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1.
Hepatology ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38768260

RESUMEN

BACKGROUND AND AIMS: No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. APPROACH AND RESULTS: This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. CONCLUSIONS: Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

2.
Bioorg Chem ; 147: 107365, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636436

RESUMEN

Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs, and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS.


Asunto(s)
Alquinos , Astrocitos , Neuronas Motoras , Prenilación de Proteína , Astrocitos/metabolismo , Astrocitos/citología , Animales , Alquinos/química , Alquinos/síntesis química , Neuronas Motoras/metabolismo , Neuronas Motoras/citología , Terpenos/química , Terpenos/síntesis química , Terpenos/metabolismo , Ratones , Estructura Molecular , Células Cultivadas
3.
Hum Genet ; 142(8): 1293-1302, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37004545

RESUMEN

Aging is a progressive multifaceted functional decline of a biological system. Chronic age-related conditions such as neurodegenerative diseases are leading causes of death worldwide, and they are becoming a pressing problem for our society. To address this global challenge, there is a need for novel, safe, and effective rejuvenation therapies aimed at reversing age-related phenotypes and improving human health. With gene expression being a key determinant of cell identity and function, and in light of recent studies reporting rejuvenation effects through genetic perturbations, we propose an age reversal strategy focused on reprogramming the cell transcriptome to a youthful state. To this end, we suggest using transcriptomic data from primary human cells to predict rejuvenation targets and develop high-throughput aging assays, which can be used in large perturbation screens. We propose neural cells as particularly relevant targets for rejuvenation due to substantial impact of neurodegeneration on human frailty. Of all cell types in the brain, we argue that glutamatergic neurons, neuronal stem cells, and oligodendrocytes represent the most impactful and tractable targets. Lastly, we provide experimental designs for anti-aging reprogramming screens that will likely enable the development of neuronal age reversal therapies, which hold promise for dramatically improving human health.


Asunto(s)
Reprogramación Celular , Transcriptoma , Humanos , Reprogramación Celular/genética , Envejecimiento/genética , Células Madre , Neuronas
4.
New Phytol ; 240(2): 529-541, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37491742

RESUMEN

Evidence for secondary growth extends into the Early Devonian, 407 million years ago, raising questions about tempo and mode of origination of this key developmental feature. To address such questions, we analyze anatomy in the four oldest fossil plants with well-characterized woody tissues; one of these represents a new genus, described here formally. The new fossil is documented using the cellulose acetate peel technique and associated methods. We use the paradigm of structural fingerprints to identify developmental components of cambial growth based on fossil anatomy. We integrate developmental inferences within a theoretical framework of modular regulation of secondary growth. The fossils possess structural fingerprints consistent with four different combinations of regulatory mechanisms (modules) acting in cambial growth, representing four distinct modes of secondary growth. The different modes of secondary growth demonstrate that cambial growth is an assemblage of regulatory modules whose deployment followed a mosaic pattern across woody plants, which may represent ancestors of younger lineages that exhibit woody growth. The diverse modes of wood development occupy a wide morphospace in the anatomy of wood in the Early Devonian, suggesting that the origins of secondary growth and of its modular components pre-date this interval.


Asunto(s)
Evolución Biológica , Madera , Cámbium , Plantas , Fósiles
5.
New Phytol ; 239(1): 388-398, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37010090

RESUMEN

We analyze the oldest fossil occurrences of wound-response periderm to characterize the development of wound responses in early tracheophytes. The origin of periderm production by a cambium (phellogen), an innovation with key roles in protection of inner plant tissues, is poorly explored; understanding periderm development in early tracheophytes can illuminate key aspects of this process. Anatomy of wound-response tissues is characterized in serial sections in a new Early Devonian (Emsian; c. 400 Ma) euphyllophyte from Quebec (Canada) - Nebuloxyla mikmaqiana sp. nov. - and compared to previously described euphyllophyte periderm from the same fossil locality to reconstruct periderm development. Characterizing development in these oldest periderm occurrences allows us to propose a model for the development of wound-response periderm in early tracheophytes: by phellogen activity that is poorly coordinated laterally but bifacial, producing secondary tissues initially outwardly and subsequently inwardly. The earliest occurrences of wound periderm pre-date the oldest known periderm produced systemically as a regular ontogenetic stage (canonical periderm), suggesting that periderm evolved initially as a wound-response mechanism. We hypothesize that canonical periderm evolved by exaptation of this wound sealing mechanism, whose deployment was triggered by tangential tensional stresses induced in the superficial tissues by vascular cambial growth from within.


