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The structure of the loading of the intervertebral disc: from the macroscopic to the cel cartilaginous end-plates in elder people medications not to take with blood pressure meds generic herbolax 100caps on-line. Degenerative changes in interverte anatomical-clinical observations in arthritis. Clinical anatomy of the cervico Osteoporosis: Etiology, Diagnosis, and Management. New joints in response to external loads: a biomechanical study using York: Raven; 1994. Progressive senile scolio sis: seven cases of increasing spinal curves in elderly patients. Norbert Boos Zentrum fur Wirbelsaulen und Ruckenmarkchirurgie Universitat Zurich Universitatsklinik Balgrist Forchstra e 340, 8008 Zurich Switzerland Prof. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Printed in Germany the use of general descriptive names, registered names, trademarks, etc. In every individual case the user must check such information by consulting the relevant literature. Simply stated, the shape of a building or object should be predicated by or based upon its intended function or purpose. Initially the peer review aspect was lost and the quality of available knowledge suffered. By an intensive editing pro cess, the different chapters have been woven into a homogeneous book combin ing personal experience with evidence based knowledge. No topic is superfluous or perceived as more important than another and the book reads as one continuous flow, one topic logically leading to the next. As a therapeutic measure, spinal surgery is still one of the most rapidly growing areas in clinical medicine, and is a major contributor to the continuously increasing costs of modern-day medicine. Therefore, a basic knowledge of the state of the art of the diagnosis and treatment of spinal disorders is required, not only for spine specialists but also for general orthopedic surgeons, rheumatologists, neurologists, rehabilitation doctors, psychiatrists, chiropractors, physiothera pists, basic scientists and health care executives, to enable them to choose and/or evaluate appropriate diagnostic and therapeutic approaches. Owing to the rapid development of knowledge of spinal disorders over the past 20 years, a comprehensive new textbook which incorporates all the latest knowledge has become necessary, and we have become aware again and again of innumerable residents, fellows and colleagues searching for a comprehensive introductory learning tool for the study of spinal disorders. Although excellent textbooks on specific issues of the spine and specifically spinal surgery are already available, none fulfills the criterion of being an easily readable teaching tool that focuses systematically on the fundamentals and basic principles in a standardized manner. Unlike many other spinal textbooks, the editors did not want simply to collect and edit chap ters from many different authors, which often leads to an inhomogeneous book with overlapping, redundant and incoherent chapters. Althoughwehavebasedtheinformationinthisbookonanextensivesurvey of the peer-reviewed literature, we have moderated this information in a synthe sis with research and clinical experience. We have, however, refrained specifically from an in-depth description of sophisticated surgical procedures. For this field of expertise, there are already a number of excellent manuals and textbooks available. It is our hope that this book may become the standard basic textbook for spinal disor ders if you, the reader, decides to make this happen. We owe many thanks to Doris Stettler and Grit Gagel mann for their support and help with the editing process. We also want to acknowledge the Medical Pictorial Documentation team of the University Hospi tal Balgrist (Heidi Wylenmann, Helene Uhlmann and Christian Streng) for their invaluable help with the editorial preparation of the medical images and figures. We also thank Springer, the publisher, and specifically Gabriele Schroder for making this book happen. The ample use of visual aids mediates the core messages and allows for a gradual and repetition-based learning approach starting with the core messages and going on to an in-depth reading of each chapter. Marginal notes and a short recapitulation facilitate the learning by repe tition. A pictorial and anecdotal learning method is enabled by the many case studies, which exemplify the core messages. Functionalcorrectionandearlier tionsorped-turedisloca 33operative:brace 1superficialinfectionand2brokenscrews similaroutcomeat2yearsis SpinalInjuries iclefractures posteriorfixa-tion hospitalchargeswere4timeshigherinthe polytraumatizedpatientsAbout30%of Itisobviousthatthemanagementandtheprioritiesdifferbetweenalife-threat-eningpolytraumathatincludesaspinalinjuryandamonotraumaofthespine. Cross references facilitate Tables also provide a topical state a quick orientation of-the-art review of the literature and throughout the textbook. Hyperextensionmayresultinrupture neouspatientpopulationsandtreatmentstrate-cause of their retrospective design, heteroge Case studies aim to compressioninjuriesoftheposteriorelements, i. Thehistorytantinjuries;themostfrequentare:headinjuries, tweentheoperativeandnon-operativetreatment, substantialdifferenceinfunctionaloutcomebe recollection by the principle demonstrateacorrectpositioningofthescrewsintheanteroposteriorview(e)andlateralview(f);inaddition, thelocal shouldincludethetypeoftrauma(highvs. Nowadays, it is used to describe a specific clinical condition con sisting of lateral deviations of the spine associated with vertebral rotation. This medical papyrus is an outstanding witness of a very accurate and rational medicine in Old Egypt foremost in traumatology. Now afterward moor (him) at his mooring stakes until the period of his injuries passes by. Galen identified the number of vertebrae in each segment of the spinal column, and described the ligamentum flavum as a ligamentous structure distinct from the underlying dura and pia mater. He was also able to correlate neurological findings with a specific spinal level, because he performed frequent experiments on primates. During the Middle Ages, no progress was made in the understanding of spinal anatomy. By publishing the cut of modern spinal anatomy ting-edge anatomical textbook De Humani Corporis Fabrica Libri Septi, Vesalius became the founder of modern spinal anatomy in 1543. He illus trated the blood supply of the spinal cord with an accuracy that is still unsur passed. Weitbrecht is also credited with providing a very concise description of the intervertebral disc for his time. Furthermore it was believed that in the spinal cord the spinal cord consisted of bundles of nerve fibers grouped into columns. After the microscope entered clinical and pathological practice, the cellular contents of the gray matter were identified, and since then there have been steady advances in our understanding of the spinal cord. Anesthesia and Supportive Techniques An invasive and effective spinal surgery would not have been possible without major advances in anesthesia and supportive techniques such as antisepsis, anti biotics and diagnostic imaging.

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Another participant discussed the benefits of vending machines as alternative means of accessing food and drink on campus without the stress of entering the busy cafes treatment interstitial cystitis 100 caps herbolax fast delivery, although noted that this was limited by the lack of healthy options available. These include both coping mechanisms to support learning and wellbeing as well as tactics that are both subversive and assertive. Another common coping mechanism was the careful selection of seats in lecture theatres and tutorial rooms to reduce sensory stimuli and render the individual more invisible: I tend to pick a spot all the time. It is the option of escape rather than the need to actually escape that can be the critical factor in reducing anxiety. Some lecture theatres and tutorials rooms were seen to be less anxiety-provoking as they more readily facilitated escape. The consequences of feeling trapped through a blocked or highly visible escape route are feelings of stress and an inability to focus and even self-exclusion from classes. Owen, McCann, Rayner, Devereaux, Sheehan & Quarmby 62 Supporting students with Autism Spectrum Disorder in Higher Education this kind of deliberate, but controlled, exposure to challenging situations is not always feasible, however, and managing the consequent stress can be difficult. One coping mechanism employed by participants is to study at home, either through minimising required contact time on campus or through distance education. Technology is not only employed by this participant to enhance his learning within units he is enrolled in, but he also uses technology to access content in other units to pursue learning of his own interest. Two other participants in the study, who are coming to terms with and even celebrating their autistic identity, also articulated this sense of control and of agency. Owen, McCann, Rayner, Devereaux, Sheehan & Quarmby 64 Supporting students with Autism Spectrum Disorder in Higher Education 5. Students have identified difficulties with study skills, time management, communication, social skills and anxiety (Hastwell et al. The provision of study and organisational skills and transition support, that includes the provision of an understanding of the tertiary learning environment, were mentioned most frequently as effective and best practice ways to support students. Additionally it can be argued that core features of the peer mentoring approaches provided encompassed study and organisational skills, and transition support. However, despite these supports being identified most frequently as most effective and best practice, the proportion of institutions supporting students with specific transitional programs was the second lowest method currently utilised. Hence it appears that most institutions are recognising the need for this type of support and are addressing it through referrals to internal staff, rather than instigating specific programs. Where specific programs are instigated, these tend to be limited to transition programs at the point of entering higher education. Implicit in approaches that use transitional and mentoring programs is the fostering of social connections and the utilisation of a proactive approach. As Macleod & Green (2009) argue, often by the time a need has been identified academic achievement Owen, McCann, Rayner, Devereaux, Sheehan & Quarmby 66 Supporting students with Autism Spectrum Disorder in Higher Education and student wellbeing has already been adversely affected. This study therefore supports the emerging evidence in the literature for peer mentoring programs. Further research on a comparison between mentoring programs, the approaches within institutions that would best supplement this approach, and the effectiveness of the approaches in terms of student experience and academic progression is required. Additionally, these findings favour the call for the provision of support that extends beyond academic related skills. Similar to the provision of transition programs and study and organisation programs it appears that few institutions are implementing programs to provide these supports, but those that do regard them as highly effective ways to support their students. It is recognised through the literature and this study that providing direct support to students is only one side of the coin, and effective support also requires the provision of professional development and supports to teaching and professional staff within institutions (Knott & Taylor, 2014; McKeon, Aspern & Zager, 2013; Morrrison, Sansosti, & Hadley, 2009). Further support is provided through web-based and non-web-based resources and information. Whilst the education of staff is encouraged, little evidence exists to determine the most effective mechanisms for the provision of supports. Some students found online or distance learning to be extremely beneficial, while others found this approach to study unmanageable. Students differed in their response to unstructured, student-directed learning in comparison to incremental, structured learning (some preferring the former, others the latter). Indeed, the findings of this research are consistent with the recommendation of Beardon et al. The self-directed photography and interview data of this survey provide rich examples of the ways in which students resolve the mismatches between the learning environment and their individual characteristics. Notable examples included the use of exit and avoidance strategies, deliberate and progressive desensitisation experiences, and the utilisation of information and communication technologies. Owen, McCann, Rayner, Devereaux, Sheehan & Quarmby 68 Supporting students with Autism Spectrum Disorder in Higher Education 5. It is important that the design of both learning spaces and the informal spaces on campus are considered in this context. The learning environment does not end with the classrooms and lecture theatres and likewise, the accommodation of social nuance does not cease at the classroom door. Impacts can range from reduced cognitive functioning, sickness that can result in incapacitation for hours or even days, and self-exclusion from classes resulting in reduced academic performance and even failure to graduate. The issues experienced by students are not limited to learning and teaching spaces, but can affect access to all campus facilities including the library, social spaces and cafeterias. Key issues identified in the research related to sensory overload from acoustic and visual stimuli, difficulties in navigation of both campus and online environments and problems of social engagement including both a lack of opportunities for structured social encounters and the ability to avoid or escape from of social encounters. Addressing these problems does not require a radical redesign and major investment in campus infrastructure. While we are not suggesting that this approach should be abandoned in favour of more sensory neutral learning environments, it is important that alternative provisions are made that enable choice and retreat from the hyper-stimulating environments. More broadly, however, such facilities should be considered as part of the whole campus environment for the benefit of all students. Threshold spaces and particularly external spaces on campus offer valuable opportunities for this kind of retreat. Key features of these spaces include quiet environments with visual access to natural features, daylight or soft electric lighting, muted, solid colours, comfortable couches, easy to navigate, bounded but not enclosed and with easy access to water.

Syndromes

• Oxygen, if needed
• Slow bleeding and iron deficiency anemia (due to a large hernia)
• Uteropelvic junction obstruction - blockage of the kidney at the point where the ureter enters the kidney
• Laminectomy
• Name of the product (ingredients and strengths, if known)
• Night sweats
• Does not respond well to a medicine called nitroglycerin
• Enteroscopy
• Infection, including in the surgical wound, lungs (pneumonia), bladder, or kidney
• Over time, however, nasal polyps often return.

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It might be expected that phylloquinone dissolved in oil would be more avail able than from a food matrix treatment 3rd stage breast cancer order 100 caps herbolax free shipping, but this may not be true. Vitamin K is not well absorbed by patients exhibiting lipid malabsorption syn dromes (Savage and Lindenbaum, 1983), and efficient absorption of this fat-soluble vitamin from the digestive tract does require dietary fat. Dietary intake of this form of the vitamin in the United States is estimated to be about 20 percent of phylloquinone (Booth et al. Neither the biological activity nor the bioavailability of this form of vitamin K is known. The amount of dietary fat needed for optimal absorp tion has not been determined. Drug-Nutrient Interactions Oral 4-hydroxycoumarin derivatives such as warfarin are widely prescribed anticoagulants for the prevention of thrombotic dis orders. These drugs function through the inhibition of a hepatic vitamin K-epoxide reductase. This enzyme reduces the coproduct of the glutamyl carboxylase reaction, the vitamin K 2, 3-epoxide, to the hydronaphthoquinone form of the vitamin, which is the sub strate for the enzyme. The result is an acquired cellular vitamin K deficiency and a decrease in the synthesis of the vitamin K-depen dent plasma clotting factors. Alterations in vitamin K intake can, therefore, influence warfarin efficacy, and numerous case reports of these occurrences have been reviewed (Booth et al. These data suggest that alterations in vitamin K intake might influence warfarin dosage. As an effective warfarin dose varies widely within individuals, patients are closely monitored. Once a dose has been established, patients can avoid any complications resulting from variations in vitamin K intake by continuing to follow their normal dietary patterns. Nutrient-Nutrient Interactions the ability of elevated intakes of vitamin E to antagonize vitamin K action has been clearly established. Woolley (1945) first demonstrated that increased dietary or parenteral tocopherol or tocopherol quinone could induce a hemorrhagic syndrome in the rat, and vita min K administration was demonstrated to reverse this response (Rao and Mason, 1975). Studies of the microsomal vitamin K dependent carboxylase have demonstrated that the enzyme can be inhibited by tocopherol and that it is even more sensitive to tocopherol quinone (Bettger and Olson, 1982; Dowd and Zheng, 1995). Increased intakes of vitamin E have not been reported to antago nize vitamin K status in healthy humans. More sensitive measures of vitamin K status are now available and should be used to assess the potential impact of vitamin E supple mentation in anticoagulated patients or subjects with low vitamin K intakes. The metabolic basis for vitamin E antagonism of vitamin K func tion has not been completely elucidated. Antagonism of vitamin K action in animal models by retinoids (retinyl acetate, 13-cis retinoic acid, and N-(7-hydroxyphenyl retina mide) has been reported by a group of investigators (McCarthy et al. High doses of these compounds have been used in animal studies, and adverse responses in humans have not been reported. In two studies, Golding and coworkers (1990, 1992) reported an increased risk (odds ratio, 1. Subsequent studies conducted in the United States and European countries (Ansell et al. Method Used to Set the Adequate Intake No functional criteria of vitamin K status have been demonstrated that reflect response to dietary intake in infants. Vitamin K content of colostrum is slightly higher than that of mature milk, but concentrations do not vary significantly through the first 6 months of lactation (Canfield et al. Vitamin K content of human milk can be increased by maternal intakes of pharmacological doses of vitamin K (Greer et al. In a study by Greer and coworkers (1997), supplementing mothers with a dose of 5 mg/day of phyllo quinone for 12 weeks increased the vitamin K concentration of milk by 70-fold (82. However, these values exclude intakes from human milk and in clude only intakes from other food sources. Vitamin K has been shown to specifically and reversibly bind to a protein complex in cow milk (Fournier et al. Reported phylloquinone intakes of older adults have generally been higher than those of younger individuals, a finding explained by their higher intakes of vegetables (Booth et al. Older subjects have been found to be more resistant to vitamin K deficien cy than younger adults (Ferland et al. Furthermore, there are no data on the vitamin K content of fetal tissue for estimating additional needs during preg nancy. In the Total Diet Study, phylloquinone intakes of pregnant women were lower than those of nonpregnant women (Appendix Table E-1). Although supplementation with pharmacological doses of vitamin K during the later stages of pregnancy has been shown to increase plasma concentrations of vitamin K and improve coagulation func tion of pregnant women in some studies (Anai et al. Reported vitamin K intake of pregnant women does not differ significantly from those of nonlactating women. There was no significant correlation between phylloquinone intake and breast milk concen tration. Although the phylloquinone content in maternal milk can be in creased after treatment of mothers with pharmacological doses of vitamin K (Greer et al. Over the last decade, rapid and reliable chromatographic proce dures for vitamin K have been developed, and data for the phyllo quinone content of most commonly consumed foods are available (Booth et al. Only a relatively small number of food items (Table 5-3) contribute substantially to the dietary phylloquinone intake of most people. Plant oils and margarine are the second major source of phylloquinone in the diet. Prepared foods contain variable amounts of vitamin K depending on their content of green vegetables and the source and amount of oil used in their preparation. Spinach, collards, broccoli, and iceberg lettuce are the major contributors of vitamin K in the diet of U. Hydrogenation of plant oils to form solid shortenings results in some conversion of phylloquinone to 2, 3 dihydrophylloquinone (Davidson et al.

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He gazed at her face for a few seconds medications to treat bipolar buy herbolax 100 caps visa, as if trying to read the expression, and then off he went. She looked out of the kitchen window and watched him run across the grass towards Alicia. As he ran through a group of four girls, she noticed one of them deliberately put out her foot to trip him up. A lack of social understanding, limited ability to have a reciprocal conversa tion and an intense interest in a particular subject are the core features of this syndrome. It was not until the late twentieth century that we had a name to describe such individuals. By the mid-1940s, the psychological study of childhood in Europe and America had become a recognized and growing area of science with significant advances in descriptions, theoretical models and assessment instruments, but Asperger could not find a description and explanation for the small group of similar and unusual children that he found intriguing. The children had difficulty making friends and they were often teased by other children. There were impairments in verbal and non-verbal communication, espe cially the conversational aspects of language. The grammar and vocabulary may have been relatively advanced but, at the end of the conversation, one had the impression that there was something unusual about their ability to have the typical conversation that would be expected with children of that age. Asperger also observed and described conspicuous impairments in the com munication and control of emotions, and a tendency to intellectualize feelings. The children also had an egocentric preoccupation with a specific topic or interest that would dominate their thoughts and time. Some of the children had difficulty maintain ing attention in class and had specific learning problems. Asperger noted that they often needed more assistance with self-help and organizational skills from their mothers than one would expect. He also noted that some children were extremely sensitive to particular sounds, aromas, textures and touch. Asperger considered that the characteristics could be identified in some children as young as two to three years, although for other children, the characteristics only became conspicuous some years later. He also noticed that some of the parents, especially the fathers of such children, appeared to share some of the personality characteristics of their child. He wrote that the condition was probably due to genetic or neurological, rather than psychological or environmental, factors. In his initial and subsequent publi cations and a recent analysis of his patient records for children he saw over three decades, it is apparent that he considered autistic personality disorder as part of a natural continuum of abilities that merges into the normal range (Asperger 1944, 1952, 1979; Hippler and Klicpera 2004). He conceptualized the disorder as a life-long and stable personality type, and did not observe the disintegration and fragmentation that occurs in schizophrenia. He also noted that some of the children had specific talents that could lead to successful employment and some could develop life-long relationships. She had observed that some children who had the clear signs of severe autism in infancy and early childhood could achieve remarkable progress and move along the autism continuum as a result of early diagnosis and inten sive and effective early intervention programs (Wing 1981). The previously socially aloof and silent child now wants to play with children and can talk using complex sen tences. Where previously there was motivation for isolation, the child is now motivated to be included in social activities. After many hours in intensive programs to encourage communication abilities, the problem is no longer encouraging the child to speak, but encouraging him or her to talk less, listen and be more aware of the social context. Many adults who are diagnosed in their mature years say that the first time they felt different to others was when they started school. They describe being able to understand and relate to family members, including playing socially with brothers and sisters, but when they were expected to play with their peers at school and relate to a teacher, they recognized themselves as being very different from children their age. When I ask these adults to describe those differences, the replies usually refer to not being interested in the social activities of their peers, not wanting to include others in their own activities, and not understanding the social conventions in the playground or classroom. The diagnostic pathway commences when an experienced teacher observes a child who has no obvious history of characteristics associated with autism, but who is very unusual in terms of his or her ability to understand social situations and conventions. The child is also recognized as immature in the ability to manage emotions and to express empathy. There can be an unusual learning style with remarkable knowledge in an area of interest to the child, but significant learning or attention problems for other academic skills. The teacher may also notice problems with motor coordination such as handwriting, running, and catching a ball. The child may also cover his or her ears in response to sounds that are not perceived as unpleasant by other children. When in the playground, the child may actively avoid social play with peers or be socially naive, intrusive or dominating. The teacher may also notice that the child becomes extremely anxious if routines are changed or he or she cannot solve a problem. The child is obviously not intellectually impaired but appears to lack the social understanding of his or her peers. The teacher knows that the child would benefit from programs to help in his or her understanding of the social conventions of the classroom and school playground. At a subsequent meeting of parents and representatives of the school, parents are encouraged to seek a diagnostic assessment both to explain the unusual behaviour and profile of abilities, and for the parents and school to achieve access to appropriate programs and resources. The two diagnoses are not mutually exclusive and a child may benefit from the medical treatment and strategies used for both disorders.

