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Numerous publica tions in the eld of pediatrics antibiotics for uti macrodantin purchase doxycycline toronto, child health, and human development, rehabilitation, intellectual disability, disability, health, welfare, abuse, advocacy, quality of life, and prevention. Omar has completed residency training in obstetrics and gynecology as well as pediatrics. He has also completed fellow ships in vascular physiology and adolescent medicine. He is well known internationally with numerous publications in child health, pediatrics, adolescent medicine, pediatric, and adolescent gynecology. He has published numerous papers on a wide-ranging topics in these areas and has edited several special symposia and books. Major disabili ties include intellectual disability, learning disabilities, communication disorders, autism spectrum disorders, cerebral palsy, and neural tube defects. This chapter provides an introduction and reviews epidemiology of major disabilities. Introduction Developmental disabilities or neurodevelopmental disabilities (include intellectual disability) are a diverse group of chronic disorders (see Table 1. The underlying basis for these disorders lies in fundamental de cits in the developing brain due to genetic, prenatal, perinatal, metabolic, and other factors [2]. Developmental disabil ities affect 17% of individuals younger than 18 years of age in the United States [1]. Prevention along with early recognition and intervention is critically important to mitigate the enormous personal and socioeconomic impact of these disorders. The three key components of func tioning and disability are inter-related and may interact with the health condition. The term infant or toddler with a disability means an individual under 3 years of age who needs early intervention services because she/he is experiencing develop mental delays, as measured by appropriate diagnostic instruments and procedures in 1 Neurodevelopmental Disabilities: Introduction and Epidemiology 3 one or more of the areas of cognitive development, physical development, communi cation development, social or emotional development, and adaptive development or has a diagnosed physical or mental condition that has a high probability of resulting in developmental delay. Major life activities include, but are not limited to , caring for oneself, performing man ual tasks, seeing, hearing, eating, sleeping, walking, standing, lifting, bending, speaking, breathing, learning, reading, concentrating, thinking, communicating, and working. A major life activity also includes the operation of a major bodily function, including, but not limited to , functions of the immune system, normal cell growth, digestive, bowel, bladder, neurological, brain, respiratory, circulatory, endocrine, and reproductive functions. The in uence on cog nitive assessment of sensory, motor, communication, or behavioral factors should also be appropriately considered in administration of assessment instruments and interpretation of their results [8]. The severity of intellectual disability can be categorized based on a combination of level of intellectual functioning, adaptive functioning, and intensity of supports needed [8, 9, 12]. When the level of intellectual functioning cannot be reliably assessed, but there is a high level of con dence based on clinical judgment, a 4 D. Merrick diagnosis of intellectual disability can be made without specifying the severity of intellectual functioning [7, 8]. The reported prevalence of intellectual disability re ects consideration of the de nition used, method of ascertainment of the data, and the characteristics of the population studied [13, 14]. Based on the typical bell-shaped distribution of intelli gence in the general population and 2 standard deviations below the mean as a cutoff point, approximately 2. Intellectual disabil ity is reported to be twice as common in males as in females. The recurrence risk of intellectual disability in families with one previous child with severe intellectual disability is reported to be between 3 and 9% [8, 11, 12]. On the other hand, underlying biological or neurological etiology can be identi ed in more than two-thirds of affected individuals who have severe dis ability [8, 11, 13]. Learning Disabilities the term learning disability describes dif culties in speci c areas of learning that have a direct relation to academic performance. The public agency must promptly request parental consent to evaluate the child to determine if the child needs special education and related services. Dyslexia is highly comorbid with other developmental prob lems, including impairments in language, motor skills, and behavioral control [20]. Reading disability is also a contributor to juvenile delinquency and leads to higher rates of recidivism [21]. It is more common in girls than in boys, possibly related to environmental, rather than biological, factors. Communication Disorders Language is a system of symbolic knowledge represented in the brain used for meaningful communication. Persons who have autistic disorder have signi cant language delays, social and communication chal lenges, and unusual behaviors and interests [30]. Persons who have Asperger syndrome manifest de cits in social domain and have unusual behaviors and interest; however, they typically do not have de cits in language or intellectual ability. Persons with perva sive developmental disorder, not otherwise speci ed, have some features of autistic disorder and some features of Asperger syndrome, but do not meet all the criteria for either disorder [30]. It is unclear if there is something inher ent in those syndromes that predisposes to the development of autistic features or whether the risk is secondary to the intellectual impairment that is commonly seen in many genetic disorders. This trend is partly explained by the fact that most low birth weight and premature babies now survive. Although any segment of spinal level can be affected, 75% of cases involve the lumbosacral level [49]. In Wales and Ireland, the prevalence is three to four times higher, whereas in Africa it is much lower [49]. Hearing Loss Sounds can be described in terms of their frequency (or pitch) and intensity (or loudness).

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At the very least get antibiotics for sinus infection 200mg doxycycline with amex, it seems that to be receptive to teaching and to be effective learners we need to be well rested, well ventilated and well nourished, including having an adequate supply of water. We can talk either in terms of what the learner needs or what the brain needs, in this case. Schools cannot impose bedtimes, nor can they ensure healthy diets (though they can teach about them), but water and oxygen can be supplied very easily: water in the form of access and encouragement, and oxygen in the form of good ventilation and movement of one sort or another. There will be occasions when there is, for example, 20 little opportunity for collaborative work, or limited scope for assuring that the social or cultural 1 context is ideal for the class in question. However, efforts can be made and steps taken to work 2 towards meeting the conditions implied by this list. In situations where work continues 4 from one lesson to the next, an opportunity to refresh the aims in the minds of the class should 5 be taken. All lessons should in some way have the purpose of moving on knowledge and 6 understanding; even lessons that are for the purpose of revision can be seen to be moving on 7 and revitalising what has been covered before. Teaching approaches will be tailored to what is known about learning and will 1 encompass what has been discovered in recent years about learning and the brain. This will 2 lead to a new learning environment in the classroom when compared with what has gone 3 before. Curriculum Fragmented knowledge and Multidisciplinary themes, characteristics disciplinary separation. Social Teacher-controlled setting with Teacher functions as facilitator characteristics pupils working independently. Assessment Measurement of fact Assessment of knowledge knowledge and discrete skills. Teacher role Present information and Guide pupil enquiry and model manage classroom. Possible use Source of information for Source of information for of the Internet absorption. They are able to take a very strong lead in the process of helping children 6 to reach their potential while enjoying themselves in the process. Both Piaget and Vygotsky believed that individuals actively construct their own knowledge and understanding;Vygotsky stressed the importance of the social interaction in which an individual participates; Piaget stressed the inner motivation to balance new information with existing knowledge and understanding. Vygotsky Piaget Social Constructivism Cognitive Constructivism Children learn through being active. Development is an internalisation of social Children are unable to extend their experience; children can be taught concepts cognitive capabilities beyond their stage of that are just beyond their level of development. Hansen (eds) Chicken Soup for the Soul: Stories that RestoreYour Faith in Human Nature. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standard accepted at the time of publication. However, in view of the possibility of human error or changes in medical sci ences, neither the editors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the infor mation contained herein is in every respect accurate or complete, and they dis claim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for adminis tration. This recommendation is of particular importance in connection with new or infrequently used drugs. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. McGraw-Hill eBooks are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. For more information, please contact George Hoare, Special Sales, at george hoare@mcgraw-hill. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. McGraw-Hill and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. Kaplan, whose generosity, clinical and educational excellence, and impeccable character have set a high standard for so many of us. He received his medical degree in 1955 from Columbia University of Physicians and Surgeons in New York. He then served two years in the Army, following which he returned to Columbia Presbyterian Medical Center for fellowship training, which he completed in 1963. He joined Baylor College of Medicine in 1963 and was with the Department of Obstetrics and Gynecology for 42 years. Kaplan became a certified Diplomate of the American Board of Obstetrics and Gynecology in 1966, and earned his certification in Gynecologic Oncology in 1974. He has served on various editorial boards and is active on committees of both the professional organi zations and the hospitals at which he practices. In his clinical practice, he cares for women with gynecologic surgical problems and female cancers. Ericka Simpson, a brilliant, compassionate and dedicated teacher and the other talented neurologists. I am greatly indebted to my editor, Catherine Johnson, whose exuberance, experience, and vision helped to shape this series. Likewise, I am indebted to the numerous excellent physicians in the Obstetrics/Gynecology department, among whom I particu larly appreciate Drs. Joseph Medical Center, I applaud the excellent administrators: Phil Robinson, Pat Mathews, Laura Fortin, Dori Upton, Janet Matthews, and Drs. Taylor for their commitment to medical education, and Marla Buffington for her sage advice and support. I owe a huge debt to gratitude to Martin Paukert, probably the most brilliant medical student who has walked through our hos pital doors, for agreeing to meticulously review the manuscript on such a short timeline. It is even more difficult to draw on that knowledge, procure and filter through the clinical and laboratory data, develop a differential diagnosis, and finally to form a rational treatment plan. To gain these skills, the student often learns best at the bedside, guided and instructed by experienced teachers, and inspired toward self-directed, diligent reading. Unfortunately, clinical situations usually do not encompass the breadth of the specialty. Perhaps the best alter native is a carefully crafted patient case designed to stimulate the clinical approach and decision-making.

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The word potent bacteria taxonomy best doxycycline 200mg, the root of potential, an opinion questionnaire they completed captures the property of accessibility that it some time earlier. Alternatively, they are contributes to the likelihood that the knowl more likely to judge a fctitious name to be edge will be used in judgments, inferences, that of a well-known public fgure if they have and other responses. The term potential also encountered the name in a different exper includes notions of energy or effectiveness iment 24 hours earlier. In each case, peo from chemical or electrical properties or ple may attribute the ease of retrieving this from the position of a piece of matter in an knowledge to having encountered it in other, arrangement, and these notions cover the nonlaboratory contexts, thus inferring that major models that have been proposed for the event or name is generally well known. In understanding the nature and functions of fact, people may often base their judgment of accessibility. In contrast, When people are aware that the accessibil excitation transmission models understand ity of knowledge in memory might be due to accessibility in terms of the heightening and factors that are irrelevant to a stimulus they the dissipation of excitation (or energy levels) are judging, they may sometimes discount it from stimulation and decay. Individuals who are aware they have used In mechanistic models, a knowledge unit a trait concept in performing an initial task that has been recently or frequently activated might sometimes avoid using the concept to has a position within the structural arrange interpret the information they receive in an ment of categories that makes it likely to be unrelated task they perform subsequently. Once activated, the knowledge they are distracted from thinking about the unit is then compared to the stimulus input judgment they are asked to make, however, or and its use in judgment or inference depends if they are chronically unmotivated to devote on there being a reasonably good ft between thought to the task, they might use the acti the knowledge unit and the input. In excita vated concept as a basis for judgment despite tion transmission models, the accessibility their awareness that its use may be biased by of the knowledge unit and the input features extraneous factors. Knowledge the input must be very good for it to become availability refers to