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求翻译：MADE IN SCOTLAND ST ALBANS HOUSE 18-22 HAYMARKET LONDON SW1Y 4BL是什么意思？是什么意思？
MADE IN SCOTLAND ST ALBANS HOUSE 18-22 HAYMARKET LONDON SW1Y 4BL是什么意思？
问题补充：
MADE IN SCOTLAND圣奥尔本斯HOUSE 18-22 HAYMARKET伦敦SW1Y 4BL是什么意思？
做在苏格兰圣奥尔本斯房子18-22 HAYMARKET伦敦SW1Y 4BL是什么意思？
做在苏格兰ST ALBANS议院18-22 HAYMARKET伦敦SW1Y 4BL是什么意思？
在苏格兰圣奥尔本斯房子取得 18 22 赫马基特伦敦 SW1Y 4BL是什么意思？
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请输入您需要翻译的文本！　　Kay Kwok对我来说一点也不陌生,来伦敦前我已认识他,在香港理工大学的毕业展和其后一些香港的时装设计比赛他都不断吸引着众人的目光,从得知他要前来英国升学那天我便期待着这个系列的到来,最后他没有让支持他的人失望,这个灵感源自古埃及的系列早在微博上疯传,我想也是时候让他自己重新介绍自己。　　能为我们介绍一下自己吗?你为何会选择LCF的MA课程? 　　我于2009年在香港理工大学毕并曾获得Hong Kong Design Talent Award也曾被提名为WGSN的亚洲15大时装设计师(学生组),事实上我在出发来伦敦前是从来没有想过会到这里留学,而选择LCF也是非常巧合的,当时我在香港有几位同校的朋友邀请我一同申请LCF的课程,最后我们全部被取录了,这就成为了我来伦敦的起点。 　　你怎样形容自己的穿衣风格?什么是你衣柜里的must-have? 　　我的风格根据不同的场合改变,但street fashion是我主要的风格,深蓝色牛仔裤是我的must-have。 　　你如何形容自己的时装美学? 　　经典和创新的融合!我喜欢在经典的剪裁上配上精致又带有玩味的物料来表达有启发性的意念。 　　你对成为一名成功的设计师有什么看法?　　当你集热诚,坚持,梦想和创意于一身便没有任何事可以难到你了。 　　可为我们介绍一下你的系列吗?在设计过程中有遇到什么难题? 　　我的系列灵感来自古埃及的木乃伊和天国文化,当中包括制作木乃伊的过程和古埃及的占星学,我的设计结合了光与影同时希望于经典男装剪裁中把digital printing推至另一层次,我更用了大量制作潜水衣Neoprene来塑造肉身的质感。 　　最大的难题是时间的管理,我时常认为没有足够的时间完成榻个系列,拿不定主意也是另一个难题因为我时常认为可以做得更好,所以我一直更改直至不可改的那天,我想这是引致时间不够用的原因。 　　在行内有很多新进的设计师,有哪位是特别想合作的? 　　这条问题的答案我从来没有想过,但如果有机会我会希望跟Viktor &Rolf合作,我十分喜欢他们。 　　作为LCF的毕业生,有什么建议可与现在的时装学生分享? 　　享受设计的过程和保持热诚,做自己但切记不要太固执,保持开放的态度,同时乐于接受帮助和时常鼓励自己去做好的设计,LCF是个拥有积极学校环境的地方。 　　毕业后的下一步是什么? 　　我会找寻工作去丰富自己的经验但我在伦敦的最后目标是拥有自己的品牌,它不需要很大,我只想有个地方去表达我对时装的看法和吸引一些与我有相同品味的人。我也会参加一些比赛,我喜欢比赛,它们都是向他人学习的好机会。　　如希望了解Kay更多,可到访他的LCF专页　　原文链接
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　　在朋友介绍下早在去年年中已认识May Tang,虽然知道她是London College of Fashion的学生但从未看过她的作品,在毕业展中最吸引我的一个女装系列是以脊椎疾病为题的中性系列,当中的独特的lace设计和刚柔并重的剪裁一直叫我难以忘怀,静下来看设计师简介才知道是May的作品,除了lace系列中的配饰也是值得留意的亮点,称赞的说话不再多说,就让May自己介绍一下修读课程十五个月努力后的成果。能为我们介绍一下自己吗?你为何会选择LCF的MA课程? 　　我是香港的时装设计师,完成香港理工大学的BA课程后我便来到LCF修读MA课程,来LCF进修算是一次巧合,当时我正为前途感到困惑,我不希望在办公室从事单调的工作,刚好收到LCF将来港招生的通知,抱着尝试的心态申请,在面试后便收到取录的通知,最后我决定修读MA课程,除了增添知识同时也希望体验伦敦和欧洲的时装文化和气氛。老实说,在MA课程的学习水平与BA给予我的知识完全不同,同学间的互相影响十分重要,我的同学的水平十分高,而我们都在互相切磋中进步,在这里跟不同的设计师,造型师和摄影师作交流开创了很多新机会,让我在这里的时光十分有趣和快乐! 　　你怎样形容自己的穿衣风格?什么是你衣柜里的must-have?　　我会以方便和轻松形容我的风格,这对于我的工是十分重要的,我衣柜有很多紧身裤,我也不知道为什么,但它们都十分容易配衬,另外我喜欢收集包含特殊布料的衣服和配饰,它们容易为平凡的造型带来亮点。 　　你如何形容自己的时装美学? 　　我较热衷于含蓄中的美态,我喜欢微小的细节和优良的工艺,在我的作品中我倾向为女性创造刚强的形象,我希望穿我作品的女性是酷而不只是美,这是我的系列带有很多男性线条和平底鞋的原因,而虽然我用上lace,但它们没有表达得太过于女性化。 　　你对成为一名成功的设计师有什么看法?　　成功有太多不同的定义,大多是取决于你的目标,有人会希望拥有自己的品牌,其他人可能会希望在其他品牌工作或当个兼职设计师只为个别客人工作,当你实现了目标,同时感到满意和享受,你便是成功的一位。 　　可为我们介绍一下你的系列吗?在设计过程中有遇到什么难题?　　我的系列名为Writhe In Parade,起点是常在婴儿或儿童发现的先天性脊椎疾病,在取材过程中看到的照片都感到他们很可怜,这个结构性的缺陷启发我改变一些基本的裁剪纸样,最后成为了意想不到的有趣作品,主题的基础是研究加入塑料纱线的lace设计,这是器官组织结构案与人造物料的融合,灵感来自治疗先天性脊椎疾病的矫正带。系列配衬加入lace的鞋和帽子后刚强味较女性味重,也像古老的布料在现在的剪裁中重生。 　　在整个设计的过程从开始到最后line up都有很多修改,这限制了制作衣服的时间,特别是lace是要从零开始的,而我同时辰制作鞋子,手袋和帽子,时间管理是整个设计元素最大的挑战。 　　在行内有很多新进的设计师,有哪位是特别想合作的?　　我没想过一位特别希望合作的,但我希望进一步研究lace,我想如可以跟一些textile designer或graphic designer合作会十分有趣和带来特别的成果! 　　作为LCF的毕业生,有什么建议可与现在的时装学生分享?　　在这个MA课程中,我除了学习到为设计元素取材的技巧,对意念运用的技巧也是十分有启发性的,而销售性也是十分重要的,虽然每个项目都是我们的作品,但系列需要平衡创意和商业性,这将为未来的事业打好基础。 　　毕业后的下一步是什么?　　我会留在伦敦一段时间找寻工作的机会,我想我现在最需要一些工作经验来丰富自己的知识,我也希望可以欧游,我需要为这15个月的努力给自己一点奖励。　　
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　　Joseph Turvey跟早前介绍的各个毕业生不同,作为本地学生早已为不同媒体绘画时装插图,虽然没在毕业展中胜出却是同期的毕业生当中首位于毕业展两星期后的London Fashion Week再次展出自己作品的设计师, Joseph的系列简单而易懂,在男生日常衣服中加入自己擅长的画作元素,并配以鲜明的色彩让人爱不释手,时常有人提醒设计师要创意和可穿性并重,我想这个系列是成功的例子。　　能为我们介绍一下自己吗?你为何会选择LCF的MA课程?　　我完成了女装设计的BA课程并认为自己还有很多东西需要学习,而LCF的男装设计和制作高级衣服的技术十分有名,我认为这会是一个让我学习这些技巧的地方所以选择了LCF。 　　你怎样形容自己的穿衣风格?什么是你衣柜里的must-have?　　我不是十分时尚的人,但我十分喜欢色彩缤纷的袜子,我想它们是我的must-have。 　　你如何形容自己的时装美学?　　我想我的美学是在简洁的剪裁中加入一点花样,对我来说最重要的是在发展创意的同时保持可穿性。 　　你对成为一名成功的设计师有什么看法? 我认为一名成功的设计师必须要具有商业头脑,你可以得到全世界的媒体报导但如你没有买家这只会是个自我沈溺和昂贵的兴趣。 　　可为我们介绍一下你的系列吗?在设计过程中有遇到什么难题?　　我希望我的系列保持原创性的同时是可穿性高的作品,现在有太多学生创作一些惊人的设计但从没可穿性可言,我花了很多时间以我less is more的坚持说服我的导师和朋友,但我想他们现在会认同了。 　　作为LCF的毕业生,有什么建议可与现在的时装学生分享?　　不要花光你的金钱,去寻找一些乐意支持你设计的公司,你会发现他们数目多得让你惊讶。 　　毕业后的下一步是什么?　　我希望继续展示我的系列,只是在等待一个机会。
