Orthotopic liver transplantation in U.S. veterans under primary tacrolimus immunosupression.

The evolution and refinement of surgical techniques, per ioperative patient care, and immunosuppression hav~ estab~ished orthoto~ic li~er transplantation (OLTX) as a ~ighly successful therapeutic modality for patients wrth end-stage hver disease. In February 1989,Tacrohmus (Prograf®, formerly FK 506)was first used successfully at the University of Pittsburgh Medical Center to treat patients with rejection refractory to cyclosporine-based immunosuppression." Clinical trials utilizing Tacrolimus in solid organ transplantation followed, and in April of 1994 it was approved for use by the Food and Drug Administration

Chlamydia trachomatis Biovar L2 Infection in Women in South Africa

We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified

Using economic evidence to set healthcare priorities in low-income and lower-middle-income countries: a systematic review of methodological frameworks

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks - which incorporate economic evaluation evidence - for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence

Folding of small proteins: A matter of geometry?

We review some of our recent results obtained within the scope of simple lattice models and Monte Carlo simulations that illustrate the role of native geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic

Appointments, pay and performance in UK boardrooms by gender

This article uses UK data to examine issues regarding the scarcity of women in boardroom positions. The article examines appointments, pay and any associated productivity effects deriving from increased diversity. Evidence of gender-bias in the appointment of women as non-executive directors is found together with mixed evidence of discrimination in wages or fees paid. However, the article finds no support for the argument that gender diverse boards enhance corporate performance. Proposals in favour of greater board diversity may be best structured around the moral value of diversity, rather than with reference to an expectation of improved company performance

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Identifying Causal Risk Factors for Violence among Discharged Patients

This study was funded by the UK National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407-10500)

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury