The X-ray spectra and spectral variability of intermediate type Seyfert galaxies: ASCA observations of NGC 4388 and ESO 103-G35

The X-ray spectra of two intermediate type Seyfert galaxies are investigated using ASCA observations separated by more than a year. Both NGC 4388 and ESO 103-G35 exhibit strong, narrow Fe K alpha line emission and absorption by cold neutral gas with a column density ~ 10^23 cm^-2, characteristic of the X-ray spectra of type 2 Seyfert galaxies. The power law continuum flux has changed by a factor of 2 over a time-scale of ~ 2 years for both objects, declining in the case of NGC 4388 and rising in ESO 103-G35. No variation was observed in the equivalent width of the Fe K alpha line in the spectra of NGC 4388, implying that the line flux declined with the continuum. We find that the strength of the line cannot be accounted for by fluorescence in line-of-sight material with the measured column density unless a `leaky-absorber' model of the type favored for IRAS 04575-7537 is employed. The equivalent width of the Fe K alpha emission line is seen to decrease between the observations of ESO 103-G35 while the continuum flux increased. The 1996 observation of ESO 103-G35 can also be fitted with an absorption edge at 7.4 $\pm$ 0.2 keV due to partially ionized iron, and when an ionized absorber model is fitted to the data it is found that the equivalent column of neutral hydrogen rises to 3.5 x 10^23 cm^-2. The Fe K alpha line flux can be accounted by fluorescence in this material alone and this model is also a good representation of the 1988 and 1991 Ginga observations. There is then no requirement for a reflection component in the ASCA spectra of ESO 103-G35 or NGC 4388.Comment: 45 pages, 5 tables, 11 figures. Accepted for publication in the Astrophysical Journa

Toxigenic Clostridium difficile colonization among hospitalised adults; risk factors and impact on survival

Objectives: To establish risk factors for Clostridium difficile colonization among hospitalized patients in England. Methods: Patients admitted to elderly medicine wards at three acute hospitals in England were recruited to a prospective observational study. Participants were asked to provide a stool sample as soon as possible after enrolment and then weekly during their hospital stay. Samples were cultured for C. difficile before ribotyping and toxin detection by PCR. A multivariable logistic regression model of risk factors for C. difficile colonization was fitted from univariable risk factors significant at the p < 0.05 level. Results: 410/727 participants submitted ≥1 stool sample and 40 (9.8%) carried toxigenic C. difficile in the first sample taken. Ribotype 106 was identified three times and seven other ribotypes twice. No ribotype 027 strains were identified. Independent predictors of colonization were previous C. difficile infection (OR 4.53 (95% C.I. 1.33–15.48) and malnutrition (MUST score ≥2) (OR 3.29 (95% C.I. 1.47–7.35)). Although C. difficile colonised patients experienced higher 90-day mortality, colonization was not an independent risk for death. Conclusions: In a non-epidemic setting patients who have previously had CDI and have a MUST score of ≥2 are at increased risk of C. difficile colonization and could be targeted for active surveillance to prevent C. difficile transmission

Testing the priority-of-access model in a seasonally breeding primate species

In mammals, when females are clumped in space, male access to receptive females is usually determined by a dominance hierarchy based on fighting ability. In polygynandrous primates, as opposed to most mammalian species, the strength of the relationship between male social status and reproductive success varies greatly. It has been proposed that the degree to which paternity is determined by male rank decreases with increasing female reproductive synchrony. The priority-of-access model (PoA) predicts male reproductive success based on female synchrony and male dominance rank. To date, most tests of the PoA using paternity data involved nonseasonally breeding species. Here, we examine whether the PoA explains the relatively low reproductive skew in relation to dominance rank reported in the rhesus macaque, a strictly seasonal species. We collected behavioral, genetic, and hormonal data on one group of the free-ranging population on Cayo Santiago (Puerto Rico) for 2 years. The PoA correctly predicted the steepness of male reproductive skew, but not its relationship to male dominance: the most successful sire, fathering one third of the infants, was high but not top ranking. In contrast, mating success was not significantly skewed, suggesting that other mechanisms than social status contributed to male reproductive success. Dominance may be less important for paternity in rhesus macaques than in other primate species because it is reached through queuing rather than contest, leading to alpha males not necessarily being the strongest or most attractive male. More work is needed to fully elucidate the mechanisms determining paternity in rhesus macaques

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Benchmarking Chancengleichheit Oesterreich im EU-Vergleich

