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

Курортное лечение в комплексе реабилитационных мероприятий больных бронхиальной астмой

In the article, aspects of the sanatorial treatment efficacy that is valuable in the rehabilitational measures complex during bronchial asthma (BA) are discussed. According to data of sanatorial physicians based on parameters of the clinical course of the disease, respiratory function, and data of the inflammational process activity in the bronchial tree, the most of patients with BA were discharged with relief. In conditions of the Kislovodsk sanatorium, the relief was observed in 90.8—98.4% of the patients while remission may be durated near 7.6 months. In 60—70% of the patients the vital capacity increased in 380±20.7 ml, the maximal voluntary ventilation increased in 14.6±2 1, and FEV1 increased in 320±17.5 ml. The normalization of the cholinergic system as the increase of the cholinestherase level 245.8±7. to 254.8±12.1 mkM/hml, p<0.05 promoted to the respiration activation. It was noted, that in 64% of the arriving to the Kislovodsk sanatorium persons the level of IgE and the level of IgG decreased to 217 KI/1 and 1014±25. mg/% respectively.The obtained data testify about the increase of the natural resistance of the organism that assisted the most of patients with BA in the favorable course of the disease and in successful acclimatization. These data pointed to the availability of direction to the sanatorium of patients with early signs of the disease such as predasthma or non pulmonary allergy forms complicated with the occupational harm and cold.В данной статье рассматриваются вопросы эффективности курортного лечения, занимающего видное место в комплексе реабилитационных мероприятий при бронхиальной астме. Согласно данным курортологов на основе показателей клинического течения, функции внешнего дыхания и данных, отражающих активность воспалительного процесса в бронхолегочном аппарате, подавляющее большинство больных БА выбывают после лечения с улучшением. В условиях Кисловодского курорта улучшение наступило у 90,8—98,4% больных, при этом ремиссия может составлять до 7,6 месяца. У 60—70% больных увеличивалась жизненная емкость на 380±20,7 мл, максимальная произвольная вентиляция — на 14,6±2 л, ОФВ1 — на 320±17,5 мл. Активации внешнего дыхания способствовала нормализация деятельности холинергической системы в виде повышения уровня холинэстеразы с 245,8±7 до 254,8+12,1 мкМ/ч*мл, p<0,05. Отмечено также, что у 64% поступивших на Кисловодский курорт снижались уровень LgЕ с 300—560 КИ/л до 217 КИ/л и уровень LgG до 1014+25,0 мг/%.Полученные данные свидетельствуют о повышении естественной резистентности организма, что способствовало у большинства больных БА благоприятному течению заболевания и успешной акклиматизации на курорте. Эти данные также указывают на целесообразность направления на курорт больных с ранними проявлениями заболевания, рассматриваемыми в последние годы как предастма, или лиц, страдающих нелегочными формами аллергии, осложненными профессиональными вредностями и простудными заболеваниями

Determination of power level for low intensity training reactor at Oak Ridge /

"Date Declassified: December 5, 1955.""Engineering Practice School, Massachusetts Institute of Technology."Prepared from work performed at the X-10 Plant of the Carbide and Carbon Chemicals Division, Union Carbide and Carbon Corporation, Oak Ridge, Tennessee, Subcontract 70.""K-864.""January 29, 1952."Includes bibliographical references (p. 33-34).Mode of access: Internet

Risk and preventive negotiations

Preventive negotiation is associated with terms such as farsightedness and vision, and so inherently involves uncertainties. Risk is used here to refer to dangerous uncertainty: a shorthand summary for the definition used in the Introduction as "the expectation of negative consequences of current or potential, future phenomena or events." It refers to losses and so is the negative side of opportunity, which is the positive side of uncertainty and refers to gains. Probably chance, as commonly used, spans both. You run or take a chance or risk, but you seize a chance or opportunity: all three are uncertainties with different values. But risk is not just cost, loss, or expected damage; it is uncertain damage, the combination of loss and uncertainty. Indeed, risk depends on uncertainty, the replacement of 'certainty of no damageby no certainty of no damage'. However, preventive negotiations do not just have a risk aspect; among other things, risk is their subject