2,283 research outputs found
Spatial distribution of Schistosoma mansoni infection before and after chemotherapy with two praziquantel doses in a community of Pernambuco, Brazil
Praziquantel chemotherapy has been the focus of the Schistosomiasis Control Program in Brazil for the past two decades. Nevertheless, information on the impact of selective chemotherapy against Schistosoma mansoni infection under the conditions confronted by the health teams in endemic municipalities remains scarce. This paper compares the spatial pattern of infection before and after treatment with either a 40 mg/kg or 60 mg/kg dose of praziquantel by determining the intensity of spatial cluster among patients at 180 and 360 days after treatment. The spatial-temporal distribution of egg-positive patients was analysed in a Geographic Information System using the kernel smoothing technique. While all patients became egg-negative after 21 days, 17.9% and 30.9% reverted to an egg-positive condition after 180 and 360 days, respectively. Both the prevalence and intensity of infection after treatment were significantly lower in the 60 mg/kg than in the 40 mg/kg treatment group. The higher intensity of the kernel in the 40 mg/kg group compared to the 60 mg/kg group, at both 180 and 360 days, reflects the higher number of reverted cases in the lower dose group. Auxiliary, preventive measures to control transmission should be integrated with chemotherapy to achieve a more enduring impact
Clustering Algorithms for Spatial Big Data
In our time people and devices constantly generate data. User activity generates data about needs and preferences as well as the quality of their experiences in different ways: i. e. streaming a video, looking at the news, searching for a restaurant or a an hotel, playing a game with others, making purchases, driving a car. Even when people put their devices in their pockets, the network is generating location and other data that keeps services running and ready to use. This rapid developments in the availability and access to data and in particular spatially referenced data in a different areas, has induced the need for better analysis techniques to understand the various phenomena. Spatial clustering algorithms, which groups similar spatial objects into classes, can be used for the identification of areas sharing common characteristics. The aim of this paper is to analyze the performance of three different clustering algorithms i.e. the Density-Based Spatial Clustering of Applications with Noise algorithm (DBSCAN), the Fast Search by Density Peak (FSDP) algorithm and the classic K-means algorithm (K-Means) as regards the analysis of spatial big data. We propose a modification of the FSDP algorithm in order to improve its efficiency in large databases. The applications concern both synthetic data sets and satellite images
Ethanol reversal of tolerance to the respiratory depressant effects of morphine
Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths
The Intensive Care Unit as a Research Laboratory: Developing Strategies to Prevent Antimicrobial Resistance
A single sub-km Kuiper Belt object from a stellar Occultation in archival data
The Kuiper belt is a remnant of the primordial Solar System. Measurements of
its size distribution constrain its accretion and collisional history, and the
importance of material strength of Kuiper belt objects (KBOs). Small, sub-km
sized, KBOs elude direct detection, but the signature of their occultations of
background stars should be detectable. Observations at both optical and X-ray
wavelengths claim to have detected such occultations, but their implied KBO
abundances are inconsistent with each other and far exceed theoretical
expectations. Here, we report an analysis of archival data that reveals an
occultation by a body with a 500 m radius at a distance of 45 AU. The
probability of this event to occur due to random statistical fluctuations
within our data set is about 2%. Our survey yields a surface density of KBOs
with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out
inferred surface densities from previous claimed detections by more than 5
sigma. The fact that we detected only one event, firmly shows a deficit of
sub-km sized KBOs compared to a population extrapolated from objects with r>50
km. This implies that sub-km sized KBOs are undergoing collisional erosion,
just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until
1800 hours London time on 16 December. 19 pages; 7 figure
Risk, reassurance and routine: a qualitative study of narrative understandings of the potential for HIV self-testing among men who have sex with men in England
