Glimepiride
"Cheap 4mg glimepiride amex, diabetes mellitus type 2 essay."
By: Paul Reynolds, PharmD, BCPS
- Critical Care Pharmacy Specialist, University of Colorado Hospital
- Clinical Assistant Professor, Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado
http://www.ucdenver.edu/academics/colleges/pharmacy/Departments/ClinicalPharmacy/DOCPFaculty/Q-Z/Pages/Paul-Reynolds,-PharmD.aspx
The most recent study by the National Sleep Foundation suggests that adults should get between 7 and 9 hours of sleep per night (Figure 5 diabetes symptoms signs high blood sugar generic glimepiride 1mg with visa. Getting needed rest is difficult in part because school and work schedules still follow the early to-rise timetable that was set years ago diabetes prevention nutrition 4mg glimepiride with amex. We tend to diabetes symptoms of colon cancer discount glimepiride online amex stay up late to what happens if diabetes in dogs goes untreated glimepiride 1mg mastercard enjoy activities in the evening but then are forced to get up early to go to work or school. The situation is particularly bad for college students, who are likely to combine a heavy academic schedule with an active social life and who may, in some cases, also work. Continued over time, a nightly deficit of even only 1 or 2 hours can have a substantial impact on mood and performance. Sleep has a vital restorative function, and a prolonged lack of sleep results in increased anxiety, diminished performance, and, if severe and extended, may even result in death. Many road accidents involve sleep deprivation, and people who are sleep deprived show decrements in driving performance similar to those who have ingested alcohol (Hack, Choi, Vijayapalan, [15] Davies, & Stradling, 2001; Williamson & Feyer, 2000). Poor treatment by doctors (Smith [16] Coggins, Rosekind, Hurd, & Buccino, 1994) and a variety of industrial accidents have also been traced in part to the effects of sleep deprivation. It is no surprise that we sleep more when we are sick, because sleep works to fight infection. Sleep deprivation suppresses immune responses that fight off infection, and can lead to obesity, hypertension, and memory impairment [17] (Ferrie et al. The content of our dreams generally relates to our everyday experiences and concerns, and frequently our fears and failures (Cartwright, Agargun, Kirkby, & Friedman, 2006; Domhoff, Meyer-Gomes, & Schredl, [20] 2005). Many cultures regard dreams as having great significance for the dreamer, either by revealing something important about the dreamer’s present circumstances or predicting his future. The [21] Austrian psychologist Sigmund Freud (1913/1988) analyzed the dreams of his patients to help him understand their unconscious needs and desires, and psychotherapists still make use of this technique today. Freud believed that the primary function of dreams was wish fulfillment, or the idea that dreaming allows us to act out the desires that we must repress during the day. Freud believed that the real meaning of dreams is often suppressed by the unconscious mind in order to protect the individual from thoughts and feelings that are hard to cope with. By uncovering the real meaning of dreams through psychoanalysis, Freud believed that people could better understand their problems and resolve the issues that create difficulties in their lives. Although Freud and others have focused on the meaning of dreams, other theories about the causes of dreams are less concerned with their content. One possibility is that we dream primarily to help with consolidation, or the moving of information into long-term memory [22] (Alvarenga et al. Payne and Nadel (2004) argued that the content of dreams is the result of consolidation—we dream about the things that are being moved into long-term memory. The activation-synthesis theory of dreaming (Hobson & McCarley, 1977; Hobson, [26] 2004) proposes still another explanation for dreaming—namely, that dreams are our brain’s interpretation of the random firing of neurons in the brain stem. As a result, the cortex strings the messages together into the coherent stories we experience as dreams. Although researchers are still trying to determine the exact causes of dreaming, one thing remains clear—we need to dream. Sleep disorders, including insomnia, sleep apnea, and narcolepsy, may make it hard for us to sleep well. Other theories of dreaming propose that dreaming is related to memory consolidation. If you happen to be home alone one night, try this exercise: At nightfall, leave the lights and any other powered equipment off. Does this influence what time you go to sleep as opposed to your normal sleep time. Consider how each of the theories of dreaming we have discussed would explain your dreams. Dream consciousness: Our understanding of the neurobiology of sleep offers insight into abnormalities in the waking brain. Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Dreams as the expression of conceptions and concerns: A comparison of German and American college students. Paradoxical sleep deprivation impairs acquisition, consolidation and retrieval of a discriminative avoidance task in rats. The brain as a dream state generator: An activation-synthesis hypothesis of the dream process. Summarize the major psychoactive drugs and their influences on consciousness and behavior. A psychoactive drug is a chemical that changes our states of consciousness, and particularly our perceptions and moods. These drugs are commonly found in everyday foods and beverages, including chocolate, coffee, and soft drinks, as well as in alcohol and in over-the-counter drugs, such as aspirin, Tylenol, and cold and cough medication. Psychoactive drugs are also frequently prescribed as sleeping pills, tranquilizers, and antianxiety medications, and they may be taken, illegally, for recreational purposes. Some psychoactive drugs are agonists, which mimic the operation of a neurotransmitter; some are antagonists, which block the action of a neurotransmitter; and some work by blocking the reuptake of neurotransmitters at the synapse. Moderate Moderate Moderate opioids is similar to the cardiac endorphins, the depression, and Restlessness, neurotransmitters that the rapid irritability, serve as the body’s development of headache and body “natural pain reducers. For instance, sleeping pills are prescribed to create drowsiness, and benzodiazepines are prescribed to create a