whether or not a knowl activated. The to become activated because the accessibility term potential in the defnition of accessibility will compensate for the poor ft. The 11th of the 12 pairs of nerves which or recently activating the unit prior to the sit leave the skull independently of the spinal uation in which the knowledge might be used. The accessory nerve has two branches, Many studies have found that prior exposure one of which controls the large muscles on to a knowledge-related word in one situation, the side (sternocleidomastoid) of the neck even subliminally, increases the likelihood and upper back (trapezeus) and another that the knowledge will be used several min which joins with the vagus nerve. Accountability is the implicit or explicit seeks out, avoids, and frequently encounters. A person tion, the accountability literature posits that has high chronic accessibility for a given individuals do not operate in a social vacuum knowledge unit if he or she lists that unit frst but rather are immersed in interdependent in response to one or more questions and/ relationships and pressures to adhere to or lists it frequently in response to the ques culturally shared norms and practices. A person has low chronic accessibility such, accountability can be viewed as a crit for a given knowledge unit. Failure to act in ways for that chronically accessible social knowledge which one can construct acceptable explana units can be relatively stable for months or tions will lead to varying degrees of censure even years, and they infuence memory, and punishment. Acculturation refers to the process of attitude toward some object and his or her change in a person as a result of extended behavior toward that object. At 8 acculturative stress achievement motive some point or another in their lives, vir acetylcholine tually all people have contact with people n. Some rotransmitter secreted by efferent (motor) groups of people, however, are more likely axon terminals in the central nervous system. A need or desire to make no or few errors is pharmacologically blocked, cholinergic in accomplishing a task. A desire to achieve social status, recogni motivation to do the task accurately may skew tion, and rewards through the accomplish results. This is particularly important in bor ment of diffcult goals, competition, and ing and/or repetitive tasks. A test in which the score is derived from found to be correlated with a combination of the accuracy of answers rather than from high parental support, high parental demand, the speed at which answers are given. An accuracy test is in some ways the opposite of a speed test, achievement motive in which the primary measure is the speed at n. An inferred drive to accomplish diffcult which a subject performs a task up to a prede tasks at a high standard of competence and termined level of accuracy. A desire to master 9 achievement need acoustic confusion tasks, to manipulate and control objects and brightness a light of a particular wavelength other human beings, and to do so better than needs to have to be seen and the brightness others are able to do. An inferred drive to accomplish diffcult achromatism tasks at a high standard of competence and n. Total color blindness; in human beings it is tasks, to manipulate and control objects and a lack of the capacity to perceive either color other human beings, and to do so better than or saturation of color. Congenital achromatopsia (daltonism or achievement test maskun) is a hereditary vision defect found in n. Any test which measures a mental or physi 1/33,000 persons in the United States (inci cal competence to perform certain actions dence is different in different world areas). Such tests are usually refer absence of cells, or morphologically malformed enced to specifc age or group norms and are cone cells. Individuals who have achromatopsia sometimes used to predict future academic may be either totally color-blind or almost totally or vocational achievement. Achromatopsia appearance requires two recessive genes and achromat it is more frequently found in men than in n. Achromatopsia can also be due to an see no color and is unable to distinguish ei acquired brain condition (acquired or cerebral ther color or saturation of colored light. This achromatopsia), associated with stroke, trauma, is also called total color blindness. Persons who develop cere bral achromatopsia report that they only can see achromatic shades of gray. Without color (hue) or saturation, con lobe damage involving the lingual and fusiform taining only black, white, and shades of gray. An achro matic color is a neutral shade of gray without acoustic any admixture of other hue or color. Eyes are able to see light at a lower level acoustic confusion than they can see the color of light. Any confusion in perception or memory matic interval is the difference between the related to similarities in sound, as in hearing 10 acoustic cue acquisition or remembering bat when hat has been said. An inferred memory that contains all from inattention or confusion as to the mean sound information heard within the last ing of something. Any acoustic character used as of a meaningful perception of either syllable an aid in remembering; particularly remem or word. Any device or mechanism that blocks or believes to be the opinion or desire of others. Many acoustic yes/no questions regardless of the content of flters block particular frequencies or tones the question. This is counteracted in test con while others partially block the amplitude or struction by counterbalancing the meaning loudness of very loud sounds regardless of of test questions so that saying yes to one ques tone. The tendency to react to one sound as one acquired drives has previously learned to react to another, n. Dogs conditioned to salivate that organisms are born with some drives to one bell will salivate (although somewhat to act. Drives to act are inferred in organ less) when bells of similar but different tones isms which have had opportunities to learn are heard. This cranial nerve includes two dif of those original drives and become function ferent branches: a cochlear branch (hearing ally autonomous drives in their own right.

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Thus he failed to recognise people he people are unable to remember events that had recently encountered even when these individuals had been in frequent con happened before the onset tact with him antibiotics in poultry cheap doxycycline 200mg line. In spite of this, the causes outlined below are important as these have been the most informative in the neuropsychological investigation of memory. The Korsakoff syndrome Amnesia can actually result from nutritional de ciency that is often associated with chronic alcoholism. Thiamine itself plays an important role in cerebral metabolism and thus a reduction in the amount of thiamine reaching the brain has serious consequences for healthy neural functioning. The memory disorder resulting from thiamine depletion is called the Korsakoff syndrome or sometimes the Wernicke-Korsakoff syndrome (after the two researchers, Carl Wernicke and Sergei Korsakoff, who were initially involved in studying this disorder). The precise neuropathology associated with this syndrome is still the subject of investigation but research has implicated the neural structures within the diencephalon (including the mamillary bodies and the thalamus) and even the frontal lobes (Colchester et al. Hypoxia Hypoxia refers to an inadequate supply of oxygen to the tissues (including neural tissue). Hypoxia can result from heart disorders, carbon monoxide poisoning, arterial disorders, and impaired respiratory function. The neuropathology associated with hypoxia is variable and often widespread (Caine & Watson, 2000) but in terms of memory disorders the hippocampus, thalamus, and fornix are often implicated (Aggleton & Saunders, 1997; Kesler et al. Vascular disorders the brain needs a constant supply of blood and this is carried to the brain by a dedicated vascular system. This vascular system consists of a number of major arteries that branch outwards throughout the brain into smaller and smaller arteries, which eventually merge with veins that carry the blood back to the heart. Interruptions to the supply of blood can occur for a number of reasons, such as a blockage from a blood clot or embolism, or damage to the walls of the artery. In both these cases, the cessation of the supply of blood leads to the brain being deprived of oxygen and nutrients, and brings about cell death. Depending on which arteries are damaged