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Results indicated significant visual recovery to the change in orientation following unimodal visual habituation, but not following bimodal audiovisual habituation. Thus, consistent with predictions of the intersensory redundancy hypothesis, 5-month-olds discriminated changes in orientation, a visual property, following unimodal visual exposure, but not following redundant, bimodal exposure. Apparently, the addition of the soundtrack created intersensory redundancy and selectively recruited attention away from unimodally conveyed properties and toward redundantly specified properties of stimulation (as in Bahrick & Lickliter, 2000, and Bahrick, Flom, & Lickliter, 2002). In contrast, the unimodal, visual stimulation promoted attention to visual properties of the event without competition from salient redundant properties. Thus, attention to modality-specific or nonredundantly specified properties is likely best fostered in the context of unimodal exploration when competition from concurrent redundantly specified properties is minimized. This observation is consistent with insights gained from comparative studies regarding the sequential onset of the functioning of the senses (Gottlieb, 1971b; Turkewitz & Kenney, 1982). In prenatal development, earlier-developing senses are able to differentiate without competition from later-developing senses. Thus, auditory perception develops during the last trimester of gestation without competition from visual stimulation. Similarly, the Development of Perception 111 competition appears to play an important role in regulating attentional allocation to different properties of events during postnatal development. Our research suggests that after birth, unimodal exploration (of a face or voice, for example) is promoted when there is little competition from concurrent, amodal, redundant stimulation. This unimodal exploration likely fosters differentiation of auditory or visual information in a manner that is not supported when redundant stimulation is available. Thus, differentiation of the appearance of a face would be best promoted when the face is silent and relatively still, whereas when the individual is speaking and moving, competition from audiovisual redundancy would be more likely to focus attention on amodal properties such as prosody, rhythm, tempo, and intensity variations common to the speech and facial movement. The attentional salience of intersensory redundancy and its facilitation of perceptual learning have also been observed recently in comparative studies of animal infants. Bobwhite quail embryos were exposed to an individual maternal call for 6, 12, or 24 hours, under conditions of unimodal auditory stimulation, concurrent but asynchronous auditory and visual stimulation, or redundant and synchronous auditory and visual stimulation. They were then tested one day after hatching to determine if they preferred the familiar maternal call over an unfamiliar version of the maternal call. They indicated that chicks who received the redundant audiovisual exposure significantly preferred the familiar maternal call following all exposure durations, whereas those who received the nonredundant audiovisual exposure showed no preference for the familiar call after any exposure duration. Chicks who received the unimodal auditory familiarization showed eventual learning and preferred the familiar call following the longest period (24 hours) of prenatal exposure. These results demonstrate that bobwhite quail chicks show greatly enhanced learning of the maternal call when amodal information (tempo, rhythm, duration) is presented redundantly, across two sense modalities. These findings extend the facilitating effects of intersensory redundancy to the prenatal period and to a different species. This converging evidence across species, developmental periods, and properties of events highlights the fundamental importance of intersensory redundancy for promoting attention and fostering perceptual differentiation of amodal properties of events. Bahrick 20 18 16 18* 16* 16* 16* Number of chicks 14 12 10 8 6 4 2 0 Unimodal Auditory Synchronous Asynchronous Auditory-visual Auditory-visual (redundant) Familiarization condition 6 10 10 9 10 6 hours 12 hours 24 hours *p < 0. Note: in each group 26 chicks were tested and their data were classified into one of three categories, a preference for the familiar call (shown here), a preference for the novel call, or a preference for neither/both calls (from Lickliter et al. These findings also converge to demonstrate that there are conditions under which attention to amodal properties is not facilitated, and attention to modalityspecific properties and nonredundant aspects of stimulation is favored. That is, when a given event provides stimulation to only a single sense modality, attention and learning about unimodally specified properties of events are enhanced. Modalityspecific properties are best differentiated when competition from intersensory redundancy is not present. The Development of Perception 113 Conclusion In this chapter, I have described a number of basic principles underlying the development of attention, perception, and cognition as it emerges in a multimodal environment. The intersensory redundancy hypothesis provides a working framework for viewing the allocation of attention and its effects on the development of perception and learning in an environment that provides both redundancy across the senses and modality-specific information about objects and events in an interdependent system. The intersensory redundancy hypothesis highlights an important and previously unexplored interaction (depicted in figure 4.

