Background: All jawed-vertebrates have four T cell receptor (TCR) chains: alpha (TRA), beta (TRB), gamma (TRG) and delta (TRD). Marsupials appear unique by having an additional TCR: mu (TRM). The evolutionary origin of TRM and its relationship to other TCR remain obscure, and is confounded by previous results that support TRM being a hybrid between a TCR and immunoglobulin locus. The availability of the first marsupial genome sequence allows investigation of these evolutionary relationships.

The Medicaid expansion enrolled a population no more likely to be prescribed opioids than the base Medicaid population while significantly increasing uptake of 2 drugs used in medication-assisted treatment.

IntroductionAs access to antiretroviral therapy (ART) increases, the success of treatment programmes depends on ensuring high patient retention in HIV care. We examined retention and attrition among adolescents in ART programmes across clinics operated by The AIDS Support Organization (TASO) in Uganda, which has operated both facility- and community-based distribution models of ART delivery since 2004.MethodsUsing a retrospective cohort analysis of patient-level clinical data, we examined attrition and retention in HIV care and factors associated with attrition among HIV-positive adolescents aged 10–19 years who initiated ART at 10 TASO clinics between January 2006 and December 2011. Retention in care was defined as the proportion of adolescents who had had at least one facility visit within the six months prior to 1 June 2013, and attrition was defined as the proportion of adolescents who died, were lost to follow-up, or stopped treatment. Descriptive statistics and Cox proportional hazards regression models were used to determine the levels of retention in HIV care and the factors associated with attrition following ART initiation.ResultsA total of 1228 adolescents began ART between 2006 and 2011, of whom 57% were female. The median duration in HIV care was four years (IQR=3–6 years). A total of 792 (65%) adolescents were retained in care over the five-year period; 36 (3%) had died or transferred out and 400 (32%) were classified as loss to follow-up. Factors associated with attrition included being older (adjusted hazard ratio (AHR)=1.38, 95% confidence interval (CI) 1.02–1.86), having a higher CD4 count (250+ cells/mm3) at treatment initiation (AHR=0.49, 95% CI 0.34–0.69) and HIV care site with a higher risk of attrition among adolescents in Gulu (AHR=2.26; 95% CI 1.27–4.02) and Masindi (AHR=3.30, 95% CI 1.87–5.84) and a lower risk of attrition in Jinja (AHR=0.24, 95% CI 0.08–0.70). Having an advanced WHO clinical stage at initiation was not associated with attrition.ConclusionsWe found an overall retention rate of 65%, which is comparable to rates achieved by TASO's adult patients and adolescents in other studies in Africa. Variations in the risk of attrition by TASO treatment site and by clinical and demographic characteristics suggest the need for early diagnosis of HIV infection, use of innovative approaches to reach and retain adolescents living with HIV in treatment and identifying specific groups, such as older adolescents, that are at high risk of dropping out of treatment for targeted care and support.

BackgroundTuberculosis (TB) now ranks alongside HIV as the leading infectious disease cause of death worldwide and incurs a global economic burden of over $12 billion annually. Directly observed therapy (DOT) recommends that TB patients complete the course of treatment under direct observation of a treatment supporter who is trained and overseen by health services to ensure that patients take their drugs as scheduled. Though the current WHO End TB Strategy does not mention DOT, only “supportive treatment supervision by treatment partners”, many TB programs still use it despite the fact that the has not been demonstrated to be statistically significantly superior to self-administered treatment in ensuring treatment success or cure.DiscussionDOT is designed to promote proper adherence to the full course of drug therapy in order to improve patient outcomes and prevent the development of drug resistance. Yet over 8 billion dollars is spent on TB treatment each year and thousands undergo DOT for all or part of their course of treatment, despite the absence of rigorous evidence supporting the superior effectiveness of DOT over self-administration for achieving drug susceptible TB (DS-TB) cure. Moreover, the DOT component burdens patients with financial and opportunity costs, and the potential for intensified stigma.To rigorously evaluate the effectiveness of DOT and identify the essential contributors to both successful treatment and minimized patient burden, we call for a pragmatic experimental trial conducted in real-world program settings, the gold standard for evidence-based health policy decisions. It is time to invest in the rigorous evaluation of DOT and reevaluate the DOT requirement for TB treatment worldwide.SummaryRigorously evaluating the choice of treatment supporter, the frequency of health care worker contact and the development of new educational materials in a real-world setting would build the evidence base to inform the optimal design of TB treatment protocol. Implementing a more patient-centered approach may be a wise reallocation of resources to raise TB cure rates, prevent relapse, and minimize the emergence of drug resistance. Maintaining the status quo in the absence of rigorous supportive evidence may diminish the effectiveness of TB control policies in the long run.

Marsupials are a lineage of mammals noted for giving birth to highly altricial young, which complete much of their “fetal” development externally attached to a teat. Postnatal B cell ontogeny and diversity was investigated in a model marsupial species, the gray short-tailed opossum, Monodelphis domestica. The results support the initiation of B cell development late in gestation and progressing into the first two weeks of postnatal life. Transcription of CD79a and CD79b was detected in embryonic tissue prior to birth, while immunoglobulin heavy chain locus transcription was not detected until the first postnatal 24 hours. Transcription of the Ig light chains was not detected until postnatal day 7 at the earliest. The predicted timing of the earliest appearance of mature B cells and completion of gene rearrangements is consistent with previous analyses on the timing of endogenous antibody responses in newborn marsupials. The diversity of early B cell IgH chains is limited, as has been seen in fetal humans and mice, but lacks bias in the gene segments used to encode the variable domains. Newborn light chain diversity is, from the start, comparable to that of the adult, consistent with an earlier hypothesis that light chains contribute extensively to antibody diversity in this species.