state of relaxation. In other cases psychoactive drugs are taken for recreational purposes with the goal of creating states of consciousness that are pleasurable or that help us escape our normal consciousness. The use of psychoactive drugs, and especially those that are used illegally, has the potential to create very negative side effects (Table 5. This does not mean that all drugs are dangerous, but rather that all drugs can be dangerous, particularly if they are used regularly over long periods of time. Psychoactive drugs create negative effects not so much through their initial use but through the continued use, accompanied by increasing doses, that ultimately may lead to drug abuse. As the use of the drug increases, the user may develop a dependence, defined as a need to use a drug or other substance regularly. Dependence can be psychological, in which the drug is desired and has become part of the everyday life of the user, but no serious physical effects result if the drug is not obtained; or physical, in which serious physical and mental effects appear when the drug is withdrawn. Cigarette smokers who try to quit, for example, experience physical withdrawal symptoms, such as becoming tired and irritable, as well as extreme psychological cravings to enjoy a cigarette in particular situations, such as after a meal or when they are with friends. Users may wish to stop using the drug, but when they reduce their dosage they experience withdrawal—negative experiences that accompany reducing or stopping drug use, including physical pain and other symptoms. When the user powerfully craves the drug and is driven to seek it out, over and over again, no matter what the physical, social, financial, and legal cost, we say that he or she has developed an addiction to the drug. It is a common belief that addiction is an overwhelming, irresistibly powerful force, and that withdrawal from drugs is always an unbearably painful experience. For one, even drugs that we do not generally think of as being addictive, such as caffeine, nicotine, and alcohol, can be very difficult to quit using, at least for some people. On the other hand, drugs that are normally associated with addiction, including amphetamines, cocaine, and heroin, do not immediately create addiction in their users. Even for a highly addictive drug like cocaine, only about 15% of users become addicted [1] (Robinson & Berridge, 2003; Wagner & Anthony, 2002). Furthermore, the rate of addiction is lower for those who are taking drugs for medical reasons than for those who are using drugs recreationally. Patients who have become physically dependent on morphine administered during the course of medical treatment for a painful injury or disease are able to be rapidly weaned off [2] the drug afterward, without becoming addicts. Robins, Davis, and Goodwin (1974) found that the majority of soldiers who had become addicted to morphine while overseas were quickly able to stop using after returning home. These drugs are generally illegal and carry with them potential criminal consequences if one is caught and arrested. Snorting (“sniffing”) drugs can lead to a loss of the sense of smell, nosebleeds, difficulty in swallowing, hoarseness, and chronic runny nose.
Multiple regression is a statistical technique blood glucose guidelines glimepiride 4 mg with amex, based on correlation coefficients among variables diabetes mellitus long term effects generic glimepiride 1 mg amex, that allows predicting a single outcome variable from more than one predictor variable diabetes medicine over the counter purchase glimepiride 1mg without a prescription. The use of multiple regression analysis shows an important advantage of correlational research designs—they can be used to diabetes type 1 case study order 2 mg glimepiride overnight delivery make predictions about a person’s likely score on an outcome variable. An important limitation of correlational research designs is that they cannot be used to draw conclusions about the causal relationships among the measured variables. Consider, for instance, a researcher who has hypothesized that viewing violent behavior will cause increased aggressive play in children. He has collected, from a sample of fourth-grade children, a measure of how many violent television shows each child views during the week, as well as a measure of how aggressively each child plays on the school playground. From his collected data, the researcher discovers a positive correlation between the two measured variables. Although the researcher is tempted to assume that viewing violent television causes aggressive play, Figure 2. One alternate possibility is that the causal direction is exactly opposite from what has been hypothesized. Perhaps children who have behaved aggressively at school develop residual excitement that leads them to want to watch violent television shows at home: Figure 2. A common causal variable is a variable that is not part of the research hypothesis but that causes both the predictor and the outcome variable and thus produces the observed correlation between them. In our example a potential common-causal variable is the discipline style of the children’s parents. Parents who use a harsh and punitive discipline style may produce children who both like to watch violent television and who behave aggressively in comparison to children whose parents use less harsh discipline: Figure 2. When the predictor and outcome variables are both caused by a common-causal variable, the observed relationship between them is said to be spurious. A spurious relationship is a relationship between two variables in which a common-causal variable produces and “explains away” the relationship. If effects of the common-causal variable were taken away, or controlled for, the relationship between the predictor and outcome variables would disappear. In the example the relationship between aggression and television viewing might be spurious because by controlling for the effect of the parents’ disciplining style, the relationship between television viewing and aggressive behavior might go away. Common-causal variables in correlational research designs can be thought of as “mystery” variables because, as they have not been measured, their presence and identity are usually unknown to the researcher. Since it is not possible to measure every variable that could cause both the predictor and outcome variables, the