The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV‐1 infection in children in Europe and are an update to those ...published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short‐term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long‐term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first‐ and second‐line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART ‘pipeline’ of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.
The search for the standard model Higgs boson at the Large Hadron Collider (LHC) started more than two decades ago. Much innovation was required and diverse challenges had to be overcome during the ...conception and construction of the LHC and its experiments. The ATLAS and CMS Collaboration experiments at the LHC have discovered a heavy boson that could complete the standard model of particle physics.
Background. Severely immunocompromised individuals are highly susceptible to Candida infection of the esophagus. This randomized, double-blind study assessed the dose-response relationship of the new ...echinocandin antifungal, micafungin, compared with that of standard fluconazole treatment. Methods. A total of 245 patients (age, ⩾18 years) with a prior diagnosis of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection and esophageal candidiasis, confirmed by endoscopy and culture, were randomized to receive micafungin (50, 100, or 150 mg per day) or fluconazole (200 mg per day). Both agents were administered once per day by a 1-h intravenous infusion for 14–21 days. The primary efficacy end point was endoscopic cure rate, defined as endoscopy grade of 0 at the end of therapy. Results. The endoscopic cure rate (grade 0) was dose-dependent with 50, 100, and 150 mg of micafungin per day at 68.8%, 77.4%, and 89.8%, respectively. Symptoms improved or resolved rapidly (3–7 days of treatment in the majority of patients). The endoscopic cure rate for 100 and 150 mg of micafungin per day (83.5%) was comparable to that for 200 mg of fluconazole per day (86.7%; 95% confidence interval for the difference in endoscopic cure rate, -14.0% to 7.7%). The overall safety and tolerability was acceptable, with no important differences between micafungin (all doses) and fluconazole. Conclusions. The dose-response findings demonstrate a greater efficacy with micafungin at 100 and 150 mg per day than at 50 mg per day. This study also indicates that the efficacy of micafungin (at dosages of 100 and 150 mg per day) was comparable to that of fluconazole, suggesting that micafungin represents a valuable new treatment option for esophageal candidiasis in HIV-positive patients.
Short chained triesters of glycerol and citric acid were systematically investigated as novel dual-functional dispersants and plasticisers for use in ceramic processing. Additional systematic studies ...on a series of diesters having structural similarities with the citrate and glycerol triesters were performed to further assess the significance of specific functional groups for the stabilisation of suspensions.
The overall purpose of this work consists in simplifying the formulation for ceramic processing slurries while at the same time limiting the environmental impact and toxicity. The use of multifunctional additives reduces the risk of unwanted interactions between different components. Additionally, the possible use of one additive in more than one role opens the opportunity for an overall reduction in the number and amount of chemicals and therefore reduction of costs and risks.
For the citrate ester candidates, different alkoxy groups were tested as well as the acetylation on the hydroxyl group. The glycerol esters differed by the length of the carboxylic chain.
Especially triethyl and tributyl citrate are proposed as promising dual-functional additives for ceramic processing. Specifically, for triethyl citrate the dual-function was finally demonstrated by producing a dense piece of 8YSZ through tape casting and subsequent sintering.
Centres participating in the Paediatric European Network for Treatment of AIDS (PENTA), including Thailand and Brazil.
To describe the incidence, presentation, treatment and treatment outcomes of ...tuberculosis (TB) in human immunodeficiency virus (HIV) infected children.
Observational study of TB diagnosed in HIV-infected children in 2011-2013.
Of 4265 children aged <16 years, 127 (3%) were diagnosed with TB: 6 (5%) in Western Europe, 80 (63%) in Eastern Europe, 27 (21%) in Thailand and 14 (11%) in Brazil, with estimated TB incidence rates of respectively 239, 982, 1633 and 2551 per 100 000 person-years (py). The majority (94%) had acquired HIV perinatally. The median age at TB diagnosis was 6.8 years (interquartile range 3.0-11.5). Over half (52%) had advanced/severe World Health Organization stage immunodeficiency; 67 (53%) were not on antiretroviral therapy (ART) at TB diagnosis. Preventive anti-tuberculosis treatment was given to 23% (n = 23) of 102 children diagnosed with HIV before TB. Eleven children had unfavourable TB outcomes: 4 died, 5 did not complete treatment, 1 had recurrent TB and 1 had an unknown outcome. In univariable analysis, previous diagnosis of acquired immune-deficiency syndrome, not being virologically suppressed on ART at TB diagnosis and region (Brazil) were significantly associated with unfavourable TB outcomes.
Most TB cases were from countries with high TB prevalence. The majority (91%) had favourable outcomes. Universal ART and TB prophylaxis may reduce missed opportunities for TB prevention.
