Safety, Tolerability, and Preliminary Efficacy of TAR-200 in Patients with Muscle-invasive Bladder Cancer Who Refused or Were Unfit for Curative-intent Therapy : A Phase 1 Study

Half of patients with muscle-invasive bladder cancer worldwide may not receive curative-intent therapy. Elderly or frail patients are most affected by this unmet need. TAR-200 is a novel, intravesical drug delivery system that provides sustained, local release of gemcitabine into the bladder over a 21-day dosing cycle. The phase 1 TAR-200-103 study evaluated the safety, tolerability, and preliminary efficacy of TAR-200 in patients with muscle-invasive bladder cancer who either refused or were unfit for curative-intent therapy.Materials and Eligible patients had cT2-cT3bN0M0 urothelial carcinoma of the bladder. TAR-200 was inserted for 4 consecutive 21-day cycles over 84 days. The primary end points were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response as determined by cystoscopy, biopsy, and imaging; duration of response; and overall survival. Median age of the 35 enrolled patients was 84 years, and most were male (24/35, 68.6%). Treatment-emergent adverse events related to TAR-200 occurred in 15 patients. Two patients experienced treatment-emergent adverse events leading to removal of TAR-200. At 3 months, complete response and partial response rates were 31.4% (11/35) and 8.6% (3/35), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI 10.1-not estimable) and 14 months (95% CI 10.6-22.7), respectively. Progression-free rate at 12 months was 70.5%. TAR-200 was generally safe, well tolerated, and had beneficial preliminary efficacy in this elderly and frail cohort with limited treatment options

Mapping of QTL for Resistance against the Crucifer Specialist Herbivore Pieris brassicae in a New Arabidopsis Inbred Line Population, Da(1)-12×Ei-2

In Arabidopsis thaliana and other crucifers, the glucosinolate-myrosinase system contributes to resistance against herbivory by generalist insects. As yet, it is unclear how crucifers defend themselves against crucifer-specialist insect herbivores.We analyzed natural variation for resistance against two crucifer specialist lepidopteran herbivores, Pieris brassicae and Plutella xylostella, among Arabidopsis thaliana accessions and in a new Arabidopsis recombinant inbred line (RIL) population generated from the parental accessions Da(1)-12 and Ei-2. This RIL population consists of 201 individual F(8) lines genotyped with 84 PCR-based markers. We identified six QTL for resistance against Pieris herbivory, but found only one weak QTL for Plutella resistance. To elucidate potential factors causing these resistance QTL, we investigated leaf hair (trichome) density, glucosinolates and myrosinase activity, traits known to influence herbivory by generalist insects. We identified several previously unknown QTL for these traits, some of which display a complex pattern of epistatic interactions.Although some trichome, glucosinolate or myrosinase QTL co-localize with Pieris QTL, none of these traits explained the resistance QTL convincingly, indicating that resistance against specialist insect herbivores is influenced by other traits than resistance against generalists

An investigation of neurophysical outcome in paediatric heart surgery patients

Advances in open-heart surgery have resulted in operations being carried out in early infancy.  Numerous studies have been conducted with adults that indicate a variety of neuropsychological deficits after open-heart surgery (e.g. Vingerhoets, Van Nooten,  Vermassen, de Soete &amp; Jannes, 1997) which may be associated with the influence of ischaemic-hypoxic injury upon the brain.  However, little is known about the effect of cardiac surgery in the cognitive development of children. This thesis consists of two papers, the first being a literature review which provides a critique of the existing research in the field of infant cardiac surgery, with particular reference to factors that could contribute to postoperative neurological and neuropsychological morbidity.  Given the paucity of evidence, the second paper (empirical) documents the findings from a neuropsychological outcome study of paediatric heart surgery patients which was conducted to contribute to current knowledge in this area.  The findings of this study are outlined and recommendations are made regarding the direction in which future research should proceed.</p

An investigation of neuropsychological outcome in paediatric heart surgery patients

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

ZERO EMISSION POWER PLANTS USING SOLID OXIDE FUEL CELLS AND OXYGEN TRANSPORT MEMBRANES

Over 16,700 hours of operational experience was gained for the Oxygen Transport Membrane (OTM) elements of the proposed SOFC/OTM zero-emission power generation concept. It was repeatedly demonstrated that OTMs with no additional oxidation catalysts were able to completely oxidize the remaining depleted fuel in a simulated SOFC anode exhaust at an O{sub 2} flux that met initial targets. In such cases, neither residual CO nor H{sub 2} were detected to the limits of the gas chromatograph (&lt;10 ppm). Dried OTM afterburner exhaust streams contained up to 99.5% CO{sub 2}. Oxygen flux through modified OTMs was double or even triple that of the standard OTMs used for the majority of testing purposes. Both the standard and modified membranes in laboratory-scale and demonstration-sized formats exhibited stable performance over extended periods (2300 to 3500 hours or 3 to 5 months). Reactor contaminants, were determined to negatively impact OTM performance stability. A method of preventing OTM performance degradation was developed and proven to be effective. Information concerning OTM and seal reliability over extended periods and through various chemical and thermal shocks and cycles was also obtained. These findings were used to develop several conceptual designs for pilot (10 kWe) and commercial-scale (250 kWe) SOFC/OTM zero emission power generation systems