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Factors influencing outcomes in the offspring of mothers with phenylketonuria during pregnancy: the importance of variation in maternal blood phenylalanine keratin intensive treatment purchase lotensin visa. Maternal phenylketonuria: low phenylalaninemia might increase the risk of intra uterine growth retardation medications via g tube purchase lotensin online. Management of pregnancy in women with genetic disorders: part 2: inborn errors of metabolism medicine 003 generic lotensin 5mg online, cystic fibrosis, neurofibromatosis type 1, and turner syndrome in pregnancy. Psychosocial factors in maternal phenylketonuria: prevention of unplanned pregnancies. A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention. Pregnancy in phenylketonuria: dietary treatment aimed at normalising maternal plasma phenylalanine concentration. Congenital heart disease in maternal phenylketonuria: effects of blood phenylalanine and nutrient intake. Maternal Phenylketonuria international collaborative study revisited: evaluation of maternal nutritional risk factors besides phenylalanine for fetal congenital heart defects. Recommendations for the nutrition management of phenylalanine hydroxylase deficiency. Tyrosine supplementation during pregnancy in a woman with classical phenylketonuria. Genetic failure of fetal amino acid "justification": a common basis for many forms of metabolic, nutritional, and "nonspecific" mental retardation. Lack of fetal effect on blood phenylalanine concentration in maternal phenylketonuria. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Dietary reference intakes for energy, carbohydrate, fibre, fat, fatty acids, cholesterol, protein and aminoacids. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Effects of n-3 long chain polyunsaturated fatty acid supplementation on visual and cognitive development throughout childhood: a review of human studies. Current information and Asian perspectives on long-chain polyunsaturated fatty acids in pregnancy, lactation, and infancy: systematic review and practice recommendations from an early nutrition academy workshop. Long-term beneficial effects of the phenylalanine-restricted diet in late-diagnosed individuals with phenylketonuria. Descriptive epidemiology of missed cases of phenylketonuria and congenital hypothyroidism. Phenylketonuria presenting in adulthood as progressive spastic paraparesis with dementia. Adult-onset phenylketonuria revealed by acute reversible dementia, prosopagnosia and parkinsonism. Measurement of functional independence level and falls-risk in individuals with undiagnosed phenylketonuria. Late-treated phenylketonuria and partial reversibility of intellectual impairment. Effect of a low-phenylalanine diet on older Phenylketonuria patients (long range controlled study). Phenylalanine restricted diet treatment of the aggressive behaviours of a person with mental retardation. An investigation into diet treatment for adults with previously untreated phenylketonuria and severe intellectual disability. Use of a restricted protein diet in the treatment of behaviour disorder in a severely mentally retarded adult female phenylketonuric patient. The use of a low phenylalanine diet with amino acid supplement in the treatment of behavioural problems in a severely mentally retarded adult female with phenylketonuria. Effects of diet and behavior therapy on social and motor behavior of retarded phenylketonuric adults: an experimental analysis. A case report on long-term follow-up of an adolescent with untreated phenylketonuria. Late diagnosed phenylketonuria patients: clinical presentation and results of treatment. Improvements in behaviour and physical manifestations in previously untreated adults with phenylketonuria using a phenylalanine-restricted diet: a national survey. Effect of dietary phenylalanine restriction on visual attention span in mentally retarded subjects with phenylketonuria. Economic impact of feeding a phenylalanine-restricted diet to adults with previously untreated phenylketonuria. Behavioural effects of phenylalanine-free amino acid tablet supplementation in intellectually disabled adults with untreated phenylketonuria. Introduction of sapropterin dihydrochloride as standard of care in patients with phenylketonuria. Knowledge, compliance and serum phenylalanine concentrations in adolescents and adults with phenylketonuria and the effect of a patient-focused educational resource. Impact of a camp experience on phenylalanine levels, knowledge, attitudes, and health beliefs relevant to nutrition management of phenylketonuria in adolescent girls. Social factors and the meaning of food in adherence to medical diets: results of a maternal phenylketonuria summer camp. Effectiveness of self-management training in type 2 diabetes: a systematic review of randomized controlled trials. Long-term pharmacological management of phenylketonuria, including patients below the age of 4 years. The effect of blood phenylalanine concentration on Kuvan response in phenylketonuria. Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria. Clinical and nutritional evaluation of phenylketonuric patients on tetrahydrobiopterin monotherapy. Using change in plasma phenylalanine concentrations and ability to liberalize diet to classify responsiveness to tetrahydrobiopterin therapy in patients with phenylketonuria. Pharmacokinetics of orally administered tetrahydrobiopterin in patients with phenylalanine hydroxylase deficiency. Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy. Potential role of tetrahydrobiopterin in the treatment of maternal phenylketonuria. Long-term treatment of patients with mild and classical phenylketonuria by tetrahydrobiopterin.
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Creating structural shifts in consumption behaviours through both economic and regulatory incentives and cultural transformations of norms and practices can also contribute to medicine lake mn purchase cheap lotensin line the protection of global commons medications known to cause miscarriage purchase 5mg lotensin with amex. Transnational agreements are key to treatment example discount 5mg lotensin the protection of the commons, and adaptive governance involving a wide range of institutions and stakeholders can help ensure their sustainable management. Science diplomacy can further strengthen the protection of global commons and help establish partnerships for solving conflicts and for the sustainable management of commons. Discussions of sustainable development and environmental protection have lately included other commons, which may lie within well-defined national or regional jurisdictions, but whose continuing existence confers benefits beyond them. The current report focuses on the global environmental commons defined in that broader sense, comprising various large-scale biomes and systems that contribute directly or indirectly to the functioning of the Earth system and hence to supporting life, including biodiversity, the atmosphere, oceans, the cryosphere, forests and the hydrosphere. For some, such as forests, holdings, tenure rights and usufruct may overlap, but are not necessarily mutually exclusive with the concept of commons. Actions on global environmental commons should help secure human well-being and the survival of all living species. The stock of natural capital is currently deteriorating far beyond its rate of renewal. Our actual demands on the global environmental commons have become so great that they are influencing the Earth system as a whole. Achieving the Sustainable Development Goals requires that we reduce the pressure on those commons. Hence, there is an urgent need to decarbonize human activities, manage how resources are extracted from the commons, how efficiently they are used, how they are distributed and how waste is managed. However, the 2019 report of the Intergovernmental SciencePolicy Platform on Biodiversity and Ecosystem Services warns that an average of around 25 per cent of species in assessed animal and plant groups are threatened, suggesting that around 1 million species already face extinction, many within decades, unless action is taken to reduce the intensity of drivers of biodiversity loss. Many pollinating species have declined in abundance, or are threatened by chemical use and agricultural expansion, putting the production of 75 per cent of our food crops at risk. That loss of diversity, including genetic diversity, poses a serious risk to global food security by undermining the resilience of many agricultural systems to threats such as pests, pathogens and climate change. That unprecedented loss of biodiversity is driven by several interrelated drivers including climate change, resource overexploitation, chemical pollution, fragmentation of land, invasive species, poaching and the disposal of plastics. It is likely that most of the Aichi Biodiversity Targets for 2020 will be missed, in spite of the fact that supporting conservation and securing a safe operating space706 for future generations is key for sustainable development. The interaction between the living organisms on this planet and the physical climate