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1.
Ashcroft R 《Bioethics》1999,13(3-4):314-326
It is widely maintained that a clinical trial is ethical only if some form of equipoise between the treatments being compared obtains. To be in equipoise between two treatments A and B is to be cognitively indifferent between the statement 'A is strictly more effective than B' and its negation. It is natural to claim that equipoise regarding A and B is necessary for randomised assignment to treatments A and B to be beneficent and non-maleficent and is sufficient for such an assignment to be fair. Cashing this out precisely is difficult, and various forms of equipoise have been discussed which consider whose equipoise is relevant to the decision. This is to make judgement of equipoise something to be managed socially, while its prima facie significance is supposedly cognitive. Recent reconstructions of equipoise-like concepts in epistemology give clues about how to understand equipoise cognitively. In this paper I examine some of this work and discuss how successful it has been. I suggest that while this work is promising, it still has far to go, and that while equipoise remains the best theory we have of the cognitive justification for clinical trials, it is nonetheless incoherent. 相似文献
2.
J T Wang 《Journal of biomechanical engineering》1989,111(2):128-135
The viscous criterion is a recently developed criterion to assess injury severity of the human thorax. In the viscous criterion, the peak viscous response, which is defined as the maximum product of deformation velocity and compression of an object, is proposed as a predictor of injury risk. However, the physical meaning of the criterion is not very clear. In this paper, the mathematical properties of the viscous criterion are analyzed. A mechanical thorax model is then used to relate the criterion to the physical quantities of the model using energy concepts. It is found that the so-called peak viscous response is strongly related to the peak energy storing rate of the thorax which is not related to the viscosity of the thorax. It is also shown that the viscous response of the thorax is given by the integral of the velocity squared with respect to time. The analysis is further expanded to a more general case to result in four criteria based upon the energy concepts. A hypothesis for injury assessment is proposed by using the four criteria. 相似文献
3.
Site of graviperception in roots: a re-examination 总被引:1,自引:0,他引:1
Two lines of evidence have been cited to support the assertion that the root cap is the sole site of graviperception in the root. The first evidence is based on surgical removal of the cap, which abolishes the response to gravity. This is sufficient to conclude that the cap is involved in gravitropism, but not to conclude that the cap is the site of graviperception. The second is based on the results of centrifugation experiments, in which different parts of the plant are subjected to different centrifugal forces. The data from such experiments have been cited to support the conclusion that the perception of gravity is limited to the rootcap. However, these data actually support the conclusion that gravity is perceived throughout the root tip, and not only in the root cap. We believe that the data support the conclusion that the root cap is involved in root gravitropism, but that there is inadequate evidence to conclude that the cap is the sole site of graviperception. 相似文献
4.
Failure to Maintain Glycolysis in Anoxic Nerve Terminals 总被引:8,自引:6,他引:2
Synaptosomal glycolysis is stimulated eight- to 10-fold when the respiratory chain is inhibited by cyanide or by anoxia. However, the stimulation is transient and after 15 min declines toward the preanoxic rate. The decline is not seen when Ca2+ is absent or when the respiratory chain is inhibited by rotenone. The decline in glycolysis is reversible, is not due to substrate exhaustion, and is the cause, rather than the effect, of lowered synaptosomal ATP/ADP ratios. The failure to maintain glycolysis when the terminal oxidase of the respiratory chain is inhibited may have relevance to the sensitivity of the brain to anoxic damage. 相似文献
5.
T A Louis 《Biometrics》1977,33(4):627-634
The problem of comparing two medical treatments with respect to survival is considered. Treatment outcome is assumed to follow an exponential distribution. The ratio of expected survivals associated with the two treatments is the clinical parameter of interest. A nuisance parameter is present, but it is removed by an invariance reduction and a sequential probability ratio test is applied to the invariant likelihood ratio. A class of data-dependent treatment assignment rules is identified over which the probability of correct treatment selection at the termination of the trial is approximately constant. A cost function, the weighted sum of total patients in the trial and the number assigned to the inferior treatment is introduced, and a treatment allocation rule conjectured to minimize the expected cost is constructed. Both analytic and simulation results show that it is an improvement over rules previously proposed. The methodology contained herein can be used to construct near-optimal rules in other testing contexts. 相似文献
6.
Gynecomastia: suction lipectomy as a contemporary solution 总被引:9,自引:0,他引:9
G J Rosenberg 《Plastic and reconstructive surgery》1987,80(3):379-386
Suction lipectomy is adapted for the correction of gynecomastia. Previous attempts using suction lipectomy for gynecomastia still required the use of sharp dissection for removal of the glandular breast tissue as well as excision of redundant skin. With this new technique, gynecomastia is corrected solely with the use of suction lipectomy. The technique is successful if the gynecomastia is due to excess fat or parenchymal hypertrophy. A 7-mm cannula is inserted first, to remove the adipose tissue. Then a 2.4-mm cannula is used to remove the glandular and ductal tissue. The 7-mm cannula is then reinserted to remove subareolar parenchyma and to make final contour adjustments. The surrounding subcutaneous tissue is easily undermined to avoid a saucer deformity and to allow for skin contraction. Patients return to full activities in 48 hours. A compressive garment is worn for 4 to 6 weeks. The results of 10 patients are discussed. 相似文献
7.
An object extraction problem based on the Gibbs Random Field model is discussed. The Maximum a'posteriori probability (MAP) estimate of a scene based on a noise-corrupted realization is found to be computationally exponential in nature. A neural network, which is a modified version of that of Hopfield, is suggested for solving the problem. A single neuron is assigned to every pixel. Each neuron is supposed to be connected only to all of its nearest neighbours. The energy function of the network is designed in such a way that its minimum value corresponds to the MAP estimate of the scene. The dynamics of the network are described. A possible hardware realization of a neuron is also suggested. The technique is implemented on a set of noisy images and found to be highly robust and immune to noise. 相似文献
8.
Risk assessment for quantitative responses using a mixture model 总被引:5,自引:0,他引:5
A problem that frequently occurs in biological experiments with laboratory animals is that some subjects are less susceptible to the treatment than others. A mixture model has traditionally been proposed to describe the distribution of responses in treatment groups for such experiments. Using a mixture dose-response model, we derive an upper confidence limit on additional risk, defined as the excess risk over the background risk due to an added dose. Our focus will be on experiments with continuous responses for which risk is the probability of an adverse effect defined as an event that is extremely rare in controls. The asymptotic distribution of the likelihood ratio statistic is used to obtain the upper confidence limit on additional risk. The method can also be used to derive a benchmark dose corresponding to a specified level of increased risk. The EM algorithm is utilized to find the maximum likelihood estimates of model parameters and an extension of the algorithm is proposed to derive the estimates when the model is subject to a specified level of added risk. An example is used to demonstrate the results, and it is shown that by using the mixture model a more accurate measure of added risk is obtained. 相似文献
9.
C DeLisi 《Journal of theoretical biology》1975,51(2):337-345
Equations are presented which can be used to describe the inhibition of plaques by multifunctional antigen which binds γG antibody bivalently. The interaction is treated as a bimolecular reaction which is irreversible within the time of the experiment. It is shown that under these conditions the characteristics of the inhibition curve, and their relationship to kinetic and thermodynamic parameters are strongly dependent upon how antibody interacts with RBCs. When the epitope coating is dense, multivalent attachment of antibody is likely and the interaction is considered irreversible. When the epitope coating is sparse, only rapid, reversible univalent attachment is considered and local equilibrium is assumed to hold.The first case leads to an abrupt inhibition curve whose position is determined by the forward rate constant and RBC density. The second case leads to broad asymmetric curves. For this situation the relation between the extent of inhibition and the affinity of the population is generally complicated and reliable affinity information is difficult to obtain. This is contrasted to results obtained previously for unifunctional inhibitors from which reliable affinity information can, in principle, be obtained. The results emphasize the need for carefully designed experiments if affinity information is to be obtained from inhibition studies. 相似文献
10.
V S Barsukov 《Tsitologiia》1975,17(7):846-853
The entity of radiation damage of viruses, bacteria and cells is defined by the organization of genetic structures. Asimmetrical chromosome exchanges have been proposed as the main reason of inactivation of di- and polyploid eukaryotic cells. If a single molecule of DNA is taken for the core of chromosome, the exchange is believed to be a consequence of cross-polymerization of two polypeptid strands of the single DNA molecule. Thus, the double strand break of DNA is necessary to produce aberration. A hypothesis is put forward on the identity of primary lesion of chromosome with the double strand break. The experimental survival curve is approximated according to the formula derived from the model. The yield of primary lesions of chromosomes is proposed to be equal to that of double strand breaks of chromosomes in order to examine the validity of the hypothesis. The optimal interaction distance of primary lesions in correspondence with parameters of the survival curve is equal to 0.8 mkm. This estimation is in good agreement with the microdosimetrical data, and the proposed hypothesis is not contradicted. 相似文献
11.
