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The malformation may be related to disturbances in the external granule cell layer (Henion et al prehypertension american heart association quality 4 mg cardura. The brain stem is affected in nearly all patients, manifesting enlarged quadrigeminal plates, fusion of the colliculi, and hypoplasia of the pons, often with a longitudinal ventral midline pontine cleft (Figs 10 and 11) (Barkovich et al. The small pons with midline cleft may be caused by hypoplasia of the middle cerebellar peduncles resulting in hypoplasia of their decussation; another component of the pontine hypoplasia may relate to impaired tangential migration of pontine nuclear neurons as shown in murine models of Large mutations (Qu et al. Thus, as in the cerebral hemispheres, the midbrain-hindbrain disorder appears to be the result of both abnormal neuronal migration and abnormal formation of white matter tracts. Most have subtle cerebellum hypoplasia; a few have mild or moderate cerebellum hypoplasia. Periventricular nodular heterotopia with overlying polymicrogyria and prominent brainstem and cerebellum hypoplasia (Wieck et al. From most to least severe, the spectrum of cobblestone malformations-associated phenotypes includes Walker-Warburg syndrome, muscle-eyebrain disease, Fukuyama congenital muscular dystrophy and congenital muscular dystrophy without recognized brain malformations. Cobblestone-like malformations with variable glycosylation defects Brain imaging studies closely resemble those of classic muscle-eye-brain disease in all of these disorders, which thus differ from polymicrogyria. In the cerebellum, mouse models demonstrate that granule cells show loss of adhesion to extracellular matrix molecules of the pial basement membrane (Koirala et al. These disorders have abnormalities of white matter tracts in the brain stem and abnormal superior cerebellar peduncles. Thus, the two disorders represent different points along a single spectrum of malformations (Baala et al. Although the precise mechanisms by which these mutations affect brain development are only starting to be elucidated (Arts et al. Sagittal T1-weighted image shows massive hydrocephalus, a very small, dysplastic vermis (small arrowheads), large, round tectum (small arrows) and small, ventrally kinked pons (large arrowhead). Regional developmental defects (localized brain malformations that significantly affect the brainstem and cerebellum, pathogenesis partly or largely understood) Patients in this group (Table 8) have malformations of the brain stem or cerebellum that are localized and manifest clinically with neurological signs that are attributable to one anatomofunctional system rather than diffuse. Most are present from the time of birth, although some may not become evident until childhood. These may be seen in the dorsal or ventral midline surface of the pons, particularly in patients with cerebellar hypoplasia or dysplasia, but also in patients with normal cerebella (Barkovich et al. These are believed to result from impaired pathfinding of axons in the developing brain stem. These are likely to be due to absence of the decussation of the middle cerebellar peduncles and possibly the transverse pontine axons migrating from the cerebellar cortex to the pontine nuclei. They are often associated with cerebellar hypoplasia, although they are also reported as a manifestation of generalized axonal midline crossing defects; when the midline-crossing defect is more generalized, the corpus callosum is often abnormal (Barkovich et al. Midline dorsal clefts are thought to result from abnormal development of the median longitudinal fasciculus and the tectospinal tract (Barkovich et al. Diffusion tensor tractography shows more extensive white matter abnormalities including absence of major pontine crossing axons and absence of decussation of the superior cerebellar peduncles in addition to reduced volume of dorsal longitudinal tracts in the pontine tegmentum (Sicotte et al. Several other brain stem disorders purportedly secondary to abnormal axonal pathfinding have been described (Barkovich et al. These include the recently reported pontine tegmental cap dysplasia, a malformation in which the ventral pons is hypoplastic due to absence of normal ventral decussation of the middle cerebellar peduncles while a band of horizontally oriented axons is present, instead, along the dorsal surface of the pons. Other disorders that are presumably due the white matter guidance disruptions in the brain stem have been described recently (Barkovich et al. It is likely that an increasing number will be discovered as the quality of brain imaging improves, with higher field strength magnetic resonance scanners and as diffusion tensor tractographic methods become more robust. Human by phenotype Oro-facio-digital syndrome type 6 (Varadi) Comments and references (Saar et al. Syndromes affecting the brain, eyes, kidneys, liver and variable other systems (Keeler et al. The neurological phenotype includes cognitive and behavior problems, congenital oculomotor apraxia, ataxia and alternating hyperpneaapnea. All syndromes in this group have autosomal recessive inheritance, and all genes so far identified code for ciliary proteins. They appear to be clinically asymptomatic when minor (abnormal orientation of vermian fissures) but may be associated with developmental delay when more extensive (Demaerel, 2002). Another disorder included in this group is cerebellar heterotopia, formed of clusters of neurons that typically lie within the white matter of a cerebellar hemisphere (Friede, 1989; Norman et al. Defects secondary to combined hypoplasia and atrophy in putative prenatal onset degenerative disorders the final group of defects is composed of progressive disorders in which the cerebellum is already small at birth and subsequently undergoes further atrophy (Table 9). Axial T2-weighted image shows midline pontine dorsoventral cleft (arrows) caused by lack of midline crossing of axons. Figure 12 Molar tooth malformation in patient with ataxia, developmental delay, and nephronophthisis. Type 1 has spinal motor neuron loss; type 2 is characterized pathologically by normal spinal motor neurons and clinically by chorea/dystonia; type 3 has absence of dyskinesias, optic atrophy, and linkage to chromosome 7q11-21; types 4 and 5 have C-shaped inferior olivary nuclei with relative vermian sparing in type 4 (Hevner, 2007). This observation suggests that the causative gene(s) are important both for cerebellar neuronal development and for postmitotic neuronal survival (Hevner, 2007). The other major disorders in this group are unilateral cerebellar hypoplasia and cerebellar cortical dysplasia [also called cerebellar polymicrogyria and cerebellar heterotaxia (Friede, 1989; Norman et al. Both disorders are most often detected incidentally on neuroimaging studies for patients with unrelated complaints. If assessed carefully, these patients typically have abnormal foliation (Soto-Ares et al.

There is another category of poor and destitute migrants who have virtually no assets in the areas of origin arrhythmia 2013 order 4mg cardura with visa, and have lost all contact with their origin. Thus not all poor migrants would fall within the category of seasonal/short-term migrants. But, as stated earlier, for one reason or another, all these categories are likely to be underestimated. Informal estimates of seasonal/short-term migration made from time to time suggest that these flows might be underestimated in national surveys. Large numbers of migrants were found in agriculture and plantations, brick kilns, quarries, on construction sites and in fish processing. A number of recent field studies conducted during the 90s also provide rough estimates of the magnitude of seasonal migration in different parts of India. The bulk of this migration is rural-rural, ranges from a few weeks to a few months, and takes place in unorganized industry, mining and agriculture. Although males predominate in most labour migration streams, in a number of other cases, both men and women migrate together for work. A little less than 50 per cent of the urban and rural migrants, and over 50 per cent of male migrants in both sectors are in the top two consumption quintiles. Among other factors, this may reflect the higher work participation rates among migrants as well as the propensity to migrate among the better off. Micro studies show a bimodal relationship in respect of wealth/income and land, viz. Data on individual migrants from micro surveys show a significant clustering of migrants in the 16 to 40 year age group (Conell et al. In terms of education, migration rates are high among both the highly educated and the least educated, while there is a high preponderance of illiterates among seasonal migrants (Connell et al. Migration in India reflects household subsistence strategies in the face of social, cultural, demographic and other constraints. The National Commission on Rural Labour, focusing on seasonal migration, concluded that uneven development was the main cause of seasonal migration. In the tribal region intrusion of outsiders, settlements in tribal areas, displacement and deforestation have also contributed significantly to the seasonal outmigration of tribals. Mobility occurs when workers in source areas lack suitable options for employment/livelihood, and there is some expectation of improvement in circumstances through migration. The sought-for improvement may concern better employment opportunities or higher wages/incomes, as well as the wish to maximize family employment, or to smooth employment/income/consumption impacts over time. At one end of the migration spectrum workers could be locked into a debt-migration cycle through some form of labour bondage, where earnings from migration are used to repay debts incurred at home or in the destination areas, thereby cementing the migration cycle. Where migration is essentially involuntary, and induced by debt relations or other coercive factors in the source or destination areas, it makes little sense to use voluntaristic models to explain the phenomenon. At the other end, however, migration is largely voluntary, although shaped by limited choices. The growth of intensive agriculture and the commercialization of agriculture in different parts of the country since the late 1960s, have led to peak periods of labour demand, often also coinciding with a decline in local labour