Active analog tuning of the phase of light in the visible regime by bismuth-based metamaterials

Active and analog tuning of the phase of light is needed to boost the switching performance of photonic devices. However, demonstrations of this type of tuning in the pivotal visible spectral region are still scarce. Herein we report active analog tuning of the phase of visible light reflected by a bismuth-based metamaterial, enabled by a reversible solid-liquid transition. This metamaterial, fabricated by a lithography-free approach, consists of two-dimensional assemblies of polydisperse plasmonic bismuth nanostructures embedded in a refractory and transparent aluminum oxide matrix. Analog tuning of the phase is achieved by controlled heating of the metamaterial to melt a fraction of the nanostructures. A maximum tuning of 320 deg (1.8pi) is observed upon complete melting of the nanostructures at 230 degrees Celsius. This tuning is reversible by cooling to 25 degrees Celsius. In addition, it presents a wide hysteretic character due to liquid bismuth undercooling. This enables the phase achieved by this analog approach to remain stable over a broad temperature range upon cooling and until re-solidification occurs around 100 degrees Celsius. Therefore, bismuth-based metamaterials are appealing for applications including optical data storage with enhanced information density or bistable photonic switching with a tunable "on" state

Enhancing the use of Asthma and COPD Assessment Tools in Balearic Primary Care (ACATIB):a region-wide cluster-controlled implementation trial

Asthma and chronic obstructive pulmonary disease (COPD) health status assessment tools have demonstrated their value in guiding clinical management. Their use in primary care is still suboptimal. The objective of this study was to assess the effect of an educational intervention programme on the use of the Asthma Control Test (ACT), modified Medical Research Council (mMRC) and COPD Assessment Test (CAT) among primary care settings of the Balearic Islands, Spain. In this region-wide cluster-controlled implementation study, an educational intervention on the use of respiratory health status tools was provided to primary care practices in Mallorca (intervention group). Practices in Ibiza and Menorca functioned as control practices. Written and multimedia materials were provided to all participants to educate their colleagues. Primary outcome was the difference between intervention and control practices in the percentage of practices that increased the use-and recording-of ACT, CAT and mMRC tests between the 6-month period before intervention and the 6-month period after intervention. In the intervention group, 32 out of 45 (71%) centres enhanced the total number of tests, compared with 4 out of 12 (33%) in the non-intervention group (χ(2); P=0.02). Before intervention, 399 test scores were recorded in 88,194 patients (asthma: 57,339; COPD: 30,855). After intervention, 1,576 test scores were recorded in 92,714 patients (asthma: 61,841; COPD: 30,873). An educational intervention programme targeted on primary care physicians enhances the use of respiratory health status tools and promotes behavioural changes. However, the effect is very low and difficult to measure in clinical terms

Parámetros fisicoquímicos para la síntesis de ácido láctico ó etanol de la bacteria (corynebacterium glutamicum)

El interés por obtener productos para la industria de biocombustibles a partir de desechos agrícolas, conduce a las investigaciones en la búsqueda de sistemas microbianos resistentes y costo-efectivos. La Corynebacterium glutamicum, es un microorganismo usado para producir amino-ácidos, crece en gran variedad de sustratos y es resistente durante la fermentación, a variaciones en el pH, temperatura, presión osmótica y acumulación de alcohol, características que lo hacen candidato a ser mejorado para la síntesis de ácido láctico y etanol. Aún se desconocen aspectos de su fisiología que aumenten su eficiencia en convertir azúcares (C5 y C6) en estos dos metabolitos. Por tanto, este trabajo se basó en estudiar e identificar los parámetros fisicoquímicos que tuvieron un mayor efecto sobre el crecimiento bacteriano y la síntesis de ácido láctico. Para lograr este objetivo, ocho variables fueron evaluadas en un modelo estadístico producido en erlenmeyer, con estos resultados se hallaron las condiciones óptimas que fueron evaluadas en un cultivo por lotes en biorreactor. La temperatura, la concentración de biotina y azúcar fueron las variables con mayor impacto (p and lt; 0,05) sobre el cultivo. Usando las condiciones óptimas, 36 °C; 6,1 mg/L de biotina y 50 g/L de glucosa, se obtuvo una max de 0,394 h-1, 16 g/L de ácido láctico a las 15 h del proceso con un rendimiento del 32%; observándose un mayor consumo de sustrato durante el crecimiento y poca disponibilidad para la fermentación, que sugiriendo una alimentación del cultivo al final de la fase exponencial que aumente los rendimientos de producción

