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1.
MANN  D. G. 《Annals of botany》1983,52(4):573-581
The development and final morphology of the valve in raphe-bearingdiatoms exhibit a cryptic lateral polarity, and hence two typesof frustule can be distinguished. In the cis type both valveshave the same orientation; in the trans type they have oppositeorientations. Examination of a variety of taxa suggests thatin all dividing raphid diatoms, both new valves have the sameorientation and so only three types of division are possible:cis; cis + cis, cis trans + trans, trans; cis+trans. The possessionof different combinations of these explains the observed ratiosof cis: trans in different taxa, viz all cis; 1: 2 cis: trans;and roughly 1: 1 cis: trans. The implications of the resultsfor diatom systematics are examined, with special referenceto Navicula Bory. Diatom systematic, diatom valve morphogenesis, cell symmetry, raphe structure  相似文献   

2.
 理论上,土壤呼吸通量的量值可以通过观测土壤呼吸CO2扩散速率(əc/ət)计算得到。但是为获得əc/ət,通常须允许土壤呼吸箱内CO2浓度升高,因此,如何估算外界大气CO2浓度条件下的əc/ət是土壤呼吸观测技术的关键,关系到观测结果的准确性。通常əc/ət的估算会受土壤表层大气CO2扩散梯度(即土壤呼吸箱内CO2扩散梯度和大气CO2浓度昼夜变化)的影响。目前,线性回归方法是土壤呼吸观测中估算əc/ət的基本方法。然而,常用的线性回 归方法会低估əc/ət,而指数回归方法则可以准确地估算əc/ət。夜间əc/ət的变化与大气CO2 浓度之间存在非常明显的负相关关系。夜间土壤表层大气CO2扩散梯度的减小导致线性回归方法明显低估əc/ət。əc/ət的昼夜变化过程存在明显的非对称性现象,而指数回归方法可以更好地描述əc/ət昼夜变化的非对称性响应。  相似文献   

3.
NEWTON  MARTHA E. 《Annals of botany》1972,36(1):163-178
As Mnium undulatum was shown to be homosporous, it was concludedthat neither male nor female derived an advantage from sporesize that might be related to the observed excess of femaleplants. The rate of germination was greater at 20 °C thanat 10 °C in M. hornum and M. undulatum, and was also reducedin short days (7.25 hours) at both temperatures. Spores of M.undulatum germinated more slowly than those of M. hornum undereach of the environmental regimes used. Isolated spores of M.undulatum showed a ratio of 1: 4.1 compared with 1: 0.89 inM. hornum. The excess of female plants of M. undulatum thathad been established by the end of germination, was maintainedamongst the first protonemal buds produced (1: 3.5), whereasan excess of male M. hornum was observed in the first protonemalbuds (1: 0.45). Frost reduced the rate of germination in M.undulatum, but unlike desiccation did not affect the final percentage.Male and female were amongst the spores which survived desiccationat 10 °C. Regeneration of detached leaves occurred more rapidly in M.undulatum than in M. hornum, and no difference between maleand female was detected. It was found that frost prior to orduring regeneration did not produce long-term harmful effectsin M. undulatum. None of the young male gametophytes producedby regeneration from leaves survived desiccation, compared with77 per cent of similarly produced female gametophytes.  相似文献   

4.
Water-relations parameters were measured on sections of secondaryphloem from red oak (Quercus borealis michx. f.) and white ash(Fraxinus americana var. biltmoreana [Beadle] J. Wright) usinga linear displacement transducer. Changes in tissue thicknessin response to changes in the osmotic pressure of the bathingsolution were used to calculate the volumetric elastic modulusplus osmotic pressure (v + ) of the tissue, and an applied forcemethod was used to estimate the time constant for water equilibration(T). The hydraulic conductivity of the cell membranes (Lp) wascalculated utilizing v + and r values. The time-dependent behaviour of the tissue was much more complexthan originally expected. A correction for a time-dependentprocess that we call ‘drift’ was required to obtainnumbers for v + . Furthermore, v + was calculated on two assumptionsin order to relate changes in tissue dimensions to sieve elementparameters. In the first case, a lower limit for v + of thesieve elements was determined by attributing all changes intissue dimensions to these cells. For red oak the average v+ on this assumption is 72 bars. Assuming that all cell typeswere equally responsible for the changes in tissue dimensionsresulted in an v + value of 192 bars for oak. If v + and rare the same for all cells in the tissue, Lp for the sieve elementsof oak is 9.6 x 10–8 cm s–1 bar–1. Exudationfrom the sieve elements of white ash during excision of thephloem led to artificially high values of v + for that species. Quercus borealis michx. f., Fraxinus americana var, biltmoreana (Beadle) J. Wright, red oak, white ash, water relations, phloem, volumetric elastic modulus, membrane hydraulic conductivity  相似文献   

5.
The effects of -hydroxy-2-pyridinemethanesulphonic acid (-HPMS)upon net photosynthesis (Pn, the CO2 compensation point (),post-lower illumination burst of CO2 (PLIB) and post-lower temperatureburst of CO2 (PLTB) in detached rye (Secale cereale L.) leaveswere investigated. At low concentrations ( 0.5 mol m–3),-HPMS initially stimulated Pn and decreased the magnitude ofboth PLIB and PLTB. The decreased at all concentrations of-HPMS (0.05–5.0 mol m–3. The effects of -HPMS onPn and were time-dependent and, after a few minutes, the Pnwas inhibited while values increased considerably. At a higherconcentration (5.0 mol m –3), the transient effects of-HPMS were shorter () or not observed at all (Pn. Both PLIBand PLTB, when expressed in relation to Pn, increased at higherlevels of this compound. Similar data with respect to the effectsof -HPMS on PLIB and PLTB were found for leaves of dandelion(Taraxacum officinale L.). The results suggest that -HPMS may stimulate Pn by inhibitingphotorespiration, as originally suggested by Zelitch (1966),but only at low concentrations and over a short time span. Thedecrease of PLIB and PLTB values at low -HPMS levels is consistentwith these processes being a residual activity of the glycolatepathway. Key words: CO2 compensation point, -hydroxy-2-pyridinemethanesulphonic acid, photorespiration, photosynthesis  相似文献   

6.
Water Relations of Tropical Epiphytes: II. PERFORMANCE DURING DROUGHTING   总被引:2,自引:0,他引:2  
Relative water content R, water potential and leaf diffusiveconductance C5 were monitored while five tropical epiphyteswere subjected to an extended period of drought. The speciesstudied were: ferns Pyrrosia adnascens (Forst.) Ching and Pyrrosiaangustata (Sw.) Ching, family Polypodiaceae; orchids: Eria velutinaLindl., Dendrobium tortile Lindl. and Dendrobium crumenatumSw. The ferns reached zero turgor rapidly and after only small declinesin relative water content (R) and . Beyond this point stomatalmovement seemed strongly suppressed, but the leaves continuedto lose water vapour until very low values of R were reached.Nevertheless, on re-watering water potential (), R and diffusiveconductance (C5) returned to pre-stress levels within 3 d. The orchids showed a more gradual decline in R and , stomatalactivity was not so strongly suppressed, and night opening ofstomata was observed under stress. The relationship between and R was found for each species,curves being fitted to the data points by non-linear regression.From these analyses it was concluded that these species hadvery dilute cell sap, and consequently the change in for agiven decline in R was smaller than for most other species recordedin the literature. Key words: Orchid, Fern, Drought, Relative water content, Diffusive conductance, Water potential  相似文献   

7.
Information on the biosynthesis of the D-arabinans of the cellwall of Mycobacterium tuberculosis is rapidly emerging, withthe promise of new targets for drug development against tuberculosis.Accordingly, arabinosyl transferase assays were developed utilizingsynthesized [1–14C]-β-D-arabinofuranosyl-1-monophosphoryldecaprenolas donor and a variety of O- and S-alkyl arabinosides as acceptors.These were: -D-Araf-(15)--D-Araf-O- and -S-alkyl di-arabinosidesand -D-Araf-(15)--D-Araf-(15)--D-Araf-O- and -S-alkyl triarabinosides.Whereas the O- and S-alkyl monosaccharide acceptors were inactive,the O- and S-alkyl disaccharide and the O- and S-alkyl trisaccharideacceptors (<C12) possessed considerable acceptor activity,and the trisaccharide acceptors were more potent than the correspondingdisaccharides. The O-alkyl disaccharide acceptors with a C8alkyl chain were more active than those containing the C6 orC10 analogs. Chemical analysis of the enzymatically synthesizedproducts of the reactions demonstrated that β-D-arabinofuranosyl-1-monophosphoryldecaprenolwas an effective donor for two of the three potential arabinosyltransferases: β-D-arabinofuranosyl-1-monophosphoryldecaprenol:arabinan (15) arabinosyl transferase and β-D-arabinofuranosyl-1-monophosphoryl-decaprenol:arabinan β(12) arabinosyl transferase. The β(12) arabinosyltransferase activity was more in evidence in the presence ofthe O-alkyl disaccharide acceptor, whereas both transferaseswere about equivalent in the presence of the S-alkyl trisaccharideacceptor. The tuberculosis drug, ethambutol, a known mycobacterialarabinosyl transferase inhibitor, was inactive within thesearabinosyl transferase/acceptor based assay systems, supportingother evidence that a third activity, responsible for the formationof 13 linkage, is the drug target. acceptor arabinan biosynthesis glycosyltrans-ferase assay mycobacteria  相似文献   

