167 research outputs found

    Integrated Management: A Coastal Community Perspective

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    This paper was prepared for the Food and Agriculture Organisation of the United Nations Regional Workshops on Small-Scale Fisheries "Securing Sustainable Small-Scale Fisheries: Bringing together responsible fisheries and social development". It presents a review of what are seen as 'good practices' globally in policy and governance of small-scale fisheries, with a particular focus on addressing rights-based issues, viewed broadly as incorporating fishery rights, other rights to natural resources, and rights and entitlements in relation to human, social and economic rights. It draws extensively on the 1995 Code of Conduct for Responsible Fisheries and related technical guidelines, particularly those concerning small-scale fisheries and their roles in poverty alleviation and food security, and the human dimensions of the ecosystem approach to fisheries. The paper is also strongly informed by the papers prepared for and outcomes of the 2008 Global Conference on "Securing Sustainable Small-Scale Fisheries: Bringing together responsible fisheries and social development" and the relevant rights-oriented components of the 'Bangkok Statement' produced by the Civil Society Preparatory Workshop for the Global Conference. It also draws upon a set of research documents in the international literature focusing on small-scale fisheries and related policy issues [e.g., Allison et al. (2010), Charles (2009, 2011), McConney and Charles (2009); Kurien (2000, 2007)]

    Performance evolution and tensile behaviour of long-term exposed UHPC under sustained load, aggressive environments and autogenous healing

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    An extended experimental campaign was conducted to analyse the evolution of UHPC tensile performance over time as affected by sustained flexural load and aggressive environments both interacting with its autogenous self-healing capacity. A new methodology including both destructive and non-destructive tests was proposed. Three different mix designs were tested, with steel fibres, crystalline admixture, and various nanomaterials. Specifically, the first batch included alumina nano-fibres, while the second one cellulose nanocrystals. The last one was used as a reference and did not include nanomaterials. Thin beam specimens (500x100x30 mm) were pre-cracked and exposed to three different environments, under four-point bending sustained load. The specimens were cured for 1, 2, 3, 6, 9, and 12 months respectively, being exposed to a chloride solution, geothermal water, and tap water as a reference. After the aforesaid scheduled exposure times, two nominally identical specimens were tested for each condition, the first in four-point bending and the second in direct tension. To compare the results, a simplified five-point inverse analysis was adapted for beams with different slenderness, providing a quadrilinear constitutive law derived from the structural flexural behaviour of four-point bending tests. Test results allowed to highlight the effects of each parameter – type of material and exposure – on the self-healing effectiveness and the tensile response, also defining their evolution over time. The self-healing process resulted in an almost complete recovery after the first two or three months, and the materials were able to maintain a constant performance over longer periods, regardless of the conditions they were exposed to

    125. Engineered Nucleases-Mediated In Situ Correction of a Genetic Defect By Homologous Recombination Into the Native Locus

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    Engineered nucleases specific for genomic targets are extensively used to generate DSBs that increase the rate and efficiency of homologous recombination (HR). We seek to determine the efficacy of nucleases in a clinical relevant genetic defect.The genetic defect we are addressing as model to test the nucleases-mediated genome editing technology is the junctional epidermolysis bullosa (JEB), a family of severe skin adhesion disorders due to autosomal recessive mutations in the LAMB3 gene coding for the laminin-332 heterotrimer, a key component of the dermal-epidermaljunction. Recently, we provided proof of principle that ZFN-mediated, AAVS1-targeted GFP addition can be achieved in human keratinocytes and in long-term repopulating epithelial stem cells in a validated preclinical model of xenotransplantation of human skin equivalents on immunodeficient mice.This project aims at the demonstration of a successful in situ correction of the LAMB3 gene in primary keratinocytes from Herlitz JEB patients. Recently TALEN-based gene correction for dystrophic EB has been reported. Similarly, we have developed a genome editing approach for JEB. In particular we have designed TALENs specific for the second intron of LAMB3 gene and a HR cassette including a splicible LAMB3 cDNA (from exon 3 to the end of the gene). In particular immortalized JEB keratinocytes were transfected with TALEN mRNAs and infected with an IDLV vector carrying the HR cassette. The in situ gene correction has been evaluated by site-specific PCR and knock-in expression of the corrected LAMB3 gene on bulk population. We then assessed targeting efficiency and specificity by extensive molecular analyses of single-cell clones isolated by limiting dilution from the TALENs/IDLV-treated immortalized JEB population. We isolated 256 clones and expanded 69 of them. Sixteen out of 69 clones showed an in vitro adhesion advantage, hosted the HR cassette correctly integrated into the predetermined locus, expressed the corrected LAMB3 gene and produced the laminin-332 protein. In parallel, CRISPR-Cas9 nuclease has been designed on the same locus to compare the transduction efficiency and cleavage activity and to translate the knock-in targeting platform to primary JEB keratinocytes

    Prevalence and time course of post-stroke pain: A multicenter prospective hospital-based study

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    OBJECTIVE: Pain prevalence data for patients at various stages after stroke. DESIGN: Repeated cross-sectional, observational epidemiological study. SETTING: Hospital-based multicenter study. SUBJECTS: Four hundred forty-three prospectively enrolled stroke survivors. METHODS: All patients underwent bedside clinical examination. The different types of post-stroke pain (central post-stroke pain, musculoskeletal pains, shoulder pain, spasticity-related pain, and headache) were diagnosed with widely accepted criteria during the acute, subacute, and chronic stroke stages. Differences among the three stages were analyzed with χ(2)-tests. RESULTS: The mean overall prevalence of pain was 29.56% (14.06% in the acute, 42.73% in the subacute, and 31.90% in the chronic post-stroke stage). Time course differed significantly according to the various pain types (P < 0.001). The prevalence of musculoskeletal and shoulder pain was higher in the subacute and chronic than in the acute stages after stroke; the prevalence of spasticity-related pain peaked in the chronic stage. Conversely, headache manifested in the acute post-stroke stage. The prevalence of central post-stroke pain was higher in the subacute and chronic than in the acute post-stroke stage. Fewer than 25% of the patients with central post-stroke pain received drug treatment. CONCLUSIONS: Pain after stroke is more frequent in the subacute and chronic phase than in the acute phase, but it is still largely undertreated

    Genomic Analysis of Sleeping Beauty Transposon Integration in Human Somatic Cells

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    The Sleeping Beauty (SB) transposon is a non-viral integrating vector system with proven efficacy for gene transfer and functional genomics. However, integration efficiency is negatively affected by the length of the transposon. To optimize the SB transposon machinery, the inverted repeats and the transposase gene underwent several modifications, resulting in the generation of the hyperactive SB100X transposase and of the high-capacity \u2018\u2018sandwich\u2019\u2019 (SA) transposon. In this study, we report a side-by-side comparison of the SA and the widely used T2 arrangement of transposon vectors carrying increasing DNA cargoes, up to 18 kb. Clonal analysis of SA integrants in human epithelial cells and in immortalized keratinocytes demonstrates stability and integrity of the transposon independently from the cargo size and copy number-dependent expression of the cargo cassette. A genome-wide analysis of unambiguously mapped SA integrations in keratinocytes showed an almost random distribution, with an overrepresentation in repetitive elements (satellite, LINE and small RNAs) compared to a library representing insertions of the first-generation transposon vector and to gammaretroviral and lentiviral libraries. The SA transposon/SB100X integrating system therefore shows important features as a system for delivering large gene constructs for gene therapy application

    N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation

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    An unmet clinical goal in demyelinating pathologies is to restore the myelin sheath prior to neural degeneration. N-acetylaspartate (NAA) is an acetylated derivative form of aspartate, abundant in the healthy brain but severely reduced during traumatic brain injury and in patients with neurodegenerative pathologies. How extracellular NAA variations impact the remyelination process and, thereby, the ability of oligodendrocytes to remyelinate axons remains unexplored. Here, we evaluated the remyelination properties of the oligodendroglial (OL) mouse cell line Oli-neuM under different concentrations of NAA using a combination of biochemical, qPCR, immunofluorescence assays, and in vitro engagement tests, at NAA doses compatible with those observed in healthy brains and during brain injury. We observed that oligodendroglia cells respond to decreasing levels of NAA by stimulating differentiation and promoting gene expression of myelin proteins in a temporally regulated manner. Low doses of NAA potently stimulate Oli-neuM to engage with synthetic axons. Furthermore, we show a concentration-dependent expression of specific histone deacetylases essential for MBP gene expression under NAA or Clobetasol treatment. These data are consistent with the idea that oligodendrocytes respond to lowering the NAA concentration by activating the remyelination process via deacetylase activation