Clinical recommendations for dry powder inhaler use in the management of COPD in primary care

Acknowledgements The study sponsor was the General Practitioners Research Institute; data collection and analysis were performed by General Practitioners Research Institute. Boehringer Ingelheim was the funding and scientific partner. The members of the PIFotal study group would like to acknowledge Dr. Jaco Voorham from Data to Insights Research Solutions for his assistance with the statistical analyses, Dr Wilma Zijlema for her assistance with the review, drafting and editing of the paper, and Dr. Hans Wouters for his contribution to the project administration in the initial phase of the project. They would also like to thank all contributing researchers: Maria João Barbosa, Ana Margarida Cruz, Liliana Silva, Duarte Araújo, Eurico Silva, Daniel Castro, João Ramires, Ana Fernandes, Catarina Carvalho, Raquel Castro, Jerzy Zientek, Ewa Pasko, Witold Drzastwa, Tomasz Kachel, Kornelia Ciekalska, Krzysztof Wytrychowski, Bernard Panaszek, Krzysztof Kowal, Ebian Brill, Willemien Feenstra, Geert Struik, Hans Schuurman, Mariette van Oostrum, Hennie Holwerda Meekma, Boudewijn Dierick, George Amofa, Esther Kuipers, Lennard Ringnalda, Boris Tyndall, Mark Drenth, Peter Mast, Hilbert Talsma, Raoul Wolfs, Cobie Hoogeboom, Hanneke van Andel, Paul Stoutenberg, Nancy van de Laak, Tessa Hillaert, Laura Holtzer, Natascha Fehrmann, Anniek Makkinga – Maassen van den Brink, Annemarie Hilbink, Erik Feenstra, Murat Tek, Sabrina Burer, Jan van Ginkel, Rinze Boersma, Alyssa Bonger, Miguel Roman Rodriguez, Marina García Pardo, Alejandra Valero Suau, Laura López Velasco, Cecilia Amato, Francisco Palmer Simó, Alberto Abenza, Rosa Llull Vila, Bartolomé Llompart Van Belzen, Silvia Jimeno Martínez, Francesc Moranta Ribas, Margarita Perelló Oliver, Yolanda Gómez López, Patricia Ibañez Gómez, María Nieves Mendieta Lagos, Laura Bueno López, Virginia María Mirabal Sánchez, Ana Delia Rodríguez Delgado, Nils Fischer, Alicia González Sansó, Nayra Ramírez Mendoza, Valeria Gazzaneo, Paula Merced Guillama Rodríguez, Virginia Naranjo Guerrero, Jose Angel Suarez Caballero, Isidoro Souto Bethencourt, Juan R. Dominguez Beatell, Elena Vanesa Rojas Manrique, Maria Jose Sanz Orejas, Cary Perez Lorenzo, Jesús Antonio Pérez Jiménez, Silvia 480 Lara Afonso Trujillo, Bartolomé Dominguez Del Río Boada, Stavroula Papageorgakopoulou, Eleytheria Vakouti, Claire Gkatzoudi, Thodoris Krasanakis, Dimitris Kounalakis , Izoldi Bouloukaki , Nikolaos Tsakountakis, Emmanouela Chronaki, Katherine Mary Borg and Kamila Abutalieva for their time and efforts to perform the study measurements and complete patient inclusion, even in the challenging times of the pandemic. Finally, they would like to thank the participants who generously gave their time to participate in the study.Peer reviewedPublisher PD

Sufficient inspiratory effort for a dry powder inhaler - do we have to measure it, or can we observe it? : Post hoc analysis of the PIFotal study.

