n-type chalcogenides by ion implantation.

Carrier-type reversal to enable the formation of semiconductor p-n junctions is a prerequisite for many electronic applications. Chalcogenide glasses are p-type semiconductors and their applications have been limited by the extraordinary difficulty in obtaining n-type conductivity. The ability to form chalcogenide glass p-n junctions could improve the performance of phase-change memory and thermoelectric devices and allow the direct electronic control of nonlinear optical devices. Previously, carrier-type reversal has been restricted to the GeCh (Ch=S, Se, Te) family of glasses, with very high Bi or Pb 'doping' concentrations (~5-11 at.%), incorporated during high-temperature glass melting. Here we report the first n-type doping of chalcogenide glasses by ion implantation of Bi into GeTe and GaLaSO amorphous films, demonstrating rectification and photocurrent in a Bi-implanted GaLaSO device. The electrical doping effect of Bi is observed at a 100 times lower concentration than for Bi melt-doped GeCh glasses.This work was supported by the UK EPSRC grants EP/I018417/1, EP/I019065/1 and EP/I018050/1.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms634

A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway

Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum

Correlation between CD4 counts of HIV patients and enteric protozoan in different seasons – An experience of a tertiary care hospital in Varanasi (India)

<p>Abstract</p> <p>Background</p> <p>Protozoan infections are the most serious among all the superimposed infections in HIV patients and claim a number of lives every year. The line of treatment being different for diverse parasites necessitates a definitive diagnosis of the etiological agents to avoid empirical treatment. Thus, the present study has been aimed to elucidate the associations between diarrhoea and CD4 counts and to study the effect of HAART along with management of diarrhoea in HIV positive patients. This study is the first of its kind in this area where an attempt was made to correlate seasonal variation and intestinal protozoan infestations.</p> <p>Methods</p> <p>The study period was from January 2006 to October 2007 wherein stool samples were collected from 366 HIV positive patients with diarrhea attending the ART centre, inpatient department and ICTC of S.S. hospital, I.M.S., B.H.U., Varanasi. Simultaneously, CD4 counts were recorded to assess the status of HIV infection vis-à-vis parasitic infection. The identification of pathogens was done on the basis of direct microscopy and different staining techniques.</p> <p>Results</p> <p>Of the 366 patients, 112 had acute and 254 had chronic diarrhea. The percentages of intestinal protozoa detected were 78.5% in acute and 50.7% in chronic cases respectively. Immune restoration was observed in 36.6% patients after treatment on the basis of clinical observation and CD4 counts. In 39.8% of HIV positive cases <it>Cryptosporidium </it>spp. was detected followed by <it>Microsporidia </it>spp. (26.7%). The highest incidence of intestinal infection was in the rainy season. However, infection with <it>Cyclospora </it>spp. was at its peak in the summer. Patients with chronic diarrhea had lower CD4 cell counts. The maximum parasitic isolation was in the patients whose CD4 cell counts were below 200 cells/μl.</p> <p>Conclusion</p> <p>There was an inverse relation between the CD4 counts and duration of diarrhea. <it>Cryptosporidium </it>spp. was isolated maximum among all the parasites in the HIV patients. The highest incidence of infection was seen in the rainy season.</p

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

<p>Abstract</p> <p>Background</p> <p>Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.</p> <p>Methods</p> <p>A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.</p> <p>Results</p> <p>A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.</p> <p>Conclusions</p> <p>Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.</p