system controls the state of the overall global environment, so the loss of biodiversity reduces the resilience of the biosphere, which is essential for maintaining the climate conditions we enjoy on Earth. The pace at which biodiversity is being lost is unprecedented with currently nearly 1 million species, or 25 per cent of the assessed animals and plants, being threatened by extinction in the coming decades. Transformations Damage to the atmosphere Climate change, air pollution, stratospheric ozone depletion, and persistent organic pollutants are the four main challenges impacting the state of the atmosphere, and they have important deleterious effects on oceanic and terrestrial ecosystems. Climate change due to human activity disrupts the support, regulation and provision of services of ecosystems while increasing the intensity of hazards such as extreme heat, intense rainfall, floods, landslides, sea level rise and drought. Infections and diseases may emerge and spread faster with climate change, especially when coupled with human mobility. Least developed countries and small island developing States in tropical areas are likely to feel irreversible consequences of climate change before other countries,416 and they have less capacity to prepare and respond. Air pollution presents one of the highest health risks globally, especially in fast-growing cities in developing countries. Low- and middle-income countries are home to more than 90 per cent of deaths attributed to air pollution. In cities in cold regions, where energy for heating is in high demand, special attention should be given to fumes from inefficient stoves, particularly in cities in valleys, where reversed temperatures keep the contaminated air trapped above urban dwellers. In developing countries, black carbon produced by incomplete combustion of fossil fuels and biomass has increased along with the human exploitation of forest resources. Black carbon, together with increases in regional fire frequency and intensity, plays a critical role in aerosol-planetary boundary layer interaction and the further deterioration of near-surface air pollution in most megacities. Changes in the oceans the ocean needs urgent protection to maintain its pivotal role in providing regulating and provisioning services which, in turn, support most other Sustainable Development Goals. Securing the oceans can feed and provide livelihoods for people while maintaining habitats, protecting its biodiversity and coastal areas and regulating climate change. Projected changes in the ocean are, therefore, expected to create impacts in the Earth system that will lead to greater global warming. Warming, coupled with ocean acidification due to carbon uptake, creates a double challenge for coral reefs, by reducing their growth, causing increased bleaching and decreasing their storm-protective function. The destruction of coral reefs affects oceans biodiversity because they serve as habitats for 25 per cent of oceanic species. Additionally, reefs play a vital role in the economy and coastal protection of numerous tropical and subtropical countries, including islands and developing countries. The oceans support the livelihoods of 60 million fishers who derive an income from ocean resources, livelihoods that are threatened because acidification reduces the survival of larval and adult stages of several commercially important fishes. Global marine fish stocks are at risk with overfished stocks, having increased from 10 per cent in 1974 to 33. Oceans receive an ever-growing amount of landbased garbage, sewage, plastic debris, anthropogenic nanoparticles, fertilizers, hazardous chemicals and oil spills as a result of hazardous technologies. Those endanger marine species and biodiversity, contaminate food chains, pose risks to human immune systems, reduce fertility and increase the risk of cancer. Plastic debris constitutes 60 to 80 per cent of marine debris and converges at high concentration (200,000 pieces per square kilometre) in ocean currents. The situation will ultimately deteriorate if no interventions are carried out, especially since demand for water is expected to increase by 50 per cent. As populations increase, especially in dryland areas, more and more people are becoming dependent on freshwater supplies in land that are becoming degraded. Drought and water scarcity are considered to be the most farreaching of all natural disasters, causing short- and long-term economic and ecological losses. Addressing land degradation upstream improves access to water in downstream areas. Restoring land raises groundwater levels, increases crop yields and induces positive changes in the fauna of the region, as exemplified by recent evidence from Ethiopia and Niger. Those people have high levels of poverty, and, in developing countries, around 40 per cent face food insecurity. If they are to have a sustainable future and cope with climate change, they will need greater capacity and resilience. That calls for considering the specific context of mountains in implementing measures and reviewing progress towards the 2030 Agenda. The assessments highlight how targets that promote sustainable use of natural resources and conserving terrestrial ecosystems (targets 6. The experts considered that addressing the slow economic development of remote mountain areas involves sustainable tourism (target 8. Land is becoming an increasing scarce resource, especially for growing food, with a yearly loss of arable land estimated at 100,000 square kilometres. In some parts of the world, notably drylands and other resource-scarce areas where no other crop can be grown, raising livestock may be an efficient use of land, where non-edible plants are converted into meat and milk to feed people. However, in other areas, allocating land to livestock rearing is a non-rational use of resources, because contaminants and greenhouse gases are emitted and more efficient ways of producing more food with fewer resources are excluded.
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Data for the most recent year show that quality was better for Whites than for Asians on 27% of all quality measures and that quality was better for Asians than for Whites on 28% of all quality measures (Figure 69) lb 95 medications order 5 mg lotensin otc. Heparin is among the highest risk medications and incorrect prescribing or administration of this medicine may result in an adverse event medications for migraines cheap lotensin 5 mg overnight delivery. Home health performance is examined through several types of quality measures that look at areas such as efficiency medicine cabinet cheap 5mg lotensin amex, patient safety, and patient-centered care. Evaluation of patient experience of care is conducted with the Consumer Assessment of Healthcare Providers and Systems Home Health Care Survey. Adults who reported that home health providers always treated them with courtesy and respect in the last 2 months of care, 2017 100 2017 Achievable Benchmark: 95% 90 Percent 80 70 60 50 Total Asian White Source: Agency for Healthcare Research and Quality, Home Health Consumer Assessment of Healthcare Providers and Systems, 2017. The top states that contributed to the achievable benchmark are Alabama, Kentucky, Louisiana, Mississippi, South Carolina, and West Virginia (more than 5 states contributed to the benchmark due to ties). Providers With Language Assistance Current research shows that Asians continue to experience health disparities in several quality areas, including patient-centered care and satisfaction. The Limited English Proficiency website69 offers a repository of resources collated by the Department of Justice to support improved communication with patients. Number and percentage of all quality measures that were improving, not changing, or worsening, total for Asians and by priority area, from 2000 through 2011, 2013, 2014, 2015, 2016, or 2017 Improving 100% 80% 60% 40% 64 20% 2 0% Total (n=113) PersonPatient Healthy Effective Care Affordable Centered Safety (n=9) Living (n=50) Treatment Coordination Care (n=3) Care (n=19) (n=24) (n=8) 6 6 43 6 1 Not Changing 1 16 10 3 1 2 1 Worsening 13 33 13 3 2 Key: n = number of measures. Across the 113 measures of healthcare quality tracked in the report for Asians, 57% were improving, 38% were not changing, and 5% were getting worse from 2000 to 2017 (Figure 73). Number and percentage of quality measures with disparity at baseline for which disparities related to race and ethnicity were improving, not changing, or worsening, total for Asians and by priority area, 2000 through 2013, 2015, 2016, or 2017 Improving 100% 80% 60% 29 40% 20% 0% 2 Total (n=32) 1 PersonPatient Healthy Effective Care Affordable Centered Safety (n=1) Living (n=13) Treatment Coordination Care (n=0) Care (n=13) (n=3) (n=2) 13 1 2 12 2 1 Not Changing Worsening 1 Key: n = number of measures. From 2000 through 2017, disparities in quality of care between Asians and Whites remained the same for most measures. Of 32 quality measures with a disparity at baseline, disparities were not changing for 29 (91%) (Figure 74). One measure showed a widening disparity: Home health patients whose management of oral medications improved. Pneumococcal Immunization Two kinds of pneumococcal vaccines are available in the United States: Pneumococcal conjugate vaccine (for children under 2 years, adults over 65 years of age, and adults with certain health conditions) and Pneumococcal polysaccharide vaccine (for people ages 2-64 with certain medical conditions, adults ages 19-64 who smoke cigarettes, and adults age 65 years and over). Hospital patients who received pneumococcal immunization, 2012-2015 Asian 100 90 80 70 60 50 2012 2013 2014 2015 Source: Centers for Medicare & Medicaid Services, Quality Improvement Organization Program, 2012-2015. The trend was changing in 2015 with Asians performing better than Whites for this measure. At the current rate of increase, overall, the benchmark could be achieved in 1 year. The top 5 states that contributed to the achievable benchmark are Hawaii, Maine, New Hampshire, South Carolina, and Wisconsin. White Data from 2000 to 2015 show that the disparity between Asians and Whites is narrowing due to an increase in the percentage of Asians (70. The top 5 states that contributed to the achievable benchmark are Idaho, New Jersey, Pennsylvania, South Dakota, and Vermont. Percent 2018 National Healthcare Quality and Disparities Report 87 Quality and Quality Disparities Disparities for American Indians and Alaska Natives American Indians and Alaska Natives performed worse on almost 55% of Person-Centered Care quality measures. Number and percentage of quality measures for which American Indians and Alaska Natives experienced better, same, or worse quality of care compared with reference group (White), 2013, 2015, 2016, or 2017 Better 100% 80% 60% 40% 20% 0% 14 Total (n=106) 42 12 6 8 50 9 7 1 1 5 23 3 1 16 9 5 Same Worse PersonPatient Healthy Effective Care Affordable Centered Safety (n=7) Living (n=44) Treatment Coordination Care (n=1) Care (n=22) (n=24) (n=8) Key: n = number of measures. These resources include the Guide to Improving Patient Safety in Primary Care Settings by Engaging Patients and Families, which features a teach-back intervention. Percent 2018 National Healthcare Quality and Disparities Report 89 Quality and Quality Disparities Adequate Time With Doctor Both providers and patients report not having enough time during patient appointments and this challenge continues to affect the quality of healthcare services. The top states that contributed to the achievable benchmark are Florida, Indiana, Maine, Massachusetts, New Jersey, Tennessee, Virginia, and Utah (more than 5 states contributed to the benchmark due to ties). While current clinical guidelines show that people who are 6 months or older should receive an annual flu vaccine, not all patients can access vaccines or treatment if they become ill. Number and percentage of all quality measures that were improving, not changing, or worsening, total for American Indians and Alaska Natives and by priority area, from 2000 through 2013, 2014, 2015, 2016, or 2017 100% 80% 51 60% 40% 12 20% 0% Total (n=93) 38 3 20 2 1 11 4 6 1 23 Improving 4 1 1 Not Changing 1 6 Worsening 1 PersonPatient Healthy Effective Care Affordable Centered Safety (n=7) Living (n=43) Treatment Coordination Care (n=1) Care (n=15) (n=19) (n=8) Key: n = number of measures. Effective Treatment showed the most improvement (63% of measures) and Affordable Care, Care Coordination, and Person-Centered Care showed less improvement. Number and percentage of quality measures with disparity at baseline for which disparities related to race and ethnicity were improving, not changing, or worsening, total for American Indians and Alaska Natives and by priority area, from 2000 through 2013, 2015, 2016, or 2017 Improving 100% 80% 60% 40% 20% 1 0% 2 Total (n=33) 1 PersonPatient Healthy Effective Care Affordable Centered Safety (n=0) Living (n=14) Treatment Coordination Care (n=0) Care (n=11) (n=4) (n=4) 3 31 11 13 4 Not Changing Worsening Key: n = number of measures. Of 33 quality measures with a disparity at baseline, 31 (94%) were not changing (Figure 82). According to the National Institute of Diabetes and Digestive and Kidney Diseases, Whites experience diabetes and kidney disease at a lower rate than other racial and ethnic groups. Number and percentage of quality measures for which Native Hawaiians/Pacific Islanders experienced better, same, or worse quality of care compared with reference group (White), 2015, 2016, or 2017 Better 100% 1 80% 60% 5 40% 20% 0% 8 Total (n=57) 26 6 1 2 2 2 10 4 1 23 9 5 4 4 Same Worse 1 PersonPatient Healthy Effective Care Affordable Centered Safety (n=7) Living (n=17) Treatment Coordination Care (n=0) Care (n=16) (n=10) (n=7) Key: n = number of measures. Adults who reported that home health providers always treated them with courtesy and respect in the last 2 months of care. Number and percentage of all quality measures that were improving, not changing, or worsening, total for Native Hawaiians/Pacific Islanders and by priority area, from 2008 through 2012, 2013, 2014, 2015, 2016, or 2017 Improving 100% 80% 60% 40% 20% 0% Total (n=48) 7 14 2 1 32 8 5 6 2 1 8 Not Changing Worsening 1 5 3 1 PersonPatient Healthy Effective Care Affordable Centered Safety (n=7) Living (n=15) Treatment Coordination Care (n=0) Care (n=10) (n=8) (n=8) Key: n = number of measures. Worsening = Quality is going in a negative direction at an average annual rate greater than 1% per year. Number and percentage of all quality measures with disparity at baseline for which disparities related to race and ethnicity were improving, not changing, or worsening, total for Native Hawaiians/Pacific Islanders and by priority area, from 2008 through 2015, 2016, or 2017 Improving 100% 80% 60% 40% 20% 0% 1 Total (n=12) PersonCentered Care (n=5) Patient Healthy Safety (n=0) Living (n=2) Effective Care Affordable Treatment Coordination Care (n=0) (n=2) (n=3) 1 Not Changing Worsening 1 11 5 2 3 Key: n = number of measures. Of the 12 quality measures with a disparity at baseline, disparities were not changing for 11 measures (92%) (Figure 89). At the current rate of increase, overall, the benchmark could be achieved in 6 years. Percent 2018 National Healthcare Quality and Disparities Report 101 Quality and Quality Disparities Disparities for Hispanics Hispanics performed worse than non-Hispanic Whites on almost 59% of Person-Centered Care quality measures and 37% of Healthy Living measures. Number and percentage of quality measures for which Hispanics experienced better, same, or worse quality of care compared with reference group (non-Hispanic White), 2013, 2015, 2016, or 2017 Better 100% 80% 60% 40% 20% 39 0% Total (n=167) 70 5 2 18 1 10 9 9 8 1 58 10 11 8 27 2 22 15 6 3 Same Worse PersonPatient Healthy Effective Care Affordable Centered Safety (n=23) Living (n=58) Treatment Coordination Care (n=5) Care (n=17) (n=42) (n=22) Key: n = number of measures. Data for the most recent year show that quality was better for non-Hispanic Whites than for Hispanics on 35% of all quality measures and quality was better for Hispanics than for non-Hispanic Whites on 23% of all quality measures (Figure 91). People without a usual source of care who indicated a financial or insurance reason for not having a source of care. At the current rate of increase, overall, the benchmark could not be achieved for 20 years. People without a usual source of care who indicated a financial or insurance reason for not having a source of care, 2016 25 20 Percent 15 10 5 0 Total Hispanic Non-Hispanic White Source: Agency for Healthcare Research and Quality, Medical Expenditure Panel Survey, 2016. In 2016, the percentage of people without a usual source of care who indicated a financial or insurance reason for not having a source of care was lower for nonHispanic Whites (10. Number and percentage of all quality measures that were improving, not changing, or worsening, total for Hispanics and by priority area, from 2000 through 2013, 2014, 2015, 2016, or 2017 Improving 100% 80% 47 60% 40% 20% 0% Total (n=127) PersonPatient Healthy Effective Care Affordable Centered Safety (n=12) Living (n=54) Treatment Coordination Care (n=5) Care (n=19) (n=28) (n=9) 69 10 4 11 1 1 Not Changing 2 16 8 7 3 36 3 16 2 1 2 10 4 Worsening 1 Key: n = number of measures. Of the 127 quality measures with data for Hispanics, 54% were improving, 37% were not changing, and 9% were getting worse from 2000 through 2017 (Figure 95). Number and percentage of all quality measures with disparity at baseline for which disparities related to race and ethnicity were improving, not changing, or worsening, total for Hispanics and by priority area, from 2000 through 2013, 2014, 2015, 2016, or 2017 Improving 100% 80% 60% 40% 20% 0% 5 Total (n=49) PersonCentered Care (n=7) 4 1 2 Not Changing 2 Worsening 42 7 3 18 11 3 Patient Healthy Effective Care Affordable Safety (n=3) Living (n=24) Treatment Coordination Care (n=3) (n=12) (n=0) Key: n = number of measures. Of the 49 quality measures with a disparity at baseline, disparities between Hispanics and non-Hispanic Whites did not change for 42 (86%) from 2000 through 2017 (Figure 96). Five measures showed narrowing disparities-one Effective Treatment measure and four Healthy Living measures.