Lipton P 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2005,360(1458):1259-1269
The attitudes of scientists towards the philosophy of science is mixed and includes considerable indifference and some hostility. This may be due in part to unrealistic expectation and to misunderstanding. Philosophy is unlikely directly to improve scientific practices, but scientists may find the attempt to explain how science works and what it achieves of considerable interest nevertheless. The present state of the philosophy of science is illustrated by recent work on the 'truth hypothesis', according to which, science is generating increasingly accurate representations of a mind-independent and largely unobservable world. According to Karl Popper, although truth is the aim of science, it is impossible to justify the truth hypothesis. According to Thomas Kuhn, the truth hypothesis is false, because scientists can only describe a world that is partially constituted by their own theories and hence not mind-independent. The failure of past scientific theories has been used to argue against the truth hypothesis; the success of the best current theories has been used to argue for it. Neither argument is sound. 相似文献
12.
Piepho HP 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2005,111(1):95-99
It is often found that heterosis tends to increase with genetic distance of the parents, though the correlation is not usually very close. It is therefore important to test the null hypothesis that the correlation is zero. The present work shows that standard procedures tend to yield too liberal tests, owing to the lack of independence among genetic distances and among heterosis estimates. A valid alternative is to use a permutation test, which was first suggested by Mantel [(1967) Cancer Res 27: 209–220). This test is well-known among plant breeders and geneticists, who often use it to test the correlation among two distance matrices. Its use is not restricted to the comparison of distance matrices. This is demonstrated in the present work, using two published datasets on marker-based genetic distances of maize inbreds or populations and heterosis of their crosses. It is shown that the test is also applicable in the presence of missing data. 相似文献
13.
PduS is a corrin reductase and is required for the reactivation of the cobalamin-dependent diol dehydratase. It is one component encoded within the large propanediol utilisation (pdu) operon, which is responsible for the catabolism of 1,2-propanediol within a self-assembled proteinaceous bacterial microcompartment. The enzyme is responsible for the reactivation of the cobalamin coenzyme required by the diol dehydratase. The gene for the cobalamin reductase from Citrobacter freundii (pduS) has been cloned to allow the protein to be overproduced recombinantly in E. coli with an N-terminal His-tag. Purified recombinant PduS is shown to be a flavoprotein with a non-covalently bound FMN that also contains two coupled [4Fe-4S] centres. It is an NADH-dependent flavin reductase that is able to mediate the one-electron reductions of cob(III)alamin to cob(II)alamin and cob(II)alamin to cob(I)alamin. The [4Fe-4S] centres are labile to oxygen and their presence affects the midpoint redox potential of flavin. Evidence is presented that PduS is able to bind cobalamin, which is inconsistent with the view that PduS is merely a flavin reductase. PduS is also shown to interact with one of the shell proteins of the metabolosome, PduT, which is also thought to contain an [Fe-S] cluster. PduS is shown to act as a corrin reductase and its interaction with a shell protein could allow for electron passage out of the bacterial microcompartment. 相似文献
14.
Oxidation of glycine by Phaseolus leghaemoglobin with associated catabolic reactions at the haem. 总被引:1,自引:0,他引:1
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P Lehtovaara 《The Biochemical journal》1978,176(2):351-358
Leghaemoglobin from the root nodules of kidney bean (Phaseolus vulgaris) reacts in alkaline glycine solutions as a glycine oxidase in a reaction that may also be regarded as a coupled oxidation. Leghaemoglobin is reduced to the ferrous form by glycinate, the oxygen complex is formed, and finally the haem is attacked to yield a green reaction product. Glycine is simultaneously oxidized to glyoxylate, and hydrogen peroxide is generated. The initial velocity of the formation of the green product is proportional to the concentrations of leghaemoglobin and glycine, and the optimum pH for the reaction is 10.2. The green product is not formed if carbon monoxide, azide of imidazole is bound to the haem, whereas oxidation of glycine to glyoxylate is not inhibited by azide and not essentially by carbon monoxide. Haem breakdown is activated by digestion of leghaemoglobin by carboxypeptidase, and partly inhibited by catalase and superoxide dismutase. 相似文献
15.
