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  • Public Library of Science (CrossRef)  (129)
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  • 1
    Language: English
    In: 2012, Vol.7(11), p.e49591
    Description: With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure. ; We performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change. ; Of the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65–147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based second-line ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p = 0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p = 0.38) between children with and without genotype testing. ; NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Infectious Diseases ; Pediatrics And Child Health
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: PLoS ONE, 2011, Vol.6(3), p.e17323
    Description: Context-dependent adjustment of mating tactics can drastically increase the mating success of behaviourally flexible animals. We used the ant Cardiocondyla obscurior as a model system to study adaptive adjustment of male mating tactics. This species shows a male diphenism of wingless fighter males and peaceful winged males. Whereas the wingless males stay and exclusively mate in the maternal colony, the mating behaviour of winged males is plastic. They copulate with female sexuals in their natal nests early in life but later disperse in search for sexuals outside. In this study, we observed the nest-leaving behaviour of winged males under different conditions and found that they adaptively adjust the timing of their dispersal to the availability of mating partners, as well as the presence, and even the type of competitors in their natal nests. In colonies with virgin female queens winged males stayed longest when they were the only male in the nest. They left earlier when mating partners were not available or when other males were present. In the presence of wingless, locally mating fighter males, winged males dispersed earlier than in the presence of docile, winged competitors. This suggests that C. obscurior males are capable of estimating their local breeding chances and adaptively adjust their dispersal behaviour in both an opportunistic and a risk-sensitive way, thus showing hitherto unknown behavioural plasticity in social insect males.
    Keywords: Research Article ; Biology ; Ecology ; Evolutionary Biology
    E-ISSN: 1932-6203
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  • 3
    In: PLoS ONE, 2015, Vol.10(10)
    Description: The neural correlates of rejection in bargaining situations when proposing a fair or unfair offer are not yet well understood. We measured neural responses to rejection and acceptance of monetary offers with event-related potentials (ERPs) in mid-adolescents (14–17 years) and early adults (19–24 years). Participants played multiple rounds of the Ultimatum Game as proposers, dividing coins between themselves and a second player (responder) by making a choice between an unfair distribution (7 coins for proposer and 3 for responder; 7/3) and one of two alternatives: a fair distribution (5/5) or a hyperfair distribution (3/7). Participants mostly made fair offers (5/5) when the alternative was unfair (7/3), but made mostly unfair offers (7/3) when the alternative was hyperfair (3/7). When participants’ fair offers (5/5; alternative was 7/3) were rejected this was associated with a larger Medial Frontal Negativity (MFN) compared to acceptance of fair offers and rejection of unfair offers (7/3; alternative was 3/7). Also, the MFN was smaller after acceptance of unfair offers (7/3) compared to rejection. These neural responses did not differ between adults and mid-adolescents, suggesting that the MFN reacts as a neural alarm system to social prediction errors which is already prevalent during adolescence.
    Keywords: Research Article
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: PLOS ONE, 2015
    Description: Lack of self-control has been suggested to facilitate norm-transgressing behaviors because of the operation of automatic selfish impulses. Previous research, however, has shown that people having a high moral identity may not show such selfish impulses when their self-control resources are depleted. In the present research, we extended this effect to prosocial behavior. Moreover, we investigated the role of power in the interaction between moral identity and self-control depletion. More specifically, we expected that power facilitates the externalization of internal states, which implies that for people who feel powerful, rather than powerless, depletion decreases prosocial behavior especially for those low in moral identity. A laboratory experiment and a multisource field study supported our predictions. The present finding that the interaction between self-control depletion and moral identity is contingent upon people's level of power suggests that power may enable people to refrain from helping behavior. Moreover, the findings suggest that if organizations want to improve prosocial behaviors, it may be effective to situationally induce moral values in their employees.
