2,710 research outputs found
Tivozanib for the treatment of renal cell carcinoma: patient selection and perspectives
No full textRJ Rodenburg, FALM EskensErasmus MC Cancer Institute, Department of Medical Oncology, Rotterdam, The NetherlandsAbstract: Tivozanib is an oral selective vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor that is recently approved by the European Medicines Agency for the treatment of previously untreated patients with metastatic renal cell carcinoma (mRCC) as well as for those patients with disease progression during or after cytokine therapy. Nowadays, in first-line and second-line treatment of mRCC, there is an abundance of options, mainly consisting of VEGFR-directed tyrosinekinase inhibitors. This review focusses on the role of tivozanib with respect to patient selection and future perspectives in this fast-changing landscape.Keywords: tivozanib, metastatic renal cell cancer, tyrosine kinase inhibito
Adapting weed management in rice to changing climates
No full textThis paper provides some of the scientific background on how projected environmental conditions could affect weeds and weed management in rice in Africa. Elevated CO2 levels may have positive effects on rice competitiveness with C4 weeds, but these are generally outnumbered by C3 species in weed populations of rice in Africa. Moreover, higher temperatures and drought will favor C4 over C3 plants. Increased CO2 levels may also improve tolerance of rice against parasitic weeds, while invasiveness of such species may be stimulated by soil degradation and more frequent droughts or floods. Elevated CO2 may increase belowground relative to aboveground growth, in particular of perennial (C3) species, rendering mechanical control less effective or even counterproductive. Increased CO2 levels, rainfall and temperature may also reduce the effectiveness of chemical control. The implementation of climate change adaptation technologies, such as drought-tolerant germplasm and water-saving irrigation regimes, will also have consequences for rice–weed competition. Rainfed production systems are hypothesized to be most vulnerable to direct effects of climate change (e.g. changes in rainfall patterns) and are likely to face increased competition from C4 and parasitic weeds. Bioticstress- tolerant rice cultivars to be developed for these systems should encompass weed competitiveness and parasitic-weed resistance. In irrigated systems, indirect effects will be more important and weed management strategies should be diversified to lessen dependency on herbicides and mechanical control, and be targeted to perennial rhizotomous (C3) weeds. Water-saving production methods that replace the weed-suppressive flood water layer by intermittent or continuous periods of aerobic conditions, necessitate additional weed management strategies to address the inherent increases in weed competition
Reformulating the rj-McMC Algorithm for 3D Inversion of Passive Seismic Data for Near-Surface Characterization
No full textGeophysical subsurface characterization techniques could, due to their non-invasive nature, play a crucial role in the design and subsequent construction of infrastructure in urban & industrial environ- ments. Geo-data specialist company Fugro sees potential in upgrading their current ambient-seismic- noise-tomography workflow, to make use of state-of-the-art inversion schemes with the main goal of increasing the quality and accuracy of the initial-site characterization delivered to clients. In this thesis I explore the feasibility of utilizing the reverse-jump Markov chain Monte Carlo (rj-McMC) algorithm for the inversion of ambient seismic noise for characterization in urban & industrial environments. Specif- ically, testing the potential of scaling down this inversion algorithm to fit in a small scale, near-surface framework. To achieve this, I first carried out analyses to evaluate the appropriate Rayleigh wave frequency range, after which realistic noise hyperparameters, suited for this reduced scale problem, were obtained. Because of the potential exploitation of in-situ borehole measurements, I reformulated the Bayesian prior within the rj-McMC algorithm to implement these constraining shear wave velocity values appropriately. I conducted extensive synthetic experiments to gain insight into the behavior of this adapted algorithm, from which it was concluded that the inherent dynamic discretization partially prevents these constraints from being implemented to their full extent. Nevertheless, promising results lead me to conclude that the use of the rj-McMC algorithm for application in near-surface urban & industrial environments is feasible.Applied Geophysics | IDEA Leagu
Phenylbutyrate increases pyruvate dehydrogenase complex activity in cells harboring a variety of defects.
No full textOBJECTIVE: Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. PDHC deficiency is genetically heterogenous and most patients have defects in the X-linked E1-alpha gene but defects in the other components of the complex encoded by PDHB, PDHX, DLAT, DLD genes or in the regulatory enzyme encoded by PDP1 have also been found. Phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of pyruvate dehydrogenase kinases and thus, has potential for therapy of patients with PDHC deficiency. In the present study, we investigated response to phenylbutyrate of multiple cell lines harboring all known gene defects resulting in PDHC deficiency.
METHODS: Fibroblasts of patients with PDHC deficiency were studied for their enzyme activity at baseline and following phenylbutyrate incubation. Drug responses were correlated with genotypes and protein levels by Western blotting.
RESULTS: Large deletions affecting PDHA1 that result in lack of detectable protein were unresponsive to phenylbutyrate, whereas increased PDHC activity was detected in most fibroblasts harboring PDHA1 missense mutations. Mutations affecting the R349-alpha residue were directed to proteasome degradation and were consistently unresponsive to short-time drug incubation but longer incubation resulted in increased levels of enzyme activity and protein that may be due to an additional effect of phenylbutyrate as a molecular chaperone.