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We observe that for all attributes, a significant affinity is observed, showing that links in the Rice network are correlated with attributes. It is interesting to note that certain attributes are stronger than others: for example, graduate students have a much strong affinity for other students in the same department when compared to other students in the same matriculation year. In some cases, the affinity is as high as 10, implying that users connected by a link are 10 times more likely to share an attribute that would be expected in a random graph. In summary, 127 Users Attribute college undergrads major year department grads school year Affinity 5. Note that the previous observation is a necessary, but not sufficient, condition for attribute-based communities to exist, since users with common attributes may be linked together but may not form a dense community. In order to investigate whether attribute communities are present in our network, we artificially divide the network into communities based on user attributes, and then quantify the strength of that division into communities using modularity [118]. Also shown is the modularity of the partitionings that are obtained when multiple attributes are used. The results show a significant modularity for the communities defined by residential college and matriculation year ­ a relatively high Q of 0. However, the modularity of the communities defined by major is almost 0, indicating that no community structure exists based on academic major. Overall, these results indicate that users who share the same college or matriculation year form tightly-knit communities in the social network. Attributes college, major, year college, major year, major major college, year year college Communities 660 488 270 163 36 4 9 Modularity 0. With some knowledge of the actual social network at Rice, the above results are 129 not unexpected. Undergraduate students are randomly assigned to a residential college upon matriculation, and they remain members of that college for the duration of their undergraduate studies. Additionally, the strong communities among undergraduate students of the same matriculation year are not surprising. Incoming students attend an orientation week together, are mostly assigned to share dormitory rooms with students of their year, and tend to spend time in courses with students of their year. Thus, it is also natural that a community structure exists among undergraduates of the same matriculation year. Finally, the lack of a strong community structure around majors can be explained by the fact that Rice undergraduates obtain liberal arts education (taking courses from many departments), and they often do not choose majors until the end of their sophomore year. A similar modularity is observed when partitioning according to school ­ this is because each department is a member of exactly one school, and the partitioning 1 Note that graduate students are not assigned to residential colleges, so that attribute is disre- garded here. This indicates a very strong community structure for the graduate students based on department, and a weak community structure based on matriculation year. Attributes year department, school, year department, year school, year school department, school department Communities 11 139 139 45 9 36 36 Modularity 0. Graduate students are accepted into a specific department at the beginning of their studies, and usually spend their entire tenure in the same department. Moreover, the variable length of graduate programs and the greater tendency of graduate students to interact across seniority levels explains why the partitioning according to matriculation year has a weak community structure. Moreover, we observe a significant community structure, indicated by a high modularity value, for the communities defined by users who share certain attributes. For the undergraduates, we observe significant modularity when partitioning according to residential college and matriculation year. For the graduate students, we observe significant modularity when partitioning according to department and a weaker modularity according to matriculation year. For the undergraduates, the partitionings according to college and matriculation year both showed significant correlation with the communities in the network. For the graduates, partitionings according to department and year showed similar behavior. We now consider the use of automatic clustering algorithms to detect a specific community among the multiple communities that exist. To do so, we split the problem into two parts: first, if partial membership information about all communities in the network is known, we examine the problem 132 of detecting a specific community partitioning. Second, if partial membership information about only one community is known, we look at the problem of detecting a specific community given a partial membership list. For example, some users on Facebook list their college and matriculation year in their profile.

