Characterizing solute hydrogen and hydrides in pure and alloyed titanium at the atomic scale

Ti has a high affinity for hydrogen and are typical hydride formers . Ti -hydride are brittle phases which probably cause premature failure of Ti -alloys. Here, we used atom probe tomography and electron microscopy to investigate the hydrogen di stribution in a set of specimens of commercially pure Ti , model and commercial Ti -alloys. Although likely partly introduced during specimen preparation with the focused- ion beam, we show formation of Ti-hydrides along α grain boundaries and α / β phase boundaries in commercial pure Ti and α + β binary model alloys . No hydrides are observed in the α phase in alloys with Al addition or quenched-in Mo supersaturation

Geographical Distribution of Intestinal Schistosomiasis and Soil-Transmitted Helminthiasis and Preventive Chemotherapy Strategies in Sierra Leone

The common intestinal roundworm, whipworm and hookworm (together known as soil-transmitted helminthes - STHs) together with schistosomes or bilharzia are responsible for extensive ill health, reduced life expectancy and death in sub-Saharan Africa. These diseases are transmitted in areas of poor water supply and sanitation. In order to implement an appropriate national control program, knowledge of the prevalence and geographical distribution of these diseases is required. A national survey was performed in Sierra Leone in 2008. Overall prevalence of intestinal schistosomiasis was 18.4% and that of STHs was 39.1%. Intestinal schistosomiasis was mainly prevalent in the northern and eastern regions while STH is widespread in the country. The results justify routine de-worming for pre-school children, school age children, women of childbearing age, and adults at high risk twice a year. The results also justify using anti-schistosomiasis drug (praziquantel) in school age children, all women of childbearing age, and adults at high risk annually or biennially depending upon the prevalence in the areas

Cross-Protection against Lethal H5N1 Challenge in Ferrets with an Adjuvanted Pandemic Influenza Vaccine

Background. Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential

Evaluation of Current Knowledge, Awareness and Practice of Spirometry among Hospital -based Nigerian Doctors

<p>Abstract</p> <p>Background</p> <p>Spirometry is a cost-effective diagnostic tool for evaluation of lung function and for case-finding in a resource-limited setting. The acceptance of this test depends on the awareness of its indications and the ability to interpret the results. No studies have assessed the knowledge of spirometry among Nigerian doctors. The aim of this study was to evaluate the current knowledge, awareness and practice of spirometry among hospital-based Nigerian doctors.</p> <p>Methods</p> <p>We carried out a cross-sectional survey among 321 doctors working in Nigerian hospitals between March 2008 and June 2008. Information on knowledge, awareness, practice of and barriers to spirometry were obtained using a pre-tested, self-administered structured questionnaire and the data were then analysed.</p> <p>Results</p> <p>Of the 321 doctors that participated, 108 (33.6%) reported that they have good knowledge of spirometry. One hundred and ninety-five (60.7%) were aware of the importance of spirometry in aiding the diagnosis of respiratory diseases; 213(66.4%) were aware of the importance of spirometry in determining the severity of diseases. Medical school was the most common source of knowledge on spirometry (64.5%). Eighty-one (25.2%) doctors reported having a spirometer in their hospitals. Doctors having access to a spirometer used it more frequently for aiding the diagnosis of COPD (40.7% vs.27.5%) and for monitoring of asthma (18.5% vs.11.3%) than those without access to a spirometer. The doctors working in University Teaching Hospitals and Federal Medical Centres (FMC) (22.4% vs. 4.5%) and those having access to a spirometer (40.7 vs.11.3%) were very confident of interpreting spirometry results compared to those working in District and General Hospitals and without access to a spirometer. Irrespective of access to a spirometer or the type of hospital they were employed in, doctors reported that unavailability of a spirometer was the greatest barrier to its use (62.5%) followed by lack of awareness about its usefulness (17.2%).</p> <p>Conclusion</p> <p>The knowledge and practice of spirometry were poor among hospital-based Nigerian doctors because of unavailability of spirometers in most hospitals. These findings have implications for further evaluation, planning and management of patient care in respiratory disease. Spirometers should be made available in all hospitals, and the knowledge of spirometry should be improved among doctors.</p

Oseltamivir–Resistant Pandemic H1N1/2009 Influenza Virus Possesses Lower Transmissibility and Fitness in Ferrets

