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If a left diagonal line was drawn through the matrix best bupron sr 150 mg depression out of the shadows, it can be seen that the information above the diagonal line is the same as the information below the line. The correlation values would have a single asterisk if they were significant at the P < 0. A comparison of the Pearson correlations (r values) in the Correlations table shows that the best predictor of weight is length with an r value of 0. Despite their differences in magnitude, the correlation coefficients are all highly sig- nificant at the P < 0. In the Non-parametric Correlations table, the Kendall’s tau-b coefficients are all lower than the Pearson’s coefficients indicating that there are some tied ranks in the data set, that is, babies with the same weight and length as one other. The Spearman’s coefficients are similar in magnitude to the Pearson’s correlation coefficients. Non-parametric Correlations Correlations Head circumference Weight (kg) Length (cm) (cm) Kendall’s Weight (kg) Correlation coefficient 1. With this type of correlation, the linear relationship between two variables can be examined, while controlling or holding constant the effects of another confounding variable. The null hypothesis for a partial correlation is that there is no linear relationship between two variables after controlling for the effects of a confound- ing variable. For example, partial correlations could be conducted for the association between weight and head circumference after controlling for body length. The assump- tions for a partial correlation are the same as for Pearson’s correlation shown in Box 7. Therefore, both the effect size and the sample size should be considered when interpreting P values and statistical significance. Conversely, a large effect size will be statistically significant with a relatively small sample size. To examine the correlation in a selected sample, the data set can be restricted to babies less than 55. In addition, a filter variable to indicate the status of each case in the analysis is generated at the end of the spreadsheet with the coding 0 = not selected and 1 = selected. Correlations Correlations Head circumference Weight (kg) Length (cm) (cm) Weight (kg) Pearson correlation 1 0. When compared with Pearson’s r values from the full data set, the correlation coeffi- cient between weight and length is substantially reduced from 0. In general, r values are higher when the range of the explanatory variable is wider even though the relationship between the two variables is unchanged. For this reason, only the coefficients from random population samples have an unbiased value and can be compared with one another. Once the correlation coefficients are obtained, the full data set can be reselected using the command sequence Data → Select Cases → All cases. In reporting Pearson’s correlation coefficient in this example, it could be reported as ‘The weight of babies at 1 month was significantly related to their length (r = 0. There was also a significant association between the length of babies and their head circumference (r = 0. These results indicate that as the length of babies increases, so does their head circumference and weight’. In this, a regression model is used to fit a straight line through the data, where the regression line is the best predictor of the outcome variable using one or more explanatory variables. Normal values are the range of values that occur naturally in the general population. In developing a model to predict normal values, the emphasis is on building an accurate predictive model. The second purpose of using a regression model is to examine the effect of an explana- tory variable on an outcome variable after adjusting for other important explanatory factors. By using regression, additional information about the rela- tionships between variables and the between-group differences is obtained. In regres- sion, the distance between an observed value and the overall mean is partitioned into two components – the variation about the regression, which is also called the residual 206 Chapter 7 10 Variation about the regression 8 Variation due to the regression 6 Mean of the outcome value (Y) 4 2 Regression line 0 0 Explanatory variable Figure 7. The variation about the regression is the explained variation and the variation due to the regression is the unexplained variation. The F value, which is calculated as the regression mean square divided by the residual mean square, ranges from 1 to a large number. If the two sources of variance are similar, there is no association between the variables and the F value is close to 1.

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For general surveys of Greek thought on dreams see van Lieshout (1980) and Guidorizzi (1988); for discussions of early and classical Greek thought on sleep see Calabi (1984) buy cheap bupron sr 150 mg line depression test during pregnancy, Marelli (1979–80) and (1983), Wohrle (¨ 1995) and Byl (1998). In the fifth and the fourth centuries bce we can see a growing concern with the nature of dreams and with the kind of information they were believed to provide among philosophers (Heraclitus, Plato, Democritus), physicians (such as the Hippocratic author just quoted), poets (Pindar) and historians (Herodotus). In this context of intellectual and theoreti- cal reflection on the phenomenon of dreaming, Aristotle’s two works On Dreams (Insomn. At the same time, Aristotle’s style in these treatises is characteristically elliptical, and they present numerous problems of inter- pretation. In this chapter I will of course say something about the contents of this theory and its connection with other parts of Aristotle’s work; but the emphasis will be on the methodology which Aristotle adopts in these writings. First, I will deal with how Aristotle arrived at his theory, with particular consideration of the relation between theoretical presuppositions and empirical observations in both works. We know that Aristotle in his biological works often insists on the importance of collecting empirical evidence in order to substantiate ‘theories’ or ‘accounts’ (logoi) of nature. He sometimes takes other thinkers to task for their lack of concern with empirical corroboration of their theories, or he even accuses his opponents of manipulating the facts in order to make them consistent with their theories. My second question concerns the ratio underlying Aristotle’s treatment, especially the selection of topics he deals with and the order in which they are 5 For a translation with introduction and commentary of these works see van der Eijk (1994); see also Pigeaud (1995); Gallop (1996) (a revised edition of his [1990]); Dont (¨ 1997); Morel (2000); Repici (2003). For although Aristotle, within the scope of these short treatises, covers an admirable amount of topics and aspects of the phenomenon of dreaming with a sometimes striking degree of sophistication, it is at the same time remarkable that some important aspects of dreaming are not treated at all – aspects which are of interest not only to us, but also to Aristotle’s contemporaries. Nor does he pay serious attention to the interpretation of dreams: he only makes some very general remarks about this towards the end (464 b 9–16); he does not specify the rules for a correct interpretation of dreams. Yet the meaning of dreams was what the Greeks were most concerned with, and we know that in Aristotle’s time there existed professional dream interpreters who used highly elaborated techniques to establish the meaning of dreams. This lack of interest calls for an explanation, for not only does experience evidently suggest that these mental operations are possible in sleep, but there was also a powerful tradition in Greek thought, widespread in Aristotle’s time, that some mental operations, such as abstract thinking (nous), could function better and more accurately in sleep than in the waking state, because they were believed to be ‘set free’ in sleep from the restrictions posed by the soul’s incorporation in the body. Now, in response to this, one could argue that Aristotle was under no constraint from earlier traditions to discuss these points, for early and clas- sical Greek thought tends to display rather ambivalent attitudes to the phenomenon of sleep, and in particular to whether we can exercise our cognitive faculties in sleep. On the one hand, there was a strand in Greek thought, especially in some medical circles, in which sleep was defined negatively as the absence of a number of activities and abilities that are characteristic of the waking life, such as sense-perception, movement, con- sciousness and thinking. And as we shall see in a moment, Aristotle’s theory of sleep shows strong similarities to this tradition. On the other hand, there was also a strand in Greek thought, represented both in Orphic circles but 8 See del Corno (1982). These experiences and impulses can be subdivided into stimuli that have their origin within the dreamer and those that come from outside. The external stimuli can in their turn be subdivided into two categories: those that have their origin in the natural world, and those that come from the supernatural (gods, demons, etc. A similar, related ambivalence surrounded the question whether the sleeping life of an individual presents a complete negation of the character and personality of his/her waking life, or whether there is some connection or continuity between the two states. It would seem that if one defines sleep negatively (as Aristotle does) as an incapacitation of our powers of consciousness, the consequence would be that in the sleeping state the characteristics of our individual personalities are somehow inactivated: it would be as if, in sleep, we lose our identity and temporarily become like a plant. Yet, paradoxically, this