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In general treatment effect definition buy herbolax with paypal, the scope of knowledge required for the various categories of personnel is as follows. Training syllabus the level of training in radiation safety required depends on the type of facilities available and techniques performed, and may differ considerably between institutions. The training course for trainers, however, must be of a consistently high standard. Both syllabus and duration of training will depend not only on the target group (see above) but also on whether the course to be conducted is, for example, an introductory course, a specialized or customized course, or a course leading to the award of a degree, diploma or certificate. Provision of training In some countries, radiation safety is included in the training of technolo gists and nuclear medicine physicians. Depending on their background, physicists may or may not have had any radiation safety training. Alternatively, some countries may wish to establish a centre of excellence with advanced facilities to work as a hub and disseminate learning to an entire region. Experts from reputable centres could also provide training at the local site, depending on its requirements. The use of radionuclides is proposed in a large variety of molecular biology protocols as they can be easily traced. The availability of practical ways of detecting the presence of a radionuclide in a specific molecule (qualitative result) and its potential to be measured (quanti tative analysis) are the main reasons why radionuclides are important in molecular biology. In the theoretical and practical training in molecular biology techniques and also in radionuclide handling, some specific points should be considered, such as the transfer of technology to scientists and technicians from other research fields (immunology, pathology and microbiology) who are not familiar with molecular biology and radionuclide techniques, and upgrading the skills of experienced scientists regarding the use of new protocols in molecular biology. If these aspects are not recognized, there may be a real risk of courses being either too profound to those who are not familiar with the techniques or very superficial to others who have these skills already. Selection of the participants the best way of selecting those who will be attending the training initiative is to evaluate the previous involvement of the candidate in the course topic. Sometimes a simple curriculum vitae analysis is not sufficient to determine the suitability of candidates. Therefore, alternative criteria have to be used in addition, such as prospective participants supplying a summary of work they propose doing linked to the training theme and a list of their recent publications. The candidate should be able to specify the objectives of their project, to detail the importance of the methodology that will be learnt and how the techniques will be applied in solving specific problems. Course content Owing to the complexity of the protocols that are usually carried out in molecular biology training courses, the trainees should have access to the theoretical and practical programmes in advance. Participants should be informed beforehand about the possibility of bringing samples, when possible and allowed, to be tested in the course. Participants should also be asked to present ongoing relevant work they are involved with. In addition, they should be asked beforehand to bring results, if they have any, illustrating the problems they have experienced and thus be actively involved in the troubleshooting section. One point that needs to be emphasized in the course is the handling of radioactive material and disposable waste. Guest visits and fellowships In the vast majority of cases, the simple transfer of technology during a training course is not enough to allow participants to set up the methodologies in their own setting. Difficulties are always encountered and adaptations of the protocols are necessary. It is important to emphasize during training that there are specific points related to the performance of the protocols which can be modified without compromising the perfect outcome of the assay. The possibility of making adaptations to a formal protocol is linked to a previous professional background in the area. If local expertise in molecular biology is lacking, an alternative could be an expert guest visit. This professional will take into consideration the local conditions and the availability of equipment and supplies, analysing the real situation on the spot. Experiments will be performed, in conjunction with the group, by the expert and eventual difficulties can be solved, alternatives proposed and the best logistics worked out. Fellowships should also be offered by the training institution to junior scientists who could spend more than one month analysing samples collected in their settings. The interesting point of this possibility is that the trainee will learn the protocols as they are performed in standard conditions and will also gain experience of the logistics of the reference laboratory. New and specific binders can be produced in large quantities because of the availability of the technology to generate monoclonal antibodies from hybridomas, heterohybri domas, recombinant phages, oligonucleotide arrays (for construction of antibody arrays) and, recently, synthetic binders from polymers or plastic moulds. Protein binders can also be engineered according to design by molecular modelling and point mutagenesis, then humanized by the recombinant phage technique. The availability of non-isotopic labels such as silver and gold sol has further stimulated the development of sensitive dipstick immunochromatographic assays which enable semi-quantitative point-of-care testing and self-testing to be carried out in clinics, wards and the home. The recent invention of conductive polymers and the rapid advances in optics enable the design of immunosensors. In addition, there have also been rapid advances in solid phase design, techniques in immobilization of chemicals such as self-assembly of monolayers, and molecular visualization and micromachinery by atomic force microscopy. These will certainly be applied to immunoassays in future to increase assay sensitivity and specificity. In more developed countries which are striving to achieve a comprehensive long term development of diagnostic biotechnology, the method will be used more frequently in the production processes of monoclonal antibodies. Principle Radioimmunoassay continues to maintain a favoured position among microanalytical procedures not only because of its sensitivity, acceptable precision, robustness (working best in non-optimal conditions) and wide appli cability, but also because it is comparatively the least expensive of numerous methods available for the detection and measurement of substances of clinical diagnostic interest. It is amenable to bulk reagent based methodology, using at least some locally produced reagents, in contrast to methods totally dependent on black box type commercial kits. It has been computed that, while the dose from a single transatlantic flight equals 0. Academic personnel who will serve as laboratory managers need to be trained to a higher level, preferably postgraduate, than laboratory technicians, additionally learning interpretative skills according to their study approach (technical, scientific and/ or medical). It should be borne in mind that technicians using bulk reagents for in-house assays need a more thorough training than those who are merely using protocols provided with commercial kits. Similarly, greater use is being made of solid phase separation methods, particularly of those not requiring centrifugation, despite a possible slight increase in cost. In these and similar areas where a range of alternative approaches is available, the technical and economic advantages and disadvantages of each should be considered so that the workers concerned may arrive at informed decisions as to the most suitable approach for their particular situation. Academics and technicians would all require training in these areas, although academics would require more in-depth knowledge of, for example, the theoretical and mathematical concepts involved in designing an assay to suit a particular need. Laboratories in countries with high socioeconomic strength should place additional emphasis on cost effective overall laboratory management, critical evaluation of reagent supplies and on making the methodology more friendly to the user. Training should, however, also include the accepted standard operation procedures that manufacturers are expected to carry out before the batch release of the reagents. Training should include standard methods of assay validation (cross-reactivity, recovery and parallelism) and the means by which all essential features of an assay such as precision, bias, working range or sensitivity are ascertained before it is made available for clinical or research use. Workers should also be made aware that these characteristics cannot be fully determined and that they may change with fresh batches of reagents or other changes in assay conditions. In this context, knowledge of the stability and storage conditions