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Background: Moderate–severe atopic dermatitis (AD) has a significant impact on patients’ lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. Methods: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. Results: Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. Conclusions: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD. Resumen: Antecedentes: La dermatitis atópica (DA) moderada-grave tiene un impacto significativo en la vida de los pacientes, muchos de los cuales requieren tratamiento sistémico para controlar los síntomas (p. ej., prurito). Algunos tratamientos son usados fuera de indicación. Este estudio describió características sociodemográficas y clínicas, patrones de tratamiento, uso de recursos sanitarios (URS) y costes asociados en adultos con DA que iniciaron tratamiento sistémico o fototerapia en la práctica habitual. Métodos: Este estudio observacional retrospectivo de historias clínicas electrónicas en la base de datos BIG-PAC identificó adultos con diagnóstico previo de DA (CIE-9: 691.8 o 692.9) que comenzaron con corticosteroides orales, inmunosupresores, biológicos o fototerapia entre el 01/01/2012 y el 31/12/2016. Se siguió a los pacientes durante 3 años desde el inicio del tratamiento, hasta 31/12/2019. Los datos sobre las características clínicas de los pacientes, patrones de tratamiento, URS y costes se analizaron de forma descriptiva. Resultados: Los pacientes (N = 1995) tenían una edad media de 60 años, el 64% eran mujeres, con una media de 23 años desde el diagnóstico (84% tenían ≥ 18 años al inicio de la DA). Las principales comorbilidades fueron ansiedad (38%), hipertensión arterial (36%) y dislipidemia (35%). La mayoría de los pacientes utilizaron corticosteroides orales como primer tratamiento sistémico (84%; duración media 29 días) e inmunosupresores en el 13% de los pacientes (duración media 117 días, ciclosporina en el 5% y metotrexato en el 4%). La mitad de los pacientes requirieron una segunda línea de tratamiento sistémico y el 12% una tercera. El uso de inmunosupresores y biológicos aumentó simultáneamente con las líneas de tratamiento. Aproximadamente el 13% de los pacientes recibieron tratamientos sistémicos de forma continua durante los 3 años de seguimiento. El coste medio por paciente a 3 años fue de 3.835 euros, con un coste medio anual de 1.278 euros. Conclusiones: Los resultados sugieren una alta carga económica y de comorbilidad en esta población del mundo real de adultos con DA, y la necesidad de nuevos tratamientos sistémicos indicados para DA.

Resumen: La citoquina IL-31 es una neurocitoquina que estimula las neuronas sensoriales relacionadas con el picor, contribuye a la inflamación, la disfunción y remodelación de la barrera epidérmica. Al interrelacionar los sistemas inmunológico y nervioso constituye un factor clave en el tratamiento de dermatitis atópica y del prurigo nodular. Nemolizumab es un anticuerpo monoclonal humanizado que bloquea la subunidad α del receptor de la IL-31 y modula la respuesta neuroinmunitaria, bloquea directamente la señalización del prurito y alivia rápidamente el prurito, controlando la inflamación y reduciendo la gravedad del eccema en dermatitis atópica y las lesiones pruriginosas del prurigo nodular al restaurar la función epitelial y promover la integridad de la barrera cutánea.Este artículo resume la nueva información relacionada con las funciones de la IL-31 y presenta la evidencia y resultados disponibles hasta el momento de los ensayos clínicos de nemolizumab en dermatitis atópica y prurigo nodular. Abstract: Interleukin 31 (IL-31) is a neurocytokine that stimulates sensory neurons involved in pruritus. It contributes to skin barrier inflammation, dysfunction, and remodeling. As the immune and nervous systems are interrelated, IL-31 has a key role in the treatment of atopic dermatitis and prurigo nodularis. Nemolizumab is a humanized monoclonal antibody that blocks the α subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling. It reduces inflammation and lesion severity in atopic dermatitis and prurigo nodularis by restoring epithelial function and promoting skin barrier integrity.This review synthesizes the latest information on the functions of IL-31 and presents the current evidence, including clinical trial results, on the use of nemolizumab in the treatment of atopic dermatitis and prurigo nodularis.

