Geotourism spans a range of visitor interests, from the specialist geotourist to the more general visitor. As well as supporting geoconservation outcomes, it provides economic, cultural, relational ...and social benefits for both visitors and host communities. The interconnections between geoheritage and the cultural components of the landscape have antecedents in concepts of landscape aesthetics in different cultures. These interconnections provide a range of opportunities for enhancing the geotourist experience and promoting geoconservation and geoeducation by means of activities that involve aesthetic and emotional experiences and interpretation through different cultural filters that encourage the rediscovery of a sense of wonder both about the geological stories in the landscape and the human interactions. A cultural ecosystem services framework provides a holistic approach for informing conservation policy, management and planning for geotourism, enabling assessment of multiple benefits and trade-offs for visitors and communities based on the values of the geoheritage assets. Geotourism studies could also benefit from integration of existing theory, conceptual analysis and practice from broader heritage and nature-based tourism and closer collaboration with relevant social sciences. Adhering to sound geoethical practice is an essential part of geotourism, which can also play a role in the promotion of geoethics among the public and professionals.
Geodiversity—the variability of Earth's surface materials, forms, and physical processes—is an integral part of nature and crucial for sustaining ecosystems and their services. It provides the ...substrates, landform mosaics, and dynamic physical processes for habitat development and maintenance. By determining the heterogeneity of the physical environment in conjunction with climate interactions, geodiversity has a crucial influence on biodiversity across a wide range of scales. From a literature review, we identified the diverse values of geodiversity; examined examples of the dependencies of biodiversity on geodiversity at a site-specific scale (for geosites <1 km2 in area); and evaluated various human-induced threats to geosites and geodiversity. We found that geosites are important to biodiversity because they often support rare or unique biota adapted to distinctive environmental conditions or create a diversity of microenvironments that enhance species richness. Conservation of geodiversity in the face of a range of threats is critical both for effective management of nature's stage and for its own particular values. This requires approaches to nature conservation that integrate climate, biodiversity, and geodiversity at all spatial scales. La geodiversidad—la variabilidad de materiales, formas y procesos físicos de la superficie terrestre—es una parte integral de la naturaleza y es crucial para mantener a los ecosistemas y a sus servicios. Proporciona los sustratos, los mosaicos de accidentes geográficos y los procesos físicos dinámicos para el desarrollo y mantenimiento de los hábitats. Al determinar la heterogeneidad del ambiente físico en conjunto con las interacciones del clima, la geodiversidad ha sido una influencia importante sobre la biodiversidad a través de una gama amplia de escalas. A partir de una revisión bibliográfica, identificamos los valores diversos de la geodiversidad; examinamos ejemplos de las dependencias de la biodiversidad hacia la geodiversidad en una escala específica de sitio (para geositios < 1 Km2 de área); y evaluamos varias amenazas inducidas por humanos para los geositios y la geodiversidad. Encontramos que los geositios son importantes para la biodiversidad ya que generalmente mantienen una biota rara o única, la cual está adaptada a condiciones ambientales características o la cual crea una diversidad de microambientes que mejoran la riqueza de especies. La conservación de la geodiversidad de cara a una gama de amenazas es crítica tanto para el manejo efectivo del estado de la naturaleza como para sus propios valores particulares. Esto requiere de enfoques para la conservación de la naturaleza que integran al clima, a la biodiversidad y a la geodiversidad en todas las escalas espaciales.
The programmed cell death 1 (PD-1) surface receptor binds to two ligands, PD-L1 and PD-L2. Studies have shown that PD-1-PD-L interactions control the induction and maintenance of peripheral T cell ...tolerance and indicate a previously unknown function for PD-L1 on nonhematopoietic cells in protecting tissues from autoimmune attack. PD-1 and its ligands have also been exploited by a variety of microorganisms to attenuate antimicrobial immunity and facilitate chronic infection. Here we examine the functions of PD-1 and its ligands in regulating antimicrobial and self-reactive T cell responses and discuss the therapeutic potential of manipulating this pathway.
•As of May 27, 2020 there are over 1,678,843 confirmed cases of COVID-19 claiming more than 100,000 lives in the Unites States. Currently there is no known effective therapy or vaccine.•According to ...a protocol-based treatment algorithm, among hospitalized patients, use of hydroxychloroquine alone and in combination with azithromycin was associated with a significant reduction in-hospital mortality compared to not receiving hydroxychloroquine.•Findings of this observational study provide crucial data on experience with hydroxychloroquine therapy, providing necessary interim guidance for COVID-19 therapeutic practice.
The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies.
The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19.
Multi-center retrospective observational study.
The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan.
Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48h unless expired within 24h.
Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither.
The primary outcome was in-hospital mortality.
Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine+azithromycin, 157/783 (20.1% 95% CI: 17.3%–23.0%), hydroxychloroquine alone, 162/1202 (13.5% 95% CI: 11.6%–15.5%), azithromycin alone, 33/147 (22.4% 95% CI: 16.0%–30.1%), and neither drug, 108/409 (26.4% 95% CI: 22.2%–31.0%). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 95% CI:1.9–3.3), white race (HR:1.7 95% CI:1.4–2.1), CKD (HR:1.7 95%CI:1.4–2.1), reduced O2 saturation level on admission (HR:1.5 95%CI:1.1–2.1), and ventilator use during admission (HR: 2.2 95%CI:1.4–3.3). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine+azithromycin 71% compared to neither treatment (p<0.001).
In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.
