Consensus on the Clinical Approach to Moderate-to-Severe Atopic Dermatitis in Spain: A Delphi Survey

Background. The purpose of this study was to gather information on the current assessment and management of patients with moderate-to-severe AD in routine daily practice. Methods. A cross-sectional two-round Delphi survey with the participation of dermatologists and allergologists throughout Spain was conducted. They completed a 46-item questionnaire, and consensus was defined when responses of >= 80% of participants coincided in the categories of a 5-point Likert scale for that item. Results. A total of 105 specialists (aged 40-59 years) completed the two rounds. Participants agreed regarding the consideration of AD as a multifaceted disease and the differences in clinical presentation of AD according to the patient's age. It is recommendable to perform a skin biopsy to exclude early stage T-cell cutaneous lymphoma, psoriasis, or dermatitis herpetiformis, among others (99.1%). Also, consensus was reached regarding the use of the SCORAD index to quantify the severity of the disease (86.7%), the use of wet wraps to increase the effect of topical corticosteroids (90.4%), the usefulness of proactive treatment during follow-up (85.6%) and tacrolimus ointment (91.2%) to reduce new flares, and the fact that crisaborole is not the treatment of choice for severe AD (92.4%). AD was not considered a contraindication for immunotherapy in patients with allergic respiratory diseases (92.4%). In patients with severe AD, the use of immune response modifier drugs (97.6%) or phototherapy (92.8%) does not sufficiently cover their treatment needs. Consensus was also obtained regarding the role of the new biologic drugs (93.6%) targeting cytokines involved in the Th2 inflammatory pathway (92.0%) and the potential role of dupilumab as first-line treatment (90.4%) in moderate-to-severe AD patients. Conclusion. This study contributes a reference framework to the care of AD patients. There is no diagnostic test or biomarkers to direct treatment or to assess the severity of the disease, and many therapeutic challenges remain

Cerebrospinal fluid Presenilin-1 increases at asymptomatic stage in genetically determined Alzheimer’s disease

[Background] Presenilin-1 (PS1), the active component of the intramembrane γ-secretase complex, can be detected as soluble heteromeric aggregates in cerebrospinal fluid (CSF). The aim of this study was to examine the different soluble PS1 complexes in the lumbar CSF (CSF-PS1) of individuals with Alzheimer’s disease (AD), particularly in both symptomatic and asymptomatic genetically determined AD, in order to evaluate their potential as early biomarkers.[Methods] Western blotting, differential centrifugation and co-immunoprecipitation served to determine and characterize CSF-PS1 complexes. We also monitored the assembly of soluble PS1 into complexes in a cell model, and the participation of Aβ in the dynamics and robustness of the stable PS1 complexes.[Results] There was an age-dependent increase in CSF-PS1 levels in cognitively normal controls, the different complexes represented in similar proportions. The total levels of CSF-PS1, and in particular the proportion of the stable 100–150 kDa complexes, increased in subjects with autosomal dominant AD that carried PSEN1 mutations (eight symptomatic and six asymptomatic ADAD) and in Down syndrome individuals (ten demented and ten non-demented DS), compared with age-matched controls (n = 23), even prior to the appearance of symptoms of dementia. The proportion of stable CSF-PS1 complexes also increased in sporadic AD (n = 13) and mild-cognitive impaired subjects (n = 12), relative to age-matched controls (n = 17). Co-immunoprecipitation demonstrated the association of Aβ oligomers with soluble PS1 complexes, particularly the stable complexes.[Conclusions] Our data suggest that CSF-PS1 complexes may be useful as an early biomarker for AD, reflecting the pathology at asymptomatic state.This study was funded in part by the EU BIOMARKAPD-Joint Programming on Neurodegenerative Diseases (JPND) project, by the Instituto de Salud Carlos III (ISCIII grants PI11/03026 to JSV, PI11/02425 and PI14/01126 to JF, PI11/03035 and PI14/1561 to AL, PI08/0036 and PI12/00013 to RSV, and PI11/03023 to JLM), co-financed by the Fondo Europeo de Desarrollo Regional, under the aegis of JPND, and through CIBERNED, ISCIII. This work was also supported by the Fundació Catalana de Síndrome de Down and by a “Marató TV3” grant (20141210 to JF) and a grant from the Griffols Foundation. The funding bodies played no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. We also acknowledge the support for the publication fee to the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Climatic and lacustrine morphometric controls of diatom paleoproductivity in a tropical Andean lake

