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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EIt has been 15 years since the results of the United Kingdom Prospective Diabetes Study (UKPDS) were reported at the Barcelona European Association for the Study of Diabetes (EASD) 1998 Annual Meeting. This article discusses the global impact of the UKPDS findings, which have been reported in 82 publications.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EExclusive Article - For home page\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EIt has been 15 years since the results of the United Kingdom Prospective Diabetes Study (UKPDS) were reported at the Barcelona European Association for the Study of Diabetes (EASD) meeting. David Matthews, MA, DPhil, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, United Kingdom, discussed the global impact of the UKPDS findings, which have been reported in 82 publications.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EUKPDS, which was conducted in newly diagnosed patients with type 2 diabetes mellitus (T2DM) on monotherapy (for as long as possible), provided the first definitive evidence that intensive glycemic control could reduce microvascular events by a large (25%) and highly significant margin [UKPDS Study Group. \u003Cem\u003ELancet\u003C\/em\u003E 1998 (UKPDS 33)]. In this study, a policy of intensive glucose control maintained a median HbA1C of 7% over a median 10 years from diagnosis (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Conventional Versus Intensive Glucose Control on HbA1C\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2128220286\u0022 data-figure-caption=\u0022Effect of Conventional Versus Intensive Glucose Control on HbA1C\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13819\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EEffect of Conventional Versus Intensive Glucose Control on HbA1C\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EReproduced from the UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). \u003Cem\u003ELancet\u003C\/em\u003E 1998;352(9131):83853. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EOver the 10 years of the study, HbA1C was 7.0% (range, 6.2% to 8.2%) in the intensive group compared with 7.9% (6.9% to 8.8%) in the conventionally treated group\u2014an 11% reduction. This resulted in a 12% significant reduction in the risk of any diabetes endpoint (95% CI, 1% to 21%; RR, 0.88; p=0.029) and a 25% reduction in microvascular endpoints (95% CI, 7% to 40%; RR, 0.75; p=0.0099), as well as reductions in myocardial infarction (MI), cataract extraction, retinopathy, and albuminuria [UKPDS Study Group. \u003Cem\u003ELancet\u003C\/em\u003E 1998 (UKPDS 33)]. Importantly, the results of UKPDS have led to many additional studies in very different populations, the results of which continue to influence diabetes care. Current recommendations are that an HbA1C target of \u0026lt;7.0% is generally recommended, although a target of \u0026lt;6.5% may be reasonable for patients with a short duration of T2DM and without extensive atherosclerosis [Laakso M, Cederberg H. \u003Cem\u003EJ Intern Med\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EElevated blood pressure (BP) may also increase the risk of diabetes-related events, and although tight BP control (130\/80 mm Hg in patients with diabetes) has been shown to reduce the risk of diabetes events by 24% (p=0.0046; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [UKPDS Study Group. \u003Cem\u003EBMJ\u003C\/em\u003E 1998], the forthcoming Joint National Committee (JNC) 2013 Update is likely to recommend a hypertension treatment target of 140\/90 mm Hg for all but older adults. Prof. Matthews noted that this is not that much different from the mean systolic BP in the UKPDS which was 144 mm Hg.\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effects of Tight Blood Pressure Control on Diabetes-Related Events\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2128220286\u0022 data-figure-caption=\u0022Effects of Tight Blood Pressure Control on Diabetes-Related Events\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13820\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EEffects of Tight Blood Pressure Control on Diabetes-Related Events\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EAdapted from UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). \u003Cem\u003EBMJ\u003C\/em\u003E 1998; 317:703\u2013713.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EEpidemiology data support the concept that low HbA1C (\u0026lt;6%) and low systolic BP (\u0026lt;130 mm Hg) results in fewer diabetes-related endpoints [Adler AI et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2000; Stratton IM et al. \u003Cem\u003EBMJ\u003C\/em\u003E 2000].\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003EThe UKPDS study addressed the issue of whether intensive glucose lowering with sulfonylureas increases the risk of cardiovascular mortality in patients with T2DM. Sulfonylurea (chlorpropamide, glibenclamide, or glipizide) or insulin substantially decreased the risk of microvascular complications, but not macrovascular disease compared with conventional treatment. Patients in the intensive treatment group had more hypoglycemic episodes (p\u0026lt;0.0001) and weight gain (p\u0026lt;0.001) [UKPDS Study Group. \u003Cem\u003ELancet\u003C\/em\u003E 1998 (UKPDS 33)]. Metformin was not associated with any weight increase compared with the conventionally treated group. Because of UKPDS the principle of intensive therapy was widely accepted and the concept of agent failure was switched to \u03b2-cell failure. The study also changed the thinking about \u03b2-blockers and the treatment of T2DM in patients with hypertension.