The role of delamanid in the treatment of drug-resistant tuberculosis

Tuberculosis (TB) remains a significant cause of death worldwide, and emergence of drug-resistant TB requires lengthy treatments with toxic drugs that are less effective than their first-line equivalents. New treatments are urgently needed. Delamanid, previously OPC-67863, is a novel drug of the dihydro-nitroimidazole class with potent anti-TB activity and great promise to be effective in the treatment of drug-resistant TB. This review examines the preclinical and clinical development of delamanid, reviews current guidance on its use and evaluates the opportunities and challenges for its future role in TB management.Publisher PDFPeer reviewe

Management of multidrug-resistant TB : novel treatments and their expansion to low resource settings

This article received no specific funding. JL is supported by the Wellcome Trust as a clinical PhD fellow [grant number 109105/Z/15/Z].Despite overall progress in global TB control, the rising burden ofmultidrug-resistant TB (MDR-TB) threatens to undermine efforts to end theworldwide epidemic. Of the 27 countries classified as high burden for MDR-TB, 17 are in 'low' or 'low-middle' income countries. Shorter, all oral and less toxic multidrug combinations are required to improve treatment outcomes in these settings. Suitability for safe co-administration with HIV drugs is also desirable. A range of strategies and several new drugs (including bedaquiline, delamanid and linezolid) are currently undergoing advanced clinical evaluations to define their roles in achieving these aims. However, several clinical questions and logistical challenges need to be overcome before these new MDR-TB treatments fulfil their potential.Publisher PDFPeer reviewe

Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis

Background Aetiology and outcomes of sepsis in sub-Saharan Africa (sSA) are poorly described; we performed a systematic review and meta-analysis to summarise the available data. Methods Systematic searches of PubMed and Scopus were undertaken to identify prospective studies recruiting adults (> 13 years) with community-acquired sepsis in sSA post-2000. Random effects meta-analysis of in-hospital and 30-day mortality was undertaken and available aetiology data also summarised by random effects meta-analysis. Results Fifteen studies of 2800 participants were identified. Inclusion criteria were heterogeneous. The majority of patients were HIV-infected, and Mycobacterium tuberculosis was the most common cause of blood stream infection where sought. Pooled in-hospital mortality for Sepsis-2-defined sepsis and severe sepsis was 19% (95% CI 12–29%) and 39% (95% CI 30–47%) respectively, and sepsis mortality was associated with the proportion of HIV-infected participants. Mortality and morbidity data beyond 30 days were absent. Conclusions Sepsis in sSA is dominated by HIV and tuberculosis, with poor outcomes. Optimal antimicrobial strategies, including the role of tuberculosis treatment, are unclear. Long-term outcome data are lacking. Standardised sepsis diagnostic criteria that are easily applied in low-resource settings are needed to establish an evidence base for sepsis management in sSA

Long-term Trends and the Trophic Status of Conesus Lake 2012: A report to the Livingston County Planning Department Geneseo, NY

Conesus Lake monitoring conducted by personnel from The College at Brockport during the summer of 2012 determined the current trophic status of the lake and if any improvements or further degradation of water quality had occurred. To accomplish this goal, lake chemistry was monitored from 22 May to 14 August 2012 and the following were completed: a trophic state assessment of the lake and an evaluation of long-term trends in lake chemistry. Recommendations 1. The monitoring of Conesus Lake should continue. Current results suggest a slow improvement in it’s surface water. The status of the lake’s water quality has been an issue for many years. If it is indeed improving as suggested, this success story needs to be communicated to the general public. 2. The importance of managing nutrients and soil loss from the watershed is now even more important to prevent a relapse or return to less desirable conditions. Continuing efforts to reduce nutrient losses from sources in agriculture, from septic systems above the ring sewer, and from lawn fertilizers should be emphasized

The population of propellers in Saturn's A Ring

We present an extensive data set of ~150 localized features from Cassini images of Saturn's Ring A, a third of which are demonstrated to be persistent by their appearance in multiple images, and half of which are resolved well enough to reveal a characteristic "propeller" shape. We interpret these features as the signatures of small moonlets embedded within the ring, with diameters between 40 and 500 meters. The lack of significant brightening at high phase angle indicates that they are likely composed primarily of macroscopic particles, rather than dust. With the exception of two features found exterior to the Encke Gap, these objects are concentrated entirely within three narrow (~1000 km) bands in the mid-A Ring that happen to be free from local disturbances from strong density waves. However, other nearby regions are similarly free of major disturbances but contain no propellers. It is unclear whether these bands are due to specific events in which a parent body or bodies broke up into the current moonlets, or whether a larger initial moonlet population has been sculpted into bands by other ring processes.Comment: 31 pages, 10 figures; Accepted at A

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BackgroundFew adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).MethodsUsing AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.ResultsOverall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).ConclusionNot only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed

A comparative study of WASP-67b and HAT-P-38b from WFC3 data

Atmospheric temperature and planetary gravity are thought to be the main parameters affecting cloud formation in giant exoplanet atmospheres. Recent attempts to understand cloud formation have explored wide regions of the equilibrium temperature-gravity parameter space. In this study, we instead compare the case of two giant planets with nearly identical equilibrium temperature ($T_\mathrm{eq}$ $\sim 1050 \, \mathrm{K}$) and gravity ($g \sim 10 \, \mathrm{m \, s}^{-1})$. During $HST$ Cycle 23, we collected WFC3/G141 observations of the two planets, WASP-67 b and HAT-P-38 b. HAT-P-38 b, with mass 0.42 M$_\mathrm{J}$ and radius 1.4 $R_\mathrm{J}$, exhibits a relatively clear atmosphere with a clear detection of water. We refine the orbital period of this planet with new observations, obtaining $P = 4.6403294 \pm 0.0000055 \, \mathrm{d}$. WASP-67 b, with mass 0.27 M$_\mathrm{J}$ and radius 0.83 $R_\mathrm{J}$, shows a more muted water absorption feature than that of HAT-P-38 b, indicating either a higher cloud deck in the atmosphere or a more metal-rich composition. The difference in the spectra supports the hypothesis that giant exoplanet atmospheres carry traces of their formation history. Future observations in the visible and mid-infrared are needed to probe the aerosol properties and constrain the evolutionary scenario of these planets.Comment: 16 pages, 17 figures, 8 tables, accepted for publication in The Astronomical Journa

Phytoplankton, Zooplankton, Macrobenthos and lchthyoplankton Abundance, Biomass and Species Composition in Onondaga Lake, 1994

Once a pristine recreational center and a productive fishery that supplied New York City markets with fresh fish, Onondaga Lake is now considered one of the most badly degraded bodies of water in the entire world (Sage 1993). The Onondaga Lake Management Conference was established to develop a comprehensive restoration, conservation, and management plan for Onondaga Lake that recommends priority corrective actions and a compliance schedule for cleanup of the lake. Biological assessment of the lake has been infrequent and concentrated on a few biological groups. This study either updates or establishes baseline characteristics for the following biological components of the Onondaga Lake ecosystem: phytoplankton, zooplankton, ichthyoplankton and macrobenthos