to which different reagents may be subjected, such as stock and working solutions of standards and antisera, buffers and protein binding inhibitors, is necessary for preventing possible later problems. They should understand the concepts of within and between batch variability, the construction of quality control charts and curves, and of imprecision profiles and how these are used, in order to decide upon statistical acceptance or rejection of an assay result (or an entire assay on the basis of pre-set standards of precision and bias). The main causes of poor precision or unacceptable bias, especially when these are seen to occur in an assay that had previously been performing well, need to be understood so that remedial action can be taken at an early stage. Radioimmunoassay workers should be trained to use a suitable data processing package in their day-to-day work. A laboratory attached to a small hospital may provide only a clinical service confined to analytes of common clinical importance, such as thyroid related hormones, and find it most practical and economical to meet all of its reagent requirements from outside sources, whether abroad or local. Other centres that provide an expanded service may choose to produce at least some of the required primary reagents. These may range from the simplest, such as standards and quality control material for simple analytes of unique molecular structures for the commonest assays such as thyroid hormones and cortisol, to more sophisticated materials such as solid phases, tracers and antisera. Consequently, appropriate training in reagent production techniques should correspond to the type of laboratory the workers concerned are employed in. It would, however, be economically wasteful for a small centre with a workload of a few hundred samples per month to produce its own 125I tracer using imported 125I. In general, the larger the centre and the wider the scope of activity, the more worthwhile it is to train staff to produce their own working reagents.

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Relation of serum C reactive protein and erythrocyte sedimentation rates to disease activity symptoms multiple sclerosis purchase 100caps herbolax overnight delivery. Infliximab for recurrent, sight threatening ocular inflammation in Adamantiades-Behcet disease. Progressive aortic valve inflammation occurring despite apparent remission of relapsing polychondritis. Association of myelodysplastic syndrome with relapsing polychondritis: Further evidence. Relapsing polychondritis: Prospective study of 23 patients and a review of the literature. A new animal model for relapsing polychondritis, induced by cartilage matrix protein (matrilin-1). The occurrence of autoantibodies to matrilin 1 reflects a tissue-specific response to cartilage of the respiratory tract in patients with relapsing polychondritis. Sustained response to infliximab in 2 patients with refractory relapsing polychondritis. Treatment of respiratory complications in recalcitrant relapsing polychondritis with infliximab. Incidence of ocular complications in rheumatoid arthritis and the relation of keratoconjunctivitis sicca with its systemic activity. Sterile corneal ulceration after cataract extraction in patients with collagen vascular disease. Scleritis associated with Rheumatoid Arthritis and with other systemic immunemediated diseases. A study of their clinical manifestations and association with rheumatoid arthritis. Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. In Pleyer U, Mondino B (eds) Essentials in Ophthalmology: Uveitis and Immunological Disorders. Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondylarthropathy. The spectrum of eye involvement in patients with systemic lupus erythematodes without ocular symptoms. Incidence of hydroxychloroquine retinopathy in 1207 patients in a large multicenter outpatient practice. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy: a report by the American Academy of Ophthalmology. Sulfazalazine in the prevention of anterior uveitis associated with ankylosing spondylitis. Panuveitis and multifocal chorioretinitis in a patient with leucocytoclastic vasculitis. Cogan-syndrome: studies in thirteen patients, long term follow up, and a review of the literature. Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation. Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death. Human telomerase is regulated by erythropoietin and transforming growth factor-beta in human erythroid progenitor cells. Role of cytokines in the pathogenesis of anemia of chronic disease in rheumatoid arthritis. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Hepcidin, iron status, and renal function in chronic renal failure, kidney transplantation, and hemodialysis. Serum Pro-hepcidin Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus. Anemia in early rheumatoid arthritis is associated with interleukin 6-mediated bone marrow suppression, but has no effect on disease course or mortality. Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade. Effect of recombinant human erythropoietin on anaemia and disease activity in patients with rheumatoid arthritis and anaemia of chronic disease: a randomised placebo controlled double blind 52 weeks clinical trial.

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The researchers background symptoms kidney failure dogs purchase 100 caps herbolax overnight delivery, interests and context were declared, and measures were taken to ensure reflexivity throughout the research process. Sampling bias was minimised by inviting all children that participated in study one to take part in in study two. All children that participated in the first study were invited to participate in the second study. Participants were asked if they would like a familiar adult to accompany them in the interview, as suggested by Brewster and Coleyshaw (2011) as a method to reduce anxiety. Participants were asked if the interview could be recorded using a Dictaphone; however, no children objected to the use of a Dictaphone. Language used in interviews was adapted to meet the needs of individual children to promote understanding and reduce anxiety. The researcher was familiar with each of the participants so was able to adapt language accordingly. After the introduction, the main body of the interview began with an open question about how the children found Lego Club. Picture cards were introduced only when it became apparent that children required non-verbal prompts to elicit further information. Three visual cards were laid out to represent emotions relating to enjoyment, to help make an abstract concept more concrete (see Appendix 30). Picture cards were designed to represent different aspects of Lego Therapy, and the children were asked to order the cards from the things they enjoyed the most through to the things that they enjoyed the least. This provided children with the opportunity to focus on a task, which was a method recommended by Beresford (2004) to reduce social anxiety. The term enjoyment is familiar and accessible to the age of the participants involved. The positions that the children placed the cards in were used to prompt further questions about Page | 109 aspects of Lego therapy. Consequently, the order of the interview was determined by the order of the cards rather than by the interview schedule. The interview ended with an open question to enable participants to discuss anything else that had not been covered. The hierarchical focussing method provided a framework for structuring initial open questions and prompts. Individual interviews were favoured over focus groups in this particular study because there was often conflict in relationships within Lego therapy groups. Individual interviews were chosen to provide children with the opportunity to openly discuss their perceptions on relationships with others in the group. Visual support cards were used to aid memory of events and to help make abstract concepts more concrete (see Appendix 30). Thematic analysis was first compared to alternative methods of analysis to ensure that it was the most appropriate technique (see Appendix 34). Thematic analysis was considered to be the most appropriate method of analysis because it can be used within a range of theoretical approaches (Braun & Clarke, 2006) and was therefore suitable for the Page | 111 post-positivist paradigm adopted in this study. Conversely, in an inductive method of analysis codes and themes emerge from the data. Thematic analysis was conducted following a hybrid approach to thematic analysis (Fereday & Muir-Cochrane, 2008). Whilst previous research has made suggestions about the theoretical assumptions that underpin motivation to engage in Lego Therapy, previous research has not explored or tested such assumptions. The research questions were underpinned by psychological theory; namely systemising and intrinsic motivation. Inductive coding of the data enabled themes to emerge freely without being limited to existing theories. Table 9: Stages followed in thematic analysis Stage Details of process (from Braun and Clarke, 2006) 1. This involved merging themes together and deleting or merging themes with insufficient data to support theme. Defining and naming Definitions for each theme were generated themes and names of themes were altered to reflect what each theme represented 6. Further amalgamation of themes occurred at this stage, and names and definitions were amended to reflect the changes to themes. The meaning attached to the codes was comparable so the decision was made to proceed with the analysis. Children were informed of the aims of the research and interview, the time that the interview would take, who the interview would be shared with, limits of confidentiality, and how results will be shared with them. Electronic data were anonymised when inputted, and all data were stored on a password protected laptop. The researcher emphasised that participation was optional to ensure that participants did not feel that they were expected to take part. The children were also told that there were no right or wrong answers to reduce anxiety and acquiescence in responses. All participants were given the opportunity to ask questions at the end of the interview and were verbally debriefed. Contact details of the researcher were given to both parents and school staff in case any follow up questions emerged. The themes will be presented according to the research questions for this study, and additional illustrative data for each theme can be found in Appendices 40-43. Page | 118 Inherent interest and ability in Lego There was a sense of passion and enthusiasm conveyed when children spoke about Lego. Comments made suggested that children were inherently interested in Lego as a medium and it was an activity that they felt they were successful in. Many children spoke about spending time building Lego at home, suggesting that it is an activity that they engage in out of choice in their free time. Many children spoke about enjoying being able to build lots of different things with Lego and enjoyed the creative aspect of Lego building. So they were very stable, but I think the skyscrapers could fall over just by being touched. No children spoke negatively about Lego as either a medium or in relation to their abilities. Children felt like they were part of a team, suggesting that they understood and accepted that Lego therapy session required group work and a division of labour. It is possible that children enjoyed the social aspects of Lego therapy because interactions were centred on a shared task focus and children had similar interests. Freestyle building All of the children interviewed spoke positively about freestyle building, and the majority of the children rated freestyle building as their favourite aspect of Lego Therapy.

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Stage 6: resting state Cricopharyngeus resumes its tonic state of closure once the bolus has passed symptoms nasal polyps order cheap herbolax on-line. The absence of any stimulus in or around the vestibule will allow reopening of the glottis, and the larynx to lower. When studying the physiological sequence of a swallow it must be remembered that all of this occurs with split-second timing. Our outline above suggests that one event follows neatly after the next and then the next. In reality the timing of the oral phase for a liquid bolus is a second, and the timing of the pharyngeal phase for all boluses is also a second. New research has opened our eyes to the crucial role the cortex and other parts of the brain all play in execution of this task, while offering an insight into many clinical manifesta tions of dysphagia that until recently have been incorrectly explained. In addition, an appreciation of exactly where a swallow becomes automatic has been gained, increasing the need for a clinician to understand, for example, that residual pooling of material in the valleculae may in fact be normal (see Chapter 3). As you progress through this text, let your grounding in what is normal be your guide in order that your diagnosis and treatment of dysphagia be achieved from rst principles. Mosier K, Bereznaya I (2001) Parallel cortical networks for volitional control of swallowing in humans. Jean A (2001) Brain stem control of swallowing: Neuronal network and cellular mechanisms. Yamamoto F, Nishino T (2002) Phasic vagal in uence on the rate and timing of re ex swal lowing. There are, however, some important differences between the adult and infant swallow and even between adult and infant oropharyn geal structures. This chapter will cover the process of suckle, suck and swallow in the infant and will also discuss transitional feeding. Humans, do not, however, reach a stable state once normal chewing and swallowing patterns have been achieved. Many of these are discussed in other chapters of this text; however, the broad changes that occur with ageing will be highlighted here. This involves a high degree of coordina tion in order to feed effectively and, at the same time, to protect the airway. As infants grow they also develop skills that allow them to move from thin liquids to the wide variety of textures that adults enjoy. Excellent texts have been devoted to the paediatric feeding and swallowing mechanism, pattern of development, and pathology (Wolf and Glass, 1994; Arvedson and Brodsky, 2002). This section serves to alert the reader to some important considerations when examining the infant swallow and its maturation. Certainly it seems like overkill to start as far back as embryologic development; Dysphagia: Foundation, Theory and Practice. The following brief discussion highlights aspects of the development of the branchial arches that may be of interest to the dysphagia clinician. These are the ec toderm, mesoderm and endoderm and they are otherwise known as the neural crest cells. These layers provide the basis for the development of the skin and nervous system (ectoderm), smooth muscle, connective tissue and blood vessels (mesoderm), and digestive and respiratory systems (endoderm). The three germ layers give rise to all tissues and organs of the embryo (Moore, 1973). Early in the fourth week after conception, the branchial arches develop from these neural crest cells. All ver tebrae, and speci cally the head and neck, develop from the branchial arches and their constituents. More speci cally the face, neck, nasal cavities, mouth, larynx and pharynx along with muscular attachments for the head and neck are all derived from the branchial arches (Arvedson and Brodsky, 2002). There are six pairs of branchial arches with each being separated from each other by obvious branchial grooves (also known as clefts). Each branchial arch develops into speci c skeletal structures and muscles and their nerve supply. In short, this is because the tongue is formed by a number of the branchial arches. Taste for the anterior two-thirds of the tongue is supplied by the facial nerve (second branchial arch), whereas taste for the poste rior third of the tongue is supplied by the glossopharyngeal nerve (third branchial arch). In addition, a small area of the tongue anterior to the epiglottis is supplied by the superior laryngeal nerve of the vagus nerve (fourth branchial arch) (Moore, 1973). Although it is confusing it helps to explain the many dimensions of this single structure. The rst branchial arch gives rise to the upper and lower jaw, the malleus and incus of the inner ear and the trigeminal nerve. The second branch provides por tions of the hyoid bone and stapes of the inner ear, among other structures, and the facial nerve. The rst and second arches provide the mouth, tongue and muscles of mastication, and the facial nerve (Moore, 1973; Tuchman, 1994). The third brancial arch contributes portions of the hyoid bone, the posterior third of the tongue and a portion of the epiglottis and pyriform sinuses, while the fourth and sixth arches give rise to the tongue, laryngeal cartilages, epiglottis and inferior pharyngeal constric tors (fourth arch). The third branchial arch provides the glossopharyngeal nerve and the hypoglossal nerve. The fourth and sixth branchial arches give rise to the vagus nerve and speci cally the recurrent laryngeal nerve and the superior laryngeal nerve (Arvedson and Brodsky, 2002). Brie y, these pouches de velop into the Eustachian tube, the tonisllar fossa region, the parathyroid glands and the thymus (Moore, 1973). The fact that these systems develop from the one embryonic structure shows that these systems are by nature linked together. The underbelly of the laryngotracheal tube eventually becomes the larynx, tra chea, bronchi and lungs. This early development (fourth week) shows that the respiratory and deglutitory systems are tightly woven together from the very early stages of gesta tion. It is hardly surprising to nd the two systems working in the harmony that is required to sustain life, both by breathing and swallowing. It also provides excellent reason to look at the syncrhonization of the respiratory and swallowing systems (see Chapter 4). They indi cate that this would account for the concurrent limb abnormalities found in children with orofaciodigital syndromes. The epiglottis and larynx are clearly identi able by day 41 of life (approximately 6 weeks) (Koempel and Holinger, 1998). These mostly concern the relative size of the various structures relating to swallowing. Beginning with the oral cavity, note that the distance between the velopharyngeal region and tongue base increases from around 20mm at 3 months to 27mm at 4 years.

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Phosphorus-32 has the advantage over other radionuclides in that high specific activities can be readily attained symptoms of flu buy herbolax 100caps without prescription. However, precautions must 32 be taken when handling P because of the radiation emitted (Chapter 2). Detection by autoradiography, while sensitive, may take a long time if there are few counts in the hybrids. The probes should be boiled prior to addition to the hybridization solution in order to be single stranded. In some cases, it is preferable to apply these labelled probes directly to cells and tissues to localize the source of the signal. Following several washing steps, a detection method is used to localize the signal indicating areas in which the probe has bound to the tissue. When radioactive probes are used, the tissue sections on microscope slides are dipped in a silver emulsion similar to an X ray film. These slides are kept in the dark for a period of time (from days to weeks) after which the emulsion is developed in a fashion similar to developing a film. Introduction the therapeutic use of radionuclides may be a potential radiation risk for both family members and individuals close to the patient, as well as health workers and the environment. Radionuclides must be used in strict accordance with safety measures and any special instructions, and all precautions must be taken to avoid unnecessary exposure to radiation. This chapter summarizes the steps to be taken before commencing therapy procedures. Licensing the administration of therapeutic doses of radionuclides must be under the responsibility of a physician who is licensed under national regulations to administer radioactive materials to humans. Radioactive material for diagnosis or therapy should only be used and stored at medical institutions which have purpose designed facilities. Licensing requirements vary from country to country and may even include minimum design and construction requirements for the facility. Facility design and construction the general principles for the design of nuclear medicine units are discussed in Chapter 3, and further information regarding therapy units is provided in Section 6. When designing therapy units, it is important to bear in mind the following: (a) Patients must be housed in a separate room, with dedicated bathroom and toilet. Close cooperation between the nuclear medicine staff and architects and builders is vital. If an existing space is to be modified, it may be necessary to determine experimentally the adequacy of walls and floors as radiation shields. If any building work is to be performed, a regular inspection of work in progress is advisable to ensure adherence to agreed plans and specifications. Responsibilities the physician administering the therapeutic radionuclide dose is ultimately responsible for taking every precaution to avoid unnecessary radiation to staff, other patients, visitors and the general public. Before commencing therapy, agreement should be reached on medical and radiation safety protocols. Training Radionuclide therapy may involve staff outside the nuclear medicine department, especially nurses and medical staff. A little effort devoted to famil iarization and training in the medical and safety aspects of radionuclide therapy can avoid potentially serious problems later. General principles Radionuclide therapy presents relatively few hazards to staff and patients, but there are a number of common principles of radiation safety that have to be observed. This section will consider the requirements for patient accommodation (design requirements including shielding), as well as radiation safety procedures necessary for safe practice. For safety purposes, each therapy can be divided into different stages, with specific safety issues that may need to be considered (Table 6. The specific radiation safety issue for each of the common therapies is discussed later in this section. Discharge limits Patients may be discharged only when the remaining activity is less than that prescribed by the local regulatory authority. This can be estimated using a simple ratio of dose rates at a standard distance referenced to the dose rate immediately following dose administration, or by measurement of a dose rate alone. This information is often modified to take into account the specific circumstances of each patient. Normally, the only difference between therapy areas is in the degree of any shielding required and the issues involved in integrating inpatient areas into a ward, such as access control and toilet facilities. Patient comfort should be catered for by radio, music, television and/or videotape facilities as well as a comfortable (but easily decontaminated) chair. A floor drain is advisable in case of spillage of the therapy radiopharmaceutical. General inpatient therapy guidelines Most inpatient therapies involve 131I, as reflected in the guidelines given below. If radiopharmaceuticals with a low risk of contamination are involved, the guidelines may be suitably modified. No member of staff should enter the therapy room without wearing a radiation monitor. Where digital dosimeters are in use, a record of the dose and the name of the staff member should be kept with the monitors outside the treatment suites. No blood samples, urine or faecal samples should be collected without nuclear medicine approval. As the barrier is crossed on leaving the room, this protective clothing must be removed and placed in the disposal bag provided. Guidelines relating to the patient the following guidelines apply: (a) the patient must be aware of the basic regulations listed below before the administration of a radionuclide. Before therapy, the patient should be given a booklet of common questions and answers. If they wish to wear their own clothes, they must be advised on what should be done with garments on discharge. Ideally, there should be a refrig erator to keep milk fresh, and to store cold drinks if required. This encourages the patient to drink freely and reduces the radiation exposure to nursing staff. Under no condition should it be sent to the laundry until checked for contamination. This may involve storage prior to incineration in a licensed incinerator or storage until complete decay of the contamination. Patients should only leave the therapy room for the purpose of a scan or in an emergency, in which case protective clothing. Unless an emergency precludes this, protective clothing should be put on upon leaving the room and removed on re-entry to the suite. Any other belongings that may have become contaminated must be stored for a suitable length of time to allow the radioactivity to decay. The patient should be given a discharge card listing the radionuclide and activity administered, the activity on discharge and any necessary precautions. Contamination With any radionuclide therapy, there is a high potential for contami nation. It is, however, strongly advisable to keep a small decontamination kit in or near the therapy area (inpatient or outpatient) for immediate access if required. Radioiodine therapy (a) Pre-therapy It is imperative that a doctor explain to female patients that therapy cannot be given to pregnant patients. If there is any chance that a patient may have become pregnant by the time the therapy administration is to commence, she must report this to a nuclear medicine doctor or technologist. Because of the significantly greater radiation hazards from liquid sources, the comments below assume the use of capsules.

