A comparison of health-related quality of life (health utility) between insulin degludec and insulin glargine: a meta-analysis of phase 3 trials

Aim: To evaluate health-related quality of life (health utility) scores in patients with diabetes receiving insulin degludec (IDeg) or insulin glargine (IGlar). Methods: Patient-level data from six, randomized, controlled, open-label, multicentre, confirmatory, treat-to-target trials of 26- or 52 weeks' duration were pooled in this analysis. The Short Form 36 (SF-36) version-2 health questionnaire was completed by patients at baseline and end-of-trial. SF-36 scores for 4001 individual patients were then mapped onto the EuroQol-5D health utility scale, which has a range from −0.59 (a state worse than death) to 1.00 (perfect health). Results: IDeg treatment exhibited a significant improvement in health status of 0.005 (CI: 0.0006; 0.009) points compared with IGlar (p < 0.024). Gender, region, trial and age also had a significant influence on estimated utility scores as did baseline utility scores, p < 0.05. Prior to the removal of interaction variables a difference of 0.008 points was observed, p < 0.045. Previous insulin treatment did not have an impact on the final outcome. Conclusion: This study shows that IDeg is associated with a modest, but statistically significant, improvement in health utility compared with IGlar in patients with diabetes

Morphological characterization of sweet and sour cherry cultivars in a germplasm bank at Portugal

Nine sweet cherry and eight sour cherry varieties located in a germplasm bank at Fundauo, Portugal, were studied from the viewpoint of characterization. Most of them were autochthonous cultivars that have a high risk of extinction since at the present they are markedly minor varieties. Morphological characteristics were evaluated in different organs: crown and trunk of the trees, leaves, flowers and fruits, over a three consecutive years period. Statistical analyses were carried out in order to detect similarities between cultivars as well as the existence of synonymies. Qualitative characteristics of the fruits were scored in order to carry out the multivariate analysis. A dendrogram of the evaluated characters shows the marked differentiation between sour and sweet cherries and suggests the existing synonymies. Conservation of the autochthonous cultivars in the future is highly recommended

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability

THE RHYTHM OF FAIRALL 9. I. OBSERVING THE SPECTRAL VARIABILITY WITH XMM-NEWTON AND NuSTAR

© 2016. The American Astronomical Society. All rights reserved. We present a multi-epoch X-ray spectral analysis of the Seyfert 1 galaxy Fairall 9. Our analysis shows that Fairall 9 displays unique spectral variability in that its ratio residuals to a simple absorbed power law in the 0.5-10 keV band remain constant with time in spite of large variations in flux. This behavior implies an unchanging source geometry and the same emission processes continuously at work at the timescale probed. With the constraints from NuSTAR on the broad-band spectral shape, it is clear that the soft excess in this source is a superposition of two different processes, one being blurred ionized reflection in the innermost parts of the accretion disk, and the other a continuum component such as a spatially distinct Comptonizing region. Alternatively, a more complex primary Comptonization component together with blurred ionized reflection could be responsible

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Measuring the Invisible Higgs Width at the 7 and 8 TeV LHC

The LHC is well on track toward the discovery or exclusion of a light Standard Model (SM)-like Higgs boson. Such a Higgs has a very small SM width and can easily have large branching fractions to physics beyond the SM, making Higgs decays an excellent opportunity to observe new physics. Decays into collider-invisible particles are particularly interesting as they are theoretically well motivated and relatively clean experimentally. In this work we estimate the potential of the 7 and 8 TeV LHC to observe an invisible Higgs branching fraction. We analyze three channels that can be used to directly study the invisible Higgs branching ratio at the 7 TeV LHC: an invisible Higgs produced in association with (i) a hard jet; (ii) a leptonic Z; and (iii) forward tagging jets. We find that the last channel, where the Higgs is produced via weak boson fusion, is the most sensitive, allowing branching fractions as small as 40% to be probed at 20 inverse fb for masses in the range between 120 and 170 GeV, including in particular the interesting region around 125 GeV. We provide an estimate of the 8 TeV LHC sensitivity to an invisibly-decaying Higgs produced via weak boson fusion and find that the reach is comparable to but not better than the reach at the 7 TeV LHC. We further estimate the discovery potential at the 8 TeV LHC for cases where the Higgs has substantial branching fractions to both visible and invisible final states.Comment: 23 pages, 7 figures. v2: version published in JHEP. 8 TeV analysis adde

Discovering the composite Higgs through the decay of a heavy fermion

A possible composite nature of the Higgs could be revealed at the early stage of the LHC, by analyzing the channels where the Higgs is produced from the decay of a heavy fermion. The Higgs production from a singly-produced heavy bottom, in particular, proves to be a promising channel. For a value \lambda=3 of the Higgs coupling to a heavy bottom, for example, we find that, considering a 125 GeV Higgs which decays into a pair of b-quarks, a discovery is possible at the 8 TeV LHC with 30 fb^{-1} if the heavy bottom is lighter than roughly 530 GeV (while an observation is possible for heavy bottom masses up to 650 GeV). Such a relatively light heavy bottom is realistic in composite Higgs models of the type considered and, up to now, experimentally allowed. At \sqrt{s}=14 TeV the LHC sensitivity on the channel increases significantly. With \lambda=3 a discovery can occur, with 100 fb^{-1}, for heavy bottom masses up to 1040 GeV. In the case the heavy bottom was as light as 500 GeV, the 14 TeV LHC would be sensitive to the measure of the \lambda\ coupling in basically the full range \lambda>1 predicted by the theory.Comment: 25 pp. v2: Minor changes. v3: Version accepted for publication in JHEP. v4: typos fixe

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Gaugino production in proton-proton collisions at a center-of-mass energy of 8 TeV

Motivated by hints for a light Standard Model-like Higgs boson and a shift in experimental attention towards electroweak supersymmetry particle production at the CERN LHC, we update in this paper our precision predictions at next-to-leading order of perturbative QCD matched to resummation at the next-to-leading logarithmic accuracy for direct gaugino pair production in proton-proton collisions with a center-of-mass energy of 8 TeV. Tables of total cross sections are presented together with the corresponding scale and parton density uncertainties for benchmark points adopted recently by the experimental collaborations, and figures are presented for up-to-date model lines attached to them. Since the experimental analyses are currently obtained with parton showers matched to multi-parton matrix elements, we also analyze the precision of this procedure by comparing invariant-mass and transverse-momentum distributions obtained in this way to those obtained with threshold and transverse-momentum resummation.Comment: 28 pages, 7 figures, 9 tables; version to appear in JHE