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We present the first spatial analysis of "fingerprints" of the El Niño/Southern Oscillation (ENSO) and atmospheric aerosol load after major volcanic eruptions (El Chichón and Mt. Pinatubo) in extreme low and high (termed ELOs and EHOs respectively) and mean values of total ozone for the northern and southern mid latitudes (defined as the region between 30° and 60° north and south respectively). Significant influence on ozone extremes was found for the warm ENSO phase in both hemispheres during spring especially towards low latitudes indicating the enhanced ozone transport from the tropics to the extra tropics. Further the results confirm findings of recent work on the connection between the ENSO phase and the strength and extent of the southern ozone "collar". For the volcanic eruptions the analysis confirms findings of earlier studies for the northern mid latitudes and gives new insights for the Southern Hemisphere. The results provide evidence that the negative effect of the eruption of El Chichón might be partly compensated by a strong warm ENSO phase in 1982–1983 at southern mid latitudes. The strong west east gradient in the coefficient estimates for the Mt. Pinatubo eruption and the analysis of the relationship between the AAO and ENSO phase the extent and the position of the southern ozone "collar" and the polar vortex structure provide clear evidence for a dynamical "masking" of the volcanic signal at southern mid latitudes. The paper also analyses the contribution of atmospheric dynamics and chemistry to long term total ozone changes. Here quite heterogeneous results have been found on spatial scales. In general the results show that EESC and the 11 yr solar cycle can be identified as major contributors to long term ozone changes. However a strong contribution of dynamical features (El Niño/Southern Oscillation (ENSO) North Atlantic Oscillation (NAO) Antarctic Oscillation (AAO) Quasi Biennial Oscillation (QBO)) to ozone variability and trends is found at a regional level. For the QBO (at 30 and 50 hPa) strong influence on total ozone variability and trends is found over large parts of the northern and southern mid latitudes especially towards equatorial latitudes. Strong influence of ENSO is found over the Northern and Southern Pacific Central Europe and central southern mid latitudes. For the NAO strong influence on column ozone is found over Labrador/Greenland the Eastern United States the Euro Atlantic Sector and Central Europe. For the NAO's southern counterpart the AAO strong influence on ozone variability and long term changes is found at lower southern mid latitudes including the southern parts of South America and the Antarctic Peninsula and central southern mid latitudes.

Four methods were used to assess gentamicin concentrations in 37 sera of patients treated with gentamicin. It was shown that the bioassay (agar diffusion) and the enzyme immunoassay correlated well, and the latex agglutination inhibition test badly, with the radioenzyme assay which was used as the reference method. Among presently available methods only the bioassay can be performed with relatively little equipment.

Contains fulltext : 96402.pdf (Publisher’s version ) (Open Access) The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Isoniazid preventive therapy (IPT) is recognised as an important component of collaborative tuberculosis (TB) and human immunodeficiency virus (HIV) activities to reduce the burden of TB in people living with HIV (PLHIV). However, there has been little in the way of IPT implementation at country level. This failure has resulted in a recent call to arms under the banner title of the 'Three I's' (infection control to prevent nosocomial transmission of TB in health care settings, intensified TB case finding and IPT). In this paper, we review the background of IPT. We then discuss the important challenges of IPT in PLHIV, namely responsibility and accountability for the implementation, identification of latent TB infection, exclusion of active TB and prevention of isoniazid resistance, length of treatment and duration of protective efficacy. We also highlight several research questions that currently remain unanswered. We finally offer practical suggestions about how to scale up IPT in the field, including the need to integrate IPT into a package of care for PLHIV, the setting up of operational projects with the philosophy of 'learning while doing', the development of flow charts for eligibility for IPT, the development and implementation of care prior to antiretroviral treatment, and finally issues around procurement, distribution, monitoring and evaluation. We support the implementation of IPT, but only if it is done in a safe and structured way. There is a definite risk that 'sloppy' IPT will be inefficient and, worse, could lead to the development of multidrug-resistant TB, and this must be avoided at all costs.

Scatter factor (SF), a secretory protein of fibroblasts, dissociates and increases the motility of epithelial cells and may be involved in cell migration processes during embryogenesis and tumor progression. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and other cells, and is thought to play a role in liver regeneration. We have presented structural and functional evidence that human SF and human HGF are identical proteins encoded by a single gene, since (i) no differences could be found by protein sequencing, by cDNA analysis, or by immunological comparison, and (ii) SF acts as a hepatocyte growth factor--i.e., stimulates DNA synthesis of primary hepatocytes and is a morphogen of kidney epithelial cells--whereas HGF exhibits SF activity--i.e., dissociates and induces invasiveness of various epithelial cells. Furthermore, there exists only one gene for human HGF-SF which is located on chromosome 7, bands q11.2-21 (Weidner et al., Proc. Natl. Acad. Sci. USA 88, 7001-7005, 1991). HGF-SF has been found to be the ligand of the c-met receptor tyrosine kinase (Naldini et al., EMBO J. 10, 2867-2878, 1991b). We have recently used transient expression of naturally occurring and in vitro mutagenized cDNAs of HGF-SF in order to delineate the protein domains necessary for biological activity and c-met receptor activation. (i) A single-chain HGF-SF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg494 to Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A HGF-SF splice variant encoding a protein with a 5 amino acid deletion in the first kringle domain was as highly active as the wild type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N-terminus and the first two kringle domains bound the met receptor, stimulated its tyrosine phosphorylation, and induced dissociation of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N-terminal region and/or the first two kringle domains of HGF-SF is sufficient for binding to and activation of the met receptor (Hartmann et al., Proc. Natl. Acad. Sci. USA, in press).

The activities of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase(6PGDH), malic enzyme (ME) and isocitrate dehydrogenase (ICDh) were investigated with optimized histochemical methods (Rieder it al 1978), and the activity of 3-hydroxybutyrate dehydrogenase (3HBDH) and neutral fat content with conventional techniques in the liver of male rats under the following experimental dietary conditions: (A) Fasting for 0, 12 and 84h; (B) 84-h fasting followed by refeeding with a low-fat, high-carbohydrate diet for 6 h and for 2, 3, 5, 7, 11 and 14 nights; (C) refeeding with standard diet for 5 nights; (D) low-fat high-carbohydrate diet for 7 an 14 nights. The activities of G6PDH, 6PGDH and ME decreased slightly during fasting primarily in zone 1 and increased dramatically on refeeding with a low-fat, high-carbohydrate diet. This activity increase was confined mainly to zone 3 during the first 3 days and was accompanied by a deposition of neutral fats that began in zone 3 and progressed to zone 1. Neutral for accumulation was maximal after 3 nights, with a uniform accumulation of large droplets in all the hepatocytes; this was followed by a release that started in zone 3 and proceeded in a periportal direction. On the other hand, G6PDH, 6PGDH and ME attained their maximum activities after 5 amd 7 nights of low-fat diet, the activities being nearly homogeneously distributed over the liver acinus in a few cases. Subsequently the activities fill mainly in zone 1, causing the activity patterns and levels to approach those of the animals in group (D). In contrast to this, the activity of ICDH increased during fasting principally in zone 1, so that the otherwise steep activity gradient in favor of zone 3 lessened. Refeeding led at first to a fall of activity below the initial value, but later the normal distribution pattern was restored. The activity of 3HBDH showed a behavior similar to that of ICDH. The findings are discussed with reference to the functional heterogeneity of the liver parenchyma, and the existence of a liponeogenic area in zone 3 is proposed.

