Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers

Item does not contain fulltextBACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population

The 2014-2017 outburst of the young star ASASSN-13db: A time-resolved picture of a very low-mass star between EXors and FUors

ASASSN-13db is a M5-type star with a protoplanetary disk, the lowest mass star known to experience accretion outbursts. Since its discovery in 2013, it has experienced two outbursts, the second of which started in November 2014 and lasted until February 2017. We use high- and low-resolution spectroscopy and time-resolved photometry from the ASAS-SN survey, the LCOGT and the Beacon Observatory to study the lightcurve and the dynamical and physical properties of the accretion flow. The 2014-2017 outburst lasted for nearly 800 days. A 4.15d period in the lightcurve likely corresponds to rotational modulation of a star with hot spot(s). The spectra show multiple emission lines with variable inverse P-Cygni profiles and a highly variable blueshifted absorption below the continuum. Line ratios from metallic emission lines (Fe I/Fe II, Ti I/Ti II) suggest temperatures of $\sim$5800-6000 K in the accretion flow. Photometrically and spectroscopically, the 2014-2017 event displays an intermediate behavior between EXors and FUors. The accretion rate (\.{M}=1-3$\times$10$^{-7}$M$_\odot$/yr), about 2 orders of magnitude higher than the accretion rate in quiescence, is not significantly different from the accretion rate observed in 2013. The absorption features in the spectra suggest that the system is viewed at a high angle and drives a powerful, non-axisymmetric wind, maybe related to magnetic reconnection. The properties of ASASSN-13db suggest that temperatures lower than those for solar-type stars are needed for modeling accretion in very low-mass systems. Finally, the rotational modulation during the outburst reveals that accretion-related structures settled after the begining of the outburst and can be relatively stable and long-lived. Our work also demonstrates the power of time-resolved photometry and spectroscopy to explore the properties of variable and outbursting stars. (Abridged)

Planck 2013 results. I. Overview of products and scientific results

Peer reviewe

Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial

Background Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection. Methods We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio [INR] 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460. Findings Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% [95% CI −4 to 21], non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group. Interpretation - Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection

Isopropyl benzene (cumene) [MAK Value Documentations, 2013]

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated isopropyl benzene to derive a maximum concentration at the work place (MAK value), considering all toxicity endpoints. Available publications are described in detail. Isopropyl benzene caused adenomas in the nose of rats, and in mice adenomas and carcinomas in the lungs and adenomas in the liver. Genotoxic effects do not seem to be responsible for the carcinogenicity. Concerning the lung tumours of mice, it is assumed that ring hydroxylated metabolites stimulate cell proliferation, which can lead to tumour formation. In humans, the metabolism of aromatic molecules in the respiratory tissues is not yet clarified in detail and therefore carcinogenic effects of isopropyl benzene in humans cannot be excluded. Isopropyl benzene is therefore classified in Carcinogen Category 3B. Isopropyl benzene is not genotoxic, therefore, the derivation of a MAK value is possible. In agreement with the procedures used by the Commission, a MAK value of 10 ml/m3 was set, derived from a calculated BMDL of 35 ml/m3 for liver weight increase in the 14‐week study with rats and from the calculated BMDL of 42 ml/m3 for nasal adenomas in the 2‐year study in rats. On the basis of the mainly systemic effects, the classification in Peak Limitation Category II is retained. The half‐life in humans is considerably longer than 2 hours, so that the excursion factor of 4 is also retained. No foetotoxic or teratogenic effects were found in rats and rabbits up to 1200 and 2300 ml/m3, respectively. As the difference between the NOAEC for developmental toxicity and the MAK value is sufficiently large, damage to the embryo or foetus is unlikely when the MAK value is observed. The assignment to Pregnancy Group C is confirmed. Skin contact may contribute significantly to systemic toxicity and the designation with an “H” notation is retained. Sensitisation is not expected based on the result of a maximisation test

The intra-cell layout problem in automated manufacturing systems

Programme 5 : traitement du signal, automatique et productiqueAvailable at INIST (FR), Document Supply Service, under shelf-number : 14802 E, issue : a.1992 n.1603 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc