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Contains fulltext : 232479.pdf (Publisher’s version ) (Open Access), BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy (ART) is highly effective and well-tolerated in adults and is rapidly being adopted globally. We describe the design of the ODYSSEY trial which evaluates the efficacy and safety of DTG-based ART compared with standard-of-care in children and adolescents. The ODYSSEY trial includes nested pharmacokinetic (PK) sub-studies which evaluated pragmatic World Health Organization (WHO) weight-band-based DTG dosing and opened recruitment to children < 14 kg while dosing was in development. METHODS: ODYSSEY (Once-daily DTG based ART in Young people vS. Standard thErapY) is an open-label, randomised, non-inferiority, basket trial comparing the efficacy and safety of DTG + 2 nucleos(t) ides (NRTIs) versus standard-of-care (SOC) in HIV-infected children < 18 years starting first-line ART (ODYSSEY A) or switching to second-line ART (ODYSSEY B). The primary endpoint is clinical or virological failure by 96 weeks. RESULTS: Between September 2016 and June 2018, 707 children weighing ≥14 kg were enrolled; including 311 ART-naïve children and 396 children starting second-line. 47% of children were enrolled in Uganda, 21% Zimbabwe, 20% South Africa, 9% Thailand, 4% Europe. 362 (51%) participants were male; median age [range] at enrolment was 12.2 years [2.9-18.0]. 82 (12%) children weighed 14 to < 20 kg, 135 (19%) 20 to < 25 kg, 206 (29%) 25 to < 35 kg, 284 (40%) ≥35 kg. 128 (18%) had WHO stage 3 and 60 (8%) WHO stage 4 disease. Challenges encountered include: (i) running the trial across high- to low-income countries with differing frequencies of standard-of-care viral load monitoring; (ii) evaluating pragmatic DTG dosing in PK sub-studies alongside FDA- and EMA-approved dosing and subsequently transitioning participants to new recommended doses; (iii) delays in dosing information for children weighing 3 to < 14 kg and rapid recruitment of ART-naïve older/heavier children, which led to capping recruitment of participants weigh

Cedrus libani ssp. libani (Pinaceae) is a plant used in traditional medicine for the treatment of various diseases. 2-Himachalene-7-ol, previously isolated from the plant, possesses in vitro anticancer activity [1]. The present study investigates the chemopreventive effects of 2-himachalene-7-ol on 7,12-dimethyl benz(a)anthracene (DMBA)/12-O-tetradecanoyl phorobol-13-acetate (TPA) skin tumorigenesis model in mice. The stem xylem was extracted with hexane and the obtained oil was subjected to silica gel chromatography to isolate 2-himachalen-7-ol. Papilloma were initiated on shaved dorsal skin using DMBA and promoted twice weekly using TPA for 20 weeks [2]. Animal groups were treated once weekly with 2-himachalen-7-ol via different routes: gavage (50 mg/kg), intraperitoneally (IP 10, 25, or 50 mg/kg) or topically (0.2mL of 0.5, 1 or 2.5%). Tumor yield, and volume were compared with those of non-treated control and cisplatinum-treated groups (IP 2.5 mg/kg). Liver and kidney toxicity as well as body weight changes were also investigated. Data were analysed using ANOVA. At week 16 all animal groups treated with either 2-himachalen-7-ol or cisplatinum had relatively less papilloma number (0 – 52%) and volume (30 – 66%; p < 0.05). At week 20 the number of papilloma was highest in the cisplatinum and lowest in the 2-himachalen-7-ol IP 10 mg/kg groups. Inhibition of papilloma volume was maximal in the 2-himachalen-7-ol IP 25, IP 50 and gavage (48 – 52%; p < 0.01) followed by IP 10 and topical 2.5% (43%: p < 0.05) then cisplatinum (28%; NS) groups. The least gain in body weight was observed with the cisplatinum group. Liver enzymes (ALP, ALT and AST) were not affected in all treated groups; however creatinine and urea levels were significantly higher (p < 0.05) in the cisplatinum group compared to control. In conclusion, 2-himachalen-7-ol has potent antitumor activity against DMBA/TPA skin carcinogenesis with relatively lower toxicity than commonly used chemotherapeutic drug

