 % CI = 0.30–0.52), and Zambia (OR = 0.60, 95 % CI = 0.47–0.76). Malian youth workers were more likely to travel to areas of relatively high malaria prevalence (OR = 23, 95 % CI = 17–31) and for longer durations (mean of 70 days cf 21 days, p < 0.001) compared to other travellers. Conclusions: Women travelling with children were a remarkably consistent traveller group across all four countries surveyed. They are expected to contribute greatly towards spatial malaria transmission because the children they travel with tend to have high parasite prevalence. Youth workers were a significant traveller group in Mali and are expected to contribute greatly to spatial malaria transmission because their movements correlate with seasonal rains and hence peak mosquito densities. Interventions aimed at interrupting spatial transmission of parasites should consider these traveller groups

Integration of biological ion channels onto optically addressable micro-fluidic electrode arrays for single molecule characterization.

The challenge of modeling the organization and function of biological membranes on a solid support has received considerable attention in recent years, primarily driven by potential applications in biosensor design. Affinity-based biosensors show great promise for extremely sensitive detection of BW agents and toxins. Receptor molecules have been successfully incorporated into phospholipid bilayers supported on sensing platforms. However, a collective body of data detailing a mechanistic understanding of membrane processes involved in receptor-substrate interactions and the competition between localized perturbations and delocalized responses resulting in reorganization of transmembrane protein structure, has yet to be produced. This report describes a systematic procedure to develop detailed correlation between (recognition-induced) protein restructuring and function of a ligand gated ion channel by combining single molecule fluorescence spectroscopy and single channel current recordings. This document is divided into three sections: (1) reported are the thermodynamics and diffusion properties of gramicidin using single molecule fluorescence imaging and (2) preliminary work on the 5HT{sub 3} serotonin receptor. Thirdly, we describe the design and fabrication of a miniaturized platform using the concepts of these two technologies (spectroscopic and single channel electrochemical techniques) for single molecule analysis, with a longer term goal of using the physical and electronic changes caused by a specific molecular recognition event as a transduction pathway in affinity based biosensors for biotoxin detection

Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

BACKGROUND: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756

Stabilization of angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system (RAAS), is a promising candidate as a treatment for cancer that reflects its antiproliferative and anti-angiogenic properties. However, the peptide’s therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer

Beyond the security paradox:Ten criteria for a socially informed security policy

This article is based on a research that has been funded by the EU project “SurPriSe: Surveillance, Privacy and Security: A large scale participatory assessment of criteria and factors determining acceptability and acceptance of security technologies in Europe”, which received funding from the FP7 program, under the grant number: 285492.This article investigates the normative and procedural criteria adopted by European citizens to assess the acceptability of surveillance-oriented security technologies. It draws on qualitative data gathered at 12 citizen summits in nine European countries. The analysis identifies 10 criteria, generated by citizens themselves, for a socially informed security policy. These criteria not only reveal the conditions, purposes and operation rules that would make current European security policies and technologies more consistent with citizens’ priorities. They also cast light on an interesting paradox: although people feel safe in their daily lives, they believe security could, and should, be improved.PostprintPeer reviewe

Postural development in school children: a cross-sectional study

BACKGROUND: Little information on quantitative sagittal plane postural alignment and evolution in children exists. The objectives of this study are to document the evolution of upright, static, sagittal posture in children and to identify possible critical phases of postural evolution (maturation). METHODS: A total of 1084 children (aged 4–12 years) received a sagittal postural evaluation with the Biotonix postural analysis system. Data were retrieved from the Biotonix internet database. Children were stratified and analyzed by years of age with n = 36 in the youngest age group (4 years) and n = 184 in the oldest age group (12 years). Children were analyzed in the neutral upright posture. Variables measured were sagittal translation distances in millimeters of: the knee relative to the tarsal joint, pelvis relative to the tarsal joint, shoulder relative to the tarsal joint, and head relative to the tarsal joint. A two-way factorial ANOVA was used to test for age and gender effects on posture, while polynomial trend analyses were used to test for increased postural displacements with years of age. RESULTS: Two-way ANOVA yielded a significant main effect of age for all 4 sagittal postural variables and gender for all variables except head translation. No age × gender interaction was found. Polynomial trend analyses showed a significant linear association between child age and all four postural variables: anterior head translation (p < 0.001), anterior shoulder translation (p < 0.001), anterior pelvic translation (p < 0.001), anterior knee translation (p < 0.001). Between the ages of 11 and 12 years, for anterior knee translation, T-test post hoc analysis revealed only one significant rough break in the continuity of the age related trend. CONCLUSION: A significant linear trend for increasing sagittal plane postural translations of the head, thorax, pelvis, and knee was found as children age from 4 years to 12 years. These postural translations provide preliminary normative data for the alignment of a child's sagittal plane posture

