908 resultados para ASHRAE Standard 55
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Infectious coryza is an upper respiratory tract disease of chickens with the major impact occurring in multi-age flocks. We investigated the relationship between the level of antibodies, as detected by a haemagglutination-inhibition (HI) assay, in infectious coryza-vaccinated chickens and the protection against challenge in those chickens. In one experiment, chickens given a single dose of either of two infectious coryza vaccines lacked a detectable HI response to vaccination but showed significant levels of protection 11 weeks after vaccination. In contrast, in chickens given two doses of an infectious coryza vaccine and challenged 3 weeks after the second vaccine dose, there was a strong serological response with 36/40 birds having a HI titre of 1/20 or greater. In this trial there was an apparent relationship between titre and subsequent protection, with none of the 32 chickens with a titre of 1/40 or 1/80 showing any clinical signs and only one of the same group yielding the challenge organism on culture. In contrast, three of the four vaccinated chickens with a HI titre less than 1/5 developed the typical clinical signs of coryza and yielded the challenge organism on culture. Overall, our results suggest that HI titres cannot be regarded as a definitive predictor of vaccine efficacy. We suggest that the vaccination-challenge trial is the gold standard for the evaluation of the immune response to infectious coryza vaccines.
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Mellitochory, seed dispersal by bees, has been implicated in long-distance dispersal of the tropical rain forest tree, Corymbia torelliana (Myrtaceae). We examined natural and introduced populations of C. torelliana for 4 years to determine the species of bees that disperse seeds, and the extent and distance of seed dispersal. The mechanism of seed dispersal by bees was also investigated, including fruit traits that promote dispersal, foraging behaviour of bees at fruits, and the fate of seeds. The fruit structure of C. torelliana, with seed presented in a resin reward, is a unique trait that promotes seed dispersal by bees and often results in long-distance dispersal. We discovered that a guild of four species of stingless bees, Trigona carbonaria, T. clypearis, T. sapiens, and T. hockingsi, dispersed seeds of C. torelliana in its natural range. More than half of the nests found within 250 m of fruiting trees had evidence of seed transport. Seeds were transported minimum distances of 20-220 m by bees. Approximately 88% of seeds were dispersed by gravity but almost all fruits retained one or two seeds embedded in resin for bee dispersal. Bee foraging for resin peaked immediately after fruit opening and corresponded to a peak of seed dispersal at the hive. There were strong correlations between numbers of seeds brought in and taken out of each hive by bees (r = 0.753-0.992, P < 0.05), and germination rates were 95 ± 5%. These results showed that bee-transported seeds were effectively dispersed outside of the hive soon after release from fruits. Seed dispersal by bees is a non-standard dispersal mechanism for C. torelliana, as most seeds are dispersed by gravity before bees can enter fruits. However, many C. torelliana seeds are dispersed by bees, since seeds are retained in almost all fruits, and all of these are dispersed by bees.
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Better understanding of root system structure and function is critical to crop improvement in water-limited environments. The aims of this study were to examine root system characteristics of two wheat genotypes contrasting in tolerance to water limitation and to assess the functional implications on adaptation to water-limited environments of any differences found. The drought tolerant barley variety, Mackay, was also included to allow inter-species comparison. Single plants were grown in large, soil-filled root-observation chambers. Root growth was monitored by digital imaging and water extraction was measured. Root architecture differed markedly among the genotypes. The drought-tolerant wheat (cv. SeriM82) had a compact root system, while roots of barley cv. Mackay occupied the largest soil volume. Relative to the standard wheat variety (Hartog), SeriM82 had a more uniform rooting pattern and greater root length at depth. Despite the more compact root architecture of SeriM82, total water extracted did not differ between wheat genotypes. To quantify the value of these adaptive traits, a simulation analysis was conducted with the cropping system model APSIM, for a wide range of environments in southern Queensland, Australia. The analysis indicated a mean relative yield benefit of 14.5% in water-deficit seasons. Each additional millimetre of water extracted during grain filling generated an extra 55 kg ha-1 of grain yield. The functional implications of root traits on temporal patterns and total amount of water capture, and their importance in crop adaptation to specific water-limited environments, are discussed.
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Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, characterized especially by myelin and axon damage. Cognitive impairment in MS is common but difficult to detect without a neuropsychological examination. Valid and reliable methods are needed in clinical practice and research to detect deficits, follow their natural evolution, and verify treatment effects. The Paced Auditory Serial Addition Test (PASAT) is a measure of sustained and divided attention, working memory, and information processing speed, and it is widely used in MS patients neuropsychological evaluation. Additionally, the PASAT is the sole cognitive measure in an assessment tool primarly designed for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). The aims of the present study were to determine a) the frequency, characteristics, and evolution of cognitive impairment among relapsing-remitting MS patients, and b) the validity and reliability of the PASAT in measuring cognitive performance in MS patients. The subjects were 45 relapsing-remitting MS patients from Seinäjoki Central Hospital, Department of Neurology and 48 healthy controls. Both groups underwent comprehensive neuropsychological assessments, including the PASAT, twice in a one-year follow-up, and additionally a sample of 10 patients and controls were evaluated with the PASAT in serial assessments five times in one month. The frequency of cognitive dysfunction among relapsing-remitting MS patients in the present study was 42%. Impairments were characterized especially by slowed information processing speed and memory deficits. During the one-year follow-up, the cognitive performance was relatively stable among MS patients on a group level. However, the practice effects in cognitive tests were less pronounced among MS patients than healthy controls. At an individual level the spectrum of MS patients cognitive deficits was wide in regards to their characteristics, severity, and evolution. The PASAT was moderately accurate in detecting MS-associated cognitive impairment, and 69% of patients were correctly classified as cognitively impaired or unimpaired when comprehensive neuropsychological assessment was used as a "gold standard". Self-reported nervousness and poor arithmetical skills seemed to explain misclassifications. MS-related fatigue was objectively demonstrated as fading performance towards the end of the test. Despite the observed practice effect, the reliability of the PASAT was excellent, and it was sensitive to the cognitive decline taking place during the follow-up in a subgroup of patients. The PASAT can be recommended for use in the neuropsychological assessment of MS patients. The test is fairly sensitive, but less specific; consequently, the reasons for low scores have to be carefully identified before interpreting them as clinically significant.
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This joint DPI/Burdekin Shire Council project assessed the efficacy of a pilot-scale biological remediation system to recover Nitrogen (N) and Phosphorous (P) nutrients from secondary treated municipal wastewater at the Ayr Sewage Treatment Plant. Additionally, this study considered potential commercial uses for by-products from the treatment system. Knowledge gained from this study can provide directions for implementing a larger-scale final effluent treatment protocol on site at the Ayr plant. Trials were conducted over 10 months and assessed nutrient removal from duckweed-based treatments and an algae/fish treatment – both as sequential and as stand-alone treatment systems. A 42.3% reduction in Total N was found through the sequential treatment system (duckweed followed by algae/fish treatment) after 6.6 days Effluent Retention Time (E.R.T.). However, duckweed treatment was responsible for the majority of this nutrient recovery (7.8 times more effective than algae/fish treatment). Likewise, Total P reduction (15.75% reduction after 6.6 days E.R.T.) was twice as great in the duckweed treatment. A phytoplankton bloom, which developed in the algae/fish tanks, reduced nutrient recovery in this treatment. A second trial tested whether the addition of fish enhanced duckweed treatment by evaluating systems with and without fish. After four weeks operation, low DO under the duckweed blanket caused fish mortalities. Decomposition of these fish led to an additional organic load and this was reflected in a breakdown of nitrogen species that showed an increase in organic nitrogen. However, the Dissolved Inorganic Nitrogen (DIN: ammonia, nitrite and nitrate) removal was similar between treatments with and without fish (57% and 59% DIN removal from incoming, respectively). Overall, three effluent residence times were evaluated using duckweed-based treatments; i.e. 3.5 days, 5.5 days and 10.4 days. Total N removal was 37.5%, 55.7% and 70.3%, respectively. The 10.4-day E.R.T. trial, however, was evaluated by sequential nutrient removal through the duckweed-minus-fish treatment followed by the duckweed-plus-fish treatment. Therefore, the 70.3% Total N removal was lower than could have been achieved at this