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

The tarantula toxin GxTx detains K+ channel gating charges in their resting conformation.

Allosteric ligands modulate protein activity by altering the energy landscape of conformational space in ligand-protein complexes. Here we investigate how ligand binding to a K+ channel's voltage sensor allosterically modulates opening of its K+-conductive pore. The tarantula venom peptide guangxitoxin-1E (GxTx) binds to the voltage sensors of the rat voltage-gated K+ (Kv) channel Kv2.1 and acts as a partial inverse agonist. When bound to GxTx, Kv2.1 activates more slowly, deactivates more rapidly, and requires more positive voltage to reach the same K+-conductance as the unbound channel. Further, activation kinetics are more sigmoidal, indicating that multiple conformational changes coupled to opening are modulated. Single-channel current amplitudes reveal that each channel opens to full conductance when GxTx is bound. Inhibition of Kv2.1 channels by GxTx results from decreased open probability due to increased occurrence of long-lived closed states; the time constant of the final pore opening step itself is not impacted by GxTx. When intracellular potential is less than 0 mV, GxTx traps the gating charges on Kv2.1's voltage sensors in their most intracellular position. Gating charges translocate at positive voltages, however, indicating that GxTx stabilizes the most intracellular conformation of the voltage sensors (their resting conformation). Kinetic modeling suggests a modulatory mechanism: GxTx reduces the probability of voltage sensors activating, giving the pore opening step less frequent opportunities to occur. This mechanism results in K+-conductance activation kinetics that are voltage-dependent, even if pore opening (the rate-limiting step) has no inherent voltage dependence. We conclude that GxTx stabilizes voltage sensors in a resting conformation, and inhibits K+ currents by limiting opportunities for the channel pore to open, but has little, if any, direct effect on the microscopic kinetics of pore opening. The impact of GxTx on channel gating suggests that Kv2.1's pore opening step does not involve movement of its voltage sensors

A frictionless microswimmer

We investigate the self-locomotion of an elongated microswimmer by virtue of the unidirectional tangential surface treadmilling. We show that the propulsion could be almost frictionless, as the microswimmer is propelled forward with the speed of the backward surface motion, i.e. it moves throughout an almost quiescent fluid. We investigate this swimming technique using the special spheroidal coordinates and also find an explicit closed-form optimal solution for a two-dimensional treadmiler via complex-variable techniques.Comment: 6 pages, 4 figure

Suppression of Heating Rates in Cryogenic Surface-Electrode Ion Traps

Dense arrays of trapped ions provide one way of scaling up ion trap quantum information processing. However, miniaturization of ion traps is currently limited by sharply increasing motional state decoherence at sub-100 um ion-electrode distances. We characterize heating rates in cryogenically cooled surface-electrode traps, with characteristic sizes in 75 um to 150 um range. Upon cooling to 6 K, the measured rates are suppressed by 7 orders of magnitude, two orders of magnitude below previously published data of similarly sized traps operated at room temperature. The observed noise depends strongly on fabrication process, which suggests further improvements are possible.Comment: 4 pages, 4 figure

Transition from cMyc to L-Myc during dendritic cell development coordinated by rising levels of IRF8

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development

Development of a Self-report Measure of Dual Diagnosis Capability for Addiction and Mental Health Programs

The purpose of this study is to develop and test the psychometrics of a self-report version of a measure of the capacity of addiction and mental health programs to deliver dual-diagnosis treatment, that is, to provide treatment for both addiction problems and mental health problems. Traditionally these services are provided by very different service providers that did not until recently interact very well, if at all. The increasing recognition that patients who suffer from both kinds of problems – who are dually diagnosed – would benefit from integrated delivery of addiction and mental health services has led to efforts to encourage provision of such integrated services in programs that have tended to focus primarily on the delivery of either addiction or mental health services to the exclusion of the other. In order to assess how well the integration of these services is progressing, various measures have been developed, one of which is the original Dual Diagnosis Capability in Addiction Treatment (DDCAT) Index. The DDCAT, as it now stands, however, is a very time-intensive tool. It requires a rater to visit a site and spend one half to a full day there interviewing administrators, therapists, and patients, reviewing medical records, and attending meetings. The purpose of this study is to test a self-report version of the DDCAT that will be administered to administrators and therapists to see how well it performs compared to the more time- intensive procedures of the original DDCAT