8.
KASSAM  A. H. 《Annals of botany》1975,39(2):265-271
Wilting of leaves of Vicia faba L., which occurs when the pressurepotential (p) is zero, and the leaf-water potential () at wiltingboth depend entirely upon the solute potential at incipientplasmolysis (so) and not on soil-water status. Wilting in V.faba is acropetal; this is consistent with the hypothesis thatthere is a gradient of decreasing so up the plant and that wateris transferred from the lower to the upper leaves, hasteningthe overall water loss from the lower leaves to the point whenp is zero. The gradient in so up the plant is of the order of3–8 bar. It is proposed that wilting when p>0 (i.e. > so) shouldbe ‘apparent wilting’ and that when p0 (i.e. so),‘true wilting’.  相似文献   

9.
Summary: Suffix tree is one of the most fundamental data structuresin string algorithms and biological sequence analysis. Unfortunately,when it comes to implementing those algorithms and applyingthem to real genomic sequences, often the main memory size becomesthe bottleneck. This is easily explained by the fact that whilea DNA sequence of length n from alphabet = {A, C, G, T } canbe stored in n log ||= 2n bits, its suffix tree occupies O(nlog n) bits. In practice, the size difference easily reachesfactor 50. We provide an implementation of the compressed suffix tree veryrecently proposed by Sadakane (Theory of Computing Systems,in press). The compressed suffix tree occupies space proportionalto the text size, i.e. O(n log} | |) bits, and supports alltypical suffix tree operations with at most log n factor slowdown.Our experiments show that, e.g. on a 10 MB DNA sequence, thecompressed suffix tree takes 10% of the space of normal suffixtree. Typical operations are slowed down by factor 60. Availability: The C++ implementation under GNU license is availableat http://www.cs.helsinki.fi/group/suds/cst/. An example programimplementing a typical pattern discovery task is included. Experimentalresults in this note correspond to version 0.95. Contact: vmakinen{at}cs.helsinki.fi  相似文献   

10.
It was shown in the previous paper of this series that the Mexicanspecies Solanum bulbocastanum, S. cardiophyllum subsp. cardiophyllumand subsp. ehrenbergii, S. michoacanum and S. pinnatisectummay be differentiated to some extent by the double diffusiontechnique, and more fully by immuno-electrophoretic analysis.Above all, the relative electrophoretic mobilities of certaincomponents, as expressed by the index have been found to be very constant for each species, with the apparent exception of S. bulbocastanum. A detailed investigation of S. bulbocastanum has now shown thatalthough the many clones of this species appeared similar whenexamined by double diffusion, differences were exposed by immuno-electrophoreticanalysis. In particular, the values fell into two discrete groups, 0.15 to 0.23 and 0.30 to 0.46. Theplants in these groups had been collected from Oaxaca and Guatemala,and from Central Mexico, respectively. Most of the former grouphad been identified as S. bulbocastanum subsp. partitum, andall the latter group as subsp. bulbocastanum and subsp. dolichophyllum.Not only was the wide variation in values of index resolved into two meaningful groups, but it was also found thatall lines within any one collection had almost identical values. The index value for S. cardiophyllum subsp.cardiophyllum is 1.0, and for subsp. ehrenbergii is 0.7. The F1 hybrids between either ofthese subspecies and S. bulbocastanum had fairly uniform valuesclose to the calculated means of the parental values. The shapesof the leaves of these hybrids were also uniform and more orless intermediate between those of the parents in each case. The F2 hybrids between S. bulbocastanum and S. pinnatisectum,and also the triple hybrids between these two species and eitherS. cardiophyllum or S. michoacanum, showed a wide range of valuesof index and of leaf shapes, with partial segregation towards the parental types. The serological andmorphological characters segregated independently. S. X sambucinum was found to have a wide variation in serologicaland morphological characters. This variation was consistentwith the theory that S. X sambucinum is a natural hybrid betweenS. pinnatisectum and S. cardiophyllum subsp. ehrenbergii. Within the groups of species investigated, the relative electrophoreticmobilities of certain antigens as displayed by immuno-electrophoreticanalysis were found to vary significantly in different species,in different subspecies of the same species, and in specieshybrids.  相似文献   

11.
Background and Aims Although density-specific stiffness,E/, (where E is Young's modulus and is wood density) is oftenassumed constant by the elastic similarity model, and in determinationof critical buckling height (Hcrit), few studies have testedthis assumption within species. Here this assumption is testedfor Pinus radiata growing across an environmental gradient,and theory is combined with data to develop a model of Young'smodulus. • Methods Analyses use an extensive series of environmentalplots covering the range of climatic and edaphic conditionsover which P. radiata is grown in New Zealand. Reduced majoraxis regression was used to determine scaling exponents betweenlog–log plots of Hcrit vs. groundline diameter (D), andE/ vs. D. Path analysis was used to identify significant directand indirect (through stem slenderness) edaphic and climaticinfluences on E. • Key Results Density-specific stiffness exhibited 3-foldvariation. As E/ scaled positively with D, the exponent of 0·95between Hcrit and D exceeded the assumed value of 0·67under constant E/. The final path analysis model included meanair temperature in early autumn (Taut) and slenderness as significant(P < 0·05) positive direct influences on E. Tree leafarea index and Taut were indirectly associated with E throughtheir significant (P < 0·05) positive direct relationshipwith stem slenderness. Young's modulus was most sensitive toTaut, followed by stem slenderness then leaf area index, andthe final model explained 76 % of the variance in E. • Conclusions The findings suggest that within speciesE/ variation may influence Hcrit and the scaling exponent betweenD and Hcrit so important in assumptions regarding allometricrelationships. The model presented may provide a useful meansof determining variation in E, E/ and Hcrit across environmentalgradients.  相似文献   

12.
Monte Carlo Estimation for Nonlinear Non-Gaussian State Space Models   总被引:2,自引:0,他引:2  
We develop a proposal or importance density for state spacemodels with a nonlinear non-Gaussian observation vector y p(y¦)and an unobserved linear Gaussian signal vector p(). The proposaldensity is obtained from the Laplace approximation of the smoothingdensity py). We present efficient algorithms to calculatethe mode of py) and to sample from the proposal density.The samples can be used for importance sampling and Markov chainMonte Carlo methods. The new results allow the application ofthese methods to state space models where the observation densityp(y¦) is not log-concave. Additional results are presentedthat lead to computationally efficient implementations. We illustratethe methods for the stochastic volatility model with leverage.  相似文献   

13.
Calcium dependence of C-type natriuretic peptide-formed fast K+ channel   总被引:2,自引:0,他引:2  
The lipid bilayertechnique was used to characterize theCa2+ dependence of a fastK+ channel formed by a synthetic17-amino acid segment [OaCNP-39-(1-17)] ofa 39-amino acid C-type natriuretic peptide (OaCNP-39) found in platypus (Ornithorhynchusanatinus) venom (OaV). TheOaCNP-39-(1-17)-formed K+ channel was reversiblydependent on1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-buffered cis (cytoplasmic)Ca2+ concentration([Ca2+]cis).The channel was fully active when[Ca2+]ciswas >104 M andtrans (luminal)Ca2+ concentration was 1.0 mM, butnot at low[Ca2+]cis.The open probability of single channels increased from zero at1 × 106 McisCa2+ to 0.73 ± 0.17 (n = 22) at103 McisCa2+. Channel openings to themaximum conductance of 38 pS were rapidly and reversibly activated when[Ca2+]cis,but not transCa2+ concentration(n = 5), was increased to >5 × 104 M(n = 14). Channel openings to thesubmaximal conductance of 10.5 pS were dominant at5 × 104 MCa2+.K+ channels did not open whencisMg2+ orSr2+ concentrations were increasedfrom zero to 103 M or when[Ca2+]ciswas maintained at 106 M(n = 3 and 2). The Hill coefficientand the inhibition constant were 1 and 0.8 × 104 McisCa2+, respectively. Thisdependence of the channel on high[Ca2+]cissuggests that it may become active under1) physiological conditions whereCa2+ levels are high, e.g., duringcardiac and skeletal muscle contractions, and2) pathological conditions that leadto a Ca2+ overload, e.g., ischemicheart and muscle fatigue. The channel could modify a cascade ofphysiological functions that are dependent on theCa2+-activatedK+ channels, e.g., vasodilationand salt secretion.