    Value of split-bolus multidetector-row CT technique in the quantitative assessment of pancreatic enhancement [Pankreatik tutulumun kantitatif değerlendirilmesinde bölünmüş-bolus multidetektör-dizi BT tekniğinin değeri]

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    The aim of this study is to quantitatively assess radiation comma, and pancreatic enhancement by split-bolus intravenous injection of contrast material using 64-slice CT. Single-pass split-bolus MDCT of the chest and abdomen was performed in 37 patients (female: 18, male: 9; mean age, 66.1±14.2 years; range 17-80 years) without pancreatic disease. Regions of interest in the pancreatic head, body and tail were drawn, and mean attenuation values for pancreatic parenchymal phase (PPP) of the standard MDCT protocol and split-bolus were calculated. P&lt;0.05 was considered statistically significant. Mean effective dose by split-bolus was measured. In all MDCT examinations split-bolus protocol allowed acquisition of optimal images. Mean pancreatic enhancement was higher by split-bolus with respect to PPP of standard triphasic MDCT (131.35 HU±20.63 vs 126.1 HU±20.01). Reduction of dose using MDCT split-bolus was approximately 17%. In conclusion MDCT split-bolus protocol provides an optimal pancreatic enhancement, significantly greater than the enhancement of standard MDCT on PPP which confers an advantage for the detection and staging of pancreatic tumors

    Health Technology Assessment for In Silico Medicine: Social, Ethical and Legal Aspects

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    The application of in silico medicine is constantly growing in the prevention, diagnosis, and treatment of diseases. These technologies allow us to support medical decisions and self- management and reduce, refine, and partially replace real studies of medical technologies. In silico medicine may challenge some key principles: transparency and fairness of data usage; data privacy and protection across platforms and systems; data availability and quality; data integration and interoperability; intellectual property; data sharing; equal accessibility for persons and populations. Several social, ethical, and legal issues may consequently arise from its adoption. In this work, we provide an overview of these issues along with some practical suggestions for their assessment from a health technology assessment perspective. We performed a narrative review with a search on MEDLINE/Pubmed, ISI Web of Knowledge, Scopus, and Google Scholar. The following key aspects emerge as general reflections with an impact on the operational level: cultural resistance, level of expertise of users, degree of patient involvement, infrastructural requirements, risks for health, respect of several patients’ rights, potential discriminations for access and use of the technology, and intellectual property of innovations. Our analysis shows that several challenges still need to be debated to allow in silico medicine to express all its potential in healthcare processes

    DIAMANTINA: CENÁRIO DO PRIMEIRO DIÁRIO ESCRITO POR UMA MULHER NO BRASIL – MINHA VIDA DE MENINA DE HELENA MORLEY

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    Primeiro diário escrito por uma mulher no Brasil, Minha vida de menina traz a descrição do cotidiano e da vida pacata de Diamantina, cidade do interior de Minas Gerais. Helena Morley, uma adolescente do final do século XIX, apresenta-nos desde os loucos da cidade, até questões da libertação dos escravos. A visão de mundo da jovem narradora proporciona também uma visão de como o papel da mulher mudou na nossa sociedade

    Locally advanced leiomyosarcoma of the spleen. A case report and review of the literature

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    <p>Abstract</p> <p>Background</p> <p>Leiomyosarcomas are rare tumours, predominantly localized in the stomach, small intestine and retroperitoneum. Only one case of primary leiomyosarcoma of the spleen is described in human beings in literature.</p> <p>Case presentation</p> <p>We report a case of locally advanced primary leiomyosarcoma of the spleen in a 54 year-old woman, diagnosed only after splenectomy, performed with the suspicion of splenic haematoma.</p> <p>Conclusion</p> <p>Due to the lack of cases, no specific chemotherapy regimen has been tested to provide a longer survival.</p
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