15 páginas, 6 figuras, 1 tablaThe coupling of lake dynamics with catchment biogeochemistry is considered the key element controlling primary production in mountain lakes at time scales of a few decades to millennia, yet little is known on the impacts of the morphometry of lakes throughout their ontogeny. As Lake Chungará (Central Andean Altiplano, northern Chile) experienced long-term lake-level fluctuations that strongly modified its area:volume ratio, it is an ideal system for exploring the relative roles that long-term climatic shifts and lake morphometry play on biosiliceous lacustrine productivity. In this paper, we review previous data on the percent contents of total organic carbon, total inorganic carbon, total nitrogen, total biogenic silica, isotopic composition of organic matter, carbonates, and diatom frustules, as well as data on the abundance of the chlorophycean Botryococcus braunii in this lake for the period 12,400–1300 cal yr BP. We also include new data on organic carbon and biogenic silica mass accumulation rates and the diatom assemblage composition of an offshore core dated using 14C and U/Th. Biosiliceous productivity in Lake Chungará was influenced by shifts in allochthonous nutrient inputs related to variability in precipitation. Humid phases dated at approx. 12,400 to 10,000 and 9600 to 7400 cal yr BP coincide with periods of elevated productivity, whereas decreases in productivity were recorded during arid phases dated at approx. 10,000 to 9600 and 7400 to 3550 cal yr BP (Andean mid-Holocene Aridity Period). However, morphometry-related in–lake controls led to a lack of a linear response of productivity to precipitation variability. During the late Glacial to early Holocene, lowstands facilitated complete water column mixing, prompting episodic massive blooms of a large centric diatom, Cyclostephanos cf. andinus. Thus, moderate productivity could be maintained, regardless of aridity, by this phenomenon of morphometric eutrophy during the early history of the lake. The subsequent net increase in lake level introduced modifications in the area of the epilimnion sediments versus the total volume of the epilimnion, preventing complete overturn. Surpassing a certain depth threshold at approx. 8300 cal yr BP caused cessation of the morphometric eutrophy conditions associated with Cyclostephanos cf. andinus superblooms. After 7300 cal yr BP, the lake experienced a decrease in biosiliceous productivity and a change of state that involved a stronger dependence on precipitation variability, with a lesser contribution of diatoms to the total primary productivity. Our results show that the interpretation of lacustrine paleoproductivity records as paleoclimatic archives needs to take into account the effects of changes in the epilimnion sediment area to epilimnion volume ratio in association with lake ontogenyThe Spanish Ministry of Science and Innovation funded this research through the projects ANDESTER (BTE2001-3225), Complementary Action (BTE2001-5257-E), LAVOLTER (CGL2004-00683/BTE), GEOBILA (CGL2007-60932/BTE) and CONSOLIDER-Ingenio 2010 GRACCIE (CSD2007-00067)Peer reviewe

AI: Can It Make a Difference to the Predictive Value of Ultrasound Breast Biopsy?

