Risk factors for meningococcal meningitis in northern Ghana

Meningococcal meningitis is a major cause of morbidity and mortality in the meningitis belt of sub-Saharan Africa where it occurs in epidemics every 8-12 years. Risk factors for the disease in this setting remain largely unknown. We carried out a case-control study to investigate possible risk factors among survivors of a meningitis epidemic occurring in 1997 in northern Ghana. A structured questionnaire on socio-economic factors, housing and household overcrowding, smoking and exposure to smoke and close contact with a case was administered to 505 of the survivors and 505 of age-, sex- and location-matched controls. Cooking in kitchens with firewood stoves (OR 9·00, CI 1·25-395) and sharing a bedroom with a case (OR 2·18 CI 1·43-3·4) were found to be risk factors for disease. Socio-economic factors, overcrowding, smoking and passive exposure to tobacco smoke were not found to be risk factors. Exposure to smoke from cooking fires or close contact with a case puts people at risk of contracting meningococcal meningitis. In the hot dry months, exposure to smoke from cooking fires should be minimized by encouraging alternatives to cooking over wood fires, or cooking outside. If wood-burning stoves cannot be avoided, kitchens should be made larger with improved ventilation. Meningitis cases should be nursed in well-ventilated rooms and the number of people sharing a room with a case kept at a minimu

Parallax and Luminosity Measurements of an L Subdwarf

We present the first parallax and luminosity measurements for an L subdwarf, the sdL7 2MASS J05325346+8246465. Observations conducted over three years by the USNO infrared astrometry program yield an astrometric distance of 26.7+/-1.2 pc and a proper motion of 2.6241+/-0.0018"/yr. Combined with broadband spectral and photometric measurements, we determine a luminosity of log(Lbol/Lsun) = -4.24+/-0.06 and Teff = 1730+/-90 K (the latter assuming an age of 5-10 Gyr), comparable to mid-type L field dwarfs. Comparison of the luminosity of 2MASS J05325346+8246465 to theoretical evolutionary models indicates that its mass is just below the sustained hydrogen burning limit, and is therefore a brown dwarf. Its kinematics indicate a ~110 Myr, retrograde Galactic orbit which is both eccentric (3 <~ R <~ 8.5 kpc) and extends well away from the plane (Delta_Z = +/-2 kpc), consistent with membership in the inner halo population. The relatively bright J-band magnitude of 2MASS J05325346+8246465 implies significantly reduced opacity in the 1.2 micron region, consistent with inhibited condensate formation as previously proposed. Its as yet unknown subsolar metallicity remains the primary limitation in constraining its mass; determination of both parameters would provide a powerful test of interior and evolutionary models for low-mass stars and brown dwarfs.Comment: Accepted to ApJ 10 September 2007; 13 pages, 5 figures, 3 tables, formatted in emulateapj styl

Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3Kγ pathway

Aims Elastin is degraded during vascular ageing and its products, elastin-derived peptides (EP), are present in the human blood circulation. EP binds to the elastin receptor complex (ERC) at the cell surface, composed of elastin-binding protein (EBP), a cathepsin A and a neuraminidase 1. Some in vitro functions have clearly been attributed to this binding, but the in vivo implications for arterial diseases have never been clearly investigated. Methods and results Here, we demonstrate that chronic doses of EP injected into mouse models of atherosclerosis increase atherosclerotic plaque size formation. Similar effects were observed following an injection of a VGVAPG peptide, suggesting that the ERC mediates these effects. The absence of phosphoinositide 3-kinase γ (PI3Kγ) in bone marrow-derived cells prevented EP-induced atherosclerosis development, demonstrating that PI3Kγ drive EP-induced arterial lesions. Accordingly, in vitro studies showed that PI3Kγ was required for EP-induced monocyte migration and ROS production and that this effect was dependent upon neuraminidase activity. Finally, we showed that degradation of elastic lamellae in LDLR−/− mice fed an atherogenic diet correlated with atherosclerotic plaque formation. At the same time, the absence of the cathepsin A-neuraminidase 1 complex in cells of the haematopoietic lineage abolished atheroma plaque size progression and decreased leucocytes infiltration, clearly demonstrating the role of this complex in atherogenesis and suggesting the involvement of endogenous EP. Conclusion Altogether, this work identifies EP as an enhancer of atherogenesis and defines the Neuraminidase 1/PI3Kγ signalling pathway as a key mediator of this function in vitro and in viv