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But this belief is supported neither by theory nor by actual data on the sex ratio in human sibships 9 medications that cause fatigue buy discount lotensin 10 mg. The data indicate that human families are equally likely to symptoms renal failure buy lotensin 10 mg online have a girl or a boy on any birth pure keratin treatment order lotensin discount, irrespective of the sex distribution in previous births. Although statistics guarantees that the sex ratio will balance out when averaged over a very large number of sibships, this does not imply that it will equalize in any individual sibship. To be concrete, among families in which there are five children, sibships consisting of five boys balance those consisting of five girls, yielding an overall sex ratio of 1: 1; nevertheless, both of these sibships have an unusual sex ratio. When events are independent (such as independent traits or successive offspring from a cross), the probabilities are combined by means of the multiplication rule. Multiplication Rule: the probability of two independent events, A and B, being realized simultaneously is given by the product of their separate probabilities. The multiplication rule can be used to answer questions such as this: For two offspring from the mating A4A5 A4A6, what is the probability of one homozygous genotype and one heterozygous genotype These possibilities are mutually exclusive, so the overall probability is 14 34 34 14 2(1 4)(3 4) 38 Each offspring results from an independent event of fertilization. In these cases, the probabilities of the individual outcomes of segregation or fertilization are multiplied to obtain the overall probability. The multiplication rule can also be used to calculate the probability of a specific genotype among the progeny of a complex cross. For example, if a quadruple heterozygous genotype Aa Bb Cc Dd is self-fertilized, what is the probability of a quadruple heterozygous offspring, Aa Bb Cc Dd Assuming independent assortment, the answer is (1 2)(1 2)(1 2)(1 2) (1 2)4 1 16, because each of the inde- Chapter 3 Transmission Genetics: the Principle of Segregation pendent genes yields a heterozygous offspring with probability 1 2. There are situations of incomplete dominance, in which the phenotype of the heterozygous genotype is intermediate between the phenotypes of the homozygous genotypes. A classic example of incomplete dominance concerns flower color in the snapdragon Antirrhinum majus (Figure 3. In wildtype flowers, a red type of anthocyanin pigment is formed by a sequence of enzymatic reactions. A wildtype enzyme, encoded by the I allele, is limiting to the rate of the overall reaction, so the amount of red pigment is determined by the amount of enzyme that the I allele produces. The alternative i allele codes for an inactive enzyme, and ii flowers are ivory in color. Because the amount of the critical enzyme is reduced in Ii heterozygotes, the amount of red pigment in the flowers is reduced also, and the effect of the dilution is to make the flowers pink. A cross between plants differing in flower color therefore gives direct phenotypic evidence of segregation (Figure 3. In the F2 progeny obtained by self-pollination of the F1 hybrids, one experiment resulted in 22 plants with red flowers, 52 with pink flowers, and 23 with ivory flowers, which fits the expected ratio of 1: 2: 1. Multiple alleles are relatively common in natural populations and, as in this example, can be detected most easily by molecular methods. The number of possible single-nucleotide differences in a gene of length n is therefore 3 n. If n 5000, for example, there are potentially 15,000 alleles (not counting any of the possibilities with more than one nucleotide substitution). Some are absent because they did not occur, others did occur but were eliminated by chance or because they were harmful, and still others are present but at such a low frequency that they remain undetected. Recall from Chapter 1 that more than 400 mutant forms of the phenylalanine hydroxylase gene have been identified in patients with phenylketonuria. In some cases, the multiple alleles of a gene exist merely by chance and reflect the history of mutations that have taken place in the population and the dissemination of these mutations among population subgroups by migration and interbreeding. In other cases, there are biological mechanisms that favor the maintenance of a large number of alleles. For example, genes that control self-sterility in certain flowering plants can have large numbers of allelic types. This type of self-sterility is found in species of red clover that grow wild in many pastures. The self-sterility genes prevent self-fertilization because a pollen grain can undergo pollen tube growth and fertilization only if it contains a self-sterility allele different from either of the alleles present in the flower on which it lands. In other words, a pollen grain containing an allele already present in a flower will not function on that flower. Because all pollen grains produced by a plant must contain one of the self-sterility alleles present in the plant, pollen cannot function on the same plant that produced it, and self-fertilization cannot take place. Under these conditions, any plant with a new allele has a selective advantage, because pollen that contains the new allele can fertilize all flowers except those on the same plant. Many of the alleles differ at multiple nucleotide sites, which implies that the alleles in the population are very old. One of two different polysaccharides, A or B, can be formed from a precursor molecule that is modified by the enzyme product of the I A or the I B allele. The gene product is a glycosyl transferase enzyme that attaches a sugar unit to the precursor (Figure 3. The third allele, I O, encodes an enzymatically inactive protein that leaves the precursor unchanged; neither the A nor the B type of polysaccharide is produced. In this multiple allelic series, the I A and B alleles are codominant: the heterozygous I genotype has the characteristics of both homozygous genotypes-the presence of both the A and the B carbohydrate on the red blood cells. O O O O O O O Galactose added to precursor O this is the B antigen; it reacts with anti-B antibody. They are formed from a precursor carbohydrate by the action of transferase enzymes encoded by alleles of the I gene. Allele I O codes for an inactive enzyme and leaves the precursor (called the H substance) unmodified. The I A allele encodes an enzyme that adds Nacetylgalactosamine (purple) to the precursor. The other colored sugar units are N-acetylglucosamine (orange) and fucose (yellow). An antibody is a protein made by the immune system in response to a stimulating molecule called an antigen and is capable of binding to the antigen. Some antibodies combine with antigen and form large molecular aggregates that may precipitate. Production of these antibodies may be stimulated by antigens that are similar to polysaccharides A and B and that are present on the surfaces of many common bacteria. However, a mechanism called tolerance prevents an organism from producing antibodies against its own antigens. This mechanism ensures that A antigen or B antigen elicits antibody production only in people whose own red blood cells do not contain A or B, respectively. When the blood cells agglutinate, many blood vessels are blocked, and the recipient of the transfusion goes into shock and may die. Incompatibility in the other A antigen + Red blood cells in type-A person Anti-A antibody Antibody causes agglutination of type-A red blood cells B antigen + No agglutination of type-B red blood cells Figure 3.
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Class C gene products together with Class B gene products induce the third whorl to medicine park oklahoma buy lotensin 5 mg mastercard develop into stamens medicine 600 mg lotensin 10mg visa. The products of the different gene classes and their effects are summarized in the conclusion of Figure 22 treatment quad tendonitis cheap lotensin 5mg with visa. To explain the results, they also proposed that the genes of some classes affect the activities of others. Where class A is active, class C is repressed, and where class C is active, class A is repressed. Class A genes are normally expressed in whorls 1 and 2, class B genes are expressed in whorls 2 and 3, and class C genes are expressed in whorls 3 and 4 (Figure 22. The interaction of these three classes of genes explains the different classes of mutants in Figure 22. For example, class A mutants are lacking class A gene products, and therefore class C genes are active in all tissues because, when A is inactivated, C becomes active. Therefore whorl 1, with only class C gene products, will consist of carpels; whorl 2, with class C and class B gene products, will produce stamens; whorl 3, with class B and class C gene products, will produce stamens; and whorl 4, with only class C gene activity, will produce carpels (see Figure 22. Findings from studies of other species have demonstrated that this system of flower development exists not only in Arabidopsis but also in other flowering plants. It is important to note that these genes are necessary but not sufficient for proper flower development; other genes also take part in the identity of the different parts of flowers. The products of four classes of homeotic genes interact to determine the formation of the four whorls that constitute a complete flower. Carpels, carpels, carpels carpels carpels (1st whorl) stamens (2nd whorl) stamens (3rd whorl) carpels (4th whorl) 22. Cells in many tissues have a limited life span, and they die and are replaced continually by new cells. As discussed in the introduction to this chapter, the death of lens cells causes the absence of eyes in blind cavefish. Cell death is also used to eliminate dangerous cells that have escaped normal controls (see section on mutations in cell-cycle control and cancer in Chapter 23). To confirm this explanation, Meyerowitz and his colleagues bred double and triple mutants and predicted the outcome. When one caspase is activated, it cleaves other procaspases that trigger even more caspase activity. The resulting cascade of caspase activity eventually cleaves proteins essential to cell function, such as those supporting the nuclear membrane and cytoskeleton. Procaspases and other proteins required for cell death are continuously produced by healthy cells, and so the potential for cell suicide is always present. A number of different signals can trigger apoptosis; for instance, infection by a virus can activate immune cells to secrete substances onto an infected cell, causing that cell to undergo apoptosis. This process is believed to be a defense mechanism designed to prevent the reproduction and spread of viruses. Damage to mitochondria and the accumulation of a misfolded protein in the endoplasmic reticulum also stimulate programmed cell death. Apoptosis in development Apoptosis plays a critical 4 Macrophage phagocytizes apoptotic cell. Cells that are injured, on the other hand, die in a relatively uncontrolled manner called necrosis. In this process, a cell swells and bursts, spilling its contents over neighboring cells and eliciting an inflammatory response (Figure 22. Apoptosis is essential to embryogenesis; most multicellular animals cannot complete development if the process is inhibited. Regulation of apoptosis Surprisingly, most cells are programmed to undergo apoptosis and will survive only if the internal death program is continually held in check. The process of apoptosis is highly regulated and depends on numerous signals inside and outside the cell. Geneticists have identified a number of genes having roles in various stages of the regulation of apoptosis. Some of these genes encode enzymes called caspases, which cleave other proteins at specific sites (after aspartic acid). As animals develop, excess cells are often produced and then later culled by apoptosis to produce the proper number of cells required for an organ or a tissue. For example, early mammalian embryos develop both male and female reproductive ducts, but the Wolffian ducts degenerate in females and the Mullerian ducts degenerate in males. Three genes in Drosophila activate caspases that are essential for apoptosis: reaper (rpg), grim, and head involution defective (hid). Embryos possessing a deletion that removes all three genes exhibit no apoptosis and die in the course of embryogenesis with an excess of cells. Apoptosis is also crucial in metamorphosis, the process by which larval structures are transformed into adult structures. For example, the large salivary glands of larval fruit flies regress during metamorphosis. Ecdysone induces the expression of rpg and hid and inhibits the expression of other genes, which then leads to apoptosis of salivary gland cells. Apoptosis in disease the symptoms of many diseases and disorders are caused by apoptosis or, in some cases, its absence. In neurodegenerative diseases such as Parkinson disease and Alzheimer disease, symptoms are caused by a loss of neurons through apoptosis. In heart attacks and stroke, some cells die through necrosis, but many others Developmental Genetics and Immunogenetics 625 undergo apoptosis. Cancer is often stimulated by mutations in genes that regulate apoptosis, leading to a failure of apoptosis that would normally eliminate cancer cells. Apoptosis plays an important role in animal development and is implicated in a number of diseases. Scientists have long recognized that organisms do not pass through the adult stages of their ancestors during their development, but the embryos of these related organisms often display similarities. Sometimes called "evo-devo," the study of evolution through the analysis of development is revealing that the same genes often shape developmental pathways in distantly related organisms. Biologists once thought that segmentation in vertebrates and invertebrates was only superficially similar, but we now know that, in both Drosophila and the primative chordate Branchiostoma, the engrailed gene divides the embryo into specific segments. A gene called distalless, which creates the legs of a fruit fly, plays a role in the development of crustacean branched appendages. This same gene also stimulates body outgrowths of many other organisms, from polycheate worms to starfish. An amazing example of how the same genes in distantly related organisms can shape similar developmental pathways is seen in the development of eyes in fruit flies, mice, and humans. Walter Gehring and his collaborators examined the effect of the eyeless gene in Drosophila, which is required for proper development of the fruit-fly eye. Gehring and his coworkers genetically engineered cells that expressed eyeless in parts of the fly where the gene is not normally expressed. When these flies hatched, they had eyes on their wings, antennae, and legs (Figure 22. These structures were not just tissue that resembled eyes, but complete eyes with a cornea, cone cells, and photoreceptors that responded to light, although the flies could not use these eyes to see, because they lacked a connection to the nervous system.
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For two reasons medications dispensed in original container cheap 10 mg lotensin otc, the Department also declines to treatment 7th march bournemouth order 5mg lotensin with mastercard import the additional provision in Fed symptoms 7 days after implantation discount lotensin 5mg with mastercard. This modification provides protection to respondents exercising Fifth Amendment rights against self-incrimination (though it applies equally to protect complainants who choose not to appear or testify). Constitution, including the First Amendment, Fifth and Fourteenth Amendment, or any other constitutional provision. Nothing in the final regulations precludes a recipient from including in its training of decision-makers information about the purpose and scope of rape shield language in Fed. As noted by the Supreme Court, rape shield protections generally are designed to protect complainants from harassing, irrelevant inquiries into sexual behavior at trial. The second of the two exceptions to the rape shield protections refers to "if offered to prove consent" and thus the scope of that exception will turn in part on the definition of consent adopted by each recipient. Because of the flexibility recipients have under these final regulations to adopt a definition of consent, the Department disagrees that the scope of the second exception to the rape shield protections is too broad or favors respondents. Rather, the first exception applies to the narrow circumstance where a respondent contends that someone other than the respondent committed the misconduct, and the second applies narrowly to allow sexual behavior questions or evidence concerning incidents between the complainant and respondent if offered to prove consent. Not all definitions of consent, for example, require a verbal expression of consent; some definitions of consent inquire whether based on circumstances the respondent reasonably understood that consent was present (or absent), thus potentially making relevant evidence of past sexual interactions between the complainant and the respondent. The Department reiterates that the rape shield language in this provision does not pertain to the 1354 the Department notes that where a decision-maker determines, for example, that the respondent is not responsible for the allegations in the formal complaint, but also determines that the complainant did suffer the alleged sexual harassment but it was perpetrated by someone other than the respondent, the recipient is free to provide supportive measures to the complainant designed to restore or preserve equal access to education. The Department declines to require questions or evidence that may meet one of the rape shield exceptions to be allowed to be asked or presented at a hearing only if a neutral evaluator first decides that one of the two exceptions applies. As discussed above, the decision-maker will be trained in how to conduct a grievance process, including how to determine relevance and how to apply the rape shield protections, and at the live hearing the decision-maker must determine the relevance of a cross-examination question before a party or witness must answer. As discussed above, the Department declines to import a balancing test that would exclude sexual behavior questions and evidence (even meeting the two exceptions) unless probative value substantially outweighs potential harm or undue prejudice, because that open-ended, complicated standard of admissibility would render the adjudication more difficult for a layperson decision1197 maker competently to apply. Unlike the two exceptions in this provision, a balancing test of probative value, harm, and prejudice contains no concrete factors for a decision-maker to look to in making the relevance determination. The final regulations clarify the rape shield language to state that questions and evidence subject to the rape shield protections are "not relevant," and therefore the rape shield protections apply wherever the issue is whether evidence is relevant or not. The Department declines to require respondents to "lay a foundation" before asking questions, or to impose rules excluding questions based on hearsay or speculation. For reasons described above, relevance is the sole gatekeeper evidentiary rule in the final regulations, but decision-makers retain discretion regarding the weight or credibility to assign to particular evidence. The Department notes that the rape shield language does not limit the "if offered to prove consent" exception to when the question or evidence is offered by the respondent. The Department therefore declines to extend the rape shield language to encompass situations where the respondent wishes to prove the conduct was "welcome" as opposed to "unwelcome. Commenters asserted that this provision appropriately acknowledges the intimidating nature of cross-examination. Commenters also asserted that this provision reaches a reasonable balance between allowing cross-examination and protecting victims from personal confrontation with a perpetrator. Some commenters supported this provision but expressed concern that the live question-and-answer format, even avoiding face-to-face trauma, will still impose significant trauma for both parties. Commenters stated that many recipients already effectively utilize technology to enable parties to testify at live hearings without being physically conclusion of the grievance process. Some commenters opposed this provision, asserting that complainants should not be forced to be "live streamed" and instead should have the right to remain anonymous. Some commenters argued that "watering down" the Sixth Amendment right to face-to-face confrontation just to avoid traumatizing victims is not appropriate because the Constitution expects victims to endure the experience of making their accusations directly in front of an accused 1356 and the proposed rules do not even require a threshold showing of the potential for trauma before granting a request to permit virtual testimony. Other commenters argued that separating the parties does not adequately diminish the intimidating, retraumatizing prospect of a live hearing. Commenters argued that survivors of sexual violence will still be aware that their attacker is witnessing the proceedings and may feel less safe as a result. At least one commenter argued that remote cross-examination puts survivors at a distinct disadvantage because assessing non-verbal and behavioral evidence of trauma is necessary in sexual violence incidents. At least one commenter argued that witnesses must also be given the right to request to testify in a separate room. One commenter recounted a case in which a witness had also been raped by the respondent but the recipient did not allow the witness to testify in a separate room and the witness had to frequently leave the room during testimony due to sobbing too hard to speak. Commenters opposed requiring testimony in separate rooms on the basis that internet functionality on campus is not always reliable, and thus a rule that depends on technology is not realistic. Commenters supported use of technology to facilitate parties being in separate rooms as "ideal" but expressed concern that the cost of technology that is both reliable and secure could be prohibitive for some recipients because while software enabling simultaneous viewing of parties 1203 in separate rooms may be relatively inexpensive, acquiring additional hardware that may be necessary and expensive, such as audio-visual equipment, monitors, and microphones. Commenters requested that the Department provide grant funding for acquiring technology needed to meet this provision. Other commenters asserted that it is reasonable for separate rooms to be used to ensure complete, comfortable honesty by each party and that numerous low cost, secure presentation videoconferencing technologies are available and already in use by many recipients to ensure that participants can view and hear questions and responses in real time. Commenters correctly asserted that this provision is a direct acknowledgment of the potential for cross-examination to feel intimidating and retraumatizing in sexual harassment cases. Because the decision-maker cannot know until the conclusion of a fair, reliable grievance process whether a complainant is a victim of sexual harassment perpetrated by the respondent, cross-examination is necessary to test party and witness statements for veracity and accuracy, but the Department has determined that the full value of cross-examination can be achieved while shielding the complainant from being in the physical presence of the respondent. The Department disagrees that only in-person, face-to-face confrontation enables parties and decision-makers to adequately evaluate credibility, 1359 and declines to remove this shielding provision. As discussed above, assessing demeanor is just one of the ways in which crossexamination tests credibility, which includes assessing plausibility, consistency, and reliability; judging truthfulness based solely on demeanor has been shown to be less accurate than, for instance, evaluating credibility based on consistency. The Department disagrees that complainants should have to make a threshold showing that trauma is likely because the Department is persuaded by the many commenters who asserted that facing a perpetrator is H. These measures are intended to balance the need for statements to be tested for credibility so that accurate outcomes are reached, with accommodations for the sensitive nature of the underlying matters at issue. The Department notes that decision-makers are obligated to serve impartially and thus should not endeavor to "develop a personal relationship" with one party over another regardless of whether one party is located in a separate room or not.
