Division of Sleep Medicine, Harvard Medical School,
Boston, MA, USA
Illusions occur when the perceptual processes that normally help us correctly perceive the world around us are fooled by a particular situation so that we see something that does not exist or that is incorrect gastritis symptoms burning sensation purchase pariet 20 mg on-line. Square A in the right-hand image looks very different from square B chronic gastritis no h pylori generic pariet 20 mg on-line, even though they are exactly the same gastritis translation buy generic pariet 20 mg line. The line segment in the bottom arrow looks longer to us than the one on the top gastritis radiology purchase pariet 20mg free shipping, even though they are both actually the same length gastritis keeps coming back purchase 20 mg pariet free shipping. It is likely that the illusion is gastritis losing weight purchase pariet 20 mg mastercard, in part, the result of the failure of monocular depth cues-the bottom line looks like an edge that is normally farther away from us, whereas the top one looks like an edge that is normally closer. The illusion is caused, in part, by the monocular distance cue of depth-the bottom line looks like an edge that is normally farther away from us, whereas the top one looks like an edge that is normally closer. The moon illusion refers to the fact that the moon is perceived to be about 50% larger when it is near the horizon than when it is seen overhead, despite the fact that both moons are the same size and cast the same size retinal image. The skyline of the horizon (trees, clouds, outlines of buildings) also gives a cue that the moon is far away, compared to a moon at its zenith. If we look at a horizon moon through a tube of rolled up paper, taking away the surrounding horizon cues, the moon will immediately appear smaller. The monocular depth cue of linear perspective leads us to believe that, given two similar objects, the distant one can only cast the same size retinal image as the closer object if it is larger. Illusions demonstrate that our perception of the world around us may be influenced by our prior knowledge. But the fact that some illusions exist in some cases does not mean that the perceptual system is generally inaccurate-in fact, humans normally become so closely in touch with their environment that that the physical body and the particular environment that we sense and perceive becomes embodied-that is, built into and linked with-our cognition, such that the worlds around us become part of our brain (Calvo & Gamila, 2008). And even experts can be fooled: Professional referees tended to assign more penalty cards to soccer teams for videotaped fouls when they were told that the team had a history of aggressive behavior than when they had no such expectation (Jones, Paull, & Erskine, 2002). Chua, Boland, and Nisbett (2005) [19] showed American and Asian graduate students different images, such as an airplane, an animal, or a train, against complex backgrounds. Furthermore, Asian-American students focused more or less on the context depending on whether their Asian or their American identity had been activated. Human factors has worked on a variety of projects, ranging from nuclear reactor control centers and airplane cockpits to cell phones and websites (Proctor & Van Zandt, 2008). Knowledge of the visual system also helped engineers create new kinds of displays, such as those used on notebook computers and music players, and better understand how using cell phones while driving may contribute to automobile accidents (Lee & Strayer, 2004). About two thirds of accidents on commercial airplane flights are caused by human error (Nickerson, 1998). Psychologist Conrad Kraft (1978) [23] hypothesized that as planes land, with no other distance cues visible, pilots may be subjected to a type of moon illusion, in which the city lights beyond the runway appear much larger on the retina than they really are, deceiving the pilot into landing too early. On the left is the initial design in which the controls were crowded and cluttered, in no logical sequence, each control performing one task. The controls were more or less the same in color, and the gauges were not easy to read. More of the controls are color-coded and multifunctional so that there is less clutter on the dashboard. Text sizes are changeable-increasing readability-and many of the functions have become automated, freeing up the pilots concentration for more important activities. Displays that are easy to see in darker conditions quickly become unreadable when the sun shines directly on them. It takes the pilot a relatively long time to adapt to the suddenly much brighter display. The display cannot be so bright at night that the pilot is unable to see targets in the sky or on the land. Human factors psychologists used these principles to determine the appropriate stimulus intensity needed on these displays so that pilots would be able to read them accurately and quickly under a wide range of conditions. The psychologists accomplished this by developing an automatic control mechanism that senses the ambient light visible through the front cockpit windows and that detects the light falling on the display surface, and then automatically adjusts the intensity of the display for the pilot (Silverstein, Krantz, Gomer, Yeh, & Monty, 1990; Silverstein & Merrifield, 1985). Sensory adaptation occurs when we become less sensitive to some aspects of our environment, freeing us to focus on more important changes. Cognitive illusions are examples of how our expectations can influence our perceptions. Our emotions, motivations, desires, and even our culture can influence our perceptions. Consider some cases where your expectations about what you think you might be going to experience have influenced your perceptions of what you actually experienced. The role of vection, eye movements, and postural instability in the etiology of motion sickness. The distorted room illusion, equivalent configurations, and the specificity of static optic arrays. Journal of Experimental Psychology: Human Perception and Performance, 14(2), 295304. Altering expectancy dampens neural response to aversive taste in primary taste cortex. Talis pater, talis filius: Perceived resemblance and the belief in genetic relatedness. Marketing actions can moderate neural representations of experienced pleasantness. See the ball, hit the ball: Apparent ball size is correlated with batting average. A psychophysical approach to air safety: Simulator studies of visual illusions in night approaches. The effects of spatial sampling and luminance quantization on the image quality of color matrix displays. The development and evaluation of color systems for airborne applications: Phase I Fundamental visual, perceptual, and display systems considerations(Tech. Each sense accomplishes the basic process of transduction-the conversion of stimuli detected by receptor cells into electrical impulses that are then transported to the brain-in different, but related, ways. Psychophysics is the branch of psychology that studies the effects of physical stimuli on sensory perceptions. Most of our cerebral cortex is devoted to seeing, and we have substantial visual skills. The eye is a specialized system that includes the cornea, pupil, iris, lens, and retina. Neurons, including rods and cones, react to light landing on the retina and send it to the visual cortex via the optic nerve. The shade of a color, known as hue, is conveyed by the wavelength of the light that enters the eye. The Young-Helmholtz trichromatic color theory and the opponent-process color theory are theories of how the brain perceives color. The ear detects both the amplitude (loudness) and frequency (pitch) of sound waves. Important structures of the ear include the pinna, eardrum, ossicles, cochlea, and the oval window. The frequency theory of hearing proposes that as the pitch of a sound wave increases, nerve impulses of a corresponding frequency are sent to the auditory nerve. The place theory of hearing proposes that different areas of the cochlea respond to different frequencies. Sounds that are 85 decibels or more can cause damage to your hearing, particularly if you are exposed to them repeatedly. Sounds that exceed 130 decibels are dangerous, even if you are exposed to them infrequently. The tongue detects six different taste sensations, known respectively as sweet, salty, sour, bitter, piquancy (spicy), and umami (savory). Thousands of nerve endings in the skin respond to four basic sensations: Pressure, hot, cold, and pain, but only the sensation of pressure has its own specialized receptors. The ability to keep track of where the body is moving is provided by the vestibular system. Perception involves the processes of sensory interaction, selective attention, sensory adaptation, and perceptual constancy. There, he attacked them with a knife, killing his mother-in-law and severely injuring his fatherin-law. Parks then drove to a police station and stumbled into the building, holding up his bloody hands and saying, "I think I killed some people. He said that he remembered going to sleep in his bed, then awakening in the police station with bloody hands, but nothing in between. His defense was that he had been asleep during the entire incident and was not aware of his actions (Martin, 2009). However, further investigation established that he did have a long history of sleepwalking, he had no motive for the crime, and despite repeated attempts to trip him up in numerous interviews, he was completely consistent in his story, which also fit the timeline of events. Parks was examined by a team of sleep specialists, who found that the pattern of brain waves that occurred while he slept was very abnormal (Broughton, Billings, Cartwright, & Doucette, 1994). They also agreed that such a combination of stressors was unlikely to happen again, so he was not likely to undergo another such violent episode and was probably not a hazard to others. Given this combination of evidence, the jury acquitted Parks of murder and assault charges. We all know what it means to be conscious, and we assume (although we can never be sure) that other human beings experience their consciousness similarly to how we experience ours. The study of consciousness has long been important to psychologists and plays a role in many important psychological theories. For instance, the French philosopher Renй Descartes (15961650) was a proponent of dualism, the idea that the mind, a nonmaterial entity, is separate from (although connected to) the physical body. In contrast to the dualists, psychologists believe that consciousness (and thus the mind) exists in the brain, not separate from it. In fact, psychologists believe that consciousness is the result of the activity of the many neural connections in the brain, and that we experience different states of consciousness depending on what our brain is currently doing (Dennett, 1991; Koch & Greenfield, 2007). Although we may understand and believe that some of our behaviors are caused by forces that are outside our awareness. And yet psychologists are increasingly certain that a great deal of our behavior is caused by processes of which we are unaware and over which we have little or no control (Libet, 1999; Wegner, 2003). And consciousness is fundamental to our sense of morality-we believe that we have the free will to perform moral actions while avoiding immoral behaviors. But in some cases consciousness may become aversive, for instance when we become aware that we are not living up to our own goals or expectations, or when we believe that other people perceive us negatively. If we drink too much coffee or beer, the caffeine or alcohol influences the activity in our brain, and our consciousness may change. When we are anesthetized before an operation or experience a concussion after a knock on the head, we may lose consciousness entirely as a result of changes in brain activity. We also lose consciousness when we sleep, and it is with this altered state of consciousness that we begin our chapter. Draw a graphic showing the usual phases of sleep during a normal night and notate the characteristics of each phase. Outline and explain the similarities and differences among the different theories of dreaming. The lives of all organisms, including humans, are influenced by regularly occurring cycles of behaviors known as biological rhythms. One important biological rhythm is the annual cycle that guides the migration of birds and the hibernation of bears. Women also experience a 28-day cycle that guides their fertility and menstruation. But perhaps the strongest and most important biorhythm is the daily circadian rhythm (from the Latin circa, meaning "about" or "approximately," and dian, meaning "daily") that guides the daily waking and sleeping cycle in many animals. Many biological rhythms are coordinated by changes in the level and duration of ambient light, for instance, as winter turns into summer and as night turns into day. In some animals, such as birds, the pineal gland in the brain is directly sensitive to light and its activation influences behavior, such as mating and annual migrations. In response, the pineal gland secretes melatonin, a powerful hormone that facilitates the onset of sleep. Research Focus: Circadian Rhythms Influence the Use of Stereotypes in Social Judgments the circadian rhythm influences our energy levels such that we have more energy at some times of day than others. Galen Bodenhausen (1990) argued that people may be more likely to rely on their stereotypes. One case involved a student athlete accused of cheating on an exam, one case involved a Hispanic student who allegedly physically attacked his roommate, and a third case involved an African American student who had been accused of selling illegal drugs. Each of these offenses had been judged via pretesting in the same student population to be stereotypically (although, of course, unfairly) associated with each social group. Participants also completed a measure designed to assess their circadian rhythms-whether they were more active and alert in the morning (Morning types) or in the evening (Evening types). The participants were then tested at experimental sessions held either in the morning (9 a. Morning people used their stereotypes more when they were tested in the evening, and evening people used their stereotypes more when they were tested in the morning. Sleep Stages: Moving Through the Night Although we lose consciousness as we sleep, the brain nevertheless remains active. Each of the sleep stages has its own distinct pattern of brain activity (Dement & Kleitman, 1957). When we are awake, our brain activity is characterized by the presence of very fast beta waves. When we first begin to fall asleep, the waves get longer (alpha waves), and as we move into stage N1 sleep, which is characterized by the experience of drowsiness, the brain begins to produce even slower theta waves.