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Nicotine transdermal patch the nicotine transdermal patch takes advantage of the ready absorption of nicotine across the skin (799, 1550). It is available in four formulations: three 24-hour patches and one 16-hour patch for use while an individual is awake. Treatment initiation typically uses a 21- to 22-mg 24-hour patch or a 15-mg 16-hour patch. Patches are applied on the first morning of smoking cessation and then each morning thereafter. The nicotine is slowly absorbed so that on the first day venous nicotine levels peak 6­10 hours after administration. Thereafter, nicotine levels remain fairly steady, with a decline from peak to trough of 25%­40% with 24-hour patches (799). The 16-hour nicotine patches demonstrate similar nicotine pharmacokinetics after discontinuation of smoking. Nicotine levels obtained with the use of patches are typically half those obtained by smoking (799). Most, but not all, studies indicate abrupt discontinuation of the patch usually causes no significant withdrawal so that tapering may not be necessary (71). There are now two nicotine patches available over the counter: a 21-, 14-, and 7-mg strength patch (24-hour application) and a 22- and 11-mg strength patch (16-hour application). Nicotine gum Nicotine ingested through the gastrointestinal tract is extensively metabolized on first pass through the liver (1551). In addition, nicotine is a gastrointestinal irritant that makes orally ingested nicotine an unpleasant treatment for patients who are already experiencing nicotine withdrawal. Nicotine gum (nicotine polacrilex) avoids this problem via buccal absorption Treatment of Patients With Substance Use Disorders 133 Copyright 2010, American Psychiatric Association. The gum, which is available as an over-the-counter medication, contains 2 or 4 mg of nicotine that can be released from a resin by chewing (886). When compared with nicotine delivery via smoking, nicotine gum produces lower steadystate blood levels of nicotine and does not reach peak levels of nicotine absorption for >30 minutes (1551). Because cigarette nicotine is absorbed directly into the arterial circulation, arterial blood levels from smoking are 5­10 times higher than those from the 2- and 4-mg gum (1552). Venous nicotine levels from the 2- and 4-mg gum are about 33% and 67% of the steady-state. Absorption of nicotine in the buccal mucosa and the resulting steady-state levels are further decreased by an acidic environment; thus, patients should not drink acidic beverages. In terms of dosing, the original recommendation was to use one piece of 2-mg gum every 15­30 minutes as needed for craving. Although the original recommended treatment duration was 3 months, many experts believe longer treatment is more effective. However, two trials of longer treatment durations produced contradictory results (801). Nicotine lozenges the nicotine lozenge contains nicotine bound to a polacrilex ion-exchange resin, similar to the nicotine gum. Because it does not have to be chewed, the lozenge may be preferable for smokers with dental problems or for those who do not like to chew gum. Compared with an equal dose of nicotine gum, the lozenge delivers 25% more nicotine (802). It is recommended that the lozenge be used every 1­2 hours for the first 2­4 weeks of treatment, with the frequency of use reduced to every 2­4 hours in subsequent weeks. Nasal sprays produce droplets that average 1 mg per administration (spray solutions are dispensed at 10 mg/ml); patients administer the spray to each nostril every 1­2 hours. This formulation produces a more rapid rise in and higher nicotine levels than the nicotine gum but less than that obtained with cigarettes. There is approximately a 30% replacement of plasma nicotine levels with nasal spray use (809). Peak nicotine levels occur within 10 minutes, and venous nicotine levels are about 67% of betweencigarette levels (782). Smokers are to use the product ad libitum up to 30 times/day for 12 weeks, including a tapering period. Nicotine vapor inhalers Nicotine vapor inhalers are cartridges of nicotine containing about 1 mg of nicotine each placed inside hollow cigarette-like plastic rods. The cartridges produce a nicotine vapor when warm air is passed through them (805, 806).

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Age-specific prevalence data indicated that approximately 90% of the children were harboring patent Ascaris infections by the time they were 4 years old (114). Likewise, in a separate study in southeast Madagascar, fecal examinations revealed prevalences of 78% for A. Infection intensity was measured indirectly by fecal egg counts and directly by A. How this worm causes anemia is uncertain, as the worm feeds on gut contents rather than on blood. Infection is associated with poverty and poor diet and it has been reported to cause anorexia (102, 116). Undoubtedly, worms compete with the host for food, and infestation is linked to poor growth (116, 117). Diphyllobothrium latum is a species of tape worm that specifically causes pernicious anemia. It can grow to 20 meters in length and when present in the jejunum it selectively absorbs cyanocobalamin, hence depriving the host of vitamin B12 (118). Frequently, there was little benefit, but in a number of these studies there were adverse consequences that have been summarized elsewhere (61). The adverse reactions to iron increased awareness of avoiding iron supplements in rehabilitating malnourished children who had a high risk of infection (64), but even in apparently healthy persons, iron supplements appeared to increase the prevalence of disease. Infection-induced hypoferremia is a well-recognized phenomenon and withholding iron may both prevent growth of pathogens (119) and be anti-inflammatory by reducing a potential prooxidant (120). The recently discovered hepcidin, which is increased by inflammation and blocks absorption and mobilization of iron, is now known to be responsible for the hypoferremia of infection, and that frequent or chronic infection leads to a reduction in hemoglobin. If anemia in apparently healthy persons in the developing world is mainly due to subclinical inflammation, it explains why supplementation with iron is so ineffective in lowering the prevalence of anemia, as iron does not cure infections. The iron supplementation study in which parenteral iron dextran or a placebo was given to infants at 2 months in an area of high malaria transmission in Papua New Guinea increased the Infection and the etiology of anemia 249 prevalence of malaria, as judged by parasite and spleen rates at follow-ups at 6 and 12 months compared to those in the placebo group (121). In addition, the same workers also reported that in the placebo group, infants with higher birth hemoglobin levels (and thus higher total body iron content) were significantly more likely to have malaria at follow-up and more likely to be admitted to the hospital with malaria (65). That is, both a high "normal" hemoglobin content and receiving additional iron at 2 months of age increased the risk of malaria severity. There is no doubt that all infants in the study were bitten by malaria-positive mosquitoes during the follow-up period, since the studies were done in an area of high malaria prevalence, but the higher iron status increased the risk of that infection becoming serious. The studies done in Papua New Guinea also showed that infants appeared to be more seriously affected by malaria when given iron supplements than older children. In a separate study in the same area, prepubescent schoolchildren with hemoglobin levels of 80­120 g/L were randomly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks. Treatment did not significantly affect parasite rate, parasite density, levels of anti-malarial IgG, spleen size, or the number of reported episodes of suspected malaria during the therapy (122). Neopterin is a marker of cell-mediated immunity, and urinary excretion is high in infancy (123) but decreases markedly over the first two years of life in Tanzanian infants (124). Furthermore, pro- and antiinflammatory cytokines appear to be delicately balanced to produce a more powerful inflammatory response in younger children (96). Thus additional dietary iron given to infants exposed to frequent infections may upset this delicate balance. Vitamin A supplements have been shown to have hematopoietic properties in children and adults in the absence of additional iron (12­15). It is also now widely accepted that vitamin A supplements in many countries have consistently reduced mortality, overall by 23% (125­ 127). It is very likely that a reduction in mortality is due to a reduction in morbidity, and certainly the smaller supplementation studies in patients with serious measles showed a reduction in morbidity and a shortening in recovery times (128, 129). If mild anemia in the developing world is mainly due to subclinical inflammation, then providing vitamin A supplements should reduce some of the inflammation and enable iron mobilization to restore hematopoiesis (18). However, hematopoiesis can only occur when dietary iron or iron stores are available, thus in communities or groups where hookworms, schistosomes, and/or whipworms are serious problems, vitamin A alone may have minimal effects on anemia in the absence of added dietary iron. However, these latest announcements do not appear to have capitalized on the potential importance of vitamin A when supplementing with iron. We previously showed that when iron was given to Pakistani preschool children in a nonmalarious area, there was little evidence of increased morbidity as a result of the iron supplement, except in those children with the poorest vitamin A status. That is, the risk of adverse consequences to iron supplements may be modified by vitamin A status, and it would seem prudent that future iron interventions be preceded by vita- 250 D. Northrop-Clewes min A supplements with or without anthelminthic treatment according to local conditions.