Asunto(s)
Tracheophyta , Cámbium , Quebec , Canadá , Fósiles
6.
New Phytol ; 240(5): 2137-2150, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37697646

RESUMEN

Divergence times based on molecular clock analyses often differ from those derived from total-evidence dating (TED) approaches. For bryophytes, fossils have been excluded from previous assessments of divergence times, and thus, their utility in dating analyses remains unexplored. Here, we conduct the first TED analyses of the complex thalloid liverworts (Marchantiopsida) that include fossils and evaluate macroevolutionary trends in morphological 'diversity' (disparity) and rates. Phylogenetic analyses were performed on a combined dataset of 130 discrete characters and 11 molecular markers (sampled from nuclear, plastid and mitochondrial genomes). Taxon sampling spanned 56 extant species - representing all the orders within Marchantiophyta and extant genera within Marchantiales - and eight fossil taxa. Total-evidence dating analyses support the radiation of Marchantiopsida during Late Silurian-Early Devonian (or Middle Ordovician when the outgroup is excluded) and that of Ricciaceae in the Middle Jurassic. Morphological change rate was high early in the history of the group, but it barely increased after Late Cretaceous. Disparity-through-time analyses support a fast increase in diversity until the Middle Triassic (c. 250 Ma), after which phenotypic evolution slows down considerably. Incorporating fossils in analyses challenges previous assumptions on the affinities of extinct taxa and indicates that complex thalloid liverworts radiated c. 125 Ma earlier than previously inferred.


Asunto(s)
Briófitas , Hepatophyta , Filogenia , Hepatophyta/genética , Fósiles , Plastidios/genética , Evolución Biológica
7.
Plant Physiol ; 190(1): 85-99, 2022 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-35904762

RESUMEN

The evolution of transporting tissues was an important innovation in terrestrial plants that allowed them to adapt to almost all nonaquatic environments. These tissues consist of water-conducting cells and food-conducting cells and bridge plant-soil and plant-air interfaces over long distances. The largest group of land plants, representing about 95% of all known plant species, is associated with morphologically complex transporting tissue in plants with a range of additional traits. Therefore, this entire clade was named tracheophytes, or vascular plants. However, some nonvascular plants possess conductive tissues that closely resemble vascular tissue in their organization, structure, and function. Recent molecular studies also point to a highly conserved toolbox of molecular regulators for transporting tissues. Here, we reflect on the distinguishing features of conductive and vascular tissues and their evolutionary history. Rather than sudden emergence of complex, vascular tissues, plant transporting tissues likely evolved gradually, building on pre-existing developmental mechanisms and genetic components. Improved knowledge of the intimate structure and developmental regulation of transporting tissues across the entire taxonomic breadth of extant plant lineages, combined with more comprehensive documentation of the fossil record of transporting tissues, is required for a full understanding of the evolutionary trajectory of transporting tissues.


Asunto(s)
Embryophyta , Evolución Biológica , Embryophyta/genética , Evolución Molecular , Fósiles , Filogenia , Plantas/genética
8.
Am J Bot ; 110(1): e16082, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36219504