    Keywords: Social Sciences ; Sanctioning Systems ; Interested Behavior ; Workplace Deviance ; Limited-Resource ; Ego-Depletion ; Organizational Citizenship Behaviors ; Ethical Leadership ; Strength Model ; Identity ; Cooperation
    ISSN: 1932-6203
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  • 5
    Language: English
    In: 2012, Vol.7(8), p.e42844
    Description: Isospora belli causes diarrhoea in patients with AIDS. Most respond to targeted therapy and recommendations are that secondary prophylaxis can be stopped following immune reconstitution with ART. We report eight cases of chronic isosporiasis that persisted despite standard antimicrobial therapy, secondary prophylaxis, and good immunological and virological response to ART. Median CD4 nadir was 175.5 cells/mm 3 and median highest CD4 while symptomatic was 373 cells/mm 3 . Overall 34% of stool samples and 63% of duodenal biopsy specimens were positive for oocytes. Four patients died, two remain symptomatic and two recovered. Possible explanations for persistence of symptoms include host factors such as antigen specific immune deficiency or generalised reduction in gut immunity. Parasite factors may include accumulating resistance to co-trimoxazole. Research is required to determine the optimum dose and duration of co-trimoxazole therapy and whether dual therapy may be necessary. Mortality was high and pending more data we recommend extended treatment with high-dose co-trimoxazole in similar cases.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Infectious Diseases ; Gastroenterology And Hepatology
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(8), p.e104774
    Description: Understanding relations between climate and pollen production is important for several societal and ecological challenges, importantly pollen forecasting for pollinosis treatment, forensic studies, global change biology, and high-resolution palaeoecological studies of past vegetation and climate fluctuations. For these purposes, we investigate the role of climate variables on annual-scale variations in pollen influx, test the regional consistency of observed patterns, and evaluate the potential to reconstruct high-frequency signals from sediment archives. A 43-year pollen-trap record from the Netherlands is used to investigate relations between annual pollen influx, climate variables (monthly and seasonal temperature and precipitation values), and the North Atlantic Oscillation climate index. Spearman rank correlation analysis shows that specifically in Alnus, Betula, Corylus, Fraxinus, Quercus and Plantago both temperature in the year prior to (T-1), as well as in the growing season (T), are highly significant factors (TApril rs between 0.30 [P〈0.05[ and 0.58 [P〈0.0001]; TJuli-1 rs between 0.32 [P〈0.05[ and 0.56 [P〈0.0001]) in the annual pollen influx of wind-pollinated plants. Total annual pollen prediction models based on multiple climate variables yield R2 between 0.38 and 0.62 (P〈0.0001). The effect of precipitation is minimal. A second trapping station in the SE Netherlands, shows consistent trends and annual variability, suggesting the climate factors are regionally relevant. Summer temperature is thought to influence the formation of reproductive structures, while temperature during the flowering season influences pollen release. This study provides a first predictive model for seasonal pollen forecasting, and also aides forensic studies. Furthermore, variations in pollen accumulation rates from a sub-fossil peat deposit are comparable with the pollen trap data. This suggests that high frequency variability pollen records from natural archives reflect annual past climate variability, and can be used in palaeoecological and -climatological studies to bridge between population- and species-scale responses to climate forcing.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    In: PLoS ONE, 2014, Vol.9(6)
    Description: Quantum mechanical (QM) calculations have been used to predict the binding affinity of a set of ligands towards HIV-1 RT associated RNase H (RNH). The QM based chelation calculations show improved binding affinity prediction for the inhibitors compared to using an empirical scoring function. Furthermore, full protein fragment molecular orbital (FMO) calculations were conducted and subsequently analysed for individual residue stabilization/destabilization energy contributions to the overall binding affinity in order to better understand the true and false predictions. After a successful assessment of the methods based on the use of a training set of molecules, QM based chelation calculations were used as filter in virtual screening of compounds in the ZINC database. By this, we find, compared to regular docking, QM based chelation calculations to significantly reduce the large number of false positives. Thus, the computational models tested in this study could be useful as high throughput filters for searching HIV-1 RNase H active-site molecules in the virtual screening process.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences ; Physical Sciences
    E-ISSN: 1932-6203
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  • 8
    In: PLoS ONE, 2015, Vol.10(5)
    Description: Efavirenz, a non-nucleoside reverse-transcriptase inhibitor (NNRTI) is one of the most commonly prescribed antiretroviral drugs. The present article provides a systematic overview and meta-analysis of clinical trials comparing efavirenz and other active drugs currently recommended for treatment of HIV-infected, antiretroviral-naive patients. Electronic databases (Pubmed, Embase, the Cochrane Library, Trip Database) were searched up till 23 December 2013 for randomized controlled clinical trials published as a peer-reviewed papers, and concerning efavirenz-based regimens used as initial treatment for HIV infection. Thirty-four studies were included in the systematic review, while twenty-six trials were suitable for the meta-analysis. Efavirenz was compared with drugs from four different classes: NNRTIs other than efavirenz (nevirapine or rilpivirine), integrase strand transfer inhibitors (InSTIs), ritonavir-boosted protease inhibitors (bPI) and chemokine (C-C motif) receptor 5 (CCR5) antagonists (maraviroc), all of them were added to the background regimen. Results of the current meta-analysis showed that efavirenz-based regimens were equally effective as other recommended regimens based on NNRTI, ritonavir-boosted PI or CCR5 antagonist in terms of efficacy outcomes (disease progression and/or death, plasma viral HIV RNA 〈50 copies/ml) while statistically significant more patients treated with InSTI achieved plasma viral load 〈50 copies/ml at week 48. In comparison with both InSTI-based and CCR5-based therapy, efavirenz-based treatment was associated with a higher risk of therapy discontinuation due to adverse events. However, comparisons of efevirenz-based treatment with InSTI-based and CCR5-based therapy were based on a limited number of trials, therefore, conclusions from these two comparisons must be confirmed in further reliable randomized controlled studies. Results of our meta-analysis support the present clinical guidelines for antiretroviral-naive, HIV-infected patients, in which efavirenz is one of the most preferred regimens in the analyzed population. Beneficial safety profile of InSTI-based and CCR5-based therapy over efavirenz-based treatment needs further studies.