(1) Background: This study aims to compare the ground truth (pathology results) against the BI-RADS classification of images acquired while performing breast ultrasound diagnostic examinations that led to a biopsy and against the result of processing the same images through the AI algorithm KOIOS DS TM (KOIOS). (2) Methods: All results of biopsies performed with ultrasound guidance during 2019 were recovered from the pathology department. Readers selected the image which better represented the BI-RADS classification, confirmed correlation to the biopsied image, and submitted it to the KOIOS AI software. The results of the BI-RADS classification of the diagnostic study performed at our institution were set against the KOIOS classification and both were compared to the pathology reports. (3) Results: 403 cases were included in this study. Pathology rendered 197 malignant and 206 benign reports. Four biopsies on BI-RADS 0 and two images are included. Of fifty BI-RADS 3 cases biopsied, only seven rendered cancers. All but one had a positive or suspicious cytology; all were classified as suspicious by KOIOS. Using KOIOS, 17 B3 biopsies could have been avoided. Of 347 BI-RADS 4, 5, and 6 cases, 190 were malignant (54.7%). Because only KOIOS suspicious and probably malignant categories should be biopsied, 312 biopsies would have resulted in 187 malignant lesions (60%), but 10 cancers would have been missed. (4) Conclusions: KOIOS had a higher ratio of positive biopsies in this selected case study vis-à-vis the BI-RADS 4, 5 and 6 categories. A large number of biopsies in the BI-RADS 3 category could have been avoided

Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants

OBJECTIVE: This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID‐19) and as a post‐COVID‐19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). BACKGROUND: Headache can be present in up to 50% of individuals during the acute phase of SARS‐CoV‐2 infection and in 10% of subjects during the post‐COVID‐19 phase. There are no data on differences in the occurrence of headache in the acute‐ and post‐COVID‐19 phase according to the SARS‐CoV‐2 variants. METHODS: A cross‐sectional cohort study was conducted. Unvaccinated subjects previously hospitalized for COVID‐19 caused by the Wuhan (n = 201), Alpha (n = 211), or Delta (n = 202) SARS‐CoV‐2 variants were scheduled for a telephone interview 6 months after hospital discharge. Hospitalization data were collected from hospital medical records. RESULTS: The presence of headache as a COVID‐19 onset symptom at hospitalization was higher in subjects with the Delta variant (66/202, 32.7%) than in those infected with the Wuhan (42/201, 20.9%; odds ratio [OR] 1.83, 95% confidence interval [CI] 1.17–2.88) or Alpha (25/211, 11.8%; OR 3.61, 95% CI, 2.16–6.01) variants. The prevalence of post‐COVID‐19 headache 6 months after hospital discharge was higher in individuals infected with the Delta variant (26/202, 12.9%) than in those infected with the Wuhan (11/201, 5.5%; OR 2.52, 95% CI 1.22–5.31) or Alpha (eight of 211, 3.8%; OR 3.74, 95% CI 1.65–8.49) variants. The presence of headache as a COVID‐19 onset symptom was associated with post‐COVID‐19 headache in subjects infected with the Wuhan (OR 7.75, 95% CI 2.15–27.93) and Delta variants (OR 2.78, 95% CI 1.20–6.42) but not with the Alpha variant (OR 2.60, 95% CI 0.49–13.69). CONCLUSION: Headache was a common symptom in both the acute‐ and post‐COVID‐19 phase in subjects infected with the Wuhan, Alpha, and Delta variants but mostly in those infected with the Delta variant

Strain Switching in van der Waals Heterostructures Triggered by a Spin-Crossover Metal-Organic Framework

Van der Waals heterostructures (vdWHs) provide the possibility of engineering new materials with emergent functionalities that are not accessible in another way. These heterostructures are formed by assembling layers of different materials used as building blocks. Beyond inorganic 2D crystals, layered molecular materials remain still rather unexplored, with only few examples regarding their isolation as atomically thin layers. Here, the family of van der Waals heterostructures is enlarged by introducing a molecular building block able to produce strain: the so-called spin-crossover (SCO). In these metal-organic materials, a spin transition can be induced by applying external stimuli like light, temperature, pressure, or an electric field. In particular, smart vdWHs are prepared in which the electronic and optical properties of the 2D material (graphene and WSe2) are clearly switched by the strain concomitant to the spin transition. These molecular/inorganic vdWHs represent the deterministic incorporation of bistable molecular layers with other 2D crystals of interest in the emergent fields of straintronics and band engineering in low-dimensional materials

Path loss modeling for vehicular system performance and communicaitons protocols evaluation

Vehicular communications are receiving considerable attention due to the introduction of the intelligent transportation system (ITS) concept, enabling smart and intelligent driving technologies and applications. To design, evaluate and optimize ITS applications and services oriented to improve vehicular safety, but also non-safety applications based on wireless systems, the knowledge of the propagation channel is vital. In particular, the mean path loss is one of the most important parameters used in the link budget, being a measure of the channel quality and limiting the maximum allowed distance between the transmitter (Tx) and the receiver (Rx). From a narrowband vehicular-to-vehicular (V2V) channel measurement campaign carried out at 5.9 GHz in three different urban environments characterized by high traffic density, this paper analyzes the path loss in terms of the Tx-Rx separation distance and fading statistics. Based on a linear slope model, values for the path loss exponent and the standard deviation of shadowing are reported. We have evaluated the packet error rate (PER) and the maximum achievable Tx-Rx separation distance for a PER threshold level of 10% according to the digital short-range communications (DSRC) specifications. The results reported here can be incorporated in an easy way to vehicular networks (VANETs) simulators in order to develop, evaluate and validate new protocols and systems architecture configurations under realistic propagation conditions.Fernández González, HA.; Rubio Arjona, L.; Reig, J.; Rodrigo Peñarrocha, VM.; Valero-Nogueira, A. (2013). Path loss modeling for vehicular system performance and communicaitons protocols evaluation. Mobile Networks and Applications. 18(6):755-765. doi:10.1007/s11036-013-0463-xS755765186Gallager B, Akatsuka H, Suzuki H (2006) Wireless communications for vehicle safety: radio link performance and wireless connectivity. IEEE Veh Technol Mag 1(4):4–24Rubio L, Reig J, Fernández H (2011) Propagation aspects in vehicular networks, Vehicular technologies. Almeida M (ed) InTechWang C-X, Vasilakos A, Murch R, Shen SGX, Chen W, Kosch T (2011) Guest editorial. Vehicular communications and networks – part I. IEEE J Select Areas Commun 29(1):1–6ASTM E2213-03 (2003) Standard specification for telecommunications and information exchange between roadside and vehicle systems – 5 GHz band Dedicated Short Range Communications (DSRC) Medium Access Control (MAC) and Physical Layer (PHY) specifications. American Society for Testing Materials (ASTM), West ConshohockenIEEE 1609 – Family of Standards for Wireless Access in Vehicular Environments (WAVE). [Online]. Available: http://www.standards.its.dot.govETSI TR 102 492–2 Part 2 (2006) Technical characteristics for Pan European Harminized Communications Equipment Operating in the 5 GHz frequency range intended for road safety and traffic management, and for non-safety related ITS applications, European Telecommunications Standard Institute (ETSI), Technical Report, Sophia Antipolis, FranceThe Car-to-Car Communication Comsortium (C2CC): http:/www.car-to-car.orgMecklenbräuker C, Molisch A, Karedal J, Tufvesson F, Paier A, Bernado L, Zemen T, Klemp O, Czink N (2011) Vehicular channel characterization and its implications for wireless system design and performance. IEEE Proc 99(7):1189–1212Ghafoor KZ, Bakar KA, Lloret J, Khokhar RH, Lee KC (2013) Intelligent beaconless geographical routing for urban vehicular environments. Int J Wireless Netw 19(3):345–362Ghafoor KZ, Lloret J, Bakar KA, Sadiq AS, Mussa SAB (2013) Beaconing approaches in vehicular ad hoc networks: a survey. Int J Wirel Pers Commun. Published Online (May 2013)Michelson DG, Ghassemzadeh SS (2009) New directions in wireless communications, Springer Science+Busines Media (Chapter 1)IEEE 802.11p (2010) Wireless LAN Medium Access Control (MAC) and Physical Layer (PHY) Specifications Amendment 6: Wireless Access in Vehicular Environments, Institute of Electrical and Electronic Engineers (IEEE), New York, USA.Karedal J, Czink N, Paier A, Tufvesson F, Moisch AF (2011) Path loss modeling for vehicle-to-vehicle communications. IEEE Trans Veh Technol 60(1):323–327Cheng L, Henty B, Stancil D, Bai F, Mudalige P (2007) Mobile vehicle-to-vehicle narrow-band channel measurement and characterization of the 5.9 GHz dedicated short range communication (DSRC) frequency band. IEEE J Select Areas Commun 25(8):1501–1516Cheng L, Henty B, Cooper R, Stancil D, Bai F (2008) Multi-path propagation measurements for vehicular networks at 5.9 GHz. 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Workshop on performance evaluation of wireless ad hoc, sensor, and ubiquitous networks, pp. 49–5

