701 research outputs found
Зміна роздільної здатності зображень на основі власних векторів матриць-операторів індукованих з піксельних наборів
The method of problem solving increase resolution image sets provided that the
dimension of the set. The method is to build a matrix operator and find its
eigenvectors. Using sets of eigenvectors and matrix color images developed a practical set of algorithm changes the resolution
Evolution of resistance in paediatric patients with failure on antiretroviral therapy
INTRODUCTION: HIV-1 resistance data to inform treatment sequencing are limited for children with virological failure on first- and second-line antiretroviral therapy (ART) in Sub-Saharan Africa. METHODS: HIV-1-infected children aged ≤15 years were retrospectively identified from an ART cohort in Cape Town, South Africa (2003 to 2010). First-line ART was either non-nucleoside reverse transcriptase inhibitor (NNRTI) or lopinavir/ritonavir-based (with the exception of children <6 months old who received full-dose ritonavir as the sole protease inhibitor (PI) from 2004 to 2007). Second-line ART was the alternative regimen. Treatment outcomes, including virological failure, loss to care, death or remaining in care, were determined. Genotypic resistance testing was conducted on stored serum from children at first- or second-line virological failure (two consecutive HIV-1 RNA levels >1000 copies/ml). International AIDS Society criteria defined resistance mutations. RESULTS: Of 472 children starting first-line ART, 352 (75%) remained in care, 45 (9%) were lost and 4 (1%) died on first-line treatment. Seventy-one (15%) had observed virological failure, and 37 of these children had specimens available for genotype testing. Eight children (22%) had wild-type virus, seven (19%) had thymidine analog mutations (TAMs), 24 (65%) had NNRTI resistance and two (5.4%) had multiple protease resistance (PR). Of the 78 children who received second-line ART, 54 (71%) remained in care, 6 (8%) were lost and 1 (1%) died during second-line treatment. Fifteen (20%) had observed virological failure; 13 had samples available for genotype. Three (23%) had wild-type virus, eight (62%) had TAMs, nine (69%) had NNRTI resistance, and five (38%) had multiple PI resistance all of whom had received full-dose ritonavir. CONCLUSION: Although virological failure was infrequent in children on first- and second-line ART, rates of observed resistance including multiple PR resistance after failure were high. Reasons for high rates of resistance include use of full-dose ritonavir and continued viremia. Wild-type virus was common, suggesting poor adherence or challenges in correct dosing. Genotype resistance testing in children with virological failure may optimize selection of subsequent regimens and inform recommendations for sequencing of existing ART
Recommended from our members
The Survival Benefits of Antiretroviral Therapy in South Africa
Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa
Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability
Background
In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods
In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results
At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions
In settings with inadequate HIV treatment availability, trade-offs emerge between maximizing outcomes for individual patients already on treatment and ensuring access to treatment for all people who may benefit. While individuals may derive some benefit from ART even after virologic failure, the aggregate public health benefit is maximized by providing effective therapy to the greatest number of people. These trade-offs should be explicit and transparent in antiretroviral policy decisions
Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers
[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities
Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness
Background: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, 31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) (2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority
Empathy, engagement, entrainment: the interaction dynamics of aesthetic experience
A recent version of the view that aesthetic experience is based in empathy as inner
imitation explains aesthetic experience as the automatic simulation of actions,
emotions, and bodily sensations depicted in an artwork by motor neurons in the brain. Criticizing the simulation theory for committing to an erroneous concept of empathy and failing to distinguish regular from aesthetic experiences of art, I advance an alternative, dynamic approach and claim that aesthetic experience is enacted and skillful, based in the recognition of others’ experiences as distinct from one’s own. In combining insights from mainly psychology, phenomenology, and cognitive science, the dynamic approach aims to explain the emergence of aesthetic experience in terms of the reciprocal interaction between viewer and artwork. I argue that aesthetic experience emerges by participatory sense-making and revolves around movement as a means for creating meaning. While entrainment merely plays a preparatory part in this, aesthetic engagement constitutes the phenomenological side of coupling to an artwork and provides the context for exploration, and eventually for moving, seeing, and feeling with art. I submit that aesthetic experience emerges from bodily and emotional engagement with works of art via the complementary processes of the perception–action and motion–emotion loops. The former involves the embodied
visual exploration of an artwork in physical space, and progressively structures and organizes visual experience by way of perceptual feedback from body movements made in response to the artwork. The latter concerns the movement qualities and shapes of implicit and explicit bodily responses to an artwork that cue emotion and thereby modulate over-all affect and attitude. The two processes cause the viewer to bodily and emotionally move with and be moved by individual works of art, and consequently to recognize another psychological orientation than her own, which explains how art can cause feelings of insight or awe and disclose aspects of life that are unfamiliar or novel to the viewer
Investigating the Interplay Between Aging and Rejuvenation in Spin Glasses
Aging in a single crystal spin glass ()
has been measured using ac susceptibility techniques over a temperature range
of . In these studies, traditional aging experiments (or
``quench'' aging protocols) are compared to aging curves constructed from
finite-cooling-rate curves. By comparing the growth rates of spin glass order
between the two types of aging curves, it is determined that quantitative
comparisons between protocols which are taken by quenching and protocols using
a finite cooling rate are not possible without a deeper understanding of the
interplay between aging and rejuvenation. We then demonstrate that the data
presented indicate that rejuvenation, rather than cumulative aging, is the
cause for the discrepancies between the two growth rates.Comment: 6 pages, 4 figure
Sensitivity to differences in the motor origin of drawings:from human to robot
This study explores the idea that an observer is sensitive to differences in the static traces of drawings that are due to differences in motor origin. In particular, our aim was to test if an observer is able to discriminate between drawings made by a robot and by a human in the case where the drawings contain salient kinematic cues for discrimination and in the case where the drawings only contain more subtle kinematic cues. We hypothesized that participants would be able to correctly attribute the drawing to a human or a robot origin when salient kinematic cues are present. In addition, our study shows that observers are also able to detect the producer behind the drawings in the absence of these salient kinematic cues. The design was such that in the absence of salient kinematic cues, the drawings are visually very similar, i.e. only differing in subtle kinematic differences. Observers thus had to rely on these subtle kinematic differences in the line trajectories between drawings. However, not only motor origin (human versus robot) but also motor style (natural versus mechanic) plays a role in attributing a drawing to the correct producer, because participants scored less high when the human hand draws in a relatively mechanical way. Overall, this study suggests that observers are sensitive to subtle kinematic differences between visually similar marks in drawings that have a different motor origin. We offer some possible interpretations inspired by the idea of "motor resonance''
On the Nature of Memory and Rejuvenation in Glassy Systems
The memory effect in a single crystal spin glass
() has been measured using ac susceptibility techniques over a reduced temperature range of
and a model of the memory effect has been developed. A
double-waiting-time protocol is carried out where the spin glass is first
allowed to age at a temperature below , followed by a second aging at a
lower temperature after it has fully rejuvenated. The model is based on
calculating typical coincidences between the growth of correlated regions at
the two temperatures. It accounts for the absolute magnitude of the memory
effect as a function of both waiting times and temperatures. The data can be
explained by the memory loss being a function of the relative change in the
correlated volume at the first waiting temperature because of the growth in the
correlations at the second waiting temperature.Comment: 11 pages, 6 figure
- …