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Indices of neurological development were evaluated in 313 newborn infants (Fein et al. Of these infants, 242 were born to mothers who had consumed moderate to large quantities of Lake Michigan fish sometime during their lives, and 71 were born to mothers who did not consume Lake Michigan fish. A list of 68 potential confounders was collected from the maternal interview and medical record. The list contained data pertaining to demographic background, reproductive health history including pregnancy and delivery, anesthesia during delivery, and exposure to other substances such as caffeine, nicotine, and alcohol (Fein et al. Potential confounders were included only if the frequency in each category exceeded 15%. Consequently, data on approximately 37 potential confounders were available for inclusion in the study analyses (Fein et al. The Ballard Examination was administered at 30 to 42 hours after birth to 209 of 313 (67%) infants with maternal permission granted during the limited time frame available for assessment. These reduced clusters were derived by synthesizing the results of factor analyses from studies of six independent samples (Fein et al. The results of the tests conducted on the newborns showed that decreased neuromuscular maturity, as measured on the Ballard Scale was significantly associated with consumption of contaminated fish (Fein et al. However, when the non-fisheater and fisheater populations were divided according to cord serum level (<3 and $3 ppb, respectively), there was no significant difference in neuromuscular maturity outcome. The potential confounders were chosen based on their statistical significance in prior correlation analyses. Infants of mothers eating contaminated fish were more likely to exhibit hypoactive reflexes, more motor immaturity, poorer lability of states, and a greater amount of startle (Jacobson et al. A follow-up of 39% (92 fisheating mothers, 31 controls) of the children in the Michigan Mother-Child study occurred at 7 months of age (Jacobson et al. Recognition memory performance was not related to postnatal exposure from breast-feeding. The investigators further indicated that visual recognition was unrelated to neonatal variables such as birth size, gestational age, and neurobehavioral performance. There was no indication of perceptual motor deficits or alterations of long-term memory. Cognitive performance was unrelated to exposure from breast-feeding, which, according to the investigators (Jacobson et al. Regression analyses were performed with control for statistically selected potential confounders. Cognitive performance was unrelated to postnatal exposure via breast milk (Jacobson et al. Results using this composite score as the exposure and the McCarthy Scales, height, and weight as outcomes were similar to those reported by Jacobson et al. The outcomes studied were the Wechsler Intelligence Scales, the Wide Range Achievement tests, and the Woodcock Reading Mastery tests (Jacobson and Jacobson 1996a). These values were available for approximately 178/313 (57%) of the original group of children in the study. Additional confounders selected on the basis of their statistical relationship to the particular outcome were also included in several models. Poorer spelling was significantly associated with a higher mercury concentration at 11 years of age (Jacobson and Jacobson 1996a). Pregnant women were recruited from the office of one obstetric practice and, following interviews, were divided into three groups based on their estimated fish consumption. The three groups did not differ with regard to demographic, health and nutritional data, maternal substance use, and infant birth characteristics. The high fish consuming group had a significantly heavier pre-pregnancy weight than the nonfisheating group. A total of 58 potential confounding variables were submitted to principal components analysis. The third group of variables included labor and delivery complications as well as birth characteristics. Approximately 75% of each fish consumption group was included in the analysis (n=416). The loss of subjects occurred because only subjects with data for all variables were included. Change scores for the Habituation cluster were analyzed in a separate analysis of covariance due to the large number of subjects with missing data (n=285 in the analysis).

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The property is not be leased or rented during the five (5) years after the issuance of a building permit. The per capita fee consists of a recreational facilities component and an open space component. The amount of the fee paid by a development project shall be determined by multiplying the per capita fee by the number of people expected to reside in the project. The occupancy ratios in Table 13-1 shall be used in determining the fee, unless the applicant provides verifiable written documentation from an independent, objective source demonstrating other occupancy levels. Occupancy ratios for determining recreational facilities and open space impact fee Type Ratio (people per unit) 3. The amount of the fee shall be based upon the procedure set out in Subsection D above. The City Administrator may approve the payment of impact fees over time in accordance with an approved payment schedule, provided that appropriate arrangements are in place to guarantee collection of the fees. Acquisition of vehicles and/or purchases of equipment used by Fire Department personnel for fire, rescue, and emergency medical services. Construction of capital improvements, including the expansion or replacement of existing infrastructure facilities, or, if the improvements were constructed at municipal expense prior to the development, the fee must be reasonably related to the portion of percentage of the infrastructure used by the development. Acquisition of land or easements necessary for or related to existing and proposed Fire Department facilities. Engineering, surveying, and environmental assessment services directly related to the design, construction, and oversight of the construction of the improvement. The actual construction of the improvement, including, without limitation, demolition costs, clearing, and grading of the land, and necessary capital equipment. Legal and administrative costs associated with construction of capital improvements, including any borrowing necessary to finance the project. Debt service costs, including interest if the City borrows for the construction of the improvement. As the community