Permanence of a dispersal single-species population model where environment is partitioned into several patches is considered. The species not only requires some time to disperse between the patches but also has some possibility to die during its dispersion. The model is described by delay differential equations. The existence of 'super' food-rich patch is proved to be sufficient to ensure partial permanence of the model. It is also shown that partial permanence implies permanence if each food-poor patch is chained to the super food-rich patch. Furthermore, it is proven that partial persistence is ensured if there exist food-rich patches and the dispersion of the species among the patches are small. When the dispersion is large, the partial persistence is realized under relatively small dispersion time. 相似文献
16.
Summary A proteolipidic toxin, prymnesin, when added to the aqueous solutions around thin lipid membranes causes a marked increase in membrane conductance. The toxin-treated membrane is cation-permselective. The extent of cation permselectivity is dependent upon ionic strength of the aqueous solutions in a fashion similar to the dependence of cation permselectivity of a cation exchanger containing about 100mm of fixed negative sites. Dose-response relationship studies reveal a linear relation between log prymnesin concentration and log membrane conductance. The slope of the curve is around 3 if the toxin is applied to one side of the membrane and is around 7 if the toxin is applied to both sides of the membrane. The membrane treated with toxin on one side only is clearly asymmetric in its properties. These characteristics are expressed by an asymmetric current-voltage relationship, and by asymmetric sensitivity of membrane conductance to pH and to salt concentration. The conductance of the toxin-treated membrane is inversely proportional to temperature. It is suggested that aggregates of toxin moieties assemble in the membrane to form negatively charged aqueous pores. There is roughly a good correlation between the increase in membrane conductance and the increase in membrane permeability to urea if both were attributed to the formation of aqueous channels in the membrane. 相似文献
17.
An impulsive model of augmentative biological control consisting of a general continuous predator-prey model in ordinary differential equations, i.e. a meta-model, augmented by a discrete part describing periodic introductions of predators is considered. The existence of an invariant periodic solution that corresponds to prey eradication is shown and a condition ensuring its global asymptotic stability is given. An optimisation problem related to the preemptive use of augmentative biological control is then considered. It is assumed that the per time unit budget of biological control (i.e. the number of predators to be released) is fixed and the best deployment of this budget is sought in terms of release frequency. The cost function to be minimised is the time needed to reduce an unforeseen prey (pest) invasion occurring at a worst time instant under some harmless level. The analysis shows that the optimisation problem admits a countable infinite number of solutions. An argumentation considering the required robustness of the optimisation result with respect to the invasive prey population level and to the model parameters is then conducted. It is shown that the cost function is decreasing in the predator release frequency so that the best deployment of the biocontrol agents is to carry out as frequent introductions as possible. 相似文献
18.
M.G. Bulmer 《Journal of theoretical biology》1984,106(4):529-535
Gillespie (1974,1975) has shown that selection will tend to minimize variance in offspring number. It is shown that this effect is due to selection maximizing the average number of surviving offspring when there is density-dependent survival, and that it is unnecessary to invoke principles such as minimizing the variability of fitness (Real, 1980). The effect of this principle of selecting for laying several small clutches rather than one large clutch when there is predation on whole clutches is investigated. It is found that the selection pressure is weak, contrary to the conclusion of Rubenstein (1982), and is unlikely to be of evolutionary importance. 相似文献
19.
20.
Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum
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Hepatitis E virus (HEV) is a positive-strand RNA virus that is prevalent in much of the developing world. ORF2 is the major capsid protein of HEV. Although ORF2 is an N-linked glycoprotein, it is abundantly located in the cytoplasm in addition to having membrane and surface localization. The mechanism by which ORF2 protein obtains access to the cytoplasm is unknown. In this report, we prove that initially all ORF2 protein is present in the endoplasmic reticulum and a fraction of it becomes retrotranslocated to the cytoplasm. The ability of ORF2 to be retrotranslocated is dependent on its glycosylation status and follows the canonical dislocation pathway. However, in contrast to general substrates of the dislocation pathway, retrotranslocated ORF2 protein is not a substrate of the 26S proteasome complex and is readily detectable in the cytoplasm in the absence of any protease inhibitor, suggesting that the retrotranslocated protein is stable in the cytoplasm. This study thus defines the pathway by which ORF2 obtains access to the cytoplasm. 相似文献