Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Composition and distribution of the peracarid crustacean fauna along a latitudinal transect off Victoria Land (Ross Sea, Antarctica) with special emphasis on the Cumacea

The following study was the first to describe composition and structure of the peracarid fauna systematically along a latitudinal transect off Victoria Land (Ross Sea, Antarctica). During the 19th Antarctic expedition of the Italian research vessel “Italica” in February 2004, macrobenthic samples were collected by means of a Rauschert dredge with a mesh size of 500 m at depths between 85 and 515 m. The composition of peracarid crustaceans, especially Cumacea was investigated. Peracarida contributed 63% to the total abundance of the fauna. The peracarid samples were dominated by amphipods (66%), whereas cumaceans were represented with 7%. Previously, only 13 cumacean species were known, now the number of species recorded from the Ross Sea increased to 34. Thus, the cumacean fauna of the Ross Sea, which was regarded as the poorest in terms of species richness, has to be considered as equivalent to that of other high Antarctic areas. Most important cumacean families concerning abundance and species richness were Leuconidae, Nannastacidae, and Diastylidae. Cumacean diversity was lowest at the northernmost area (Cape Adare). At the area off Coulman Island, which is characterized by muddy sediment, diversity was highest. Diversity and species number were higher at the deeper stations and abundance increased with latitude. A review of the bathymetric distribution of the Cumacea from the Ross Sea reveals that most species distribute across the Antarctic continental shelf and slope. So far, only few deep-sea records justify the assumption of a shallow-water–deep-sea relationship in some species of Ross Sea Cumacea, which is discussed from an evolutionary point of view

The SNARE Protein, Syntaxin1a, Plays an Essential Role in Biphasic Exocytosis of the Incretin Hormone, Glucagon-Like Peptide-1

Exocytosis of the hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is essential for the incretin effect after nutrient ingestion, and is critical for the actions of dipeptidylpeptidase IV inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. 2-Photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a 1(st) peak at 1-6min and a 2(nd) peak at 7-12min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules, under basal and stimulated conditions. The core SNARE protein, syntaxin-1a (syn1a), was expressed by murine ileal L-cells. At the single L-cell level, 1(st) phase forskolin-induced exocytosis was reduced to basal (p<0.05) and 2(nd) phase exocytosis was abolished (p<0.05) by syn1a knockout. L-cells from intestinal-epithelial syn1a-deficient mice demonstrated a 63% reduction in forskolin-induced GLP-1 release in vitro (p<0.001), and a 23% reduction in oral glucose-stimulated GLP-1 secretion (p<0.05) in association with impairments in glucose-stimulated insulin release (by 60%, p<0.01) and glucose tolerance (by 20%, p<0.01). Our findings therefore identify an exquisite mechanism of metered secretory output that precisely regulates release of the incretin hormone, GLP-1 and, hence, insulin secretion following a meal

Instrumental methods and challenges in quantifying polybrominated diphenyl ethers in environmental extracts: a review

Increased interest in the fate, transport and toxicity of polybrominated diphenyl ethers (PBDEs) over the past few years has led to a variety of studies reporting different methods of analysis for these persistent organic pollutants. Because PBDEs encompass a range of vapor pressures, molecular weights and degrees of bromine substitution, various analytical methods can lead to discrimination of some PBDE congeners. Recent improvements in injection techniques and mass spectrometer ionization methods have led to a variety of options to determine PBDEs in environmental samples. The purpose of this paper is therefore to review the available literature describing the advantages and disadvantages in choosing an injection technique, gas chromatography column and detector. Additional discussion is given to the challenges in measuring PBDEs, including potential chromatographic interferences and the lack of commercial standards for higher brominated congeners, which provides difficulties in examining degradation and debromination of BDE congeners, particularly for BDE 209

Celecoxib concentration predicts decrease in prostaglandin E2 concentrations in nipple aspirate fluid from high risk women

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E₂concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE₂response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE₂concentrations from baseline to end of treatment, and 2) whether menopausal status influenced circulating levels of celecoxib.</p> <p>Methods</p> <p>Matched NAF and plasma were collected from 46 high risk women who were administered celecoxib twice daily for two weeks, 20 subjects receiving 200 mg and 26 subjects 400 mg of the agent. NAF and plasma samples were collected before and 2 weeks after taking celecoxib.</p> <p>Results</p> <p>In women taking 400 mg bid celecoxib, plasma concentrations of the agent correlated inversely with the change in NAF PGE₂levels from pre- to posttreatment. Nonsignificant trends toward higher celecoxib levels were observed in post- compared to premenopausal women. There was a significant decrease in NAF but not plasma PGE₂concentrations in postmenopausal women who took 400 mg celecoxib (p = 0.03).</p> <p>Conclusion</p> <p>In high risk women taking 400 mg celecoxib twice daily, plasma concentrations of celecoxib correlated with downregulation of PGE₂production by breast tissue. Strategies synergistic with celecoxib to downregulate PGE₂are of interest, in order to minimize the celecoxib dose required to have an effect.</p