'In Oesterreich hat das Benchmarking der Arbeitsmarktperformance seit der gemeinsamen Beschaeftigungsstrategie (also seit 1998) zunehmend an Bedeutung gewonnen, auch fuer die innenpolitische Diskussion. So wird beispielsweise immer haeufiger (auch in innenpolitischen Fragen) mit der Positionierung Oesterreichs im EU-Vergleich argumentiert, um Probleme zu verorten, Massnahmen zu legitimieren oder auch Kritik zu relativieren. Im vorliegenden Beitrag wird der Frage nachgegangen, inwieweit das Benchmarking auch fuer den Bereich der Chancengleichheitspolitik geeignet ist. Dafuer werden die zentralen Anforderungen an das Benchmarking von Chancengleichheitspolitik wie auch einige damit zusammenhaengende Probleme diskutiert und anhand des Beispiels Oesterreich veranschaulicht. Die Situation Oesterreichs im Hinblick auf Chancengleichheit ist durchaus positiv zu werten, wenn die Erwerbsintegration von Frauen im EU-Vergleich betrachtet wird. Wird aber auch die Qualitaet der Beschaeftigung und die Vereinbarkeit mit Familie beruecksichtigt, verschlechtert sich die Position Oesterreichs deutlich.' (Autorenreferat)'The concept of Benchmarking gained more and more importance at the European level as well as at the national level, since the European employment strategy was launched in 1998. The analysis of Austrians position in EU-comparison is used to identify problems, to legitimise measures and to tone down critiques. In the paper we discuss the question whether the concept of benchmarking is adequate for the analysis of equal opportunities too. Therefore we discuss the main preconditions for benchmarking of equal opportunities as well as problems in that context. The arguments will be illustrated with the indicators used by the EU for benchmarking the European Employment Strategy. Austria holds one of the top positions in European comparison concerning the integration of women in employment. However, the position of Austria changes drastically if the quality of employment and the reconciliation of family and work are also taken into account.' (author's abstract)SIGLEAvailable from UuStB Koeln(38)-20040107191 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

The Orphan Nuclear Receptor Nur77 Is a Determinant of Myofiber Size and Muscle Mass in Mice

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely, mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and myofiber size. We further show that Nur77 mediates its effects on muscle size by orchestrating transcriptional programs that favor muscle growth, including the induction of insulin-like growth factor 1 (IGF1), as well as concomitant downregulation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx), and Trim63 (MuRF1). Nur77-mediated increase in IGF1 led to activation of the Akt-mTOR-S6K cascade and the inhibition of FoxO3a activity. The dependence of Nur77 on IGF1 was recapitulated in primary myoblasts, establishing this as a cell-autonomous effect. Collectively, our findings identify Nur77 as a novel regulator of myofiber size and a potential transcriptional link between cellular metabolism and muscle growth

The Orphan Nuclear Receptor Nur77 Is a Determinant of Myofiber Size and Muscle Mass in Mice

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size. Conversely, mice with global or muscle-specific deficiency in Nur77 exhibited reduced muscle mass and myofiber size. In contrast to Nur77 deficiency, deletion of the highly related nuclear receptor NOR1 (Nr4a3) had minimal effect on muscle mass and myofiber size. We further show that Nur77 mediates its effects on muscle size by orchestrating transcriptional programs that favor muscle growth, including the induction of insulin-like growth factor 1 (IGF1), as well as concomitant downregulation of growth-inhibitory genes, including myostatin, Fbxo32 (MAFbx), and Trim63 (MuRF1). Nur77-mediated increase in IGF1 led to activation of the Akt-mTOR-S6K cascade and the inhibition of FoxO3a activity. The dependence of Nur77 on IGF1 was recapitulated in primary myoblasts, establishing this as a cell-autonomous effect. Collectively, our findings identify Nur77 as a novel regulator of myofiber size and a potential transcriptional link between cellular metabolism and muscle growth

Effects of vascular endothelial growth factor signaling inhibition on human erythropoiesis.

Inhibition of vascular endothelial growth factor (VEGF) signaling increases red blood cell (RBC) counts, and erythropoiesis markers have been proposed to guide antiangiogenic therapy in humans. We analyzed RBC measurements in patients enrolled in three studies: a phase II trial of axitinib in thyroid cancer; a study of sorafenib in advanced solid tumors; and a randomized trial of fluorouracil, hydroxyurea, and radiation with and without bevacizumab for head and neck cancer. In the sorafenib trial, plasma erythropoietin concentrations were measured at baseline, day 8, and day 35. Over the first 84 days of treatment, RBC counts increased for each day on sorafenib (2.7 M/μL [95% confidence interval (CI), 1.5-3.9]) and axitinib (4.3 M/μL [95% CI, 2.2-6.5]). RBCs declined over the first 68 days of cytotoxic chemoradiotherapy alone (-12.8 M/μL per day [95% CI, -15.7 to -9.8]) but less so with added bevacizumab (-7.2 M/μL per day [95% CI, -9.5 to -4.9]). Erythropoietin levels increased, on average, by 9.5 mIU/mL between day 8 and day 35 of sorafenib exposure. No significant relationships between elevations in RBCs and changes in volume status or blood pressure or between elevations in erythropoietin and smoking status were found. VEGF signaling inhibition is associated with increased RBC and erythropoietin production in humans. The effects of these changes are subtle at physiologic doses and are unlikely to be clinically useful biomarkers for guiding the administration of or predicting treatment responses to VEGF pathway inhibitors