retention time due to the abovementioned fish mortalities. Phosphorous removal from duckweed treatments was greatest after 10.4-days E.R.T. (13.6%). Plant uptake was considered the most important mechanism for this P removal since there was no clay substrate in the plastic tanks that could have contributed to P absorption as part of the natural phosphorous cycle. Duckweed inhibited phytoplankton production (therefore reducing T.S.S) and maintained pH close to neutral. DO beneath the duckweed blanket fell to below 1ppm; however, this did not limit plant production. If fish are to be used as part of the duckweed treatment, air-uplifts can be installed that maintain DO levels without disturbing surface waters. Duckweed grown in the treatments doubled its biomass on average every 5.7 days. On a per-surface area basis, 1.23kg/m2 was harvested weekly. Moisture content of duckweed was 92%, equating to a total dry weight harvest of 0.098kg/m2/week. Nutrient analysis of dried duckweed gave an N content of 6.67% and a P content of 1.27%. According to semi-quantitative analyses, harvested duckweed contained no residual elements from the effluent stream that were greater than ANZECC toxicant guidelines proposed for aquaculture. In addition, jade perch, a local aquaculture species, actively consumed and gained weight on harvested duckweed, suggesting potential for large-scale fish production using by-products from the effluent treatment process. This suggests that a duckweed-based system may be one viable option for tertiary treatment of Ayr municipal wastewater. The tertiary detention lagoon proposed by the Burdekin Shire Council, consisting of six bays approximately 290 x 35 metres (x 1.5 metres deep), would be suitable for duckweed culture with minor modification to facilitate the efficient distribution of duckweed plants across the entire available growing surface (such as floating containment grids). The effluent residence time resulting from this proposed configuration (~30 days) should be adequate to recover most effluent nutrients (certainly N) based on the current trial. Duckweed harvest techniques on this scale, however, need to be further investigated. Based on duckweed production in the current trial (1.23kg/m2/week), a weekly harvest of approximately 75 000kg (wet weight) could be expected from the proposed lagoon configuration under full duckweed production. A benefit of the proposed multi-bay lagoon is that full lagoon production of duckweed may not be needed to restore effluent to a desirable standard under the present nutrient load, and duckweed treatment may be restricted to certain bays. Restored effluent could be released without risk of contaminating the receiving waterway with duckweed by evacuating water through an internal standpipe located mid-way in the water column.
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Temporomandibular disorders (TMD) and psychosocial factors reportedly associate. The underlying factors remain partially obscure, however, and further studies are required to clarify the relationships. The aims of this study were thus to assess in a non-patient working population the prevalence of TMD and related symptoms, and to clinically diagnose and follow the natural courses of TMD over a one-year period. In addition, possible comorbidity of temporomandibular and/or neck muscle pain and perceived stress and their impact on work performance were investigated, as well as how various psychosocial aspects relate to TMD. A questionnaire was mailed to all 30- to 55-year-old employees of the Finnish Broadcasting Company Ltd. whose employment in the Helsinki area had lasted at least five years (n = 1784). Of the 1339 subjects, who returned the questionnaire, 241 were examined according to the RDC/TMD and standard neck muscle palpation methods. Clinical signs of temporomandibular and/or neck muscle pain were found in 118 subjects. One-year follow-up TMD examinations were conducted on 211 subjects. The prevalence of frequent painless TMJ-related symptoms was 10%, orofacial pain 7%, neck pain 38%, and headache 15%. TMD diagnoses were: myofascial pain (13%), disc displacements (16%), and arthralgia, osteoarthritis, osteoarthrosis (4%). Chronic myofascial pain was present in 7% and chronic disc displacement with reduction in 11% of the subjects. Symptoms were significantly associated with almost all the studied psychosocial symptoms. Reduced work performance was significantly positively associated with continuous pain, severity of pain, and health stress perception, and according to logistic regression, somatization with the probability of having chronic myofascial pain. It could be concluded based on the results of this study among a non-patient working population that TMD and related symptoms are common and associated with psychosocial factors. Moreover, myofascial pain and disc displacement with reduction are the most common diagnoses of TMD. In addition, self-reported health related stress, and continuous pain in temporomandibular and/or neck muscles are associated with reduced work performance, and somatization is significantly associated with chronic myofascial pain.
