The bone-derived hormone fibroblast growth factor 23 (FGF23) functions in concert with parathyroid hormone (PTH) and the active vitamin D metabolite, 1,25(OH)
vitamin D (1,25D), to control phosphate ...and calcium homeostasis. A rise in circulating levels of phosphate and 1,25D leads to FGF23 production in bone. Circulating FGF23 acts on the kidney by binding to FGF receptors and the co-receptor α-Klotho to promote phosphaturia and reduce circulating 1,25D levels. Various other biomolecules that are produced by the kidney, including lipocalin-2, glycerol 3-phosphate, 1-acyl lysophosphatidic acid and erythropoietin, are involved in the regulation of mineral metabolism via effects on FGF23 synthesis in bone. Understanding of the molecular mechanisms that control FGF23 synthesis in the bone and its bioactivity in the kidney has led to the identification of potential targets for novel interventions. Emerging approaches to target aberrant phosphate metabolism include small molecule inhibitors that directly bind FGF23 and prevent its interactions with FGF receptors and α-Klotho, FGF23 peptide fragments that act as competitive inhibitors of intact FGF23 and small molecule inhibitors of kidney sodium-phosphate cotransporters.
Thematic Analysis Nowell, Lorelli S.; Norris, Jill M.; White, Deborah E. ...
International journal of qualitative methods,
12/2017, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
As qualitative research becomes increasingly recognized and valued, it is imperative that it is conducted in a rigorous and methodical manner to yield meaningful and useful results. To be accepted as ...trustworthy, qualitative researchers must demonstrate that data analysis has been conducted in a precise, consistent, and exhaustive manner through recording, systematizing, and disclosing the methods of analysis with enough detail to enable the reader to determine whether the process is credible. Although there are numerous examples of how to conduct qualitative research, few sophisticated tools are available to researchers for conducting a rigorous and relevant thematic analysis. The purpose of this article is to guide researchers using thematic analysis as a research method. We offer personal insights and practical examples, while exploring issues of rigor and trustworthiness. The process of conducting a thematic analysis is illustrated through the presentation of an auditable decision trail, guiding interpreting and representing textual data. We detail our step-by-step approach to exploring the effectiveness of strategic clinical networks in Alberta, Canada, in our mixed methods case study. This article contributes a purposeful approach to thematic analysis in order to systematize and increase the traceability and verification of the analysis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these ...patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants.
In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related ...terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
•Listening effort modulates attention, memory, and hierarchical linguistic computation.•Listening effort is driven by a voluntary, motivation-based attention system.•Use of subjective mental effort ...questionnaires in neuroimaging contexts is valid.•fNIRS is an appropriate technique for imaging neural substrates of listening effort.
Everyday challenges impact our ability to hear and comprehend spoken language with ease, such as accented speech (source factors), spectral degradation (transmission factors), complex or unfamiliar language use (message factors), and predictability (context factors). Auditory degradation and linguistic complexity in the brain and behavior have been well investigated, and several computational models have emerged. The work here provides a novel test of the hypotheses that listening effort is partially reliant on higher cognitive auditory attention and working memory mechanisms in the frontal lobe, and partially reliant on hierarchical linguistic computation in the brain's left hemisphere. We specifically hypothesize that these models are robust and can be applied in ecologically relevant and coarse-grain contexts that rigorously control for acoustic and linguistic listening challenges. Using functional near-infrared spectroscopy during an auditory plausibility judgment task, we show the hierarchical cortical organization for listening effort in the frontal and left temporal-parietal brain regions. In response to increasing levels of cognitive demand, we found (i) poorer comprehension, (ii) slower reaction times, (iii) increasing levels of perceived mental effort, (iv) increasing levels of brain activity in the prefrontal cortex, (v) hierarchical modulation of core language processing regions that reflect increasingly higher-order auditory-linguistic processing, and (vi) a correlation between participants’ mental effort ratings and their performance on the task. Our results demonstrate that listening effort is partly reliant on higher cognitive auditory attention and working memory mechanisms in the frontal lobe and partly reliant on hierarchical linguistic computation in the brain's left hemisphere. Further, listening effort is driven by a voluntary, motivation-based attention system for which our results validate the use of a single-item post-task questionnaire for measuring perceived levels of mental effort and predicting listening performance. We anticipate our study to be a starting point for more sophisticated models of listening effort and even cognitive neuroplasticity in hearing aid and cochlear implant users.