BACKGROUND: HIV testing has seen a rapid evolution over the last decade with multiple modalities now in use globally. In recent years HIV self-testing (HIVST) has been legalised in the UK paving the way for further expansion of testing. Interventions are delivered in particular social contexts which shape uptake. It is therefore important to understand how novel interventions are likely to be received by their intended users. This study aims to understand how HIVST compliments existing testing strategies considered or adopted by men who have sex with men (MSM). We do this by analysing normative discourses surrounding HIV testing and their perceptions of HIVST's potential future roles. METHODS: Six focus group discussions (FGDs) were conducted with 47 MSM in London, Manchester and Plymouth. One focus group included only MSM who reported higher risk behaviours and one with those who had never tested for HIV. Data were analysed through a thematic framework analysis. RESULTS: Three main narratives for testing for HIV were identified: (i) testing in response to a specific risk event; (ii) as reassurance when there was a small amount of doubt or anxiety related to HIV; and (iii) in response to social norms perpetuated through peers, HIV community groups and the medical establishment to test regularly for HIV. HIVST had limited utility for men when testing in response to specific risk events except in the case of significant structural barriers to other testing opportunities. HIVST was considered to have utility when seeking reassurance, and was thought to be very useful when testing to satisfy the needs and expectations of others around regular testing. There was some ambivalence about the incursion of a clinical intervention into the home. CONCLUSIONS: HIVST following risk events will likely be limited to those for whom existing service provision is insufficient to meet immediate needs based on structural or personal barriers to testing. Obligations of biological citizenship are central to MSM's understanding of the utility of HIVST. In the context of discourses of biocitizenship, men perceive HIVST to have dual roles: firstly as a tool to manage (mild) anxiety around one's HIV status based on an acknowledgment of HIV vulnerability arising from being homosexually active. Secondly, HIVST is useful in complying with social norms and meeting the perceived demands of biomedicine
Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.
BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status
Global analyses of TetR family transcriptional regulators in mycobacteria indicates conservation across species and diversity in regulated functions
BACKGROUND: Mycobacteria inhabit diverse niches and display high metabolic versatility. They can colonise both humans and animals and are also able to survive in the environment. In order to succeed, response to environmental cues via transcriptional regulation is required. In this study we focused on the TetR family of transcriptional regulators (TFTRs) in mycobacteria. RESULTS: We used InterPro to classify the entire complement of transcriptional regulators in 10 mycobacterial species and these analyses showed that TFTRs are the most abundant family of regulators in all species. We identified those TFTRs that are conserved across all species analysed and those that are unique to the pathogens included in the analysis. We examined genomic contexts of 663 of the conserved TFTRs and observed that the majority of TFTRs are separated by 200 bp or less from divergently oriented genes. Analyses of divergent genes indicated that the TFTRs control diverse biochemical functions not limited to efflux pumps. TFTRs typically bind to palindromic motifs and we identified 11 highly significant novel motifs in the upstream regions of divergently oriented TFTRs. The C-terminal ligand binding domain from the TFTR complement in M. tuberculosis showed great diversity in amino acid sequence but with an overall architecture common to other TFTRs. CONCLUSION: This study suggests that mycobacteria depend on TFTRs for the transcriptional control of a number of metabolic functions yet the physiological role of the majority of these regulators remain unknown. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1696-9) contains supplementary material, which is available to authorized users
The Epoxygenases CYP2J2 Activates the Nuclear Receptor PPARα In Vitro and In Vivo
Peroxisome proliferator-activated receptors (PPARs) are a family of three (PPARalpha, -beta/delta, and -gamma) nuclear receptors. In particular, PPARalpha is involved in regulation of fatty acid metabolism, cell growth and inflammation. PPARalpha mediates the cardiac fasting response, increasing fatty acid metabolism, decreasing glucose utilisation, and is the target for the fibrate lipid-lowering class of drugs. However, little is known regarding the endogenous generation of PPAR ligands. CYP2J2 is a lipid metabolising cytochrome P450, which produces anti-inflammatory mediators, and is considered the major epoxygenase in the human heart.Expression of CYP2J2 in vitro results in an activation of PPAR responses with a particular preference for PPARalpha. The CYP2J2 products 8,9- and 11-12-EET also activate PPARalpha. In vitro, PPARalpha activation by its selective ligand induces the PPARalpha target gene pyruvate dehydrogenase kinase (PDK)4 in cardiac tissue. In vivo, in cardiac-specific CYP2J2 transgenic mice, fasting selectively augments the expression of PDK4.Our results establish that CYP2J2 produces PPARalpha ligands in vitro and in vivo, and suggests that lipid metabolising CYPs are prime candidates for the integration of global lipid changes to transcriptional signalling events
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