Broca thought "le grand lobe limbique" was primarily involved with olfaction gastritis nerviosa cheap pariet 20mg free shipping, because of its interconnections with the evolutionarily older rhinencephalon gastritis etiology cheap 20 mg pariet fast delivery, or "smell brain gastritis what not to eat generic 20 mg pariet with mastercard. Indeed gastritis diet x90 discount pariet 20mg without a prescription, proposing that a set of brain structures might be primarily involved in processing emotions was a bold statement at the time curing gastritis with diet cheap 20mg pariet visa. Since then gastritis vs gerd symptoms purchase pariet 20 mg overnight delivery, however, the limbic system has received much attention for its major role in the expression of emotions, as well as in olfaction, learning, and memory. Overview Gross anatomic features: structures of the amygdala, hippocampus, parahippocampal gyrus, cingulate gyrus, fornix, septum, and olfactory bulbs Function: the limbic system is closely involved in the expression of emotional behavior and the integration of olfactory information with visceral and somatic information Structure Broca defined the limbic lobe to include those structures on the medial and basal surfaces of the cerebral hemispheres. Because the limbic lobe is most developed in mammals, it is also known as the mammalian brain. In fact, in some primitive animals, such as the crocodile, the entire forebrain is limbic brain (the limbic cortex is part of the forebrain that developed first in evolution). The primary structures of the lobe include the medial cortex surrounding the corpus callosum, termed the cingulate gyrus (see Figure 5. The structures of the limbic system are often debated, but usually also include the fornix, some brainstem areas, particularly the mammillary bodies of the hypothalamus, specific basal forebrain structures, including the amygdala ("almond" because of its shape), and the septum (Figure 5. Several anatomic circuits have been described that include limbic system structures. The most likely role of the basolateral circuit, which centers around the amygdala, is in emotional processing. The Papez circuit, which centers around the hippocampus, is perhaps the most well-known loop. Function the limbic system is a most complex but important set of brain structures that has fascinated anatomists, neurologists, and neuroscientists for more than 50 years. The limbic system is a bit misnamed because there is no one-toone structurefunction relationship, as is evident in many sensory systems that are discussed in Chapter 7. The role of the limbic system in emotions and memory has generated a great deal of interest in neuropsychology. Extensive research has been conducted on several components of the highly interconnected limbic system. However, because of the interconnectivity of the system, it is often difficult to discern structurefunction relationships. The activities of the limbic system in memory consolidation, emotional behavior, and olfactory processing are topics on which we further elaborate in Chapters 7 and 9. The limbic system is closely related to the hypothalamus, which researchers have singled out as the main brain structure for integrating and organizing autonomic processes related to the emotional expression of behavior. In humans, limbic system dysfunction has been associated with a variety of abnormalities, including emotional and behavioral problems (Glaser & Pincus, 1969) and sexual dysfunction (Rosenblum, 1974). The hippocampal formation has been specifically associated with memory acquisition (Douglas & Pribram, 1966; Penfield & Milner, 1958; Scoville & Milner, 1957). The primary defect, seen after bilateral injury of the hippocampus, involves difficulty in learning new information. Such patients find themselves unable to retain newly learned information, although immediate and old memories remain relatively intact (Luria, 1971; Milner, 1968). These effects on memory functioning are less profound when only one hippocampal gyrus is affected (McLardy, 1970). Lesions of the left hippocampal gyrus may cause problems with verbal memory (Russell & Espir, 1961), whereas lesions of the right hippocampal gyrus may cause greater impairment in spatial memory, including maze learning (Corkin, 1965). The amygdala has ascending and descending connections with the cerebral hemispheres, the thalamus, the hippocampus, and even the spinal cord. The amygdala plays a specific role in fear conditioning and in impacting the strength of stored memory (LeDoux, 1994). Numerous psychological disorders are characterized by emotional disturbances, and the limbic system has been implicated in many of them. Extreme violence in patients who exhibit rage attacks and frequent aggressive behavior can follow damage to the amygdala and its connections. In fact, removal of the amygdala (amygdalotomy) has been performed on extremely violent and aggressive patients in an attempt to stem rage reactions. This is typically observed in severe alcoholics who show multiple nutritional deficiencies because they have essentially replaced solid food with alcohol. Such patients may develop a confusional state over time, as well as severe motor and new learning difficulties. In fact, some scientists suggest that neuropsychology needs to move away from the concept of the larger "system" of the limbic structures and should define them in more precise individual terms. The corpus callosum lies in the depths of the space between the two hemispheres called the longitudinal fissure and lies immediately inferior to the cingulum, a major intracerebral fiber within the cingulate gyrus (Figure 5. This happens via the corpus callosum, but also through smaller intercerebral fibers, the anterior commissure and hippocampal commissure. Because of the corpus callosum, both hemispheres share information, even though initially only one hemisphere may have received the information. The corpus callosum enables most communication and exchange of information between left and right hemispheres (Springer & Deutsch, 1993; Sperry, 1958). This is intriguing to neuropsychologists, because now information presented to only one side of the body (or brain) is not shared with the other hemisphere. In very young children, cutting the corpus callosum has little apparent effect, because the brain develops alternative pathways to help compensate for the loss. If the corpus callosum is severed surgically, which is sometimes done as a medical procedure to arrest the spread of seizures between hemispheres, the processing of some sensory information is confined to only one hemisphere. Researchers have learned from such cases that each hemisphere can function and process information in isolation. The idea that the brain might be composed of two independently functioning brain halves, perhaps even having two personalities or separate minds, is a question we explore in our later discussion of consciousness (see Chapter 16). Summary this chapter reviews the development, major structures, and functions of the brain. It is important to understand the functional aspects of the brain as they relate to brain anatomy. Knowledge of brain structures, in and of itself, is not very useful to neuropsychologists. This is most interestingly demonstrated when students with little neuropsychological knowledge dissect a brain. They proceed in a most rapid manner with the dissection, naming each structure they are able to detect as they go along. Once finished, they are typically perplexed with the mess they have made and how little they have learned. However, it is typically the more integrated behaviors that interest neuropsychologists. Therefore, it is necessary to move from discussions of groupings of structures based on ontogeny to the idea of pluripotentiality of structures within functional systems. This concept, first introduced in Chapter 1, often transverses groupings based on migration of structures during brain development. It is to the systemic organization of regions of the cerebral hemispheres in support of behavior, particularly those involving higher order mental functions that we now turn. Critical Thinking Questions Why is an understanding of the stages and processes of brain development important to the neuropsychologist? If a child was born without the telencephalon region of the brain, would the child be able to orient to visual and auditory stimuli, perform reflexive movements, and sit up? To what extent can behavioral functions be localized to specific brain structures? Why