existence of an unknown common-causal variable is always a possibility. For this reason, we are left with the basic limitation of correlational research: Correlation does not demonstrate causation. It is important that when you read about correlational research projects, you keep in mind the possibility of spurious relationships, and be sure to interpret the findings appropriately. Although correlational research is sometimes reported as demonstrating causality without any mention being made of the possibility of reverse causation or common-causal variables, informed consumers of research, like you, are aware of these interpretational problems. One strength is that they can be used when experimental research is not possible because the predictor variables cannot be manipulated. Correlational designs also have the advantage of allowing the researcher to study behavior as it occurs in everyday life. And we can also use correlational designs to make predictions—for instance, to predict from the scores on their battery of tests the success of job trainees during a training session. But we cannot use such correlational information to determine whether the training caused better job performance. In an experimental research design, the variables of interest are called the independent variable(or variables) and the dependent variable. The independent variable in an experiment is the causing variable that is created (manipulated) by the experimenter. The dependent variable in an experiment is a measured variable that is expected to be influenced by the experimental manipulation. The research hypothesis suggests that the manipulated independent variable or variables will cause changes in the measured dependent variables. We can diagram the research hypothesis by using an arrow that points in one direction. The study was designed to test the hypothesis that viewing violent video games would increase aggressive behavior. In this research, male and female undergraduates from Iowa State University were given a chance to play with either a violent video game (Wolfenstein 3D) or a nonviolent video game (Myst). During the experimental session, the participants played their assigned video games for 15 minutes. Then, after the play, each participant played a competitive game with an opponent in which the participant could deliver blasts of white noise through the earphones of the opponent. The operational definition of the dependent variable (aggressive behavior) was the level and duration of noise delivered to the opponent. For one, they guarantee that the independent variable occurs prior to the measurement of the dependent variable. Second, the influence of common-causal variables is controlled, and thus eliminated, by creating initial equivalence among the participants in each of the experimental conditions before the manipulation occurs. The most common method of creating equivalence among the experimental conditions is through random assignment to conditions, a procedure in which the condition that each participant is assigned to is determined through a random process, such as drawing numbers out of an envelope or using a random number table. Anderson and Dill first randomly assigned about 100 participants to each of their two groups (Group A and Group B). Because they used random assignment to conditions, they could be confident that, before the experimental manipulation occurred, the students in Group A were, on average, equivalent to the students in Group B on every possible variable, including variables that are likely to be related to aggression, such as parental discipline style, peer relationships, hormone levels, diet—and in fact everything else. Then, after they had created initial equivalence, Anderson and Dill created the experimental manipulation—they had the participants in Group A play the violent game and the participants in Group B play the nonviolent game. Anderson and Dill had from the outset created initial equivalence between the groups. This initial equivalence allowed them to observe differences in the white noise levels between the two groups after the experimental manipulation, leading to the conclusion that it was the independent variable (and not some other variable) that caused these differences. The idea is that the only thing that was different between the students in the two groups was the video game they had played. One is that they are often conducted in laboratory situations rather than in the everyday lives of people. Therefore, we do not know whether results that we find in a laboratory setting will necessarily hold up in everyday life. Second, and more important, is that some of the most interesting and key social variables cannot be experimentally manipulated. If we want to study the influence of the size of a mob on the destructiveness of its behavior, or to compare the personality characteristics of people who join suicide cults with those of people who do not join such cults, these relationships must be assessed using correlational designs, because it is simply not possible to experimentally manipulate these variables. The goal of these designs is to get a picture of the current thoughts, feelings, or behaviors in a given group of people. The variables may be presented on a scatter plot to visually show the relationships. The Pearson Correlation Coefficient (r) is a measure of the strength of linear relationship between two variables. The possibility of common-causal variables makes it impossible to draw causal conclusions from correlational research designs. Random assignment to conditions is normally used to create initial equivalence between the groups, allowing researchers to draw causal conclusions. There is a negative correlation between the row that a student sits in in a large class (when the rows are numbered from front to back) and his or her final grade in the class. Do you think this represents a causal relationship or a spurious relationship, and why. Think of two variables (other than those mentioned in this book) that are likely to be correlated, but in which the correlation is probably spurious. Imagine a researcher wants to test the hypothesis that participating in psychotherapy will cause a decrease in reported anxiety. Describe the type of research design the investigator might use to draw this conclusion.
To analyse the 3D images for a set of craniofacial landmarks and various facial measurements diabetes prevention yoga generic 4mg glimepiride amex. Following the association study results blood glucose random discount glimepiride 4mg visa, to blood sugar newborn purchase glimepiride 2mg fast delivery evaluate the statistically significant markers for their prediction power of specific traits diabetes mellitus latest research cheap glimepiride 4mg fast delivery. Most of the volunteers who participated in this study were Bond University students. All volunteers completed a questionnaire and gave informed consent (supplement documents S3 and S4). The samples without 3D images were accompanied with pigmentation and ancestry information. The phenotype-related information in questionaries and all the craniofacial measurements were taken by the author. Samples of volunteers who had experienced severe facial injury and/or undergone facial surgery. The 3D facial image database and recorded personal information were stored in a single user access database on a dedicated computer. An additional set of samples was used for genotyping as a part of a validation study using the GoldenGate assay on the BeadExpress instrument (Illumina). The samples of the African American ancestry were assigned with dark skin and black hair phenotype. Some web resources were used for several aspects of the candidate marker selection process and are repeated in different categories. Approximately 700 additional markers, previously shown to be associated with pigmentation traits, ancestry and identity informative markers were selected from the relevant literature and added to the final markers list. Based on the design output (failure of some markers), the marker list was resubmitted with alternative markers, showing high linkage with the markers that failed initial primer design. The final custom Ampliseq primer multiplex set was designed as two separate pools of approximately 850 primer pairs each. Two daylight fluorescent sources (3400K/5400K colour temperature) were mounted in the room. The scanner was mounted at a distance of approximately 1 meter from the volunteer’s head. Each volunteer was scanned three times from different angles (front and two sides). The final merged 3D image was produced by semi-automatically aligning all scans and deleting non-overlapping or unnecessary data. The complete coordinates of each merged 3D image were saved in a vivid file format (. This procedure automatically repaired imperfections in the polygon mesh of the scanned object. An illustration of a merged image output after initial image processing in the Geomagic software. The measurements were as follows: V-Gn (Craniofacial height) Eu-Eu (Head Width) G-Op (Head Length) Based on craniofacial and body height measurements, three craniofacial ratios were calculated using a Microsoft Excel software: Cephalic index – (eu-eu)*100/(g-op) Head width – Craniofacial height index (eu-eu)*100/(v-gn) Head – Body height index (v-gn)*100/(body height) 2. Facial measurements Facial measurements were recorded upon location of specific anthropometrical landmarks and included linear and angular distances as well as ratios between these 77 | P a g e distances. The following section describes the landmarking protocol used and provides details regarding the craniofacial measurements obtained. Landmarking protocol Each 3D image was analysed to allocate 32 facial landmarks using Geomagic software. Each landmark was represented by ‘x’, ‘y’ and ‘z’ coordinates as part of the Cartesian coordinate system (Figure 29). Illustration of 32 facial landmarks allocated on face with their corresponding coordinates. The following landmarking protocol provides a list of 32 facial landmarks that were used in this study, and describes their anthropological location, according to Farkas et. The left (l) and right (r) sides of the relevant landmarks identified according to corresponding anatomical sides of the face. The names in parentheses are commonly used alternative anthropometric names of the corresponding landmark. Landmark Number Abbreviation Left (l) or Description Notes Right (r) Gnathion 1 gn the lowest anterior Identical to the midpoint of the chin, bony gnathion. In the case of the bifid nose, the more protruding tip is chosen for prn Alare 13 al(l) Left the most protruded point of each alar contour Alare 14 al(r) Right the most protruded point of each alar contour Nasion (soft 15 n the deepest point on the nasal bridge tissue) 80 | P a g e Glabella 16 g the most prominent midline point between the eyebrows Trichion 17 tr the point of the hairline Cannot be in the midline of the determined on a forehead balding head Endocanthion 18 en(l) Left the point at the inner commissure of the eye fissure Exocanthion 19 ex(l) Left the point at the outer commissure of the eye fissure Palpebrale 20 ps(l) Left the highest point in the midportion of the free superius margin of each upper eyelid Palpebrale 21 pi(l) Left the lowest point in the inferius midportion of the free margin of each lower eyelid Endocanthion 22 en(r) Right the point at the inner commissure of the eye fissure Exocanthion 23 ex(r) Right the point at the outer commissure of the eye fissure Palpebrale 24 ps(r) Right the highest point in the midportion of the free superius margin of each upper eyelid Palpebrale 25 pi(r) Right the lowest point in the inferius midportion of the free margin of each lower eyelid Zygion 26 zy(r) Right the most lateral point of Identical to the each zygomatic arch bony zygion of the malar bones. If the angle is flat or if there is 81 | P a g e a rich soft-tissue cover, determination of this point is difficult Zygion 27 zy(l) Left the most lateral point of Identical to the each zygomatic arch bony zygion of the malar bones. If the angle is flat or if there is a rich soft-tissue cover, determination of this point is difficult Superaurale 28 sa(l) Left the highest point on the free margin of the ear lobe Subalare 29 sba(l) Left the lowest point on the free margin of the ear lobe Postaurale 30 pa(l) Left the most posterior point on the free margin of the ear Tragion 31 t(l) Left the notch on the upper margin of the tragus Tragion 32 t(r) Right the notch on the upper margin of the tragus All the facial landmarks were allocated manually, using 3D images generated by the Geomagic software. Linear measurements the data for 32 facial landmarks were processed in Excel to calculate each of the 54 linear measurements. The general formula for