INTERPRETATION: PDHC enzyme activity was enhanced by phenylbutyrate in cells harboring missense mutations in PDHB, PDHX, DLAT, DLD, and PDP1 genes. In the prospect of a clinical trial, the results of this study may allow prediction of in vivo response in patients with PDHC deficiency harboring a wide spectrum of molecular defects
Clowns, Fools, and Killers: An Exploration of Horror, Comedy, and Madness Through the Roles of Murderer 2 and Sir Richard Ratcliffe in William Shakespeare\u27s Richard III
No full textThis document is a thesis submitted in partial fulfillment of the Master of Fine Arts degree in Theatre Arts with a Concentration in Musical Theatre. It is a detailed account of author RJ Magee’s artistic and scholarly process in creating the roles of Murderer 2 and Sir Richard Ratcliffe in William Shakespeare’s Richard III. The production was performed as part of Minnesota State University, Mankato’s mainstage season in October of 2022. In five chapters, this thesis chronicles the actor’s process: a preproduction analysis, a historical and critical perspective, a rehearsal and performance journal, a post-production analysis, and a process development analysis. Appendices and works cited are included
Radiation-induced root surface caries restored with glass-ionomer cement placed in conventional and ART cavity preparations: Results at two years
No full textThe document attached has been archived with permission from the Australian Dental Association (8th Jan 2008). An external link to the publisher’s copy is included.Background: There are no published studies comparing the clinical performances of more-viscous glass-ionomer cement (GIC) restorations when placed using conventional and atraumatic restorative treatment (ART) cavity preparation methods to restore root surface caries. Methods: One dentist used encapsulated Fuji IX GP and Ketac-Molar to restore 72 conventional and 74 ART cavity preparations for 15 patients who had received cervicofacial radiation therapy. Two assessors evaluated the restorations at six, 12, and 24 months for retention, marginal defects and surface wear, and recurrent caries. Results: After two years, the cumulative restoration successes were 65.2 per cent for the conventional and 66.2 per cent for the ART cavity preparations, without statistical or clinical significance (P>0.50). Restoration dislodgement accounted for 82.8 per cent and marginal defects for 17.2 per cent of all failures. There were no instances of unsatisfactory restoration wear or recurrent caries observed. Teeth with three or more restored cervical surfaces accounted for 79.3 per cent of all failures (P<0.0001). Conclusions: For root surface caries restored with GIC, the use of hand instruments only with the ART method was an equally effective alternative to conventional rotary instrumentation for cavity preparation. Larger restorations had higher failures, usually from dislodgement.JY Hu, XC Chen, YQ Li, RJ Smales and KH Yi
Paediatric use of melatonin (Author reply to D. J. Kennaway).
No full textComment on
Paediatric use of melatonin. [Eur J Paediatr Neurol. 2015]
Current role of melatonin in pediatric neurology: clinical recommendations. [Eur J Paediatr Neurol. 2015
Platelet-rich plasma and macular hole surgery: A clue to their mode of action and the influence of anti-platelet agents
No full text\ua9 The Author(s) 2022. Purpose: To present a case of refractory full-thickness macular hole (FTMH), in which autologous platelet-rich plasma (aPRP) was used on two consecutive occasions, and associated with successful closure only after complete cessation of anti-platelet therapy. Methods: Interventional case report. Results: A 63-year-old male with Alport syndrome underwent pars plana vitrectomy with internal limiting membrane peeling and gas for a large FTMH. The patient was on systemic anti-platelet agents for coronary disease. Post-operatively, the FTMH remained open and repeated surgery, augmented with aPRP, was performed. Although a thick pre-retinal coagulum was evident on optical coherence tomography on day one post-surgery, the second surgery failed. Ultimately, successful aPRP-augmented surgical closure of the FTMH was achieved only after complete cessation of systemic anti-platelet agents. Conclusion: Appropriate management of anti-platelet therapy may be relevant when planning aPRP use, though further large-scale studies are needed to assess the precise effect of anti-platelet therapy on the efficacy of aPRP, and to confirm the potential role of aPRP in patients with Alport syndrome
Needle deflection in thermal ablation procedures of liver tumors: a CT image analysis
No full textIntroduction: Accurate needle placement is crucial in image-guided needle interventions. A targeting error may be introduced due to undesired needle deflection upon insertion through tissue, caused by e.g. patient breathing, tissue heterogeneity, or asymmetric needle tip geometries. This paper aims to quantify needle deflection in thermal ablation procedures of liver tumors by means of a CT image analysis. Methods: Needle selection was done by using all clinical CT data that were made during thermal ablation procedures of the liver, ranging from 2008-2016, in the Erasmus MC, the Netherlands. The 3D needle shape was reconstructed for all selected insertions using manual segmentation. Subsequently, a straight line was computed between the entry point of the needle into the body and the needle tip. The maximal perpendicular distance between this straight line and the actual needle was used to calculate needle deflection. Results: In total, 365 needles were included in the analysis ranging from 14G to 17G in diameter. Average needle insertion depth was 95mm (range: 32 mm – 182 mm). Needle deflection was on average 1.3 mm (range: 0.0 mm – 6.5 mm). 54% of the needles (n=196) had a needle deflection of more than one millimeter, whereas 7% of the needles (n=25) showed a large needle deflection of more than three millimeters. Conclusions: Needle deflection in interventional radiology occurs in more than half of the needle insertions. Therefore, deflection should be taken into account when performing procedures and when defining design requirements for novel needles. Further, needle insertion models need to be developed that account for needle deflection.Medical Instruments & Bio-Inspired Technolog
Pharmacological interventions for patients experiencing acute post-operative pain
No full textWhat is pain? It is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. What are goals for postoperative pain management?To increase a patients quality of life, to facilitate a full and healthy recovery, to decrease the risk for complications (Impaired mobility -
pneumonia, pressure ulcers, DVT), to allow for early discharge from the hospital. Conclusion: by using a combination of pharmacological interventions we can more accurately provide pain management to patients by addressing multiple types of pain at once. By performing a thorough pain assessment and using our clinical judgement to determine what pharmacological interventions are necessary, we can move closer to achieving our postoperative pain management goals.Not peer reviewedStudent Research Day Poster (2017
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