or blocked, different neural regions or structures can be affected. Viral infections Infection with the herpes simplex virus can bring about memory disorders as a consequence of herpes simplex encephalitis. Neuropathological features of this disease include widespread bilateral temporal lobe damage (Colchester et al. As structures important for memory reside in the temporal lobe regions (more speci cally the medial temporal lobes) then it is not surprising that herpes simplex encephalitis can bring about severe memory impairments. Head injuries As the name suggests this form of injury results from a blow to the head in one form or another. In the case of closed head injury, diffuse damage across widespread neural regions can occur as a result of compression of the brain, the shearing of axons, and haemorrhaging. Closed head injuries can often bring about post traumatic amnesia which can last from minutes, following very mild injury, to months, following more severe injury. Furthermore, if asked to keep a string of digits in mind (such as a phone number) he was able to do so very successfully if allowed to make use of mental rehearsal. However if rehearsal was prevented, his performance dropped to almost zero (Milner, 1966). For example, he was able to recognise the faces of people who became famous before but not after his surgery (Marslen-Wilson & Teuber, 1975). In addition he was able to reconstruct an accurate oor plan of the house he moved into since the onset of the amnesia, presumably due to what amounts to thousands of learning trials (Corkin, 2002). However he demonstrated intact abilities for perceptual and motor skills learning (Corkin, 2002). Two of these are addressed below: (1) What are the patterns of intact and impaired performance in amnesia By examining the patterns of performance across a wide range of experimental tasks, research into amnesia has been a valuable source of informa tion with regard to unravelling the complexity of long-term memory systems and processes. One way to think about this is the distinction made between declarative and non-declarative memory (Squire & Knowlton, 2000). Declarative memory (some times called explicit memory) refers to memory for events, episodes, and facts (see Figure 7. This type of memory is accompanied by conscious awareness that memory is being used in order to perform some task. Non declarative memory (sometimes called implicit memory), on the other hand, is a form of memory that is observed and expressed though performance without any necessary dependence on awareness. In this case, the individual uses memory without any conscious awareness that memory is guiding or directing their per formance. The ability to ride a bicycle is learned and then expressed through performance (actually riding it without falling o). This behaviour does not demand that the individual recall consciously the actual act of learning. Non-declarative memory comes in many forms and appears to be remarkably preserved in amnesic individuals (Squire 2004). Priming, classical conditioning and implicit learning are three examples of non-declarative memory, which are outlined below. When psychologists refer to implicit memory, more often than not they mean priming. Priming does not demand awareness of the study episode or the ability of the individual to remem ber any of the details of the study phase of the experiment. For example, imagine a participant in an experiment being presented with a set of words (including. Cognitive research has indicated that the priming e ects observed on tests such as word fragment completion are based on the perceptual characteristics of the word. Thus if the words are initially heard and then tested visually, priming is reduced (Rajaram & Roediger, 1993). This perhaps indicates that such priming e ects are dependent on neural regions involved in vision and perception. Research with brain-damaged individuals and neuroimaging of healthy controls has provided broad support for this idea. Subsequent work has indicated that the left occipital lobe can also support priming (Yonelinas et al. With respect to neuroimaging research, priming e ects on tasks like word fragment completion are associated with decreased activations in regions involved in perceptual processing, such as the occipital lobes and the ventral surface of the occipital/temporal region (Backman et al. The fact that decreased activations were found may sound unusual but it is thought to be due to decreased metabolic demands or synaptic strengthening following the initial processing of the word during the study phase (Wagner, Bunge, & Badre, 2004). Intact priming e ects in amnesia are not limited to relatively low-level per ceptual tasks as described above. In addition, performance on memory tasks that require conceptual or meaningful semantic processing is also spared. Participants without brain damage are more likely to respond with the meaningfully related words that were presented earlier in the experiment. Levy, Stark, and Squire (2004) assessed this form of priming, called conceptual priming, in amnesic patients and found it to be entirely intact in these respondents too, even when conscious recog nition of the presented words was no greater than chance. Again, this would appear to indicate that priming e ects are not dependent on the medial temporal lobes but instead the contribution of some other neural region which has now been identi ed by neuroimaging. Further more, when asked to make the same judgement to the words on a second occasion, a relative decrease in the activation was observed in this same area. This decrease in activation is considered to be the neural signature of priming e ects, and parallels that found with perceptual tasks. In its simplest form this involves present Anterograde amnesia and non-declarative memory 163 ing a conditioned stimulus such as a light or tone just before a pu of air, the unconditioned stimulus, is directed to the eye. The cerebellum seems to be the critical neural region for this type of non-declarative memory. For example, Woodru Pak, Papka, and Ivry (1996) found that patients with cerebellar damage were impaired at acquiring the classically conditioned eyeblink response. During conditioning (2), a conditioned stimulus such as an changes in cerebellar activity during the learning auditory tone is paired with the puff of air.

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Breast milk proteins are human specific antibiotic vs antibacterial best buy for doxycycline, thus delaying or reducing some environmental allergies. Oxytocin release during milk let-down increases uterine contractions, thereby decreasing postpartum blood loss and facilitating uterine involution. Decreased lifetime risk of ovarian and premenopausal breast cancer proportional to duration of breast-feeding. Contraindications to Breast-feeding Some structural problems make breast-feeding difficult and sometimes impossible. These include tubular breasts, hypoplastic breast tissue, true inverted nipples (rare), and surgical alterations that sever the milk ducts. Contraindications to breast-feeding include the following: Mother actively using drugs of abuse, including excessive alcohol. Women can give their infant expressed breast milk and can breast-feed once their treatment regimen is well established. Once the infant has been given varicella zoster immunoglobulin, expressed milk is allowed if there are no lesions on the breast. Within 5 days of the appearance of the rash, maternal antibodies are produced, making breast milk beneficial for passive immunity. Mothers who are receiving diagnostic or therapeutic radioactive isotopes or have had recent exposure to radioactive materials. Noncontraindications Healthy term infants with acquired or congenital cytomegalovirus should breast-feed for the benefit of maternal antibodies. Babies of mothers with hepatitis A or B may breast-feed as soon as the infant receives appropriate immunoglobulin and hepatitis vaccination. Special attention to avoid broken skin on or around the nipples of mothers with hepatitis B should be advised. Breast-feeding and Maternal Medications Nearly all antineoplastic, thyrotoxic, and immunosuppressive medications are contraindicated during breast-feeding (Table 20-2). Although all major anticonvulsants are secreted in breast milk, they need not be discontinued unless the infant exhibits excessive sedation. In the nonbreast-feeding woman, the average time to first ovulation is 45 days (range 25 to 72 days). The mean time to ovulation is 190 days in women who are breast-feeding exclusively (Fig. The