Enhanced Auditory Neuron Survival Following Cell-Based BDNF Treatment in the Deaf Guinea Pig

Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients

Total elemental composition of soils in Sub-Saharan Africa and relationship with soil forming factors

AbstractA thorough understanding of the variation in total soil element concentrations is important especially in the Sub-Saharan Africa (SSA) soil contexts for agricultural and environmental management at large scale. Fingerprinting of soil elemental composition may form a useful basis for evaluating soils in a way that relates to soil-forming factors and inherent soil functional properties. The objectives of this paper are to quantify the proportion of variability in total elemental composition by total X-ray fluorescence (TXRF) method of 1074 soil samples from the Africa Soil Information Service (AfSIS) Project baseline and to determine the relationships with soil forming factors. The samples were from 34 sentinel sites measuring 10×10km, randomized within major climate zones in SSA. Within each sentinel site there were sixteen spatially stratified 1km2 clusters, within which there were ten 100m2 plots. The within and between site patterns of variation in total element composition of 17 elements; Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Ga, Sr, Y, Ta, and Pb, were explored. Total element concentration values were within the range reported globally for soil Cr, Mn, Zn, Ni, V, Sr, and Y and higher than reported range for Al, Cu, Ta, Pb, and Ga. There were significant variations (P<0.05) in total element composition within and between the sites for all the elements analyzed with the greatest proportion of total variance and number of significant variance components occurring at the site (55–88%) followed by the cluster nested within site (10–40%) levels. The explorations of the relationships between element composition data and site factors using Random Forest regression demonstrated that soil-forming factors have important influence on total elemental composition in the soil. The fact that the soil-forming factors are related to the concentration of naturally occurring elements in the soil gives rise to the notion that they might be predicted from the soils' element composition. Results implied that >70% of variation in soil element composition patterns can be predicted using information in existing databases or readily observable features. Successful use of TXRF technique would open up possibilities for using total soil elemental composition fingerprints as a useful basis for characterizing soils in a way that relates to soil-forming factors and inherent soil functional properties

Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA-N2 non–small cell lung cancer

ObjectiveOptimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The surgical arm of the North American Intergroup 0139 trial was adopted as the standard treatment for patients with resectable N2 disease at the University Health Network. Results after 7 years of experience are reported.MethodsThis is a retrospective study of consecutive patients with biopsy-proved T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 1997 through August 2004. Induction chemotherapy consisted of cisplatin, 50 mg/m2, on days 1 and 8; etoposide, 50 mg/m2, on days 1 to 5, weeks 1 and 5; and concurrent daily external beam radiotherapy to 45 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation, followed by 2 further cycles of consolidation chemotherapy.ResultsBetween January 1997 and August 2004, 40 patients were treated according to this protocol (25% T1, 62.5% T2, 7.5% T3, and 5% T4). Overall and disease-free median survivals were 40 and 37.1 months, respectively, whereas overall and disease-free 3-year survivals were 51.7% and 52.3%, respectively. R0 resection was achieved in 92.5%. The overall operative mortality rate was 7.5% (0% for lobectomy and 27% for pneumonectomy). Notably, all mortalities occurred within the first 2 years of our experience with this regimen.ConclusionChemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can lead to improved overall and disease-free survival

The potential to narrow uncertainty in projections of stratospheric ozone over the 21st century

Future stratospheric ozone concentrations will be determined both by changes in the concentration of ozone depleting substances (ODSs) and by changes in stratospheric and tropospheric climate, including those caused by changes in anthropogenic greenhouse gases (GHGs). Since future economic development pathways and resultant emissions of GHGs are uncertain, anthropogenic climate change could be a significant source of uncertainty for future projections of stratospheric ozone. In this pilot study, using an "ensemble of opportunity" of chemistry-climate model (CCM) simulations, the contribution of scenario uncertainty from different plausible emissions pathways for ODSs and GHGs to future ozone projections is quantified relative to the contribution from model uncertainty and internal variability of the chemistry-climate system. For both the global, annual mean ozone concentration and for ozone in specific geographical regions, differences between CCMs are the dominant source of uncertainty for the first two-thirds of the 21st century, up-to and after the time when ozone concentrations return to 1980 values. In the last third of the 21st century, dependent upon the set of greenhouse gas scenarios used, scenario uncertainty can be the dominant contributor. This result suggests that investment in chemistry-climate modelling is likely to continue to refine projections of stratospheric ozone and estimates of the return of stratospheric ozone concentrations to pre-1980 levels

Coordination risk and cost impacts on economic development in poor rural areas

This paper addresses issues relevant to a critical problem in economic development: how to get rapid pro-poor economic growth in poor rural areas in Africa and South Asia where most of the world’s dollar a day poor live. It examines constraints to the development of coordinated exchange systems in poor rural areas, focusing on the core problem of thin markets and low density of economic activity in these areas. Transaction cost and risk analysis is integrated into a conventional neoclassical production economics framework to describe the existence of low level equilibrium traps in transactions and supply chains and to generate important insights for development policy

Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, respectively. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression

A high resolution record of Greenland mass balance

We map recent Greenland Ice Sheet elevation change at high spatial (5-km) and temporal (monthly) resolution using CryoSat-2 altimetry. After correcting for the impact of changing snowpack properties associated with unprecedented surface melting in 2012, we find good agreement (3 cm/yr bias) with airborne measurements. With the aid of regional climate and firn modelling, we compute high spatial and temporal resolution records of Greenland mass evolution, which correlate (R=0.96) with monthly satellite gravimetry, and reveal glacier dynamic imbalance. During 2011-2014, Greenland mass loss averaged 269±51 Gt/yr. Atmospherically-driven losses were widespread, with surface melt variability driving large fluctuations in the annual mass deficit. Terminus regions of five dynamically-thinning glaciers, which constitute less than 1% of Greenland's area, contributed more than 12% of the net ice loss. This high-resolution record demonstrates that mass deficits extending over small spatial and temporal scales have made a relatively large contribution to recent ice sheet imbalance

A Measurement of the Product Branching Ratio f(b->Lambda_b).BR(Lambda_b->Lambda X) in Z0 Decays

The product branching ratio, f(b->Lambda_b).BR(Lambda_b->Lambda X), where Lambda_b denotes any weakly-decaying b-baryon, has been measured using the OPAL detector at LEP. Lambda_b are selected by the presence of energetic Lambda particles in bottom events tagged by the presence of displaced secondary vertices. A fit to the momenta of the Lambda particles separates signal from B meson and fragmentation backgrounds. The measured product branching ratio is f(b->Lambda_b).BR(Lambda_b->Lambda X) = (2.67+-0.38(stat)+0.67-0.60(sys))% Combined with a previous OPAL measurement, one obtains f(b->Lambda_b).BR(Lambda_b->Lambda X) = (3.50+-0.32(stat)+-0.35(sys))%.Comment: 16 pages, LaTeX, 3 eps figs included, submitted to the European Physical Journal