Beyond Gross-Pitaevskii Mean Field Theory

A large number of effects related to the phenomenon of Bose-Einstein Condensation (BEC) can be understood in terms of lowest order mean field theory, whereby the entire system is assumed to be condensed, with thermal and quantum fluctuations completely ignored. Such a treatment leads to the Gross-Pitaevskii Equation (GPE) used extensively throughout this book. Although this theory works remarkably well for a broad range of experimental parameters, a more complete treatment is required for understanding various experiments, including experiments with solitons and vortices. Such treatments should include the dynamical coupling of the condensate to the thermal cloud, the effect of dimensionality, the role of quantum fluctuations, and should also describe the critical regime, including the process of condensate formation. The aim of this Chapter is to give a brief but insightful overview of various recent theories, which extend beyond the GPE. To keep the discussion brief, only the main notions and conclusions will be presented. This Chapter generalizes the presentation of Chapter 1, by explicitly maintaining fluctuations around the condensate order parameter. While the theoretical arguments outlined here are generic, the emphasis is on approaches suitable for describing single weakly-interacting atomic Bose gases in harmonic traps. Interesting effects arising when condensates are trapped in double-well potentials and optical lattices, as well as the cases of spinor condensates, and atomic-molecular coupling, along with the modified or alternative theories needed to describe them, will not be covered here.Comment: Review Article (19 Pages) - To appear in 'Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment', Edited by P.G. Kevrekidis, D.J. Frantzeskakis and R. Carretero-Gonzalez (Springer Verlag

On the origin of spaces: morphometric foundations of urban form evolution

The modern discipline of urban morphology gives us a ground for the comparative analysis of cities, which increasingly includes specific quantitative elements. In this paper, we make a further step forward towards the definition of a general method for the classification of urban form. We draw from morphometrics and taxonomy in life sciences to propose such method, which we name ‘urban morphometrics’. We then test it on a unit of the urban landscape named ‘Sanctuary Area’ (SA), explored in 45 cities whose origins span four historic time periods: Historic (medieval), Industrial (19th century), New Towns (post-WWII, high-rise) and Sprawl (post-WWII, low-rise). We describe each SA through 207 physical dimensions and then use these to discover features that discriminate them among the four temporal groups. Nine dimensions emerge as sufficient to correctly classify 90% of the urban settings by their historic origins. These nine attributes largely identify an area's ‘visible identity’ as reflected by three characteristics: (1) block perimeterness, or the way buildings define the street-edge; (2) building coverage, or the way buildings cover the land and (3) regular plot coverage, or the extent to which blocks are made of plots that have main access from a street. Hierarchical cluster analysis utilising only the nine key variables nearly perfectly clusters each SA according to its historic origin; moreover, the resulting dendrogram shows, just after WWII, the first ‘bifurcation’ of urban history, with the emergence of the modern city as a new ‘species’ of urban form. With ‘urban morphometrics’ we hope to extend urban morphological research and contribute to understanding the way cities evolve

Raman study of the anharmonicity in YBa2_2Cu3_3Ox_x

A systematic Raman study in the visible carried out on the YBa2Cu316,18Ox (x=6-7) compounds, with isotopic substitution of 18O for 16O, has detected a doping dependent deviation from harmonic behavior for the frequency shift of the in-phase mode, a smaller amount of anharmonicity for the apex mode, and almost no effect for the out-of-phase B1g-symmetry phonon. It appears that the amount of anharmonicity depends strongly on the oxygen concentration; it diminishes close to the tetragonal to orthorhombic structural phase transition and close to optimal doping, while it reaches its maximum value for the ortho-II and a tetragonal phase. The almost zero anharmonicity at optimal doping persists even at 77K. The data in the overdoped oxygen concentration, where a softening of the in-phase phonon frequency occurs, indicate that the anharmonicity is not enhanced by the sudden increase in the CuO2 buckling. The results fully agree with recent studies of the ortho-II phase but they do not comply with a static double-well potential of the apical oxygen atom at optimal doping.Comment: Dedicated to Prof. K. A. M\"uller on the Occasion of his 90th Birthda

A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A

This is the author accepted manuscript. The final version is available from American Association for the Advancement of Science via the DOI in this record.The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase activity and inhibiting translation. We propose to name BPSL1549 Burkholderia lethal factor 1