Detectable HIV Viral Load in Kenya: Data from a Population-Based Survey.

IntroductionAt the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV) transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012) provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART) coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012.MethodsBetween October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL) was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL ≥ 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non-response.ResultsOverall, 61·2% (95% CI: 56·4-66·1) of HIV-infected Kenyans aged 15-64 years had not achieved virological suppression. The base10 median (interquartile range [IQR]) and mean (95% CI) VL was 4,633 copies/mL (0-51,596) and 81,750 copies/mL (59,366-104,134), respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0-32.1) had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART.DiscussionThis report adds to the limited data of nationally-representative surveys to report population- level virological suppression. We established heterogeneity across the ten administrative and HIV programmatic regions on levels of detectable viral load. Timely initiation of ART and retention in care are crucial for the elimination of transmission of HIV through sex, needle and syringe use or from mother to child. Further refinement of geospatial mapping of populations with highest risk of transmission is necessary

Dynamic fluorescence microscopy of cellular uptake of intercalating model drugs by ultrasound-activated microbubbles

The combination of ultrasound and microbubbles can facilitate cellular uptake of (model) drugs via transient permeabilization of the cell membrane. By using fluorescent molecules, this process can be studied conveniently with confocal fluorescence microscopy. This study aimed to investigate the relation between cellular uptake and fluorescence intensity increase of intercalating model drugs. SYTOX Green, an intercalating fluorescent dye that displays > 500-fold fluorescence enhancement upon binding to nucleic acids, was used as a model drug for ultrasound-induced cellular uptake. SYTOX Green uptake was monitored in high spatiotemporal resolution to qualitatively assess the relation between uptake and fluorescence intensity in individual cells. In addition, the kinetics of fluorescence enhancement were studied as a function of experimental parameters, in particular, laser duty cycle (DC), SYTOX Green concentration and cell line. Ultrasound-induced intracellular SYTOX Green uptake resulted in local fluorescence enhancement, spreading throughout the cell and ultimately accumulating in the nucleus during the 9-min acquisition. The temporal evolution of SYTOX Green fluorescence was substantially influenced by laser duty cycle: continuous laser (100 % DC) induced a 6.4-fold higher photobleaching compared to pulsed laser (3.3 % DC), thus overestimating the fluorescence kinetics. A positive correlation of fluorescence kinetics and SYTOX Green concentration was found, increasing from 0.6 x 10(-3) to 2.2 x 10(-3) s(-1) for 1 and 20 mu M, respectively. Finally, C6 cells displayed a 2.4-fold higher fluorescence rate constant than FaDu cells. These data show that the temporal behavior of intracellular SYTOX Green fluorescence enhancement depends substantially on nuclear accumulation and not just on cellular uptake. In addition, it is strongly influenced by the experimental conditions, such as the laser duty cycle, SYTOX Green concentration, and cell line

Implementation of an innovative, integrated electronic medical record (EMR) and public health information exchange for HIV/AIDS

Louisiana is severely affected by HIV/AIDS, ranking fifth in AIDS rates in the USA. The Louisiana Public Health Information Exchange (LaPHIE) is a novel, secure bi-directional public health information exchange, linking statewide public health surveillance data with electronic medical record data. LaPHIE alerts medical providers when individuals with HIV/AIDS who have not received HIV care for >12 months are seen at any ambulatory or inpatient facility in an integrated delivery network. Between 2/1/2009 and 1/31/2011, 488 alerts identified 345 HIV positive patients. Of those identified, 82% had at least one CD4 or HIV viral load test over the study follow-up period. LaPHIE is an innovative use of health information exchange based on surveillance data and real time clinical messaging, facilitating rapid provider notification of those in need of treatment. LaPHIE successfully reduces critical missed opportunities to intervene with individuals not in care, leveraging information historically collected solely for public health purposes, not health care delivery, to improve public health

Adorno?s Grey, Taussig?s Blue: Colour, Organization and Critical Affect

In this article we seek to open up the study of affect and organization to colour. Often simply taken for granted in organizational life and usually neglected in organizational thought, colour is an affective force by default. Deploying and interweaving the languages of affect theory, critical theory, and organization studies, we discuss colour as a primary phenomenon for the study of ?critical affect?. We then trace colour?s affect in conditioning the unfolding of organization in two particular ?colour/spaces? ? Adorno?s grey and Taussig?s blue of our title ? and discuss both its ambiguity and critical potential. Finally, we ponder what colour might do to the style of an organizational scholarship attuned to affect, where sentences blur with things and forces more than they seek to represent them