availability. Migration decisions are influenced by both individual and household characteristics, as well as the social matrix, which is best captured in social-anthropological studies. Factors such as age, education level, wealth, land ownership, productivity and job opportunities influence the participation of individuals and households in migration, as do social attitudes and the presence of supporting social networks (Haberfeld et al. In many sectors, the preference by employers for migrant labour arises not because of local shortages, but because migrant labour is easy to discipline and less expensive. Not surprisingly, labour market segmentation goes hand in hand with the deployment of migrant labour in such situations. They have few personal assets and suffer from a range of severe deprivations in the destination areas. As regards the source areas, migration has both negative and positive consequences for migrants and their families. Migrant labourers, whether in agricultural or non-agricultural activities, in rural or urban areas, usually live in deplorable conditions with inadequate provision of drinking water and basic services. Seasonal migrant labourers live in open spaces or makeshift shelters in spite of the Contract Labour Act in force. Apart from seasonal workers, workers who migrate to the cities in search of work live in parks and on the pavement, in squatter settlements or slums. Obliged to work and live in harsh and unhygienic conditions, migrant labourers are particularly vulnerable to diseases and occupational health hazards. Yet, because of their temporary status, if they are registered at all, they cannot access various health and family care programmes. Having no one to look after their children, migrant families often take their children with them to their workplace. Because of their poor and unhygienic living conditions, and exposure to dust at the work site, children suffer from various health problems. Moreover, they have no opportunity to obtain an education either in their original place of residence or where their parents work. Where men migrate alone, the impact on the family unit and on women, children and the elderly left behind can be quite significant. The absence of men adds to material and psychological insecurity, causing pressures and requiring negotiations with the extended family members (Rogaly et al. On the other hand, male migration has also been seen to influence the direct participation of women in the economy as workers and decision-makers and increased the degree of their interaction with the world beyond the family and kin. But given the patriarchal tradition, women may have to cope with a number of problems that are further exacerbated by the uncertainty of the timing and size of remittances on which the precarious household economy ultimately depends. This, in turn, pushes women and children from poor labouring households to participate in the labour market under adverse conditions. The impact of male migration can be especially adverse for girls, who often have to bear the additional domestic responsibilities and take care of younger siblings.

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Migration policy needs to tackle migration at different levels blood pressure chart female cheap 4mg cardura free shipping, through institutions that are geared to different sectors (labour, gender, agriculture, rural development, social welfare and urban development). There may be a case for creating a separate coordinating body to prioritize and sequence the needed interventions. With these general guiding principles in mind, some areas for policy attention at the macro level can be identified: Fostering rural-urban linkages At the macro level there is a need for countries to foster rural-urban linkages in order to create the virtuous circles described previously and to broaden the perspective on rural and urban and not view them as distinct and separate. A principal thrust of its Central Region Development Strategy (2000) and the Viet Nam Urban Forum is to enhance rural-urban linkages. Moving away from a focus on agriculture as the sole route to poverty reduction Current poverty reduction policies tend to focus on agriculture. There is little doubt that the majority of the poor live in rural areas and are largely dependent on agriculture. But a number of authors are now questioning whether this necessarily implies that investing in agriculture is the 49 best way of reducing poverty (Song, 2004; Deshingkar, 2004). The latest figures suggest that average aggregate agricultural growth is less than 2 per cent a year, which is too slow for poverty reduction in many rural areas. The connections, if any and of what kind, between this and growing mobility need to be better understood. Given the massive scale of investment needed to install even basic infrastructure in weakly integrated rural areas, and the growing search for jobs in urban areas, donors and policy makers should be addressing the question of whether more should be done to facilitate the mobility of people. This is particularly relevant as experience shows that the prospects of strong agriculture and natural resource-based growth in the more remote and dry areas can continue to be poor even with infrastructure in place. Predicting collapse and supporting diversification In the planning process it is important to recognize which sectors are important for migrant labour and to predict how these will fare in the future. Where downsizing or collapse is predicted, it is important to anticipate, and prepare for, the consequences. In the case of the export garment industry, it appears that preparations have been inadequate in Bangladesh, one of the hardest hit countries. They urge companies to assume more responsibility for mitigating adverse impacts, including the provision of cash to compensate laid-off workers and providing retraining through mechanisms that actively encourage women to participate, and resisting the temptation to lower labour standards in an effort to compete. The informal economy Another area needing attention is the role of the informal economy and its potential for poverty reduction. Many governments continue to regard it as a low-productivity sector that perpetuates poverty and all kinds of social ills. However, many activities in the informal sector continue to be illegal because very few permits are issued. There is an overwhelming demand for and supply of services in the informal sector, which has assumed vast proportions and supports the rentseeking among petty officials and policemen who are not above benefiting from the (illegal) livelihood strategies pursued by a majority of the poor in the informal sector. Clearly, there is a need to regulate the informal sector in ways that support multi-locational livelihood strategies; but, as Box 4 shows, this is not an easy proposition and there are few successful examples. In Bangladesh this is the second most important economic activity for the poor, after cropping (personal communication with Bijoy Kumar Barua, Bangladesh Academy for Rural Development). In New Delhi there were some 73,000 licensed and 300,000 unlicensed rickshaws in 2001. Partially in response to civil society group pressure, the Government of India repealed the Cycle Rickshaw By-laws, and thus control over registration and regulation of rickshaws in 2001 in order to foster a more pro-poor environment. However, this caused the 33 numbers of rickshaws to literally explode to over 700,000 in just one year, and the emergence of so called rickshaw-lords, people who own about 10,000 rickshaws each and charge a rent of Rs 50-60 per 12 hours, confronting the government with the problem that rent-seeking by officials was replaced by rent-seeking by these rickshaw lords. In case a rickshaw driver is unable to pay the rent, he faces the threat of being beaten up by the owner and having his belongings confiscated. Because of these unforeseen problems and also because intelligence reports had suggested that many rickshaw pullers were illegal immigrants from Bangladesh, the change in legislation was reversed. At the same time, training in skills and education to help migrants to secure better-paid jobs and to match their capabilities with the emerging high-skill sectors remains a priority. They therefore recommend an emphasis on the building of human capital, and the creation of information networks. Elsewhere this is being left largely to market forces as a study of international migrant training programmes by Tan (2004b) shows. The importance of improved infrastructure cannot be overstated, and many donors and national policies have rightly identified this as a priority area. Associated with this is the need for more accessible transport services that have been shown to have a major impact on mobility. While it is probably unrealistic to expect large-scale surveys to engage everywhere with in-depth and highly time consuming analysis, it should certainly be possible to include some case studies using multidisciplinary approaches and a mix of quantitative and qualitative methods. The extent to which such studies can be undertaken to throw more light on migration processes will depend on the availability of financial, human and institutional resources, and there is a clear need for donor assistance to build the necessary capacity in these areas. Better information on migration and its potential role in poverty reduction is also likely to lead to a change in official attitudes, and help in fostering a better understanding of the ways in which policy can both support migration and respond to its effects. One example is the long-term study on rural-urban mobility being conducted by the Ford Foundation in China since 1994. This unique study provides vital information on population movements and the socio-economic consequences of such movements. Workshops and meetings involving participants from these projects could facilitate "cross learning". As mentioned before, two Indian livelihood projects have already made some progress in this direction. The World Bank is considering work on labour migration in the Mekong Subregion (personal communication with Pierre Fallavier). Besides considering means of improving the understanding of the causes and effects of migration, as well as 52 designing programmes to reduce the costs of migration, policy makers need to ask more fundamental questions about the best approaches towards reducing poverty and inequality.