RESUMEN

PREMISE: Trimerophytes are a plexus of early tracheophytes that form the base of the euphyllophyte clade and, thus, represent the link between the earliest land plants and modern-day ferns, sphenophytes, and seed plants. As the best-characterized trimerophyte, the genus Psilophyton occupies a key position in the euphyllophyte fossil record. We describe a new Psilophyton species that has implications for the evolution of plant-animal interactions. METHODS: The fossil material is preserved by permineralization in the Lower Devonian (Emsian) Battery Point Formation (Québec, Canada) and was studied in serial sections using the cellulose acetate peel technique. RESULTS: Psilophyton diakanthon sp. nov. differs from other Psilophyton species in possessing fibers that form a discontinuous layer in the inner cortex and two distinct types of spinescent emergences whose anatomy and morphology are consistent with roles in anti-herbivore defense. CONCLUSIONS: Psilophyton diakanthon adds another species to an already diverse genus. Its two morphologically distinct types of spinescence suggest that herbivory was rampant in plant-animal interactions and demonstrate that anti-herbivory defenses had reached a previously unrecognized level of sophistication by 400 million years ago, in the Early Devonian.


Asunto(s)
Embryophyta , Helechos , Quebec , Plantas , Canadá , Fósiles , Evolución Biológica
9.
J Exp Bot ; 73(13): 4273-4290, 2022 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-35394022

RESUMEN

Systematics reconstructs tempo and mode in biological evolution by resolving the phylogenetic fabric of biodiversity. The staggering duration and complexity of evolution, coupled with loss of information (extinction), render exhaustive reconstruction of the evolutionary history of life unattainable. Instead, we sample its products-phenotypes and genotypes-to generate phylogenetic hypotheses, which we sequentially reassess and update against new data. Current consensus in evolutionary biology emphasizes fossil integration in total-evidence analyses, requiring in-depth understanding of fossils-age, phenotypes, and systematic affinities-and a detailed morphological framework uniting fossil and extant taxa. Bryophytes present a special case: deep evolutionary history but sparse fossil record and phenotypic diversity encompassing small dimensional scales. We review how these peculiarities shape fossil inclusion in bryophyte systematics. Paucity of the bryophyte fossil record, driven primarily by phenotypic (small plant size) and ecological constraints (patchy substrate-hugging populations), and incomplete exploration, results in many morphologically isolated, taxonomically ambiguous fossil taxa. Nevertheless, instances of exquisite preservation and pioneering studies demonstrate the feasibility of including bryophyte fossils in evolutionary inference. Further progress will arise from developing extensive morphological matrices for bryophytes, continued exploration of the fossil record, re-evaluation of previously described fossils, and training specialists in identification and characterization of bryophyte fossils, and in bryophyte morphology.


Asunto(s)
Briófitas , Fósiles , Biodiversidad , Evolución Biológica , Briófitas/genética , Filogenia
10.
Ann Bot ; 130(6): 785-798, 2022 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-35724420

RESUMEN

BACKGROUND AND AIMS: The Early Devonian (Emsian, 400-395 Ma) tracheophyte Leptocentroxyla tetrarcha Bickner et Tomescu emend. Tomescu et McQueen combines plesiomorphic Psilophyton-type tracheid thickenings with xylem architecture intermediate between the plesiomorphic basal euphyllophyte haplosteles and the complex actinosteles of Middle Devonian euphyllophytes. We document xylem development in Leptocentroxyla based on anatomy and explore its implications, which may provide a window into the evolution of pith. METHODS: Leptocentroxyla is preserved by permineralization in the Battery Point Formation (Quebec, Canada). Serial sections obtained using the cellulose acetate peel technique document branching pattern, anatomy of trace divergence to appendages, protoxylem architecture, and variations in tracheid size and wall thickening patterns. KEY RESULTS: Leptocentroxyla has opposite decussate pseudo-whorled branching and mesarch protoxylem, and represents the earliest instance of central histological differentiation in a euphyllophyte actinostele. Tracheids at the centre of xylem exhibit simplified Psilophyton-type wall thickenings and are similar in size (at the axis centre) or smaller than the surrounding metaxylem tracheids (at the centre of appendage traces). CONCLUSIONS: The position and developmental attributes of the simplified Psilophyton-type tracheids suggest they may have been generated by the protoxylem developmental pathway. This supports the delayed and shortened protoxylem differentiation hypothesis, which explains the evolution of pith by (1) delay in the onset of differentiation and lengthening of cell growth duration in a central protoxylem strand; and (2) shortening of the interval of differentiation of those tracheids, leading to progressive simplification (and eventual loss) of secondary wall thickenings, and replacement of tracheids with a central parenchymatous area. NAC domain transcription factors and their interactions with abscisic acid may have provided the regulatory substrate for the developmental changes that led to the evolution of pith. These could have been orchestrated by selective pressures associated with the expansion of early vascular plants into water-stresses upland environments.