are the concepts of laterality, dominance, and asymmetry important in understanding brainbehavior functions? How do you account for the presumed sex difference in mental rotation and verbal fluency? Overview this chapter focuses on the cerebral cortex with regard to structure, function, lateralization, and sex differences. Our discussion of the cortex provides a foundation for subsequent chapters that explore the functional systems of the brain that support complex behavior such as language, memory, and emotions. The cortical regions of the brain can be defined in a number of ways, although the most frequently used nomenclature involves the divisions of the cortex into four lobes (occipital, temporal, parietal, and frontal). Although there is greater correspondence between region and primary sensory functions of the posterior regions of the brain, higher order cognitive, emotional, and social functions are not specifically localized to a particular lobe. Rather, multiple pathways and regions underpin functions, particularly those that involve complex behavior. The human brain is composed of two hemispheres that interact in the support of behavior. The hemispheres differ regarding structure and function, with certain human attributes being lateralized to either the left or right hemisphere. However, the lateralization of a function to one hemisphere does not mean that the other hemisphere is uninvolved in the support of the function. For example, speech and language are generally lateralized to the left hemisphere in most people (both right- and left-handed individuals), but the right hemisphere is also intimately involved in speech and language functions. Putative cognitive and behavioral differences of male and female individuals have led to neuropsychological investigations to determine whether structural and functional differences exist between the brains of the two sexes. Significant attention has focused on the role of sex hormones in the organization and activation of the brain. You will soon realize that the relation of sex hormones to behavior is complex and not fully understood. The complexity of the interhemispheric and intrahemispheric connections reflects this degree of evolution, which allows humans to use such abstract concepts as symbols, language, and art. Zillmer To understand the functioning brain, place it within the context of evolution. Two to three million years ago, humans living in East Africa were making stone tools, perhaps building simple dwellings. Their brains would, in the course of a spectacular evolution, eventually enlarge to the size and complexity of today. Humans could not possibly perform the numerous and complex behaviors that they do without brain mechanisms that have evolved over hundreds of thousands of years. Evolutionary psychology offers a coherent theory that may begin to explain the strategic differences and similarities in the structures and functions of the brain. His historic 1835 trip to the Galбpagos Islands laid the foundation of his theory of biological evolution, even though he stayed for only 5 weeks. Darwin suggested that the mechanism for explaining how species evolve from existing forms is a process based on natural selection. He identified the process of natural selection as the mechanism underlying the evolution of all organisms. He reasoned that some individuals were better able to survive and reproduce than others, and that the characteristics that made these species more successful could then be transmitted to the next generation. Perhaps the most significant legacy of evolution is a powerful brain that has evolved to a degree allowing humans to learn from experiences. Basic human psychological mechanisms related to brain processes are likely to be species specific. For example, most or all humans share certain psychological processes, including fear of darkness; characteristic emotions such as anger, love, and humor; weapon making; sexual attraction; and probably hundreds more (Wright, 1994). People often call these processes human nature, but they must be related to brain processes. One reason most humans share many psychological mechanisms relates to that natural selection tends to impose relative uniformity in complex adaptive designs, such as the brain. This is most readily apparent at the level of human physiology and anatomy: All people have two arms, a heart, and a brain; that is, they do not vary in possessing basic physiologic mechanisms. According to evolutionary psychology, however, the brain must contain a large number of specialized psychological mechanisms; each designed to solve a different or related adaptive problem. Thus, individuals also differ, and fundamental individual differences must be central to any comprehensive brain theory. One way that the human brain differs, compared with other species, is its size, particularly the size of the neocortex. For example, a general principle of neural organization indicates that the size and complexity of a structure is related to its functional importance of the structure. Anthropologists measure the internal volume of skulls, which is easily preserved over time, to estimate the weight of the brain. Using this technique, researchers estimated the brains of our earliest ancestors, dated approximately 5 million years ago, to be relatively small, about 400 cm3 (Changeux & Chavaillon, 1995). Although the human brain was always relatively large in proportion to the body, and presented a modern organization, the relative size of the brain rapidly increased in size. About 1 million years ago, the occipital lobes began to develop, followed by the frontal, parietal, and temporal lobes. This new biological foundation enabled increased memory capacity, more frequent and specific spoken communication (language), a more elaborate social life, and a more extensive exploration of the environment. Humans no longer depended on gathering rocks, carcasses, and vegetables, but became proficient in animal capture. This evolution in the structural complexity and performance of the brain corresponded directly with the formation and development of diverse cultures. Neanderthals are thought to have inhabited Europe and the Middle East as early as 100,000 years ago. It is not clear exactly how similar they were to us, but they certainly had an elaborate tool-using culture that included ritual burial (Changeux & Chavaillon, 1995). About 100,000 years ago, the growth in brain size started to level off, probably related to the fact that the female pelvis, and the size of the skull that can fit through it, had not kept pace with the evolution of the brain. This has made for a remarkable state of affairs as it relates to brain development in humans.
Technology has the potential to help change the way in which healthcare is delivered the expansion in data science and digital technologies has the potential to impact a number of areas across the healthcare value chain gastritis symptoms images generic pariet 20mg on-line. First gastritis diet on a budget discount 20mg pariet amex, digital technologies may increasingly improve the efficiency and effectiveness of researching and developing potential new therapies gastritis symptoms months order pariet 20mg mastercard. The combination of data and artificial intelligence could enable complex biological simulations that complement 94 Item 5 gastritis gluten free diet discount 20mg pariet with mastercard. Second gastritis healing diet generic pariet 20 mg, increased volumes of real-world data and the ability to analyze that data with artificial intelligence gastritis diet wiki purchase 20mg pariet, may in the future allow more accurate, faster diagnosis of patients and recommendation of appropriate treatments. Real-world evidence will be important to demonstrate the value of our innovation to payers and healthcare providers. Third, we expect that in the future patients may have the opportunity to be much more engaged in managing their own care via clinical-grade digital tools, such as those supporting adherence to instructions from healthcare professionals. Patients are also likely to have greater decision-making power regarding with whom to share their health data, as data ownership is expected to shift from central data aggregators to the patient. Loss of exclusivity for patented products Increasingly challenging business environment Pricing and reimbursement Around the world, governments and payers continue to struggle with rising healthcare costs as aging populations contribute to increased prevalence of chronic diseases. There have also been examples of significant controversies about prices for pharmaceuticals that some politicians and members of the public have considered excessive. These factors have intensified the pressures we face regarding the prices we charge for our products, and our ability to establish satisfactory rates of reimbursement for our products by governments, insurers and other payers. We expect this scrutiny to continue in 2020, and the following years, as governments and insurers around the world strive to reduce healthcare costs through steps such as restricting access to higher-priced new medicines, increasing coinsurance or copays owed by patients for medicines, increasing the use of generics, and imposing price cuts. In this environment, we believe it is more important than ever to demonstrate the value that true innovation brings to the healthcare system. To manage these pressures, we are investing in real world data and analytics to provide additional evidence of the health benefits of our products, exploring new technologies and patient management services, and working with payers to develop and scale outcomes-based commercial models. For example, we are working with customers on flexible pricing approaches where we are fully compensated only if a drug succeeds in meeting certain performance targets, or where the price for a product administered only once is paid over a period of time. We strive to price our products commensurate to the value they provide to society, which is primarily in line with external benchmarks. Importantly, our sales growth has been mainly driven by new innovations driving volume growth and not by price increases on existing drugs. The net pricing impact on our sales growth Pharmaceutical companies routinely face generic competition when their products lose patent or other intellectual property protection, and Novartis is no exception. Major products of our Innovative Medicines Division, as well as certain products of our Sandoz Division, are protected by patent or other intellectual property rights, allowing us to exclusively market those products. The loss of exclusivity has had, and will continue to have, an adverse effect on our results. The impact of generic competition on sales growth in 2019 was lower than the historical average. Some of our best selling products face, or are expected to face, considerable competition due to the expiration of patent or other intellectual property protection. For example, our former top-selling product Gleevec/Glivec continues to face increasing generic competition in major markets. Looking forward, intellectual property protecting a number of our major products will expire at various times in the coming years, raising the likelihood of further generic competition. To counter the impact of intellectual property expirations, we continuously invest in research and development to rejuvenate our portfolio. One measure of the output of our efforts is the performance of our growth drivers, including Cosentyx, Entresto, and Kisqali, and our Sandoz Division biosimilars. We also have a number of late-stage product candidates in our pipeline with the potential to come to market in the next few years. We launched five products with blockbuster potential in 2019: Zolgensma, Piqray, Mayzent, Beovu, and Adakveo. Commercial success of key products Our ability to maintain and grow our business and to replace revenue and income lost to generic and other competitors depends in part on our commercial success, particularly with respect to our key growth driver products, which we consider to be an indicator of our ability to renew our portfolio. Operating and Financial Review and Prospects addition, our revenue could be significantly impacted by the timing and rate of commercial acceptance of new products. All of our businesses face intense competition from new products and scientific advances from competitors. Physicians, patients and payers may choose competitor products instead of ours if they perceive them to be better in terms of efficacy, safety, cost or convenience. Business practices Ability to deliver new products Our ability to grow depends not only on the commercial success of our marketed products, but also on the success of our R&D activities in identifying and developing new treatments that address unmet medical needs, are accepted by patients and physicians, and are reimbursed by payers. Developing new healthcare products and bringing them to market is a costly, lengthy and uncertain process. R&D for a new product in our Innovative Medicines Division can take 15 years or more, from discovery to commercial launch. With time limits on intellectual property protections, the longer it takes to develop a product, the less time we may have to recoup our costs. During each stage of development, there is a significant risk that we will encounter obstacles or fail. This may cause a delay or add substantial expense, limit the potential for commercial success, or force us to abandon a development project in which we have invested substantial amounts of time and money. In addition, as healthcare costs continue to rise, governments and payers around the world are increasingly focused on health outcomes, rewarding new products that represent truly breakthrough innovation versus those that offer an incremental benefit over other products in the same therapeutic class. This has led to requests for more clinical trial data than has been required in the past, the inclusion of significantly higher numbers of patients in clinical trials, and more detailed analyses of the trials. Our Sandoz Division faces similar challenges, particularly in the development of biosimilars. While Sandoz was a pioneer in introducing biosimilars to the European market in 2006, and was the first company to win approval for a biosimilar under the new regulatory pathway in the United States in 2015, many countries still lack fully developed regulatory frameworks for the development, approval and marketing of biosimilars. Further delays in establishing regulatory frameworks, or any other difficulties that may arise in the development or marketing of biosimilars, could put at risk the significant investments that Sandoz has made, and will continue to make, in this area. In spite of our significant investments, there can be no guarantee that our R&D activities will produce commercially viable new products that will enable us to grow There is a continued focus on government investigations and litigation against companies operating in our industry, including in the United States and other countries. We are obligated to comply with the laws of all countries in which we operate, as well as any new requirements that may be imposed upon us. In addition, governments and regulatory authorities worldwide are increasingly challenging practices previously considered to be legal and compliant. Beyond legal requirements, we strive to meet evolving public expectations for ethical behavior. We have a significant global compliance program in place, and we devote substantial time and resources to efforts to ensure that our business is conducted