Chitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the ...finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis.
Evaluating the potential for crown fires remains a pivotal concern in wildfire management because it affects fire behavior, causing them to spread further. In this work, we propose a methodology to ...assess crown fire potential based on the tree connectivity at crown level from UAS (Unmanned Aircraft Systems)-based Structure-from-Motion Photogrammetry. The approach is usable in a large landscape with the aim of reducing crown fire potential by considering the spatial variability of fuels within a stand. The utilization of UAS for photogrammetry holds immense promise in transforming the approach to assessing and managing forest fires. This cutting-edge technology offers the potential to deliver highly precise and comprehensive data concerning forest structure and connectivity, thereby presenting a groundbreaking opportunity for enhanced forest fire analysis and control.
In this paper, several techniques applied to different studies of artistic or archaeological objects carried out on different scenarios ranging from prehistoric works to the more modern paintings, ...passing through Roman or mediaeval samples, are described.
Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses that is often associated with nasal polyposis (CRSwNP) in the most severe cases. As in other complex ...diseases, genetic factors are thought to play an important role in the risk and development of the disease. Environment may also modulate the epigenetic signature in affected patients. In the present systematic review, we aimed to compile all published data on genetic and epigenetic variations in CRSwNP since 2000. We found 104 articles, 24 of which were related to epigenetic studies. We identified more than 150 genetic variants in 99 genes involved in the pathogenesis of nasal polyposis. These were clustered into 8 main networks, linking genes involved in inflammation and immune response (eg, MHC), cytokine genes (eg, TNF), leukotriene metabolism, and the extracellular matrix. A total of 89 miRNAs were also identified; these are associated mainly with biological functions such as the cell cycle, inflammation, and the immune response. We propose a potential relationship between genes and the miRNAs identified that may open new lines of investigation. An in-depth knowledge of gene variants and epigenetic traits could help us to design more tailored treatment for patients with CRSwNP.
Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall ...survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4).
The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection.
We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma.
NCT02614534 ( clinicaltrial.gov ) Nov-2015.
Gross α and β indices for water samples are generally determined simultaneously when a gas-flow proportional counter is used. The thickness of the source and the α-particle energy are factors of ...great importance due to self-absorption or energy loss effects. Two variables have been studied: the use of different salts to produce standards with several thicknesses and the use of different radionuclides for the calibration process. Samples of known activity were prepared and measured for checking the procedures.
•Gross alpha and beta indices are measured with a gas-flow proportional counter.•Sample thickness is important due to self-absorption or energy loss effects.•Sodium carbonate, nitrate and sulphate were used for the attenuation curves.•226Ra, Natural uranium, 241Am, 209Po, and 242Pu were used for calibration.
Global radiation is a fundamental source of energy in the climate system. A significant impact of global radiation on temperature change is expected due to the widespread dimming/brightening ...phenomenon observed since the second half of the twentieth century. This work describes the analysis of 312 stations with sunshine duration (SD) series, a proxy for global radiation, and temperature series in the European Climate Assessment & Dataset (ECA&D) with data over the period 1961–2010. The relationship between SD and temperature series is analyzed for four temperature variables: maximum (Tmax), minimum (Tmin), mean temperature (Tmean), and diurnal temperature range (DTR). The analyses are performed on annual and seasonal basis. The results show strong positive correlations between SD and temperatures over Europe, with highest correlation for DTR and Tmax during the summer period. These results confirm the strong relationship between SD and temperature trends over Europe since the second half of the twentieth century. This study supports previous suggestions that dimming (brightening) has partially decreased (increased) temperatures thereby modulating the greenhouse gas induced warming rates over Europe.
Key Points
Strong relationship between sunshine duration and temperatures in Europe
DTR and Tmax show the strongest signal, especially in summer
Dimming/brightening has modulated temperature decadal changes since the 1960s
Background
Postzygotic KRAS, HRAS, NRAS, and FGFR1 mutations result in a group of mosaic RASopathies characterized by related developmental anomalies in eye, skin, heart, and brain. These ...oculocutaneous disorders include oculoectodermal syndrome (OES) encephalo‐cranio‐cutaneous lipomatosis (ECCL), and Schimmelpenning‐Feuerstein‐Mims syndrome (SFMS). Here, we report the results of the clinical and molecular characterization of a novel cohort of patients with oculocutaneous mosaic RASopathies.
Methods
Two OES, two ECCL, and two SFMS patients were ascertained in the study. In addition, two subjects with unilateral isolated epibulbar dermoids were also enrolled. Molecular analysis included PCR amplification and Sanger sequencing of KRAS, HRAS, NRAS, and FGFR1 genes in DNA obtained from biopsies (skin/epibulbar dermoids), buccal mucosa, and blood leukocytes. Massive parallel sequencing was employed in two cases with low‐level mosaicism.
Results
In DNA from biopsies, mosaicism for pathogenic variants, including KRAS p.Ala146Thr in two OES subjects, FGFR1 p.Asn546Lys and KRAS p.Ala146Val in ECCL patients, and KRAS p.Gly12Asp in both SFMS patients, was demonstrated. No mutations were shown in DNA from conjunctival lesions in two subjects with isolated epibubar dermoids.
Conclusion
Our study allowed the expansion of the clinical spectrum of mosaic RASopathies and supports that mosaicism for recurrent mutations in KRAS and FGFR1 is a commonly involved mechanism in these rare oculocutaneous anomalies.
Mosaic RASopathies are a group of developmental disorders exhibiting related skin, eye, brain, and heart anomalies. A cohort of patients with mosaic RASopathies was clinically and molecularly characterized. Our results expand the phenotypic spectrum of these disorders and support the involvement of recurrent KRAS and FGFR1 postzygotic mutations.
The sedimentary successions of the Permian-Triassic rifting related to the Alpine Tethys in the easternmost Lower Alpujarride units (Internal Betic Zone, south Spain) host shallow-intrusive basic ...bodies of Mesozoic age. These gabbroic bodies experienced low-grade Alpine metamorphic overprint, singularly recorded in three outcrops nearby Alicante city in southeast Spain: Callosa and Orihuela Ranges and Nueva Tabarca Island. Overall, the metabasic bodies still preserve magmatic ophitic/subophitic texture and relicts of magmatic augite and ferropargasite-ferroedenite-edenite and kaersutite. In contrast, metamorphic minerals include magnesioriebeckite, actinolite, albite, stilpnomelane, phengite, and chlorite. Major and trace element geochemical data suggest crystallization of the igneous protoliths from subalkaline (tholeiitic) to alkaline within-plate (continental) basaltic magmas slightly enriched in incompatible elements. These magmas with E-MORB geochemical affinity very likely intruded at shallow crustal levels in an extensional-synrift-geodynamic setting related to the breakoff of Pangea in the region. Pressure-Temperature (P-T) conditions estimated by average P-T method and pseudosection calculations suggest metamorphic peak at ca. 6 kbar at 340°C consistent with burial metamorphism down to ca. 18 km depth with intermediate thermal gradients of ca. 18°C/km. These conditions are different to the typical subduction-related blueschist facies conditions of the Lower Alpujarride units and suggest, instead, a collisional (Barrovian) event. This can be explained by a late-stage accretion of the studied units after the main subduction-related event, pointing to the dispersion of the corresponding Lower Alpujarride sections along the margin in different palaeogeographic positions before deformation and movement to their actual structural position. The metamorphic correlation of the studied units with the accreted passive margin of South Iberia (Subbetic zone) is also discussed.
The analysis of solid environmental samples by α-particle spectrometry generally involves processes requiring an initial treatment to destroy the complexes in the matrix, and dissolve the ...radionuclides of interest. This study compared the activities obtained for several natural radionuclides (238U, 234U, 230Th, 226Ra, and 210Po) in previously well-characterized materials, using two procedures: acid leaching and digestion in a microwave oven. The measured activities were in general very similar for the two procedures, with a strong statistical correlation between the two sets of values.
•Acid leaching and microwave digestion methods for solid samples are compared.•Both techniques are applied to uranium, radium, or polonium in solid samples.•Results using both procedures were similar with high statistical correlation.
PDF