The neuraminidase (NA) inhibitor oseltamivir offers an important immediate option for the control of influenza, and its clinical use has increased substantially during the recent H1N1 pandemic. In view of the high prevalence of oseltamivir-resistant seasonal H1N1 influenza viruses in 2007–2008, there is an urgent need to characterize the transmissibility and fitness of oseltamivir-resistant H1N1/2009 viruses, although resistant variants have been isolated at a low rate. Here we studied the transmissibility of a closely matched pair of pandemic H1N1/2009 clinical isolates, one oseltamivir-sensitive and one resistant, in the ferret model. The resistant H275Y mutant was derived from a patient on oseltamivir prophylaxis and was the first oseltamivir-resistant isolate of the pandemic virus. Full genome sequencing revealed that the pair of viruses differed only at NA amino acid position 275. We found that the oseltamivir-resistant H1N1/2009 virus was not transmitted efficiently in ferrets via respiratory droplets (0/2), while it retained efficient transmission via direct contact (2/2). The sensitive H1N1/2009 virus was efficiently transmitted via both routes (2/2 and 1/2, respectively). The wild-type H1N1/2009 and the resistant mutant appeared to cause a similar disease course in ferrets without apparent attenuation of clinical signs. We compared viral fitness within the host by co-infecting a ferret with oseltamivir-sensitive and -resistant H1N1/2009 viruses and found that the resistant virus showed less growth capability (fitness). The NA of the resistant virus showed reduced substrate-binding affinity and catalytic activity in vitro and delayed initial growth in MDCK and MDCK-SIAT1 cells. These findings may in part explain its less efficient transmission. The fact that the oseltamivir-resistant H1N1/2009 virus retained efficient transmission through direct contact underlines the necessity of continuous monitoring of drug resistance and characterization of possible evolving viral proteins during the pandemic

Effect of Neuraminidase Inhibitor–Resistant Mutations on Pathogenicity of Clade 2.2 A/Turkey/15/06 (H5N1) Influenza Virus in Ferrets

The acquisition of neuraminidase (NA) inhibitor resistance by H5N1 influenza viruses has serious clinical implications, as this class of drugs can be an essential component of pandemic control measures. The continuous evolution of the highly pathogenic H5N1 influenza viruses results in the emergence of natural NA gene variations whose impact on viral fitness and NA inhibitor susceptibility are poorly defined. We generated seven genetically stable recombinant clade 2.2 A/Turkey/15/06-like (H5N1) influenza viruses carrying NA mutations located either in the framework residues (E119A, H274Y, N294S) or in close proximity to the NA enzyme active site (V116A, I117V, K150N, Y252H). NA enzyme inhibition assays showed that NA mutations at positions 116, 117, 274, and 294 reduced susceptibility to oseltamivir carboxylate (IC50s increased 5- to 940-fold). Importantly, the E119A NA mutation (previously reported to confer resistance in the N2 NA subtype) was stable in the clade 2.2 H5N1 virus background and induced cross-resistance to oseltamivir carboxylate and zanamivir. We demonstrated that Y252H NA mutation contributed for decreased susceptibility of clade 2.2 H5N1 viruses to oseltamivir carboxylate as compared to clade 1 viruses. The enzyme kinetic parameters (Vmax, Km and Ki) of the avian-like N1 NA glycoproteins were highly consistent with their IC50 values. None of the recombinant H5N1 viruses had attenuated virulence in ferrets inoculated with 106 EID50 dose. Most infected ferrets showed mild clinical disease signs that differed in duration. However, H5N1 viruses carrying the E119A or the N294S NA mutation were lethal to 1 of 3 inoculated animals and were associated with significantly higher virus titers (P<0.01) and inflammation in the lungs compared to the wild-type virus. Our results suggest that highly pathogenic H5N1 variants carrying mutations within the NA active site that decrease susceptibility to NA inhibitors may possess increased virulence in mammalian hosts compared to drug-sensitive viruses. There is a need for novel anti-influenza drugs that target different virus/host factors and can limit the emergence of resistance

Adaptation of High-Growth Influenza H5N1 Vaccine Virus in Vero Cells: Implications for Pandemic Preparedness

Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15) was generated and can grow over 108 TCID50/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes