32 research outputs found

    IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

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    Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype

    Modelling infragravity waves and currents across a fringing reef : Ningaloo reef, Western Australia (using XBEACH)

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    Reef systems are prevalent along most of the world's coastlines (up to 80%). However, only a handful of studies to date have focused on physical processes in the vicinity of nearshore reef systems. Although, it has been long thought that the same physical processes operating on sandy coasts would also dominate reef environments, the few studies conducted to date in reef environments and submerged breakwaters imply that this may not be the case. Particularly processes such as infragravity waves, partitioning of momentum flux into wave setup and onshore flow over the reef, offshore directed return flow in reef gaps, which do not operate on sandy coasts, appear to be of crucial importance in reef environments. A good understanding of these processes is important because waves and wave-induced flows ultimately drive sediment transport, nutrient dynamics and uptake by benthic communities, as well as the transport and dispersal of larval fish and other organisms; all of which may be significantly impacted upon by environmental changes (e.g. sea level rise, climate change) and /or human interventions (e.g. dredging of channels, beach nourishment, recreation). This study attempts to make a small initial step towards addressing this vast knowledge gap. This thesis particularly focuses on hydrodynamic processes operating at fringing reef systems via XBeach model applications to idealized and real-life situations. XBeach (Roelvink et at. 2009), a new process based model that for the first time includes a robust capability to simulate infragravity waves and resulting hydrodynamic/sediment transport processes that are crucial in reef environments provides an efficient method to study physical processes dominant operating in reef systems

    Parentage Assignment in Striped Catfish (Pangasianodon hypophthalmus) Based on Microsatellite Marke

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    In this study, five microsatellite markers from two multiplex PCR sets were used to determine the pedigree of five striped catfish (Pangasianodon hypophthalmus) families that came from a breeding program in Vietnam. The number of alleles per locus and polymorphic information content (PIC) were 4 to 7 and 0.551-0.803, respectively. In the parentage analysis based on five microsatellites, 62.7% of offspring could be allocated unambiguously to their parental pairs using the perfect mismatch setting, and assignment rate improved to 89.3% after a single mismatch was allowed. Parentage analysis when only four microsatellites were used (a locus with a high frequency of null alleles was excluded) increased the assignment rate to 68% for a perfect mismatch and to 90% for assignment with a single mismatch. Results here confirm that a DNA markerbased approach to parentage assignment in P. hypophthalmus will be useful in genetic improvement programs for this important aquaculture species in Vietnam.

    Assessment of women's benefits and constraints in participating in agroforestry exemplar landscapes

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    Participating in AFLi Exemplar project has positive impacts on ethnic women such as increasing their network, decision making skills, public speaking skills. However, the rate of female farmers accessing and using project extension materials or participated in project nurseries and applying agroforestry techniques remains limited. This requires understanding of the real needs and interests grounded in those socio-cultural contexts as the ethnic groups living in the Northern mountain areas in Vietnam have unique social and cultural norms and values. The case studies have shown that agricultural activities are highly gendered, in which men and women play specific roles and have different particular constraints and interests. Women are highly constrained by gender norms, access to resources, decision-making power and a prevailing positive-feedback loop of time poverty, especially in H'mong community. A holistic, time-saving approach to addressing women’s daily activities could reduce the effects of time poverty and increase project participation. As women were highly willing to share project information, project impacts would be more successful with increased participation from women by utilizing informal channels of communication and knowledge dissemination. Extension materials designed for ethnic women should have less text and more visualization. Access to information is a vital constraint that perpetuates the norm that men are decision-makers thereby enhancing their perceived ownership, where women have limited access to information and so leave final decisions to men, especially in Hmong families. Old H'mong women have Vietnamese language barrier which prevent them from accessing project materials. Further research into an adaptive framework which can be applied in a variety of contexts is recommended. This framework should prioritize time-saving activities for women and include materials highlighting key considerations to maintain accountability among project support staff

    Gender and Ethnicity in Vietnam Agroforestry Landscapes: Lessons for Project Implementation

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    The brief summarizes learnings and outcomes from the Agroforestry for Livelihoods (AFLi) project, implemented by World Agroforestry (ICRAF) in Northwestern Vietnam. The project took place in two phases over the period of 2011 to 2021, it sought to encourage farmers to adopt agroforestry systems to combat environmental degradation and to diversify their agricultural products. The second phase of the project (AFLi-II) focused on the development of market-based agroforestry and forest rehabilitation

    PCN154 Challenges Posed by Patient Crossover for Cost-Effectiveness Analysis of Oncology Products: A Case Study in Metastatic Pancreatic Cancer

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    A qualitative assessment of climate change impacts on the stability of small tidal inlets via schematised numerical modelling

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    Tidal inlets are of great societal importance and are also the most morphologically dynamic regions in the coastal zone. Therefore, they are of great scientific interest. Their behaviour is governed by the delicate balance of oceanic processes such as tides, waves and mean sea level (MSL), and fluvial/estuarine processes such as riverflow. All of these processes can be significantly affected by climate change (CC) processes, which may result in negative physical impacts such as inlet closure/relocation, creation of new inlets, erosion of the coast adjacent to the inlet etc. Although CC impacts on some large tidal inlets (e.g. Wadden Sea inlets) have received some attention recently, the potential CC impacts on small tidal inlets (STIs) remain virtually unknown to date. Furthermore, whether currently available predictive tools are capable of simulating CC impacts on these systems also remains unknown. These knowledge gaps are a serious threat to effective adaptation to CC in STI environments. Just, this study attempts to investigate the potential range of CC impacts on the stability (i.e. closed/open state and locational stability) of STIs via the application of a sophisticated process based morphodynamic model (Delft3D) to strategically selected schematised inlet morphologies and forcing conditions.Results indicate that CC driven variations in system forcing are likely have profound impacts on inlet stability and also show that a process based coastal morphodynamic model (eg. Delft3D) is suitable for investigating potential CC impacts at small tidal inlets

    A qualitative assessment of climate change impacts on the stability of small tidal inlets via schematised numerical modelling

    No full text
    Tidal inlets are of great societal importance and are also the most morphologically dynamic regions in the coastal zone. Therefore, they are of great scientific interest. Their behaviour is governed by the delicate balance of oceanic processes such as tides, waves and mean sea level (MSL), and fluvial/estuarine processes such as riverflow. All of these processes can be significantly affected by climate change (CC) processes, which may result in negative physical impacts such as inlet closure/relocation, creation of new inlets, erosion of the coast adjacent to the inlet etc. Although CC impacts on some large tidal inlets (e.g. Wadden Sea inlets) have received some attention recently, the potential CC impacts on small tidal inlets (STIs) remain virtually unknown to date. Furthermore, whether currently available predictive tools are capable of simulating CC impacts on these systems also remains unknown. These knowledge gaps are a serious threat to effective adaptation to CC in STI environments. Just, this study attempts to investigate the potential range of CC impacts on the stability (i.e. closed/open state and locational stability) of STIs via the application of a sophisticated process based morphodynamic model (Delft3D) to strategically selected schematised inlet morphologies and forcing conditions.Results indicate that CC driven variations in system forcing are likely have profound impacts on inlet stability and also show that a process based coastal morphodynamic model (eg. Delft3D) is suitable for investigating potential CC impacts at small tidal inlets
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