negative view also allowed a positive valuation of the state of sleep. For it can be argued that in sleep our souls or minds are released from our bodies (and from experiences associated with the body, such as perception and emotion) and acquire a temporary state of detachedness and purity, thus anticipating the state of the immortal soul after its definitive detachment from the body after death. This latter view – that in sleep the soul is set free from the body and regains its ‘proper nature’ (idia phusis) – was especially found in Orphic and Pythagorean thought, with its negative view of the body and its dualistic concept of the relation between soul and body, and found its expression in stories 9 See Aristotle, Insomn. Aristotle on sleep and dreams 173 about ‘ecstatic’, clairvoyant experiences such as told about Hermotimus of Clazomenae and other ‘shamans’. For, at other places in his work, Plato seems to allow that our sleeping lives somehow reflect our mental state in the waking life. Thus in a well-known passage in the Republic, he suggests that dreams reflect an individual’s spiritual state in that they show whether the soul is calm and orderly, guided by reason, or subjected to emotions and desires: (I mean) those desires that are awakened in sleep, when the rest of the soul – the rational, gentle, and ruling part – slumbers. Then the beastly and savage part, full of food and drink, casts off sleep and seeks to find a way to gratify itself. You know that there is nothing it won’t dare to do at such a time, free of all control by shame or reason. It doesn’t shrink from trying to have sex with a mother, as it supposes, or with anyone else at all, whether man, god, or beast.

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A 36-year-old male comes to his primary care physician complaining of 3 days of worsening head- ache buy bupron sr 150mg otc depression symptoms icd 9, left frontal facial pain, and yellow nasal discharge. Acts at β1-adrenergic receptors and dopaminergic into your clinic requesting treatment for “the flu. It also causes vasodilatation and increased sweats, headaches, myalgias, and a nonproductive cough. Acts at β1- and, to a lesser extent, β2-adrenergic re- cently finished doing structural repairs on his old house. Acts at α and β1-adrenergic receptors to increase min, and SaO2 is 88% on room air. A 42-year-old male presents with progressive dyspnea ing and obtunded, localizes to pain, and has flat neck veins. He also is complaining of a primarily dry cough, for initial laboratory testing sent off, and electrocardio- although occasionally he coughs up a thick mucoid spu- gram and chest x-ray are obtained. He does not smoke been called to the bedside and is assessing the patient’s air- cigarettes. A 24-year-old woman is brought to the emergency room after attempting suicide with an overdose of heroin. An 86-year-old nursing home resident is brought by On arrival at the emergency department in Jacksonville, ambulance to the local emergency room. She is hypotensive with a blood pressure of had been coughing and complaining of chills for the past 84/60 mmHg and a heart rate of 80 beats/min. The oxy- few days; no further history is available from the nursing gen saturation is 70% on room air. His past medical history is remarkable for Alz- is performed showing the following: pH 7. Which of the following state- gency responders were able to appreciate a faint pulse and ments is true regarding the patient’s arterial blood gas? The patient is hypoxic due to hypoventilation with 88/51 mmHg and heart rate is 131 beats/min. The patient is hypoxic due to hypoventilation with a stable on transfer; however, 20 min after arrival he is normal A – a gradient. The patient is hypoxic due to shunt with an in- tremities are cool, and blood pressure is difficult to ob- creased A – a gradient. The patient is hypoxic due to ventilation-perfusion turns to you and asks what you would like to do next. Which of the following accurately represents the physio- logic characteristics of this patient’s condition? Which of the following statements best describes the functional residual capacity of the lung? The volume of gas at which the tendency of the A lungs to collapse (elastic recoil pressure) and the B tendency of the chest wall to expand are equal. The volume of gas remaining in the lungs at the end D of a normal tidal exhalation E C. Diminished protein C level ited due to her fatigue, and there is significant orthopnea. Diminished protein S level During her evaluation, laboratory analysis reveals: So- E. A chest is hospitalized about three times yearly for infectious ex- x-ray is interpreted as “poor inspiratory effort. A ventilation-perfu- nosa and Staphylococcus aureus, but has never had sion scan has normal perfusion. He remains active and is in tests will most likely identify the cause of this patient’s college studying architecture. Forced vital capacity (supine and upright) indication for referral for lung transplantation? A 42-year-old woman presents to the emergency room with acute onset of shortness of breath. A 52-year-old man presents with crushing sub-ster- cently had been to visit her parents out of state and rode nal chest pain.

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These transporters are the direct target receptors for numerous drugs bupron sr 150 mg generic depression symptoms emedicine, including antidepressants and cocaine. Allelic variations, in particular of the serotonin transporter, are associated with the modulation of com- plex behavior and may play a significant role in therapy with specific serotonin transporter inhibitors. Variation in neurotransmitter receptors can also be the cause of treatment failure. Genetic polymorphism of the β2-adrenoreceptor can alter the process of signal transduction by these receptors. Polymorphisms in drug target genes that can influence drug response are listed in Table 4. Protein kinases are coded by more than 2,000 genes and thus constitute the largest single enzyme family in the human genome. Amplicon modeling, primer design and assay vali- dation have been established for over 1,600 amplicons within 92 different kinase genes. Kinase mutation mapping can be used to pinpoint responder populations and facilitate the development of person- alized medicine. Effect of Genetic Polymorphisms on Disease Response to Drugs Genetic polymorphism of genes and gene products may influence the disease- modifying effects of drugs. It offers 1,936 high value, biologically relevant markers in 225 drug metabolism enzyme, trans- porter, and transferase genes. Such informa- tion is useful in identifying the responders to drugs and is discussed further in sub- sequent chapters. Ethnic Differences in Drug Metabolism Ethnic differences in drug metabolism are well documented for a number of drugs. The molecular mechanisms responsible for ethnic differences in drug metabolism have been partly clarified because of the advances in molecular biology. Genotype analysis indicates a different frequency for the mutant alleles in different ethnic populations, which results in variations in the frequency of subjects who are homo- zygous for the mutant allele among the extensive metabolizers in different ethnic populations. Ethnic differences in drug metabolism may result from differences in distribution of a polymorphic trait and mutations, which code for enzymes with abnormal activity which occur with altered frequency in different ethnic groups. Ethnic factors, therefore, are an important consideration in individualization of therapy. Gender Differences in Pharmacogenetics There are gender-related differences in pharmacokinetics, which may be related to pharmacogenetic differences in to drug-metabolizing enzymes. Other gender differences in pharmacokinetics may be due to fluctuations in hormone levels in women with menstruation and pregnancy. Moreover, development of diseases such as heart disease and cancer may affect women differently from men. There is no data to support the efficacy of statins in preventing heart attacks and stroke in women with hypercholesterolemia, partly because there have not been adequate representation of women in clinical Universal Free E-Book Store Role of Pharmacogenetics in Pharmaceutical Industry 115 trials as compared to men. Use of statins in women is associated with a higher rate of complications such as myositis and cognitive impairment. Statin therapy in women without cardiovascular disease is controversial, given the insufficient evidence of benefit. Participants included 6,800 women and 11, 000 men with high- sensitivity C-reactive protein and low-density lipoprotein cholesterol randomized to rosuvastatin versus placebo. Meta-analysis studies were randomized placebo- controlled statin trials with predominantly or exclusively primary prevention in women and sex-specific outcomes. This study demonstrated that in primary preven- tion rosuvastatin reduced cardiovascular disease events in women with a relative risk reduction similar to that in men, a finding supported by meta-analysis of pri- mary prevention statin trials. Role of Pharmacogenetics in Drug Safety Variability in drug response among patients is multifactorial, including environmen- tal, genetic, and disease determinants that affect the disposition of the drug. Children may be exposed to these drugs through in utero exposure during preg- nancy, through breast feeding, and through exposure during adolescence. Adverse Drug Reactions Related to Toxicity of Chemotherapy Neurotoxicity and myelotoxicity are well known adverse reactions of chemother- apy in cancer patients.