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In other diseases medicine buy lotensin on line amex, the repeat is outside the coding region of a gene and affects its expression medicine xyzal buy discount lotensin 5 mg on-line. The mechanism that leads to medications and mothers milk buy lotensin master card the expansion of nucleotide repeats is not completely understood. Such structures may interfere with normal replication by causing strand slippage, misalignment of the sequences, or stalling of replication. One model of how repeat hairpins might result in repeat expansion is shown in Figure 18. Increased numbers of nucleotide repeats are associated with several genetic diseases. Phenotypic Effects of Mutations Another way that mutations are classified is on the basis of their phenotypic effects. At the most general level, we can distinguish a mutation on the basis of its phenotype compared with the wild-type phenotype. A mutation that alters the wild-type phenotype is called a forward mutation, whereas a reverse mutation (a reversion) changes a mutant phenotype back into the wild type. Geneticists use other terms to describe the effects of mutations on protein structure. A base substitution that results in a different amino acid in the protein is referred to as a missense mutation (Figure 18. Leu Ser the new codon is a stop codon; there is premature termination of translation. The new codon encodes the same amino acid; there is no change in amino acid sequence. The new codon encodes a different amino acid; there is a change in amino acid sequence. Because of the redundancy of the genetic code, some different codons specify the same amino acid. A silent mutation changes a codon to a synonymous codon that specifies the same amino acid (Figure 18. Not all silent mutations, however, are truly silent: some do have phenotypic effects. The rate of protein synthesis can influence the phenotype by affecting the amount of protein present in the cell and, in a few cases, the folding of the protein. A neutral mutation is a missense mutation that alters the amino acid sequence of the protein but does not change its function. Neutral mutations occur when one amino acid is replaced by another that is chemically similar or when the affected amino acid has little influence on protein function. For example, neutral mutations occur in the genes that encode hemoglobin; although these mutations alter the amino acid sequence of hemoglobin, they do not affect its ability to transport oxygen. Loss-of-function mutations cause the complete or partial absence of normal protein function. A loss-of-function mutation so alters the structure of the protein that the protein no longer works correctly or the mutation can occur in regulatory regions that affect the transcription, translation, or splicing of the protein. Loss-of-function mutations are frequently recessive, and an individual diploid organism must be homozygous for a loss-of-function mutation before the effects of the loss of the functional protein can be exhibited. The mutations that cause cystic fibrosis are loss-of-function mutations: these mutations produce a nonfunctional form of the cystic fibrosis transmembrane conductance regulator protein, which normally regulates the movement of chloride ions into and out of the cell (see Chapter 5). In contrast, a gain-of-function mutation produces an entirely new trait or it causes a trait to appear in an inappropriate tissue or at an inappropriate time in development. For example, a mutation in a gene that encodes a receptor for a growth factor might cause the mutated receptor to stimulate growth all the time, even in the absence of the growth factor. Still other types of mutations are conditional mutations, which are expressed only under certain conditions. For example, some conditional mutations affect the phenotype only at elevated temperatures. This type of mutation is distinct from a reverse mutation, in which the mutated site changes back into the original wild-type sequence (Figure 18. A suppressor mutation occurs at a site that is distinct from the site of the original mutation; thus, an individual with a suppressor mutation is a double mutant, possessing both the original mutation and the suppressor mutation but exhibiting the phenotype of an unmutated wild type. Geneticists distinguish between two classes of suppressor mutations: intragenic and intergenic. Red eyes White eyes Red eyes Intragenic suppressor mutation An intragenic suppressor mutation is in the same gene as that containing the mutation being suppressed and may work in several ways. The suppressor may change a second nucleotide in the same codon altered by the original mutation, producing a codon that specifies the same amino acid as that specified by the original, unmutated codon (Figure 18. If the original mutation is a one-base deletion, then the addition of a single base elsewhere in the gene will restore the former reading frame. This deletion shifts the reading frame by one nucleotide and alters all the amino acids that follow the mutation. A third way in which an intragenic suppressor may work is by making compensatory changes in the protein. A first missense mutation may alter the folding of a polypeptide chain by changing the way in which amino acids in the protein interact with one another. A second missense mutation at a different site (the suppressor) may recreate the original folding pattern by restoring interactions between the amino acids. Intergenic suppressors mutations An intergenic suppressor mutation, in contrast, occurs in a gene other than the one bearing the original mutation. Full-length, functional protein Shortened, nonfunctional protein Full-length, functional protein 18. The effect of this change would depend on the role of this amino acid in the overall structure of the protein, but the effect of the suppressor mutation is likely to be less detrimental than the effect of the nonsense mutation, which would halt translation prematurely. A mutation in one gene may alter the encoded polypeptide such that the interaction between the two polypeptides is destroyed, in which case a functional protein is not produced. A suppressor mutation in the second gene may produce a compensatory change in its polypeptide, therefore restoring the original interaction. Characteristics of some of the different types of mutations are summarized in Table 18. An intragenic suppressor mutation occurs within the same gene as that containing the original mutation, whereas an intergenic suppressor mutation occurs in a different gene. A second single-nucleotide mutation occurs in the same gene and suppresses the effects of the first mutation (an intragenic suppressor). With the original mutation and the intragenic suppressor present, the protein has the following amino acid sequence: Met-Asp-Gly-Ile-Lys-Arg What is the nature and location of the first mutation and of the intragenic suppressor mutation Insertions and deletions affect the reading frame; the original mutation consists of a single-nucleotide insertion or deletion in the second codon.