grows, increased capacity is required to meet the public safety needs of greater numbers of residents. Any construction or development that involves the creation of a new dwelling unit, as defined by this chapter, including single-family homes, apartment units, mobile home units, and mobile homes, shall be subject to the payment of a Fire Department/emergency medical services impact fee, except as provided below: 1. No impact fee shall be paid if a new dwelling unit is to be constructed on a lot where a dwelling unit has been demolished or permanently removed from use within the last twelve (12) months. No impact fee shall be paid if a dwelling unit is moved from one lot within the City to another lot within the City. No impact fee shall be paid if a proposed dwelling unit is created as the result of a conveyance of a parcel to a family member. No impact fee shall be paid for the creation of an accessory apartment in a singlefamily dwelling. The amount 173 of the fee shall be based upon the procedure set out in Subsection D above. This impact fee shall be applicable to activities subject to the impact fee 30 days after the date of amendment of this article. Changing one nonconforming use to another use that is equally or more appropriate to the zoning district and meets the standards of Article V and this section. Review and Approval Authority the Planning Board shall review and approve, or approve with conditions, or deny applications for a Conditional Use Permit. If the development proposal under conditional use permit review is also subject to site plan review, conditional use permit review, and site plan review may occur simultaneously. Applicants may submit a written request for a waiver of submission requirements with their Conditional Use Permit application. The Planning Board may grant a waiver(s) of application submission requirement(s) if it finds that, due to special circumstances of a particular plan, the submission of required exhibits is not necessary or is inappropriate because of the nature of the proposed development. The Planning Board may request additional information as it deems necessary for proper review to ensure that sufficient information is presented to the Planning Board when it initially reviews an application. An application is not deemed to be complete until declared to be so by vote of the Planning Board, which may, in any case, request additional information and materials. The Planning Board shall cause public notice to be posted and published in both the City Building and at least one (1) newspaper of circulation in the area, of any 175 public hearing which the Planning Board shall conduct, indicating the property involved, the nature of the application, and the time and place of the public hearing.


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Initial treatment of homocystinuria consists of providing the baby with a formula that does not contain methionine. A methionine-restricted cysteine-supplemented diet may be required throughout life and administration of vitamin B6 (pyridoxine) is also often prescribed. The birth prevalence homocystinuria in the United States is approximately 1 in 200,000. Besides ocular abnormalities, affected individuals also have tall, thin statures with long limbs, spidery fingers and pectus deformity of the chest. Mental disability, psychiatric disturbances, and thinning and weakness of the bones are also common. Individuals frequently develop blood clots, which can cause life threatening thromboembolic episodes. At least nine genetic defects have been shown to disrupt the major pathway in which methionine is metabolized. Cystathionine -synthase deficiency is the most common and results in high levels of serum methionine. Slightly less than 50% respond to vitamin B6 therapy, and those that do should continue throughout their life. Treatment appears to reduce the risk of thromboembolic episodes, seizures, and mental disability and delays lens dislocation. Treatment must continue throughout life and people with homocystinuria should receive specialized treatment through a metabolic clinic that has experience in treating this disorder. The homocystinuria screening test may yield equivocal results for babies who have received hyperalimentation or other therapeutic infusions. The result will be reported as "invalid" and a followup screen will be recommended when treatment is concluded. Symptoms include poor feeding and failure to thrive, vomiting, lethargy, hypotonia or hypertonia and the characteristic maple syrup smell of their urine. Glucose and insulin infusions are commonly given during episodes of acute metabolic decompensation. The result will be reported as "invalid" and a follow-up screen will be recommended when treatment is concluded. Affected infants develop normally with early identification and proper dietary management. Although the exact pathogenesis of the damage to the central nervous system is still not clear, it seems likely that an increased concentration of phenylalanine in the blood is associated in some way with the neurodegenerative effects. Strict dietary restriction of natural protein is required to reduce high blood phenylalanine levels. Phenyl-Free) supplemented by low-protein foods and avoidance of aspartame (NutraSweet). Treatment should be started as soon as the diagnosis is confirmed and should be continued indefinitely to optimize normal physical and mental development. The staff consists of a pediatric biochemical geneticist, nutritionists, a social worker, and genetic counselor. It is especially critical that women of childbearing age maintain very strict dietary control. Women with high levels of phenylalanine during pregnancy are at increased risk of fetal loss, fetal brain damage, and other birth defects. A small percentage will be missed if the screening is done very early (prior to 12 hours of age). The result will be reported as "invalid" and a follow-up screen will be recommended when the infusion treatment is concluded. Deficiency of this enzyme causes a build-up of tyrosine and succinylacetone in the bloodstream. This is severely toxic to the liver, kidneys, heart and the nervous system, which can lead to multi-organ failure, seizures, coma and death. Early detection and treatment can reduce the mortality and morbidity associated with this disorder. Without early treatment, both forms may present with diarrhea, vomiting, poor weight gain, jaundice, enlarged liver, edema (swelling of the abdomen or feet), painful abdominal crises, irritability and a characteristic "cabbage-like" odor in the skin and urine.