Geoconservation includes the protection of geoheritage features and geosites and the application of geoconservation principles more generally in the sustainable management of protected areas and in ...the wider landscape. This article reviews: 1) geoconservation principles and objectives for geosite management planning; and 2) the wider relevance of geoconservation and how the application of geoconservation principles across the full range of IUCN protected area management categories, UNESCO Global Geoparks and Biosphere Reserves, World Heritage sites, Ramsar sites and marine protected areas would benefit conservation of biodiversity and geodiversity and support wider nature conservation objectives, including climate change adaptation, connecting people and nature and sustainable development. In particular, the concepts of ‘nature and people’ and ‘conserving nature's stage’ provide opportunities for developing more holistic approaches to nature conservation.
Climate change and rising sea levels present significant challenges for geotourism destinations and activities. Accelerated changes in geomorphological processes threaten or diminish both the ...physical existence and aesthetic qualities of geoheritage assets, and hence the visitor experience, as well as presenting increased or new risks from natural hazards. This is particularly a concern in mountain and coastal areas, and also where greater extremes of temperature and precipitation affect visitor comfort. A literature review was conducted to assess the extent to which the consequences of climate change have been recognised in geotourism research. With the exception of glacier-based geotourism, few studies have considered the impacts of climate change and reported the planning or development of adaptation measures. However, the didactic potential of geotourism in raising awareness of climate change has been commonly recognised. A review of the wider tourism literature identified additional destination-supply and visitor-demand issues that will affect the sustainability of geotourism in the face of climate change. These include changes in visitor motivations, travel behaviour, perceptions of destination image, and reactions to local, national, and international mitigation and adaptation responses, as well as geoethical considerations around carbon footprints and sustainable modes of travel. Situating geotourism within a broader body of multidisciplinary tourism research should help inform adaptation strategies in conjunction with measures to adapt to the physical impacts of climate change on geotourism sites.
On the Stability of BOLD fMRI Correlations Laumann, Timothy O; Snyder, Abraham Z; Mitra, Anish ...
Cerebral cortex (New York, N.Y. 1991),
10/2017, Letnik:
27, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Measurement of correlations between brain regions (functional connectivity) using blood oxygen level dependent (BOLD) fMRI has proven to be a powerful tool for studying the functional organization of ...the brain. Recently, dynamic functional connectivity has emerged as a major topic in the resting-state BOLD fMRI literature. Here, using simulations and multiple sets of empirical observations, we confirm that imposed task states can alter the correlation structure of BOLD activity. However, we find that observations of "dynamic" BOLD correlations during the resting state are largely explained by sampling variability. Beyond sampling variability, the largest part of observed "dynamics" during rest is attributable to head motion. An additional component of dynamic variability during rest is attributable to fluctuating sleep state. Thus, aside from the preceding explanatory factors, a single correlation structure-as opposed to a sequence of distinct correlation structures-may adequately describe the resting state as measured by BOLD fMRI. These results suggest that resting-state BOLD correlations do not primarily reflect moment-to-moment changes in cognitive content. Rather, resting-state BOLD correlations may predominantly reflect processes concerned with the maintenance of the long-term stability of the brain's functional organization.
The PD-1 pathway regulates dysfunctional T cells in chronic infection and cancer, but the role of this pathway during acute infection remains less clear. Here, we demonstrate that PD-1 signals are ...needed for optimal memory. Mice deficient in the PD-1 pathway exhibit impaired CD8+ T cell memory following acute influenza infection, including reduced virus-specific CD8+ T cell numbers and compromised recall responses. PD-1 blockade during priming leads to similar differences early post-infection but without the defect in memory formation, suggesting that timing and/or duration of PD-1 blockade could be tailored to modulate host responses. Our studies reveal a role for PD-1 as an integrator of CD8+ T cell signals that promotes CD8+ T cell memory formation and suggest PD-1 continues to fine-tune CD8+ T cells after they migrate into non-lymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.
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•Early loss of PD-1 leads to overactivation of CD8+ T cells during acute infection•Mice constitutively lacking PD-1 or PD-L develop impaired CD8+ T cell memory•Cell-intrinsic PD-1 signals suppress effector cell expansion and promote memory•Timing of PD-1 blockade determines impact on memory generation
The role of PD-1 in memory development is poorly understood. Here, Pauken et al. show that constitutive loss of PD-1 during acute infection causes overactivation of CD8+ T cells during the effector phase and impairs memory and recall responses. These data indicate PD-1 is required for optimal memory.
Obesity and increased lipid availability have been implicated in the development and progression of chronic kidney disease. One of the major sites of renal lipid accumulation is in the proximal ...tubule cells of the kidney, suggesting that these cells may be susceptible to lipotoxicity. We previously demonstrated that loss of hepatic biliverdin reductase A (BVRA) causes fat accumulation in livers of mice on a high-fat diet. To determine the role of BVRA in mouse proximal tubule cells, we generated a CRISPR targeting BVRA for a knockout in mouse proximal tubule cells (BVRA KO). The BVRA KO cells had significantly less metabolic potential and mitochondrial respiration, which was exacerbated by treatment with palmitic acid, a saturated fatty acid. The BVRA KO cells also showed increased intracellular triglycerides which were associated with higher fatty acid uptake gene cluster of differentiation 36 as well as increased de novo lipogenesis as measured by higher neutral lipids. Additionally, neutrophil gelatinase-associated lipocalin 1 expression, annexin-V FITC staining, and lactate dehydrogenase assays all demonstrated that BVRA KO cells are more sensitive to palmitic acid-induced lipotoxicity than wild-type cells. Phosphorylation of BAD which plays a role in cell survival pathways, was significantly reduced in palmitic acid-treated BVRA KO cells. These data demonstrate the protective role of BVRA in proximal tubule cells against saturated fatty acid-induced lipotoxicity and suggest that activating BVRA could provide a benefit in protecting from obesity-induced kidney injury.
Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the ...site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1(+) T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4(+)FoxP3(+) Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity.
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