Treatment and timing in invasive mould disease

Invasive mould disease is a growing threat for immunocompromised patients. The optimum time to use mould-active antifungal agents is much debated. Current approaches to antifungal prophylaxis, early treatment (empirical and pre-emptive therapy) and treatment of documented mould infections in onco-haematology patients are discusse

Flight performance of actively foraging honey bees is reduced by a common pathogen

ArticleSudden and severe declines in honey bee (Apis mellifera) colony health in the US and Europe have been attributed, in part, to emergent microbial pathogens, however, the mechanisms behind the impact are unclear. Using roundabout flight mills, we measured the flight distance and duration of actively foraging, healthy-looking honey bees sampled from standard colonies, before quantifying the level of infection by Nosema ceranae and Deformed Wing Virus complex (DWV) for each bee. Neither the presence nor quantity of N. ceranae at low, natural levels of infection had any effect on flight distance or duration, but presence of DWV reduced flight distance by two thirds and duration by one half. Quantity of DWV was shown to have a significant, but weakly positive relation with flight distance and duration, however, the low amount of variation that was accounted for suggests further investigation by dose-response assays is required. We conclude that widespread, naturally occurring levels of infection by DWV weaken the flight ability of honey bees and high levels of within-colony prevalence are likely to reduce efficiency and increase the cost of resource acquisition. Predictions of implications of pathogens on colony health and function should take account of sub-lethal effects on flight performance.This work was funded by the Insect Pollinators Initiative (IPI) grants BB/I000100/1, BB/I000097/1 and BB/I000097/2, C.B. Dennis British Beekeepers' Research Trust and the High Wycombe Beekeepers’ Association. The IPI is funded jointly by the BBSRC, Defra, NERC, The Scottish Government and The Wellcome Trust, under the LWEC Partnership. Rothamsted Research is a national institute of bioscience strategically funded by the BBSRC

Specifics of intercultural communication: professional dialogue, etiquette, appearance in the different countries

The purpose of this study is to examine the features of etiquette around the world and get some idea of the peoples inhabiting them. Theoretical methods have been used to achieve this goal. The result of this research is more in-depth understanding of communication with representatives of other countries. Цель данного исследования заключается в том, чтобы изучить особенности этикета различных стран мира и получить определенное представление о народах, их населяющих. Для достижения этой цели были использованы общетеоретические методы. Результатом данного исследования является более углубленное понимание особенностей общения с представителями других стран

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

BACKGROUND Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited PK data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. OBJECTIVES To describe the pharmacokinetics of LAmB in children aged 1-17 years with suspected or documented IFD. METHODS Thirty-five children were treated with LAmB at dosages of 2.5-10 mg kg(-1) daily. Samples were taken at baseline and at 0.5-2.0 hourly intervals for twenty-four hours after receipt of the first dose (n=35 patients) and on the final day of therapy (n=25 patients). LAmB was measured using high performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. RESULTS An evolution in PK was observed during the course of therapy resulting in a proportion of patients (n=13) having significantly higher maximum serum concentration (Cmax) and area under the concentration time curve (AUC0-24) later in the course of therapy, without evidence of drug accumulation (Cmin accumulation ratio, AR < 1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (OR 2.37; 95% CI 1.84-3.22, p=0.004). CONCLUSIONS LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation or observed clinical factors

Роль хемокинов в рекрутировании клеток-предшественников в опухолевую нишу при раке молочной железы

Развитие первичной опухоли сопровождается формированием опухолевой ниши, котораясоздает благоприятные условия для выживания и пролиферации раковых клеток. Одним из ключевых элементов эволюции опухолевой ниши является рекрутирование костномозговых клеток-предшественников, включая клетки-предшественники макрофагов, мезенхимальные столовые клетки, эндотелиальные и гемопоэтические клетки-предшественники. Миграция упомянутых клеток в опухоль регулируется рядом хемокинов, в том числе CCL2, CXCL12, MSP (macrophage stimulating protein) и MIF (macrophage inhibitory factor). Целью настоящего исследования являлось изучение параметров опухолевой ниши при раке молочной железы. Исследование включало 24 больных с инвазивной карциномой неспецифического типа молочной железы. В суспензии опухолевых клеток методом проточной цитофлюориметрии определяли содержание клеток-предшественников. Концентрацию хемокинов CCL2, CXCL12, MSP и MIF в венозной крови больных оценивали с помощью твердофазного иммуноферментного анализа. Достоверных различий в содержании исследованных клеточных популяций, а также концентрации изученных хемокинов между пациентами, разделенными на группы взависимости от наличия или отсутствия лимфогенных метастазов и неоадъювантного лечения, обнаружено не было. В то же время, установлена прямая корреляционная связь между содержанием гемопоэтических клеток-предшественников в опухоли и концентрацией CXCL12 и MIF в крови

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde