883 resultados para WARFARIN DOSE REQUIREMENTS


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Businesses need property in order to generate turnover and profits. If real estate owners are to be able to provide properties and related services that are desirable, it is crucial that they understand tenants’ requirements and preferences. Changes in the way businesses operate might well lead to an overall reduction in space requirements in all sectors. Faced with reductions in demand, landlords will find themselves in an increasingly competitive marketplace for tenants. Of the array of strategies available to landlords, what strategies should they employ for maximum effect? This paper examines what United Kingdom tenants want from commercial property (retail, industrial and office). The first part provides an analysis of data from several hundred interviews with occupiers of commercial properties owned by some of the largest UK real estate investment companies. Results are presented for each of the asset classes separately. The second part compares the findings with previous research and discusses the strategic implications for landlords.

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Position in the social hierarchy can influence brain dopamine function and cocaine reinforcement in nonhuman primates during early cocaine exposure. With prolonged exposure, however, initial differences in rates of cocaine self-administration between dominant and subordinate monkeys dissipate. The present studies used a choice procedure to assess the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys with extensive cocaine self-administration histories. Responding was maintained under a concurrent fixed-ratio 50 schedule of food and cocaine (0.003-0.1 mg/kg per injection) presentation. Responding on the cocaine-associated lever increased as a function of cocaine dose in all monkeys. Although response distribution was similar across social rank when saline or relatively low or high cocaine doses were the alternative to food, planned t tests indicated that cocaine choice was significantly greater in subordinate monkeys when choice was between an intermediate dose (0.01 mg/kg) and food. When a between-session progressive-ratio procedure was used to increase response requirements for the preferred reinforcer (either cocaine or food), choice of that reinforcer decreased in all monkeys. The average response requirement that produced a shift in response allocation from the cocaine-associated lever to the food-associated lever was higher in subordinates across cocaine doses, an effect that trended toward significance (p = 0.053). These data indicate that despite an extensive history of cocaine self-administration, most subordinate monkeys were more sensitive to the relative reinforcing strength of cocaine than dominant monkeys.

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Changes to client requirements are inevitable during construction. Industry discourse is concerned with minimizing and controlling changes. However, accounts of practices involved in making changes are rare. In response to calls for more research into working practices, an ethnographic study of a live hospital project was undertaken to explore how changes are made. A vignette of a meeting exploring the investigation of changes illustrates the issues. This represents an example from the ethnographic fieldwork, which produced many observations. There was a strong emphasis on using change management procedures contained within the contract to investigate changes, even when it was known that the change was not required. For the practitioners, this was a way of demonstrating best practice, transparent and accountable decision-making regarding changes. Hence, concerns for following procedures sometimes overshadowed considerations about whether or not a change was required to improve the functionality of the building. However, the procedures acted as boundary objects between the communities of practice involved on the project by coordinating the work of managing changes. Insights suggest how contract procedures facilitate and impede the making of changes, which can inform policy guidance and contract drafting.

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Flexibility of information systems (IS) have been studied to improve the adaption in support of the business agility as the set of capabilities to compete more effectively and adapt to rapid changes in market conditions (Glossary of business agility terms, 2003). However, most of work on IS flexibility has been limited to systems architecture, ignoring the analysis of interoperability as a part of flexibility from the requirements. This paper reports a PhD project, which proposes an approach to develop IS with flexibility features, considering some challenges of flexibility in small and medium enterprises (SMEs) such as the lack of interoperability and the agility of their business. The motivation of this research are the high prices of IS in developing countries and the usefulness of organizational semiotics to support the analysis of requirements for IS. (Liu, 2005).

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Risk assessment for mammals is currently based on external exposure measurements, but effects of toxicants are better correlated with the systemically available dose than with the external administered dose. So for risk assessment of pesticides, toxicokinetics should be interpreted in the context of potential exposure in the field taking account of the timescale of exposure and individual patterns of feeding. Internal concentration is the net result of absorption, distribution, metabolism and excretion (ADME). We present a case study for thiamethoxam to show how data from ADME study on rats can be used to parameterize a body burden model which predicts body residue levels after exposures to LD50 dose either as a bolus or eaten at different feeding rates. Kinetic parameters were determined in male and female rats after an intravenous and oral administration of 14C labelled by fitting one-compartment models to measured pesticide concentrations in blood for each individual separately. The concentration of thiamethoxam in blood over time correlated closely with concentrations in other tissues and so was considered representative of pesticide concentration in the whole body. Body burden model simulations showed that maximum body weight-normalized doses of thiamethoxam were lower if the same external dose was ingested normally than if it was force fed in a single bolus dose. This indicates lower risk to rats through dietary exposure than would be estimated from the bolus LD50. The importance of key questions that should be answered before using the body burden approach in risk assessment, data requirements and assumptions made in this study are discussed in detail.

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Recent evidence from animal and adult human subjects has demonstrated potential benefits to cognition from flavonoid supplementation. This study aimed to investigate whether these cognitive benefits extended to a sample of school-aged children. Using a cross-over design, with a wash out of at least seven days between drinks, fourteen 8-10 year old children consumed either a flavonoid-rich blueberry drink or matched vehicle. Two hours after consumption, subjects completed a battery of five cognitive tests comprising the Go-NoGo, Stroop, Rey’s Auditory Verbal Learning Task, Object Location Task, and a Visual N-back. In comparison to vehicle, the blueberry drink produced significant improvements in the delayed recall of a previously learned list of words, showing for the first time a cognitive benefit for acute flavonoid intervention in children. However, performance on a measure of proactive interference indicated that the blueberry intervention led to a greater negative impact of previously memorised words on the encoding of a set of new words. There was no benefit of our blueberry intervention for measures of attention, response inhibition or visuo-spatial memory. While findings are mixed, the improvements in delayed recall found in this pilot study suggest that, following acute flavonoid-rich blueberry interventions, school aged children encode memory items more effectively.

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This paper describes an application of Social Network Analysis methods for identification of knowledge demands in public organisations. Affiliation networks established in a postgraduate programme were analysed. The course was executed in a distance education mode and its students worked on public agencies. Relations established among course participants were mediated through a virtual learning environment using Moodle. Data available in Moodle may be extracted using knowledge discovery in databases techniques. Potential degrees of closeness existing among different organisations and among researched subjects were assessed. This suggests how organisations could cooperate for knowledge management and also how to identify their common interests. The study points out that closeness among organisations and research topics may be assessed through affiliation networks. This opens up opportunities for applying knowledge management between organisations and creating communities of practice. Concepts of knowledge management and social network analysis provide the theoretical and methodological basis.

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The evolution of fungicide resistance in the cereal pathogen Zymoseptoria tritici, is a serious threat to the sustainability and profitability of wheat production in Europe. Application of azole fungicides has been shown to affect fitness of Z. tritici variants differentially, so it has been hypothesised that combinations of azoles could slow the evolution of resistance. This work was initiated to assess the effects of dose, mixtures and alternations of two azoles on selection for isolates with reduced sensitivity and on disease control. Naturally infected field trials were carried out at six sites across Ireland and the sensitivity of Z. tritici isolates monitored pre- and post-treatment. The azoles epoxiconazole and metconazole were applied as solo products, in alternation with each other and as a pre-formulated mixture. Full and half label doses were tested. The two azoles were partially cross-resistant, with a common azole resistance principal component accounting for 75% of the variation between isolates. Selection for isolates with reduced azole sensitivity was correlated with disease control. Decreased doses were related to decreases in sensitivity but the effect was barely significant (P = 0.1) and control was reduced. Single applications of an active ingredient (a.i.) caused smaller decreases in sensitivity than double applications. Shifts in sensitivity to the a.i. applied to a plot were greater than to the a.i. not applied, and the decrease in sensitivity was greater to the a.i. applied at the second timing. These results confirm the need to mix a.i.s with different modes of action.

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Callosobruchus maculatus has for years remained a serious menace in cowpea in Sub-Sahara Africa. The objective of this study was to investigate the effect of genotypic cowpea (Vigna unguiculata (L.) Walp) varieties, time and dose on C. maculatus exposed to powders of Piper guineense and Eugenia aromatica. Irrespective of duration and botanicals, bruchid reared on KDV showed the highest tolerance to both plant materials; while their counterparts from IAR48V were the most susceptible. Median lethal time (LT50) also varied according to the plant materials; with the highest in KDV reared bruchid [P. guineense: KDV (18.31), IAR48V (9.27), IFBV (13.17); E. aromatica: KDV (76.01), IAR48V (5.59), IFBV (6.49)]. There was a significant impact of cowpea variety (V), exposure time (T) and dose (D) on the tolerance of C. maculatus to both plant materials. The effect of all two-way (VxT, VxD, DxT) and three way interactions (V×T×D) on the tolerance of C. maculatus to both plant materials was also significant. Varietal effect was more pronounced in bruchids exposed to E. aromatica; while exposure time was more pronounced in bruchids exposed to P. guineense.

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Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

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BACKGROUND: The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown. METHOD: We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales. RESULTS: Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv. CONCLUSION: Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.

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As a prelude to leaf-specific weed control using droplets targeted by a robotic weeder, amounts of herbicide required to control individual weed seedlings were estimated. Roundup Biactive was applied at doses equivalent to 1/128th to four times the recommended rate in addition to undiluted Roundup and water controls. Based on the mean ground cover of the seedlings, the recommended dose (1.5 l ha 1) was estimated and droplets were applied to individual plants by micropipette. All treatments contained 1% AS 500 SL, Agromix (adjuvant). Three weeks after application dry weights (DW) of each seedling was recorded. DW reductions of 50% were achieved in the five species tested at less than the recommended rate whereas only in one species was a 90% reduction obtained at that rate. In Galium aparine for example, 19.3 μg of glyphosate reduced DW per plant by 90% compared to the recommended dose of 8.4 μg.