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11.
  • Razavi, H., et al. (författare)
  • The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
  • Tidskriftsartikel (refereegranskat)abstract
    • The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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12.
  • Wedemeyer, H., et al. (författare)
  • Strategies to manage hepatitis C virus (HCV) disease burden
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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13.
  • Razavi, Homie A., et al. (författare)
  • Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
  • 2023
  • Ingår i: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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14.
  • Brandão, Andreia, et al. (författare)
  • The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
  • 2020
  • Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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17.
  • Lange, Jonathan, et al. (författare)
  • Novel lithographic printing techniques enabling sustainable and high quality multi material manufacturing process for future space outposts
  • 2021
  • Ingår i: IAC 2021 Congress Proceedings, 72nd International Astronautical Congress (IAC), Dubai, United Arab Emirates. - : International Astronautical Federation (IAF).
  • Konferensbidrag (refereegranskat)abstract
    • Several challenges remain before the full potential of on-orbit manufacturing can be realized. There may be some limitations to the types of items that can be manufactured in space. Such limitations could be caused by a variety of factors, including the materials required for a particular structure, the size of the object to be manufactured, the time required to execute the architecture, the configuration of the object being manufactured, and the raw material needed to support the manufacturing process. The complementary challenge to the relevant fabrication processes is the possibility to achieve the required precision demanded by geometrically complex structures and the ability to be versatile in processing a broad material spectrum. In this context, novel lithographic 3D printing techniques will be an asset to pave the way towards overcoming these challenges. Currently, the European Space Agency (ESA) is investigating the implementation of such technology in the context of a lunar base. In particular, two different applications are being studied: • Lithography-Based Ceramic Manufacturing (LCM), where the ceramic powder is distributed in a photocurable monomer formulation in presence of a photoinitiator. Ceramic materials are extensively used in a vast number of technological processes as well as in space applications. They are usually considered as the material of choice for applications where other materials such as plastic and metal fail to deliver the required performance. The LCM process will also allow processing lunar regolith simulant adding value to the current material portfolio of this technique, as well as to the range of processes potentially applicable on the lunar or Martian surface. • Lithography-based Metal Manufacturing (LMM) for processing metallic powders. In contrast to the currently predominantly used powder bed fusion (direct metal laser melting) techniques, this process uses a paste/suspension as feedstock and hence, does not rely on the use of highly spherical gas atomized powders. This will enable the utilization of recycled powders from scrap metals that are available at Moon bases or of metallic alloys reduced from lunar regolith, thus providing higher flexibility in accepting raw material with poor quality and purity. The paper addresses the results from both activities in terms of printed parts quality (roughness, density, resolution and accuracy) as well as the implementation requirements for the whole process chain, including suitable pre- and post-processing steps, with the aim to achieve a zero-waste flow in a lunar environment.
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18.
  • Leonardo, Diego A., et al. (författare)
  • Orientational Ambiguity in Septin Coiled Coils and its Structural Basis
  • 2021
  • Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836. ; 433:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.
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19.
  • Riede, M., et al. (författare)
  • Material characterization of AISI 316L flexure pivot bearings fabricated by additive manufacturing
  • 2019
  • Ingår i: Materials. - : MDPI. - 1996-1944 .- 1996-1944. ; 12:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, additive manufacturing (AM) by laser metal deposition (LMD) has become a key technology for fabricating highly complex parts without any support structures. Compared to the well-known powder bed fusion process, LMD enhances manufacturing possibilities to overcome AM-specific challenges such as process inherent porosity, minor build rates, and limited part size. Moreover, the advantages aforementioned combined with conventional machining enable novel manufacturing approaches in various fields of applications. Within this contribution, the additive manufacturing of filigree flexure pivots using 316L-Si by means of LMD with powder is presented. Frictionless flexure pivot bearings are used in space mechanisms that require high reliability, accuracy, and technical cleanliness. As a contribution to part qualification, the manufacturing process, powder material, and fabricated specimens were investigated in a comprehensive manner. Due to its major impact on the process, the chemical powder composition was characterized in detail by energy dispersive X-ray spectroscopy (EDX) and inductively coupled plasma optical emission spectrometry (ICP-OES). Moreover, a profound characterization of the powder morphology and flowability was carried out using scanning electron microscopy (SEM) and novel rheological investigation techniques. Furthermore, quantitative image analysis, mechanical testing, laser scanning microscopy, and 3D shape measurement of manufactured specimens were conducted. As a result, the gained knowledge was applied for the AM-specific redesign of the flexure pivot. Finally, a qualified flexure pivot has been manufactured in a hybrid manner to subsequently ensure its long-term durability in a lifetime test bench.
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