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EAnother UKPDS study compared diabetes-related event outcomes in patients (some overweight) receiving sulfonylurea or metformin. Patients given metformin had improved diabetes-related endpoints (p=0.0034), all-cause mortality (p=0.021), and stroke (p=0.032) compared with patients receiving sulfonylurea or insulin. Metformin was also associated with less weight gain and fewer hypoglycemic events [UKPDS Study Group. \u003Cem\u003ELancet\u003C\/em\u003E 1998 (UKPDS 34)].\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EVirtually all guidelines quote the UKPDS as justification for using metformin as first-line therapy and the background medication on which all other pharmacotherapy are added citing its substantial effects on outcomes in overweight patients, the elderly, and its cost effectiveness. With the worldwide population of people with diabetes expected to grow to 330 million by 2030, data indicates morbidity can be reduced, lives prolonged, and blindness and renal failure prevented. Because of UKPDS, millions of people will have better outcomes and better lives.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EIn a continuation of this subject, Rury Holman, FMedSci, University of Oxford, Churchill Hospital, Headington, United Kingdom, presented the post-trial monitoring results of the UKPDS sulfonylurea plus metformin substudy.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EThe UKPDS provided the first definitive evidence that T2DM is a progressive condition, with increasing hyperglycaemia over time (\u003Ca id=\u0022xref-fig-1-2\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). As a result, a UKPDS substudy was introduced in which patients who continued to have fasting hyperglycemia despite maximal sulfonylurea therapy were randomized to remain on therapy with sulfonylurea alone or to have metformin added.\u003C\/p\u003E\u003Cp id=\u0022p-14\u0022\u003EGiven the main UKPDS findings demonstrating the beneficial effects of metformin on myocardial infarction and all-cause mortality it was a concern to the diabetes community when the sulfonylurea plus metformin substudy appeared to show a 96% increased risk of diabetes-related death (RR, 1.96; 95% CI, 1.02 to 2.75; p=0.039) compared with continued sulfonylurea alone (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E) [UKPDS \u003Cem\u003ELancet\u003C\/em\u003E 1998 (UKPDS 34)]. The authors pointed out that the actual number of deaths were small; 26 in the sulfonylurea plus metformin group and 14 in the sulfonylurea-alone group. There were no differences in the incidence of MI, stroke, or microvascular events. The incidence of fatal and nonfatal events did not differ between the groups. Similar follow-up studies have produced conflicting results. Thus, a meta-analysis of nine studies that examined the association between combination therapy of sulfonylureas and metformin on risk of cardiovascular disease (CVD) or all-cause mortality between was conducted [Rao AD et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Increase in Diabetes-Related Deaths\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-2128220286\u0022 data-figure-caption=\u0022Increase in Diabetes-Related Deaths\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/13\/17\/4\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/13821\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n            \u003Cp id=\u0022p-15\u0022 class=\u0022first-child\u0022\u003EIncrease in Diabetes-Related Deaths\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced from Rao AD et al. Is the Combination of Sulfonylureas and Metformin Associated With an Increased Risk of Cardiovascular Disease or All-Cause Mortality?: A meta-analysis of observational studies. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2008;31:1672-1678. With permission from the American Diabetes Association.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-16\u0022\u003EIn this study, the pooled RRs (95% CIs) of outcomes for individuals with T2DM prescribed combination therapy with sulfonylureas and metformin were 1.19 (0.88 to 1.62) for all-cause mortality, 1.29 (0.73 to 2.27) for CVD mortality, and 1.43 (1.10 to 1.85) for a composite endpoint of CVD hospitalizations or mortality (fatal or nonfatal events) [Rao AD et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2008]. No significant effects with this combination therapy on either CVD mortality or all-cause mortality alone were evident.\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003ENew data presented at the EASD showed that during the 10-year post-trial monitoring of all surviving UKPDS patients the differential impact on diabetes-related death diminished and became statistically insignificant, while the hazard ratios for other prespecified clinical outcomes remained essentially unchanged.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/17\/4.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nznkre\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznkre\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}