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Dairy farms located in the subtropical cereal belt of Australia rely on winter and summer cereal crops, rather than pastures, for their forage base. Crops are mostly established in tilled seedbeds and the system is vulnerable to fertility decline and water erosion, particularly over summer fallows. Field studies were conducted over 5 years on contrasting soil types, a Vertosol and Sodosol, in the 650-mm annual-rainfall zone to evaluate the benefits of a modified cropping program on forage productivity and the soil-resource base. Growing forage sorghum as a double-crop with oats increased total mean annual production over that of winter sole-crop systems by 40% and 100% on the Vertosol and Sodosol sites respectively. However, mean annual winter crop yield was halved and overall forage quality was lower. Ninety per cent of the variation in winter crop yield was attributable to fallow and in-crop rainfall. Replacing forage sorghum with the annual legume lablab reduced fertiliser nitrogen (N) requirements and increased forage N concentration, but reduced overall annual yield. Compared with sole-cropped oats, double-cropping reduced the risk of erosion by extending the duration of soil water deficits and increasing the time ground was under plant cover. When grown as a sole-crop, well fertilised forage sorghum achieved a mean annual cumulative yield of 9.64 and 6.05 t DM/ha on the Vertosol and Sodosol, respectively, being about twice that of sole-cropped oats. Forage sorghum established using zero-tillage practices and fertilised at 175 kg N/ha. crop achieved a significantly higher yield and forage N concentration than did the industry-standard forage sorghum (conventional tillage and 55 kg N/ha. crop) on the Vertosol but not on the Sodosol. On the Vertosol, mean annual yield increased from 5.65 to 9.64 t DM/ha (33 kg DM/kg N fertiliser applied above the base rate); the difference in the response between the two sites was attributed to soil type and fertiliser history. Changing both tillage practices and N-fertiliser rate had no affect on fallow water-storage efficiency but did improve fallow ground cover. When forage sorghum, grown as a sole crop, was replaced with lablab in 3 of the 5 years, overall forage N concentration increased significantly, and on the Vertosol, yield and soil nitrate-N reserves also increased significantly relative to industry-standard sorghum. All forage systems maintained or increased the concentration of soil nitrate-N (0-1.2-m soil layer) over the course of the study. Relative to sole-crop oats, alternative forage systems were generally beneficial to the concentration of surface-soil (0-0.1 m) organic carbon and systems that included sorghum showed most promise for increasing soil organic carbon concentration. We conclude that an emphasis on double-or summer sole-cropping rather than winter sole-cropping will advantage both farm productivity and the soil-resource base.
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Field studies were conducted over 5 years on two dairy farms in southern Queensland to evaluate the impacts of zero-tillage, nitrogen (N) fertiliser and legumes on a winter-dominant forage system based on raingrown oats. Oats was able to be successfully established using zero-tillage methods, with no yield penalties and potential benefits in stubble retention over the summer fallow. N fertiliser, applied at above industry-standard rates (140 vs. 55 kg/ha.crop) in the first 3 years, increased forage N concentration significantly and had residual effects on soil nitrate-N at both sites. At one site, crop yield was increased by 10 kg DM/ha. kg fertiliser N applied above industry-standard rates. The difference between sites in fertiliser response reflected contrasting soil and fertiliser history. There was no evidence that modifications to oats cropping practices (zero-tillage and increased N fertiliser) increased surface soil organic carbon (0-10 cm) in the time frame of the present study. When oats was substituted with annual legumes, there were benefits in improved forage N content of the oat crop immediately following, but legume yield was significantly inferior to oats. In contrast, the perennial legume Medicago sativa was competitive in biomass production and forage quality with oats at both sites and increased soil nitrate-N levels following termination. However, its contribution to winter forage was low at 10% of total production, compared with 40% for oats, and soil water reserves were significantly reduced at one site, which had an impact on the following oat production. The study demonstrated that productive grazed oat crops can be grown using zero tillage and that increased N fertiliser is more consistent in its effect on N concentration than on forage yield. A lucerne ley provides a strategy for raising soil nitrate-N concentration and increasing overall forage productivity, although winter forage production is reduced.
