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Background: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results: We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received >= 22 weeks of alternating therapy; 78% received >= 22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.
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There is a demand for effective training methods that encourage exercise adherence during advancing age, particularly in sedentary populations. This study examined the effects of high-intensity interval training (HIIT) exercise on health-related quality of life (HRQL), aerobic fitness and motivation to exercise in ageing men. Participants consisted of males who were either lifelong sedentary (SED; N = 25; age 63 +/- 5 years) or lifelong exercisers (LEX; N = 19; aged 61 +/- 5 years). [Formula: see text] and HRQL were measured at three phases: baseline (Phase A), week seven (Phase B) and week 13 (Phase C). Motivation to exercise was measured at baseline and week 13. [Formula: see text] was significantly higher in LEX (39.2 +/- 5.6 ml kg min(-1)) compared to SED (27.2 +/- 5.2 ml kg min(-1)) and increased in both groups from Phase A to C (SED 4.6 +/- 3.2 ml kg min(-1), 95 % CI 3.1 - 6.0; LEX 4.9 +/- 3.4 ml kg min(-1), 95 % CI 3.1-6.6) Physical functioning (97 +/- 4 LEX; 93 +/- 7 SED) and general health (70 +/- 11 LEX; 78 +/- 11 SED) were significantly higher in LEX but increased only in the SED group from Phase A to C (physical functioning 17 +/- 18, 95 % CI 9-26, general health 14 +/- 14, 95 % CI 8-21). Exercise motives related to social recognition (2.4 +/- 1.2 LEX; 1.5 +/- 1.0 SED), affiliation (2.7 +/- 1.0 LEX; 1.6 +/- 1.2 SED) and competition (3.3 +/- 1.3 LEX; 2.2 +/- 1.1) were significantly higher in LEX yet weight management motives were significantly higher in SED (2.9 +/- 1.1 LEX; 4.3 +/- 0.5 SED). The study provides preliminary evidence that low-volume HIIT increases perceptions of HRQL, exercise motives and aerobic capacity in older adults, to varying degrees, in both SED and LEX groups.
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This paper analyses the results of a survey of large Australian firms to determine (a) the scale and scope of ethical practices in the firm; and (b) the relationship between the different types of firm manager and the firm's ethical practices. The results suggest that whether or not a firm follows a written code of ethics appears to be strongly related to the age category of the senior manager. The level of education and the employment background of the senior manager do not seem to be related to whether the firm has a written code or not. [ABSTRACT FROM AUTHOR]
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The article reports on additional data collected during interviews for a project investigating the different ways rate may be experience by pre-calculus students. It evaluates the participants' understanding in a specific rate context. Insights into perceptions of rate in several different representations were provided by detailed analysis of the video record of each participant's interview. The article also presents the Victorian Essential Learning Standards (VELS) expectations with respect to the concept of rate.
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Objectives The efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) has been demonstrated to reverse multidrug resistance in Acinetobacter baumannii. We investigated the interaction of NMP with tigecycline and three other tetracyclines on clinical isolates of A. baumannii. Methods One hundred and four clinical isolates of Acinetobacter were tested for susceptibility to tigecycline, minocycline, doxycycline and tetracycline by disc diffusion, and tigecycline MICs were determined by Etest, both in the presence and absence of NMP. Tigecycline MICs and zones of inhibition were interpreted using the BSAC guidelines. An OXA carbapenemase multiplex PCR was also performed on each isolate. Results Mean zones of inhibition for tetracycline, doxycycline and minocycline increased by 11.3%, 22.9% and 11.2%, respectively, in the presence of NMP. In contrast, tigecycline susceptibility was decreased in the presence of NMP, with mean zones of inhibition decreasing by 8.4%. Based on PCR results, all but six isolates belonged to the OXA-23 clone 1. Conclusions Susceptibility to tigecycline of the A. baumannii OXA-23 clone 1 prevalent in the UK is reduced (∼2-fold) by the presence of the efflux inhibitor NMP. NMP does not have the same effect on susceptibility to other tetracyclines.
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William Le Souëf 1 was the fifth and final person to be appointed an assistant protector in the Port Phillip Aboriginal Protectorate when he replaced James Dredge in the Goulburn River District in July 1840. Despite some procrastination by Chief Protector, George Augustus Robinson, but with the urging of Superintendent Charles Joseph La Trobe, Le Souëf filled the vacancy created by Dredge’s resignation. Yet by the end of the year, those in authority were in agreement that he was unfit for service. This paper is the first detailed exploration of William Le Souëf and his relationships with both Robinson and La Trobe.
