4,274 research outputs found

    HIV infection and domestic smoke exposure, but not human papillomavirus, are risk factors for esophageal squamous cell carcinoma in Zambia: a case-control study

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    (c) 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

    Pharmacokinetic studies in children: recommendations for practice and research.

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    Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight

    Lesiones faciales en niños y adolescentes víctimas de agresiones

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    Child maltreatment may occur as the intentional use of power, effective or attempted, against children under 18 years old, that results or may result in actual or potential harm. It affects a vulnerable population, causing physical and/or emotional consequences persisting throughout their lives. This study aimed to characterize episodes of child maltreatment, with focus on facial injuries, in a Brazilian city (Teresina, PI). This is a retrospective study with a quantitative approach, carried out in the database at the Institute of Forensic MedicineinTeresina, between the years 2017 and 2019. All reports of bodily injury of children from 0 to 18 years were collected and statistically analyzed (SPSS 22.0). During the period analysis, 811 reports of bodily injury were identified. There was a predominance of female victims aged between 12 and 18 years old, the involvement of men with some family relationship with the victim was highly associated. Facial injuries represented 35.8% of the whole sample and 98.6% of those found in the head and neck region (41,6% of the total). The orbital (29.0%) was the most affected site, followed by the frontal (25.9%), malar (23.4%), labial (17.6%) and cheek area (11.4%). There is a high prevalence of injuries to the head and neck region, this factemphasizes the importance of a trained professional, especially a dental surgeon, in the analysis and interpretation of these injuries during forensic examination.info:eu-repo/semantics/publishedVersio

    Influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel Australian hospitals in 2014: The influenza complications alert network (FluCAN)

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    The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6–77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6%, 95% CI: 36.0–98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm0

    Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

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    Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

    Geographic Coincidence of Increased Malaria Transmission Hazard and Vulnerability Occurring at the Periphery of two Tanzanian Villages.

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    The goal of malaria elimination necessitates an improved understanding of any fine-scale geographic variations in transmission risk so that complementary vector control tools can be integrated into current vector control programmes as supplementary measures that are spatially targeted to maximize impact upon residual transmission. This study examines the distribution of host-seeking malaria vectors at households within two villages in rural Tanzania. Host-seeking mosquitoes were sampled from 72 randomly selected households in two villages on a monthly basis throughout 2008 using CDC light-traps placed beside occupied nets. Spatial autocorrelation in the dataset was examined using the Moran's I statistic and the location of any clusters was identified using the Getis-Ord Gi* statistic. Statistical associations between the household characteristics and clusters of mosquitoes were assessed using a generalized linear model for each species. For both Anopheles gambiae sensu lato and Anopheles funestus, the density of host-seeking females was spatially autocorrelated, or clustered. For both species, houses with low densities were clustered in the semi-urban village centre while houses with high densities were clustered in the periphery of the villages. Clusters of houses with low or high densities of An. gambiae s.l. were influenced by the number of residents in nearby houses. The occurrence of high-density clusters of An. gambiae s.l. was associated with lower elevations while An. funestus was also associated with higher elevations. Distance from the village centre was also positively correlated with the number of household occupants and having houses constructed with open eaves. The results of the current study highlight that complementary vector control tools could be most effectively targeted to the periphery of villages where the households potentially have a higher hazard (mosquito densities) and vulnerability (open eaves and larger households) to malaria infection

    Analysis of motion during the breast clamping phase of mammography

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    Objectives: To measure paddle motion during the clamping phase of a breast phantom for a range of machine/paddle combinations. Methods: A deformable breast phantom was used to simulate a female breast. Twelve mammography machines from three manufacturers with twenty two flexible and twenty fixed paddles were evaluated. Vertical motion at the paddle was measured using two calibrated linear potentiometers. For each paddle, the motion in millimeters was recorded every 0.5 seconds for 40 seconds while the phantom was compressed with 80 N. Independent t-tests were used to determine differences in paddle motion between flexible and fixed, small and large, GE Senographe Essential and Hologic Selenia Dimensions paddles. Paddle tilt in the medial-lateral plane for each machine/paddle combination was calculated. Results: All machine/paddle combinations demonstrate highest levels of motion during the first 10s of the clamping phase. Least motion is 0.17±0.05 mm/10s (n=20) and the most is 0.51±0.15 mm/10s (n=80). There is a statistical difference in paddle motion between fixed and flexible (p<0.001), GE Senographe Essential and Hologic Selenia Dimensions paddles (p<0.001). Paddle tilt in the medial-lateral plane is independent of time and varied from 0.04° to 0.69°. Conclusions: All machine/paddle combinations exhibited motion and tilting and the extent varied with machine and paddle sizes and types. Advances in knowledge: This research suggests that image blurring will likely be clinically insignificant 4 seconds or more after the clamping phase commences

    Extra patient movement during mammographic imaging : an experimental study

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    Objectives: To determine if movement external to the patient occurring during mammography may be a source of image blur. Methods: Four mammography machines with seven flexible and nine fixed paddles were evaluated. In the first stage, movement at the paddle was measured mechanically using two calibrated linear potentiometers. A deformable breast phantom was used to mimic a female breast. For each paddle, the movement in millimeters and change in compression force in Newton was recorded at 0.5 and 1 second intervals respectively for 40 seconds with the phantom in an initially compressed state under a load of 80N. In the second stage, clinical audit on 28 females was conducted on one mammography machine with the 18x24cm and 24x29cm flexible paddles. Results: Movement at the paddle followed an exponential decay with a settling period of approximately 40 seconds. The compression force readings for both fixed and flexible paddles decreased exponentially with time while fixed paddles have a larger drop in compression force than flexible paddles. There is a linear relationship between movement at the paddle and change in compression force. Conclusions: Movement measured at the paddle during an exposure can be represented by a second order system. The amount of extra-patient movement during the actual exposure can be estimated using the linear relationship between movement at the paddle and the change in compression force. Advances in knowledge: This research provides a possible explanation to mammography image blurring caused by extra patient movement and proposes a theoretical model to analyze the movement
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