Ocular tolerability and efficacy of intravitreal and subconjunctival injections of sirolimus in patients with non-infectious uveitis: primary 6-month results of the SAVE Study.

BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6. RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p \u3c 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug. CONCLUSION: Local administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids

Six jet production at lepton colliders

We study electron-positron annihilations into six jets at the parton level in perturbative Quantum Chromo-Dynamics (QCD), via the elementary processes e^+e^-\ar q\bar q gggg, e^+e^-\ar q\bar q q'\bar q' gg and e^+e^-\ar q\bar q q'\bar q' q''\bar q'', for massive quarks $q, q'$ and $q''$ and massless gluons $g$. Several numerical results of phenomenological relevance are given, at three different collider energies and for a representative selection of jet clustering algorithms. We also present helicity amplitudes and colour factors needed for the tree-level calculatio

Picking Up the PiecesHarmonising and Collating Seabed Substrate Data for European Maritime Areas

The poor access to data on the marine environment is a handicap to government decision-making, a barrier to scientific understanding and an obstacle to economic growth. In this light, the European Commission initiated the European Marine Observation and Data Network (EMODnet) in 2009 to assemble and disseminate hitherto dispersed marine data. In the ten years since then, EMODnet has become a key producer of publicly available, harmonised datasets covering broad areas. This paper describes the methodologies applied in EMODnet Geology project to produce fully populated GIS layers of seabed substrate distribution for the European marine areas. We describe steps involved in translating national seabed substrate data, conforming to various standards, into a uniform EMODnet substrate classification scheme (i.e., the Folk sediment classification). Rock and boulders form an additional substrate class. Seabed substrate data products at scales of 1:250,000 and 1:1 million, compiled using descriptions and analyses of seabed samples as well as interpreted acoustic images, cover about 20% and 65% of the European maritime areas, respectively. A simple confidence assessment, based on sample and acoustic coverage, is helpful in identifying data gaps. The harmonised seabed substrate maps are particularly useful in supraregional, transnational and pan-European marine spatial planning

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3per year [95% CI, -6.49×10-3to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH