Şunu aradınız:: i have been impressed in a speech (Arapça - İngilizce)

♪ i have been changed ♪
♪ i have been changed ♪

- *lt ought a have been washed in a jug*
- *lt ought a have been washed in a jug*

he is said to have been taken in a taxi to the menegai police station.
he is said to have been taken in a taxi to the menegai police station.

♪ ♪ lucky to have been where i have been.
♪ lucky to have been where i have been ♪

at about 2.30-3 a.m., they were said to have been placed in a cell.
at about 2.30-3 a.m., they were said to have been placed in a cell.

i set the trap and when i am done you will know what i have been through
i set the trap and when i am done you will know what i have been through

the questionnaires included in this section are those which have been reflected in a report by a special procedure mandate holder.
the questionnaires included in this section are those which have been reflected in a report by a special procedure mandate holder.

photos of alleged child combatants have been shown in a public exhibition, on sudanese television and in several sudanese newspapers.
photos of alleged child combatants have been shown in a public exhibition, on sudanese television and in several sudanese newspapers.

i won't hesitate to kill you in a second, if i have to.
i won't hesitate to kill you in a second, if i have to.

in addition, the serious backlog of cases in the formal justice system has remained a challenge and not enough resources have been put at the disposal of the judiciary to address this situation efficiently and in a timely manner.
in addition, the serious backlog of cases in the formal justice system has remained a challenge and not enough resources have been put at the disposal of the judiciary to address this situation efficiently and in a timely manner.

though sewage treatment stations have been built in a couple of locations (including ain ghazal and khirbet as samara), these stations often receive more water than they can handle.
though sewage treatment stations have been built in a couple of locations (including ain ghazal and khirbet as samara), these stations often receive more water than they can handle.

i have been instructed to assure the commission that as the planned demarcation process gets under way, the government of eritrea is committed to supporting unmee's operations as they bear on the demarcation, as provided in the algiers agreements.
i have been instructed to assure the commission that as the planned demarcation process gets under way, the government of eritrea is committed to supporting unmee's operations as they bear on the demarcation, as provided in the algiers agreements.

when their mother came to see them the following day, she was reportedly arrested and placed in a cell from which she was said to have been moved 15 minutes later.
when their mother came to see them the following day, she was reportedly arrested and placed in a cell from which she was said to have been moved 15 minutes later.

in a joint effort with the mexico office, a regional seminar on violence against indigenous women in guatemala and mexico was held, with participation by indigenous women who have been victims of violence.
in a joint effort with the mexico office, a regional seminar on violence against indigenous women in guatemala and mexico was held, with participation by indigenous women who have been victims of violence.

any person arrested, detained or interned for actions related to the armed conflict shall be informed promptly, in a language he understands, of the reasons why these measures have been taken.
any person arrested, detained or interned for actions related to the armed conflict shall be informed promptly, in a language he understands, of the reasons why these measures have been taken.

when a suspect is apprehended they must also be informed, in a language they understand, that they have been apprehended by coalition forces, the reason for their apprehension, where they are being taken, and that a member of their family will be informed of their apprehension.
when a suspect is apprehended they must also be informed, in a language they understand, that they have been apprehended by coalition forces, the reason for their apprehension, where they are being taken, and that a member of their family will be informed of their apprehension.

the studies carried out by the office in colombia in a number of important state institutions, and the recommendations contained in them, have been the subject of accompaniment and follow-up aimed at contributing to their implementation.
the studies carried out by the office in colombia in a number of important state institutions, and the recommendations contained in them, have been the subject of accompaniment and follow-up aimed at contributing to their implementation.

3. sugar on the body, brain, and behavior 3.1 fructose vs. glucose monosaccharides differ in how they are processed by the brain and influence brain activity. although some consumers may believe that fructose is healthier because it comes from fruit (5), this notion is misguided. the body does not respond in the same way to fructose in fruit as to added fructose. as an added sugar, fructose is particularly implicated in metabolic syndrome, hypertension, insulin resistance, lipogenesis, diabetes and associated retinopathy, kidney disease, and inflammation (4,6,7,8,9). accordingly, reduction of fructose in the diet of at risk individuals appears to reduce these symptoms. when added fructose was replaced by glucose (in the form of starch) in the diets of obese children, liver fat, de novo lipogenesis, diastolic blood pressure, triglycerides, and ldl cholesterol decreased while insulin sensitivity improved (10,11). furthermore, in fruit, fructose is accompanied by antioxidants, flavonols, potassium, vitamin c and high fiber, which may collectively outweigh any negative consequences of fructose content (4, 12). importantly, the quantities of fructose in a piece of fruit and a sweetened beverage are drastically different. for example, the fructose in a peach represents approximately 1% of the fruit’s weight whereas fructose accounts for half the weight of hfcs (7). differences in health effects between glucose and fructose may be caused by the different metabolic pathways they follow. digestion and absorption of sugars takes place in the top half of the digestive tract (13). most of the glucose in the blood stream is not stored in the liver but rather, through the action of insulin, quickly passes through to muscle, adipose, and other peripheral tissues where it can immediately be used as energy (13). fructose, on the other hand, is a less direct source of energy. independent of insulin, the liver converts fructose to glucose, lactate, and/or fatty acids before passing it to the blood stream where it can be oxidized in other tissues for energy (14,15,8). compared to glucose, fructose produces smaller increases in plasma glucose and circulating satiety hormones such as glucagon-like peptide-1 (glp-1) and insulin (16). fructose also attenuates suppression of ghrelin, an appetitive hormone, while glucose does not (17). therefore, fructose allows overconsumption of calories by failing to activate the body’s signals to stop eating. beyond weight gain and obesity, other diseases are linked to fructose’s metabolic pathway. high dietary fructose can increase de novo lipogenesis in the liver (18) in a way that is reminiscent of ethanol (19). this is because fructose bypasses the main rate limiting step of glycolysis to act as a precursor for fatty acid synthesis (20,21,8). this bypass may also explain the increased rates of non-alcoholic fatty liver disease and resulting insulin resistance associated with fructose ingestion (20). fructose also seems to contribute to inflammation in the body. when in excess in the intestinal lumen, fructose generates advanced glycation end products (age’s), which are related to neurodegenerative diseases, atherosclerosis, and chronic inflammatory diseases such as asthma, diabetes, and associated cognitive decline (22,9,23,24,25). glucose and fructose have differing impacts on the brain. compared to other organs, the brain has vastly disproportionate energy requirements relative to its weight. neurons have an especially high energy demand for generating postsynaptic potentials and action potentials, necessitating large amounts of energy (26). glucose from the bloodstream is the main source of energy for the brain (26,27). glucose transporters in astrocytes and the epithelial cells of the blood brain barrier (bbb) are responsible for transporting glucose into the brain (16,26). neurons then absorb glucose from astrocytes using glucose transporters. in contrast, fructose cannot directly supply the brain with energy as it crosses the blood brain barrier to a much lesser degree than glucose (16,26). however, fructose administered intraperitoneally in rodents crossed the bbb to some degree and triggered neuronal activation. this fructose was metabolized into lactate, an alternate energy source, in the hypothalamus (16). fructose’s ability to cross the bbb has not yet been studied in humans, so more research is needed on the direct effects of fructose in the brain. nonetheless, the differential effects of the two monosaccharides may be attributed in part to glucose’s more immediate and direct availability to the brain as an energy source as compared to fructose. sugar’s impact on the body, brain, and behavior 2257 © 1996-2018 3.2 hedonic response to sugar and rewards of sugar intake while the hypothalamus regulates food intake in terms of energetic needs, the dopamine reward/motivation circuitry