In this study ideas from extreme value theory are for the first time applied in the field of stratospheric ozone research, because statistical analysis showed that previously used concepts assuming a Gaussian distribution (e.g. fixed deviations from mean values) of total ozone data do not adequately address the structure of the extremes. We show that statistical extreme value methods are appropriate to identify ozone extremes and to describe the tails of the Arosa (Switzerland) total ozone time series. In order to accommodate the seasonal cycle in total ozone, a daily moving threshold was determined and used, with tools from extreme value theory, to analyse the frequency of days with extreme low (termed ELOs) and high (termed EHOs) total ozone at Arosa. The analysis shows that the Generalized Pareto Distribution (GPD) provides an appropriate model for the frequency distribution of total ozone above or below a mathematically well-defined threshold, thus providing a statistical description of ELOs and EHOs. The results show an increase in ELOs and a decrease in EHOs during the last decades. The fitted model represents the tails of the total ozone data set with high accuracy over the entire range (including absolute monthly minima and maxima), and enables a precise computation of the frequency distribution of ozone mini-holes (using constant thresholds). Analyzing the tails instead of a small fraction of days below constant thresholds provides deeper insight into the time series properties. Fingerprints of dynamical (e.g. ENSO, NAO) and chemical features (e.g. strong polar vortex ozone loss), and major volcanic eruptions, can be identified in the observed frequency of extreme events throughout the time series. Overall the new approach to analysis of extremes provides more information on time series properties and variability than previous approaches that use only monthly averages and/or mini-holes and mini-highs.

This work investigates the occurrence frequency of days with high erythemal UV doses at three stations in Switzerland and Austria (Davos, Hoher Sonnblick and Vienna) for the time period 1974-2003. While several earlier studies have reported on increases in erythemal UV dose up to 10% during the last decades, this study focuses on days with high erythema! UV dose, which is defined as a daily dose at least 15% higher than for 1950s clear-sky conditions (which represent preindustrial conditions with respect to anthropogenic chlorine). Furthermore, the influence of low column ozone, clear-sky/partly cloudy conditions and surface albedo on UV irradiance has been analyzed on annual and seasonal basis. The results of this study show that in the Central Alpine Region the number of days with high UV dose increased strongly in the early 1990s. A large fraction of all days with high UV dose occurring in the period 1974-2003 was found especially during the years 1994-2003, namely 40% at Davos, 54% at Hoher Sonnblick and 65% at Vienna. The importance of total ozone, clear-sky/partly cloudy conditions and surface albedo (e.g. in dependence of snow cover) varies strongly among the seasons. However, overall the interplay of low total ozone and clear-sky/partly cloudy conditions led to the largest fraction of days showing high erythemal UV dose. Furthermore, an analysis of the synoptic weather situation showed that days with high erythemal UV dose, low total ozone and high relative sunshine duration occur at all three stations more frequently during situations with low pressure gradients or southerly advection. (C) 2010 Elsevier B.V. All rights reserved.

To examine the influence of age and sex on the grading of tuberculosis (TB) sputum smear microscopy results.Laboratories in Moldova, Mongolia, Uganda and Zimbabwe.Data from nationally representative samples of laboratory registers were double-entered and validated, and discordances were resolved by rechecking against the registers.The dataset comprised 128,808 examinees from 23 laboratories in Moldova, all 31 in Mongolia, 30 in Uganda and 23 in Zimbabwe, each covering at least one calendar year. Among all examinees, 89,362 had a diagnostic examination, 13,577 (15.2%) of whom were cases. A non-quantified positive result was recorded among 1272 (9.4%) of these. Scanty results were most frequent in Zimbabwe (8.5%) and most infrequent in Uganda (1.1%). In contrast, the highest grade, of 3+ positive, was most frequent (43.9%) in Mongolia. The lowest proportion of low-grade positivity was recorded for males aged 15-24 years and the highest among females agedor=65 years.Differences in the frequency of low-grade positivity between the four countries were striking. Females tended to have lower bacillary counts, and low-grade positivity was more frequent at the extremes of age. These results reinforce the need for appropriate instructions on how to produce high-quality sputum to improve yield.

The Tuberculosis Surveillance and Research Unit (TSRU) held its last annual meeting in Helsinki, Finland, from 1 to 4 April 2008. Several topics of current interest for tuberculosis (TB) research and new research projects were presented and discussed in depth by 60 delegates from Europe, Africa and Asia. This paper summarises some of the highlights of the meeting which may be of interest to epidemiologists and managers active in the field of TB