Asunto(s)
Ácido Abscísico , Xilema , Xilema/anatomía & histología , Quebec
11.
New Phytol ; 232(2): 914-927, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34031894

RESUMEN

An abrupt transition in the fossil record separates Early Devonian euphyllophytes with a simple structure from a broad diversity of structurally complex Middle-Late Devonian plants. Morphological evolution and phylogeny across this transition are poorly understood due to incomplete sampling of the fossil record. We document a new Early Devonian radiatopsid and integrate it in analyses addressing euphyllophyte relationships. Anatomically preserved Emsian fossils (402-394 Ma) from the Battery Point Formation (Gaspé, Quebec, Canada) are studied in serial sections. The phylogenetic analysis is based on a matrix of 31 taxa and 50 characters emphasising vegetative morphology (41 discrete, nine continuous). The new plant, Kenrickia bivena gen. et sp. nov., is one of very few structurally complex euphyllophytes documented in the Early Devonian. Inclusion of Kenrickia overturns previously established phylogenetic relationships among Radiatopses, reiterating the need for increased density of Early Devonian taxon sampling. Kenrickia is recovered as the sister lineage to all other radiatopsids, a clade in which paraphyletic Stenokoleales led to a lignophyte clade where archaeopterids and seed plants fall into sister clades. Our results shed light on early euphyllophyte relationships and evolution, indicating early exploration of structural complexity by multiple lineages and reiterating the potential of a single origin of secondary growth in euphyllophytes.


Asunto(s)
Fósiles , Tracheophyta , Evolución Biológica , Filogenia , Plantas , Semillas
12.
Am J Bot ; 108(10): 2066-2095, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34664712

RESUMEN

PREMISE: Cladoxylopsids formed Earth's earliest forests and gave rise to the ancestors of sphenopsids and ferns. Lower Devonian (Emsian) strata of the Battery Point Formation (Quebec, Canada) contain new anatomically preserved cladoxylopsids, one of which is described in this article. To assess the phylogenetic position of this fossil and address questions of cladoxylopsid phylogeny, we conducted a comprehensive phylogenetic study. METHODS: Permineralized axes were studied in serial sections using the cellulose acetate peel technique. We evaluated phylogenetic relationships among cladoxylopsids using a data set of 36 new morphological characters and 31 species, in parsimony-constrained analyses. RESULTS: We describe Adelocladoxis praecox gen. et sp. nov., a cladoxylopsid with small actinostelic axes bearing dichotomously branched, helically arranged ultimate appendages and fusiform sporangia. Adelocladoxis provides the oldest evidence of cladoxylopsid anatomy, including ultimate appendages and sporangia. In agreement with non-phylogenetic classification schemes, our phylogenetic analysis resolves a basal grade of iridopterids and a clade of cladoxylopsids s.s., which includes a pseudosporochnalean cladoxylopsid clade, a cladoxylalean cladoxylopsid clade, and Adelocladoxis. CONCLUSIONS: Our phylogenetic analysis illuminates aspects of tempo and mode of evolution in the cladoxylopsid plexus. Originating prior to the Emsian, cladoxylopsids reached global distribution by the Frasnian. Iridopterids and cladoxylopsids s.s. radiated in the Emsian-Eifelian. The sequence of character change recovered by our phylogeny supports a transition from actinostelic protosteles to dissected steles, associated with an increase in xylem rib number and medullation generating a central parenchymatous area.