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Maremmani I, Zolesi O, Aglietti M, Marini G, Tagliamonte A, Shinderman M, Maxwell S: Methadone dose and retention during treatment of heroin addicts with axis I psychiatric comorbidity. Maremmani I, Canoniero S, Pacini M: Methadone dose and retention in treatment of heroin addicts with bipolar I disorder comorbidity: preliminary results. Langrod J, Lowinson J, Ruiz P: Methadone treatment and physical complaints: a clinical analysis. Lexington, Ky, National Academy of Sciences, National Research Council, 1967 [G] 1357. Darke S, Sims J, McDonald S, Wickes W: Cognitive impairment among methadone maintenance patients. Adv Alcohol Subst Abuse 1984; 4:89­96 [B] Treatment of Patients With Substance Use Disorders 253 Copyright 2010, American Psychiatric Association. Cami J, de Torres S, San L, Sole A, Guerra D, Ugena B: Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin. Spencer L, Gregory M: Clonidine transdermal patches for use in outpatient opiate withdrawal. Nyswander M, Winick C, Berstein A, Brill I, Kauger G: the treatment of drug addicts as voluntary outpatients: a progress report. Arch Gen Psychiatry 1987; 44:281­284 [C] Treatment of Patients With Substance Use Disorders 255 Copyright 2010, American Psychiatric Association. Stimmel B, Cohen M, Sturiano V, Hanbury R, Korts D, Jackson G: Is treatment for alcoholism effective in persons on methadone maintenance? American Thoracic Society: Diagnostic standards and classification of tuberculosis. Suffet F, Brotman R: A comprehensive care program for pregnant addicts: obstetrical, neonatal, and child development outcomes. Psychiatr Ann 2003; 33:585­592 [F] Treatment of Patients With Substance Use Disorders 257 Copyright 2010, American Psychiatric Association. Substance Abuse and Mental Health Services Administration: Results from the 1992 National Household Survey on Drug Abuse: Main Findings 1992. Substance Abuse and Mental Health Services Administration: Results From the 2004 National Survey on Drug Use and Health: National Findings. Centers for Disease Control: Alcohol-related mortality and years of potential life lost: United States, 1987. National Institute on Drug Abuse: National Pregnancy and Health Survey: Drug Use Among Women Delivering Livebirths. Centers for Disease Control: Current trends: statewide prevalence of illegal drug use by pregnant women: Rhode Island. Centers for Disease Control: the Health Benefits of Smoking Cessation: A Report of the Surgeon General. Lerman C, Patterson F, Berrettini W: Treating tobacco dependence: state of the science and new directions. Clin Chest Med 2002; 23:1­25 [F] Treatment of Patients With Substance Use Disorders 259 Copyright 2010, American Psychiatric Association. Centers for Disease Control: the Health Consequences of Involuntary Smoking: A Report of the Surgeon General. Office of Health and Environmental Assessment: Respiratory Health Effects of Passive Smoking: Lung Cancer and Other Disorders. Fagerstrцm K: the epidemiology of smoking: health consequences and benefits of cessation. Bauman A, Phongsavan P: Epidemiology of substance use in adolescence: prevalence, trends and policy implications. Centers for Disease Control and Prevention: Youth tobacco surveillance: United States, 1998­1999. Berglund M, Ojehagen A: the influence of alcohol drinking and alcohol use disorders on psychiatric disorders and suicidal behavior. Farrell M, Howes S, Bebbington P, Brugha T, Jenkins R, Lewis G, Marsden J, Taylor C, Meltzer H: Nicotine, alcohol and drug dependence, and psychiatric comorbidity: results of a national household survey.