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　　来自奥地利的Tine Elisabeth Reiter是本年度的男装冠军,系列以流浪汉为灵感,以浪人在全球化的影响下寻找故乡的故事作基础,把自己故乡民族服装的元素放到系列中,我十分喜欢这个色彩柔和的系列,The Sound of Homeless(ness),在全球一体化的情况下让Tina与你找寻故乡。　　能为我们介绍一下自己吗?你为何会选择LCF的MA课程?　　我在奥地利出生并毕业于一间结合了高中和专业培训的中学校,我在那里完成高中公开试同时是一名裁缝学徒,其后我丁德国慕尼黑的AMD Academy for Fashion &Design进修,在2010年我们以第一所以德语作教学语言的大学参加London Graduate Fashion Week,我的毕业系列也在那里展出,其后我收到来自不同大学的MA课程邀请,最后我选择LCF的同时申请了他们的奖学金,如没有经济的支持我想我不能完成MA课程,我十分幸运从获得的奖项中得到Harold Tillman奖学金来支持我修读LCF的男装设计课程。 　　你怎样形容自己的穿衣风格?什么是你衣柜里的must-have?　　多变的,我穿我喜欢穿的,但重点是我只穿让我感到舒适的衣服,我想身处在行业一后时间最让我烦恼的是去购物,我的衣柜中多是灰和黑色的衣服,而must-have我会说是一件德得体的西装外套,它会让你在每个场合都好看。 　　你如何形容自己的时装美学?　　跟我的穿亡风格一样,是古怪多变的,我做的时装不是为时装而创作的,其他人可能会以清新和创新来形容自己,我会说这是十分有领导性的,特别是我的MA毕业系列的成功是经由特定的剪裁技术制作的独特剪裁带来的。 　　你对成为一名成功的设计师有什么看法?　　你需要努力,专注同时带有热诚,作为一个时装设计师不只是一个职业而是一种生活态度。很多事情会同时发生但你要像个海绵只吸收正面的部分,一个设计师的真正生活不是只有那些华丽的部分,像一个精心打扮的艺术家只在绘图,事实正正相反,作为专业的设计师最常遇到的是大量的工作和紧张的情绪,你需要明白自己需要什么和希望到达的位置。 　　可为我们介绍一下你的系列吗?在设计过程中有遇到什么难题? 　　坦白说我必须承认整个设计过程都不容易,特别是我把不同的曲线应用到男装之中,我参考了一些奥地利的民族服饰并把它们带来了现在,而那些曲线是我系列的重点。 　　在行内有很多新进的设计师,有哪位是特别想合作的?　　有时候世界十分细,我最希望合作的新进设计师是毕业展上颁奖给我的christopher Raeburn我认为他是一位十分明确方向的新进设计师,他十分直接,他说自己十分固执也只依自己的想法做事,他作品的材料用的都是可再生的资源和保持生产线在英国让我十分惊叹。 　　作为LCF的毕业生,有什么建议可与现在的时装学生分享?　　努力和尽力而为!特别因为MA课程很短,你更需要善用时间,这不是一件容易的事但如果你十分希望完成你会突破所有障碍,最后你需要相信自己同时让别人相信你,这是十分有帮助的。 　　毕业后的下一步是什么? 　　我希望在伦敦找到工作,我十分喜欢这里所以我希望留下来,所以我需要找到一份合适的工作,如果有人在寻求男装设计的毕业生,最合适的人选会是我!　　Photography by Jayden Tang　　Hair &Makeup by Pei Chen 　　Fashion by Tina Elisabeth Reiter　　Footwear (& dungarees) by Elin Melin　　Models - Paul Farley &Jaco Norman
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　　剑桥公爵夫人凯特?米德尔顿（The Duchness of Cambridge, Kate Middleton) 于日穿着RUPERT SANDERSON出席FORTNUM & MASON LONDON官方活动。 　　王妃在去年夏天在嘉德胛坏淅(The Order of Garter)上并曾穿上Rupert Sanderson经典的Malone。这双圆头幼t高鞋是日间造型的理想配衬，丝绒灰麂皮更散发历久不衰的雍容气派。
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　　跟Cherry Yuen的遇见可算十分偶然,我获邀参与London College of Fashion的毕业展,当中展出非时装设计课程的毕业生作品,那天我在一款特别的鞋履前停了下来,鞋上的流线型皱折一直吸引我的目光,这位来自香港的设计师除了精于设计鞋履也擅长设计女装,这个鞋履系列以超现实主义作灵感,参考了多位艺术家的作品,如Meret Oppenheim的Fur Breakfast, Rene Magritte的Les Amants和Salvador Dali的Persistence Memory,并以独特的材质完成,那些充满女性线条美的作品会否是你一直找寻的那一双?　　能为我们介绍一下自己吗?你为何会选择LCF的MA课程?　　在成为鞋履设计师前,我是钻研女装设计的,并在School of the Art Institute of Chicago完成了一个Fine Art课程,其后分别于Celine和Alexnader Wang工作,我最后选择修读LCF的鞋履设计课程是为了更了解如何设计鞋子,同时增进我处理不同设计元素的能力。 　　你怎样形容自己的穿衣风格?什么是你衣柜里的must-have? 　　我的设计集精致,鲜明,性感,现代和时尚于一身而我的must-have是一双制作良好的高跟鞋。 　　你如何形容自己的时装美学?　　圆滑和简约的。 　　你对行业在概念和商业的平衡有什么看法?　　这的确是很难平衡的,保持创意十分重要但把有趣的概念加以发展并加添实用性才是最完美的。 　　可为我们介绍一下你的系列吗?在设计过程遇到的难题跟设计衣服有什么分别?　　它们都有分别的难处,两者在技术上已十分不同,在我MA课程的设计元素上我想把衣服上的draping应用到鞋履上,在制作模板和切割物料的过程都遇上困难,因为它们需要的不只是传统的制作技术。 　　在行内有很多新进的设计师,有哪位是特别想合作的?　　Phoebe English 　　作为LCF的毕业生,有什么建议可与现在的时装学生分享?　　认真对待他们真正相信的。 　　毕业后的下一步是什么?　　我会在一些知名的品牌寻找设计顾问的职位,同时创立自己的品牌去继续完成我的一些设计元素。 　　如希望了解Cherry更多,可到访她的个人网页或LCF专页　　原文链接
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Hala Ghattas,
Diana L Wallace,
Juan A Solon,
Sian M Henson,
Yan Zhang,
Pa T Ngom,
Richard Aspinall,
Gareth Morgan,
George E Griffin,
Andrew M Prentice and
Derek C Macallan
1 From the Centre for Infection, St George’s, University of London, London, United Kingdom (HG, YZ, GEG, and DCM); the MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London, United Kingdom (HG, JAS, and AMP); the Edward Jenner Institute for Vaccine Research, Compton, United Kingdom (DLW); the Medical Research Council Keneba, Keneba, Gambia (JAS, PTN, and AMP); the Department of Immunology and Molecular Pathology, University College London, London, United Kingdom (SMH); the Department of Immunology, Imperial College London, London, United Kingdom (PTN and RA); and the Clinical School, University of Wales, Swansea, United Kindgom (GM)
2 Supported by the Medical Research Council of the United Kingdom and by an MRC-Glaxo Wellcome Clinician Scientist Fellowship (to DCM).
3 Reprints not available. Address correspondence to DC Macallan, Centre for Infection, Department of Cellular and Molecular Medicine, St George’s, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom. E-mail: macallan{at}sghms.ac.uk.
&Background: Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life.
Objective: We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults.
Design: T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography–mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18–24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight.
Results: In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0+) subsets of T cells than in na&ve (CD45R0–) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season.
Conclusion: In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise.
Key Words: Nutritional programming • T cell kinetics • lymphocytes • Gambia • stable isotopes
INTRODUCTION
&In humans, several studies have found relations between markers of nutritional status at birth and immunologic outcomes in adolescence and adulthood (1-3). However, the nature of the mechanisms by which these relations may occur remains a subject of debate (4).
In terms of critical target components, the thymus has long been known in animal models to be highly susceptible to fetal malnutrition. Starvation-induced changes include thymic involution, thymic atrophy, circulation of immature lymphocytes, and greater thymocyte apoptosis (5-8). Zinc deficiency leads to glucocorticoid-mediated thymocyte apoptosis and consequently to decreased lymphopoiesis. Such losses of precursor T and B cells ultimately result in lymphopenia and thymic atrophy (9). In magnesium-deficient weaned rats, thymic involution appears as early as 7 d after the introduction of a magnesium-deficient diet and is associated with an increase in sites of active cell death within the thymus (8, 9).
Because thymic development mainly occurs in utero and in early postnatal life, a nutritional insult at a critical stage in thymic development may lead to a permanent impairment in T cell immunity. In The Gambia, further studies have shown that infants have a smaller thymus (10), a lower CD4:CD8, and lower concentrations of T cell receptor excision circles (TRECs; 11) during the hungry season than during the harvest season. Lower TREC concentrations are associated with lower concentrations of interleukin (IL) 7 in the breast milk of mothers (11). In addition, infection-related mortality in adults born during the hungry season was 10 times that in adults born durin these findings indicate a long-term effect on immunocompetence of season of birth (12, 13).
An early nutritional insult to the thymus may therefore have long-term consequences for thymic activity and immunocompetence, similar to the effects immunosenescence (aging of the immune system), which can be characterized by morphologic and functional changes in the thymus (14). In the elderly, the decline in thymic activity with age results in a decrease in thymic output as measured by TRECs (15). A nutritionally deprived thymus at birth may be reset to produce smaller numbers of T cells in later life, leading to long-term effects on the numbers of recent thymic emigrants (RTEs) within the peripheral T cell pool and alterations in T cell homeostasis that parallel those observed during the aging process but at an accelerated rate.
The effects of perinatal malnutrition on specific components of T cell immunity have thus far not been defined. We therefore set out to explore the hypothesis that a defect in the underlying kinetics and distribution of T cells may explain observations of decreased immunocompetence in those born with nutritional deprivation.
SUBJECTS AND METHODS
&We measured T cell phenotype and turnover and TREC concentrations in young Gambian adults whose birth details were known. Field studies were conducted at the Medical Research Council field station in Keneba, The Gambia, which is located in a rural area with a population predominantly made up of subsistence farmers for whom nutrition has a very predictable seasonality. Because migration has been relatively limited and because detailed birth records have been kept and collated in this area since 1949, it was possible to select young adults on the basis of their season of birth and birth weight. These characteristics were used as surrogate markers for nutritional status. Previous studies (13, 16) have shown that the effect of reduced food availability is maximal during the wet season (September through November) and that food is most available during the dry, harvest period (February through April); these periods were therefore defined as the "hungry" and "harvest" seasons, respectively, for the purposes of this study. To maximize the chance that the difference in exposures was nutritional, subjects were further defined according to birth weight, and 2 groups were identified. Group 1 consisted of those with hungry-season birth and with birth weight below the population mean—ie, those born in the months characterized by extreme food shortage and weighing &3 kg at birth. A high likelihood exists that these persons experienced some form of nutritional deprivation in utero and early postnatal life, and they are therefore referred to as nutritionally deprived. Group 2 consisted of those with harvest-season births and birth weight above the population mean (&3 kg). These criteria ensure minimal exposure to malnutrition in utero and early postnatal life, and the group is referred to as nutritionally replete.
Twenty-eight healthy young (aged 18–24 y) men for whom date of birth and birth weight data were available were recruited. Preterm births as defined by gestational age & 38 wk were excluded from the study to eliminate the potentially confounding effect of premature birth. Subjects were screened with a medical questionnaire, fixed blood film, hemoglobin measurement, and ur they were excluded if found to have any current medical condition, anemia, parasitemia, or glycosuria. Sample size was based on pragmatic criteria for a descriptive study. At the time the study was designed, no reliable comparable CV data were available for lymphocyte lifespan studies.
The study was explained to subjects in their local language with the use of trained fieldworkers, and written informed consent was obtained. All procedures were approved by the Joint Gambia Government/MRC Gambia Ethics Committee and the Scientific Coordinating Committee (SCC) of the MRC Gambia.
Differential countDifferential counts were conducted manually on thin films of blood that had been drawn into EDTA and then stained with Leishman’s stain for 2 min and buffered at pH 6.8 for 8 min. One hundred cells were counted and classified as neutrophils, lymphocytes, monocytes, eosinophils, or basophils. Total granulocytes were calculated as neutrophils + eosinphils + basophils.
T cell kineticsT cell kinetics were measured by using deuterated glucose labeling of cellular DNA as detailed elsewhere (17, 18). In brief, subjects received deuterated glucose (6,6-D2 glucose) orally at half-hour intervals and were given frequent small meals over a period of 10 h. Blood samples were drawn at baseline (10 mL) and on days 3 and 10 after labeling (28 mL). Peripheral blood mononuclear cells (PBMCs), isolated by density gradient centrifugation, were separated on site by antibody-coated magnetic beads (Miltenyi Biotec, Bergisch Gladbach, Germany) into 4 T cell subsets (CD8+CD45R0+, CD8+CD45R0–, CD4+CD45R0+, and CD4+CD45R0–) by using a protocol designed to ensure maximal yield but minimal contamination of low-turnover R0– cells with high-turnover R0+ cells, as described elsewhere (17). For some samples, on-site magnetic bead sorting was not possible because of logistic constraints. In these cases, samples were frozen, shipped, and separated by flow cytometry sorting as described previously (18). The number of samples handled in this way was similar for the 2 study groups, and reanalysis of the final data, including analysis of the method of separation as an independent variable, did not affect the results. Aliquots of cell subsets were stained for purity analysis, fixed and stored at 4 °C, and analyzed on a FACSCalibur flow cytometer (Becton Dickinson, Oxford, United Kingdom) within 7 d.
T cell subsets were analyzed for deuterium incorporation into DNA (18, 19) at 3 and 10 d after labeling. This analysis was conducted by resuspending cells in RNAlater (Ambion, Austin, TX), before DNA extraction, derivatization, and gas chromatography–mass spectrometry analysis ( GCMS; Agilent Technologies, Bracknell, United Kingdom) of the aldonitrile tetraacetate derivative (17).
Published modeling approaches (18, 20) were adapted to describe the appearance and disappearance of labeled cells (17). Two variables, proliferation (p) and disappearance (d) rate constants, were estimated with the use of nonlinear least-squares regression (Levenberg-Marquardt method) to fit the model for experimental data.
Flow cytometryWhole blood (200 µL) was stained for 3-color flow cytometry with CD3-PE, CD8-cychrome, and CD45RA-FITC (Becton Dickinson).
T cell receptor excision circlesOne hundred ng DNA extracted from separated T cells (CD4+CD45RA+, CD4+CD45R0+, and CD8+CD45RA+) was added to a mix of 1x Quantitect SYBR Green polymerase chain reaction (PCR) master mix (Qiagen, Crawley, United Kingdom), 200 ng/mL BSA, 1.5 mmol MgCl2/L, 0.5 µmol forward primer/L (5 agg ctg atc ttg tct gac att tgc tcc g 3), and 0.5 µmol reverse primer/L (5 aaa gag ggc agc cct ctc caa ggc aaa 3). Signal joint TRECs (sjTRECs) were amplified and directly quantified by using the Light Cycler (Roche Diagnostics, Mannheim, Germany) and known starting numbers of standard sjTREC molecules.
Real-time PCR was then performed with the use of Quantitect SYBR Green. PCR conditions were an initial activation step at 95 °C for 15 min, which was followed by 40 cycles of denaturation at 95 °C for 5 s, annealing at 60 °C for 25 s, extension at 72 °C for 20 s, and a fluorescence acquisition step at 84 °C for 5 s. Samples were analyzed in triplicate (average CV: 12%), and the mean number of copies was taken as the final concentration.
Statistical analysisAll data were normally distributed as assessed by using a Shapiro-Wilk W test and are therefore presented as means ± SDs or means ± SEMs. Data were compared by using the Student’s t test, and P & 0.05 was considered to be significant. We conducted a 2-factor multilevel analysis to investigate an underlying interaction between na&ve and memory T cell proliferation, disappearance, TRECs, and nutritional status at birth. We used SPSS software (version 10; SPSS Inc, Chicago, IL) for all statistical analyses.
&Subjects and nutritional variablesForty-nine eligible subjects were identified on the basis of birth weight and season of birth. Nine of the 49 were not located, and 8 refused participation. Of the 32 who gave informed consent, 4 subjects were excluded after screening for malaria and other infections. Of the 28 subjects therefore entered into the study, 13 were born in the hungry season with a birth weight & 3 kg, and 15 were born in the harvest season with a birth weight & 3 kg. Mean age and current nutritional status did not differ between the 2 groups. Mean birth weight, age, and current body mass index (BMI) of subjects studied are shown in Table 1; differences between the 2 groups were tested by using a 2-tailed Student’s t test.
View this table:TABLE 1. Mean birth weight, age, and BMI of subjects according to perinatal nutritional exposure
&White blood cell counts and lymphocyte phenotypeIn persons perinatally exposed to nutritional deprivation, a trend was seen toward higher total white blood cell counts and a higher percentage of granulocytes than in subjects with nutritionally replete births. When absolute cell counts were compared, it became obvious that the apparent leukopoenia in those born nutritionally replete could be fully attributed to low numbers of granulocytes. This difference in granulocyte count is shown in Table 2 (P = 0.01, Student’s t test).
View this table:TABLE 2. White blood cell (WBC) and differential cell counts in subjects according to perinatal nutritional exposure
&Whole-blood phenotyping according to markers of na&ve and memory T cell subsets was conducted to investigate a potential accumulation of memory T cells (typical of immunosenescence) in those born with nutritional deprivation in Keneba. Lymphocyte subsets as a proportion of CD3+ cells showed no significant differences in CD4:CD8 and na&ve and memory cell distribution by perinatal nutritional exposure when compared with the use of a two-tailed Student’s t test (Table 3). This finding is contrary to the hypothesis that subjects with nutritionally deprived births would have higher proportions of memory cells because of premature immunosenescence.
View this table:TABLE 3. Mean percentage of CD3+ lymphocyte subsets according to perinatal nutritional exposure
&In vivo T cell kineticsTo investigate the hypothesis that perinatal undernutrition affects the life span of lymphocyte pools, T cell proliferation and disappearance rates were analyzed for differences by perinatal nutritional exposure. A flaw in the capacity of persons born with nutritional deprivation to maintain T cell homeostasis may predispose those persons to premature adult death from infection.