Disentangling the influence of lithology from the respective roles of climate, topography and tectonic forcing on catchment denudation is often challenging in mountainous landscapes due to the diversity of geomorphic processes in action and of spatial and temporal scales involved. The Dora Baltea catchment (western Italian Alps) is an ideal setting for such investigation, since its large drainage system, extending from the Mont Blanc Massif to the Po Plain, cuts across different major lithotectonic units of the western Alps, whereas this region has experienced relatively homogeneous climatic conditions and glacial history throughout the Quaternary. We acquired new 10Be-derived catchment-wide denudation rates from 18 river-sand samples collected both along the main Dora Baltea river and at the outlet of its main tributaries. The inferred denudation rates vary between 0.2 and 0.9 mm yr−1, consistent with previously published values across the European Alps. Spatial variability in denudation rates was statistically compared with topographic, environmental and geological metrics. 10Be-derived denudation rates do not correlate with modern precipitation and rock geodetic uplift. We find, rather, that catchment topography, in turn conditioned by bedrock structures and erodibility (lithotectonic origin) and glacial overprint, is the main driver of 10Be-derived denudation patterns. We calculated the highest denudation rate for the Mont Blanc Massif, whose granitoid rocks and long-term tectonic uplift support high elevations, steep slopes and high relief and thus favour intense glacial and periglacial processes and recurring rockfall events. Finally, our results, in agreement with modern sediment budgets, demonstrate that the high sediment input from the Mont Blanc catchment dominates the Dora Baltea sediment flux, explaining the constant low 10Be concentrations measured along the Dora Baltea course even downstream the multiple junctions with tributary catchments.

Resumen: Antecedentes: La dermatitis de las manos (DM) es frecuente en los pacientes con dermatitis atópica (DA). Pocos estudios describen las características de estos pacientes a partir de poblaciones amplias y representativas de ámbitos geográficos y laborales diferentes. Objetivos: Describir el perfil epidemiológico, clínico y alérgico de los pacientes con DM a los que se realizan pruebas epicutáneas, comparando los pacientes con DA con los pacientes sin DA. Métodos. El estudio se ha realizado a partir de los datos del REIDAC, un registro multicéntrico nacional de pacientes a los que se realizan pruebas epicutaneas. Resultados: Se incluyeron 1466 pacientes parcheados por DM desde enero de 2018 hasta junio de 2020. Los pacientes con DA fueron más jóvenes y con una duración de los síntomas mayor. Los antecedentes ocupacionales como desencadenantes se registraron en menor medida que en los pacientes no atópicos (38 vs 53%). La única profesión en la que se encontraron diferencias significativas fue la peluquería. Los alérgenos más detectados fueron el sulfato de níquel, la metilcloroisotiazolinona/metilisotiazolinona, el cloruro de cobalto, el dicromato potásico, mezcla de fragancias I y II, y el formaldehido. Los diagnósticos más frecuentes fueron dermatitis alérgica de contacto (DAC); 24% en atópicos vs 31% en no atópicos (p 0.0224) y el eccema de contacto irritativo; 18% atópicos vs 35% no atópicos (p

Resumen: Antecedentes: La dermatitis atópica (DA) moderada-grave tiene un impacto significativo en la vida de los pacientes, muchos de los cuales requieren tratamiento sistémico para controlar los síntomas (p. ej., prurito). Algunos tratamientos son usados fuera de indicación. Este estudio describió características sociodemográficas y clínicas, patrones de tratamiento, uso de recursos sanitarios (URS) y costes asociados en adultos con DA que iniciaron tratamiento sistémico o fototerapia en la práctica habitual. Métodos: Este estudio observacional retrospectivo de historias clínicas electrónicas en la base de datos BIG-PAC identificó adultos con diagnóstico previo de DA (CIE-9: 691.8 o 692.9) que comenzaron con corticosteroides orales, inmunosupresores, biológicos o fototerapia entre el 01/01/2012 y el 31/12/2016. Se siguió a los pacientes durante tres años desde el inicio del tratamiento, hasta el 31/12/2019. Los datos sobre las características clínicas de los pacientes, patrones de tratamiento, URS y costes se analizaron de forma descriptiva. Resultados: Los pacientes (n = 1995) tenían una edad media de 60 años, 64% eran mujeres, con una media de 23 años desde el diagnóstico (84% tenían ≥ 18 años al inicio de la DA). Las principales comorbilidades fueron ansiedad (38%), hipertensión arterial (36%) y dislipidemia (35%). La mayoría de los pacientes utilizaron corticosteroides orales como primer tratamiento sistémico (84%; duración media 29 días) e inmunosupresores en 13% de los pacientes (duración media 117 días, ciclosporina en 5% y metotrexato en 4%). La mitad de los pacientes requirieron una segunda línea de tratamiento sistémico y 12% una tercera. El uso de inmunosupresores y biológicos aumentó simultáneamente con las líneas de tratamiento. Aproximadamente 13% de los pacientes recibieron tratamientos sistémicos de forma continua durante los tres años de seguimiento. El coste medio por paciente a tres años fue de 3.835 euros, con un coste medio anual de 1.278 euros. Conclusiones: Los resultados sugieren una alta carga económica y de comorbilidad en esta población del mundo real de adultos con DA, y la necesidad de nuevos tratamientos sistémicos indicados para DA. Abstract: Background: Moderate–severe atopic dermatitis (AD) has a significant impact on patients’ lives, with many requiring systemic treatment to manage symptoms (e.g., pruritus). Several drugs are used off-label to treat AD. This study describes sociodemographic/clinical characteristics, treatment patterns, health resource use (HRU) and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice. Methods: This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD (ICD-9: 691.8 or 692.9) starting oral corticosteroids, immunosuppressants, biologics or phototherapy between 01/01/2012 and 31/12/2016. Patients were followed for 3 years from treatment initiation, up to 31/12/2019. Data on patient characteristics, treatment patterns, HRU and costs were analyzed descriptively. Results: Patients (N = 1995) had a mean age of 60 years, 64% were female, with a mean time of 23 years since diagnosis (84% were ≥ 18 years at AD onset). Main comorbidities were anxiety (38%), arterial hypertension (36%) and dyslipidemia (35%). Most patients used oral corticosteroids as first systemic (84%; median duration 29 days) and immunosuppressants in 13% of patients (median duration 117 days, 5% cyclosporine and 4% methotrexate). Half of patients required a second line systemic and 12% a third line. The use of immunosuppressants and biologics increased with treatment lines. About 13% of patients received systemic treatments continuously over the 3-year follow-up. The average 3-year per patient cost was 3835 euros, with an average annual cost of 1278 euros. Conclusions: Results suggest a high comorbidity and economic burden in this real-world adult population with AD, and the need for systemic treatments indicated for use in AD.