in a legal and publicly acceptable manner. Despite these efforts, any failure to comply with the law could lead to substantial liabilities that may not be covered by insurance and could affect our business and reputation. Investigations and litigation may affect our reputation, create a risk of potential exclusion from government reimbursement programs in the United States and other countries, and potentially lead to large damage payments and agreements intended to regulate company behavior. For all our new medicines, we are systematically integrating access strategies into how we research, develop and launch products globally. Supply continuity the manufacture of our products relies on technically complex processes and, in some cases, highly specialized raw materials, and is highly regulated. Deviations, difficulties or delays in production, or failure to obtain specialized raw materials, have in the past resulted in some of the following, and may in the future result in, shut-downs, work stoppages, approval delays, voluntary market withdrawals, product recalls, penalties, supply disruptions or shortages, increased costs, product liability or reputational harm. Operating and Financial Review and Prospects Beyond regulatory requirements, many of our products involve technically sophisticated manufacturing processes or require specialized raw materials. As a result, even slight deviations at any point in their production processes may lead to production failures or recalls. We continue to optimize our manufacturing process and have expanded our manufacturing capacity significantly in 2019. Our facilities in Stein, Switzerland and Les Ullis, France, have started manufacturing for clinical study patients. Given the complexity of our manufacturing processes, we have worked for several years to adopt a single high quality standard across the company. Of 177 inspections of our facilities by health authorities around the world in 2019, all but seven were found to be good or acceptable (96%). Any significant impairment charges could have a material adverse effect on our results of operations and financial condition. The outcome of these efforts remains subject to change and could end up in a materially different form from what is currently proposed, or could be administered or implemented in a manner different from our expectations. In Switzerland, the Basel-Stadt Cantonal Tax Reform was approved by voters in February 2019, with parts retroactive from January 1, 2019. With the enactment of this tax reform, new elements will be introduced into law, for example the abolishment of special taxed regimes, notional interest deduction, and an implementation of a Patent-Box, which provides tax advantages on income generated from intellectual property rights. As a result, such tax reform efforts, including with respect to tax base or rate, transfer pricing, intercompany dividends, cross border transactions, controlled corporations, and limitations on tax relief allowed on the interest on intercompany debt, will require us to continually assess our organizational structure against tax policy trends, could lead to an increased risk of international tax disputes and an increase in our effective tax rate, and could adversely affect our financial results. C Board practices-Corporate governance-Board of Directors-Information and control systems of the Board vis-а-vis management-Risk management" and "Item 18. However, the integrated nature of our worldwide operations can produce conflicting claims from revenue authorities in different countries as to the profits to be taxed in the individual countries, including potential disputes relating to the prices our subsidiaries charge one 97 Item 5. To provide additional information that may be useful to investors, including changes in sales volume, we present information about our net sales and various values relating to operating and net income that are adjusted for such foreign currency effects. However, in performing our evaluation, we also consider equivalent measures of performance that are not affected by changes in the relative value of currencies. Free cash flow is a measure of the net cash generated that is available for investment in strategic opportunities, returning to shareholders and for debt repayment. Novartis defines free cash flow as net cash flows from operating activities and cash flows associated with the purchase or sale of property, plant and equipment, as well as intangible, other non-current and financial assets, excluding marketable securities. Cash flows in connection with the acquisition or divestment of subsidiaries, associated companies and non-controlling interests in subsidiaries are not taken into account to determine free cash flow. Novartis calculates net debt as current financial debts and derivative financial instruments plus non-current financial debt less cash and cash equivalents and marketable securities, commodities, time deposits and derivative financial instruments. Generally, this results in amortization and impairment of intangible assets and acquisition-related restructuring and integration items having a full tax impact. There is usually a tax impact on other items, although this is not always the case for items arising from legal settlements in certain jurisdictions. Adjustments related to income from associated companies are recorded net of any related tax effect. Due to these factors and the differing effective tax rates in the various jurisdictions, the tax on the total adjustments, excluding the non-taxable, non-cash gain on the distribution (spin-off) of Alcon Inc. The 2019 core tax rate, excluding the effect of the gain on the distribution of Alcon Inc. In 2018, net cash flows used in financing activities from continuing operations mainly included the cash out- 111 Item 5. Group liquidity, financial debts and net debt Novartis calculates net debt as current financial debts and derivative financial instruments plus non-current financial debt less cash and cash equivalents and marketable securities, commodities, time deposits and derivative financial instruments. The renewed facility matures in September 2024 and was undrawn as per December 31, 2019, and December 31, 2018. Operating and Financial Review and Prospects For a description of risks and restrictions on the ability of subsidiaries to transfer funds to the company via cash dividends, loan or advances please see "Item 5. Financial instruments-Nature and extent of risks arising from financial instruments. This in turn may significantly affect reported earnings (both positively and negatively) and the comparability of period-to-period results of operations. As a result, even if the amounts or values of these items remain unchanged in the respective local currency, changes in exchange rates have an impact on the amounts or values of these items in our consolidated financial statements. If this occurs, it could impact the effective prices we would be able to charge for our products and also have an adverse impact on both our consolidated income statement and balance sheet. The most significant countries in this respect are Argentina and Venezuela, where the governments have implemented capital controls. The net outstanding intercompany payable balance of Argentina and Venezuela subsidiaries were not material for the Group at December 31, 2019, and at December 31, 2018. The hyperinflationary economies in which Novartis operates are Argentina and Venezuela. The Group manages its global currency exposure by engaging in hedging transactions where management deems appropriate, after taking into account the natural hedging afforded by our global business activity. For 2019, we entered into various contracts that change in value with movements in foreign exchange rates to preserve the value of assets, commitments and expected