The genetic organisation of prokaryotic two-component system signalling pathways

<p>Abstract</p> <p>Background</p> <p>Two-component systems (TCSs) are modular and diverse signalling pathways, involving a stimulus-responsive transfer of phosphoryl groups from transmitter to partner receiver domains. TCS gene and domain organisation are both potentially informative regarding biological function, interaction partnerships and molecular mechanisms. However, there is currently little understanding of the relationships between domain architecture, gene organisation and TCS pathway structure.</p> <p>Results</p> <p>Here we classify the gene and domain organisation of TCS gene loci from 1405 prokaryotic replicons (>40,000 TCS proteins). We find that 200 bp is the most appropriate distance cut-off for defining whether two TCS genes are functionally linked. More than 90% of all TCS gene loci encode just one or two transmitter and/or receiver domains, however numerous other geometries exist, often with large numbers of encoded TCS domains. Such information provides insights into the distribution of TCS domains between genes, and within genes. As expected, the organisation of TCS genes and domains is affected by phylogeny, and plasmid-encoded TCS exhibit differences in organisation from their chromosomally-encoded counterparts.</p> <p>Conclusions</p> <p>We provide here an overview of the genomic and genetic organisation of TCS domains, as a resource for further research. We also propose novel metrics that build upon TCS gene/domain organisation data and allow comparisons between genomic complements of TCSs. In particular, '<it>percentage orphaned TCS genes</it>' (or 'Dissemination') and '<it>percentage of complex loci</it>' (or 'Sophistication') appear to be useful discriminators, and to reflect mechanistic aspects of TCS organisation not captured by existing metrics.</p

How do Zimbabweans value health states?

Background Quality of life weights based on valuations of health states are often used in cost utility analysis and population health measures. This paper reports on an attempt to develop quality of life weights within the Zimbabwe context. Methods 2,384 residents in randomly selected small residential plots of land in a high-density suburb of Harare valued descriptors of 38 health states based on different combinations of the five domains of the EQ-5D (mobility, self-care, usual activities, pain or discomfort and anxiety or depression). The English version of the EQ-5D was used. The time trade-off method was used to determine the values, and 19,020 individual preferences for health states were analysed. A residual maximum likelihood linear mixed model was used to estimate a function for predicting the values of all possible combinations of levels on the five domains. The model was fit to a random subset of two-thirds of the observations, with the remaining observations reserved for analysis of predictive validity. The results were compared to a similar study undertaken in the United Kingdom. Results A credible model was developed to predict the values of states that were not valued directly. In the subset of observations reserved for validation, the mean absolute difference between predicted and observed values was 0.045. All domains of the EQ-5D were found to contribute significantly to the model, both at the moderate and severe levels. Severe pain was found to have the largest negative coefficient, followed by the inability to wash and dress oneself. Conclusion Despite a generally lower education level than their European counterparts, urban Zimbabweans appear to value health states in a consistent manner, and the determination of a global method of establishing quality of life weights may be feasible and valid. However, as the relative weightings of the different domains, although correlated, differed from the standard set of weights recommended by the EuroQol Group, the locally determined coefficients should be used within the Zimbabwean context

Implicator-conjunctor based models of fuzzy rough sets: definitions and properties

Ever since the first hybrid fuzzy rough set model was proposed in the early 1990' s, many researchers have focused on the definition of the lower and upper approximation of a fuzzy set by means of a fuzzy relation. In this paper, we review those proposals which generalize the logical connectives and quantifiers present in the rough set approximations by means of corresponding fuzzy logic operations. We introduce a general model which encapsulates all of these proposals, evaluate it w.r.t. a number of desirable properties, and refine the existing axiomatic approach to characterize lower and upper approximation operators

Ideologies of time: How elite corporate actors engage the future

Our paper deals with how elite corporate actors in a Western capitalist-democratic society conceive of and prepare for the future. Paying attention to how senior officers of ten important Danish companies make sense of the future will help us to identify how particular temporal narratives are ideologically marked. This ideological dimension offers a common sense frame that is structured around a perceived inevitability of capitalism, a market economy as the basic organizational structure of the social and economic order, and an assumption of confident access to the future. Managers envisage their organization?s future and make plans for organizational action in a space where ?business as usual? reigns, and there is little engagement with the future as fundamentally open; as a time-yet-to-come. In using a conceptual lens inspired by the work of Fredric Jameson, we first explore the details of this presentism and a particular colonization of the future, and then linger over small disruptions in the narratives of our interviewees which point to what escapes or jars their common sense frame, explore the implicit meanings they assign to their agency, and also find clues and traces of temporal actions and strategies in their narratives that point to a subtly different engagement with time

Costly mating delays drive female ornamentation in a capital breeder

How fecundity might be traded off with mate attraction and other aspects of reproduction in females remains poorly understood. We investigated these allocation trade-offs using the common glowworm (Lampyris noctiluca), a lampyrid beetle, in which flightless, sedentary females only use resources gathered during the larval stage to attract flying males by glowing. While sexual signaling was not found to have a significant fecundity cost, a delay in successfully attracting a mate greatly increased the risk of reproductive failure, with fecundity losses being more severe in small females. These findings are among the first to show that failure to quickly attract a mate can decrease female fecundity. The results also show how the length of delay before mating can drive the evolution of female sexual ornamentation.Peer reviewe