An innovative integral field unit upgrade with 3D-printed micro-lenses for the RHEA at Subaru

In the new era of Extremely Large Telescopes (ELTs) currently under construction, challenging requirements drive spectrograph designs towards techniques that efficiently use a facility's light collection power. Operating in the single-mode (SM) regime, close to the diffraction limit, reduces the footprint of the instrument compared to a conventional high-resolving power spectrograph. The custom built injection fiber system with 3D-printed micro-lenses on top of it for the replicable high-resolution exoplanet and asteroseismology spectrograph at Subaru in combination with extreme adaptive optics of SCExAO, proved its high efficiency in a lab environment, manifesting up to ~77% of the theoretical predicted performance

A phase I study of the oral gamma secretase inhibitor R04929097 in combination with gemcitabine in patients with advanced solid tumors (PHL-078/CTEP 8575)

PURPOSE: To establish the recommended phase II dose of the oral γ-secretase inhibitor RO4929097 (RO) in combination with gemcitabine; secondary objectives include the evaluation of safety, tolerability, pharmacokinetics, biomarkers of Notch signaling and preliminary anti-tumor activity. METHODS: Patients with advanced solid tumors were enrolled in cohorts of escalating RO dose levels (DLs). Tested RO DLs were 20 mg, 30 mg, 45 mg and 90 mg. RO was administered orally, once daily on days 1-3, 8-10, 15-17, 22-24. Gemcitabine was administered at 1,000 mg/m(2) on d1, 8, and 15 in 28 d cycles. Dose limiting toxicities (DLTs) were assessed by CTCAE v4. Serial plasma was collected for RO (total and unbound) and gemcitabine pharmacokinetic analysis. Biomarkers of Notch signaling were assessed by immunohistochemistry in archival tissue. Antitumor activity was evaluated (RECIST 1.1). RESULTS: A total of 18 patients were enrolled to establish the recommended phase II dose. Of these, 3 patients received 20 mg RO, 7 patients received 30 mg RO, 6 patients received 45 mg RO and 2 patients received 90 mg RO. DLTs were grade 3 transaminitis (30 mg RO), grade 3 transaminitis and maculopapular rash (45 mg RO), and grade 3 transaminitis and failure to receive 75 % of planned RO doses secondary to prolonged neutropenia (90 mg); all were reversible. The maximum tolerated dose was exceeded at 90 mg RO. Pharmacokinetic analysis of both total and free RO confirmed the presence of autoinduction at 45 and 90 mg. Median levels of Notch3 staining were higher in individuals who received fewer than 4 cycles (p = 0.029). Circulating angiogenic factor levels did not correlate with time to progression or ≥ grade 3 adverse events. Best response (RECIST 1.1) was partial response (nasopharyngeal cancer) and stable disease > 4 months was observed in 3 patients (pancreas, tracheal, and breast primary cancers). CONCLUSIONS: RO and gemcitabine can be safely combined. The recommended phase II dose of RO was 30 mg in combination with gemcitabine 1,000 mg/m(2). Although RO exposure was limited by the presence of autoinduction, RO levels achieved exceeded the area under the concentration-time curve for 0-24 h (AUC(0-24)) predicted for efficacy in preclinical models using daily dosing. Evidence of clinical antitumor activity and prolonged stable disease were identified

Modeling large diffusio-phoretic suspensions

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