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An inbred strain of mouse was shown to have non-optimal physiology when the mitochondrial genome from a different inbred line was crossed in (10 backcrosses to the nuclear line all using the female descendent from the frst mitochondrial donor) [107] treatment laryngitis cheap herbolax 100caps line. On the other hand, hu man mitochondrial transfer experiments have found no analogous effect [109], arguably, owing to the different genetic structure of our species when compared to inbred mouse strains [110]. Mytilus mussels exhibit complex patterns of mitochondrial and nuclear introgression, refecting multiple historical and recent hybridization events, some following introduction of non-native species for aquaculture. No matter which mecha nism for speciation is responsible in any specifc case, the 0. The variable distance between the most closely related living species presumably refects differing numbers of extinct intermediate sequences. Conditions that favor clonal uniformity are frequent in biology Bottlenecks, founder effects, lineage sorting, and gene sweeps decrease genetic di versity in a population [111]. The question is how widespread these effects are in the context of defning animal species and if it is possible distinguish them in other than a rhetorical manner. Based on contemporary mitochondrial sequence data alone it is impossible to distin guish an organismal bottleneck from mitochondrial and Y chromosome specifc lineage sorting since both mechanisms make the same prediction of a uniform mitochondrial sequence in the past [112]. A positively selected allele has the potential to sweep through a population and by hitchhiking [113, 114] or genetic draft [115] carry the entirety of the linked genome along thereby resetting mitochondrial variation to zero. It is reasonable to hypothesize that somewhere on the mitochondrial genome there arises a positively selected amino acid substitution leading to the replacement of the entire linked genome in the entire population. These three pathways toward sequence uniformity should not be thought of as en emies because they converge in both cause and effect. Lineage sorting is most effcient when the population is small, when the number of different mitochondrial genotypes is small, and when the population is either stable or shrinking [116]. An extreme di minishment of population size followed by population expansion is the defnition of a bottleneck. Lineage sorting is diminished during periods of population growth and does not occur at all during exponential growth when all neutral lineages leave progeny [117, 118]. The same conditions that favor lineage sorting also favor gene sweeps, which in the context of a totally-linked genome means one mitochondrial genome. Ever since Koch, microbiologists have streaked out their bacteria to begin experiments with pure, i. The frst experiments showing evolu tion of new mutants from clonal starting populations were the classical cases of proof that bacterial genes follow the patterns expected from random mutation that grow indis tinguishably from sibs when unselected ([117, 121-123]). Clonal outgrowth and replace ment of the inoculating population was inferred from the earliest chemostat [124] as well as later serial transfer experiments [125]. Epidemiology shows that repeated bottlenecks play dominant roles in the natural evolution of microbial pathogens including protists, bacteria and viruses [126-132]. A visually impressive demonstration of successive clonal selection and population outgrowth is seen in time lapse studies of bacteria serially mu tating to new heights of antibiotic resistance [133]. Average effective population size in the birds shown is 70 thousand (range 0-300 thousand); average census population size is 30 million (range 5 thousand to 500 million). Mayr made a specifc proposal for the role of extreme bottlenecks in speciation that followed from a founder effect (originally 1942, here quoted from a reprise based on interviews in 2004 [136]): the reduced variability of small populations is not always due to accidental gene loss, but sometimes to the fact that the entire population was started by a single pair or by a single fertilized female. Eldredge and Gould used this idea of allopatric speciation in small isolated popula tions that then rapidly expanded to account for the abrupt transitions seen in the broad range of the fossil record [137]. Models of allopatric or peripatetic speciation invoke a bottleneck with an additional feature: What emerges from the bottleneck looks or acts differently, i. It may be more frequent that what emerges from a bottleneck looks and acts like a middling representative of what went in. A number of different processes could lead to the mitochondrial sequence becoming clonal. Candidate processes include bottlenecks and lineage sorting on three different levels: Within organelles, among organelles in the same cells, among cells in an organism (particularly in the germ line) and among organ isms. Not certain is whether different processes have led to a similar result throughout the animal kingdom or if a single process operates throughout. Purifying selection in linked genomes slows but does not stop the accumulation of neutral variation [139]. Drift and lineage sorting during population stasis or shrinkage decrease variation. The effciency of decrease depends on the number of haplotypes in the population, as well as the numbers and distributions of female offspring among parents with different haplotypes [10]. A key prediction of naive neutral theory that does not hold up against extensive barcode data from across the animal kingdom is that larger populations or older species should harbor more neutral variation [20, 140, 141]. The evolution of modern humans offers a specifc solution to the animal-kingdom-wide dilemma of missing neutral mutations. Modern humans More approaches have been brought to bear on the emergence and outgrowth of Homo sapiens sapiens. The congruence of these felds supports the view that modern human mitochondria and Y chromosome originated from conditions that imposed a single sequence on these genetic elements between 100, 000 and 200, 000 years ago [145-147]. Contemporary sequence data cannot tell whether mitochondrial and Y chromosomes clonality occurred at the same time, i. Speciation occurs via alter native pathways distinct in terms of the number of genes involved and the abruptness of transitions [148]. Nuclear variance in modern humans varies by loci in part due to unequal selection [149] and the linkage of neutral sites to those that undergo differential selection. Complexity is the norm when dealing with variance of the nuclear ensemble [150-154]. It is remarkable that despite the diversity of speciation mechanisms and path ways the mitochondrial sequence variance in almost all extant animal species should be constrained within narrow parameters. Mostly synonymous and apparently neutral variation in mitochondria within spe cies shows a similar quantitative pattern across the entire animal kingdom. The molecu lar clock as a heuristic marks 1% sequence divergence per million years which is consis tent with evidence for a clonal stage of human mitochondria between 100, 000 200, 000 years ago and the 0. The simple hypothesis is that the same explanation offered for the sequence variation found among modern humans applies equally to the modern populations of essentially all other animal species. Namely that the extant population, no matter what its current size or similarity to fossils of any age, has expanded from mitochondrial uniformity within the past 200, 000 years. Fossil evidence for mammalian evolution in Africa implies that most species started with small founding populations and later expanded [157] and sequence analysis has been interpreted to suggest that the last ice age created widespread conditions for a subsequent expansion [158]. The characteristics of contemporary mitochondrial vari ance may represent a rare snapshot of animal life evolving during a special period. Al ternatively, the similarity in variance within species could be a sign or a consequence of coevolution [159]. There is irony but also grandeur in this view that, precisely because they have no phenotype, synonymous codon variations in mitochondria reveal the structure of species and the mechanism of speciation. Sloan Foundation and Monmouth University/Rockefeller Univer sity Marine Science and Policy Initiative for support.