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Malabsorption due to disorders that affect the upper small intestine can also cause iron deficiency. The most common appear to be celiac disease (86, 87) and Helicobacter pylori infections (88­91). Celiac disease may be more prevalent in some Mediterranean and south Asian countries than previously realized (92­94). It is also important to note that inadequate absorption of multiple nutrients associated with histological abnormalities of the intestinal mucosa was thought to contribute to the high prevalence of iron deficiency in countries such as India, Pakistan, Bangladesh and Haiti in earlier studies (3). The prevalence of "tropical sprue" appears to be declining and the specificity of this entity, as well as the overlap with tropical enteropathy, has been questioned recently (95). The possible relevance of these entities to nutritional iron deficiency is unclear and further research is needed. Finally, surgical procedures that alter the anatomy of the stomach and duodenum may also decrease iron absorption. It can be considered under three headings, primary systemic iron overload, secondary iron overload, both of which affect several different Iron metabolism 69 Table 6. The regulation of iron absorption as iron stores increase in human beings with normal mucosal function is remarkable effective. There are only isolated case reports of clinically significant iron overload resulting from the ingestion of large quantities of supplemental iron over extended periods of time (3). In contrast to iron deficiency, primary systemic iron overload appears virtually always to result from the phenotypic expression of an inherited abnormality related to the regulation of iron transport. Men who are at greatest risk for the disorder consume large quantities of highly bioavailable iron (97, 98) and there is little doubt that this excessive intake is an important contributory factor (99). However more recent observations have provided strong circumstantial evidence for an underlying genetic mutation (100) suspected of affecting the function of Fpn (101­104). Dysregulation of hepcidin and abnormal function of its receptor Fpn, resulting in inappropriate iron release from stores and excessive absorption, are now considered to be the most important etiological factors in patients with primary systemic iron overload (Table 6. Hepcidin levels are inappropriately low, but not as severely decreased as they are in other related disorders (22). However, a report from Australia demonstrates that many more may have laboratory evidence of organ damage (108). If unrecognized, a small minority of individuals, particularly men, will develop signs and symptoms, usually in middle age when the body iron content has reached 15­40 g. Two much rarer types of hemochromatosis have their clinical onset in the second or third decades of life and present a more severe phenotype (juvenile hereditary hemochromatosis). The phenotype associated with the gene encoding TfR 2 (Type 3) occurs early in life, but is milder than Type 2 juvenile hereditary hemochromatosis (112). The function of TfR2 is unknown, although recent observations indicate that it also modulates hepcidin production (113). Finally, mutations of the hepcidin target, Fpn, may affect its functionality or responsiveness to hepcidin (114­116). Secondary iron overload leads to severe morbidity in patients with thalassemia and sideroblastic anemia who have accelerated ineffective erythropoiesis (117). They continue to absorb excessive quantities of iron despite increasing iron stores if they are anemic (118). Finch proposed the existence of two regulators of iron absorption, a "stores regulator" and an "erythropoietic regulator" (119). The "erythropoietic regulator" was postulated to override the control exerted by the "stores regulator" in these conditions. Recent studies point to a common mediator, hepcidin, for both regulators (22), but also provide support for the apparent dominance of erythropoietic rate in the control of iron absorption. Hepcidin production has been reported to be decreased despite elevated serum ferritin levels (indicative of increased iron stores) in the presence of accelerated erythropoiesis (120, 121), leading to continued iron accumulation. Repeated blood transfusions also contribute significantly to the iron overload in these patients. They include atransferrinemia as well as conditions that lead to organ/tissue specific iron overload. Examples include abnormalities of iron trafficking in the mitochondrion (122) and aceruloplasminemia (123, 124). Anemia of inflammation (anemia of chronic disease) the anemia of inflammation is a mild or moderate anemia that is characterized by decreased iron release from macrophage stores, reduced absorption, restriction of the supply available for red cell production and reduced plasma iron and transfer- Iron metabolism 71 rin concentrations (125). Many investigators have postulated that it is a vital host response that evolved to deprive pathogens of iron, and that it is one of the mechanisms that constitute "nutritional immunity" (126, 127).


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