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Increased synthesis of ketone bodies: the liver is unique in being mmol/l blood 4 Fatty acids 2 0 0 10 20 30 Days of starvation 40 Figure 24 pulse pressure less than 10 generic cardura 2mg amex. The availability of circulating water-soluble ketone bodies is important in fasting because they can be used for fuel by most tissues, including brain tissue, once their level in the blood is sufficiently high. This reduces the need for gluconeogenesis from amino acid carbon skeletons, thus preserving essential protein. Ketogenesis as part of the overall hepatic response to fasting is shown in Figure 24. These compounds, which are released from the sympathetic nerve endings in adipose tissue, are physiologically important activators of hormone-sensitive lipase (Figure 24. They also can be re-esterified to glycerol 3-phosphate (from glyceroneogenesis, see p. By contrast, exercising muscle initially uses its glycogen stores as a source of energy. During intense exercise, glucose 6-phosphate derived from glycogen is converted to lactate by anaerobic glycolysis (see p. Lipid metabolism During the first 2 weeks of fasting, muscle uses fatty acids from adipose tissue and ketone bodies from the liver as fuels (Figure 24. After about 3 weeks of fasting, muscle decreases its use of ketone bodies and oxidizes fatty acids almost exclusively. The Feed/Fast Cycle leads to a further increase in the already elevated level of circulating ketone bodies. Because muscle does not have glucagon receptors, muscle proteolysis likely is initiated by the fall in insulin and sustained by the rise in glucocorticoids. This reduces the need for protein catabolism for gluconeogenesis: ketone bodies spare glucose and, thus, muscle protein. The metabolic changes that occur during fasting ensure that all tissues have an adequate supply of fuel molecules. The response of the major tissues involved in energy metabolism during fasting is summarized in Figure 24. Kidney expresses the enzymes of gluconeogenesis, including glucose 6-phosphatase, and in late fasting about 50% of gluconeogenesis occurs here. In long-term fasting, then, there is a switch from nitrogen disposal in the form of urea to disposal in the form of ammonia. In the absorptive state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol, and protein (Figure 24. The absorptive state is the two- to four-hour period after ingestion of a normal meal. During this interval, transient increases in plasma glucose, amino acids, and triacylglycerols occur, the last primarily as components of chylomicrons synthesized by the intestinal mucosal cells. The pancreas responds to the elevated levels of glucose and amino acids with an increased secretion of insulin and a decrease in the release of glucagon by the islets of Langerhans. In addition, the liver replenishes its glycogen stores, replaces any needed hepatic proteins, and increases triacylglycerol synthesis. The latter are packaged in very-low-density lipoproteins, which are exported to the peripheral tissues. The adipose increases triacylglycerol synthesis and storage, whereas the muscle increases protein synthesis to replace protein degraded since the previous meal. In the absence of food, plasma levels of glucose, amino acids, and triacylglycerols fall, triggering a decline in insulin secretion and an increase in glucagon and epinephrine release. The decreased insulin to glucagon ratio, and the decreased availability of circulating substrates, makes the period of fasting a catabolic period. This sets into motion an exchange of substrates among liver, adipose tissue, muscle, and brain that is guided by two priorities: 1) the need to maintain adequate plasma levels of glucose to sustain energy metabolism of the brain and other glucose-requiring tissues; and 2) the need to mobilize fatty acids from adipose tissue and ketone bodies from liver to supply energy to all other tissues. To accomplish these goals, the liver degrades glycogen and initiates gluconeogenesis, using increased fatty acid oxidation as a source of the energy needed for gluconeogenesis, and to supply the acetyl coenzyme A building blocks for ketone body synthesis. The adipose degrades stored triacylglycerols, thus providing fatty acids and glycerol to the liver. The muscle can also use fatty acids as fuel, as well as ketone bodies supplied by the liver. Muscle protein is degraded to supply amino acids for the liver to use in gluconeogenesis. Most enzymes that are regulated by covalent modification are in the phosphorylated state. The increased insulin and decreased glucagon levels characteristic of the fed state promote the synthesis of fructose 2,6bisphosphate. Most covalently modified enzymes are in the dephosphorylated state and are active. Free fatty acids bound to albumin are increased as a result of an increased activity of hormone-sensitive lipase in adipose tissue. The carbon skeletons of glucogenic amino acids are used by the liver for gluconeogenesis. Liver glycogen is nearly depleted by 12 hours after a meal, and muscle glycogen cannot give rise to free glucose because muscle lacks glucose 6-phosphatase. Lactate can arise from anaerobic glycolysis in muscle and red blood cells, but is less important than amino acids as a source of glucose.

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