calculating a distance between two landmarks in the Euclidean space is: v where ‘x, y and z’ are the coordinates of each landmark in the Cartesian space. The formula was used in the Excel spreadsheet for automatic calculation of the linear distances. For images of a good quality (full set of 32 facial landmarks available), a full set of measurements was generated. The data for the following facial measurements were generated for each 3D image: Total face height: tr-gn Face width: zy-zy Morphological face height: n-gn Physiognomical face height: n-sto Lower profile height: prn-gn Lower face height: sn-gn Lower third face depth: t(l)-gn Middle face depth: t(l)-prn Middle face height (right): go(r)-zy(r) Middle face height (left): go(l)-zy(l) Middle face width 1: t(r)-t(l) Middle face width 2 (left): zy(l)-al(l) Middle face width 2 (right): zy(r)-al(r) Upper face depth: (left): t(l)-tr Upper face depth: (right): t(r)-tr Upper third face depth: t(l)-n Forehead height: g-tr Extended forehead height: tr-n Glabella –Gnathion distance: g-gn Supraorbital depth: t(l)-g Trichion – Zygion distance (left): tr-zy(l) Trichion – Zygion distance (right): tr-zy(r) Nasion Zygion distance (left): n-zy(l) 83 | P a g e Nasion Zygion distance (right): n-zy(r) Zygion – Gnathion distance (left): zy(l)-gn Zygion – Gnathion distance (right): zy(r)-gn Intercanthal width: en-en Biocular width: ex-ex Eye fissure width (left): en(l)-ex(l) Eye fissure width (right): en(r)-ex(r) Eye fissure height (left): ps(l)-pi(l) Eye fissure height (right): ps(r)-pi(r) Ear height (left): sa(l)-sba(l) Ear width (left): t(l)-pa(l) Nasal bridge width: n-prn Nose height: n-sn Nose width: al-al Nasal tip protrusion: sn-prn Ala length (left): prn-al(l) Ala length (right): prn-al(r) Gonion Trichion distance (left): go(l)-tr Gonion Trichion distance (right): go(r)-tr Gonion – Glabella distance: g-pg Pronasale Gonion distance (left): prn-go(l) Pronasale Gonion distance (right): prn-go(r) Chin height: sl-gn Mandibular region depth (right): t(r)-gn Mandible width: go-go Mandible height: sto-gn Lower jaw depth (left): gn-go(l) Lower jaw depth (right): gn-go(r) Mouth width: ch-ch Upper vermilion height: ls-sto Lower vermilion height: li-sto 84 | P a g e 2. Angular measurements Ten angular measurements were calculated based on previously allocated Euclidean coordinates for facial landmarks. Angular measurements were calculated between two 3D vectors of the three corresponding landmarks. As shown at the following scheme, each three landmarks for any angular measurement form two vectors (“ac” and “bc”), and the angle is measured between vectors: c a b the general formula for calculating an angle between two vectors in the Cartesian coordinates system is: Cos = (a. An example of angular distances on a 3D image a) with and b) without facial surface texture. The following list summarizes ten angular measurements, obtained from 3D facial images. Ratios the data acquired from linear measurements were used to calculate 21 facial indices (ratios), according to the following list: Forehead height ratio (tr-n)x100/(go(r)-go(l)) Upper face height ratio (n-sn)x100/(go(r)-go(l)) Lower face height ratio: (sn-gnx100/(go-go) Anterior face height 1 ratio: (n-gn)x100/(go-go) Anterior face height 2 ratio: (n-gn)x100/(zy-zy) Face height index: (n-gn)x100/(tr-gn) Upper – Lower face ratio: (tr-g)x100/(sn-gn) Upper face height ratio: (n-sn)x100/(sn-gn) Upper face width ratio: (n-sn)x100/(zy-zy) Total anterior face height ratio: (tr-gn)x100/(zy-zy) Mouth width ratio: (ch-ch)x100/(en-en) Mandible – Face width ratio: (go-go)x100/(zy-zy) Mandible index: (sto-gn)x100/(go-go) Mandible – Interexocanthion distance ratio (go-go)x100/(ex-ex) Interendocanthion distance ratio: (en-en)x100/(al-al) Intercanthal index: (en(R)-en(L))x100/(ex(R)-ex(L)) Intercanthal – Intracanthal index: (ex(R)-en(R))x100/(en(L)-ex(L)) Nasal index: (al-al)x100/(n-sn) Nose-face height index: (n-sn)x100/(n-gn) Nose-face width index: (al-al)x100/(zy-zy) Nasal tip protrusion – nose width index: (sn-prn)/(al-al) Nasal tip protrusion –Nose height index: (sn-prn)x100/(n-sn) 2. Principal components All the craniofacial measurements and indexes (n=85) generated in this study were used for calculation of 20 principal components, as discussed in details in Section 4. The original amplification reaction was split into two 10µl reactions for each of the multiplex pools, as per manufacturer’s recommendations. The master mix included 2µl of 5x Ion AmpliSeq™ HiFi Master Mix and 5µl of each 2x Ion AmpliSeq™ Primer Pool. The amplification conditions included 0 0 an initial ‘hold’ step of 99 C for 2 minutes, 15 cycles of 99 C for 15 seconds followed 0 0 by 60 C for 8 minutes and a final hold step of 10 C for up to 1 hour. The resulting amplicons were treated with 2µl FuPa reagent to partially digest the primers and phosphorylate the amplicons. The sample plate was placed in a thermal 0 0 cycler and incubated at 50 C for 10 minutes, followed by 10 minutes incubation at 55 C 0 and then by 60 C incubation for 20 minutes. Subsequent to primer digestion, the amplicons were ligated to Ion Adapters with up to 32 unique barcodes (according to the number of samples). The final libraries were quantified using an Ion Library Quantitation Kit as per manufacturer recommendations. The amplification reaction was performed in 10µl (half of the recommended reaction volume). The 0 0 amplification step included 50 C for 2 minutes, 95 C for 20 seconds, followed by 40 0 0 cycles of 95 C for 3 seconds and 60 C for 30 seconds each. Template preparation Each library was diluted to approximately 10 pM to 20 pM and mixed in equimolar ratios. The sequencing round lasted approximately 8 hours and included sequencing of two 316 chips (up to 32 libraries per chip). The red-coloured areas in Figure 33 represent fully loaded wells, while the yellow colour represents less loaded and blue and green areas shows very poorly loaded wells. The blue areas usually represent air bubbles, which can be “trapped” inside the chip, during the loading process. Alternatively, these areas may be caused by a technical failure in the chip manufacturing process. In this image, red indicates good loading, yellow is passable, and green and blue (air bubbles) show very poor loading. This value depends on the initial concentration of the libraries, used for enrichment and efficiency of the template preparation on OneTouch™ instrument.