involving striatal, limbic and cortical areas also drives eating behavior (28). other neurotransmitters including serotonin, endogenous opioids, and endocannabinoids confer the rewarding effects of food in part by modulating its hedonic properties (29). ingestion of palatable food releases dopamine (da) in the ventral and dorsal striatum and dorsal striatal da release is proportional to the selfreported level of pleasure gained by eating the food (30). highly palatable foods, namely those rich in sugar or fat, can strongly trigger these reward/motivation and hedonic systems, encouraging food intake beyond the necessary energy requirements (31). while this may have been evolutionarily advantageous by encouraging fat storage when food was scarce, overeating becomes a liability in our current environment, which has no shortage of highly caloric and processed foods. there are two principal rewarding aspects of sugar consumption: nutrition and taste. rodent studies have indicated that these two aspects are distinct and dissociable and may follow different neural pathways (32,33). one path for the nutritive rewards of sugar comes from melanin-concentrating hormone (mch) neurons in the lateral hypothalamus (32). in rodents, these neurons fire in response to extracellular glucose levels, independent of gustatory input, and project to dopamine neurons in the midbrain that in turn project to the ventral and dorsal striatum. though animals typically prefer sucrose over sucralose (non-nutritive sweetener), transgenic mice who lack mch neurons do not, showing that this pathway is essential for encoding nutritive reward. when mch neurons are optogenetically stimulated during the consumption of sucralose, the mouse brain is tricked into responding as if it is receiving caloric energy with a resultant increase in striatal da and even preference of sucralose over sucrose (32). the nutritive reward value of sugar is associated with increases in da release in the dorsal striatum (34). when infused intra-gastrically in mice to avoid the confounds of taste, glucose elicited da release in the dorsal striatum while sucralose did not (34). the sweet taste of sugar is also rewarding— offering an explanation as to why artificial sugars like sucralose are still consumed despite their lack of nutritive value. the reward of the sweet taste, however, activates a different neural pathway than the caloric input. while the nutritive reward of sugar in mice causes da release primarily in the dorsal striatum, the sweetness reward is concentrated in the ventral striatum (32). consumption of sucralose in mice was associated with increased da in the ventral striatum except when tainted by a bitter additive, suggesting that the reward is derived from the palatable taste rather than another feature of sucralose (34). although both the nutritive and taste rewards of sugar are, to some extent, neurologically distinct, they occur in tandem and are interrelated. a recent study showed that mice modified to have disrupted da d-2 receptor (drd2) signaling in the nucleus accumbens (nac) shell of the ventral striatum exhibited more perseverative and impulsive sucrose-taking, increased sucrose reinforcement, increased reinforcement/ reward learning of glucose-paired flavors, and worsened learning flexibility (35). additionally, these mice were less efficient in metabolizing glucose. this suggests that drd2 in the nac are essential both for regulating peripheral glucose levels as well as the reinforcement/reward learning of glucose consumption (35), which explains why dysregulation of this system may lead to overeating. 3.3 hedonic response: fructose vs. glucose just as fructose and glucose have different metabolic pathways, they have different hedonic effects on the brain and behavior. fifteen minutes after subjects received a drink of either pure fructose or glucose during a functional mri (fmri) scan, those receiving glucose showed a significantly reduced amount of cerebral blood flow (cbf) in the hypothalamus, insula, anterior cingulate cortex, and striatum when compared to baseline (17). they also showed greater functional connectivity between the hypothalamus, thalamus, caudate, and putamen. the increased connectivity between the hypothalamus and the dorsal striatum after glucose was interpreted to reflect engagement of the nutritive reward pathway. the reduction in hypothalamic activity and increased connectivity with reward centers was accompanied by a perceived increase in fullness and satiety. in contrast, consuming a fructose drink was not associated with reduced cbf in the hypothalamus, but instead with reduced cbf in the thalamus, hippocampus, posterior cingulate cortex, fusiform gyrus, and visual cortex. although those in the fructose group did have increased connectivity between the thalamus and hypothalamus, there was no increase detected with the dorsal striatum as observed in the glucose group. correspondingly, fructose consumption did not significantly reduce hunger. fructose consumption has also been associated with a stronger fmri response in the visual cortex to high calorie foods compared that with glucose consumption (14). as fructose delivers a sweet taste without an immediate nutritive input, it follows that fructose consumption should be associated with increased appetitive behavior and reactivity to food. 3.4 sugar and addiction sugar has been characterized by some as
last september, the united nations declared that, for the first time in human history, chronic non-communicable diseases such as heart disease, cancer and diabetes pose a greater health burden worldwide than do infectious diseases, contributing to 35 million deaths annually. this is not just a problem of the developed world. every country that has adopted the western diet — one dominated by low-cost, highly processed food — has witnessed rising rates of obesity and related diseases. there are now 30% more people who are obese than who are undernourished. economic development means that the populations of low- and middle-income countries are living longer, and therefore are more will have a normal lifespan. conversely, up to 40% of normal-weight people manifest the diseases that constitute the metabolic syndrome: diabetes, hypertension, lipid problems, cardiovascular disease, non-alcoholic fatty liver disease, cancer and dementia. obesity is not the cause; rather, it is a marker for metabolic dysfunction, which is even more prevalent. the un announcement targets tobacco, alcohol and diet as the central risk factors in non-communicable disease. two of these three — tobacco and alcohol — are regulated by governments to protect public health, leaving one of the primary culprits behind this worldwide health crisis unchecked. of course, regulating food is more summary ● sugar consumption is linked to a rise in non-communicable disease ● sugar’s effects on the body can be similar to those of alcohol ● regulation could include tax, limiting sales during school hours, and placing age limits on purchasing illustration by mark smith 2 febru a ry 2012 | vol 482 | nat ure | 27 comment complicated — food is required, whereas tobacco and alcohol are non-essential consumables. the key question is: what aspects of the western diet should be the focus of intervention? denmark first chose, in october 2011, to tax foods high in saturated fat, despite the fact that most medical professionals no longer believe that fat is the primary culprit. but now, the country is considering taxing sugar as well — a more plausible and defensible step. indeed, rather than focusing on fat and salt — the current dietary ‘bogeymen’ of the us department of agriculture (usda) and the european food safety authority — we believe that attention should be turned to ‘added sugar’, defined as any sweetener containing the molecule fructose that is added to food in processing. over the past 50 years, consumption of sugar has tripled worldwide. in the united states, there is fierce controversy over the pervasive use of one particular added sugar — high-fructose corn syrup (hfcs). it is manufactured from corn syrup (glucose), processed to yield a roughly equal mixture of glucose and fructose. most other developed countries eschew hfcs, relying on naturally occurring sucrose as an added sugar, which also consists of equal parts glucose and fructose. authorities consider sugar as ‘empty calories’ — but there is nothing empty about these calories. a growing body of scientific evidence shows that fructose can trigger processes that lead to liver toxicity and a host of other chronic diseases1 . a little is not a problem, but a lot kills—slowly (see ‘deadly effect’). if international bodies are truly concerned about public health, they must consider limiting fructose — and its main delivery vehicles, the added sugars hfcs and sucrose — which pose dangers to individuals and to society as a whole. no ordinary commodity in 2003, social psychologist thomas babor and his colleagues published a landmark book called alcohol: no ordinary commodity, in which they established four criteria, now largely accepted by the public-health community, that justify the regulation of alcohol — unavoidability (or pervasiveness throughout society), toxicity, potential for abuse and negative impact on society2 . sugar meets the same criteria, and we believe that it similarly warrants some form of societal intervention. first, consider unavoidability. evolutionarily, sugar as fruit was available to our ancestors for only a few months a year (at harvest time), or as honey, which was guarded by bees. but in recent years, sugar has been added to virtually every processed food, limiting consumer choice3 . nature made sugar hard to get; man made it easy. in many parts of the world, people are consuming an average of more than 500 calories per day from added sugar alone (see ‘the global sugar glut’). now, let’s consider toxicity. a growing body of epidemiological and mechanistic evidence argues that excessive sugar consumption affects human health beyond simply adding calories4 . importantly, sugar induces all of the diseases associated with metabolic syndrome1,5. this includes: hypertension (fructose increases uric acid, which raises blood pressure); high triglycerides and insulin resistance through synthesis of fat in the liver; diabetes from increased liver glucose production combined with insulin resistance; and the ageing process, caused by damage to lipids, proteins and dna through nonenzymatic binding of fructose to these molecules. it can also be argued that fructose exerts toxic effects on the liver similar to those of alcohol1 . this is no surprise, because alcohol is derived from the fermentation of sugar. some early studies have also linked sugar consumption to human cancer and cognitive decline. sugar also has a clear potential for abuse. like tobacco and alcohol, it acts on the brain to encourage subsequent intake. there are now numerous studies examining the dependence-producing properties of sugar in humans6 . specifically, sugar dampens the suppression of the hormone ghrelin, which signals hunger to the brain. it also interferes with the normal transport and signalling of the hormone leptin, which helps to produce the feeling of satiety. and it reduces dopamine signalling in the brain’s reward centre, thereby decreasing the pleasure derived from food and compelling the individual to consume more1,6. finally, consider the negative effects of sugar on society. passive smoking and drink-driving fatalities provided strong arguments for tobacco and alcohol control, respectively. the long-term economic, health-care and human costs of metabolic syndrome place sugar overconsumption in the same category7 . the united states spends $65 billion in lost productivity and $150 billion on health-care resources annually for co-morbidities associated with metabolic syndrome. seventy-five per cent of all us health-care dollars are now spent on treating these diseases and resultant disabilities. because 75% of military applicants are now rejected for obesity-related reasons, the past three us surgeons general and the chairman of the us joint chiefs of staff have declared obesity a “threat to national security”. how to intervene how can we reduce sugar consumption? after all, sugar is natural. sugar is a nutrient. sugar is pleasure. so is alcohol, but in both cases, too much of a good thing is toxic. it may be helpful to look to the many generations of international experience with alcohol and tobacco to find models that work8,9. so far, evidence shows that individually focused approaches, such as school-based interventions that teach children about diet and exercise, demonstrate little efficacy. conversely, for both alcohol and tobacco, there is robust evidence that gentle ‘supply side’ control strategies which stop far short of all-out prohibition — taxation, distribution controls, age limits — lower both consumption of the product and accompanying health harms. successful interventions all share a common end-point: curbing availability2,8,9. taxing alcohol and tobacco products — in the form of special excise duties, value added taxes and sales taxes — are the most popular deadly effect excessive consumption of fructose can cause many of the same health problems as alcohol. chronic ethanol exposure chronic fructose exposure hematologic disorders electrolyte abnormalities hypertension hypertension (uric acid) cardiac dilatation cardiomyopathy myocardial infarction (dyslipidemia, insulin resistance) dyslipidemia dyslipidemia (de novo lipogenesis) pancreatitis pancreatitis (hypertriglyceridemia) obesity (insulin resistance) obesity (insulin resistance) malnutrition malnutrition (obesity) hepatic dysfunction (alcoholic steatohepatitis) hepatic dysfunction (non-alcoholic steatohepatitis) fetal alcohol syndrome addiction habituation, if not addiction source: ref. 1 “sugar is cheap, sugar tastes good, and sugar sells, so companies have little incentive to change.” 