transactions. For more information on how these transactions affect our consolidated financial statements and on how foreign exchange rate exposure is managed, see "Item 18. Operating and Financial Review and Prospects Free cash flow Novartis defines free cash flow as net cash flows from operating activities and cash flows associated with the purchase or sale of property, plant and equipment, as well as intangible, other non-current and financial assets, excluding marketable securities. The December 31, 2019, consolidated balance sheet excludes the assets and liabilities of the Alcon business, due to the derecognition of the Alcon business at the date of the spin-off. The consolidated balance sheet discussion and analysis that follows excludes the impacts of the derecognition of the Alcon business at the date of the spin-off. For details on the net assets derecognized at April 9, 2019, the completion date of the spin-off, see "Item 18. Goodwill and other non-current assets were broadly in line compared to December 31, 2018. Operating and Financial Review and Prospects nition of the Alcon business current assets as a result of the spin-off. Income tax receivable and assets of disposal group held for sale remained broadly in line compared to December 31, 2018. We continue to monitor the level of trade receivables, particularly in Argentina, Brazil, Greece, Italy, Portugal, Russia, Saudi Arabia, Spain and Turkey. Should there be a substantial deterioration in our economic exposure with respect to those countries, we may change the terms of trade on which we operate.
For information on reservations gastritis kefir purchase pariet 20 mg mastercard, accessible coaches and sleeping accommodations gastritis diet cabbage order pariet 20 mg with visa, boarding gastritis kaffee purchase pariet 20 mg with visa, use of oxygen gastritis diet menu plan generic pariet 20 mg on-line, service animals gastritis diet bland buy discount pariet 20mg online, etc gastritis uptodate buy pariet 20mg cheap. Editor Candy Harrington has also written several books, including Barrier-Free Travel, Inns and B&Bs for Wheelers and Slow Walkers, and 22 Accessible Road Trips 22accessibleroadtrips. Whether you are looking for something exotic or close by, let the community help you find what is out there. Lloyd, from Bethesda, Maryland, was injured during a high school swim practice in 1983 and is a C4 quad. In Costa Rica, after almost twenty years in a chair, I was almost moved to tears at being able to trek through a genuine rainforest! It was such a unique experience, and one I never would have dared to dream could be a reality for me after my accident. The RoughRider Wheelchair, targeted for use in areas of rugged terrain and poor infrastructure. Ralf Hotchkiss, who began redesigning wheelchairs after he became disabled in a motorcycle accident in college, co-founded Whirlwind Wheelchair International in order to design sturdy wheelchairs that could be easily built and repaired in developing countries from locally available materials. The RoughRider frame is made from thin-walled steel tubing, available almost anywhere. The chairs are now made in Mexico, Turkey, South Africa, Vietnam, and Indonesia; see There are many people thriving in their communities who would have been locked away in institutions a generation or two ago. The "right" device might be a simple cane, or it might be a power stand-up wheelchair that can climb a stair or two when necessary. The gamut of mobilityassistive devices also includes walkers, crutches, prosthetics and orthotic devices, manual and motorized wheelchairs, and scooters. Specialized chairs are available for children, sports enthusiasts, and off-road use. Technology is advancing rapidly, and sci-fi scenarios like exoskeletons and eye-gaze controls are gradually becoming more than science fiction (though still not commercially available). There is no one-size-fits-all answer to the mobility needs of people living with paralysis. Determining what will work best for any individual must take into account the nature of their injury and degree of functional capacity as well as their lifestyle and day-to-day activities. Other considerations include: · Mobility goals: what are they and what will it entail to meet them? A person with paralysis can get around as quickly in a wheelchair as anyone else can walking, or faster. A wheelchair offers people access to work, shopping, appointments, or any other travel outside the home. For those who are so inclined, a wheelchair accommodates participation in races, basketball, tennis, and other sports. In some ways a wheelchair is like a bicycle: There are many designs and styles to choose from including manuals, lightweights, racing models, ruggedwheeled models, and so on. Distinct styles of chairs fit special purposes, just as a bicycle is specialized for street or trail use. An ill-fitting wheelchair can increase the risk of pressure sores, which can be painful and even life-threatening if not identified early and treated properly. Innovations in materials and engineering have made them lighter, faster, and easier to use. Many now use sophisticated computer technology and electronic controls that can be operated with a simple joystick or, for quadriplegics, a "sip-and-puff" system activated with a straw. Of course, insurance-coverage limits and budget constraints must also be taken into consideration. People who have sufficient upper-body strength may choose a selfpropelled manual chair, which typically has rims on the outside of the large rear wheels that are grabbed and pushed. Depending on the needs of the user, chairs may be adapted for propulsion with the legs, or with one arm and one leg. Whether with a rigid (non-folding) frame or a folding frame, lightweight materials make it easier to lift the chair in and out of cars for transport. The primary advantage of a folding chair, of course, is portability; some can even fit in the overhead bin of an airplane. The hardware and mechanisms required to enable a chair to fold up typically add modest weight to the chair. Rigid chairs are more durable while folding chairs do not always hold up over time. Shock Absorbers Suspension systems designed to make the ride smoother and minimize spasticity are an increasingly common option; they also can add weight to the chair, as well as expense. Lightweight Models the weight of the chair can be an important consideration, not just for when the chair needs to be picked up but also for ease of mobility. Lightweight chairs require less exertion to push, and therefore less strain on muscles. The use of high-tech materials such as super-light titanium in wheelchair frames has made it possible to bring the weight of chairs down considerably. Titanium is advantageous not only for its lightness, but also its strength, durability and built-in shock absorption. Titanium wheelchairs are generally more expensive, and custom-built options may take a little longer to have made. Paralysis Resource Guide 234 6 Wheels and Rims the options for wheels, tires and push rims have also expanded, including innovations for high performance, off-road traction, and style. A number of companies are now making alternative systems to the standard wheel-rim chair propulsion, including chairs and aftermarket systems that can be used to modify a manual chair. These systems typically incorporate either a side-lever design, or a rowing-action design. The user turns the handlebars like a bicycle to steer and with a rowing motion, propels the chair with both the forward and backward strokes. Extending the lever up adds more power to the propulsion and pulling it back all the way engages the powerful rear hub brake. Force applied to the levers propel the chair forward with less muscle power than a rim-based wheel drive. NuDrive claims the system reduces the effort of propulsion by 40 percent and minimizes wear and tear on shoulders and arms. Wijit wheels replace the standard wheels of a manual chair with a simple installation kit. A sort of hybridization is occurring in the assisted-mobility world as manual wheelchairs are tricked out with compact power packs that can make a manual chair act like a motorized one when needed. On the downside, the devices add significant weight to the chair (up to 50 pounds, though there are some lightweight models) and can be quite expensive (with prices typically in the $5,000 to $8,000 range). The increasing number of options for a power boost range from do-it-yourself motorization kits to removable front ends that essentially turn a manual chair into a power scooter. The most common iterations rely on a small, powerful motor that typically attaches to the wheels or chair base. The rugged Swiss-Trac looks like a small lawnmower that attaches to the front of the chair to power through rough terrain or ease the burden of long-distance rolling. Resembling an upright vacuum cleaner, it attaches to the back of any manual chair to provide a power boost via 12 volt rechargeable batteries. It weighs about 60 pounds (48 with a 9 volt battery) and is narrow enough to fit into most car trunks. A sensor in the wheel registers the propelling movement and activates the electrical motor. The e-fix version of the e-motion adds an armrest joystick for controlling the motor. Developed by Quickie and Yamaha, the Xtender features quick-release motorized rear wheels that increase the force applied to the handrims by up to four times. Weighing about 38 pounds with a seven-hour battery life, it is available from chair and accessory dealers for some Quickie models. New models come with the PushTracker motion-sensing control wristband that communicates with the drive motor via Bluetooth technology, and a smartphone app that enables you to individualize speed and other parameters and monitor activity. The SmartDrive + PushTracker is typically priced around $6,000, comparable to rim-based power-assist units. A joystick on the armrest (adaptable to either side) controls the unit, which operates off 12-volt lead gel mat batteries or an optional lithium ion battery, which reduces the weight of the unit from 82 pounds to 75 pounds and doubles the range of the motor from 5 miles to 10. Compact and quiet, the wheel hub drives use built-in lithium ion batteries to ensure greater propulsion force on push-rim wheels. Suitable for almost all common active wheelchairs, the drives attach with a lightweight, quick-release bracket that is fitted to the wheelchair without removing the original wheels. Available in many iterations, power chairs operate with an electric motor driven by rechargeable batteries. Steering and power are controlled by a joystick (most commonly), a keypad, or, for people without the use of their hands, a "sip-and-puff" system that the user controls by manipulating air flow through a straw-like tube to the mouth. There are also joystick controls operable by chins or sensors built into headrests. Newer models incorporate hands-free technologies like Bluetooth and smartphone apps that monitor activity. Twenty years or so ago, the power-chair market was limited to just a few brands and models that were bulky, heavy and expensive. Innovation has expanded the choices toward lighter, more powerful and much faster chairs. The traditional power chair looks like a beefed-up standard-issue wheelchair with extra bulk comprised of batteries, Paralysis Resource Guide 238 6 motor, and control systems. Tilting, reclining, and stand-up chairs comprise the higher end of the power-chair market, and custom-built chairs are available from a number of manufacturers to meet special needs. Most power chairs have rear-wheel drive, but mid-wheel and front-wheel drives have grabbed a share of the market. These are easier to turn and can be especially useful for negotiating tight spaces. Some models are rugged and built for off-road use; some are designed for portability. There are ultra-lightweight three-wheelers for road racing; sporting chairs with extra camber to prevent tip-overs; heavy-duty four-wheelers for off-road use; chairs with big puffy tires for navigating sandy beaches or other challenging surfaces, and even chairs with tractor treads for those who want to negotiate the roughest terrain. Almost any chair can be customized for the individual needs of people with paralysis. With so many options available, doing some research is critical to finding the right chair and supplier. Read user reviews of products to understand how the chairs function in real-world situations. It was created by the designer of the two-wheel standup Segway, Dean Kamen, but was discontinued in 2009 by Johnson & Johnson because of low sales most likely related to the lack of reimbursement for the chair, which cost about $24,000. The Segfree is one of these; essentially a Segway with a seat, it has a range of about 24 miles, top speed of 12. A New Zealand firm has developed a self-balancing, hands-free chair with similar specs that it calls the Ogo ( The high-tech chair includes advanced software that can evolve as developments in autonomous driving become more integrated with online mobility resources and mapping; a mobile app is also in development to support the user experience. Since chairs are expensive and insurance providers often place limitations on replacement, most manufacturers offer adjustable chairs to accommodate a growing child. The updated looks offer more streamlined designs, kid-friendly upholstery, and a variety of frame colors. Sunrise Quickie Zippie A few organizations offer free or low-cost wheelchairs to children in need, including Kids Mobility ( Several kinds of cushion materials are available, each with benefits for certain types of users, including air, foam, or liquid gel. Air flotation cushions provide support using a rubber bladder of evenly distributed air. These generally work well to equalize pressure over bony prominences and promote good blood circulation to reduce the danger of damaging the skin. They can, however, be prone to leaking, and they require air adjustments with changes in altitude. Many cushions combine a gel pack with foam to reduce the weight of the cushion and improve comfort. Paralysis Resource Guide 242 6 A fairly recent development in cushion technology is the pressure-changing cushion, which is based on the theory that alternating the pressure in the seat can reduce the risk of skin compression and enable the user to sit for longer periods of time without requiring "lift and shift" adjustments as frequently. These cushions rely on battery power to inflate and deflate the cells, which adds weight to the wheelchair and makes this option less carefree than a static cushion. Another option is a reclining chair, which changes the seatto-back angle by flattening out the back of the chair and, in some cases, raising the legs to form a flat surface. Both tilt and recline options must be fitted and prescribed by seating and positioning experts. A tilt system redistributes pressure from the buttocks and posterior thighs to the posterior trunk and head. The system maintains posture and prevents shearing (the friction on Old school: recline yes; tilt no. One drawback is that if the user sits at a workstation, tilting requires that he or she move back from the table to avoid hitting it with the knees or footrests. Recline systems open the seat-to-back angle and, when used in combination with elevating leg rests, open the knee angle. There are some advantages to a recline system for eating, making transfers, or assisting with bowel or bladder programs. Generally speaking, the recline system offers more pressure relief than tilt, but with a higher risk of shear.
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