Resumen: Antecedentes y objetivo: La actualización de las series estándar de pruebas epicutáneas debe basarse en datos objetivos de frecuencia de sensibilización de los alérgenos que componen cada batería. La última renovación de la batería estándar española se realizó en 2016 y de la europea en 2019, quedando pendiente valorar la inclusión de alérgenos emergentes. Material y método: Desarrollamos un estudio observacional, prospectivo y multicéntrico de los pacientes consecutivos del registro del Grupo Español de Investigación en Dermatitis y Alergia Cutánea sometidos a pruebas epicutáneas con hidroperóxido de linalool, hidroperóxido de limoneno, 2-hidroxi-etil-metacrilato, benzisotiazolinona, octilisotiazolinona, mezcla textil, metabisulfito sódico, propóleo, bronopol, mezcla de compuestas II, diazolidinil urea, imidazolidinil urea, decil glucósido y lauril glucósido, durante los años 2019 y 2020. Resultados: Se analizó una muestra de 4.654 pacientes estudiados con diazolidinil urea, imidazolidinil urea y bronopol, y de 1.890 pacientes con el resto de los alérgenos. El índice MOAHLFA fue: M 30%, O 18%, A 15%, H 29%, L 6,5%, F 23%, A 68%. Siete alérgenos mostraron una frecuencia de sensibilización mayor del 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato, benzisotiazolinona, hidroperóxido de limoneno, mezcla textil, metabisulfito sódico y propóleo. Tres alérgenos mostraron una frecuencia de relevancia presente superior al 1%: hidroperóxido de linalool, 2-hidroxi-etil-metacrilato e hidroperóxido de limoneno; para benzisotiazolinona y mezcla textil, esta frecuencia fue de entre el 0,9 y el 1%. Conclusiones: Nuestros resultados indican que debería valorarse la inclusión de siete nuevos alérgenos en la batería estándar española. Estos resultados podrían contribuir a la próxima actualización de la batería basal europea. Abstract: Background: Standard patch test series must be updated using objective data on allergen sensitization. The Spanish standard series was last updated in 2016 and the European series in 2019, and the inclusion of several emerging allergens needs to be evaluated. Material and methods: We conducted a prospective, observational, multicenter study of consecutive patients from the registry of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) who were patch tested in 2019 and 2020 with linalool hydroperoxide, limonene hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, octylisothiazolinone, textile dye mix (TDM), sodium metabisulfite, propolis, bronopol, Compositae mix II, diazolidinyl urea, imidazolidinyl urea, decyl glucoside, and lauryl glucoside. Results: We analyzed data for 4654 patients tested with diazolidinyl urea, imidazolidinyl urea, and bronopol, and 1890 tested with the other allergens. The values for the MOAHLFA index components were 30% for male, 18% for occupational dermatitis, 15% for atopic dermatitis, 29% for hand, 6.5% for leg, 23% for face, and 68% for age > 40 years. Sensitization rates above 1% were observed for 7 allergens: linalool hydroperoxide, 2-hydroxyethyl-methacrylate, benzisothiazolinone, limonene hydroperoxide, TDM, sodium metabisulfite, and propolis. Three allergens had a current relevance rate of over 1%: linalool hydroperoxide, 2-hydroxyethyl-methacrylat, and limonene hydroperoxide. Benzisothiazolinone and TDM had a relevance rate of between 0.9% and 1%. Conclusions: Our results indicate that 7 new allergens should be considered when extending the Spanish standard patch test series. The data from our series could be helpful for guiding the next extension of the European baseline series.