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There is reason for hope: human well-being need not depend on intensive resource use symptoms anemia purchase lotensin with amex. In order to medicine hunter buy 5 mg lotensin accelerate progress in that way medicine hat horse purchase lotensin online now, a more integrated approach that addresses multiple goals simultaneously is needed, rather than narrow, sectoral approaches that focus on one or an excessively narrow subset of goals at a time. An important key to doing that is to recognize that, while the present state of imbalance across the three dimensions of sustainable development arises from not having fully appreciated the interlinkages across them or having unduly prioritized the short term, it is those same interlinkages that will lead to the desired transformative change, when properly taken into account. Translating that insight into practical action for the Sustainable Development Goals needs to be informed by knowledge that emphasizes the need for urgency, forward-looking expectations about a growing global population seeking higher levels of well-being, and normative considerations such as leaving no one behind. Accordingly, the present Report identifies six entry points that offer the most promise for achieving the desired rebalancing at the scale and speed needed for the 2030 Agenda. These are not entry points into 21 the transformative power of sustainable development Figure 1-9 Striking the balance: no country is meeting basic human goals within biophysical boundaries 12 11 10 9 8 No countries are in top left quadrant where basic human needs and sustainable resource use are more in balance. The six entry points are: f f f f f f Human well-being and capabilities Sustainable and just economies Food systems and nutrition patterns Energy decarbonization and universal access Urban and peri-urban development Global environmental commons education and skills, especially looking to the future; unequal access to health care, exposure to disease, and attainment of high standards of health; insufficient resilience to recover from shocks; and inadequate preparation for dealing with ageing. Many of the needed transformations in this area are demonstrably possible within more balanced economic paths. Sustainable and just economies: Economic activity provides livelihoods, jobs, incomes and the means to attain many other elements of a better life, however, current production and consumption systems also threaten the well-being of present and future generations through increasingly negative impacts on the environment and, in many cases, inequality. A fundamental reconfiguration is needed in the production and consumption of goods and services, guided by a lowered environmental footprint and greater distributional justice. Moreover, national and international financial systems must be aligned to the Sustainable Development Goals. Achieving the 2030 Agenda for sustainable development will require leadership from both the public and the private sector, Human well-being and capabilities: this is key to the overarching mission of eradicating poverty in all its forms and manifestations and reducing inequalities to leave no one behind. However, we are at risk of not succeeding due to inequalities in opportunities; persistent gender inequality; mismatches between Global Sustainable Development Report 2019 targeted policy interventions, and shifts in social and lifestyle norms. Food systems and nutrition patterns: this is essential for sustenance and health, yet current practices along the entire food production and consumption chain lead to unsustainable resource use, biodiversity loss, land degradation, river and ocean pollution, climate change, undernutrition, as well as obesity and noncommunicable diseases. Energy decarbonization and universal access: Energy is key to economic growth, poverty eradication and the realization of human potential, but it is also the single largest contributor to climate change and particulate air pollution, as well as other negative impacts on people and the planet. Technologies exist for moving towards universal access and increased efficiency along decarbonized pathways, but major difficulties persist in achieving adoption at scale. Areas of concern include unsustainable natural resource use, large volumes of waste, and stark inequalities. Decisions on urban and peri-urban infrastructure investment can lock populations into unsustainable development for the very long term. Global environmental commons: this is essential for the overall balance between nature and humanity. Natural systems are interconnected on a global scale and affected by actions at all levels that have implications across the world. Achieving transformation in the entry points would help to secure the global environmental commons. However, the entry points alone may not be sufficient, especially if actions do not adequately address global interconnections or take full account of the non-economic, but intrinsic value of nature. The Report also identifies four levers: f f f f Governance, Economy and finance, Individual and collective action, and Science and technology. The levers can be deployed to bring about the necessary transformations through each entry point. They are related to the means of implementation characterized in Goal 17 but are also different in that they accommodate the multiple, complementary roles that individual actors and entities play in bringing about change. For example, engineers develop technology solutions (included in the science and technology lever) but can also collaboratively set standards for ethical applications of advanced technologies (as part of both the governance and the collective action levers). Each of the levers can contribute to systemic change, however, in this Report, it is argued that only through their context-dependent combinations will it be possible to achieve the transformations necessary for balancing across the dimensions of sustainable development and achieving the 2030 Agenda. The space for moving to a sustainable development trajectory lies at the interface between these two components of the Earth System (panel A). Currently, however, the world is not set on a trajectory that lies within this space. The 2030 Agenda for Sustainable Development defines a political space within which United Nations Member States have committed themselves to managing both the relationships among human beings and between human activities and the planet. That space is delineated by a set of social targets that define human wellbeing and capabilities, as well as environmental targets to secure nature and the global commons (panel B). As those social and environmental targets are intractably linked, it is not possible to carry out one intervention without influencing another. Therefore, choices need to be made with respect to balancing the gains and tradeoffs of all activities. The overarching objectives provide essential guidance for making choices (panel C). Achieving more equitable and balanced development within the political space of the 2030 Agenda is possible only by engaging with the systems that connect people and nature to their guiding goals (panel D). Taking a systemic perspective on the Sustainable Development Goals and their interactions, the present Report identifies six key entry points for successful transformations towards sustainable development, and four levers that are critical to maximizing impacts in different parts of the world. As stated previously, the biggest transformative potentials of the 2030 Agenda do not lie in pursuing single Goals or targets but rather in a systemic approach that manages their myriad interactions. This chapter sets out options for knowledge-based transformations towards sustainable development, using the six entry points introduced in the previous chapter that relate to human well-being; sustainable and just economies; sustainable food systems and nutrition patterns; energy decarbonization and universal access to energy; sustainable urban and peri-urban development; and the global environmental commons. Although some of those entry-points may seem to single out individual Goals, the Report focuses on the systems in which they are embedded. Progress on any Sustainable Development Goal will depend on a range of interactions with other Goals that either support achievement through co-benefits or hinder achievement through trade-offs. Harnessing the transformative potential of those systems as accessed through the identified entry points, implies a careful and structured management of interactions. Progress on all the Goals will only be achieved if important trade-offs are addressed and transformed, and if co-benefits are deliberately realized. In other words, managing the arrows is more important than managing the boxes/circles of individual targets. Each lever is a powerful agent of change in its own right and impact the Goals through the identified entry points. It should be pointed out, however, that true transformation is possible only when the levers are deployed together in an integrated and intentional manner. The central innovation needed to advance the implementation of the 2030 Agenda must therefore come from novel combinations of different levers and the novel collaboration of the respective actors in governance, economy and finance, individual and collective action, and science and technology. There is no one-size-fits-all solution for achieving sustainable societal development.
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In this situation treatment 4 lung cancer purchase discount lotensin on-line, natural selection will favor genotypes at other loci that cause assortative mating (matings between like individuals medicine 1700s order online lotensin, see Chapter 25) medications used to treat fibromyalgia buy lotensin master card, and so no matings take place between A1A1 and A2A2, which would produce A1A2 offspring with low fitness. Now imagine that alleles at a second locus affect mating behavior, such that C1C1 individuals prefer mating only with other C1C1 individuals, and C2C2 individuals prefer mating with other C2C2 individuals. If alleles at the A locus are nonrandomly associated with alleles at the C locus so that only A1A1 C1C1 individuals and A2A2 C2C2 individuals exist, then gene flow will be restricted between individuals using the different resources, allowing the two groups to evolve further genetic differences that might lead to reproductive isolation and sympatric speciation. The difficulty with this model is that recombination quickly breaks up the nonrandom associations between genotypes at the two loci, producing individuals such as A1A1 C2C2, which would prefer to mate with A2A2 C2C2 individuals. Thus, even limited recombination will prevent the evolution of the mating-preference genes. Sympatric speciation is more probable if the genes that affect resource utilization also affect mating preferences. Genes that affect both resource utilization and mating preference are indeed present in some host races-populations of specialized insects that feed on different host plants. Guy Bush studied what appeared to be initial stages of speciation in host races of the apple maggot fly (Rhagoletis pomonella, Figure 26. Mating takes place near the fruits, and the flies lay their eggs on the ripened fruits, where their larvae grow and develop. Because mating takes place on and near the fruits, flies that use apples are more likely to mate with other flies using apples, leading to genetic isolation between flies using hawthorns and those using apples. Indeed, Bush found that some genetic differentiation has already taken place between the two host races. Flies lay their eggs on ripening fruit, and there has been strong selection for the flies to synchronize their reproduction with the period when their host species has ripening fruit. Correspondingly, the peak mating period of the apple host races is 3 weeks earlier than that of the hawthorn race. These differences in the timing of reproduction between apple and