    Keywords: Research Article
    E-ISSN: 1932-6203
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  • 9
    In: PLoS ONE, 2013, Vol.8(9)
    Description: The increasing resistance to current therapeutic agents for HIV drug regiment remains a major problem for effective acquired immune deficiency syndrome (AIDS) therapy. Many potential inhibitors have today been developed which inhibits key cellular pathways in the HIV cycle. Inhibition of HIV-1 reverse transcriptase associated ribonuclease H (RNase H) function provides a novel target for anti-HIV chemotherapy. Here we report on the applicability of conceptually different in silico approaches as virtual screening (VS) tools in order to efficiently identify RNase H inhibitors from large chemical databases. The methods used here include machine-learning algorithms (e.g. support vector machine, random forest and kappa nearest neighbor), shape similarity (rapid overlay of chemical structures), pharmacophore, molecular interaction fields-based fingerprints for ligands and protein (FLAP) and flexible ligand docking methods. The results show that receptor-based flexible docking experiments provides good enrichment (80–90%) compared to ligand-based approaches such as FLAP (74%), shape similarity (75%) and random forest (72%). Thus, this study suggests that flexible docking experiments is the model of choice in terms of best retrieval of active from inactive compounds and efficiency and efficacy schemes. Moreover, shape similarity, machine learning and FLAP models could also be used for further validation or filtration in virtual screening processes. The best models could potentially be use for identifying structurally diverse and selective RNase H inhibitors from large chemical databases. In addition, pharmacophore models suggest that the inter-distance between hydrogen bond acceptors play a key role in inhibition of the RNase H domain through metal chelation.
    Keywords: Research Article
    E-ISSN: 1932-6203
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  • 10
    Language: English
    In: 2012, Vol.7(11), p.e47260
    Description: We aimed to characterize changes in patterns of new HIV diagnoses, HIV-related mortality, and HAART use in Canada from 1995 to 2008. ; Data on new HIV diagnoses were obtained from Health Canada, HIV-related mortality statistics were obtained from Statistics Canada, and information on the number of people on HAART was obtained from the single antiretroviral distribution site in British Columbia (BC), and the Intercontinental Marketing Services Health for Ontario and Quebec. Trends of new HIV-positive tests were assessed using Spearman rank correlations and the association between the number of individuals on HAART and new HIV diagnoses were estimated using generalized estimating equations (GEE). ; A total of 34,502 new HIV diagnoses were observed. Rates of death in BC are higher than those in Ontario and Quebec with the rate being 2.03 versus 1.06 and 1.21 per 100,000 population, respectively. The number of HIV infected individuals on HAART increased from 5,091 in 1996 to 20,481 in 2008 in the three provinces (4 fold increase). BC was the only province with a statistically significant decrease (trend test p〈0.0001) in the rate of new HIV diagnoses from 18.05 to 7.94 new diagnoses per 100,000 population. Our analysis showed that for each 10% increment in HAART coverage the rate of new HIV diagnoses decreased by 8% (95% CI: 2.4%, 13.3%) ; Except for British Columbia, the number of new HIV diagnoses per year has remained relatively stable across Canada over the study period. The decline in the rate of new HIV diagnoses per year may be in part attributed to the greater expansion of HAART coverage in this province.
    Keywords: Research Article ; Biology ; Medicine ; Virology ; Public Health And Epidemiology ; Infectious Diseases ; Pharmacology
    E-ISSN: 1932-6203
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