T cell kinetic analyses were completed in 25 subjects (in 3 others, phenotype data are available but follow-up samples were lost). Mean data for T cell subsets in the 2 groups of subjects—those exposed and those not exposed to perinatal nutritional deprivation—are shown in Figure 1. Because higher peak (day 3) fractional enrichments indicate faster rates of proliferation of the cells within the sorted T cell subpopulation, it can be seen that, in both groups of subjects, memory (CD45R0+) subsets had higher proliferation rates than did their na&ve (CD45R0–) counterparts. This was true for both CD4+ and CD8+ cell populations and is consistent with data from previous studies conducted in both young and elderly persons in the United Kingdom (18, 21, 22).
View larger version (19K):FIGURE 1.. Mean measured enrichment of deuterium in DNA on days 3 and 10 from selected T lymphocyte populations in subjects exposed (CD45R0–; n = 13; A and C) and not exposed (CD54R0+; n = 12; B and D) to perinatal nut data are expressed as the fraction of new cells labeled per day (•, CD45R0–; , CD45R0+). Higher peak (day 3) fractional enrichments indicate faster rates of proliferation of the cells within the sorted subpopulation. Lines show the modeled enrichment curves (—, CD45R0+ - - -, CD45R0– model) derived from the data by using nonlinear least-squares regression (Levenberg-Marquardt method). Curve fits for mean data are shown. The variables proliferation rate constant (p) and disappearance rate constant (d) were estimated from the modeled curve fit for each subject.
&For each set of individual day 3 and day 10 data, model curves were constructed to derive individual proliferation and disappearance rate constants, as shown in Table 4. Mean values for the proliferation rate constant (p) of 1.2%/d and 1.4%/d were obtained for CD45R0– and 3.8%/d and 4.0%/d for CD45R0+ cells within CD4+ and CD8+ populations, respectively. As in previous studies, significant interindividual variation was observed.
View this table:TABLE 4. Proliferation (p) and disappearance (d) rate constants for T cell populations according to perinatal nutritional exposure, calculated from best-fit model
&When T cell proliferation rates were compared in the 2 groups (Table 4), no significant differences were found between subjects who were nutritionally deprived and those who were not. A trend was seen toward slower death rates in the CD4+CD45R0+ population in the nutritionally deprived group than in the nutritionally replete group, but these differences were not significant.
Modeling also yielded values for the disappearance rate constant (d) for each cell type in each subject (Table 4). It should be noted, as discussed elsewhere (18, 20), that these values represent the disappearance rates only of labeled cells, not those of the whole because dividing cells are more likely to die than are nondividing cells, values for d generally exceed values for p. Mean disappearance rates within all cell subsets ranged between 4.8%/d and 7.5%/d. As in previous studies, no clear distinction was seen between d in CD45R0+ and CD45R0– cells.
T cell receptor excision circlesThe measurement of thymic output through the quantification of RTEs allows for the assessment of the relative contribution of the thymus to the T cell pool (23). The T cell receptor (TCR) gene rearrangements that occur during the proliferation and differentiation of intrathymic progenitor cells result in extrachromosomal excision products or TRECs. Because TRECs are stable over time but cannot multiply, they remain within T lymphocytes as they transit and are diluted during T cell proliferation (23, 24). The reduction in thymopoiesis witnessed in aging is paralleled by a decrease in thymic output (15, 25) as measured by increased dilution of TRECs.
In a previous comparison of elderly persons, who would be expected to have age-related immune compromise, and young persons, we found no significant differences in the rates of in vivo proliferation of CD4+ and CD8+ na&ve and memory T cell subsets (22). Similarly, T cell kinetics of those born in the nutritionally deprived group in the Gambia in the current study were not found to differ significantly from those in the nutritionally replete group. Thus, it remained possible that the increase in infection-related deaths in the nutritionally deprived group was due to premature immunosenescence, manifest as decreased thymic output rather than impaired proliferation within T cell pools. Therefore, sjTRECs were quantified in T cell subpopulations of subjects exposed to perinatal nutritional deprivation and those that were not, to investigate potential differences in thymic output between these 2 groups. In accordance with other studies (15, 26-28), measurement units of TREC concentrations are expressed here as TREC copies per unit of DNA. This approach removes any variance due to different degrees of efficiency in the DNA-extraction method that may occur when TRECs are expressed per number of cells.
When TREC concentrations (per 100 ng DNA) were compared for the different cell subsets assayed, no differences were found between the 2 groups (Table 5). Because no differences were detected in T cell phenotype and measured T cell proliferation and disappearance rates between the 2 groups, the lack of difference in TREC concentrations may reflect a lack of difference in RTE and therefore in thymic output.
View this table:TABLE 5. Concentrations of T cell receptor excision circles (TRECs) in different T cell subsets according to perinatal nutritional exposure1
&A 2-factor multilevel analysis of T cell kinetics (data from Table 4) and TREC concentrations (data from Table 5), using both additive and multiplicative models, found no consistent interaction between nutritional status at birth and na&ve and memory T cells (data not shown).
DISCUSSION
&The perinatal period is a phase during which the thymus is very active and the T cell repertoire is being established. If, as has been suggested elsewhere (29), this period is also a time of critical immunologic susceptibility to nutritional compromise, insults at this time may adversely affect the establishment of clonal diversity and the homeostasis of T cells for many years thereafter. Consistent with such a proposition is the observation that persons born in periods of nutritional deficit may be more susceptible to infectious mortality in adult life than are those born in periods of nutritional repletion (12). Additional evidence for the effects of early-life events on immunity includes lower concentrations of thymopoietin (30), higher concentrations of immunoglobulin E (IgE) (31), and lower responses to typhoid vaccination with purified Vi cell surface polysaccharide in adolescents (2) and adults (3) born with low birth weight. These data suggest that fetal undernutrition, or other factors associated with season of birth in The Gambia and with low birth weight in other settings, may permanently impair the immune system (32).
In view of this, we investigated T cell numbers, phenotype, in vivo kinetics, and TREC content in young men in The Gambia. We compared the results in those who were very likely to have experienced perinatal nutritional compromise according to birth season and birth weight and in those who appeared to have had a well-nourished perinatal phase.
In terms of cell numbers and phenotype, perinatal thymic injury may be expected to result in young adults with low numbers of T cells, particularly in the na&ve compartment, and thus populations would be skewed toward a memory phenotype. When we analyzed cell counts and na&ve and memory phenotypes by season of birth and birth weight to investigate such a potential "memory bias" (typical of immunosenescence) in those exposed to perinatal malnutrition, we found that na&ve populations were actually well maintained in this group and that, if anything, na&ve cell numbers tended to exceed those in persons in the nutritionally replete group (Table 3). Although subjects exposed to perinatal nutritional deprivation had a lower proportion of lymphocytes in the peripheral blood than did those not so deprived, that lymphocyte count could be accounted for by an increase in the absolute granulocyte count in this group.
These findings do not support our initial hypothesis that persons with nutritionally deprived births would have deficiencies in na&ve T cell populations. In the overall population of the current study, total absolute lymphocyte numbers (CD4 and CD8 counts) were also well maintained, and CD4:CD8 was similar to normative values in the United Kingdom, which indicated no evidence in this population for a "CD8 bias." These results contrast with those of other studies that describe lower CD4:CD8 and an increase in memory CD8 cells in other African settings (33-35).
The increase in granulocyte counts in the nutritionally deprived group was significant (Table 2) and appears somewhat paradoxical, unless it is driven by a relative deficit in the adaptive immune response in this group. Certainly, in African populations, normal granulocyte counts tend to be lower than those in white populations, and these results are thus consistent with results from other African countries (33, 35).
In vivo T cell kinetic analyses were consistent with results of other studies that have
proliferation rates were found to be within ranges similar to those found in both young and elderly, healthy British controls (18). When individual disappearance curves were reviewed (data not shown) and compared with those seen in young and elderly UK residents, the observed pattern paralleled findings in young UK controls. No evidence was found for prolonged label retention and therefore of the persistence of CD8+CD45RA+ cells in the circulation, such as that observed in some elderly UK subjects (22). Thus, in young Gambian men, T cell labeling occurred at a rate and in a pattern similar to those in previous studies in other young adult populations. No clear evidence was seen for an effect of birth season or birth weight on T lymphocyte proliferation and disappearance rates.
Perinatal nutritional deprivation did not result in the reduced levels of RTEs usually seen in elderly persons (15, 27). These data are consistent with other findings from this study, which show that T cell phenotype and kinetics in these persons resemble those in young persons in the United Kingdom more than those in elderly persons.
When cell kinetics were analyzed by perinatal exposure to malnutrition to investigate a potential deficit in the maintenance of T cell homeostasis in those who were nutritionally deprived around the time of birth, no differences were found in either proliferation or disappearance rates for CD4+ and CD8+ memory and na&ve T cell populations. It is possible that real changes may have been missed in the current, small study. Logistic constraints, local sensitivities, and the availability of demographically defined populations limited us with respect to the number of subjects that could be studied, the amount of blood that could be taken, and the number of time-points that could be analyzed. In addition, a large component of interindividual variability was present, which is a feature of lymphocyte kinetic studies in general. As a consequence, the current study was limited in its power—eg, for CD4+CD45R0+ proliferation, it had a 90% chance of detecting a 60% change. We tried to maximize our chances of finding an effect by choosing only the extremes of annual variation, rather than recruiting from births across the whole year, and by including birth weight as an additional criterion.
The nonsignificant trends apparent in kinetic differences between the 2 groups seemed primarily to affect the CD4+CD45R0+ population. Cells from persons exposed to perinatal deprivation tended toward lower proliferation and disappearance rates and less TREC content. Because slow turnover would be expected to preserve TREC content (which is diluted by division), this pattern would be consistent with a model in which thymic output
however, if that were the case, TREC content in the na&ve CD4+CD45R0– population would be expected to be low, yet it was not. An alternative model is that the memory population has previously had a high turnover rate (hence diluting TREC content), perhaps because it was derived from a relatively limited initial repertoire, but now has become relatively anergic, consisting of cells that are resistant to activation. Further studies, including additional TREC analysis and telomere length analysis, may help resolve these 2 possibilities.
In vivo lymphocyte kinetic studies can detect only fairly gross changes in whole populations of cells, whereas the effect of nutritional deprivation may be much more focused effect, only on specific elements of immune response, including non-T-cell components, which are damaged by factors related to low birth weight. Thus, for example, a large study in Pakistani adults born with low birth weight found effects on T cell–independent antibody responses to vaccination against typhoid (Vi polysaccharide) but not against T cell–dependent rabies vaccine (3).
This investigation has shown that the maintenance of CD4+CD45R0–, CD4+CD45R0+, CD8+CD45R0–, and CD8+CD45R0+ cell populations remains largely unimpaired in persons exposed to acute perinatal malnutrition. This finding is reflected in unaltered proliferation and death rates within these cell subsets, although some trends suggested subtle changes, particularly in CD4 memory populations. The significance of the changes in the innate immune system (increased granulocyte numbers) is difficult to assess and may represent a compensatory mechanism provoked by subtle changes in adaptive immunity. However, overall, these results are consistent with a surprisingly robust homeostatic system within T cell populations, which upholds the proliferative capacity of cells and maintains adequate cell distributions and numbers, despite exposure to adverse nutritional and immunologic challenges throughout life.
ACKNOWLEDGMENTS
&We thank the young men of Keneba, Manduar, and Kantongkunda who volunteered to tak Bakary Darboe for l Molipha Jammeh and Kebba Bajo for subject recruit Andrew Worth and Cathy DeLara for flow cytometry sorting, Becca Asquith for Tony Fulford fo and Peter Beverley for guidance on immunologic interpretations.
DCM and AMP were responsible for the con HG was responsible for method development, study design and execution, data analysis, data interpretation, and manuscript
DLW conducted the flow cytometry sorting and guided the inter SMH and PTN conducted the T cell receptor rearrangement exci YZ and JAS assisted in laboratory analyses and critical discussions of
RA,GM, GEG, and AMP participated in data interpretation and rev DCM was responsible for the study design and execution and data analysis and interpretation, and contributed to the writing of the final manuscript. None of the authors had a personal or financial conflict of interest.
REFERENCES
Received for publication March 21, 2006.
Accepted for publication October
日期：日 - 来自[]栏目
&&& the King’s College London (C.D.A.W., N.C.S.), Division of Health and Social Care, London, UK&&& the Chronic Disease Research Centre/Tropical Medicine Research Institute and School of Clinical Medicine & Research (D.O.C.C., G.H.E.G., A.J.H., H.S.F.), University of the West Indies, Barbados&&& Guy’s and St. Thomas’ Foundation Trust (A.G.R.), St. Thomas’ Hospital, London, UK&&& Tropical Medicine Research Institute and School of Clinical Medicine & Research (R.J.W.), University of the West Indies, Jamaica.
&&& Abstract
&&& Background and Purpose― The incidence of stroke in black populations is a public health issue, but how risk varies between black communities is unclear.
&&& Methods― Population-based registers in South London (SLSR) and Barbados (Barbados Register of Strokes [BROS]). Stroke incidence estimated by age group, gender and stroke subtype from January 1995 to December 2002 (SLSR), and October 2001 to September 2003 (BROS). Incidence rate ratios [IRR] estimated adjusting for age and sex.
&&& Results― Two hundred and seventy-one cases registered in SLSR and 628 cases in BROS. Average age of stroke was 66.1 years (SD 13.7) in SLSR and 71.5 years (SD 14.9) in BROS (P&0.001). The incidence rate/1000 population in SLSR was 1.61 (E 95% CI, 1.41 to 1.81) and 1.08 ( 95% CI, 0.95 to 1.21). For Barbados incidence rates were 1.29 (E 95% CI, 1.19 to1.39) and 0.85 ( 95% CI, 0.78 to 0.92). Overall IRR for SLSR: BROS adjusted for age and sex was 1.26 (95% CI, 1.09 to 1.46). Statistically significant subtype differences included total anterior cerebral infarction (IRR, 1.82; 95% CI, 1.23 to 2.69), posterior cerebral infarction (IRR, 2.12; 95% CI, 1.28 to 3.53), primary intracerebral hemorrhage (IRR, 1.56; 95% CI, 1.03 to 2.35) and subarachnoid hemorrhage (IRR, 5.04; 95% CI, 2.54 to 9.97).
&&& Conclusions― The risk of stroke in black Caribbeans is higher in South London than Barbados, and particularly so for specific stroke subtypes. The risk in Barbados approaches that in the white population in South London and strokes occur at an older age. Whether environmental factors mediate these differences in migrant populations requires further study.
&&& Key Words: ethnicity& incidence& stroke
&&& Introduction
&&& People categorized as black have higher stroke incidence rates than whites in the UK and the US, with an approximate 2-fold increased risk compared with white groups regardless of the country or ethnicity of the black group and as such ethnicity is an important public health issue.1C4
&&& Reports in the Caribbean have estimated the incidence of first in a lifetime stroke yet no comparisons between black communities in different settings, particularly where migration may have occurred, have been reported.5,6 The incidence rates reported in Barbados and Martinique would appear to be lower than the rates in black groups in the UK and US. The focus of research has been to address risk factor profiles in black and white groups to understand what may drive this increased risk. A case control study in South London highlighted differences in the population attributable risk for ischemic stroke. 7 In the white population there was a high attributable risk for smoking, ischemic heart disease and atrial fibrillation, whereas in the black Caribbean group the attributable risk was significantly higher for hypertension and diabetes. In South London, England and Barbados identical population-based stroke registers have separately reported incidence rates, and this study compares the overall rates and impact of stroke subtypes in the 2 distinct settings, and the influence of sociodemographic and risk factors on stroke risk.
&&& Methods
&&& The South London Stroke Register (SLSR), a population-based stroke register recording first ever strokes in patients of all age groups for a defined area of South London, was set up in January 1995. Southeast London is a deprived inner city area of a developed country with 13% black Caribbean population. All registrations between January 1995 and December 2002 were selected for this analysis, and this includes all the data presented in 2 previous publications on incidence in South London.2,3 An identical register, the Barbados Register of Strokes (BROS), was set up in October 2001, and records between October 2001 and October 2003 were used. Barbados is an island of 166 square miles and a population of 269 000 comprising 95.6% black population. Identical multiple sources of notification were used to ascertain cases that included hospitals, primary care, imaging reports, rehabilitation and death certificates.2,3,5
&&& Ethical approval was obtained from the Guy’s and St. Thomas’ Hospital Trust, Kings College Hospital, Queens Square, Westminster Hospital (London) and the Medical Research Ethics Committee of Barbados Ministry of Health (Barbados).
&&& The World Health Organization (WHO) definition of stroke was used.4,5 Ethnicity was recorded at the initial assessment using self-definition of ethnic origin (1991 UK census question was used for SLSR patients and 2000 Barbados national census for BROS). The principal analyses were restricted to black Caribbeans and mixed ethnicity black Caribbean/whites only. Mixed ethnicity was included because there are issues of categorization of ethn mixed ethnicity may not be known about and it is highly prevalent.
&&& Stroke Subtypes
&&& Classification of the pathological subtype (cerebral infarction, primary intracerebral hemorrhage, and subarachnoid hemorrhage [SAH]) was based on results from at least 1 of the following: brain imaging, cerebrospinal fluid analysis or necropsy examination. Cases without pathological confirmation of stroke subtype were unclassified. The Oxford Community Stroke Project (OCSP) clinical classification of stroke was also used, cerebral infarction being categorized as total anterior cerebral infarction, partial anterial cerebral infarction, posterior cerebral infarction (POCI) and lacunar infarction (LACI). A review of diagnostic subtypes was undertaken by A.R. and D.C. for the BROS cases.
&&& Data collected on prestroke risk factors included current smoking status and high alcohol intake (14 U per week for women, 21 U per week for men), as reported by the patient or carer, and general practice or hospital prestroke records of hypertension (blood pressure &140/90 mm Hg), atrial fibrillation, diabetes, ischemic heart disease, and transient ischemic attack.
&&& The SLSR population was estimated for each year from 1995 to 2002 by assuming a linear change based around the UK Census figure for
Office for National Statistics adjusted) and 2001. The total number of person-years was calculated as the sum of the population figure for each year. The time period 1995 to 2002 was used to have the power for a comparative analysis. For Barbados, the denominator was taken as the figure from the 2000 Census multiplied by the 2 years length of the study period.
&&& For each population, incidence rates and 95% CIs were calculated by age and sex, and by pathological and clinical subtype. Incidence rates were standardized by gender to European and world populations.8 CIs for incidence rate estimates were calculated using the Poisson distribution. Incidence rate ratios for South London relative to Barbados were calculated for strokes overall and by subtype, using Poisson regression,9 adjusting for age and gender.
&&& Results
&&& The SLSR registered 2321 patients with first in a lifetime stroke. Of these, %) were male and %) 414 (17.8%) were black and 112 (4.8%) of other ethnic origins with 74 (3.2%) of unknown ethnic origin. There were 270 black Caribbeans and 1 mixed black Caribbean/white patient, these having a mean age at first stroke of 66.1 years (range 27.8 to 95.6, SD 13.7). The number of patients having brain imaging was 230 (84.9%).
&&& BROS registered 665 patients. These comprised 282 (42.4%) males and 383 (57.6%) 30 (4.5%) were white, 578 (86.9%) were black Caribbean, 50 were mixed black Caribbean/white (7.5%), 2 (0.3%) of other ethnic origins with 5 (0.8%) of unknown ethnic origin. For the 628 black Caribbean and mixed patients, the mean age at first stroke was 71.2 years (range 16.7 to 103.7, SD 14.9). BROS patients were 5.5 years older on average than SLSR patients (95% CI, 3.4 to 7.6; P&0.001). The number of patients having brain imaging was 599 (95.4%).
&&& The crude total incidence rates/1000 population were 1.36 (95% CI, 1.20 to 1.52) for SLSR (Table 1) and 1.31 (95% CI, 1.21 to1.42) for BROS (Table 2). After age adjustment to a European population the incidence for SLSR was 1.61 (95% CI, 1.41 to 1.81) and BROS 1.29 (95% CI, 1.19 to 1.39). The overall incidence rate ratio with adjustment for age and gender (SLSR:BROS) was 1.26 (95% CI, 1.09 to 1.46).
&&& For both SLSR and BROS, European age-adjusted incidence rates were higher in males than in females (SLSR P=0.010, BROS P=0.002; Tables 1 and 2). For both SLSR and BROS incidence increased with age, rising rapidly from around 45 years in males and females. For patients aged 55 to 64, incidence was approximately double for males compared with females in both SLSR (P=0.068) and BROS (P&0.001). In BROS, female incidence was almost double that of males for those aged 85 years or more.
