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bulletConsultant in Intensive Care Medicine,Royal Marsden Hospital,Honorary Senior Lecturer,Imperial College London

The goodness-offit chi-square test can be used to hiv infection cdc order albendazole 400mg fast delivery determine the probability that a difference between observed and expected numbers is due to antiviral used for meningitis buy albendazole 400 mg line chance hiv infection rates miami 400 mg albendazole overnight delivery. A locus is a place on a chromosome where genetic information encoding a character is located antiviral drug cures hiv buy albendazole 400 mg on-line. A genotype is the set of alleles possesed by an individual organism, and a phenotype is the manifestation or appearance of a character. The principle of segregation and the principle of independent assortment both refer to the separation of alleles in anaphase I of meiosis. The principle of segregation says that these alleles separate, and the principle of independent assortment says that they separate independently of alleles at other loci. Parents short short short short short long short long long long Progeny 4 short and 2 long 8 short 12 short 3 short and 1 long 2 long · Solution For this problem, it is useful to first gather as much information about the genotypes of the parents as possible on the basis of their phenotypes. We can then look at the types of progeny produced to provide the missing information. The 2 long-haired offspring Basic Principles of Heredity 65 must be homozygous (ss) because long hair is recessive and will appear in the phenotype only when both alleles for long hair are present. Because each parent contributes one of the two alleles found in the progeny, each parent must be carrying the s allele and must therefore be Ss. It is theoretically possible, although unlikely, that both parents are heterozygous (Ss Ss). Although no long-haired progeny are observed, it is possible that just by chance no long-haired rabbits would be produced among the 8 progeny of the cross. Let p equal the probability of a kitten being black and q equal the probability of a kitten being gray. The binomial is (p q)6, the expansion of which is: (p q)6 p6 6p5q 15p4q2 20p3q3 15p2q4 6p1q5 q6 (See the section on the Binomial Expansion and Probability for an explanation of how to expand the binomial. The probabilities of p and q are both 1/2; so the overall probability is 20(1/2)3 (1/2)3 20/64 5/16. The following genotypes are crossed: Aa Bb Cc Dd Aa Bb Cc Dd Give the proportion of the progeny of this cross having each of the following genotypes: (a) Aa Bb Cc Dd, (b) aa bb cc dd, (c) Aa Bb cc Dd. It is theoretically possible, although unlikely, that the parent is heterozygous and just by chance no long-haired progeny were produced. If this female has a litter of six kittens, what is the probability that three will be black and three will be gray? To find the probability of any combination of genotypes, simply multiply the probabilities of the different genotypes: a. In corn, purple kernels are dominant over yellow kernels, and full kernels are dominant over shrunken kernels. A corn plant having purple and full kernels is crossed with a plant having yellow and shrunken kernels, and the following progeny are obtained: purple, full purple, shrunken yellow, full yellow, shrunken 112 103 91 94 66 Chapter 3 What are the most likely genotypes of the parents and progeny? If the probability that the difference between observed and expected is due to chance is low, the progeny are not really in the predicted ratio and some other, significant factor must be responsible for the deviation. The observed and expected numbers are: Phenotype purple, full purple, shrunken yellow, full yellow, shrunken Observed 112 103 91 94 Expected 400 100 400 100 400 100 400 100 Purple yellow produces approximately 1/2 purple and 1/2 yellow. A 1: 1 ratio is usually caused by a cross between a heterozygote and a homozygote. Because purple is dominant, the purple parent must be heterozygous (Pp) and the yellow parent must be homozygous (pp). The purple progeny produced by this cross will be heterozygous (Pp) and the yellow progeny must be homozygous (pp). Full shrunken produces 1/2 full and 1/2 shrunken, or a 1: 1 ratio, and so these progeny phenotypes also are produced by a cross between a heterozygote (Ff) and a homozygote (ff); the full-kernel progeny will be heterozygous (Ff) and the shrunken-kernel progeny will be homozygous (ff). Now combine the two crosses and use the multiplication rule to obtain the overall genotypes and the proportions of each genotype: P Purple, full Pp Ff Yellow, shrunken pp ff /4 /4 1 /4 1 /4 1 1 To determine the probability that the difference between observed and expected is due to chance, we calculate a chisquare value with the formula 2 [(observed expected)2/ expected]: 2 = = = (112 - 100)2 (103 - 100)2 (91 - 100)2 (94 - 100)2 + + + 100 100 100 100 32 92 62 122 + + + 100 100 100 100 144 9 81 36 + + + 100 100 100 100 = 1. To obtain this probability, we first calculate the degrees of freedom, which F1 Pp Ff = 1 2 purple * 1 2 full = 1 4 purple, full for a goodness-of-fit chi-square test are n 1, where n equals 1 1 1 the number of expected phenotypic classes. In this case, there are Pp ff = 2 purple * 2 shrunken = 4 purple, shrunken four expected phenotypic classes; so the degrees of freedom 1 1 1 pp Ff = 2 yellow * 2 full = 4 yellow, full equal 4 1 3. We must now look up the chi-square value in a pp ff = 1 2 yellow * 1 2 shrunken = 1 4 yellow, shrunken chi-square table (see Table 3.

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However antiviral paint generic albendazole 400 mg fast delivery, if the purpose of the dietary study is to hiv time between infection symptoms order albendazole 400 mg with amex determine the proportion of individuals in the group who are at risk of dietary inadequacy or excess symptoms of hiv infection in one week albendazole 400 mg with mastercard, relative to over the counter antiviral cream cheap albendazole 400 mg with visa some standard of reference, then a single day of information on each individual is no longer adequate because it is necessary to have a reliable estimate of the distribution of habitual intake in the group. To determine the distribution of habitual food intake in a group, at least 2 days (preferably not consecutive) of information from each individual or a representative subsample of individuals from the group of interest are needed. If several days of intake are available they can be used to derive a mean intake for each individual and from this the distribution of average intakes for the group. Alternatively, statistical techniques can be used to adjust 1 day intake data, for the day-to-day variation that occurs in individuals, to provide a better estimate of the underlying distribution of habitual intake for the group than is given by the 1 day data (Dodd et al. While the use of appropriate statistical techniques can improve estimates of the proportion of individuals at risk of P:S ratio, ratio of polyunsaturated to saturated fatty acids in the diet. Oxford: Oxford University Press, 1991, with permission from Oxford University Press. Other reasons may include a desire to eat less in order to lose weight or to be seen to conform with dietary recommendations. If this is what happens in practice, then what is measured in short-term dietary records may be actual intake or desired intake, but not usual intake. Many studies have now demonstrated that there is a tendency, in most population subgroups, for shortterm dietary records to provide estimates of energy intake that are on average around 16% lower than would be expected on the basis of measured and/or estimated levels of energy expenditure. The fact that for some groups measurements of energy intake and energy expenditure agree quite closely indicates that it is possible to achieve recording without a concomitant change in diet when there is full cooperation from respondents, and highlights the importance of efforts to achieve such cooperation. When the purpose of the study is to assess the diet of specific individuals it is necessary to obtain dietary information over at least a week and preferably longer. This is best done by obtaining either multiple 24 hour recalls or 24 hour food records over an extended period. The minimum number of days needed to obtain an estimate of nutrient intake with a specified level of confidence differs for different nutrients. Information on energy intake, which tends to show less day-to-day variation than other nutrients, can be obtained over a shorter period (days) than information on a nutrient for which day-to-day intake is much more variable, such as vitamin A (weeks). Precision In studies of groups, precision is primarily a function of sample size, while in studies of individuals it is a function of the number of days of information available. Precision increases with sample size and with the number of days for which information is collected, but so does the cost of the study. Usually, what is required of the nutritionist is to be able to provide the statistician with an estimate of the level of difference that it is important to be able to detect (in nutritional, not statistical terms) and an estimate of the variance or standard deviation for the measurement(s) in question. For example, when looking for differences in energy intake between two groups, would a difference of 500 kJ or 1500 kJ be regarded as biologically significant? Since the variance of a dietary measurement depends not only on the real variation within or between respondents but also on the error of the measurement, the precision of a dietary estimate can be improved not only by increasing sample size but also by reducing measurement error. Resources It is inevitable that the resources available, both financial and human, also influence the choice of method. If the method or methods needed to answer the question are beyond the resources available it is better either to abandon the study or to redefine the question than to collect inadequate data. Repeatability Assessing the repeatability (also referred to as the reproducibility) of a laboratory method is relatively straightforward because, with care, it is possible to reproduce both what is measured and the conditions of measurement. Individuals do not eat exactly the same quantities or the same foods on different days or weeks. All measures of repeatability obtained by applying the same method to the same individuals on more than one occasion include not only measurement error but also real day-to-day or week-to-week variability in intake. While at first sight it might appear easier to measure the repeatability of recall methods such as the 24 hour recall and diet histories, this process also introduces additional sources of variation since the interviews have to be conducted at different times and possibly by different interviewers. Measures of repeatability for all dietary methods will thus tend to give an overestimate of the extent of measurement error because they will always include an element of variation due to real differences in what is being measured and in the conditions under which it is being measured. Usually, the repeatability of a dietary method is determined by repeating the same method on the same individuals on two separate occasions, that is, by a test­retest study. The interval between tests depends on the time-frame of the dietary method being assessed, but should generally be short enough to avoid the effects of seasonal or other changes in food habits and long enough to avoid the possibility of the first interview or recording period influencing the second one. The difference between the results obtained on the two occasions can be expressed in a number of different ways. The correlation coefficient is widely quoted but is not a good measure of repeatability since a good correlation may be obtained even if one set of measurements has been systematically biased and has a different mean from the other set. The mean difference is not a good measure of repeatability in individuals since it depends primarily on whether the differences are random or systematic.

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Cystinosis Cystinosis hiv infection symptoms ppt generic 400mg albendazole fast delivery, first described by Aberhalden in 1903 hiv infection in south korea buy albendazole 400mg without a prescription, is a rare autosomal recessive metabolic disorder natural antiviral herbs discount 400 mg albendazole fast delivery. Three clinical types of this disorder are described based on the age at diagnosis and degree of cellular cystine deposition: infantile onset hiv infection rates caribbean discount 400 mg albendazole with mastercard, adolescent onset and adult onset. Patients with infantile cystinosis (the most common and most severe) become symptomatic at 3­18 months of age with polyuria, followed by poor growth, photophobia and, if not diagnosed and treated, renal failure by age 6 years. Although most individuals are not diagnosed until after infancy, occasionally family history hastens postnatal diagnosis or allows prenatal diagnosis based on elevated cystine in amniocytes or chorionic villus samples. The renal tubular dysfunction leads to classic renal Fanconi syndrome with impaired reabsorption of glucose, phosphate, amino and organic acids and minerals. Renal phosphate losses lead to vitamin D-resistant rickets; chronic losses of sodium bicarbonate and potassium lead to chronic acidosis and hypokalaemia. With ongoing glomerular damage, there is a progressive renal impairment and an end-stage renal disease. There are a variety of ophthalmic abnormalities of which the pathognomonic birefringent refractile corneal deposits are the first to appear. Pharmacology Mercaptamine is an amino thiol that depletes lysosomal cystine in a disulphide exchange reaction with cysteine. Mercaptamine postpones, and in some cases, even prevents the deterioration of renal function and the development of extra-renal complications. Treatment should be started as soon as the diagnosis of cystinosis is made and continued lifelong, even after renal transplantation, to protect the extra-renal organs. Sadly, therapy is not straightforward; the free thiol smells (of rotten eggs) and tastes awful, it also needs to be given regularly every 6 hours (although modified-release preparations allow older children and adults to have twice-daily treatment), and gastrointestinal side effects can make tolerance difficult ­ it causes a threefold increase in gastric acid production and a 50% rise of serum gastrin levels. Excessively high doses can cause skin lesions due to angioendotheliomatosis (these disappear if the dose is reduced). The oral drug has no effect on the corneal cystine crystal accumulation, most likely due to inadequate intraocular levels; thus, an ophthalmic preparation is also required. The best outcomes are obtained by (1) making an early diagnosis, (2) administering mercaptamine every 6 hours and (3) performing frequent assays of leucocyte cystine. Treatment Note: Treatment with these products should only be initiated after consultation with a specialist nephrology advisory centre. Oral treatment: Begin with one-sixth to one-quarter of the expected maintenance dose, increased gradually over 4­6 weeks. Best results are obtained from 6 hourly dosing, but a pragmatic approach is to medicate as soon as the child wakes and before the parents go to bed, with the other two doses given at intermediate times to spread out the medication as close to every 6 hours as possible. Eye drops: Mercaptamine eye drops are instilled into each eye four to six times a day (at least 2­4 hours apart). Monitoring treatment Leucocyte cystine levels are used to determine dosing and compliance once the maintenance dose is achieved and every 3 months thereafter. Blood is obtained 5­6 hours after mercaptamine treatment with the aim to achieve levels <1 nmol/half-cystine/mg protein. The contents of the capsules can be sprinkled on food (milk, potatoes or starch-based foods) or added to formula milk. Prenatal diagnosis of cystinosis by quantitative measurement of cystine in chorionic villi and cultured cells. A multicentre randomised double masked clinical trial of a new formulation of topical cysteamine for the treatment of corneal cystine crystals in cystinosis. In many units it is held in reserve, and only used in consultation with a microbiologist or in a research context, when no other satisfactory alternative exists. Pharmacology Meropenem is a carbapenem -lactam antibiotic active against a very wide range of Gram-positive and Gram-negative aerobic and anaerobic bacteria that first came into general clinical use in 1985. Methicillin-resistant staphylococci and Enterococcus faecium are resistant to meropenem, as are some strains of Pseudomonas aeruginosa. Meropenem is excreted in the urine, mostly unchanged, but partly as an inert metabolite. The elimination half-life in adults is only 1 hour, but a little longer in children 2­6 months old. The initial half-life in the term baby is 2 hours and in the preterm baby 3 hours, but the half-life falls significantly, irrespective of gestation, within 10­14 days of birth.

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Blackie & Son hiv primary infection symptoms duration generic albendazole 400mg otc, Glasgow) When nutrients are unavailable in the environment hiv infection rate pakistan purchase albendazole 400mg on line, microbes utilize cellular constituents antiviral for cmv buy cheap albendazole 400 mg line, including reserve materials and polymers that are not essential for survival anti viral echinamide cheap 400 mg albendazole fast delivery. Reserve material can be defined as polymers synthesized when an energy source is supplied in excess, and used as a substrate for endogenous metabolism without any other cellular functions. It is likely that the ability to accumulate reserve materials is advantageous for survival in natural habitats. Reserve materials in bacteria can be grouped into four categories according to their chemical nature. Glycogen is a polysaccharide consisting of glucose with -1,4-linkages as well as -1,6-linkages. Many prokaryotes synthesize this polysaccharide when the energy source is in excess and when one or more essential elements are limiting, such as nitrogen. Glycogen is utilized by the action of two enzymes, a debranching enzyme and glycogen phosphorylase. Pi starvation; consequently this bacterium does not survive very long under starvation conditions. On the other hand, Arthrobacter globiformis stays viable for long periods of time under starvation conditions since this bacterium utilizes the reserve polysaccharide slowly with low activity of the debranching enzyme. This disaccharide is not a reserve material in prokaryotes, but many bacteria can use trehalose as their sole carbon and energy source. Some bacteria, including Desulfovibrio halophilus and several purple sulfur and nonsulfur bacteria, synthesize trehalose under high osmotic pressure as a compatible solute, but this disaccharide is not regarded as a reserve material. This disaccharide is metabolized in three different ways depending on the organism. Trehalase hydrolyzes it to two molecules of glucose, while trehalose phosphorylase cleaves it to glucose and glucose-1-phosphate. In other organisms, trehalose is phosphorylated to trehalose-6-phosphate by the action of trehalose kinase before being cleaved to glucose-6phosphate and glucose by a hydrolase. On the other hand, only a few prokaryotes have the property of accumulating triacylglycerides as a reserve material, a property that is widespread in eukaryotes. Coenzyme A transferase activates acetoacetate to acetoacetyl-CoA consuming succinyl-CoA. Under nitrogen-limited conditions, a strain of Acinetobacter calcoaceticus accumulates up to 25% of the cell dry weight. Since acetoacetyl-CoA is an intermediate in degradation as well as in the synthesis of this reserve material, reactions involving this intermediate are tightly controlled to avoid a futile cycle which would waste a high energy bond in the form of succinyl-CoA. A strain of Vibrio furnissii isolated from a sewage works accumulated lipid material extracellularly to 1. Half of the extracellular lipid consisted of alkanes with a carbon number of 15­24. Many cyanobacteria accumulate cyanophycin as a reserve material for carbon and nitrogen. Cyanophycin has a structure composed of polyaspartate, each monomer of which is linked with a molecule of arginine (Figure 13. This peptide is synthesized under phosphate- or sulfate-limited conditions with nitrogen and light in excess. When the synthesis of protein and nucleic acids is inhibited, cyanophycin production is activated. Its synthesis is not inhibited by tetracycline, showing that cyanophycin is synthesized through a non-ribosomal mechanism. When the nitrogen supply is limited, cyanophycin is degraded producing ammonia and carbon dioxide. In heterocystous cyanobacteria, the heterocysts have a higher enzyme activity for cyanophycin synthesis than the vegetative cells. When the nitrogen supply is limited, this peptide is also degraded as a nitrogen source. Cyanobacteria have a bluish-green colour under normal conditions but become yellowish-green under nitrogen-limited conditions because the blue coloured phycocyanin is degraded. It Figure 13:5 Structure of cyanophycin, a peptide reserve material in cyanobacteria.

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