The last deglaciation in the Picos de Europa National Park (Cantabrian Mountains, northern Spain)

42 páginas, 8 figuras, 4 tablas.-- El PDF del artículo esta en formato pre-print.A sedimentological and geochemical study of the Lago Enol sequence (Cantabrian Mountains, northern Spain), together with detailed geomorphological mapping, provides a first record of glacier evolution and climate change over the last 40 ka in the Picos de Europa National Park. The Enol glacier retreated from its maximum extent prior to 40 ka BP as demonstrated by the onset of proglacial lacustrine sedimentation in two glaciated depressions: the Comella hollow to the north (before 40 ka BP) and the Lago Enol (before 38 ka BP). These results support previous evidence that the maximum extent of southern European glaciers occurred earlier than in northern Europe. Alternation of homogeneous and laminated proglacial sediments during the glacier retreat illustrate a dynamic glacial evolution during the Marine Isotope Stage (MIS) 3 (40–26 ka BP). A slight warming is detected at 26 ka ago with the change from proglacial sediments (in a lake located in contact to the glacier) to glaciolacustrine sedimentation (in a non-contact or distal lake). Finally, the onset of organic-rich sediments took place at 18 ka ago. This last transition occurred in two phases, similarly to the North Atlantic Last Termination, suggesting a link between North Atlantic Deep Water formation oscillations and palaeohydrological variability in the Cantabrian Mountains.This research has been funded through the projects LIMNOCLIBER (REN2003-09130-C02-02), IBERLIMNO (CGL2005-20236-E/CLI), LIMNOCAL (CGL2006-13327-C04-01) and GRACCIE (CSD2007-00067), provided by the Spanish Inter-Ministry Commission of Science and Technology (CICYT). Additional funding was provided by the Spanish National Parks Agency through the project ‘Evolución climática y ambiental del Parque Nacional de Picos de Europa desde el último máximo glaciar – ref: 53/2006’. A. Moreno acknowledges funding from the European Commission's Sixth Framework Program (Marie Curie Outgoing International Fellowships, proposal 021673-IBERABRUPT).Peer reviewe

Multifocus HDR VIS/NIR hyperspectral imaging and its application to works of art

The authors would like to thank Mr. Francisco Fernández Fábregas, owner of the Transfiguration of Christ for allowing us the privilege of studying this painting. We also acknowledge the collaboration of Angela Tate.This paper presents a complete framework for capturing and processing hyperspectral reflectance images of artworks in situ, using a hyperspectral line scanner. These capturing systems are commonly used in laboratory conditions synchronized with scanning stages specifically designed for planar surfaces. However, when the intended application domain does not allow for image capture in these controlled conditions, achieving useful spectral reflectance image data can be a very challenging task (due to uncontrolled illumination, high-dynamic range (HDR) conditions in the scene, and the influence of chromatic aberration on the image quality, among other factors). We show, for the first time, all the necessary steps in the image capturing and post-processing in order to obtain high-quality HDR-based reflectance in the visible and near infrared, directly from the data captured by using a hyperspectral line scanner coupled to a rotating tripod. Our results show that the proposed method outperforms the normal capturing process in terms of dynamic range, color and spectral accuracy. To demonstrate the potential interest of this processing strategy for on-site analysis of artworks, we applied it to the study of a vintage copy of the famous painting “Transfiguration” by Raphael, as well as a facsimile of “The Golden Haggadah” from the British Library of London. The second piece has been studied for the identification of highly reflective gold-foil covered areas.Spanish Ministry of Economy and Competitiveness, DPI2015-64571-R, ECQM2018-004952-