The pit is a nearly perfect cone diabetes short definition buy 2 mg glimepiride visa, whose sides slope so steeply that prey cannot climb out once they have fallen in weight watchers diabetic diet buy glimepiride 2mg otc. The antlion sits just under the sand at the bottom of the pit type 1 diabetes questions and answers buy glimepiride 2mg overnight delivery, where it lunges with its horror-film jaws at anything that falls in blood glucose finger stick order cheap glimepiride line. It costs time and energy, and satisfies the most exacting criteria for recognition as an adaptation (Williams 1966; Curio 1973). Probably an ancestral antlion existed which did not dig a pit but simply lurked just beneath the sand surface waiting for prey to blunder over it. Later, behaviour leading to the creation of a shallow depression in the sand probably was favoured by selection because the depression marginally impeded escaping prey. By gradual degrees over many generations the behaviour changed so that what was a shallow depression became deeper and wider. This not only hindered escaping prey but also increased the catchment area over which prey might stumble in the first place. Later still the digging behaviour changed again so that the resulting pit became a steep-sided cone, lined with fine, sliding sand so that prey were unable to climb out. It will be regarded as legitimate speculation about historical events that we cannot see directly, and it will probably be thought plausible. One reason why it will be accepted as uncontroversial historical speculation is that it makes no mention of genes. But my point is that none of that history, nor any comparable history, could possibly have been true unless there was genetic variation in the behaviour at every step of the evolutionary way. Pit-digging in antlions is only one of the thousands of examples that I could have chosen. Unless natural selection has genetic variation to act upon, it cannot give rise to evolutionary change. It follows that where you find Darwinian adaptation there must have been genetic variation in the character concerned. There is no need to do one, if all we Genetic Determinism and Gene Selectionism 21 want to do is satisfy ourselves of the sometime existence of genetic variation in the behaviour pattern. It is sufficient that we are convinced that it is a Darwinian adaptation (if you are not convinced that pit-digging is such an adaptation, simply substitute any example of which you are convinced). This was because it is quite likely that, were a genetic study to be mounted of antlions today, no genetic variation would be found. It is in general to be expected that, where there is strong selection in favour of some trait, the original variation on which selection acted to guide the evolution of the trait will have become used up. Functional hypotheses frequently concern phenotypic traits, like possession of eyes, which are all but universal in the population, and therefore without contemporary genetic variation. When we speculate about, or make models of, the evolutionary production of an adaptation, we are necessarily talking about a time when there was appropriate genetic variation. But this is a routine genetic practice, and one which close examination shows to be almost inevitable. Other than at the molecular level, where one gene is seen directly to produce one protein chain, geneticists never deal with units of phenotype as such. He is implicitly saying: there is variation in eye colour in the population; other things being equal, a fly with this gene is more likely to have red eyes than a fly without the gene. This happens to be a morphological rather than a behavioural example, but exactly the same applies to behaviour. A related point is that the use of single-locus models is just a conceptual convenience, and this is true of adaptive hypotheses in exactly the same way as it is true of ordinary population genetic models. When we use single-gene language in our adaptive hypotheses, we do not intend to make a point about single-gene models as against multi-gene models. Since it is difficult enough convincing people that they ought to think in genetic terms at all rather than in terms of, say, the good of the species, there is no sense in making things even more 22 Genetic Determinism and Gene Selectionism difficult by trying to handle the complexities of many loci at the outset. To phrase a functional hypothesis in terms of genes is to make no strong claims about genes at all: it is simply to make explicit an assumption which is inseparably built into the modern synthesis, albeit it is sometimes implicit rather than explicit. A few workers have, indeed, flung just such a challenge at the whole neo Darwinian modern synthesis, and have claimed not to be neo-Darwinians. But that they are generated, and that genes contribute significantly to their variation are incontrovertible facts, and those facts are all we need in order to make neo-Darwinism coherent. Goodwin might just as well say that, before Hodgkin and Huxley worked out how the nerve impulse fired, we were not entitled to believe that nerve impulses controlled behaviour. Of course it would be nice to know how phenotypes are made but, while embryologists are busy finding out, the rest of us are entitled by the known facts of genetics to carry on being neo Darwinians, treating embryonic development as a black box. It follows from the fact that geneticists are always concerned with phenotypic differences that we need not be afraid of postulating genes with indefinitely complex phenotypic effects, and with phenotypic effects that show themselves only in highly complex developmental conditions. The air was thick with the un mistakable sound of worst suspicions being gleefully confirmed. Delightedly Genetic Determinism and Gene Selectionism 23 sceptical cries drowned the quiet and patient explanation of just what a modest claim is being made whenever one postulates a gene for, say, skill in tying shoelaces. Let me explain the point with the aid of an even more radical-sounding yet truly innocuous thought experiment (Dawkins 1981). Reading is a learned skill of prodigious complexity, but this provides no reason in itself for scepticism about the possible existence of a gene for reading. All we would need in order to establish the existence of a gene for reading is to discover a gene for not reading, say a gene which induced a brain lesion causing specific dyslexia. Such a dyslexic person might be normal and intelligent in all respects except that he could not read. No geneticist would be particularly surprised if this type of dyslexia turned out to breed true in some Mendelian fashion. Obviously, in this event, the gene would only exhibit its effect in an environment which included normal education. In a prehistoric environment it might have had no detectable effect, or it might have had some different effect and have been known to cave-dwelling geneticists as, say, a gene for inability to read animal footprints. Similarly, a gene which caused total blindness would also prevent reading, but it would not usefully be regarded as a gene for not reading. This is simply because preventing reading would not be its most obvious or debilitating phenotypic effect. In both cases the character of interest is a difference, and in both cases the difference only shows itself in some specified environment. The reason why something so simple as a one gene difference can have such a complex effect as to determine whether or not a person can learn to read, or how good he is at tying shoelaces, is basically as follows. However complex a given state of the world may be, the difference between that state of the world and some alternative state of the world may be caused by something extremely simple. Shortly after a chick hatches, the parent bird grasps the empty eggshell in the bill and removes it from the vicinity of the nest. Tinbergen and his colleagues considered a number of 24 Genetic Determinism and Gene Selectionism possible hypotheses about the survival value of this behaviour pattern. For instance they suggested that the empty eggshells might serve as breeding grounds for harmful bacteria, or the sharp edges might cut the chicks. But the hypothesis for which they ended up finding evidence was that the empty eggshell serves as a conspicuous visual beacon summoning crows and other predators of chicks or eggs to the nest. They did ingenious experiments, laying out artificial nests with and without empty eggshells, and showed that eggs accompanied by empty eggshells were, indeed, more likely to be attacked by crows than eggs without empty eggshells by their side. They concluded that natural selection had favoured eggshell removal behaviour of adult gulls, because past adults who did not do it reared fewer children. As in the case of antlion digging, nobody has ever done a genetic study of eggshell removal behaviour in black-headed gulls. There is no direct evidence that variation in tendency to remove empty eggshells breeds true. Yet clearly the assumption that it does, or once did, is essential for the Tinbergen hypothesis. The Tinbergen hypothesis, as normally phrased in gene-free language, is not particularly controversial. Yet it, like all the rival functional hypotheses that Tinbergen rejected, rests fundamentally upon the assumption that once upon a time there must have been gulls with a genetic tendency to remove eggshells, and other gulls with a genetic tendency not to remove them, or to be less likely to remove them. Suppose we actually did a study of the genetics of eggshell removal behaviour in modern gulls. On the contrary, it seems much more probable that a complex behaviour pattern like eggshell removal must have been built up by selection on a large number of loci, each having a small effect in interaction with the others.
People do some things alone diabetes type 2 disease process purchase glimepiride with mastercard, but it is difficult to blood sugar goals for diabetics purchase glimepiride from india escape the evaluative scrutiny of others in a complex blood sugar blurred vision buy glimepiride 2 mg lowest price, interdependent society blood sugar 80 after eating cheap 2mg glimepiride mastercard. Escape arguably becomes impossible when we countself-accountability – the obligation that most human beings feel to internalized representations of significant others who keep watch over them when no one else is looking (Mead, 1934; Schlenker, 1985). Most people are pragmatic intuitive politicians who seek the approval of the constituencies pressing on them at the moment for combinations of intrinsic and extrinsic reasons. Evidence for an intrinsic-approval motive comes from developmental studies that point to the remarkably early emergence in human life of automatic and visceral responses to signs of censure, such as angry words and contemptuous facial expressions (Baumeister & Leary, 1995). Evidence for an extrinsic motive comes from the exchange-theory tradition that, in its crassest version, maintains that we care about what others think of us only insofar as others control resources that we value to a greater degree than we control resources that they value (asymmetric resource dependency). A realistic composite portrait requires identifying at least four potentially conflicting motives: the goals of (1) achieving cognitive mastery of causal structure, (2) minimizing mental effort and achieving reasonably rapid cognitive closure, (3) maximizing benefits and minimizing the costs of relationships, and (4) asserting one’s autonomy and personal identity by remaining true to one’s innermost convictions. A testable model must connect broad motivational assumptions to specific coping strategies by indicating how each motive can be amplified or attenuated by the prevailing accountability norms. The next sections of the chapter deploy this schematic formula to identify the optimal preconditions for activating the four strategies for coping with accountability that have received the most attention: strategic attitude shifting; preemptive self-criticism; defensive bolstering; and the decision evasion tactics of buck-passing, procrastination, and obfuscation. Strategic Attitude Shifting Decision makers are predicted to adjust their public attitudes toward the views of the anticipated audience when the approval motive is strong. Ideally, the evaluative audience should be perceived to be powerful, firmly committed to its position, and intolerant of other positions. Strategic attitude shifting is viable, however, only to the degree that decision makers think they know the views of the anticipated audience. Attitude shifting becomes psychologically costly to the degree that it requires compromising basic convictions and principles (stimulating dissonance) or back-tracking on past commitments (making decision makers look duplicitous, hypocritical, or sycophantic). Lerner and Tetlock (1999) reviewed evidence that indicates that when these obstacles have been removed and the facilitative conditions are present, attitude shifting serves as a cognitively efficient and politically expedient means of gaining approval that does not undermine the decision maker’s self concept as a moral and principled being, or his or her reputation for integrity in the wider social arena. Moreover, people are sometimes “taken in” by their own self-presentational maneuvering, internalizing positions they publicly endorse. Preemptive Self Criticism Cognitively economic and socially adaptive although the attitude shifting can be, its usefulness is limited to settings in which decision makers can discern easily what others want or expect. To maximize the likelihood of preemptive self-criticism, the evaluative audience should be perceived to be well informed (so that it cannot be tricked easily) and powerful (so that decision makers want its approval), and the decision makers should not feel constrained by prior commitments that it would now be embarrassing to reverse. In the case of accountability to conflicting audiences, the audiences should be approximately equally powerful (otherwise a low-effort expedient is to align oneself with the more powerful audience), the two audiences should recognize each other’s legitimacy (otherwise searching for complex integrative solutions is seen as futile), and there should be no institutional precedents for escaping responsibility (otherwise the evasion tactics of buck-passing, procrastination, or obfuscation become tempting). Several experiments demonstrate that the hypothesized forms of accountability do activate more complex and self-critical patterns of thinking (Ashton, 1992; Weldon & Gargano, 1988; Hagafors & Brehmer, 1983). In addition, subjects reported their thoughts (confidentiality always guaranteed) on each issue prior to committing themselves to positions. These thought protocols were subjected to detailed content analysis designed to assess the integrative complexity of subjects’ thinking on the issues: How many facets of each issue did they distinguish. Did they interpret issues in dichotomous, good–bad terms, or did they recognize positive and negative features of both sides of the issues. Subjects coped in two qualitatively distinct ways: shifting their public positions (thus making the task of justification easier) and thinking about issues in more flexible multidimensional ways (thus preparing themselves for possible counterarguments). They relied on attitude shifting when they felt accountable to an audience with known liberal or conservative views. Accountability to known audiences had minimal impact, however, on the complexity of private thoughts. Accountability now had virtually no effect on public attitudes, but a substantial effect on the complexity of private thoughts. Subjects were markedly more tolerant of evaluative inconsistency (recognizing good features of rejected policies and bad features of accepted ones) and more aware of difficult value trade-offs. Subjects accountable to unknown audiences appeared to engage in preemptive self-criticism in which they tried to anticipate arguments of potential critics. This can be viewed as an adaptive strategy to protect both one’s self-image and social image. Expecting to justify one’s views to an unknown audience raised the prospect of failure: the other person might find serious flaws in one’s position. To minimize potential embarrassment, subjects demonstrated their awareness of alternative perspectives: “You can see that I am no fool. Participants in this study reported their thoughts on four controversial issues either before or after they had committed themselves to stands. Some subjects believed that their stands were private; others believed that they would later justify their views to an audience with unknown, liberal, or conservative views. Accountable participants who reported their thoughts after making commitments became markedly less tolerant of dissonant arguments than were three other groups: unaccountable participants who reported their thoughts after making commitments and both unaccountable and accountable participants who reported their thoughts prior to taking a stand. Once people had publicly committed themselves to a position, a major function of thought became generating justifications for those positions. As a result, the integrative complexity of thoughts plunged (subjects were less likely to concede legitimacy to other points of view) and the number of pro-attitudinal thoughts increased (subjects generated more reasons why they were right and would-be critics were wrong). Ideally, each audience should deny the legitimacy of the accountability demands of the other, thereby rendering the prospects of either a log rolling or an integratively complex solution hopeless. The audiences should also be approximately equal in power, thereby reducing the attractiveness for decision makers of aligning themselves with one or the other camp. There should also be widely accepted institutional precedents for engaging in decision evasion (that is, no Trumanesque “the-buck-stops-here” norm). Finally, decision makers should have weak personal convictions and be strongly motivated to maintain good relations with both of the affected parties. Several experimental and field studies provide supportive evidence (Janis & Mann, 1977; Wilson, 1989). Consider the predicament that Tetlock and Boettger (1994) created in a laboratory simulation of Food and Drug Administration decision making on the acceptability of a controversial anti-clotting drug into the U. The experimental manipulations included: (1) whether the drug was already on the market (so decision makers would have to take responsibility for removing it) or was not yet on the market (so decision makers would have to take responsibility for introducing it); (2) whether decision makers expected their recommendations to be anonymous or scrutinized by the affected constituencies; and (3) the benefit–cost ratio of the drug which ranged from 3:1 to 9:1 in favor of the drug. Confronted by pressures to take a stand one way or the other that was guaranteed to earn the enmity of an influential constituency, subjects, especially those in the off-themarket/accountability condition, sought options that allowed them to avoid taking any stand. This was true, moreover, even when the buck-passing and procrastination options had been rendered unattractive. Subjects still performed buck-passing when they thought that the agency to which they could refer the decision had no more information than they possessed, and they still procrastinated when there was virtually no prospect that additional useful evidence would materialize in the permissible delayed-action period. These decisionavoidant respondents also had remarkably loss-averse policy preferences even by the standards of prospect theory (requiring that the new drug have a much higher benefit–cost ratio, up to 9:1, to enter the market than the old drug had to have to remain in the market). The skeptics might even dust off a slightly modified version of the disciplinary division of labor between psychology and the social sciences initially proposed by Miller and Dollard (1946): the mission of the cognitive research program is to shed light on how people think, whereas the mission of the intuitive-politician research program (and other deviant metaphoric traditions) is to shed light on what people think about and when they are willing to say what is on their minds (raising or lowering response thresholds for expressing certain views). Certain coping strategies have socially significant but cognitively uninteresting implications for the conditions under which biases and errors manifest themselves. It is easy to imagine the types of heavy-handed social pressures that trigger strategic attitude shifting also suppressing evidence of cognitive bias. People can readily learn that their boss expects them to use certain cues or to disregard others, and it is easy to see why cognitive theorists would find evidence of such bias suppression less than intriguing. There is no great surprise in learning that conformity pressures can alter response thresholds. The acceptability heuristic (as Tetlock, 1992, semi-facetiously labeled it) represents a minor content embellishment on the heuristics-and-biases portrait of the decision maker. The most salient consideration in many decisions is the justifiability of policy options to others. The cognitive research programs tell us that people often use a small number of cues in making up their minds; the intuitive-politician research program tells us that decision makers’ estimates of the probable reactions of those to whom they are accountable will be prominent among the few items considered. The self-presentational processes triggered by accountability can interact in complex ways with putatively basic cognitive processes. Within the intuitive-politician framework, a key function of private thought is preparation for public performances. Thought frequently takes the form of internalized dialogs in which people gauge the relative justifiability of alternative courses of action by imagining conversations with others in which accounts are exchanged, debated, revised, and evaluated. Indeed, converging lines of evidence demonstrate that certain forms of accountability do change how people think, not just what they are willing to say they think: 1. Predecisional forms of accountability to unknown audiences increase the complexity of argumentation, as revealed by content analysis of confidential thought protocols and the complexity of cue use as revealed by statistical modelling of judgment policies (Hagafors & Brehmer, 1983; Tetlock et al. Accountability manipulations are much more effective in attenuating certain cognitive biases – primacy, overattribution, overconfidence – when participants learn of being accountable prior to (as opposed to after) exposure to the evidence on which they are basing their judgments (Tetlock, 1983b, 1985; Tetlock & Kim, 1987). There is also evidence that increased complexity of thought at least partly mediates these debiasing demonstrations. The power of certain accountability manipulations to attenuate bias is attenuated by impositions of cognitive load that disrupt more effort and attention-demanding forms of information processing (Kruglanski & Freund, 1983; Tetlock, 1992) – disruption that should not occur if people coped with accountability by relying exclusively on low-effort attitude shifting.
Buy glimepiride mastercard. Exercise program for people w/ diabetes.