Cedrus libani ssp. libani (Pinaceae) is a plant used in traditional medicine for the treatment of various diseases. 2-Himachalene-7-ol, previously isolated from the plant, possesses in vitro anticancer activity [1]. The present study investigates the chemopreventive effects of 2-himachalene-7-ol on 7,12-dimethyl benz(a)anthracene (DMBA)/12-O-tetradecanoyl phorobol-13-acetate (TPA) skin tumorigenesis model in mice. The stem xylem was extracted with hexane and the obtained oil was subjected to silica gel chromatography to isolate 2-himachalen-7-ol. Papilloma were initiated on shaved dorsal skin using DMBA and promoted twice weekly using TPA for 20 weeks [2]. Animal groups were treated once weekly with 2-himachalen-7-ol via different routes: gavage (50 mg/kg), intraperitoneally (IP 10, 25, or 50 mg/kg) or topically (0.2mL of 0.5, 1 or 2.5%). Tumor yield, and volume were compared with those of non-treated control and cisplatinum-treated groups (IP 2.5 mg/kg). Liver and kidney toxicity as well as body weight changes were also investigated. Data were analysed using ANOVA. At week 16 all animal groups treated with either 2-himachalen-7-ol or cisplatinum had relatively less papilloma number (0 – 52%) and volume (30 – 66%; p < 0.05). At week 20 the number of papilloma was highest in the cisplatinum and lowest in the 2-himachalen-7-ol IP 10 mg/kg groups. Inhibition of papilloma volume was maximal in the 2-himachalen-7-ol IP 25, IP 50 and gavage (48 – 52%; p < 0.01) followed by IP 10 and topical 2.5% (43%: p < 0.05) then cisplatinum (28%; NS) groups. The least gain in body weight was observed with the cisplatinum group. Liver enzymes (ALP, ALT and AST) were not affected in all treated groups; however creatinine and urea levels were significantly higher (p < 0.05) in the cisplatinum group compared to control. In conclusion, 2-himachalen-7-ol has potent antitumor activity against DMBA/TPA skin carcinogenesis with relatively lower toxicity than commonly used chemotherapeutic drug

Cedrus libani is among the oldest Cedrus species in the Mediterranean region. Its essential oil has been utilized in folk medicine in Lebanon and was recently shown to possess antileukemic activity [1]. The current study aims to isolate and characterize the major compound responsible for anticancer activity. Cedrus wood (100 g) was extracted with hexane using a soxhlet apparatus to obtain 2.4 g of crude oil. The oil (1 g) was then eluted with 9:1 hexane:ethyl acetate using a silica gel-based column to yield 2-himchalene-7-ol as a white crystalline solid (125 mg, 0.3%). The identity of the sesquiterpene was determined by GC-MS, 13C NMR and X-ray Crystallography. To the best of our knowledge, this is the first time that 2-himachalene-7ol has been isolated from the wood of Cedrus libani. 2-Himachalene-7-ol was then tested against brain cancer cells (SF) and colon cancer cells (Caco-2) at doses ranging between 1 and 25 ug/mL using a WST kit. Results showed a remarkable anti-proliferative effect with IC50 values ranging between 5 – 7 ug/mL and IC99 values ranging between 11 – 13 ug/mL. In conclusion, the anticancer effect of the Cedrus Libani essential oil could be attributed to its major constituent, 2-himachalene-7-ol.

Cedrus libani is among the oldest Cedrus species in the Mediterranean region. Its essential oil has been utilized in folk medicine in Lebanon and was recently shown to possess antileukemic activity [1]. The current study aims to isolate and characterize the major compound responsible for anticancer activity. Cedrus wood (100 g) was extracted with hexane using a soxhlet apparatus to obtain 2.4 g of crude oil. The oil (1 g) was then eluted with 9:1 hexane:ethyl acetate using a silica gel-based column to yield 2-himchalene-7-ol as a white crystalline solid (125 mg, 0.3%). The identity of the sesquiterpene was determined by GC-MS, 13C NMR and X-ray Crystallography. To the best of our knowledge, this is the first time that 2-himachalene-7ol has been isolated from the wood of Cedrus libani. 2-Himachalene-7-ol was then tested against brain cancer cells (SF) and colon cancer cells (Caco-2) at doses ranging between 1 and 25 ug/mL using a WST kit. Results showed a remarkable anti-proliferative effect with IC50 values ranging between 5 – 7 ug/mL and IC99 values ranging between 11 – 13 ug/mL. In conclusion, the anticancer effect of the Cedrus Libani essential oil could be attributed to its major constituent, 2-himachalene-7-ol.

BackgroundAIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings.MethodsParticipants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations.ResultsThe median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01).ConclusionsThe study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization -recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and

The purpose of this test program was to evaluate the tracking capability of a small lightweight sensor payload, which is used in miniature remotely piloted vehicles. These tests, which were conducted at Fort Huachuca, AZ in January 1974, employed a Cessna 337 aircraft to carry the payload. This report describes this test program and discusses the results obtained. (Author)

This article analyses the political and media discourses on Roma in Hungary, Finland and the UK, in relation to the local Roma in these countries as well as those who migrated from Central and Eastern Europe countries following the fall of communism. The authors have analysed left of centre and right of centre major newspapers in these three countries, focusing on specific case studies which were the foci of public debates during the last two decades. We also examined a common case study in 2013 (“blond Maria”) that was discussed throughout Europe. In each news paper, the constructions of Roma, local and migrant, and the changes to related discourses over the period were studied. In conclusion, we examine the multi-layered processes of social and political borderings in Europe which dominate discourses on Roma, “indigenous” and migrant, and the extent to which they constitute a coherent “European” construction of “the Roma”.