lactational amenorrhea method is 95% to 99% protective in the first 6 months postpartum if strict criteria are followed. Feedings must be every 4 hr during the day and every 6 hr at night, and supplemental feedings should not exceed 5% to 10%. The progestin is detectable in breast milk, but no evidence suggests adverse effects on the infant. The levonorgestrel intrauterine device (Mirena) is a progesterone-only option with greater efficacy; it may be inserted at the 6-week postpartum visit, and some studies suggest immediate postpartum insertion is feasible. Mastitis Mastitis is a breast infection that occurs in 1% to 2% of breast-feeding women, usually between the 1st and 5th weeks postpartum. It is characterized by a localized sore, reddened, indurated area on the breast, and is often accompanied by fever, chills, and malaise. Treatment includes continued nursing, nonsteroidal anti-inflammatory pain medication, and antibiotics. Women should continue to express milk, starting on the affected side, to encourage complete emptying. If there is no improvement in 48 hr, antibiotic coverage should be changed to cephalexin or ampicillin with clavulanate (Augmentin). Continued mastitis, particularly if there is evidence of abscess formation, demands evaluation for the possibility of methacillin-resistant S. The differential diagnosis for mastitis (Table 20-3) includes the following: Clogged milk ducts: a tender lump in the breast not accompanied by systemic symptoms that resolves after application of warm compresses and massage. Unrelieved, clogged ducts can lead to galactoceles, cysts filled initially with milk that can become a thick cheesy substance that is difficult to drain. Galactoceles may require ultrasound treatment or needle aspiration if conservative methods fail. Inflammatory breast cancer: a rare disease that presents with breast tenderness and breast skin changes. Breast sonography may be required for diagnosis, and incision and drainage may be necessary for treatment. Decreased Milk Supply the normal volume of milk produced at the end of the first postpartum week is 550 mL/day. Exclusively breast-fed newborns can be expected to lose 5% to 7% of birth weight in the first week. Glycogen stores in full-term infants generally provide sufficient initial nutrition. It is characterized by postpartum lethargy, anorexia, weight loss, as well as inability to lactate. Combined hormonal versus nonhormonal versus progestin-only contraception in lactation. Improved treatment has reduced morbidity, increased survival, and markedly decreased perinatal transmission. For women who are not on antiretroviral therapy at the beginning of pregnancy, it may be delayed until after the first trimester. Women with opportunistic infections should receive appropriate prophylaxis, as outlined in Table 21-2. Decisions regarding an appropriate regimen should consider: Previous antiretroviral treatment and viral resistance. Safety and toxicity profiles for specific drugs during pregnancy (considering both mother and fetus). To optimally suppress viral replication, minimize the risk of vertical transmission, and minimize the risk of new resistance mutations, strict adherence to the treatment regimen is crucial. Patients who do not meet the criteria for antiretroviral therapy outside of pregnancy should have all antiretrovirals discontinued in the immediate postpartum period, after the umbilical cord is clamped. Recent meta-analysis of 14 clinical studies in the United States and Europe found no increase in preterm delivery in treated recipients compared to no therapy. Lamivudine Not significantly No evidence for Because of altered in pregnancy, human extensive no change in dose teratogenicity. Data from recommendation older capsule regarding formulation suggest dosing in lower blood levels with pregnancy. Serious teratogenic effects in primates and neural tube defects in humans with early in utero exposure are reported. Entry Inhibitors, Integrase Inhibitors There is little data on the use of these newer drugs in pregnancy. Augmentation to shorten the time to vaginal delivery may be considered for some patients. The complications with cesarean section are not of sufficient frequency or severity to outweigh the potential benefit for women with increased risk of vertical transmission. During cases of uterine atony, many antiretroviral drugs interact with methergine, and therefore, this drug should be avoided. With limited medications, poor health infrastructure, reduced bottle feeding options, and less laboratory testing availability, these recommendations cannot always apply. For women who do not require treatment for either disease and will be receiving antiretroviral drugs for prophylaxis of perinatal transmission only (with discontinuation postpartum), consultation with an expert is recommended. Liver function tests should be obtained 2 weeks after starting treatment and then monthly. Pegylated interferon-alpha is not recommended, and ribavirin is contraindicated during pregnancy. Colon Guzman Jamie Murphy Labor and delivery is a time of intense pain, often influenced by the psychological, emotional, social, cultural, and physical state of the parturient. Multiple techniques and procedures for pain relief during the birthing process are available.

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Individuals with bipolar I disorder perform more poorly than healthy individuals on cognitive tests hpv safe 200 mg doxycycline. Symptoms of irritability may be associated with either major depressive disorder or bipolar disorder, adding to diagnostic complexity. Generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or other anxiety disorders. These disorders need to be considered in the differential diagnosis as either the primary disorder or, in some cases, a comorbid disorder. Similarly, symptoms of posttraumatic stress disorder need to be differentiated from bipolar disorder. This disorder may be misdiagnosed as bipolar disorder, especially in adolescents and children. Personality disorders such as borderline personality disorder may have substantial symptomatic overlap with bipolar disorders, since mood lability and impulsivity are common in both conditions. A diagnosis of a personality disorder should not be made during an untreated mood episode. Comorbidity Co-occurring mental disorders are common, with the most frequent disorders being any anxiety disorder. More than half of individuals whose symptoms meet criteria for bipolar disorder have an alcohol use disorder, and those with both disorders are at greater risk for suicide attempt. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Note: Do not include symptoms that are clearly attributable to a medical condition. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation). The episode is not attributable to the physiological effects of a substance or another medical condition. Specify current or most recent episode: Hypomanie Depressed Specify if: With anxious distress (p. If self-derogatory ideation is present in grief, it typically involves perceived failings vis-a-vis the deceased. Specify course if full criteria for a mood episode are not currently met: in partial remission (p. During the mood episode(s), the requisite number of symptoms must be present most of the day, nearly every day, and represent a noticeable change from usual behavior and functioning. A hypomanie episode that causes significant impairment would likely qualify for the diagnosis of manic episode and, therefore, for a lifetime diagnosis of bipolar I disorder. Instead, the impairment results from the major depressive episodes or from a persistent pattern of unpredictable mood changes and fluctuating, unreliable interpersonal or occupational functioning. Depressive symptoms co-occurring with a hypomanie episode or hypomanie symptoms co-occurring with a depressive episode are common in individuals with bipolar disorder and are overrepresented in females, particularly hypomania with mixed features. There may be heightened levels of creativity in some individuals with a bipolar disorder. However, that relationship may be nonlinear; that is, greater lifetime creative accomplishments have been associated with milder forms of bipolar disorder, and higher creativity has been found in unaffected family members. Many individuals experience several episodes of major depression prior to the first recognized hypomanie episode. Patterns of illness and comorbidity, however, seem to differ by gender, with females being more likely than males to report hypomania with mixed depressive features and a rapid-cycling course.

