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We will restrict our consideration to the comparison of two methods of measuring a continuous variable buy cyklokapron 500mg with amex medicine natural, although similar problems can arise with categorical variables cheap cyklokapron master card treatment hyperthyroidism. Comparison of means Cater (1979) compared two methods of estimating the gestational age of human babies cheap 20gr benzac amex. He divided the babies into three groups: normal birthweight babies, low birthweight pre-term (< 36 weeks gestation) babies, and low birthweight term babies. For each group he compared the mean by each method (using an unspecified test of significance), finding the mean gestational age to be significantly different for pre-term babies but not for the other groups. His criterion of agreement was that the two methods gave the same mean measurement; “the same” appears to stand for “not significantly different”. By his criterion, the greater the measurement error, and hence the less chance of a significant difference, the better. Correlation The favourite approach is to calculate the product-moment correlation coefficient, r, between the two methods of measurement. The correlation coefficient in this case depends on both the variation between individuals (i. In some applications the “true value” will be the subject’s average value over time, and short-term within-subject variation will be part of the measurement error. In others, where we wish to identify changes within subjects, the true value is not assumed constant. The correlation coefficient will therefore partly depend on the choice of subjects. For if the variation between individuals is high compared to the measurement error the correlation will be high, whereas if the variation between individuals is low the correlation will be low. This can be seen if we regard each measurement as the sum of the true value of the measured quantity and the error due to measurement. We have: 2 variance of true values = σT 2 variance of measurement error, method A = σA 2 variance of measurement error, method B = σB In the simplest model errors have expectation zero and are independent of one another and of the true value, so that 2 2 variance of method A = σA + σT 2 2 variance of method B = σB + σT 2 covariance = σT (see appendix) Hence the expected value of the sample correlation coefficient r is 2 σ T ρ = 2 2 2 2 (σ A + σT )(σ B + σT ) 2 2 2 2 2 Clearly ρ is less than one, and it depends only on the relative sizes of σT , σA and σB. If σA and σB 2 are not small compared to σT , the correlation will be small no matter how good the agreement between the two methods. In the extreme case, when we have several pairs of measurements on the same individual, 2 σT = 0 (assuming that there are no temporal changes), and so ρ = 0 no matter how close the agreement is. They concluded that the two methods did not agree because low correlations were found when the range of cardiac output was small, even though other studies covering a wide range of cardiac output had shown high correlations. In fact the result of their analysis may be 308 explained on the statistical grounds discussed above, the expected value of the correlation coefficient being zero. Their conclusion that the methods did not agree was thus wrong - their approach tells us nothing about dye-dilution and impedance cardiography. As already noted, another implication of the expected value of r is that the observed correlation will increase if the between subject variability increases. Diastolic blood pressure varies less between individuals than does systolic pressure, so that we would expect to observe a worse correlation for diastolic pressures when methods are compared in this way. It is not an indication that the methods agree less well for diastolic than for systolic measurements.

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It has been given in various form of female weakness discount cyklokapron 500mg online medications you can take when pregnant, particularly where there was severe leucorrhea generic cyklokapron 500mg on-line treatment 02 bournemouth. Ellingwood’s American Materia Medica generic 75mg endep with amex, Therapeutics and Pharmacognosy - Page 310 The Wm. Specific Symptomatology—It is indicated where there is dropsy, especially in aged people, or general dropsical effusion, accompanied with loss of vital tone. It is not only used in anasarca and ascites, but also in pleuritic effusion, hydropericardium and hydrocele. It improves the general condition on which the dropsy depends, increasing the action of the heart and arterial tension. Smith reports several cases in which the general dropsy was relieved in a very short time. The remedy improved the general nutrition in each of the cases, overcame difficult breathing and increased the power of the heart. In the dropsy of the aged, that follows prostrating disease, oxydendron is indicated. It is indicated where there is deficient renal action, especially if there is some painful urination, and in the urinary irregularity of old people. It is not easy to define that class of cases of dropsy in which it is specific as in some it works beautifully and in others it is ineffective. Graves says that where there is general edema from dropsy of the heart, liver or kidneys—general dropsy—he has had good results. He gives from twenty to thirty drops of the specific medicine every four hours and could give even larger doses. Where there is dropsy of the serous cavities, he thinks it is not the best remedy. Manley gives sour-wood with other remedies in the dropsy of diabetes, and believes that it improves the general condition of the patient. One of our doctors said his grandfather, an old botanic physician, gathered the leaves and boiled them in water for three hours. He would then strain the decoction and reduce the fluid until it was entirely evaporated. He would roll it up in form of pills and give one of them three or four times a day, improving his cases of dropsy very generally. This remedy is considered valuable in the treatment of prostatic disease, chronic enlargement of the prostate, with irritation at the neck of the bladder, urinary irritation from other causes, especially the urinary difficulties of the aged. It is a diuretic, more or less active in proportion to Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 311 the size of the dose. It promotes the absorption and elimination of dropsical effusions in a characteristic manner, especially those of the abdominal cavity.

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The set of all possible shapes of a molecule defines the potential energy hypersurface for that molecule order 500mg cyklokapron with amex medications adhd, shown in two dimensions in Part B buy generic cyklokapron canada symptoms cervical cancer. When attempting to identify the most probable shape of a molecule discount atorlip-20 20mg with visa, it is necessary to search the hypersurface for the lowest energy shape (global minimum). Because of the many millions of valleys on such a surface (multiple minima), it is difficult to find the true global minimum and not just one particular local minimum. Conformational search algorithms permit an approach to “hopping” across the hypersurface in an attempt to sample it and, hopefully, find the region of the global minimum. Once the region of a minimum has been identified, energy minimization algorithms permit the bottom of the minimum energy well to be attained. Such molecules are ideally suited to having their structures probed and understood using quantum pharmacology calculations (see figure 1. Each analog, regardless of its bioac- tivity, undergoes extensive calculations and is described by a series of descriptors. Geometric descriptors reflect properties such as bond lengths, bond angles, and inter- atomic distances within the analogue series. Electronic descriptors represent properties such as atomic charge densities, molecular dipoles, and energy of the highest occupied molecular orbital. Topological descriptors encode aspects of molecular shape and branching and are frequently represented by graph theory indices, such as the Randic indices. Physicochemical descriptors reflect properties related to the ability of the mol- ecules to traverse biological barriers such as the blood–brain barrier, and include values such as the octanol–water partition coefficient. These descriptors, especially the geomet- ric and electronic descriptors, may be ascertained using quantum mechanics calculations. Once the descriptors have been determined, a data array is constructed with descriptors along one axis of the array and biological activity along the other axis. Statistical methods are then used to search the array and to identify the minimal descriptor set capable of differentiating between biological activity and inactivity. As a corollary to this, it is possible to deduce the bioactive face of the molecule, thereby identifying the pharmacophore. For instance, if the pharmacophore has a positively charged ammonium located 6 Å from a hydrogen bonding acceptor, then the corresponding receptor site may have a negatively charged carboxylate and a hydrogen bonding donor located in an appropriate geometric orientation. Establishing the geometry of the model receptor (or pseudoreceptor map) can be achieved using either quantum mechanics or molecular mechanics calculations. Therefore, even though the structure of the actual receptor is unknown, the nature of the molecular properties that it should have can be ascertained.

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