Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous ...spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best‐defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non‐type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point‐of‐care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
Rietveld refinements using synchrotron powder X-ray diffraction data were used to study the crystal structure and dehydration behavior of pure monoclinic palygorskite samples from Korea and Alaska. ...The 300 and 100 K palygorskite structures in air compare well with previous models but provide additional details about zeolitic H2O sites and reveal that the Al atoms are ordered into the inner M2 octahedral sites and the Mg cations into the M3 sites at the edges of the tunnels. Real-time, temperature-resolved synchrotron powder X-ray diffraction data and Rietveld refinements were used to investigate the monoclinic palygorskite structure from 300 to 1400 K (in air). Rietveld refinements showed that most of the zeolitic H2O is lost by approximately 425 K, accompanied by a decrease in the unit-cell volume of 1.3%, primarily owing to a decrease in the a unit-cell parameter and an increase in the β angle. The structurally bound H2O is lost in two stages, at temperature intervals of 475-540 and 580-725 K. Above approximately 825 K in air a portion of the Korean sample transformed to a folded structure; the Alaskan sample folded at approximately 575 K under vacuum. A structure model was refined for the folded structure. At approximately 1015 K for the sample heated in air, β-quartz diffraction peaks appeared and increased in intensity as heating continued to the maximum temperature. Cristobalite formed above approximately 1050 K, along with a small amount of clinoenstatite, and both phases persisted to the maximum temperature studied.
High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined ...significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity.
In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation.
Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O
. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged.
A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM).
https://www.isrctn.com/ISRCTN65527208 (14/05/2018).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Imperviousness is an important indicator of the impact of urbanization on storm water systems. A hydrologic analysis was performed to evaluate long-term impacts from an apartment area in Miami. The ...result shows that the directly connected impervious area (DCIA), which covers 44% of the catchment, contributes 72% of the total runoff volume during 52 years. Few studies have actually measured the DCIA with a high level of accuracy for residential areas that constitute the largest proportion of urban land. A detailed analysis of urban imperviousness was performed using geographic information systems and field investigations on a 5.81 ha residential area in Boulder, Colo. For this study area, the total impervious area is 35.9% and the DCIA is 13.0%. Transportation-related imperviousness comprises 97.2% of the DCIA. Hydrologic modeling of this area shows about a 265% difference in estimates of peak discharge with imperviousness measured at five different levels of accuracy. These results suggest the need to focus on DCIA as the key indicator of urbanization's effect on storm water quantity and quality.
Celotno besedilo
Dostopno za:
DOBA, FGGLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A method is presented to improve the tool life and cutting performance of 300
μm diameter tungsten carbide (WC) micro end mills by applying thin (<300
nm) fine-grained diamond (FGD) and ...nanocrystalline diamond (NCD) coatings using the hot-filament chemical vapor deposition (HF-CVD) process. The performance of the diamond-coated tools has been evaluated by comparing their performance in dry slot milling of 6061-T6 aluminum against uncoated WC micro end mills. Tool wear, coating integrity, and chip morphology were characterized using SEM and white light interferometry. The initial test results show a dramatic improvement in the tool integrity (i.e., corners not breaking off), a lower wear rate, no observable adhesion of aluminum to the diamond-coated tool, and a significant reduction in the cutting forces (>50%). Reduction of the cutting forces is attributed to the low friction and adhesion of the diamond coating. However, approximately 80% of the tools coated with the larger FGD coatings failed during testing due to delamination. Additional machining benefits were attained for the NCD films, which was obtained by using a higher nucleation density seeding process for diamond growth. This process allowed for thinner, smaller grained diamond coatings to be deposited on the micro end mills, and enabled continued operation of the tool even after the integrity of the diamond coating had been compromised. As opposed to the FGD-coated end mills, only 40% of the NCD-tools experienced delamination issues.
Estimates of optimal vitamin D status Dawson-Hughes, Bess; Heaney, Robert P; Holick, Michael F ...
Osteoporosis international
16, Številka:
7
Journal Article
Recenzirano
Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal ...circulating level of 25-hydroxyvitamin D 25(OH)D for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.
The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma ...remain unclear.
To identify common genetic variants affecting susceptibility to severe asthma.
A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies.
An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance.
The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
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