For small length tape casting of ceramic slurries varying green film thickness is often a problem. To optimise this, the following parameters were investigated: single blade, double blade, using a ...pump system and a modelled speed change mode have been analysed. Advantages and limitations of every method are described here. The tape casting experiments were built to be generic in order to allow the control of various processing conditions.
From these results, the single-blade technique was chosen for a study of side-by-side tape casting. The influence of the geometric parameters of partitioning the casting tank into chambers, on the quality of graded tape was studied. Tape casting experiments at different speeds and partition tongue lengths in combination with rheological tests revealed that high casting speeds and absence of the partition under the blade are detrimental to the formation of the smooth well-controlled interface between the co-cast slurries, required for most of applications.
To describe the long-term efficacy over 5 years of regimens including combinations of abacavir, lamivudine and/or zidovudine in previously untreated children in the PENTA 5 trial.
PENTA 5 was a ...48-week randomised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor (NRTI) combinations as part of first triple antiretroviral therapy (ART).
128 ART-naïve children were randomised to zidovudine\lamivudine (n = 36), zidovudine\abacavir (45) or lamivudine\abacavir (47). Asymptomatic children (n = 55) were also randomised to nelfinavir or placebo; all other children received open-label nelfinavir. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo.
Median follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had changed their randomised NRTIs in the zidovudine\lamivudine, zidovudine\abacavir and lamivudine\abacavir groups respectively, but 18%, 50% and 50% of these changes were either early single drug substitutions for toxicity or switches with viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery). At 5 years, 55%/32% zidovudine\lamivudine, 50%/25% zidovudine\abacavir and 79%/63% lamivudine\abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p = 0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02); weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V).
Five year data demonstrate that lamivudine\abacavir is more effective in terms of HIV-1 RNA suppression and growth changes, with lower rates of switching with detectable HIV-1 RNA than zidovudine\lamivudine or zidovudine\abacavir, and should be preferred as first-line NRTI backbone.
A systematic screening of plasticisers for a polyvinyl butyral based binder system revealed that dibutyl maleate, dibutyl adipate and Pycal 94 are promising and less toxic alternatives to the very ...harmful but frequently used dibutyl phthalate. Pycal 94 seems especially promising as it unlike the two other candidates did not require a co-plasticiser, such as a polyethylene glycol, thus simplifying the system and reducing the risk of unwanted cross-interactions.
An effective and systematic procedure for substitution of the plasticiser, while maintaining chemical compatibility and mechanical properties, was also demonstrated. Incompatible systems were discarded in an initial broad screening while primary systems were further evaluated based on debinding properties, mechanical properties, flow behavior as well as sintering properties of ceramic tapes. The thermomechanical characterization performed on dried drops of binder and their corresponding tapes show strong similarities in the strain/stress profiles, validating the qualitative method used.
The research activity of our group in the last few years has mainly been devoted to the study of ultrathin vanadium oxide films deposited on a (110)-oriented TiO2 single crystal, in order to prepare ...systems which may be largely thought of as simplified models for the investigation of the structure/properties relationships in real world catalysts, sensing and optical devices. The main objective of our work consists of setting up reproducible synthesis routes for the deposition of vanadium oxide ultrathin films on TiO2 (110), through strict control of the reaction parameters. The films obtained are then characterised from a chemical, electronic and structural point of view, and their properties are compared to those of their bulk-related phases. Results are presented concerning growth procedures and structural and electronic properties of vanadium oxide ultrathin films on titania, with a stoichiometry ranging from VO2, down to approximately VO. In particular, it will be shown that the oxidation product of metallic vanadium in an oxygen or water atmosphere (in the 10-6 mbar range) retains the rutile lattice structure typical of stoichiometric VO2, despite the increasing degree of oxygen defectiveness and the electronic properties, very similar to those pertaining to bulk V2O3. The peculiar behaviour of vanadium oxide on titania demonstrates how important the epitaxial influence of the substrate is on the nature of the overlayer. These results could represent a good starting point to understand why vanadium oxides on TiO2 show an enhanced catalytic activity and selectivity in many industrially relevant reactions.
We sought to identify and understand the health care needs of young people living with HIV/AIDS, particularly in terms of their psychosocial well-being. We conducted a qualitative analysis of ...HIV-positive young people and their caregivers, focusing on the implications of an HIV diagnosis for health care needs. Stigma was a recurrent issue that arose in the interviews conducted with the respondents, and it was evident that youths had been denied many rights related to health. We concluded that young people living with HIV need comprehensive care based on a human rights approach. In this regard, we offer some practical recommendations for health programs.
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