Alkali-activated materials are a new class of sustainable materials that can help supplant highly CO2-intensive ordinary Portland cement (OPC). Chemical admixtures and additives that manipulate the ...hydration and setting of OPC are readily utilized in the construction industry. However, for alkali-activated materials, the impact of these additives on the evolution of the atomic structure of the binder gel is largely unknown. Here, we utilize nano-ZnO (nanoparticles of zinc oxide), a known retarder for OPC hydration, and investigate its influence on the alkali-activation reaction in high and low calcium alkali-activated materials (slag and metakaolin systems, respectively). Using isothermal calorimetry and in situ X-ray pair distribution function analysis, the mechanism of nano-ZnO retardation in alkali-activated materials is uncovered, revealing that calcium plays a pivotal role in dictating whether nano-ZnO has an impact on the alkali-activation reaction. These results also provide important insight on the ability of slag and metakaolin-based alkali-activated materials to effectively immobilize zinc within the binder gel, which is of relevance to the waste solidification/stabilization community.
Range expansions are limited by two key factors. These are (1) dispersal, which includes a species’ intrinsic mobility, geographical barriers, and their interaction; and (2) the ability of a species ...to persist beyond its current range. I evaluate the role of these in affecting bird species distributions across the Himalayas, under a hypothesis that many species have recently expanded their range out of an eastern Pleistocene refuge. I measured wing shape as a proxy for dispersal ability and topographic complexity across the Himalayas as a proxy for dispersal barriers. As a factor affecting the potential for persistence in novel locations, I compared similarity of a species’ climatic envelope in the east, the hypothesized historical refuge, and the west, the location of recent colonization. Climatic similarity, wing shape, and the interaction of topographic complexity with wing shape all contribute significantly to the range extent of a given species. The result highlights the important interaction between morphological and landscape factors in affecting successful range expansions. The two dispersal-related parameters together explain two times the variance explained by climate, but I present additional evidence that other factors besides climate—notably biotic interactions—affect the ability of a species to persist beyond its range.
Divided into three sections, this volume firstly seeks to explore social contexts of educational leadership. The second section explores the experiences of educational leaders in various contexts, ...while the third section of this volume looks at the consequences, unintended and otherwise, of the neoliberal commodification of education.
Although multiple studies have assessed molecular changes in chronic atopic dermatitis (AD) lesions, little is known about the transition from acute to chronic disease stages, and the factors and ...mechanisms that shape chronic inflammatory activity.
We sought to assess the global transcriptome changes that characterize the progression from acute to chronic stages of AD.
We analyzed transcriptome changes in paired nonlesional skin, acute and chronic AD lesions from 11 patients and 38 healthy controls by RNA-sequencing, and conducted in vivo and histological assays to evaluate findings.
Our data demonstrate that approximately 74% of the genes dysregulated in acute lesions remain or are further dysregulated in chronic lesions, whereas only 34% of the genes dysregulated in chronic lesions are altered already in the acute stage. Nonlesional AD skin exhibited enrichment of TNF, TH1, TH2, and TH17 response genes. Acute lesions showed marked dendritic-cell signatures and a prominent enrichment of TH1, TH2, and TH17 responses, along with increased IL-36 and thymic stromal lymphopoietin expression, which were further heightened in chronic lesions. In addition, genes involved in skin barrier repair, keratinocyte proliferation, wound healing, and negative regulation of T-cell activation showed a significant dysregulation in the chronic versus acute comparison. Furthermore, our data show progressive changes in vasculature and maturation of dendritic-cell subsets with chronicity, with FOXK1 acting as immune regulator.
Our results show that the changes accompanying the transition from nonlesional to acute to chronic inflammation in AD are quantitative rather than qualitative, with chronic AD having heightened TH2, TH1, TH17, and IL36 responses and skin barrier repair mechanisms. These findings provide novel insights and highlight underappreciated pathways in AD pathogenesis that may be amenable to therapeutic targeting.
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