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Sources of Information and Review Methods the sources of information consulted and review methods used by the Duke team varied considerably by key question. Question 2 and Questions 3-4 required separate literature reviews using distinct sources, search strategies, and review methods. Because of this variability, we describe the methods used for each key question separately. Heart Valves in Use and Development We used four approaches to identify heart valves now in use or in development. First, we identified valves described in the published literature abstracted in answer to Question 2 (conventional valves) and Questions 3 and 4 (percutaneous valves). Next, we generated a list of valve manufacturers based on the published literature and expert knowledge. Finally, we supplemented these approaches by searching the Web sites of valve manufacturers. To determine the theoretical advantages and disadvantages of different valves for different populations, we relied on discussions and recommendations in clinical guidelines, review articles, and consultations with experts. Using these sources, we developed a narrative description of the valve classes, goals in valve design, and the theoretical advantages and disadvantages of different types of valves. For Question 2, we scanned the existing literature comparing different types of conventional. We sought to describe the available comparative studies in terms of the number of available studies, interventions compared, basic study design, size of study, length of followup, and outcomes assessed. We identified potentially important observational studies primarily by reviewing the individual studies included in the systematic reviews that met our full-text inclusion criteria. A single reviewer screened the titles and abstracts of all citations for potential inclusion. Articles were included if they concerned conventional heart valves and appeared to be a review article. Citations included at the title-and-abstract stage were reviewed in full-text form independently by two researchers. Articles meeting the following criteria were included for data abstraction: the article was a systematic review, defined as a review including both a Methods section describing a search strategy and analytic approach, and abstractions of primary literature; and the review directly compared two or more different types of conventional heart valves; and the review concerned valve replacement (rather than repair); and the review focused on adults (all patients 18 years of age or, if mixed population, then either 80 percent adults or results reported separately for adults); and the review was published in English in the year 2000 or later. When the two reviewers arrived at different conclusions about whether to include or exclude an article, they were asked to reconcile the difference. The inclusion criteria applied at both screening stages were: Comparison of two or more heart valves for valve replacement (rather than repair); and Randomized allocation to treatment; and Study conducted in adults (all patients 18 years of age or, if mixed population, then either 80 percent adults or results reported separately for adults); and Study published in English. If there was any uncertainty about whether an article should be included, a second investigator was consulted.

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Approximately 85 percent of all patients (adults and children) with diabetes mellitus are categorized as type 2. Since type 2 diabetes mellitus is often very subtle, the number of undiagnosed cases of diabetes mellitus is significant. The other 15 percent of patients with diabetes mellitus nationwide are categorized as type 1. In the pediatric population, type 1 diabetes makes up a larger proportion of the cases. Although our estimates are quite crude, some centers report that approximately 98 percent of their children with diabetes have the Type 1 variety. This estimate will certainly be revised in the future as we recognize more type 2 diabetes in children. Insulin is the primary hormone that suppresses hepatic glucose production, proteolysis, and lipolysis. The first phase of insulin release is followed by a nadir and then by a relatively prolonged second phase of insulin release. Catecholamines, cortisol, growth hormone, glucagon, and gastrointestinal hormones among other hormones modulate the insulin response to glucose. Due to the portal circulation in the gut, blood draining the islet cells of the pancreas goes to the liver before returning to the heart. This portal circulation exposes the liver to an immediately high concentration of insulin soon after a meal. When treating diabetes with exogenously administered insulin into the systemic circulation, we need to remember that this does not duplicate the physiologic state. Insulin is an anabolic hormone that increases the transport of glucose into cells. A high insulin state will induce glucose uptake and inhibit amino acid release in muscle cells. In the liver, insulin will decrease glucose release and decrease ketone body formation. In our current understanding of the problem, people with type 1 diabetes mellitus have an underlying genetic predisposition to developing diabetes. On top of this predisposition, they are exposed to an environmental insult that triggers the immune response. In this way, not everyone who is genetically susceptible to type 1 diabetes mellitus will develop the problem. The identical twin of the patient with type 1 diabetes mellitus has a 25 to 50 percent risk of developing the problem in their lifetime. The antigens in these presenting molecules are the targets for the immune response. Mutations that lead to defects in the structure of this antigen presenting molecule predisposes to type 1 diabetes mellitus.