Asunto(s)
Helechos , Fósiles , Evolución Biológica , Filogenia , Quebec , Esporangios
13.
Tetrahedron Lett ; 672021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-34054152

RESUMEN

This report describes the direct synthesis of dihydro-pyrrolo-pyrazole heterocycles from allylic azides and methyl vinyl sulfone. The product results from a complex cascade reaction that is operationally straightforward, with aromatization being the result of a concomitant elimination step. A variety of azides could participate in this reaction (12 examples) and the isolated yields of the desired product ranged from 51%-72%. Lastly the ethylene sulfone group could be removed by heating the product in pyrrolidine.

14.
Sensors (Basel) ; 21(23)2021 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-34883950

RESUMEN

Smartphone accelerometers and low-cost Global Navigation Satellite System (GNSS) equipment have faced rapid and important advancement, opening a new door to deformation monitoring applications such as landslide, plate tectonics and structural health monitoring (SHM). The precision potential and operational feasibility of the equipment play an important role in the decision making of campaigning for affordable solutions. This paper focuses on the evaluation of the empirical precision, including (auto)time correlation, of a common smartphone accelerometer (Bosch BMI160) and a low-cost dual frequency GNSS reference-rover pair (u-blox ZED-F9P) set to operate at high rates (50 and 5 Hz, respectively). Additionally, a high-rate (5 Hz) GPS-only baseline-based multipath (MP) correction is proposed for effectively removing a large part of this error and allowing to correctly determine the instrumental noise of the GNSS sensor. Furthermore, the benefit of smartphone-based validation for the tracking of dynamic displacements is addressed. The estimated East-North-Up (ENU) precision values (σ^) of ±7.7, 8.1 and 9.6 mms2 are comparable with the declared precision potential (σ) of the smartphone accelerometer of ±8.8mms2. Furthermore, the acceleration noise shows only mild traces of (auto)correlation. The MP-corrected 3D (ENU) empirical precision values of ±2.6, 3.6 and 6.7 mm were found to be better by 30-40% than the straight-out-of box precision of the GNSS sensor, attesting the usefulness of the MP correction. The GNSS sensors output position information with time correlation of typically tens of seconds. The results indicate exceptional precision potential of these low-power-consuming, small-scale, affordable sensors set to operate at a high-rate over small regions. The smartphone-based dynamic displacement validation shows that GNSS data of a low-cost sensor at a 5 Hz sampling rate can be successfully used for tracking dynamic processes.


Asunto(s)
Aceleración , Teléfono Inteligente , Acelerometría , Recolección de Datos
15.
Breast Cancer Res Treat ; 179(3): 671-676, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31754951

RESUMEN

PURPOSE: Magnetic Occult Lesion Localization Instrument (MOLLI) is a wireless, non-radioactive alternative for non-palpable breast lesion localization. The primary objective of this first-in-human study was to evaluate the clinical feasibility of using MOLLI for intraoperative localization of non-palpable breast lesions. METHODS: Twenty women with non-palpable breast lesions at a single institution received a lumpectomy using the MOLLI guidance system. Patients were co-localized with magnetic and radioactive markers up to 7 days before excision by a dedicated breast radiologist under sonographic guidance. Both markers were localized intraoperatively using dedicated hand-held probes. The primary outcome was successful excision of the magnetic marker, confirmed radiographically and pathologically. Demographic data, margin positivity, and re-excision rates were collected. Surgical oncologists, radiologists, and pathology staff were surveyed for user satisfaction. RESULTS: Post-radiological analysis: Post-implant mammograms verified that 17/20 markers were placed directly in the lesion center. Radiologists reported that all marker implantations procedures were "easy" or "very easy" following a single training session. Post-surgical analysis: All MOLLI markers were successfully removed with the specimen during surgical excision. In all cases, surgeons ranked the MOLLI guidance system as "very easy" for lesion localization. Pathologic analysis: All patients had negative margins. All anatomic pathology staff ranked the MOLLI system as "very easy" to localize markers. CONCLUSIONS: The MOLLI guidance system is a reliable and accurate method for intraoperative localization of non-palpable breast lesions. Further evaluation of the MOLLI system in studies against current standards of care is required to demonstrate system cost-effectiveness and improved patient-reported outcomes.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Diagnóstico por Imagen/métodos , Anciano , Neoplasias de la Mama/etiología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamografía , Mastectomía Segmentaria , Persona de Mediana Edad , Estadificación de Neoplasias , Radiografía/métodos , Resultado del Tratamiento , Carga Tumoral
16.
Health Res Policy Syst ; 18(1): 102, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32933555