&&& Table 3 shows a comparison of risk factors for the SLSR and BROS patients. Current smoking was less common in BROS (26.7% in SLSR versus 8.0% in BROS; P&0.001), along with high alcohol intake (females: 14 U/week, males: 21 U/ 8.4% in SLSR versus 4.5% in BROS; P=0.031).
&&& Table 4 compares the distribution of stroke subtypes in SLSR and BROS. Of the 271 SLSR strokes, 191 (70.5%) were infarctions compared with 521 of 628 (83.0%) in BROS. Over half (52.8%) of strokes in BROS were LACIs, whereas in SLSR they account for 28.0%. However, POCIs were relatively uncommon in BROS (9.2% in SLSR versus 5.7% in BROS).
&&& Hemorrhages formed a greater proportion of strokes in SLSR with 61 (22.5%) versus 81 (12.9%) in BROS. SAHs were particularly uncommon in BROS (13/628 (2.1%) versus 25/271 (9.2%) in SLSR; P&0.001).
&&& Table 5 shows the incidence rate ratios (IRRs) for SLSR: BROS for specific stroke subtypes. Rates were calculated adjusting for the European rather than world standard population distribution because both SLSR and BROS have an age distribution closer to that of the former. The overall rate was higher for SLSR (IRR, 1.26; 95% CI, 1.09 to1.46). Statistically significant subtypes were total anterior cerebral infarctions (IRR, 1.82; 95% CI, 1.23 to 2.69), POCIs (IRR, 2.12; 95% CI, 1.28 to 3.53), primary intracerebral hemorrhage (IRR, 1.56; 95% CI, 1.03 to 2.35) and SAH (IRR, 5.04; 95% CI, 2.54 to 9.97). LACIs had a higher incidence in Barbados (IRR, 0.78; 95% CI, 0.60 to 1.01).
&&& Discussion
&&& This study assesses the incidence of stroke in a developed and a developing black Caribbean setting using identical, jointly developed methodologies that includes detailed phenotyping of the stroke and recording of underlying sociodemographic circumstance and stroke risk factors. The study clearly demonstrates that the risk in the Caribbean setting is similar to that described in white populations in the developed world and that the risk in a Caribbean population in inner London is significantly higher and at a younger age.
&&& Stroke is a major public health issue worldwide both in developing and developed countries and the indicators used by the WHO are based on routinely collected mortality data.10 In these reports London is considered part of a developed country and Barbados a developing country, and this is why such a definition has been adopted here. The evidence that the incidence of stroke in black communities is worse than in non-black communities comes mainly from the US and suggests that minority groups have higher rates or more severe strokes, but variations in prognosis for clinical outcomes other than mortality remain less certain.11 However, more evidence is required on regional ethnic variations in treatments and outcomes.
&&& We have previously separately reported the incidence of first in a lifetime stroke in the settings of South London and Barbados using the same stroke register methodology, yet no detailed and formal comparisons have been undertaken.3,5 This combined analysis presented here clearly demonstrates the increased risk in black Caribbeans who in the main migrated from the Caribbean and Guyana from the 1950s onwards to London. It demonstrates that risk does not remain the same regardless of setting but supports findings from the field of cardiovascular disease that migrants do take on additional risk in their new settings and are at increased risk of death. In London stroke occurs 5 years younger and the overall IRR is 26% higher in London, with much increased risk of hemorrhagic stroke, and posterior and total anterior circulation infarcts and reduced risk of lacunar stroke. An interesting observation was the markedly increased risk of SAH, which may be attributable to a higher prevalence of hypertension and smoking in South London. A weakness of the study is that we did not record the island from which the SLSR patients came or whether they were born in the UK. We were also unable to estimate the effect of "years lived" in South London on risk, although analyses would be confounded by many factors such as risk factor prevalence and environmental factors. These data would support the contention that stroke in black populations is not mainly attributable to genetic considerations.12
&&& Comparison of risk factors for stroke between the settings was limited to the main behavioral and physiological factors, and other important ones such as body mass index and cholesterol were not included. The effect of diet on risk was also not feasible in such a study. There appeared to be no excess of any risk factor in the Barbados group, whereas smoking, excessive drinking and ischemic heart disease were more prevalent in South London. Abbotts et al used the Health Survey for England data to illustrate how Caribbeans are potentially at increased risk of cardiovascular disease compared with the white population.13 They demonstrated that Caribbean men smoked more but had higher mean high-density lipoprotein cholesterol levels and Caribbean women had greater body mass index and lower mean triglyceride levels. Harding showed that the strongest predictors of stroke in Caribbeans resident in the UK were duration of residence and age at migration.14 Gillum has suggested 6 stages of epidemiological evolution of patterns of cardiovascular disease among black people of sub-Saharan African origin.15 These essentially show increasing development of atherosclerotic pathology and risk until finally this is reduced when better prevention and treatment are in place. Differences in some of the major risk factors for stroke have been demonstrated in similar ethnic groups, in different settings,12,16 and it would be reasonable to expect differences in stroke risk. The findings from this study do show a poorer risk factor profile in the South London group with increased risk of stroke.
&&& Another interpretation of these observed differences includes differential ascertainment of strokes, with under ascertainment in Barbados. Multiple sources of ascertainment were used with a substantial proportion being registered at home, indicating good coverage by the field workers in Barbados. There is no gold standard for ascertainment, but intense surveillance of all sources in Barbados by a doctor and public health nurse ensures as complete ascertainment as possible.
&&& Overall, this study has raised issues about the risk of stroke in different countries for black Caribbeans that clearly support the view that within populations of similar genetic stock living in different settings, disease risk varies, and this variation is likely to be driven by environmental factors. This is consistent with previous data which examined variation in risk factor profile.12,16 The overall risk factor profile of stroke patients is worse in South London, and probably reflects Westernization, because ischemic heart disease, smoking and hypertension are more prevalent. With Westernization being observed in Caribbean populations the risk of stroke may well increase over the next few years in Barbados. Unfortunately, the effect of the years of exposure to a new culture and environment could not be assessed in the study. Further studies are needed to follow-up cohorts of blacks in different settings to assess the risk of stroke and the effect of exposure to a broad range of risk factors and environmental factors. The increased risk of stroke in South London is a public health issue that requires targeted interventions that are culturally sensitive to reduce the impact of this disease in ageing populations.
&&& Acknowledgments
&&& We wish to thank all the patients and their families and the healthcare professionals involved. Particular thanks go to all the fieldworkers for SLSR and BROS.
&&& Sources of Funding
&&& This study was supported by: (South London) Northern & Yorkshire NHS R&D Programme in Cardiovascular Disease and Stroke, Charitable Foundation of Guy’s and St Thomas’ Hospitals, Stanley Thomas Johnson Foundation, Department of Health, UK; (Barbados) Wellcome Trust.
&&& Disclosures
&&& The sponsors had no role in the design and
collection, management, analysis, or interp nor any role in preparation, review, or approval of the manuscript.
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