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This report evaluates the wood and veneer properties of plantation-grown spotted gum (Corymbia citriodora subsp. variegata, or CCV) and Dunn's white gum (Eucalyptus dunnii), grown at different stockings, in thinning trials near Ellangowan in north-east New South Wales (mean annual rainfall 1050 mm) and Kingaroy in south-east Queensland (mean annual rainfall 873 mm). Thinning trials were established at age seven years. Both species showed a significant increase in stem diameter growth of the dominant trees in response to thinning. At age 10 years, trees from the unthinned (950–1270 stems ha-1) and 300 stems ha-1 treatments were selected for veneering. Five dominant trees were felled from each combination of species x sites x thinning treatment. Diameter at breast height over bark of the selected trees ranged from 20 cm to 27 cm at Ellangowan, and 19 cm to 26 cm at Kingaroy. From each tree, 1.5 m long billets were removed at two positions: a butt billet from 0.3–1.8 m above ground and a top billet from approximately 5.5–7.0 m. Log end splitting was assessed 24 hours after harvesting and again after steaming, approximately four days after harvesting. Disks from just above both billets were collected for assessment of wood properties. Billets were peeled on a spindleless veneer lathe to produce a full veneer ribbon with a target green thickness of 2.8 to 3.0 mm. The 1.55 m wide (tangential dimension) veneer sheets were dried and graded according to AS/NZ Standard 2269:2008, which describes four veneer grades. Veneer samples taken along the length of the veneer ribbon, at regular intervals of 1.55 m, were tested for stiffness, shrinkage and density. Veneer length measurements were used to calculate the radial distance of each sample from the central axis of the billet. Overall veneer gross recoveries ranged from 50% to 70%. They were significantly lower at the Kingaroy site, for both species. The veneer recoveries achieved were 2–3 times higher than typical green off saw recoveries from small plantation hardwood logs of similar diameter. Most of the veneer recovered was classified as D-grade. CCV trees from the Ellangowan site yielded up to 38% of the better C-grade and higher grade veneers. The main limiting factors that prevented veneer from meeting higher grades were the presence of kino defects and encased knots. Splits in E. dunnii veneer also contributed to reduced grade quality. Log end splits were higher for E. dunnii than for CCV, and logs from Ellangowan exhibited more severe splitting. Split index was generally higher for top than for butt billets. Split index was strongly correlated with the average veneer grade from corresponding billets. The Ellangowan site, where rainfall was higher and trees grew faster, yielded significantly denser and stiffer veneers than did the drier sites near Kingaroy, where tree growth was slower. The difference was more pronounced for E. dunnii than for CCV. Differences in measured wood properties between thinned and unthinned treatments were generally small and not significant. On average, 10% of billet volume was lost during the peeling rounding-up process. Much of the wood laid down following thinning was removed during rounding-up, meaning the effect of thinning on veneer properties could not be effectively assessed. CCV was confirmed as having high veneer density and very good veneer stiffness, exceeding 15 GPa, making it very suitable for structural products. E. dunnii also demonstrated good potential as a useful structural plywood resource, achieving stiffness above 10 GPa. Veneer stiffness and density in CCV increased from pith to bark at both sites, while for E. dunnii there was a radial increase in these properties at the Ellangowan site only. At the drier Kingaroy site, veneer stiffness and density declined from mid-radius to the log periphery. This may be associated with prolonged drought from 2005 to 2009, corresponding to the later years of tree growth at the Kingaroy site. CCV appeared to be less sensitive to drought conditions. Standing tree acoustic velocity, determined by the Fakopp time-of-flight method, provided a reliable prediction of average veneer stiffness for both species (R2=0.78 for CCV and R2=0.90 for E. dunnii) suggesting that the Fakopp method may be a useful indicator of tree and stand quality, in terms of veneer stiffness in standing trees.