RESUMEN

BACKGROUND: Irrational prescribing has received increasing attention among policy-makers to improve drug safety and effectiveness while avoiding economic waste. The policies intended to rationalise prescribing have been grouped by WHO under a taxonomy, classifying them into two types of strategies - (1) targeted approaches (micro level) and (2) system-oriented approaches (macro level). The extent to which countries implement strategies and the existing types is currently unknown. This paper explores the following research question via expert opinions: to what extent have European countries implemented strategies to support rational prescribing (targeted and system oriented) and what are the types implemented? METHODS: We assessed the available information on policies intended to promote rational prescribing. We used the WHO taxonomy to explore our research question as the basis for a standardised questionnaire. The data were collected between August 2018 and April 2019. The questionnaire consisted of questions that solicited the opinion of experts on the implementation of prescribing control mechanisms in primary care in their respective countries. Experts were identified through the literature and relevant networks. The questionnaire was sent to 17 identified country experts from 17 different countries; 15 responded and 13 were used in our analysis. Answers were validated through follow-up correspondence, interviews and presentation at an OECD meeting. RESULTS: Expert-reported data shows that all 13 countries included in our study have several mechanisms in place for enhancing rational prescribing in primary care. All approaches were reported to have been implemented in at least two countries. We identified two groups of countries, namely a small group of countries (n = 3) with fewer mechanisms in place and a larger group of countries (n = 10) with a large number of strategies with accompanying instruments at both the micro and macro levels. CONCLUSIONS: The data reported by the experts suggests that all 13 countries included in our study have several mechanisms in place for enhancing rational prescribing in primary care on both the micro and macro levels. With respect to the extent of mechanisms being in place, two groups of countries were identified. This initial mapping of strategies forms a basis for more in-depth research to be able to assess the impact of bundles of strategies on system and targeted level on rational drug prescribing in primary care in Europe.


Asunto(s)
Prescripciones de Medicamentos , Atención Primaria de Salud , Personal Administrativo , Atención a la Salud , Europa (Continente) , Humanos
17.
New Phytol ; 222(4): 1719-1735, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30552764

RESUMEN

Secondary growth from a vascular cambium, present today only in seed plants and isoetalean lycophytes, has a 400-million-yr evolutionary history that involves considerably broader taxonomic diversity, most of it hidden in the fossil record. Approaching vascular cambial growth as a complex developmental process, we review data from living plants and fossils that reveal diverse modes of secondary growth. These are consistent with a modular nature of secondary growth, when considered as a tracheophyte-wide structural feature. This modular perspective identifies putative constituent developmental modules of cambial growth, for which we review developmental anatomy and regulation. Based on these data, we propose a hypothesis that explains the sources of diversity of secondary growth, considered across the entire tracheophyte clade, and opens up new avenues for exploring the origin of secondary growth. In this hypothesis, various modes of secondary growth reflect a mosaic pattern of expression of different developmental-regulatory modules among different lineages. We outline an approach that queries three information systems (living seed plants, living seed-free plants, and fossils) and integrates data on developmental regulation, anatomy, gene evolution and phylogeny to test the mosaic modularity hypothesis and its implications, and to inform efforts aimed at understanding the evolution of secondary growth.