28 | nat ure | vol 482 | 2 febru a ry 2012 comment and effective ways to reduce smoking and drinking, and in turn, substance abuse and related harms2 . consequently, we propose adding taxes to processed foods that contain any form of added sugars, such as hfcs and sucrose. this would include sweetened fizzy drinks (soda) and other sugar-sweetened beverages (for example, juice, sports drinks and chocolate milk), and also sugared cereal. already, canada and some european countries impose small additional taxes on some sweetened foods. the united states is currently considering a penny-per-ounce soda tax (about 34 cents per litre), which would raise the price of a can of soda by 10–12 cents. currently, each us citizen consumes an average of 216 litres of soda per year, of which 58% contains sugar; taxing at a penny an ounce could provide annual revenues in excess of $45 per capita (roughly $14 billion per year); however, this would be unlikely to reduce total consumption. statistical modelling suggests that the price would have to double to significantly reduce soda consumption — so a $1 can of soda should cost $2 (ref. 10). other successful tobacco- and alcoholcontrol strategies limit availability, such as reducing the hours that retailers are open, controlling the location and density of retail markets and limiting who can legally purchase the products2,9. a reasonable parallel for sugar would tighten licensing requirements on vending machines and snack bars that sell sugary products in schools and workplaces. many schools have removed soda and candy from vending machines, but often replaced them with juice and sports drinks, which also contain added sugar. states could apply zoning ordinances to control the number of fast-food outlets and convenience stores in low-income communities, and especially around schools, while providing incentives for the establishment of grocery stores and farmer’s markets. another option would be to limit sales during school operation, or to designate an age limit (such as 17) for the purchase of drinks with added sugar, particularly soda. indeed, parents in south philadelphia, pennsylvania, recently took this upon themselves by lining up outside convenience stores and blocking children from entering them after school. why couldn’t a public-health directive do the same? the possible dream government-imposed regulations on the marketing of alcohol to young people have been quite effective, but there is no such approach to sugar-laden products. even so, the city of san francisco, california, recently instituted a ban on including toys with unhealthy meals such as some types of fast food. a limit — or, ideally, ban — on television commercials for products with added sugars could further protect children’s health. reduced fructose consumption could also be fostered through changes in subsidization. promotion of healthy foods in us low-income programmes, such as the special supplemental nutrition program for women, infants and children and the supplemental nutrition assistance program (also known as the food-stamps programme) is an obvious place to start. unfortunately, the petition by new york city to remove soft drinks from the food-stamp programme was denied by the usda. ultimately, food producers and distributors must reduce the amount of sugar added to foods. but sugar is cheap, sugar tastes good, and sugar sells, so companies have little incentive to change. although one institution alone can’t turn this juggernaut around, the us food and drug administration could “set the table” for change8 . to start, it should consider removing fructose from the generally regarded as safe (gras) list, which allows food manufacturers to add unlimited amounts to any food. opponents will argue that other nutrients on the gras list, such as iron and vitamins a and d, can also be toxic when over-consumed. however, unlike sugar, these substances have no abuse potential. removal from the gras list would send a powerful signal to the european food safety authority and the rest of the world. regulating sugar will not be easy — particularly in the ‘emerging markets’ of developing countries where soft drinks are often cheaper than potable water or milk. we recognize that societal intervention to reduce the supply and demand for sugar faces an uphill political battle against a powerful sugar lobby, and will require active engagement from all stakeholders. still, the food industry knows that it has a problem — even vigorous lobbying by fast-food companies couldn’t defeat the toy ban in san francisco. with enough clamour for change, tectonic shifts in policy become possible. take, for instance, bans on smoking in public places and the use of designated drivers, not to mention airbags in cars and condom dispensers in public bathrooms. these simple measures — which have all been on the battleground of american politics — are now taken for granted as essential tools for our public health and wellbeing. it’s time to turn our attention to sugar. ■ robert h. lustig is in the department of pediatrics and the center for obesity assessment, study and treatment at the university of california, san francisco, california 94143, usa. laura a. schmidt and claire d. brindis are at the clinical and translational science institute and the philip r. lee institute for health policy studies, university of california, san francisco, california 94118, usa. e-mail: rlustig@peds.ucsf.edu 1. lustig, r. h. j. am. diet. assoc. 110