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Background Malnutrition is common in patients with advanced epithelial ovarian cancer (EOC), and is associated with impaired quality of life (QoL), longer hospital stay and higher risk of treatment-related adverse events. This phase III multi-centre randomised clinical trial tested early enteral feeding versus standard care on postoperative QoL. Methods From 2009 to 2013, 109 patients requiring surgery for suspected advanced EOC, moderately to severely malnourished were enrolled at five sites across Queensland and randomised to intervention (n = 53) or control (n = 56) groups. Intervention involved intraoperative nasojejunal tube placement and enteral feeding until adequate oral intake could be maintained. Despite being randomised to intervention, 20 patients did not receive feeds (13 did not receive the feeding tube; 7 had it removed early). Control involved postoperative diet as tolerated. QoL was measured at baseline, 6 weeks postoperatively and 30 days after the third cycle of chemotherapy. The primary outcome measure was the difference in QoL between the intervention and the control group. Secondary endpoints included treatment-related adverse event occurrence, length of stay, postoperative services use, and nutritional status. Results Baseline characteristics were comparable between treatment groups. No significant difference in QoL was found between the groups at any time point. There was a trend towards better nutritional status in patients who received the intervention but the differences did not reach statistical significance except for the intention-to-treat analysis at 7 days postoperatively (11.8 intervention vs. 13.8 control, p 0.04). Conclusion Early enteral feeding did not significantly improve patients' QoL compared to standard of care but may improve nutritional status.
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This work deals with the formulation and implementation of finite deformation viscoplasticity within the framework of stress-based hybrid finite element methods. Hybrid elements, which are based on a two-field variational formulation, are much less susceptible to locking than conventional displacement-based elements. The conventional return-mapping scheme cannot be used in the context of hybrid stress methods since the stress is known, and the strain and the internal plastic variables have to be recovered using this known stress field.We discuss the formulation and implementation of the consistent tangent tensor, and the return-mapping algorithm within the context of the hybrid method. We demonstrate the efficacy of the algorithm on a wide range of problems.
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Zebu (Bos indicus) crossbred beef cows (Droughtmaster) were maintained long-term (16 months) on standard nutrition (SN) or improved nutrition (IN). Cows on IN had better body condition and greater (P<0.05) circulating concentrations of leptin than cows on SN (0.7±0.1n/ml and 1.7±0.1n/ml, respectively). There were no outstanding differences between SN and IN cows in basal number of ovarian follicles (≤4mm, 5-8mm, and≥9mm) and there were also no differences in number of oocytes recovered by oocyte pick-up. Cows on IN had a greater (P<0.05) number of total follicles after stimulation with FSH than cows on SN. Oocytes from cows on IN had greater (P<0.05) lipid content than cows on SN (-0.23±0.16 and 0.20±0.18 arbitrary units, respectively) and oocytes of the former cows also tended to have more active mitochondria, although this was not significant. Cows on IN showed a positive relationship (R2=0.31, P<0.05) between plasma leptin and oocyte lipid content. Lipids are utilized by oocytes during high energy consumptive processes including fertilization and early cleavage. The greater lipid content of oocytes from IN cows could therefore confer a reproductive advantage. The present study has shown relationships between nutrition, body condition, circulating leptin, and oocyte lipid content, but a clear cause-and-effect requires further investigation in the cow. © 2013 Elsevier B.V.
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This paper describes a public pedagogy project embedded into "The Global Teacher", a subject within the Bachelor of Education program for student teachers at an Australian university. The subject provides a global perspective on socio-political issues that shape education. In 2013, The Global Teacher introduced an approach that asked student teachers to create a museum-style exhibition depicting six global education themes. This exhibition was displayed in the State Library and the public were invited to engage with the installations and the student teachers who created them. Our paper describes how the project was implemented by means of close collaboration between the QUT teacher educators, curators at the State Library of Queensland (SLQ), and student groups working on visually translating their understandings of global educational issues into a public exhibition. We discuss what was learned by our students and ourselves, as teacher educators, by engaging in this public pedagogy.
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- Background Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). - Objective This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. - Data sources Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. - Review methods A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. - Results Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. - Limitations Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. - Conclusions From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. - Funding The Health Technology Assessment Programme of the National Institute for Health Research.
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Two typical alternative conformations for double strandee polynucleotides with Watson-Crick base pairing scheme are presented. these types avoid tangling of the chains. Representative models of these types with two different views, to show the similarity and dissimilarity between these models and the Watson-Crick model, are given.