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This was the period when the Germanic peoples traditionally called the Angles best antibiotic for sinus infection while pregnant purchase 200mg doxycycline free shipping, Saxons, and Jutes invaded and settled Britain. The literary materials that have survived are of a high moral tone, including the epic poem Beowulf (ca. Numerous warnings concern the punishment awaiting the man who breaks faith and is thus ostracized to the feared condition of exile, movingly depicted as the state of a solitary wanderer. The epic, heroic, and moralizing qualities of the surviving Anglo-Saxon poetry limit the kind of swearing encountered there to asseverations. When Beowulf makes a public undertaking to the Dan ish King Hro gar and his followers to rid them of the threat of the cannibalistic monster Grendel (ll. The typical heroic response in a moment of exasperation is dignified, cool, and measured, similar to the convention in the old western films. While one would expect Beowulf to be an ideal exemplar or role-model, the importance of the self-binding oath is an essential feature of the whole verbal culture. The poem the Battle of Maldon, based on an actual battle between the men of Essex and some marauding Vikings in 991, provides a striking ethical example. When the Vikings arrogantly ask for treasure, assuming that the people of Maldon will buy them off with danegeld, or protection money, rather than fight, the local leader Byrhtnoth gives them a savagely ironic answer: the Vikings can expect spears and swords for tribute (ll. It is some nobles, in fact, who treacherously flee when Byrhtnoth falls and the battle seems lost. The Anglo-Saxon laws corroborate a similar underlying rigor and discipline in the matter of insults. As the land was invaded by the marauding Vikings, so a general demor alization set in. In fact what are now the most wounding and obscene terms in English swearing are first recorded long after the Anglo-Saxon period, which is broadly defined in historical terms as extending from the earliest written records to about 1100. The following table sets out the field in terms of etymological origin and historical evolution: Anglo-Saxon Norman French Unknown shit piss cunt (ca. All the terms listed in the table have their own entries, showing their etymological origins and semantic evolution, which are often quite complex. For some cultural reason the pig provides the richest verbal field, together with the variants sow and swine. Unlike sow, swine continues to have resonance in swearing in the British Isles, especially among the older generation, while pig has become more a feature of U. Cur and bitch are terms of such power that they have their own entries, as does son of a bitch, now well established in American English. Con temptuous terms for horses, such as jade and hack, have also lost currency and power. In English parlance rat is a term of deep contempt, meaning essentially one who has betrayed a party, a close confidant, or a lover. The original uses, dating from the late eighteenth century, referred to political deserters, alluding to the behavior of rats leaving a sinking ship. The currency has continued to the present, but is now frequently applied to personal relationships. Viper is similarly recorded in association with treachery from 1596, snake from 1593, and reptile from 1749. Other terms include cow, monkey, baboon, ape, skunk, polecat, and shrew, which has for centuries been used in a metaphorical fashion of both a disreputable man and an unpleasant woman, long after the animal term ceased to be familiar. It has since become generalized, as has skunk, first used meta phorically in 1840. This part of the anatomy and its emissions are, of course, a fruitful area for vituperation. Arse, derived from late Anglo-Saxon ears, was in common use up to the eighteenth century, the medlar fruit having been called the open-ears from the earliest times. Because of its general acceptability in medieval times, the term did not have any great personal animus. However, Francis Grose in his Classical Dictionary of the Vulgar Tongue (1785) euphemized the form of the word to a-se, an indication that it was becoming indelicate. During the same period the ancient word ass (meaning donkey) started to take on a pronun ciation that was uncomfortably close to arse. Ass (in the animal sense) had, of course, acquired associations of stupidity in uses like silly ass and complete ass. These associations continued in both varieties but were applied indiscrimi nately to both words, still found in British stupid arse and American dumb ass. However the two terms continued as homophones (words with the same sound but different meaning) in American pronunciation. This is, no doubt, a reflection of the nature of the founding population, which was made up principally of 160,000 convicts, very unlike the Pilgrim Fathers of the United States. A mere half-century after the establishment of the penal colonies in Australia, H.

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It involves a precise series of steps that include capturing T cells with magnetized beads and growing them in baglike incubators rolling on an oscillating tray virus herpes purchase generic doxycycline from india. Another, made by Kite Pharma (now owned by Gilead Sciences), is for adults with non Hodgkin lymphoma. They work alongside people who received this powerful Senior clinical research supervisor Yvette doctors, nurses, and lab monitors to experimental therapy. They are other advanced practice nurses from the more people will eventually beneft and certifed in human subjects protection, Leukemia Service on the 12th foor experience longer disease-free periods which is an important part of every of M emorial Hospital frst cared for and hopefully cures. About a month after the transplant, he got an infection that led to a severe case of pneumonia. These details are changing how cancer is treated, for patients both today and in the future. One main focus of precision oncology is to quickly translate discoveries made in the lab into treatment approaches that can beneft people with cancer. Timothy Chan studies how the immune system recognizes and responds to cancer specifc mutations. These only at genetic changes inside the tumor undergoing immunotherapy, so this immunotherapy drugs work by tissue but also at certain genes that make was a new fnding. They have been shown to genes, which are critical for regulating shrink even very advanced cancers the immune system. W e found that tumors with a greater number of mutations were more recognizable to the immune system. Both are important for maximizing the ability of the immune system to see and destroy cancer cells. There is a rush to develop genetic tests to measure how many mutations are present in tumors as a way to predict response to immunotherapy. From the early the immunotherapy drug clinical trials in 2012, it was clear that Q: What are the next steps for pembrolizumab (Keytruda) these drugs worked very well for certain this research This marked the tumors that often responded well to A:Our fndings will need to be validated the frst approval for a cancer drug these drugs, including melanoma and in prospective studies, although because that attacks tumors no matter lung cancer, tended to have a lot of we included such a large and diverse where they develop. But we think that learning more Luis Diaz led the pivotal clinical colleagues at Johns Hopkins told me about immune system recognition trial that resulted in this approval about a person with colon cancer who was can help with the development of new while he was at Johns Hopkins taking another checkpoint inhibitor drug, cancer treatments. W e looked more closely at Division of Solid Tumor Oncology the tumor and found that it had a high in the Department of Medicine in number of mutations. A:Based on the discovery with nivolumab, we began a study looking at A:Gene mutations can lead to the whether pembrolizumab, which is similar, production of foreign substances called would work in people whose tumors had neoantigens. W e included people presence in the body that fags the tumor with a dozen diferent types of cancer. The more defcient tumors were more likely to mutations you have, the more your respond to pembrolizumab than those chances increase that the immune system without the defciency, regardless of where spots the tumor because there is a much the tumor was located. Our fndings suggest many childhood cancers have a the person whose colon cancer had so that all people with advanced cancer surprising cause. The fnding also farahead of what any other cancer center provides insight into what causes is doing. W e were puzzled transposons alter the expression of continuously be fxed in order for the cell by why tumors develop in younger people, pigment-controlling genes. An emerging strategy advanced prostate cancer, as well as clinical trial of the drug olaparib in cancer therapy has been to block the pancreatic cancer, in recent studies. It can help guide their treatment Olaparib was the frst drug in the approved for these ovarian cancers as well. People with earlier-stage breast cancer a family history that would prompt them as well as other forms of cancer that have to get tested. There is a privilege to help turn promise certainly the potential to beneft, since into reality. Genetic counselors like Meg Sheehan meet with patients and families to explain the inherited risks for cancer that are passed down through generations. But some do, and thanks to rapid advances in technology, scientists have amassed a wealth of information about which genetic mistakes are most likely to lead to the disease. Doctors can use it to probe a tumor for mutations and other genetic changes in 468 genes that are seen in both common and rare cancers. In addition to guiding treatment choices, this test is producing valuable insights about how cancer grows and resists treatment. The resource Associate Director of the M arie-Josee beginning that the information they enables them to discover new links and Henry R. Knowing the diference the analysis and interpretation of the may be the most important. W hile traditional clinical trials focus on a particular cancer type, basket studies concentrate on a specifc mutation found in the tumor, regardless of where the cancer originated in the body. Although his family history did not suggest it, his test results showed he had a condition called Lynch syndrome. Also known as hereditary nonpolyposis colorectal cancer, Lynch syndrome is associated with a genetic predisposition to a number of diferent cancer types. His doctors made this diagnosis are also ofered the opportunity to because, in addition to fagging undergo genetic testing and counseling. Clinical geneticists use this who explained the risks to him and information to uncover which genetic recommended that other family members changes were inherited by a person at get tested. Katz (right) and his brother, Elliot, experienced in interpreting these were both found to have Lynch syndrome. Katz, who is still at counseling and learn about what these risk of developing additional cancers, drug atezolizumab (Tecentriq) when fndings mean.

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Something on your right as you look ahead is in the temporal field of your right eye and the nasal field of your left eye treatment for dogs kidney failure order doxycycline online. Field defects are said to be homonymous if the same part of the visual field is affected in both eyes. This can be congruous (the field defects in both eyes match exactly) or incongruous (the field defects do not match exactly). The normal field for moving objects or large objects is wider than for objects held still or small objects. The normal field for rec ognition of coloured objects is more limited than for monochrome. Look straight into the distance in front of you and put your hands out straight to your side. Wiggle your fingers and, keeping your arms straight, gradually bring your arms forward until you can see your moving fingers. Repeat this holding a small white object, and then with a red object until you can see that it is red. If you are considering exophthalmos, it is confirmed if the front of the orbital globe can be seen when looking from above. For example: 6/6 when the letter is read at the correct distance or 6/60 when the largest letter (normally seen at 60 m) is read at 6 m, or 20/20 and 20/200 when these acuities are measured in feet. If acuity improves, the visual impairment is refractive in origin and not from other optical or neurological causes. However, the result is expressed as the logarithm of the minimum angle or resolution, which in turn is the inverse of the Snellen ratio. If one side is ignored when both fingers are moved together but is seen when moved by itself, then there is visual inattention. Large objects are more easily seen than small objects; white objects are more easily seen than red. A combination of wiggling fingers (described above) and red pin provide the most sensitive and specific bedside test for field defects. Bring the pin horizontally from the side with the defect towards the point of fixation. Classified according to degree of functional preservation in the affected field. The common causes for the lesions referred to below are cerebral infarcts, haemorrhages, tumours or head injuries. If you are short or near-sighted (myopic) and not using glasses or contact lenses, you will have to turn the focus dial anticlockwise to focus to look at a normal eye; turn it clockwise if you are long or far-sighted (hypermetropic). If the patient is myopic, turn the ring anticlockwise; if hypermetropic, clockwise. If his face is smaller through his glasses, he is myopic; if his face is larger, he is hypermetropic. The acute angles of the branches and convergence of artery and vein indicate the direc tion to follow. To examine the left eye: Hold the ophthalmoscope in the left hand and use your left eye. Most people find this part of the examination difficult at first so you must persevere. Look at the blood vessels Arteries (light-coloured) should be two-thirds the diameter of veins (burgundy-coloured). This is best appreciated as you look along the length of a vein as it runs into the optic cup. A swollen optic disc is often difficult to find, the vessels disappear ing without an obvious optic disc. Retinal venous pulsation is absent in 15% of normal people, so an absence may be normal or reflect raised intracranial pressure. Common causes: multiple sclerosis, optic nerve compression, optic nerve ischaemia. Background diabetic retinopathy: blue arrow= blot haemorrhage; yellow arrow = dot haemorrhage D. You would use a saccadic eye movement to look from the page to someone in the room or if you were told to look up. For an explanation, see text the cover test What to do this is a test for latent squint. Ask the patient to look with both eyes at your right eye, then cover his left eye. What you find If one eye has to correct as it is uncovered, this indicates that the patient has a latent strabismus (squint), which can be classified as divergent or convergent. Ask him to follow it with his eyes without moving his head and to tell you if he sees double. Hold both your hands out in front of you about 30cm apart from side to side and about 30cm in front of the patient. Test convergence Ask the patient to look into the distance and then look at your finger placed 50cm in front of him. In conscious patients with limited eye movements on command or pursuit, the test can be used to demonstrate preserved eye movements on vestibulo-positional stimulation, indicating a supranuclear eye movement abnormality. Ask the patient to look into the distance at a fixed point; turn his head to the left then the right, and flex the neck and extend the neck. Common causes of lateral and vertical gaze palsies: brainstem infarction, multiple sclerosis, tumour.

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Another avenue of cross-cultural contrast is to compare attitudes and perceptions of mul tilinguals sinus infection doxycycline 200 mg for sale. In the course of learn ing a new language, we suggest that a non-native speaker, like a native child, will acquire the knowledge that some words are taboo before de veloping a nuanced understanding of how and when to use taboo words. The present experiment tested the effects of English experience and gender on ratings of offensiveness and likelihood of use of taboo words in different social and speaker contexts. This research was a replication and extension of Jay (1992), which manipulated speaker, location and word in hypothetical scenarios involving taboo words. As in Jay (1992), an inverse relationship between offensiveness and likelihood was ex pected, and ratings were expected to depend on contextual variables, with the highest offensiveness and lowest likelihood ratings pertaining to high status speakers who used highly offensive taboo words in campus locations that were not considered their turf (Jay 1992, 2000). Native English speakers were expected to have a more context-de pendent sense of appropriateness than non-native English speakers, re flected by greater variability in offensiveness and likelihood ratings rela tive to non-native speakers. We expected lower offensiveness ratings from non-native speakers to whom English was learned most recently. Both subjective estimates of taboo word offensiveness (Dewaele 2004) and measures of autonomic reactivity in response to taboo words (Harris et al. A gender difference was expected for both native and non-native speakers such that women were expected to provide higher offensiveness ratings than men. Participants were 121 undergraduate students from the University of California at Los Angeles who were compensated with course credit for participating. Non native speakers provided estimates of their amount of experience with English (M 11. The com position of our non-native sample reflected diverse native language backgrounds: 11 Chinese (Cantonese, Fukien, Mandarin, or unspeci fied); 10 Korean; 8 Spanish; 5 Indonesian; 5 Vietnamese; 3 Farsi; 3 Rus sian; 2 Bulgarian; and 1 each of the following: Hungarian, Igbo, Italian, Japanese, Polish, and Tagalog. We used a mixed 3 3 3 2 2 design to manipulate three within-subjects contextual variables and the between-subjects variables the pragmatics of swearing 277 of gender (female and male) and English experience (native or non-na tive) of our raters. All combinations of these variables were presented twice throughout the course of the experiment, once in a questionnaire meas uring the offensiveness of the scenario and once in a questionnaire meas uring the likelihood of the scenario. All ratings were made on a 1 7 Likert scale where 1 meant low offensiveness or likelihood, and 7 meant high offensiveness or likelihood. All combina tions of these taboo words and the speakers and locations mentioned above were presented in each questionnaire, creating a total of 81 scenar ios per questionnaire. Four versions of each ques tionnaire were created with scenarios in randomized order, to control for within-questionnaire order effects. No participants declined to participate after being warned about the content of the questionnaires. The demographic questionnaire was given first; following that, participants received the offensiveness and likelihood questionnaires in counterbalanced order, so that across all participants each questionnaire was presented an equal number of times first. Across all participants the different randomized orders were presented an equal number of times, and the presentation of the orders varied independently. Speaker, location and tabooness were within-sub jects factors and gender and English experience were between-subjects factors. Greenhouse-Geisser corrections were used on all significant F and associated values that violated the assumption of sphericity. All post hoc tests were evaluated using a Bonferroni correction to maintain an alpha level of. Context effects on offensiveness and likelihood ratings For offensiveness ratings, significant main effects were found for speaker (F(2, 178) 97. These effects are best summa rized in the significant speaker-location-tabooness interaction (F(7, 766) 3. As was the case for offensiveness, these effects are summarized in the significant speaker-location-taboo ness interaction (F(4, 468) 7. Effects of English experience Overall, there was no main effect of English experience (native versus non-native) on offensiveness or likelihood ratings. Certain results, how ever, supported our prediction that native English speakers would show more variability in ratings compared to non-native speakers. Significant interactions were obtained between English experience and speaker (F(2, 178) 3. In each of these cases, post hoc tests that compared English experience within a single level of the within-subjects variable were nonsignificant. However, in each case, the range between the highest and lowest average condition rating was larger for native than non-native speakers. For the speaker English experience interaction, the range between dean (highest overall offensiveness) and student (lowest overall offensiveness) was 0. For the tabooness English experience interaction, native speakers provided a greater range between high tabooness and low ta booness offensiveness ratings (2. The same pattern was obtained for the range of tabooness on likelihood ratings (1. One reason for the lack of a main effect of English experience may lie in the variability of English experience in our non-native English sample. Interactions which demonstrate effects of English experience on variability of ratings. Taken collectively, these show greater variability for native compared to non native speakers. From top to bottom: English experience speaker on offensiveness; English experience tabooness on offensiveness; English experience tabooness on likelihood. Correlation between self-reported age of fluency in English and average offen siveness and likelihood ratings for non-native English speakers. We subsequently performed a median split on the non-native English speaking group based on self-reported age of fluency, creating an early group (n 27, self-reported age of fluency 0 11 years) and a late group (n 26, self-reported age of fluency 12 26 years). The test for offensiveness confirmed that early and late groups differed significantly in average offensiveness rating (F(1, 51) 23. As is suggested by the correlational data, the test for likelihood did not show a significant main effect of English experience. It seems likely that the depen dency of age of fluency on offensiveness rating and the lack of any rela tionship between age of fluency and likelihood rating is responsible for the nonsignificance of the offensiveness-likelihood correlation. Effects of gender and language experience In support of our prediction that women would provide higher offensive ness ratings than men, a significant interaction between the gender of the rater and his or her English experience was obtained (F(1, 117) 4. Post hoc tests showed a trend toward a gender difference on overall offensiveness ratings for native English speakers (t(66) 1. There was no gender difference in offensiveness ratings for non-native speakers (p.