Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency.

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI

Considering Family and Significant Others in the Faculty Recruitment Process: A Study of Social Work Recruiting Practices

One of the most important facets of quality social work education is the recruitment and retention of faculty. This mixed methods study uses findings from an on-line survey of 106 recent (within three years) faculty hires and their (n=24) spouse/partner/significant others (S/P/SO) to determine the degree to which family- integrative recruitment strategies were being used in recruiting social work faculty and the impact with which the presence or absence of these strategies have on retention. A majority of respondents reported that S/P/SO were excluded from the recruitment process.Though the few respondents who felt included were pleased with their current position and planned to pursue tenure to stay with the school, a significant number of faculty whose S/P/SO were not involved were already contemplating their next position.The authors suggest family integrative strategies that help S/P/SO connect with the community may give social work programs the competitive edge they need to attract and retain the best and brightest social work faculty

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

Investigation of mesoscale cloud features viewed by LANDSAT

The author has identified the following significant results. Some 50 LANDSAT images displaying mesoscale cloud features were analyzed. This analysis was based on the Rayleigh-Kuettner model describing the formation of that type of mesoscale cloud feature. This model lends itself to computation of the average wind speed in northerly flow from the dimensions of the cloud band configurations measured from a LANDSAT image. In nearly every case, necessary conditions of a curved wind profile and orientation of the cloud streets within 20 degrees of the direction of the mean wind in the convective layer were met. Verification of the results by direct observation was hampered, however, by the incompatibility of the resolution of conventional rawinsonde observations with the scale of the banded cloud patterns measured from LANDSAT data. Comparison seems to be somewhat better in northerly flows than in southerly flows, with the largest discrepancies in wind speed being within 8m/sec, or a factor of two

The Importance of DNA Repair in Tumor Suppression

The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation; Minor error corrected; Minor changes to model syste

Moving Targets: Geographically Routed Human Movement Networks

We introduce a new communication paradigm, Human-to-human Mobile Ad hoc Networking (HuManet), that exploits smartphone capabilities and human behavior to create decentralized networks for smartphone-to-smartphone message delivery. HuManets support stealth command-and-control messaging for mobile BotNets, covert channels in the presence of an observer who monitors all cellular communication, and distributed protocols for querying the state or content of targeted mobile devices. In this paper, we introduce techniques for constructing HumaNets and describe protocols for efficiently routing and addressing messages. In contrast to flooding or broadcast schemes that saturate the network and aggressively consume phone resources (e.g., batteries), our protocols exploit human mobility patterns to significantly increase communication efficiency while limiting the exposure of HuManets to mobile service providers. Our techniques leverage properties of smartphones – in particular, their highly synchronized clocks and ability to discern location information – to construct location profiles for each device. HuManets’ fully-distributed and heuristic-based routing protocols route messages towards phones with location profiles that are similar to those of the intended receiver, enabling efficient message delivery with limited effects to end-to-end latency

Child-focused state cash transfers and adolescent risk of HIV infection in South Africa: A propensity-score-matched case-control study

Background: Effective and scalable HIV prevention for adolescents in sub-Saharan Africa is needed. Cash transfers can reduce HIV incidence through reducing risk behaviours. However, questions remain about their effectiveness within national poverty-alleviation programmes, and their effects on different behaviours in boys and girls.Methods: In this case-control study, we interviewed South African adolescents (aged 10–18 years) between 2009 and 2012. We randomly selected census areas in two urban and two rural districts in two provinces in South Africa, including all homes with a resident adolescent. We assessed household receipt of state-provided child-focused cash transfers, incidence in the past year and prevalence of transactional sex, age-disparate sex, unprotected sex, multiple partners, and sex while drunk or after taking drugs. We used logistic regression after propensity score matching to assess the effect of cash transfers on these risky sexual behaviours.We interviewed 3515 participants (one per household) at baseline, and interviewed 3401 at follow-up. For adolescent girls (n=1926), receipt of a cash transfer was associated with reduced incidence of transactional sex (odds ratio [OR] 0.49, 95% CI 0.26–0.93; p=0•028), and age-disparate sex (OR 0.29, 95% CI 0.13–0.67; p=0.004), with similar associations for prevalence (for transactional sex, OR 0.47, 95% CI 0.26–0.86; p=0.015; for age-disparate sex, OR 0.37, 95% CI 0.18–0.77; p=0.003). No significant effects were shown for other risk behaviours. For boys (n=1475), no consistent effects were shown for any of the behaviours.Interpretation: National, child-focused cash transfers to alleviate poverty for households in sub-Saharan Africa can substantially reduce unsafe partner selection by adolescent girls. Child-focused cash transfers are of potential importance for effective combination strategies for prevention of HIV

School, Supervision and Adolescent-Sensitive Clinic Care: Combination Social Protection and Reduced Unprotected Sex Among HIV-Positive Adolescents in South Africa

Social protection can reduce HIV-risk behavior in general adolescent populations, but evidence among HIV-positive adolescents is limited. This study quantitatively tests whether social protection is associated with reduced unprotected sex among 1060 ART-eligible adolescents from 53 government facilities in South Africa. Potential social protection included nine 'cash/cash-in-kind' and 'care' provisions. Analyses tested interactive/additive effects using logistic regressions and marginal effects models, controlling for covariates. 18 % of all HIV-positive adolescents and 28 % of girls reported unprotected sex. Lower rates of unprotected sex were associated with access to school (OR 0.52 95 % CI 0.33-0.82 p = 0.005), parental supervision (OR 0.54 95 % CI 0.33-0.90 p = 0.019), and adolescent-sensitive clinic care (OR 0.43 95 % CI 0.25-0.73 p = 0.002). Gender moderated the effect of adolescent-sensitive clinic care. Combination social protection had additive effects amongst girls: without any provisions 49 % reported unprotected sex; with 1-2 provisions 13-38 %; and with all provisions 9 %. Combination social protection has the potential to promote safer sex among HIV-positive adolescents, particularly girls