Interleukin 31 (IL-31) is a neurocytokine that stimulates sensory neurons involved in pruritus. It contributes to skin barrier inflammation, dysfunction, and remodeling. As the immune and nervous systems are interrelated, IL-31 has a key role in the treatment of atopic dermatitis (AD) and prurigo nodularis (PN). Nemolizumab is a humanized monoclonal antibody that blocks the α subunit of the IL-31 receptor, modulates the neuroimmune response, and rapidly alleviates itching by directly blocking signaling. It reduces inflammation and lesion severity in AD and PN by restoring epithelial function and promoting skin barrier integrity. This review synthesizes the latest information on the functions of IL-31 and presents the current evidence, including clinical trial results, on the use of nemolizumab in the treatment of AD and PN. Resumen: La citoquina IL-31 es una neurocitoquina que estimula las neuronas sensoriales relacionadas con el picor, contribuye a la inflamación, la disfunción y remodelación de la barrera epidérmica. Al interrelacionar los sistemas inmunológico y nervioso constituye un factor clave en el tratamiento de dermatitis atópica (DA) y del prurigo nodular (PN). Nemolizumab es un anticuerpo monoclonal humanizado que bloquea la subunidad α del receptor de la IL-31 y modula la respuesta neuroinmunitaria, bloquea directamente la señalización del prurito y alivia rápidamente el prurito, controlando la inflamación y reduciendo la gravedad del eccema en DA y las lesiones pruriginosas del PN al restaurar la función epitelial y promover la integridad de la barrera cutánea.Este artículo resume la nueva información relacionada con las funciones de la IL-31 y presenta la evidencia y resultados disponibles hasta el momento de los ensayos clínicos de nemolizumab en DA y PN.

Reconstructing the response of present-day ice sheets to past global climate change is important for constraining and refining the numerical models which forecast future contributions of these ice sheets to sea-level change. Mapping landforms is an essential step in reconstructing glacial histories. Here we present a new map of glacial landforms and deposits on nunataks in western Dronning Maud Land, Antarctica. Nunataks are mountains or ridges that currently protrude through the ice sheet and may provide evidence that they have been wholly or partly covered by ice, thus indicating a formerly more extensive (thicker) ice sheet. The map was produced through a combination of mapping from Worldview satellite imagery and ground validation. The sub-metre spatial resolution of the satellite imagery enabled mapping with unprecedented detail. Ten landform categories have been mapped, and the landform distributions provide evidence constraining spatial patterns of a previously thicker ice sheet.

Background: Hand eczema is common in patients with atopic dermatitis (AD), but few studies have described the characteristics of these patients in large, representative populations from different geographic regions and occupational settings. Objective: To describe the epidemiological, clinical, and allergy profile of patients with hand eczema who underwent patch testing and compare patients with and without AD. Methods: Analysis of data from the Spanish Contact Dermatitis Registry, a multicenter registry of patients who undergo patch testing in Spain. Results: We included 1466 patients with hand eczema who were patch tested between January 2018 and June 2020. Those with AD were younger and had had symptoms for longer before testing. They were also more likely to have been exposed to occupational triggers (38% vs 53% for patients without AD). The only profession for which significant differences were found was hairdressing. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, cobalt chloride, potassium dichromate, fragrance mixes I and II, and formaldehyde. The most common diagnoses were allergic contact dermatitis (24% vs 31% in patients with and without AD, P = .0224) and irritant contact dermatitis (18% and 35% respectively, P