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Factors associated with health status and exacerbations in COPD maintenance therapy with dry powder inhalers

Funding Information: J.K. reports grants, personal fees and non-financial support from AstraZeneca, GSK and Boehringer Ingelheim; grants and personal fees from Chiesi Pharmaceuticals and TEVA; grants from Mundipharma; personal fees from MSD and COVIS Pharma; and also holds 72.5% of shares in the General Practitioners Research Institute. H.W. has received grants from Boehringer Ingelheim, which is the financial and scientific partner of GPRI for the submitted study, and from AstraZeneca, Novartis and Chiesi for scientific projects in the area of COPD/asthma. S.B.-A. has received grants from TEVA, and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Sanofi and Mylan. J.C.d.S. reports or personal fees from AstraZeneca, Bial, Boehringer Ingelheim, GSK, Medinfar, Mundipharma and Sanofi. B.C. received honorarium from GSK and Sanofi. J.v.C., L.D., I.v.G.-P., I.v.d.H., Y.J., M.K., B.M., K.S., N.S., M.H., B.M. and M.T.L. were employed by General Practitioners Research Institute (GPRI) at the time of the study. In the past three years (2019–2021), GPRI conducted investigator- and sponsor-initiated research funded by non-commercial organizations, academic institutes, and pharmaceutical companies (including AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma, Novartis, and Teva). R.D. has received grants and personal fees from TEVA, Boehringer Ingelheim, AstraZeneca, GSK, Chiesi, Focus Care, and Glenmark. R.G. has received personal fees from AstraZeneca, GSK and Chiesi. E.D. holds 27.5% of shares in the General Practitioners Research Institute. M.G.P. receives grants from AstraZeneca, GSK and Boehringer Ingelheim. A.G. and A.d.l.H. are employees of Boehringer Ingelheim. F.L. received grants and personal fees from GSK, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini International, Novartis, Orion, and Trudell International, outside the submitted work. T.M. is an Assoicate Editor at npj Primary Care Respiratory Medicine. J.M. received grants from Boehringer Ingelheim, during the conduct of the study; and grants from AstraZeneca, Chiesi, Novartis, and GSK, outside the submitted work. D.P. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Theravance and Zentiva (Sanofi Generics); grants from the British Lung Foundation, Respiratory Effectiveness Group, UK National Health Service, and AKL Research and Development Ltd; personal fees from Cipla, GlaxoSmithKline, Kyorin, Merck, Mundipharma, Airway Vista Secretariat, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, and WebMD Global LLC; non-financial support from Efficacy and Mechanism Evaluation programme and Health Technology Assessment; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); and 5% shareholding in Timestamp, which develops adherence monitoring technology. M.R.-R. receives grants and personal fees from AstraZeneca and GSK; and personal fees from Boehringer Ingelheim, Chiesi, Menarini, Mundipharma, Novartis, Pfizer, TEVA and BIAL. I.T. reports grants and personal fees from GSK, AstraZeneca, Boehringer Ingelheim, Menarini, Novartis, Chiesi and Elpen. O.U. reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Edmond Pharma, Chiesi and GSK; grants from Edmond Pharma; and personal fees from Napp, Mundipharma, Sandoz, Takeda, Cipla, COVIS, Novartis, Mereobiopharma, Orion, and Menarini. S.B.-A. and T.M. are Associate Editors at npj Primary Care Respiratory Medicine, and I.T. is Editor in Chief. These authors were not involved in the journal’s review of, or decisions related to, this manuscript.Peer reviewedPublisher PD

Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Aim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

AimAmazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types.LocationAmazonia.TaxonAngiosperms (Magnoliids; Monocots; Eudicots).MethodsData for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny.ResultsIn the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types.Main ConclusionNumerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions

Geography and ecology shape the phylogenetic composition of Amazonian tree communities

Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran\u27s eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and várzea forest types, the phylogenetic composition varies by geographic region, but the igapó and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R$^{2}$ = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R$^{2}$ = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions