553 research outputs found

    Assumptions and implementation of climate and energy policy under the Europe 2020 strategy

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    Purpose: The essence of the "Europe 2020" initiative, that is, the strategy for smart, sustainable, and inclusive growth, is an attempt at creating conditions fostering long-term sustainable economic growth in the European Union. To this end, economies based on knowledge, promoting environment-friendly technologies must be built in the member states of the Community, at the same time taking care to maintain social and territorial cohesion. Design/Methodology/Approach: This paper contains a long-term analysis of selected indicators concerning climate policy in the period 2000-2018 and an assessment of their accomplishment. This paper aims at verifying the hypothesis that prolonged problems in accomplishing “20/20/20” targets related to climate and energy, that is, decreasing greenhouse gas emissions by 20% in comparison to 1990, increasing the share of renewable energy in gross final energy consumption to 20% and increasing the energy efficiency by 20%, undermine the success and timely accomplishment of certain priorities of the Strategy. Findings: Due to the relatively high level of greenhouse gas emissions and a high consumption of conventional energy in comparison to renewable energy, the Strategy requires a longer time horizon to be implemented successfully. In the European Community one can see a division into western countries of the Community and countries of the former Eastern bloc. Delayed technological, social, and financial development in the countries of the former Eastern bloc and insufficient awareness of the European and global climate policy may postpone the common efforts to accomplish the objectives of Europe 2020 Strategy beyond the projected time horizon. Originality/Value: It has boosted the process of building a knowledge-based economy and attempting to create conditions to reduce the share of greenhouse gases, reduce energy consumption and improve climate and energy indicators.peer-reviewe

    Diagnostics to support the control of scabies-Development of two target product profiles.

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    BACKGROUND: Scabies was added to the WHO NTD portfolio in 2017 and targets for the control of scabies were included in the 2021-2030 WHO NTD roadmap. A major component of scabies control efforts a strategy based on mass drug administration (MDA) with ivermectin. Currently diagnosis of scabies relies on clinical examination with a limited role for diagnostic testing. Under the recommendation of the WHO Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases, a working group was assembled and tasked with agreeing on priority use cases for and developing target product profiles (TPPs) for new diagnostics tools for scabies. METHODOLOGY AND PRINCIPAL FINDINGS: The working group convened three times and established two use cases: establishing if the 10% threshold for mass drug administration had been reached and if the 2% threshold for stopping mass drug administration has been achieved. One subgroup assessed the current diagnostic landscape for scabies and a second subgroup determined the test requirements for both use cases. Draft TPPs were sent out for input from stakeholders and experts. Both TPPs considered the following parameters: product use, design, performance, configuration, cost, access and equity. The group considered the use of the tests as a single step process or as part of a two step process following initial clinical examination. When used a single step test (the ideal scenario) for starting MDA a new diagnostic required a sensitivity of ≥92% and a specificity of ≥98%. When used a single step test (the ideal scenario) for stopping MDA a new diagnostic required a sensitivity of ≥80% and a specificity of ≥99%. CONCLUSIONS: The TPPs developed will provide test developers with guidance to ensure that novel diagnostic tests meet identified public health needs

    Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database.

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    Funder: New faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0049).Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines

    Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA.</p> <p>Methods</p> <p>In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods.</p> <p>Results</p> <p>Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05).</p> <p>Conclusions</p> <p>Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA.</p> <p>Trial Registration</p> <p>The study was registered with ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00393393">NCT00393393</a>).</p

    An evolutionary perspective on substance abuse

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    This article describes how recent advances in understanding the evolutionary functions of emotions can help to reconcile diverse approaches to substance abuse. Emotions can be understood as specialized states that prepare individuals to cope with opportunities and threats. Drugs that artificially induce pleasure or block normal suffering disrupt these evolved mechanisms, and thus should tend to interfere with adaptive behavior, even if the drugs are medically safe. Nonetheless, we routinely use drugs quite safely to block defenses like pain, cough, and anxiety. This apparent contradiction is explained by the relatively small costs of defenses compared to the potentially huge costs of not expressing a defensive response when it is needed. An evolutionary perspective has implications for substance abuse research, treatment, and social policy. This perspective suggests that the search for etiology needs to address the human tendency to abuse drugs separately from individual differences in these tendencies, that clinical treatments that take account of the broad range of patients' emotional life are well justified, and that social policies need to address substance use and abuse not as diseases to be cured but as human tendencies that need to be managed. To prepare for future drugs that will likely alter emotions safely, we urgently need a better understanding of the adaptive function of the emotions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31367/1/0000279.pd

    HDAC1 Inactivation Induces Mitotic Defect and Caspase-Independent Autophagic Cell Death in Liver Cancer

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    Histone deacetylases (HDACs) are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC), but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21WAF1/Cip1 and p27Kip1 expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21WAF1/Cip1 transcriptional activity through Sp1-binding sites in the p21WAF1/Cip1 promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy

    Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation

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    We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation
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