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Professor of Anatomy at the Royal a colourless oily liquid which occurs naturally Academy. They are passed out lenses which have two types of lens combined of the body in stools or urine and return to wa in the same piece of glass, the top part being ter, where they lodge and develop in the water snail, the secondary host, before going back used for seeing at a distance and the lower part into humans. Also called choluria it has been introduced or with which it is biliverdin brought into contact biliverdin /b li v!. Also called binocular /b n kj l / adjective referring to the two eyes circadian rhythm binocular vision biological parent binocular vision /b n kj l v n/ biological parent /ba l d kl noun ability to see with both eyes at the same pe r mt/ noun a parent who was physically time, which gives a stereoscopic effect and al involved in producing a child biologist lows a person to judge distances. Compare biologist /ba l d st/ noun a scientist who monocular specialises in biology binovular biology binovular /b n vj l / adjective referring to biology /ba l d i/ noun the study of living twins who develop from two different ova organisms 43 birth parent biomaterial biomaterial /ba m t ri l/ noun a syn production. Also calledmanic-depres substance in a living organism or biological sive illness, manic depression material such as blood or urine, usually to bipolar neurone bipolar neurone /ba p l nj r n/ check environmental pollution or chemical ex noun a nerve cell with two processes, a den posure drite and an axon, found in the retina. Compare plant (informal) multipolar neurone, unipolar neurone bionics birth bionics /ba n ks/ noun the process of ap birth /b!. Also called naevus treatment, especially the use of maggots or birth mother birth mother / b!. Also called fainting births per year, shown per thousand of the pop fit ulation a birth rate of 15 per thousand black spots black spots /bl k sp ts/ plural noun There has been a severe decline in the birth black spots in front of the eyes moving black rate. Compare bulla bled inside the heel, characterised by black spots bled /bled/ bleed 45 blood bank bleed blind study bleed /bli d/ verb to lose blood His knee blind study / bla nd st"di/ noun an investi was bleeding. He was bleeding from a cut on gation to test an intervention such as giving a the head.

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Therefore, a single quality-score cutoff for all four bases would alter the background base composition and may therefore bias analyses. We implemented a simple scheme that allows both for quality-score filtering and preservation of base composition. We examined the distribution of quality scores for each of the four bases for all six bones and found a quality score cutoff that allows a given percentage of the base under consideration to be included. Provided that the overall base-composition in our reads, without regard to quality score, is an accurate depiction of the underlying base-composition in the 18 library, this scheme will retain that true base composition. To achieve higher resolution than the discrete Phred scores allow, we define both quality score cutoffs and probabilities of accepting a base with quality equal to the cutoff that will exactly maintain a given percentage of the bases. The cutoffs and probabilities for each base that retain 95% of the Neandertal data are given in Table S12. These cutoffs were used for filtering low quality bases in alignments against hg18, panTro2, and the inferred common ancestor sequence. Because unusually high depth can be indicative of mapping problems or copy differences relative to the th reference sequence, we excluded sites whose coverage was above the 95 percentile. The genome-wide distribution of coverage from each Vindija bone, unfiltered for map-quality is shown in Figure S3. Peri-centromeric and peri-telomeric regions are noticeably higher covered, presumably due to the repeat content in these regions. For each of the Vindija bones, the coverage cutoff for further analysis used was 2 fold, i. We then randomly sampled at most a single base from each bone that passed the coverage and base quality cutoffs, to represent that nucleotide. Further pairs of reads were aligned and clustered together if they were over 90% identical (single linkage clustering) for all reads belonging to the same emulsion. Library Emul Pass filter Aligned Bases (hg18) Aligned Bases wells (hg18) (pantro2) (pantro2) sions L125 14 7916385 989,700 46,080,849 964,170 44,804,908 L127 9 2237902 258,574 11,585,634 250,463 11,191,005 L240+ L307 34 21691346 3,341,180 151,718,742 3,249,588 147,059,911 L241+ L308 28 25437529 3,621,903 162,107,257 3,522,842 157,226,631 L281 13 14877272 2,542,581 116,223,630 2,469,052 112,459,792 L282 12 10944779 1,816,636 81,835,788 1,761,932 79,129,241 L305 8 4082906 705,554 32,251,523 684,194 31,179,223 L306 6 2879380 536,271 24,549,000 519,858 23,722,762 L309 14 11076061 1,610,850 69,869,328 1,561,828 67,533,697 L310 16 12392471 1,956,178 85,835,292 1,898,475 83,007,661 L311 16 6896388 1,375,906 63,704,384 1,332,857 61,517,137 L262 17 13936002 2,319,563 109,090,376 2,246,742 105,386,501 L263 13 11660364 1,947,181 94,737,946 1,887,846 91,522,132 L312 19 15072677 2,133,314 98,791,555 2,066,766 339,089,415 L313 18 14555842 2,418,789 111,119,308 2,340,748 107,184,523 L314 20 14550798 1,356,737 62,113,625 1,318,085 60,144,415 L315 20 15353546 1,330,477 57,284,202 1,288,032 55,329,910 Total 277 205,561,648 30,261,394 1,378,898,439 29,363,478 1,577,488,864 21 Table S9: Summary of 454 Neandertal data used for downstream analyses based on alignments to the chimpanzee genome (pantro2). Megablast alignments were extended into semi-global alignments and discarded if the semi-global alignment produced a negative score. Further, redundancy due to library amplification was removed by clustering reads based on alignment coordinates (same chromosome, strand, start and end coordinate) and propagating the read with the best alignment score. Briggs and Michael Lachmann *To whom correspondence should be addressed (green@eva. For each sequencing library of each bone, we compared all reads to the known (Vi33. We then compared the rate in intra-bone allele matching to the rate of inter bone allele matching. We further limited the analysis to sites where exactly three Neandertals fragments were sequenced and two came from the same bone. We first identified each of these sites that were exactly two-fold covered in one individual and one-fold covered in another, filtering for map quality of 30 and base qualities specific for each bone and base. We required that each of the Neandertal bases was one of the two alleles known in humans.

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Retropharyngeal or peritonsillar abscess can cause upper airway obstruction, with soft tissue swelling evident on lateral neck x-ray (widening of the prevertebral soft tissue) or physical exam respectively. These children will often have high fever, drooling and be more toxic in appearance. Laryngitis can be seen in older children and adults, with a similar prodrome and cough, but lacking the inspiratory stridor. Foreign body aspiration should be considered in cases of sudden onset stridor without cough or fever. Acute angioneurotic edema, can cause acute swelling of the upper airway, but usually presents with external evidence of swelling of the face and neck. Laryngeal diphtheria (sometimes presents with a croup like syndrome known as membranous croup), although rare, should be considered and is another reason to assess the immunization record. Once the diagnosis of croup is made, mist therapy, corticosteroids and epinephrine are the usual treatments. Historically, mist therapy has been the mainstay of croup therapy, yet in small empiric trials, mist therapy has shown little benefit. Mist therapy (warm or cool) is thought to reduce the severity of croup by moistening the mucosa and reducing the viscosity of exudates, making coughing more productive. For patients with mild symptoms, mist therapy may be all that is required and can be provided at home. Racemic epinephrine, given by nebulizer, is thought to stimulate alpha-adrenergic receptors with subsequent constriction of arterioles and decreased laryngeal edema. Nebulized epinephrine may have marked effect to decrease inspiratory stridor and the work of breathing. The effects of this medication last less than two hours and children need to be monitored (not necessarily in the hospital) serially for the return of symptoms. Racemic epinephrine is a mixture of 50% biologically active epinephrine and 50% inactive epinephrine. Thus, 5cc of 1:1000 epinephrine solution is pharmacologically similar and can also be used for inhalation therapy with a nebulizer if racemic epinephrine is not available. Corticosteroids provide benefit for children with viral croup by reducing the severity and shortening the course of the symptoms. Clinical improvement from corticosteroids is usually not apparent until 6 hours after treatment. More recent studies have shown high dose nebulized budesonide to be as effective as dexamethasone, with more rapid onset of effect. Endotracheal intubation is reserved for children with severe symptoms who do not respond to the previous therapies. This decision should be based on criteria such as hypercarbia, impending respiratory failure and changes in mental status.

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