Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection

Background The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. Methods A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load/ml and CD4 T cell count \u3e450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count \u3e350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. Results The proportions of CD4 counts \u3e350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm. Conclusion We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur

Identifying and Characterizing Impact Melt Outcrops in the Nectaris Basin

The Nectaris Basin is an 820-km diameter, multi-ring impact basin located on the near side of the Moon. Nectaris is a defining stratigraphic horizon based on relationships between ejecta units, giving its name to the Nectarian epoch of lunar history. Lunar basin chronology based on higher resolution LRO imagery and topography, while assigning some important basins like Serenitatis to pre-Nectarian time, were generally consistent with those previously derived. Based on this stratigraphy, at least 11 large basins formed in the time between Nectaris and Imbrium. The absolute age of Nectaris, therefore, is a crucial marker in the lunar time-stratigraphic sequence for understanding the impact flux on the Moon, and by extension, the entire inner solar system. For several decades, workers have attempted to constrain the age of the Nectaris basin through radiometric dating of lunar samples. However, there is little agreement on which samples in our collection represent Nectaris, if any, and what the correct radiometric age of such samples is. The importance of the age of Nectaris goes far beyond assigning a stratigraphic marker to lunar chronology. Several dynamical models use Nectaris as their pin date, so that this date becomes crucial in understanding the time-correlated effects in the rest of the solar system. The importance of the Nectaris basin age, coupled with its nearside, mid-latitude location, make remnants of the impact-melt sheet an attractive target for a future mission, either for in-situ dating or for sample return. We have started exploring this possibility. We have begun a consortium data-analysis effort bringing multiple datasets and analysis methods to bear on these putative impact-melt deposits to characterize their extent, elemental composition and mineralogy, maturity and geologic setting, and to identify potential landing sites that meet both operational safety and science requirements

Managing contested spaces: Public managers, obscured mechanisms and the legacy of the past in Northern Ireland

Societies emerging from ethno-political and inter-communal conflict face a range of complex problems that stem directly from the recent lived experience of bloodshed and injury, militarisation, securitisation and segregation. As institutional agents in such an environment, public managers perform the dual role of both interpreting public policy and implementing it within a politically contested space and place. In this article we address how managers cope with the outworking of ethno-nationalist conflict and peace building within government processes and policy implementation and contend this is a subject of emerging concern within the wider public administration, urban studies and conflict literature. Using data from a witness seminar initiative on the Northern Ireland conflict transformation experience, we explain how public sector managers make sense of their role in post-agreement public management and highlight the importance of three identified mechanisms; ‘bricolage’, ‘diffusion’ and ‘translation’ in the management of public sector organisations and urban spaces in a context of entrenched conflict and an uncertain path to peace

The role of high frequency intra-daily data, daily range and implied volatility in multi-period Value-at-Risk forecasting

In this paper, we assess the informational content of daily range, realized variance, realized bipower variation, two time scale realized variance, realized range and implied volatility in daily, weekly, biweekly and monthly out-of-sample Value-at-Risk (VaR) predictions. We use the recently proposed Realized GARCH model combined with the skewed student distribution for the innovations process and a Monte Carlo simulation approach in order to produce the multi-period VaR estimates. The VaR forecasts are evaluated in terms of statistical and regulatory accuracy as well as capital efficiency. Our empirical findings, based on the S&P 500 stock index, indicate that almost all realized and implied volatility measures can produce statistically and regulatory precise VaR forecasts across forecasting horizons, with the implied volatility being especially accurate in monthly VaR forecasts. The daily range produces inferior forecasting results in terms of regulatory accuracy and Basel II compliance. However, robust realized volatility measures such as the adjusted realized range and the realized bipower variation, which are immune against microstructure noise bias and price jumps respectively, generate superior VaR estimates in terms of capital efficiency, as they minimize the opportunity cost of capital and the Basel II regulatory capital. Our results highlight the importance of robust high frequency intra-daily data based volatility estimators in a multi-step VaR forecasting context as they balance between statistical or regulatory accuracy and capital efficiency