hawthorn races have further reduced gene flow-to about 2%-between the two host races and have led to significant genetic differentiation between them. These differences have evolved in the past 150 years and evolution appears to be ongoing. Although genetic differentiation has taken place between apple and hawthorn host races of R. Speciation through polyploidy A special type of sympatric speciation takes place through polyploidy (see Chapter 9). As discussed in Chapter 9, allopolyploidy often arises when two diploid species hybridize, producing 2n hybrid offspring. Because this tetraploid contains exactly two copies of each chromosome, it is usually fertile and will be reproductively isolated from the two parental species by differences in chromosome number (see Figure 9. Speciation through polyploidy was observed when it led to a new species of salt-marsh grass that arose along the coast of England about 1870. This polyploid contains genomes of the European salt grass Spartina maritima (2n = 60) and the American salt grass S. Seeds from the American salt grass were probably transported to England in the ballast of a ship. Sympatric speciation may arise under special circumstances, such as when resource use is linked to mating preference (in host races) or when species hybridization leads to allopolyploidy. This question has received considerable study by evolutionary geneticists, but, unfortunately, there is no universal answer. Some newly formed species differ in many genes, whereas others appear to have undergone divergence in just a few genes. One group of organisms that have been extensively studied for genetic differences associated with speciation is the genus Drosophila. The Drosophila willistoni group consists of at least 12 species found in Central and South America in various stages in the process of speciation. Using protein electrophoresis, Francisco Ayala and his colleagues genotyped flies from different geographic populations (populations with limited genetic differences), subspecies (populations with considerable genetic differences), sibling species (newly arisen species), and nonsibling species (older species). For each group, they computed a measure of genetic similarity, which ranges from 1 to 0 and represents the overall level of genetic differentiation (Table 26. They found that there was a general decrease in genetic similarity as flies evolve from geographic populations to subspecies to sibling species to nonsibling species. These data suggest that considerable genetic differentiation at many loci is required for speciation to arise. However, other studies suggest that speciation may have arisen through changes in just a few genes. Genetic studies indicate that only a few loci (about 10) determine the differences in head shape. Genetic Differentiation Associated with Speciation As we have seen, genetic differentiation leads to the evolution of reproductive isolating mechanisms, which restrict gene flow between populations and lead to speciation. Because most evolution takes place over long periods of time and is not amenable to direct observation, biologists must reconstruct phylogenies by inferring the evolutionary relationships among present-day organisms. The discovery of fossils of ancestral organisms can aid in the reconstruction of phylogenies, but the fossil record is often too poor to be of much help. Thus, biologists are often restricted to analyses of characteristics in present-day organisms to determine their evolutionary relationships. In the past, phylogenetic relationships were reconstructed on the basis of phenotypic characteristics-often, anatomical traits. Phylogenies are reconstructed by inferring changes that have taken place in homolBranches are the evolutionary connections ogous characteristics. The length of a branch evolved from the same character in a comrepresents the amount of evolutionary mon ancestor. Zebras these two anatomical features look different and have different functions, close examination of their structure and development Grevy reveals that they are indeed homologous. And, because mouse and bat have these homologous features and others in comMountain mon, we know that they are both mammals. For common ancestor of Wild ass example, all eukaryotic organisms have a all other organisms in the tree. This gene is assumed to have arisen in a single organism Half ass (onager) in the distant past and was then passed down to descendants of that early ancestor. Today, all copies of the cytochrome c gene are homologous, because they all evolved from the same original copy in the distant ancesHorses Domestic tor of all organisms that possess this gene. A phylogenetic tree consists of nodes that represent the different organisms being compared, which might be different individuals, populations, or species. Terminal nodes (those at the end of the outermost branches of the tree) represent organisms for which data have been obtained, usually present-day organisms. Internal nodes represent common ancestors that existed before divergence between organisms took place. In most cases, the internal nodes represent past ancestors that are inferred from the analysis.
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The complementation test tells us nothing about these medications blood donation generic lotensin 10 mg amex, because we have not yet included them in any of the crosses treatment narcolepsy lotensin 10mg fast delivery. To test allelism with P and C medications without a script order lotensin 10mg free shipping, we would have to cross one mutant strain from each complementation group with strains of genotype pp and cc. If the F1 progeny are mutant, it identifies the complementation group with an already known mutation. For example, suppose we cross each of the strains x1x1, x3x3, and x4x4 with pp and cc. Suppose further that the progeny are all wildtype except in two crosses-x1x1 pp and x3x3 cc-in which the progeny are mutant. This result implies that the complementation group consisting of x1 and x5 also includes p and that the complementation group consisting of x3 also includes c. At this point in the genetic analysis, it is advisable to rename the mutations to indicate which ones are true alleles. Old names have priority, and so we must use the symbol p embellished with some sort of identifier. We might, for example, rename the x1 and x5 mutations p2 and p3 to indicate that they were the second and third mutations of P to be discovered and to convey their independent origins. The remaining complementation group consisting of x2, x4, and x6 is a new one, and we can name it arbitrarily. For example, we might call the locus albus (Latin for "white") with the gene symbol alb and call the alleles alb1, alb2, and alb3. The wildtype dominant allele of alb, which is necessary for purple coloration, would then be represented as Alb or as alb. The procedure of sorting new mutations into complementation groups and renaming them according to their allelism is an example of how geneticists identify genes and name alleles. Such renaming of alleles is the typical manner in which genetic terminology evolves as knowledge advances. This connecting line means that x1 and x5 fail to complement one another when the parents are crossed; they are alleles of the same gene. In this example, there are three complementation groups, each of which represents a single gene needed for purple flower coloration. Part A depicts the situation when two recessive mutations, x1 and x2, each resulting in white flowers, are different mutations in the same gene. Hence alleles in the same gene yield a mutant phenotype (white flowers), because neither mutation encodes a wildtype form of the protein. When the mutations are alleles of different genes, the situation is as depicted in Figure 3. Because the mutations are in different genes, the homozygous x1 strain is also homozygous for the wildtype allele x2 of the second locus; likewise, the homozygous x2 strain is also homozygous for the wildtype allele x1 of the first locus. Hence, the same cross that yields the genotype x1x2 in the case of allelic mutations (Figure 3. Because the mutations are both recessive and in different genes, they do complement each other and yield an organism with a wildtype phenotype (purple flowers). With respect to the protein rendered defective by x1, there is a functional form encoded by the 122 Chapter 3 Transmission Genetics: the Principle of Segregation wildtype allele brought in from the x2x2 parent. With respect to the protein rendered defective by x2, there is again a functional form encoded by the wildtype allele brought in from the x1x1 parent. Because a functional form of both proteins is produced, the result is a normal phenotype, or complementation. Chapter Summary Mendelian genetics deals with the hereditary transmission of genes from one generation to the next. One key principle is segregation, in which the two alleles in an individual separate during the formation of gametes so that each gamete is equally likely to contain either member of the pair. The phenotype of the F1 progeny depends on the dominance relationships among the alleles. In the formation of gametes, an Aa genotype produces A-bearing and a-bearing gametes in equal proportions. The distribution of phenotypes in the F2 generation again depends on the dominance relationships. If A is dominant to a, then the F2 ratio of dominant: recessive phenotypes is expected to be 3: 1. With codominance all three genotypes are distinguishable, and the ratio of F2 phenotypes is 1: 2: 1. Segregation of each gene implies that the ratios of A: a and of B: b gametes are both 1: 1. If the genes are unlinked, they undergo independent segregation (independent assortment), and the gametic types A B: A b: a B: a b are formed in the ratio 1: 1: 1: 1. Using a dash to represent an allele of unspecified type, we can write the F2 genotypes as 9 A B: 3 A bb: 3 aa B: 1 aa bb, and if both A and B are dominant, the phenotypic ratio in the F2 generation is 9: 3: 3: 1. This ratio can be modified in various ways by interaction between the genes (epistasis). Different types of epistasis may result in dihybrid ratios such as 9: 7 or 12: 3: 1 or 13: 3 or 9: 4: 3. The rules of probability provide the basis for predicting the outcomes of genetic crosses based on the principles of segregation and independent assortment. Two basic rules for combining probabilities are the addition rule and the multiplication rule. The addition rule applies to mutually exclusive events; it states that the probability of the realization of either one or the other of two events equals the sum of the respective probabilities. The multiplication rule applies to independent events; it states that the probability of the simultaneous realization of both of two events is equal to the product of the respective probabilities. In some organisms, including human beings, it is not possible to perform controlled crosses, and genetic analysis is accomplished through the study of pedigrees through two or more generations. Pedigree analysis is the determination of the possible genotypes of the family members in a pedigree and of the probability that an individual member has a particular genotype. The goal of pedigree analysis is often to infer the genetic basis of an inherited disease or other condition-for example, to determine whether it may be due to a simple dominant or recessive allele. Although most morphological traits do not show simple Mendelian patterns of inheritance in pedigrees, molecular markers usually do. Multiple alleles are often encountered in natural populations or as a result of mutant screens. Although there may be multiple alleles in a population, each gamete can carry only one allele of each gene, and each organism can carry at most two different alleles of each gene. If a cross between two homozygous recessive genotypes results in nonmutant progeny, the mutations are said to complement one another. On the other hand, if a cross between two homozygous recessives results in mutant progeny, then the alleles show noncomplementation (they fail to complement).