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14.
-Methyleneglutamic acid, an acidic amino-acid isolated fromgroundnut plants, was decarboxylated by enzymes present in extractsof Capsicum fruits, barley roots, and tulip leaves, and alsoby intact cells of Clostridium welchii S.R. I2. The amino-acidwas attacked in a similar manner to, but in all cases at a slowerrate than, l-glutamic acid. The nature of the enzyme responsiblefor the decarboxylation of -methyleneglutamic acid was furtherinvestigated using preparations from barley roots (which donot contain the amino-acid) and from tulip leaves (in whichthe amino-acid is normally present, together with larger amountsof its amide form, -methyleneglutamine). The effects of pH,inhibitors, and partial heat denaturation upon the enzyme systemspresent in the barley and tulip extracts indicated that a singleenzyme was responsible for the decarboxylation of both l-glutamicacid and -methyleneglutamic acid. Although the Cl. welchii rapidlydeamidated and then decarboxylated l-glutamine, -methyleneglutaminewas not attacked by the organism.  相似文献   

15.
Biophysical characterization of zebrafish connexin35 hemichannels   总被引:1,自引:0,他引:1  
A subset of connexins can form unopposed hemichannels in expression systems, providing an opportunity for comparison of hemichannel gating properties with those of intact gap junction channels. Zebrafish connexin35 (Cx35) is a member of the Cx35/Cx36 subgroup of connexins highly expressed in the retina and brain. In the present study, we have shown that Cx35 expression in Xenopus oocytes and N2A cells produced large outward whole cell currents on cell depolarization. Using whole cell, cell-attached, and excised patch configurations, we obtained multichannel and single-channel current recordings attributable to the Cx35 hemichannels (Ihc) that were activated and increased by stepwise depolarization of membrane potential (Vm) and deactivated by hyperpolarization. The currents were not detected in untransfected N2A cells or in control oocytes injected with antisense Cx38. However, water-injected oocytes that were not treated with antisense showed activities attributable to Cx38 hemichannels that were easily distinguishable from Cx35 hemichannels by a significantly larger unitary conductance (hc: 250–320 pS). The hc of Cx35 hemichannels exhibited a pronounced Vm dependence; i.e., hc increased/decreased with relative hyperpolarization/depolarization (hc was 72 pS at Vm = –100 mV and 35 pS at Vm = 100 mV). Extrapolation to Vm = 0 mV predicted a hc of 48 pS, suggesting a unitary conductance of intact Cx35 gap junction channels of 24 pS. Channel gating was also Vm dependent: open time declined with negative Vm and increased with positive Vm. The ability to break down the complex gating of intact intercellular channels into component hemichannels in vitro will help to evaluate putative physiological roles for hemichannels in vivo. connexin; gating; retina  相似文献   

16.
The following is the abstract of the article discussed in thesubsequent letter:

Venegas, José G., R. Scott Harris, and BrettA. Simon. A comprehensive equation for the pulmonarypressure-volume curve. J. Appl. Physiol. 84(1): 389-395, 1998.Quantification of pulmonary pressure-volume (P-V) curves isoften limited to calculation of specific compliance at a given pressureor the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure orvolume used in the comparison and may lead to erroneous conclusions. Weevaluated a sigmoidal equation of the form, V = a + b[1 + e(Pc)/d]1, for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal andhypocapnic pneumoconstricted dog lungs (n = 9), oleicacid-induced acute respiratory distress syndrome (n = 2), andmechanically ventilated patients with acute respiratory distresssyndrome (n = 10). In this equation, a corresponds tothe V of a lower asymptote, b to the V difference between upperand lower asymptotes, c to the P at the true inflection pointof the curve, and d to a width parameter proportional to the Prange within which most of the V change occurs. The equation fittedequally well inflation and deflation limbs of P-V curves with a meangoodness-of-fit coefficient (R2) of 0.997 ± 0.02 (SD). When the data from all analyzed P-V curves were normalized by thebest-fit parameters and plotted as (V  a)/b vs.(P  c)/d, they collapsed into a single and tightrelationship (R2 = 0.997). These resultsdemonstrate that this sigmoidal equation can fit with excellentprecision inflation and deflation P-V curves of normal lungs and oflungs with alveolar derecruitment and/or a region of gastrapping while yielding robust and physiologically useful parameters.

