The ‘centre–periphery hypothesis’ (CPH) is a long‐standing postulate in ecology that states that genetic variation and demographic performance of a species decrease from the centre to the edge of its ...geographic range. This hypothesis is based on an assumed concordance between geographical peripherality and ecological marginality such that environmental conditions become harsher towards the limits of a species range. In this way, the CPH sets the stage for understanding the causes of distribution limits. To date, no study has examined conjointly the consistency of these postulates. In an extensive literature review we discuss the birth and development of the CPH and provide an assessment of the CPH by reviewing 248 empirical studies in the context of three main themes. First, a decrease in species occurrence towards their range limits was observed in 81% of studies, while only 51% demonstrated reduced abundance of individuals. A decline in genetic variation, increased differentiation among populations and higher rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and 48%, respectively). However, demographic rates, size and population performance less often followed CPH expectations (20–30% of studies). We highlight the impact of important methodological, taxonomic, and biogeographical biases on such validation rates. Second, we found that geographic and ecological marginality gradients are not systematically concordant, which casts doubt on the reliability of a main assumption of the CPH. Finally, we attempt to disentangle the relative contribution of geographical, ecological and historical processes on the spatial distribution of genetic and demographic parameters. While ecological marginality gradients explain variation in species' demographic performance better than geographic gradients, contemporary and historical factors may contribute interactively to spatial patterns of genetic variation. We thereby propose a framework that integrates species' ecological niche characteristics together with current and past range structure to investigate spatial patterns of genetic and demographic variation across species ranges.
The severe acute respiratory syndrome coronavirus 2 associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The ...cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival. Immune modulators have the potential to inhibit cytokines and treat the cytokine storm. A literature search using PubMed, Google Scholar, and ClinicalTrials.gov was conducted through 8 July 2020 using the search terms 'coronavirus', 'immunology', 'cytokine storm', 'immunomodulators', 'pharmacology', 'severe acute respiratory syndrome 2', 'SARS-CoV-2', and 'COVID-19'. Specific immune modulators include anti-cytokines such as interleukin (IL)-1 and IL-6 receptor antagonists (e.g. anakinra, tocilizumab, sarilumab, siltuximab), Janus kinase (JAK) inhibitors (e.g. baricitinib, ruxolitinib), anti-tumor necrosis factor-α (e.g. adalimumab, infliximab), granulocyte-macrophage colony-stimulating factors (e.g. gimsilumab, lenzilumab, namilumab), and convalescent plasma, with promising to negative trials and other data. Non-specific immune modulators include human immunoglobulin, corticosteroids such as dexamethasone, interferons, statins, angiotensin pathway modulators, macrolides (e.g. azithromycin, clarithromycin), hydroxychloroquine and chloroquine, colchicine, and prostaglandin D2 modulators such as ramatroban. Dexamethasone 6 mg once daily (either by mouth or by intravenous injection) for 10 days may result in a reduction in mortality in COVID-19 patients by one-third for patients on ventilators, and by one-fifth for those receiving oxygen. Research efforts should focus not only on the most relevant immunomodulatory strategies but also on the optimal timing of such interventions to maximize therapeutic outcomes. In this review, we discuss the potential role and safety of these agents in the management of severe COVID-19, and their impact on survival and clinical symptoms.
•This leading opinion paper highlights the additive benefit of multiaxial load bioreactors in cartilage preclinical research.•It emphasizes that mechanical activation of endogenous TGFβ may be a key ...event in early cartilage repair after injury.•There is a need to implement kinematic load during in vitro/ex vivo studies to better align data obtained with that from in vivo studies.
Novel cartilage regeneration therapies often look promising in-vitro but fail when implanted in vivo. One of the possible reasons for this discrepancy is the simplified, static in-vitro chondrogenesis models typically used. Complex mechanical stimulation plays a key role in physiological cartilage and chondrogenic cell metabolism, including the development of cartilage structure, yet it is routinely lacking during in-vitro studies. Multiaxial load bioreactors are becoming more widespread and offer advantages over more simple loading devices. Within this article, we highlight some of the important findings from in-vitro assays and key aspects relating to tribological loading of cartilage and chondrogenic cells.
PLANIFICATION - MANAGER’S RESPONSABILITY I. BRAD; COSMINA–SIMONA TOADER
Lucrări științifice zootehnie şi biotehnologii,
11/2023, Letnik:
41, Številka:
1
Journal Article
Odprti dostop
In the present time, in the whole world there is planning, all types of organizations plan the future periods taking into consideration all the aspects of their activity. The planning activity is not ...based on intuition and presentiments, but on forecasting and analysis. The humanity is in strong economical, technological, social and political period where the anticipation and other activities of the manager became necessary for the survival of the organization. The continuous change and economical development are generating opportunities, but, in the same time, are generating also risks. In this context the role of planning is to reduce as much as possible the risks and to take profit of the advantages and opportunities. But, in order to make the plans successful, the planning has to find its place among the theories, principles and basic techniques of management.
Enabling athletes to achieve peak performances while also maintaining high levels of health is contextually complex. We aim to describe what a ‘health system’ is and apply the essential functions of ...stewardship, financing, provision of services and resource generation to an Australian high-performance sport context. We introduce a fifth function that health systems should not detract from athletes’ ability to achieve their sports goals. We describe how these functions aim to achieve four overall outcomes of safeguarding the health of the athletes, responding to expectations, providing financial and social protection against the costs of ill health, and efficient use of resources. Lastly, we conclude with key challenges and potential solutions for developing an integrated health system within the overall performance system in high-performance sport.
•Two typical types of defects are systematically studied via computational fluid dynamics.•Different flow structures and influence mechanisms are revealed for both types of defects.•Performance of ...the airfoil with deep defects is highly dependent on the defect opening size.•Defect equivalent depth predominates the performance of the airfoil with shallow defects.
Defects at the leading edge of blades are an important source of power loss for wind turbines. In the present work, a systematic study is carried out on two typical types of defects, i.e., the surface concaved deep defects and surface distributed shallow defects on the S809 airfoil. Different defect shapes, ranges, equivalent depths and their influence mechanisms are investigated via CFD. For deep defects, an enclosed vortex is formed in the defect cavity, which suppresses the momentum exchange between the external flow and internal flow, so that the airfoil aerodynamic performance is highly sensitive to the defect opening range and is little affected by the defect shape and equivalent depth. Flow around the leading edge is strongly hindered by the deep defects and an elongated leading-edge separation bubble is formed at the suction side of the airfoil. At large angles of attack, flow at the suction side is dominated by flow separation at both the leading edge and trailing edge. In contrast, for shallow defects, all the defect equivalent depth, opening range and shape can significantly influence the airfoil aerodynamic performance; and quantitatively, the effect of defect equivalent depth is the most significant. For the present simulation cases with defects, the maximum lift coefficient is notably decreased (by 35% to 61%) accompanied by a sharp increase in drag coefficient (by 131% to 217%). Under dynamic pitching motions, the opening of the dynamic lift (drag)-coefficient hysteresis curve is effectively enlarged. The present work aims to provide an important reference for the maintenance and management of turbine blade defects.
Sphingosine-1-phosphate (S1P) is a bioactive lipid metabolite that exerts its actions by engaging 5 G-protein-coupled receptors (S1PR1-S1PR5). S1P receptors are involved in several cellular and ...physiological events, including lymphocyte/hematopoietic cell trafficking. An S1P gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, regulates lymphocyte trafficking. Because lymphocytes live long (which is critical for adaptive immunity) and recirculate thousands of times, the S1P-S1PR pathway is involved in the pathogenesis of immune-mediated diseases. The S1PR1 modulators lead to receptor internalization, subsequent ubiquitination, and proteasome degradation, which renders lymphocytes incapable of following the S1P gradient and prevents their access to inflammation sites. These drugs might also block lymphocyte egress from lymph nodes by inhibiting transendothelial migration. Targeting S1PRs as a therapeutic strategy was first employed for multiple sclerosis (MS), and four S1P modulators (fingolimod, siponimod, ozanimod, and ponesimod) are currently approved for its treatment. New S1PR modulators are under clinical development for MS, and their uses are being evaluated to treat other immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis. A clinical trial in patients with COVID-19 treated with ozanimod is ongoing. Ozanimod and etrasimod have shown promising results in IBD; while in phase 2 clinical trials, ponesimod has shown improvement in 77% of the patients with psoriasis. Cenerimod and amiselimod have been tested in SLE patients. Fingolimod, etrasimod, and IMMH001 have shown efficacy in RA preclinical studies. Concerns relating to S1PR modulators are leukopenia, anemia, transaminase elevation, macular edema, teratogenicity, pulmonary disorders, infections, and cardiovascular events. Furthermore, S1PR modulators exhibit different pharmacokinetics; a well-established first-dose event associated with S1PR modulators can be mitigated by gradual up-titration. In conclusion, S1P modulators represent a novel and promising therapeutic strategy for immune-mediated diseases.
Many species are extending their leading‐edge (cool) range margins polewards in response to recent climate change. In the present study, we investigated range margin changes at the northern (cool) ...range margins of 1573 southerly‐distributed species from 21 animal groups in Great Britain over the past four decades of climate change, updating previous work. Depending on data availability, range margin changes were examined over two time intervals during the past four decades. For four groups (birds, butterflies, macromoths, and dragonflies and damselflies), there were sufficient data available to examine range margin changes over both time intervals. We found that most taxa shifted their northern range margins polewards and this finding was not greatly influenced by changes in recorder effort. The mean northwards range margin change in the first time interval was 23 km per decade (N = 13 taxonomic groups) and, in the second interval, was 18 km per decade (N = 16 taxonomic groups) during periods when the British climate warmed by 0.21 and 0.28 °C per decade, respectively. For the four taxa examined over both intervals, there was evidence for higher rate of range margin change in the more recent time interval in the two Lepidoptera groups. Our analyses confirm a continued range margin shift polewards in a wide range of taxonomic groups.
PDF
