Background Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks. Objective We sought to assess the efficacy and safety of crisaborole ...ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766 ; AD-302: NCT02118792 ). Methods Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. Results More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. Limitations Short study duration was a limitation. Conclusions Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the ...Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.
The current paper reviews the content and variation of fiber fractions in feed ingredients commonly used in swine diets. Carbohydrates serve as the main source of energy in diets fed to pigs. ...Carbohydrates may be classified according to their degree of polymerization: monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Digestible carbohydrates include sugars, digestible starch, and glycogen that may be digested by enzymes secreted in the gastrointestinal tract of the pig. Non-digestible carbohydrates, also known as fiber, may be fermented by microbial populations along the gastrointestinal tract to synthesize short-chain fatty acids that may be absorbed and metabolized by the pig. These non-digestible carbohydrates include two disaccharides, oligosaccharides, resistant starch, and non-starch polysaccharides. The concentration and structure of non-digestible carbohydrates in diets fed to pigs depend on the type of feed ingredients that are included in the mixed diet. Cellulose, arabinoxylans, and mixed linked β-(1,3) (1,4)-
-glucans are the main cell wall polysaccharides in cereal grains, but vary in proportion and structure depending on the grain and tissue within the grain. Cell walls of oilseeds, oilseed meals, and pulse crops contain cellulose, pectic polysaccharides, lignin, and xyloglucans. Pulse crops and legumes also contain significant quantities of galacto-oligosaccharides including raffinose, stachyose, and verbascose. Overall, understanding the structure, characteristics and measurable chemical properties of fiber in feed ingredients may result in more accurate diet formulations, resulting in an improvement in the utilization of energy from less expensive high-fiber ingredients and a reduction in reliance on energy from more costly cereal grains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We consider short-range Ising spin glasses in equilibrium at infinite system size, and prove that, for fixed bond realization and a given Gibbs state drawn from a suitable metastate, each translation ...and locally invariant function (for example, self-overlaps) of a single pure state in the decomposition of the Gibbs state takes the same value for all the pure states in that Gibbs state. We describe several significant applications to spin glasses.
GBrowse is a mature web-based genome browser that is suitable for deployment on both public and private web sites. It supports most of genome browser features, including qualitative and quantitative ...(wiggle) tracks, track uploading, track sharing, interactive track configuration, semantic zooming and limited smooth track panning. As of version 2.0, GBrowse supports next-generation sequencing (NGS) data by providing for the direct display of SAM and BAM sequence alignment files. SAM/BAM tracks provide semantic zooming and support both local and remote data sources. This article provides step-by-step instructions for configuring GBrowse to display NGS data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts ...remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth. Conversely, disruption of exosome secretion in AML cells through targeting Rab27a, an important regulator involved in exosome release, significantly delayed leukemia development. In BM stromal cells, AML-derived exosomes induced the expression of DKK1, a suppressor of normal hematopoiesis and osteogenesis, thereby contributing to osteoblast loss. Conversely, treatment with a DKK1 inhibitor delayed AML progression and prolonged survival in AML-engrafted mice. In addition, AML-derived exosomes induced a broad downregulation of hematopoietic stem cell-supporting factors (for example, CXCL12, KITL and IGF1) in BM stromal cells and reduced their ability to support normal hematopoiesis. Altogether, this study uncovers novel features of AML pathogenesis and unveils how AML cells create a self-strengthening leukemic niche that promotes leukemic cell proliferation and survival, while suppressing normal hematopoiesis through exosome secretion.
Abstract We investigate scenarios in which the low-temperature phase of short-range spin glasses comprises thermodynamic states which are nontrivial mixtures of multiple incongruent pure state pairs. ...We construct a new kind of metastate supported on Gibbs states whose edge overlap values with a reference state fall within a specified range. Using this metastate we show that, in any dimension, the variance of free energy difference fluctuations between pure states within a single mixed Gibbs state with multiple edge overlap values diverges linearly with the volume. We discuss some implications of these results.
We consider the general Landau-Lifshitz-Gilbert theory underlying the magnetization dynamics of a macrospin magnet subject to spin-torque effects and thermal fluctuations. Thermally activated ...dynamical properties are analyzed by averaging the full magnetization equations over constant-energy orbits. After averaging, all the relevant dynamical scenarios are a function of the ratio between hard and easy axis anisotropies. We derive analytically the range of currents for which limit cycles exist and discuss the regimes in which the constant energy orbit averaging technique is applicable.
The cosmic web contains filamentary structure on a wide range of scales. On the largest scales, superclustering aligns multiple galaxy clusters along intercluster bridges, visible through their ...thermal Sunyaev–Zel'dovich signal in the cosmic microwave background. We demonstrate a new, flexible method to analyze the hot gas signal from multiscale extended structures. We use a Compton y-map from the Atacama Cosmology Telescope (ACT) stacked on redMaPPer cluster positions from the optical Dark Energy Survey (DES). Cutout images from the y-map are oriented with large-scale structure information from DES galaxy data such that the superclustering signal is aligned before being overlaid. We find evidence of an extended quadrupole moment of the stacked y signal at the 3.5σ level, demonstrating that the large-scale thermal energy surrounding galaxy clusters is anisotropically distributed. We compare our ACT × DES results with the Buzzard simulations, finding broad agreement. Using simulations, we highlight the promise of this novel technique for constraining the evolution of anisotropic, non-Gaussian structure using future combinations of microwave and optical surveys.
A number of feed additives are marketed to assist in boosting the pigs' immune system, regulate gut microbiota, and reduce negative impacts of weaning and other environmental challenges. The most ...commonly used feed additives include acidifiers, zinc and copper, prebiotics, direct-fed microbials, yeast products, nucleotides, and plant extracts. Inclusion of pharmacological levels of zinc and copper, certain acidifiers, and several plant extracts have been reported to result in improved pig performance or improved immune function of pigs. It is also possible that use of prebiotics, direct-fed microbials, yeast, and nucleotides may have positive impacts on pig performance, but results have been less consistent and there is a need for more research in this area.
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