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17.
Brilli, Richard J., Brian Krafte-Jacobs, Daniel J. Smith,Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, CsabaSzabó, and Andrew L. Salzman. Intratracheal instillation ofa novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J. Appl. Physiol. 83(6):1968-1975, 1997.We examined the pulmonary and systemichemodynamic effects of administering soluble nitric oxide (NO) donorcompounds (NO/nucleophile adducts, i.e., NONOates) directly into thetrachea of animals with experimentally induced pulmonary hypertension.Steady-state pulmonary hypertension was created by using thethromboxane agonist U-46619. Yorkshire pigs were randomly assigned toone of four groups: group 1,intratracheal saline (control; n = 8);group 2, intratracheal sodiumnitroprusside (n = 6);group 3, intratracheal ethylputreanineNONOate (n = 6); andgroup 4, intratracheal2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO;n = 6). Pulmonary and systemichemodynamics were monitored after drug instillation.Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points comparedwith steady state and compared with group1 (P < 0.05), whereas systemic vascular resistance index did not change. The meanchange in mean pulmonary arterial pressure in group4 was 33.1 ± 1.2% compared with +6.4 ± 1.3% in group 1 (P < 0.001), and the mean change inmean arterial pressure was 9.3 ± 0.7% compared with acontrol value of 0.9 ± 0.5%(P < 0.05). Groups 2 and 3 hadsignificant decreases in both PVRI and systemic vascular resistanceindex compared with steady state and with group1. In conclusion, intratracheal instillation of apolar-charged tertiary amine NONOate DMAEP/NO results in the selectivereduction of PVRI. Intermittent intratracheal instillation of selectiveNONOates may be an alternative to continuously inhaled NO in thetreatment of pulmonary hypertension.

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18.
t-Cinnamic acid-2-14C, p-coumaric acid-2-14C and caffeic acid-2-14Cwere administered to discs of sweet potato roots and incorporationof each radioactive compound into chlorogenic acid was compared.The data suggest that chlorogenic acid is synthesized througheither or both of two major pathways, phenylalanine t-cinnamate t-cinnamoyl derivative p-coumaroyl derivative chlorogenicacid and phenylalanine t-cinnamate p-coumarate p-coumaroylderivative chlorogenic acid. 1Part 75 of the phytopathological chemistry of sweet potatowith black rot and injury. 2Present address : Department of Biology, Tokyo MetropolitanUniversity, Setagaya-ku, Tokyo. (Received December 23, 1968; )  相似文献   

19.
20.
Cheng  Yi; Berry  Donald A. 《Biometrika》2007,94(3):673-689
Optimal decision-analytic designs are deterministic. Such designsare appropriately criticized in the context of clinical trialsbecause they are subject to assignment bias. On the other hand,balanced randomized designs may assign an excessive number ofpatients to a treatment arm that is performing relatively poorly.We propose a compromise between these two extremes, one thatachieves some of the good characteristics of both. We introducea constrained optimal adaptive design for a fully sequentialrandomized clinical trial with k arms and n patients. An r-designis one for which, at each allocation, each arm has probabilityat least r of being chosen, 0 r 1/k. An optimal design amongall r-designs is called r-optimal. An r1-design is also an r2-designif r1 r2. A design without constraint is the special case r = 0and a balanced randomized design is the special case r = 1/k.The optimization criterion is to maximize the expected overallutility in a Bayesian decision-analytic approach, where utilityis the sum over the utilities for individual patients over a‘patient horizon’ N. We prove analytically thatthere exists an r-optimal design such that each patient is assignedto a particular one of the arms with probability 1 – (k – 1)r,and to the remaining arms with probability r. We also show thatthe balanced design is asymptotically r-optimal for any givenr, 0 r < 1/k, as N/n  . This implies that everyr-optimal design is asymptotically optimal without constraint.Numerical computations using backward induction for k = 2arms show that, in general, this asymptotic optimality featurefor r-optimal designs can be accomplished with moderate trialsize n if the patient horizon N is large relative to n. We alsoshow that, in a trial with an r-optimal design, r < 1/2,fewer patients are assigned to an inferior arm than when followinga balanced design, even for r-optimal designs having the samestatistical power as a balanced design. We discuss extensionsto various clinical trial settings.  相似文献   

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