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The paper reports soil seedbank species composition, of Eucalyptus victrix grassy woodlands, of the upper Fortescue River in the Pilbara District, Western Australia. In this study, our objectives were to investigate germinable soil seedbanks and species composition in response to three simulated seasons, using emergence. Variation in seed density from three depths was tested. Four field sites were sampled. Thirty samples were collected in late spring, after seed rain and prior to summer rainfall. From each sample spot, three soil depths (surface, 1-5, and 6-10 cm) were segregated from beneath surface areas of 100 cm(2). Samples were later incubated in a glasshouse to simulate three different seasonal conditions (autumn, winter and spring). Germinating seedlings were recorded on emergence and grown until identified. Forty-one species germinated, comprising 11 grasses (7 annuals and 4 perennials), 25 annual herbs and 5 perennial herbs. Distribution patterns of germinable seed in both the important annual grass Eragrostis japonica and the perennial Eragrostis setifolia (a preferred cattle fodder species), suggest that seedbank accumulation differs among species and between sites. In part, this may be associated with the absence of grazing. Species with most total germinable seed were E. japonica (Poaceae; 603/m(2)), and the annual herbs Calotis multicaulis (Asteraceae; 346/m(2)), and Mimulus gracilis (Scrophulariaceae; 168/m(2)). Perennial grass seed was sparse. Spring simulation gave most germination (1059), followed by autumn (892) and winter (376) sets. Greatest species diversity was produced from the spring simulation (33 species), followed by autumn (26), and winter (22). Of the total germination, 92% came from 17 species that were represented in all three simulations. Of the 1227 grass seedlings counted, most were recruited from the surface soil (735), followed by the 5 (310) and 10 (182) cm depths. Marginally more grass seedlings germinated from the spring simulation (558) than the autumn set (523). Only 11.9% of grass germinants came from the winter simulation. All grass species recruited from the soil seedbanks had a C-4 photosynthetic pathway. Except for Cenchrus ciliaris all grass species are native to Australia. Of the four sites sampled, one fenced to exclude cattle five years earlier had significantly more germination than the three unfenced sites. Seedbank sampling produced several new records for plants in the areas sampled.
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A group of people are gathered around a tree in St John's Church of England hall. In the group are Mr and Mrs Hattam, W. Armstrong, T. Hoath, R. De Carli, Vic Holland, R. Ross, J. Coulson, W. Kite, A. Henderson, Peter Cameron, Tom Dempsey, Mr and Miss Summers, Mrs Wyatt, Mr Skelly, Peter Ferguson and Mr Finlason.
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Copyright: Centre for Gippsland Studies, Federation University Australia.
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A group of people are gathered around a tree in St John's Church of England hall. In the group are Mr and Mrs Hattam, W. Armstrong, T. Hoath, R. De Carli, Vic Holland, R. Ross, J. Coulson, W. Kite, A. Henderson, Peter Cameron, Tom Dempsey, Mr and Miss Summers, Mrs Wyatt, Mr Skelly, Peter Ferguson and Mr Finlason.
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Copyright: Centre for Gippsland Studies, Federation University Australia.
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International Journal of Intelligent Systems archive Volume 22 Issue 8, August 2007 John Wiley & Sons, Inc. New York, NY, USA table of contents doi>10.1002/int.v22:8
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Gene expression differences accompany both the onset and established phases of hypertension. By an integrated genome-transcriptome approach we performed a meta-analysis of data from 74 microarray experiments available on public databases to identify genes with altered expression in the kidney, adrenal, heart, and artery of spontaneously hypertensive and Lyon hypertensive rats. To identify genes responsible for the onset of hypertension we used a statistical approach that sought to eliminate expression differences that occur during maturation unrelated to hypertension. Based on this adjusted fold-difference statistic, we found 36 genes for which the expression differed between the prehypertensive phase and established hypertension. Genes having possible relevance to hypertension onset included Actn2, Ankrd1, ApoE, Cd36, Csrp3, Me1, Myl3, Nppa, Nppb, Pln, Postn, Spp1, Slc21a4, Slc22a2, Thbs4, and Tnni3. In established hypertension 102 genes exhibited altered expression after Bonferroni correction (P<0.05). These included Atp5o, Ech1, Fabp3, Gnb3, Ldhb, Myh6, Lpl, Pkkaca, Vegfb, Vcam1, and reduced nicotinamide-adenine dinucleotide dehydrogenases. Among the genes identified, there was an overrepresentation of gene ontology terms involved in energy production, fatty acid and lipid metabolism, oxidation, and transport. These could contribute to increases in reactive oxygen species. Our meta-analysis has revealed many new genes for which the expression is altered in hypertension, so pointing to novel potential causative, maintenance, and responsive mechanisms and pathways.
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The effect of moisture content on the thermal properties of rice embryos was investigated using differential scanning calorimetry (DSC). A long grain hybrid rice variety (Jinyou 974) grown in Hunan Province of China was selected in this investigation. The temperature scanning tests were carried out from 20°C to 180°C at different heating rates from 2°C/min to 20°C/min. Consistently higher values of glass transition temperature (Tg) were measured when higher heating rates were used during DSC measurements at every set of moisture contents. The Tg values decreased from (65.28±0.38)°C to (31.08±0.26)°C with increase in moisture content from (10.7±0.3)% to (22.0±0.7)% (w/w). The analysis of variance and the regression analysis showed that both the linear function and Gordon Taylor model can adequately represent the variation of Tg with moisture content (R2 > 0.96).