Abstract Background In low transmission settings early diagnosis is the main strategy to reduce adverse outcomes of malaria in pregnancy; however, microscopy and rapid diagnostic tests (RDTs) are inadequate for detecting low-density infections. We studied the performance of the highly sensitive-RDT (hsRDT) and the loop mediated isothermal DNA amplification (LAMP) for the detection of P. falciparum in pregnant women. Methods A cross-sectional study was conducted in two malaria-endemic municipalities in Colombia. We screened pregnant women in the context of an antenatal care program in health facilities and evaluated five tests (microscopy, conventional RDT, hsRDT, LAMP and nested polymerase chain reaction-PCR) for the detection of P. falciparum in peripheral blood, using a quantitative reverse transcription PCR (qRT-PCR) as the reference standard. Diagnostic performance of hsRDT and LAMP were compared with routine testing. Results The prevalence of P. falciparum was 4.5% by qRT-PCR, half of those infections were subpatent. The sensitivity of the hsRDT (64.1%) was slightly better compared to microscopy and cRDT (59 and 53.8% respectively). LAMP had the highest sensitivity (89.7%) for detecting P. falciparum and the ability to detect very low-density infections (minimum parasite density detected 0.08 p/μL). Conclusions There is an underestimation of Plasmodium spp. infections by tests routinely used in pregnant women attending antenatal care visits. LAMP methodology can be successfully implemented at local hospitals in malaria-endemic areas. The relevance of detecting and treating this sub-patent P. falciparum infections in pregnant women should be evaluated. Trial registration ClinicalTrials.gov, Identifier: NCT03172221 , Date of registration: May 29, 2017.

In view of the integration of membrane resonators with more complex MEMS structures, we developed a general fabrication procedure for circular shape SiNx membranes using Deep Reactive Ion Etching (DRIE). Large area and high-stress SiNx membranes were fabricated and used as optomechanical resonators in a Michelson interferometer, where Q values up to 1.3 × 106 were measured at cryogenic temperatures, and in a Fabry-Pérot cavity, where an optical finesse up to 50000 has been observed.

This study investigates the efficacy of intermediate penalty kickers by comparing the effect of applying an automated WiFi (Wireless Fidelity) system on the field of play to simulate a strategy that takes account of goalkeeper action (open) with another for which goalkeeper strategy is irrelevant (closed). Intermediate penalty kickers (n=12) took a pretreatment test of 32 kicks in a “real-play” situation with intermediate goalkeepers (n=3). We established two groups of kickers who underwent 11 treatment sessions using different strategies and then conducted a posttreatment test. The variables we measured were the number of goals scored, whether the direction of the shot was the same or different from the direction of the goalkeeper’s move (DDG), ball speed and the duration of the kicking movement. The results suggest the goalkeepers demonstrated a greater capacity to identify advance cues when faced with CG (closed strategy group) kickers and that OG (open strategy group) kickers achieved lower ball speeds when modifying the contact surface of the kick. Key Words: penalty kick, anticipation, decision-making, field, training.

The aim of this study is to characterize the Pirapó, Paranapanema 3 and 4 Hydrographic Unit, emphasizing its physical attributes and processes of use and occupation, responsible for the structure of the current landscape and the state of its water resources. The recognition of the landscape’s spatial structure in the hydrographic unit and its drainage basins was obtained by integrated analysis of the main elements that compose it: geology, landforms (hypsometric and slope), soils, climate and land use. Analysis revealed that within each drainage basin several variations in the spatial structure of the landscape occur which produce an internal compartmentalization. Each compartment is defined by its own geo-ecological structure, physiognomic standards and dynamics, reflected in its potentialities and vulnerabilities and in the conditions of water resources in the wake of occupation and use over time.

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Despite the dynamic nature of communities, most research typically treated interaction networks as static entities, and only a few analysed the spatial and the temporal scales simultaneously. Here, we used spatial and temporal multilayer networks to explore the persistence of species and interactions in space and time, as well as the variation of species role (centrality) according to biotic factors. We further investigated, for the first time, the spatio‐temporal variation in multilayer network structure. Species exhibited substantial turnover across time mainly due to differences in species phenology. In contrast, interaction turnover was more pronounced across habitats, which seems to be a common strategy of pollinators to adjust interactions spatially to different ecological scenarios. Plant species were comparatively more important to the cohesiveness of spatial than temporal networks, whereas the centrality of pollinators correlated between scales. The importance of plant species fluctuated temporally due mainly to changes in flower density, whereas that of pollinators fluctuated in space and time according to their relative abundance. Module composition was highly unstable in time. Species were highly capable of changing partners and module affiliation across both scales. We conclude that plant–pollinator interactions are highly dynamic in space and time, and that there are differences between plants and pollinators in their use of resources across habitats and subseasons with implications for the understanding of functional connectivity and multilayer structure. [ABSTRACT FROM AUTHOR]