Asunto(s)
Evolución Biológica , Cámbium/crecimiento & desarrollo , Modelos Biológicos , Haz Vascular de Plantas/crecimiento & desarrollo , Meristema/crecimiento & desarrollo
19.
Ann Bot ; 121(7): 1275-1286, 2018 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-29444206

RESUMEN

Background and Aims: Widespread and diverse in modern ecosystems, mosses are rare in the fossil record, especially in pre-Cenozoic rocks. Furthermore, most pre-Cenozoic mosses are known from compression fossils, which lack detailed anatomical information. When preserved, anatomy significantly improves resolution in the systematic placement of fossils. Lower Cretaceous (Valanginian) deposits on Vancouver Island (British Columbia, Canada) contain a diverse anatomically preserved flora including numerous bryophytes, many of which have yet to be characterized. Among them is the grimmiaceous moss described here. Methods: One fossil moss gametophyte preserved in a carbonate concretion was studied in serial sections prepared using the cellulose acetate peel technique. Key Results: Tricarinella crassiphylla gen. et sp. nov. is a moss with tristichous phyllotaxis and strongly keeled leaves. The combination of an acrocarpous condition (inferred based on a series of morphological features), a central conducting strand, a homogeneous leaf costa and a lamina with bistratose portions and sinuous cells, and multicellular gemmae, supports placement of Tricarinella in family Grimmiaceae. Tricarinella is similar to Grimmia, a genus that exhibits broad morphological variability. However, tristichous phyllotaxis and especially the lamina, bistratose at the base but not in distal portions of the leaf, set Tricarinella apart as a distinct genus. Conclusions: Tricarinella crassiphylla marks the oldest record for both family Grimmiaceae and sub-class Dicranidae, providing a hard minimum age (136 million years) for these groups. The fact that this fossil could be placed in an extant family, despite a diminutive size, emphasizes the considerable resolving power of anatomically preserved bryophyte fossils, even when recovered from allochthonous assemblages of marine sediments, such as the Apple Bay flora. Discovery of Tricarinella re-emphasizes the importance of paleobotanical studies as the only approach allowing access to a significant segment of biodiversity, the extinct biodiversity, which is unattainable by other means of investigation.


Asunto(s)
Briófitas , Fósiles , Colombia Británica , Briófitas/anatomía & histología , Briófitas/clasificación , Briófitas/ultraestructura , Fósiles/anatomía & histología , Fósiles/ultraestructura , Células Germinativas de las Plantas/ultraestructura , Historia Antigua , Hojas de la Planta/anatomía & histología , Hojas de la Planta/ultraestructura
20.
Am J Bot ; 105(7): 1212-1223, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30075048

RESUMEN

PREMISE OF THE STUDY: Euphyllophytes, a clade including living ferns, horsetails, and seed plants, have a rich fossil record going back to the Early Devonian. The euphyllophyte spore wall has a complex structure, the evolutionary origins of which are incompletely understood. Psilophyton is the best-characterized basal euphyllophyte genus; thus, data on this genus can inform current hypotheses on spore wall structure and development, which propose a bilayered spore wall organization of combined spore and sporangial origin for the ancestral euphyllophyte. METHODS: We employed cellulose acetate peel sectioning of permineralized Lower Devonian (Emsian) Psilophyton dawsonii sporangia, combined with electron microscopy, to document spore wall structure and development. KEY RESULTS: The Psilophyton dawsonii spore wall is bilayered. The inner spore wall is homogeneous, probably of lamellar construction. The outer spore wall, loosely attached to the inner wall, covers distal and equatorial spore areas, and has a foveolate base layer upon which stacks of sporopollenin lumps accrete centrifugally, forming the scaffolding for the final apiculate ornamentation. CONCLUSIONS: This is the most complete account on spore wall structure, allowing developmental interpretations, in a basal euphyllophyte. The bipartite organization of the Psilophyton dawsonii spore wall reflects development as a result of two processes: an inner layer laid down by the spore cell and an outer layer of tapetal origin. Providing direct evidence on the spore wall of a basal euphyllophyte, these data confirm previous hypotheses and mark an empirically supported starting point for discussions of the evolution of spore wall development in euphyllophytes.


Asunto(s)
Helechos/ultraestructura , Fósiles/ultraestructura , Esporangios/ultraestructura , Pared Celular/ultraestructura , Microscopía Electrónica , Quebec
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