Identifying and explaining framing strategies of low carbon lifestyle movement organisations

Over the last decade we have seen the growth and development of low carbon lifestyle movement organisations, which seek to encourage members of the public to reduce their personal energy use and carbon emissions. As a first step to assess the transformational potential of such organisations, this paper examines the ways in which they frame their activities. This reveals an important challenge they face: in addressing the broader public, do they promote ‘transformative’ behaviours or do they limit themselves to encouraging ‘easy changes’ to maintain their appeal? We find evidence that many organisations within this movement avoid ‘transformative’ frames. The main reasons for this are organisers’ perceptions that transformational frames lack resonance with broader audiences, as well as wider cultural contexts that caution against behavioural intervention. The analysis draws on interviews with key actors in the low carbon lifestyle movement and combines insights from the literatures on collective action framing and lifestyle movements

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Effects of liquid metabolite combinations produced by Lactobacillus plantarum on growth performance, faeces characteristics, intestinal morphology and diarrhoea incidence in postweaning piglets

A study was carried out to investigate the effects of feeding liquid metabolite combinations produced by Lactobacillus plantarum strains on growth performance, diarrhoea incidence, faecal pH, microfloral counts, short-chain fatty acids (SCFA) and intestinal villus height and crypt depth of postweaning piglets. A total of 120 piglets (26 days old) were randomly assigned evenly into five treatment groups treated with same basal diet: (1) −ve control (free antibiotic); (2) + ve control (0.03% of chlortetracycline); (3) Com 1 (0.3% metabolite of TL1, RG11 and RI11 strains); (4) Com 2 (0.3% metabolite of TL1, RG14 and RS5 strains); (5) Com 3 (0.3% metabolite of RG11, RG14 and RI11 strains). After 5 weeks, the average daily feed intake was not significantly different (P > 0.05) among the treatments and feed conversion ratio was the highest (P < 0.05) in the −ve control group. In addition, diarrhoea incidence was reduced when piglets were fed with metabolite combinations. Faecal lactic acid bacteria (LAB) counts were significantly higher (P < 0.05) in metabolite treatment groups than in the groups without metabolites. However, the treatment of Com 2 metabolite resulted lower (P < 0.05) faecal pH and Enterobacteriaceae (ENT) than the −ve control group. In contrast, total faecal SCFA of Com 2 were significantly higher (P < 0.05) than the −ve control group. The villus height of duodenum was higher (P < 0.05) in the + ve control and Com 2 groups as compared to −ve control group. The results obtained in this study showed that feeding metabolite combinations could improve growth performance, and increase the population of gut LAB and faecal SCFA of postweaning piglets

Influenza A Virus Coding Regions Exhibit Host-Specific Global Ordered RNA Structure

Influenza A is a significant public health threat, partially because of its capacity to readily exchange gene segments between different host species to form novel pandemic strains. An understanding of the fundamental factors providing species barriers between different influenza hosts would facilitate identification of strains capable of leading to pandemic outbreaks and could also inform vaccine development. Here, we describe the difference in predicted RNA secondary structure stability that exists between avian, swine and human coding regions. The results predict that global ordered RNA structure exists in influenza A segments 1, 5, 7 and 8, and that ranges of free energies for secondary structure formation differ between host strains. The predicted free energy distributions for strains from avian, swine, and human species suggest criteria for segment reassortment and strains that might be ideal candidates for viral attenuation and vaccine development

Early Social Cognition: Alternatives to Implicit Mindreading

According to the BD-model of mindreading, we primarily understand others in terms of beliefs and desires. In this article we review a number of objections against explicit versions of the BD-model, and discuss the prospects of using its implicit counterpart as an explanatory model of early emerging socio-cognitive abilities. Focusing on recent findings on so-called ‘implicit’ false belief understanding, we put forward a number of considerations against the adoption of an implicit BD-model. Finally, we explore a different way to make sense of implicit false belief understanding in terms of keeping track of affordances