550 research outputs found
Recent advances in drug discovery for diabetic kidney disease
Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed
Living with a diagnosis of behavioural-variant frontotemporal dementia: The personâs experience.
YesResearch investigating behavioural-variant frontotemporal dementia has concentrated on identifying and quantifying peopleâs difficulties; yet few studies have considered how people with behavioural-variant frontotemporal dementia make sense of their difficulties. Five participants were interviewed and interpretive phenomenological analysis used to analyse the data. Two superordinate themes emerged: âBewildermentâ and âRelationships with othersâ. âBewildermentâ reflected the feelings of the participants from the start of their dementia, and was divided into two main themes (1) âAwareness of change: Whatâs the problem? and (2) Threats to self: This is not me. The superordinate theme, âRelationships with othersâ, reflected difficulties with social relationships and comprised two main themes (1) âFamily and friends: Things havenât changed⊠but do I say anything wrong?â and (2) Coping with threats to self: Blame others or just avoid them. The themes were discussed in relation to literature evaluating the difficulties associated with behavioural-variant frontotemporal dementia together with implications for clinical practice
Weiss Oscillations in Surface Acoustic Wave Propagation
The interaction of a surface acoustic wave (SAW) with a a two-dimensional
electron gas in a periodic electric potential and a classical magnetic field is
considered. We calculate the attenuation of the SAW and its velocity change and
show that these quantities exhibit Weiss oscillations.Comment: 4 pages REVTEX, 2 figures included as eps file
Reassessing changes in diurnal temperature range: Intercomparison and evaluation of existing global data set estimates
Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global-mean DTR has decreased significantly since 1950, with most of that decrease occurring over 1960â1980. The since-1979 trends are not significant, with inter-data set disagreement even over the sign of global changes. Inter-data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear
Existence of Integral -Varifolds minimizing and , , in Riemannian Manifolds
We prove existence and partial regularity of integral rectifiable
-dimensional varifolds minimizing functionals of the type and
in a given Riemannian -dimensional manifold , , under suitable assumptions on (in the end of the paper we
give many examples of such ambient manifolds). To this aim we introduce the
following new tools: some monotonicity formulas for varifolds in
involving , to avoid degeneracy of the minimizer, and a sort of
isoperimetric inequality to bound the mass in terms of the mentioned
functionals.Comment: 33 pages; this second submission corresponds to the published version
of the paper, minor typos are fixe
The Reliability of Global and Hemispheric Surface Temperature Records
The purpose of this review article is to discuss the development and associated estimation of uncertainties in the global and hemispheric surface temperature records. The review begins by detailing the groups that produce surface temperature datasets. After discussing the reasons for similarities and differences between the various products, the main issues that must be addressed when deriving accurate estimates, particularly for hemispheric and global averages, are then considered. These issues are discussed in the order of their importance for temperature records at these spatial scales: biases in SST data, particularly before the 1940s; the exposure of land-based thermometers before the development of louvred screens in the late 19th century; and urbanization effects in some regions in recent decades. The homogeneity of land-based records is also discussed; however, at these large scales it is relatively unimportant. The article concludes by illustrating hemispheric and global temperature records from the four groups that produce series in near-real time
The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma
Background: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. Patients and methods: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. Results: A total of 452 patients were randomized (1: 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. Conclusions: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy
Improved limits on dark matter annihilation in the Sun with the 79-string IceCube detector and implications for supersymmetry
We present an improved event-level likelihood formalism for including
neutrino telescope data in global fits to new physics. We derive limits on
spin-dependent dark matter-proton scattering by employing the new formalism in
a re-analysis of data from the 79-string IceCube search for dark matter
annihilation in the Sun, including explicit energy information for each event.
The new analysis excludes a number of models in the weak-scale minimal
supersymmetric standard model (MSSM) for the first time. This work is
accompanied by the public release of the 79-string IceCube data, as well as an
associated computer code for applying the new likelihood to arbitrary dark
matter models.Comment: 24 pages, 8 figs, 1 table. Contact authors: Pat Scott & Matthias
Danninger. Likelihood tool available at http://nulike.hepforge.org. v2: small
updates to address JCAP referee repor
An All-Sky Search for Three Flavors of Neutrinos from Gamma-Ray Bursts with the IceCube Neutrino Observatory
We present the results and methodology of a search for neutrinos produced in
the decay of charged pions created in interactions between protons and
gamma-rays during the prompt emission of 807 gamma-ray bursts (GRBs) over the
entire sky. This three-year search is the first in IceCube for shower-like
Cherenkov light patterns from electron, muon, and tau neutrinos correlated with
GRBs. We detect five low-significance events correlated with five GRBs. These
events are consistent with the background expectation from atmospheric muons
and neutrinos. The results of this search in combination with those of
IceCube's four years of searches for track-like Cherenkov light patterns from
muon neutrinos correlated with Northern-Hemisphere GRBs produce limits that
tightly constrain current models of neutrino and ultra high energy cosmic ray
production in GRB fireballs.Comment: 33 pages, 14 figures; minor changes made to match published version
in the Astrophysical Journal, 2016 June 2
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