Treatment-seeking rates in malaria endemic countries

BACKGROUND: The proportion of individuals who seek treatment for fever is an important quantity in understanding access to and use of health systems, as well as for interpreting data on disease incidence from routine surveillance systems. For many malaria endemic countries (MECs), treatment-seeking information is available from national household surveys. The aim of this paper was to assemble sub-national estimates of treatment-seeking behaviours and to predict national treatment-seeking measures for all MECs lacking household survey data. METHODS: Data on treatment seeking for fever were obtained from Demographic and Health Surveys, Malaria Indicator Surveys and Multiple Cluster Indicator Surveys for every MEC and year that data were available. National-level social, economic and health-related variables were gathered from the World Bank as putative covariates of treatment-seeking rates. A generalized additive mixed model (GAMM) was used to estimate treatment-seeking behaviours for countries where survey data were unavailable. Two separate models were developed to predict the proportion of fever cases that would seek treatment at (1) a public health facility or (2) from any kind of treatment provider. RESULTS: Treatment-seeking data were available for 74 MECs and modelled for the remaining 24. GAMMs found that the percentage of pregnant women receiving prenatal care, vaccination rates, education level, government health expenditure, and GDP growth were important predictors for both categories of treatment-seeking outcomes. Treatment-seeking rates, which varied both within and among regions, revealed that public facilities were not always the primary facility type used. CONCLUSIONS: Estimates of treatment-seeking rates show how health services are utilized and help correct reported malaria case numbers to obtain more accurate measures of disease burden. The assembled and modelled data demonstrated that while treatment-seeking rates have overall increased over time, access remains low in some malaria endemic regions and utilization of government services is in some areas limited

Macroecological patterns in flower colour are shaped by both biotic and abiotic factors

There is a wealth of research on the way interactions with pollinators shape flower traits. However, we have much more to learn about influences of the abiotic environment on flower colour. We combine quantitative flower colour data for 339 species from a broad spatial range covering tropical, temperate, arid, montane and coastal environments from 9.25ºS to 43.75ºS with 11 environmental variables to test hypotheses about how macroecological patterns in flower colouration relate to biotic and abiotic conditions. Both biotic community and abiotic conditions are important in explaining variation of flower colour traits on a broad scale. The diversity of pollinating insects and the plant community have the highest predictive power for flower colouration, followed by mean annual precipitation and solar radiation. On average, flower colours are more chromatic where there are fewer pollinators, solar radiation is high, precipitation and net primary production are low, and growing seasons are short, providing support for the hypothesis that higher chromatic contrast of flower colours may be related to stressful conditions. To fully understand the ecology and evolution of flower colour, we should incorporate the broad selective context that plants experience into research, rather than focusing primarily on effects of plant–pollinator interactions

Conservation genetics of the annual hemiparasitic plant Melampyrum sylvaticum (Orobanchaceae) in the UK and Scandinavia

Melampyrum sylvaticum is an endangered annual hemiparasitic plant that is found in only 19 small and isolated populations in the United Kingdom (UK). To evaluate the genetic consequences of this patchy distribution we compared levels of diversity, inbreeding and differentiation from ten populations from the UK with eight relatively large populations from Sweden and Norway where the species is more continuously distributed. We demonstrate that in both the UK and Scandinavia, the species is highly inbreeding (global F IS = 0.899). Levels of population differentiation were high (F’ST = 0.892) and significantly higher amongst UK populations (F’ST = 0.949) than Scandinavian populations (F’ST = 0.762; P < 0.01). The isolated populations in the UK have, on average, lower genetic diversity (allelic richness, proportion of loci that are polymorphic, gene diversity) than Scandinavian populations, and this diversity difference is associated with the smaller census size and population area of UK populations. From a conservation perspective, the naturally inbreeding nature of the species may buffer the species against immediate effects of inbreeding depression, but the markedly lower levels of genetic diversity in UK populations may represent a genetic constraint to evolutionary change. In addition, the high levels of population differentiation suggest that gene flow among populations will not be effective at replenishing lost variation. We thus recommend supporting in situ conservation management with ex situ populations and human-mediated seed dispersal among selected populations in the UK

Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer

Background:Tasquinimod is a quinoline-3-carboxamide derivative with anti-angiogenic activity. Two open-label phase I clinical trials in patients were conducted to evaluate the safety and tolerability of tasquinimod, with additional pharmacokinetic and efficacy assessments.Methods:Patients with castration-resistant prostate cancer with no previous chemotherapy were enrolled in this study. The patients received tasquinimod up to 1 year either at fixed doses of 0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to 1.0 mg per day.Results:A total of 32 patients were enrolled; 21 patients were maintained for >/=4 months. The maximum tolerated dose was determined to be 0.5 mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0 mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia and asymptomatic elevation in amylase. Common treatment-emergent adverse events included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia and pain. A serum prostate-specific antigen (PSA) decline of >/=50% was noted in two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out of 15 patients (median time on study: 34 weeks) developed new bone lesions.Conclusion:Long-term continuous oral administration of tasquinimod seems to be safe, and the overall efficacy results indicate that tasquinimod might delay disease progression.British Journal of Cancer advance online publication, 15 September 2009; doi:10.1038/sj.bjc.6605322 www.bjcancer.com

malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project

Background The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released malariaAtlas, an R package providing a direct interface to MAP’s routinely-updated malariometric databases and research outputs. Methods and results The current paper reviews the functionality available in malariaAtlas and highlights its utility for spatial epidemiological analysis of malaria. malariaAtlas enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research. malariaAtlas is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis. Conclusions malariaAtlas is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the malariaAtlas package aims to contribute to the environment of data-sharing within the malaria research community

Individual differences in the detection, matching and memory of faces

Previous research has explored relationships between individual performance in the detection, matching and memory of faces, but under limiting conditions. The current study sought to extend previous findings with a different measure of face detection, and a more challenging face matching task, in combination with an established test of face memory. Experiment 1 tested face detection ability under conditions designed to maximise individual differences in accuracy but did not find evidence for relationships between measures. In addition, in Experiments 2 and 3, which utilised response times as the primary performance measure for face detection, but accuracy for face matching and face memory, no correlations were observed between performance on face detection and the other tasks. However, there was a correlation between accuracy in face matching and face memory, consistent with other research. Together, these experiments provide further evidence for a dissociation between face detection, and face matching and face memory, but suggest that these latter tasks share some common mechanisms

Mild Cognitive Impairment as a risk factor for Parkinson's disease dementia

Background The International Parkinson and Movement Disorders Society criteria for mild cognitive impairment in Parkinson’s disease were recently formulated. Objectives The aim of this international study was to evaluate the predictive validity of the comprehensive (level II) version of these criteria by assessment of their contribution to the hazard of Parkinson’s disease dementia. Methods Individual patient data were selected from four separate studies on cognition in Parkinson’s disease that provided information on demographics, motor examination, depression, neuropsychological examination suitable for application of level II criteria, and longitudinal follow-up for conversion to dementia. Survival analysis evaluated the predictive value of level II criteria for cognitive decline towards dementia as expressed by the relative hazard of dementia. Results A total of 467 patients were included. The analyses showed a clear contribution of impairment according to level II mild cognitive impairment criteria, age and severity of Parkinson’s disease motor symptoms to the hazard of dementia. There was a trend of increasing hazard of dementia with declining neuropsychological performance. Conclusions This is the first large international study evaluating the predictive validity of level II mild cognitive impairment criteria for Parkinson’s disease. The results showed a clear and unique contribution of classification according to level II criteria to the hazard of Parkinson’s disease dementia. This finding supports their predictive validity and shows that they contribute important new information on the hazard of dementia, beyond known demographic and Parkinson’s disease specific factors of influence.Michael J. Fox Foundation Dutch Parkinson Foundatio

Angiogenesis inhibitors in the treatment of prostate cancer

Prostate cancer remains a significant public health problem, with limited therapeutic options in the setting of castrate-resistant metastatic disease. Angiogenesis inhibition is a relatively novel antineoplastic approach, which targets the reliance of tumor growth on the formation of new blood vessels. This strategy has been used successfully in other solid tumor types, with the FDA approval of anti-angiogenic agents in breast, lung, colon, brain, and kidney cancer. The application of anti-angiogenic therapy to prostate cancer is reviewed in this article, with attention to efficacy and toxicity results from several classes of anti-angiogenic agents. Ultimately, the fate of anti-angiogenic agents in prostate cancer rests on the eagerly anticipated results of several key phase III studies

Sex differences in the Simon task help to interpret sex differences in selective attention.

In the last decade, a number of studies have reported sex differences in selective attention, but a unified explanation for these effects is still missing. This study aims to better understand these differences and put them in an evolutionary psychological context. 418 adult participants performed a computer-based Simon task, in which they responded to the direction of a left or right pointing arrow appearing left or right from a fixation point. Women were more strongly influenced by task-irrelevant spatial information than men (i.e., the Simon effect was larger in women, Cohen's d = 0.39). Further, the analysis of sex differences in behavioral adjustment to errors revealed that women slow down more than men following mistakes (d = 0.53). Based on the combined results of previous studies and the current data, it is proposed that sex differences in selective attention are caused by underlying sex differences in core abilities, such as spatial or verbal cognition

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours