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Annual disease burden due to human papillomavirus (HPV) 6 and 11 infections in Finland. 芬兰人乳头瘤病毒(HPV) 6和11感染引起的年度疾病负担
Pub Date : 2009-01-01 DOI: 10.1080/00365540902887730
Kari J Syrjänen

In addition to cancer of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, precancer and cancer lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (papillomas) are associated with the low-risk (LR) HPV types, most notably with HPV6 and HPV11. Until recently, the main interest in HPV research has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. With the recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11), it has become timely to make a systematic survey on the annual disease burden due to these 2 HPV genotypes in our country. These types of data should form the foundation for all calculations of the annual costs needed to treat these diseases by conventional means. Accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV6 and HPV11 vaccines. If proven useful for any of these purposes, this document will have fulfilled its purpose. In the first step, published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. GLOBOCAN 2004 (IARC) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website for obtaining these (y 2005) numbers in Finland. The evidence linking HPV to each individual tumour category was classified as: 1) established, 2) emerging, and 3) controversial. All published evidence was weighted for each individual malignant, premalignant and benign lesion, anatomic region by region, while assessing the attributable fraction of HPV6/11 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by FCR or GLOBOCAN, different approaches had to be used to derive the best estimates for their incidence, based on published literature or other registries (e.g. genital wart registry of the UK and Wales, and mass screening registry of FCR). With a lack of reasonable consensus, a lower and an upper limit was set for the range of estimates. In cases with different age-specific incidence (e.g. genital warts), the population pyramid of Finland was used to calculate the incident cases. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The malignant neoplasms with established or emerging evidence on the causal role of HPV are listed by their ICD-10 codes in Table I. Included in this list are also 2 controversial malignancies (colorectal cancer and endometrial cancer), of which the contradictory HPV data are critically discussed. The third major cancer

除了女性下生殖道的癌症外,人乳头瘤病毒(HPV)还与两性不同解剖部位的大量良性、癌前病变和癌性病变有关。恶性肿瘤及其前体通常归因于致癌(高风险,HR) HPV类型,而良性病变(乳头状瘤)与低风险(LR) HPV类型相关,最明显的是HPV6和HPV11。直到最近,HPV研究的主要兴趣集中在HR-HPV类型及其相关病理上,而对LR-HPV类型引起的病变的关注要少得多。随着最近针对两种最重要的低密度HPV (HPV6和HPV11)有效的预防性疫苗获得许可,对我国这两种HPV基因型每年造成的疾病负担进行系统调查已是及时的。这些类型的数据应成为计算用常规手段治疗这些疾病所需的年度费用的基础。对预防HPV6和HPV11疫苗的成本效益进行所有建模时,对疾病负担的准确估计也是必须的。如果证明对这些目的中的任何一个有用,则本文档将实现其目的。第一步,使用已发表的HPV文献在不同解剖部位创建与该病毒相关的良性、癌前和恶性病变列表。GLOBOCAN 2004 (IARC)数据库用于得出2002年每种恶性肿瘤的全球病例数,并使用芬兰癌症登记处(FCR)网站获得芬兰的这些(2005年)数字。将HPV与每个肿瘤类别联系起来的证据分为:1)已建立的,2)新出现的,以及3)有争议的。所有已发表的证据按解剖区域对每个恶性、癌前和良性病变进行加权,同时评估每个病变中HPV6/11基因型的归因比例。由于良性和大多数癌前病变未被FCR或GLOBOCAN登记,因此必须使用不同的方法,根据已发表的文献或其他登记(例如,英国和威尔士的生殖器疣登记以及FCR的大规模筛查登记),得出其发病率的最佳估计。由于缺乏合理的共识,为估计范围设定了一个下限和上限。对于不同年龄段发病率的病例(如生殖器疣),采用芬兰人口金字塔来计算发病率。在确定的情况下,使用男性和女性之间的不同发病率来计算按性别划分的事件病例数。根据ICD-10编码,已确定或新出现的与HPV因果关系相关证据的恶性肿瘤列于表1。在此列表中,还有2种有争议的恶性肿瘤(结直肠癌和子宫内膜癌),其中对相互矛盾的HPV数据进行了批判性讨论。同一类别中的第三种主要癌症(前列腺癌)没有包括在列表中,因为即使在新出现的HPV相关恶性肿瘤中,数据显然也不足以对这种实体进行分类。芬兰由HPV6/11引起的估计疾病负担,按解剖区域和肿瘤类型计算为每年新病例数,见表2,并总结于图1。目前的分析表明,如果所有病例都进行了登记,芬兰每年至少会发现12,666至13,066例HPV6或hpv11相关临床病变的新病例。值得注意的是,这些数字代表了这两种HPV类型造成的疾病负担。然而,这些临床病变仅代表由这两种HPV基因型感染引起的总病毒负担的一小部分。这是因为这些无处不在的病毒的绝大多数感染是潜伏的,本质上是短暂的,并在几个月内(最多1年)自行消退,而不会发展为临床可检测的疾病。然而,这种自发清除并不会使这些潜伏性感染变得不那么重要,因为只要病毒库存在,它就会成为病毒传播给易感个体的来源,如本文所述,具有多种HPV6/11相关病理作为潜在的结果。这些数据在有效预防HPV6和HPV11的HPV疫苗接种时代的意义应该是明确的。
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引用次数: 13
Annual disease burden due to human papillomavirus 16 and 18 infections in Finland. 芬兰人乳头瘤病毒16和18感染引起的年度疾病负担。
Pub Date : 2009-01-01 DOI: 10.3109/00365540903331985
Kari J Syrjänen

Apart from cancers of the lower female genital tract, human papillomaviruses (HPV) are associated with a large number of benign, premalignant and malignant lesions at different anatomic sites in both genders. Malignant tumours and their precursors are usually attributed to the oncogenic (high-risk, HR) HPV types, whereas benign lesions (mostly papillomas) are ascribed to the low-risk (LR) HPV types, most notably HPV6 and HPV11. To date, the main interest has been focused on HR-HPV types and their associated pathology, and much less attention has been paid to the lesions caused by the LR-HPV types. The recent licensing of an effective prophylactic vaccine against the 2 most important LR-HPV types (HPV6 and HPV11) has resulted in considerably increased interest in these LR-HPV types as well. This author recently conducted a systematic survey of the annual disease burden due to HPV6/11 infections in Finland. As a rational continuation, the present survey was conducted to estimate the annual disease burden due to HPV16 and HPV18 infections in our country. Together, these 2 documents form the foundation for calculations of the annual costs needed to treat the diseases caused by these 2 most common LR and HR HPV types. Similar to HPV6/11, accurate estimates of disease burden are also mandatory for all modelling of the cost-effectiveness of prophylactic HPV16/18 vaccines. In the first step, the published HPV literature was used to create a list of benign, premalignant and malignant lesions associated with this virus at different anatomic sites. The GLOBOCAN 2004 (IARC; International Agency for Research on Cancer) database was used to derive the global numbers of incident cases for each of these malignancies in 2002, and the Finnish Cancer Registry (FCR) website was used to obtain these numbers for Finland (y 2005). The evidence linking HPV to each individual tumour category was classified as: (1) established, (2) emerging, and (3) controversial. All published evidence was weighted for each individual malignant, premalignant and benign lesion, anatomic region-by-region, while assessing the attributable fraction of HPV16/18 genotypes in each lesion. Because benign and most of the precancer lesions are not registered by the FCR or GLOBOCAN, different approaches had to be used to derive the estimates for their incidence, based on published literature or other registries. In cases with no reasonable consensus, a lower and an upper boundary was set for the range of these estimates. Where well established, the different incidence rates among males and females were used to calculate the numbers of incident cases by gender. The present survey implicates that a minimum of 7859 to 8316 new cases of HPV16- or HPV18-associated clinical lesions would be detected each y in Finland, if all were registered. In other words, these numbers represent the annual disease burden due to these 2 most common HR-HPV genotypes. In the Finnish population, these lower and upper

除了女性下生殖道的癌症外,人乳头瘤病毒(HPV)还与两性不同解剖部位的大量良性、癌前和恶性病变有关。恶性肿瘤及其前体通常归因于致瘤性(高风险,HR) HPV型,而良性病变(主要是乳头状瘤)归因于低风险(LR) HPV型,最明显的是HPV6和HPV11。迄今为止,主要的兴趣集中在HR-HPV类型及其相关病理上,而对LR-HPV类型引起的病变的关注要少得多。最近,针对两种最重要的低级别hpv类型(HPV6和HPV11)的有效预防性疫苗获得许可,这也大大增加了人们对这些低级别hpv类型的兴趣。本文作者最近在芬兰进行了一项由HPV6/11感染引起的年度疾病负担的系统调查。作为合理的延续,本调查旨在估计我国因HPV16和HPV18感染而造成的年度疾病负担。这两份文件共同构成了计算治疗这两种最常见的LR型和HR型HPV引起的疾病所需的年度费用的基础。与HPV6/11类似,对预防性HPV16/18疫苗的成本效益进行所有建模时,也必须准确估计疾病负担。第一步,使用已发表的HPV文献在不同解剖部位创建与该病毒相关的良性、癌前和恶性病变列表。GLOBOCAN 2004 (IARC;利用国际癌症研究机构(International Agency for Research on Cancer)的数据库得出2002年每种恶性肿瘤的全球病例数,并利用芬兰癌症登记处(FCR)网站获得芬兰的这些数字(2005年)。将HPV与每个肿瘤类别联系起来的证据分为:(1)已建立的,(2)新出现的,和(3)有争议的。在评估HPV16/18基因型在每个病变中的归因比例的同时,对每个恶性、癌前和良性病变的解剖区域进行加权。由于良性和大多数癌前病变未被FCR或GLOBOCAN登记,因此必须使用不同的方法来根据已发表的文献或其他登记来得出其发生率的估计。在没有达成合理共识的情况下,为这些估计的范围设定了一个下限和一个上限。在确定的情况下,使用男性和女性之间的不同发病率来计算按性别划分的事件病例数。目前的调查表明,芬兰每年至少会发现7859至8316例HPV16或hpv18相关临床病变的新病例,如果所有病例都登记在案的话。换句话说,这些数字代表了由这两种最常见的HR-HPV基因型引起的年度疾病负担。在芬兰人口中,这些下限和上限转化为粗年发病率分别为147/100,000和156/100,000。根据欧洲标准人口进行调整后,年龄调整后的发病率分别为137/100,000和145/100,000。与该国HPV6/11的年度疾病负担(12,666-13,066新病例)相比,HPV16/18的这些数字要小得多。HPV6/11和HPV16/18之间的另一个主要区别是,前者造成的疾病负担在性别之间的分布更为均匀,只有轻微的女性优势(约7500例对5500例)。这与HPV16/18的疾病负担形成鲜明对比,到目前为止,HPV16/18的主要比例是由女性造成的(大约7000例对1300例)。值得注意的是,本报告中统计的HPV16/18的临床病变仅占这两种HR-HPV基因型感染引起的总病毒负担的一小部分。这是因为这些HR-HPV感染绝大多数是短暂的,并在几个月内自行消退,而不会发展为临床疾病。然而,这种自发清除并不会降低这些潜伏感染的重要性,因为只要病毒库存在,它就会成为病毒传播给易感个体的来源,从而导致大量hpv16 /18相关病理。在有效预防性HPV疫苗接种时代,这些数据的含义应该是直截了当的。然而,未来HPV疫苗和疫苗接种规划的设计者面临两个迫在眉睫的挑战:(1)HPV16/18疾病负担在性别之间的明显不平衡;(2)HPV6/11年度疾病负担远远超过HPV16/18,而且男女之间的贡献更加均匀。
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引用次数: 15
HIV viral resistance to antiretroviral drugs: foreword. HIV病毒对抗逆转录病毒药物的耐药性:前言。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310017129
Giuseppe Ippolito
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引用次数: 0
Epidemiological aspects of transmitted HIV drug resistance. 传播性艾滋病毒耐药性的流行病学方面。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310009597
Enrico Girardi

Transmitted human immunodeficiency virus (HIV) resistance to antiretrovirals (i.e. resistance in antiretroviral naive patients) emerged during the 1990s as a potentially relevant public health problem. HIV variants resistant to all classes of approved antiretroviral agents have been identified in significant proportions antiretroviral naive patients, and this phenomenon appears as a potential threat to the effectiveness of highly active antiretroviral therapy. Available data from surveys conducted between 1996 and 2001 show the prevalence of drug resistance among newly HIV-infected individuals to range from 3%, to above 20% in North America, and from 5% to 15% in Europe. Increases in prevalence observed during the late 1990s in some studies are not confirmed by most recent data. Transmission of multidrug resistance still appears to be an uncommon occurrence. However, methodological heterogeneity and problems in study design make it difficult to compare results between different surveys and to draw firm conclusions from the results. There is a clear need to improve surveillance systems aimed at identifying patients at the time of primary infection and to standardize laboratory methods for the identification of genetic markers of resistance to be used for epidemiological purposes.

传播性人类免疫缺陷病毒(艾滋病毒)对抗逆转录病毒药物的耐药性(即抗逆转录病毒初始患者的耐药性)在1990年代成为一个潜在的相关公共卫生问题。已在很大比例的未接受抗逆转录病毒治疗的患者中发现了对所有已批准的抗逆转录病毒药物耐药的艾滋病毒变异,这一现象似乎对高活性抗逆转录病毒治疗的有效性构成了潜在威胁。1996年至2001年期间进行的调查的现有数据表明,在新感染艾滋病毒的人中,抗药性的流行率在北美为3%至20%以上,在欧洲为5%至15%。在1990年代后期的一些研究中观察到的流行率的增加并没有得到最近数据的证实。多药耐药的传播似乎仍然不常见。然而,方法的异质性和研究设计的问题使得比较不同调查的结果和从结果中得出确定的结论变得困难。显然需要改进监测系统,以便在初次感染时确定患者,并使实验室方法标准化,以确定用于流行病学目的的耐药性遗传标记。
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引用次数: 15
Genotypic resistance tests for the management of patients with viro-immunological discordant response to highly active antiretroviral therapy. 基因型耐药试验对高活性抗逆转录病毒治疗病毒免疫不一致反应患者的管理。
Mauro Moroni

Single withess: Drug resistance is one of the main factors limiting the success of antiretroviral therapy. Some other factors, such as individual enzymatic pattern and immune system function, play a role in the outcome of therapy in HIV infection. Moreover, adherence to treatment could also be a pivotal factor. Thus, there is a complex network that influences patients' response and ultimately contributes to the development of drug resistance. A particular situation among HIV-infected individuals is the finding of a 'discordant' response, which means a virological failure with the maintenance of an optimal immune function. In these subjects, the mere determination of the genotypic pattern of drug resistance is not necessary. Rather, the quantification of phenotypic drug resistance together with the measurement of viral fitness and/or CD4+ T-cell dynamics will help in defining further therapeutic strategies.

单一证人:耐药性是限制抗逆转录病毒治疗成功的主要因素之一。一些其他因素,如个体酶模式和免疫系统功能,在HIV感染的治疗结果中发挥作用。此外,坚持治疗也可能是一个关键因素。因此,有一个复杂的网络影响患者的反应,并最终导致耐药性的发展。艾滋病毒感染者的一种特殊情况是发现“不协调”反应,这意味着在维持最佳免疫功能方面出现病毒学失败。在这些受试者中,仅仅确定耐药性的基因型模式是不必要的。相反,表型耐药的量化以及病毒适应度和/或CD4+ t细胞动力学的测量将有助于确定进一步的治疗策略。
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引用次数: 0
Genotypic resistance tests for the management of the HIV-infected pregnant patient in Africa. 基因型耐药试验对非洲艾滋病毒感染孕妇的管理。
Carlo Giaquinto

Single witness: The current development of guidelines for antiretroviral therapy in resource-limited settings raised the issues of the possible use of drug resistance testing (DRT) in middle- and low-income countries, especially in the context of prevention of mother-to-child transmission (MTCT) programmes. Although resource limitation make it clear that DRT cannot be recommended as an essential part of clinical management of HIV-infected pregnant women in Africa, it is important to monitor the prevalence and incidence of drug resistance on a population basis as ART is scaled up worldwide and programmes for the prevention of MTCT will be implemented. Moreover, even in low-resource countries there are some special settings where DRT may be available for patient care and its use may be considered.

单一证人:目前在资源有限的环境中制定的抗逆转录病毒治疗指南提出了在中低收入国家,特别是在预防母婴传播(MTCT)规划的背景下可能使用耐药检测(DRT)的问题。虽然资源限制明确表明,不能建议将DRT作为非洲感染艾滋病毒孕妇临床管理的重要组成部分,但随着抗逆转录病毒治疗在世界范围内的推广和预防母婴传播方案的实施,在人口基础上监测耐药性的流行和发生率是很重要的。此外,即使在资源匮乏的国家,也有一些特殊的环境,可以为患者提供DRT治疗,并且可以考虑使用DRT。
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引用次数: 0
Epidemiological changes in AIDS and HIV infection in Italy. 意大利艾滋病和艾滋病毒感染的流行病学变化。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310009588
Barbara Suligoi, Patrizio Pezzotti, Stefano Boros, Roberta Urciuoli, Giovanni Rezza

This article describes the major changes in the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/ AIDS) epidemic in Italy, using data from the National AIDS Registry and from 5 local surveillance systems for new HIV diagnoses. From 1982 to 2001, 49,063 adults with AIDS were reported to the AIDS Registry. From 1988 to 2000, the 5 local systems reported 23,252 new HIV diagnoses. The AIDS incidence increased until 1995, followed by a progressive decrease. A decrease was also observed for the incidence of new HIV diagnoses after 1989, with an apparent stabilization after 1998. Most AIDS cases have been represented by intravenous drug users (IDU), yet since 1999 the percentage of cases attributable to sexual transmission has exceeded that for IDUs. Similarly, among new HIV diagnoses, the percentage of cases attributable to sexual transmission increased from 23.6% before 1993 to 58.5% in 2000. The percentage of people with AIDS who discovered their seropositivity no earlier than 6 months before AIDS diagnosis increased from 20.6% in 1996 to 48.8% in 2001. Although the incidence of both AIDS and new HIV diagnoses has declined, a possible resurgence of the epidemic cannot be ruled out, in light of various factors that could lead to an increasing number of living infected people.

本文描述了意大利人类免疫缺陷病毒/获得性免疫缺陷综合征(HIV/ AIDS)流行的主要变化,使用了国家艾滋病登记处和5个地方艾滋病新诊断监测系统的数据。从1982年到2001年,艾滋病登记处报告了49063名患有艾滋病的成年人。从1988年到2000年,5个地方系统报告了23252例新的艾滋病毒诊断。艾滋病发病率一直上升到1995年,随后逐渐下降。1989年以后新诊断的艾滋病毒发病率也有所下降,1998年以后明显趋于稳定。大多数艾滋病病例以静脉注射吸毒者(IDU)为代表,但自1999年以来,可归因于性传播的病例百分比已经超过了静脉注射吸毒者的百分比。同样,在新诊断的艾滋病毒中,可归因于性传播的病例百分比从1993年以前的23.6%增加到2000年的58.5%。在艾滋病诊断前6个月内发现血清学阳性的艾滋病患者比例从1996年的20.6%上升到2001年的48.8%。虽然艾滋病和艾滋病毒新诊断的发病率都有所下降,但鉴于各种因素可能导致受感染人数不断增加,不能排除这一流行病可能卷土重来的可能性。
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引用次数: 13
Use of genotypic assays for the detection of HIV antiretroviral resistance. 利用基因型测定法检测艾滋病毒抗逆转录病毒耐药性。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310009614
Emanuele Nicastri, Giuseppe Ippolito

Resistance is the inherent capacity of a living being to resist untoward circumstances (disease, malnutrition or toxic agents). Resistance has developed to nearly all specific and effective antiviral agents, including all drugs against human immunodeficiency virus (HIV). Resistance develops rapidly when viral replication is not maximally suppressed. Drug-resistant viruses may be transmitted at the moment of primary infection. Assays to measure drug resistance are available in specialized laboratories and warnings are related to possible expanded use of these assays in the absence of randomized studies with prolonged clinical endpoints. Randomized clinical trials to allow general recommendations for the use of resistance assays in clinical practice are still urgently required.

抵抗力是生物抵抗不利环境(疾病、营养不良或有毒物质)的内在能力。对几乎所有特异性和有效的抗病毒药物,包括所有针对人类免疫缺陷病毒(HIV)的药物都产生了耐药性。当病毒复制没有得到最大程度的抑制时,耐药性迅速发展。耐药病毒可在初次感染时传播。在专门的实验室中可以使用测定耐药性的方法,在缺乏具有长期临床终点的随机研究的情况下,可能会扩大使用这些方法。目前仍迫切需要随机临床试验,以便在临床实践中对耐药性测定的使用提出一般性建议。
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引用次数: 1
Clinical implications of HIV-1 drug resistance in the neurological compartment. HIV-1在神经腔室耐药的临床意义。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310009650
Andrea Antinori, Antonella Cingolani, Maria Letizia Giancola, Federica Forbici, Andrea De Luca, Carlo Federico Perno

The tropism of human immunodeficiency virus type 1 (HIV-1) for the central nervous system (CNS) develops early during the course of the infection. Potent antiretroviral therapy has been demonstrated to be effective in controlling the replication of HIV-1 in cerebrospinal fluid (CSF), even though a variable response in this compartment compared with that in plasma has been observed. Different concentrations of antiretroviral drugs are found in CSF and the use of antiretroviral drugs penetrating across the blood-brain barrier is considered to be required for controlling CNS infection in advanced patients, particularly in those with neurological disorders. The compartmentalization of HIV-1 infection in the CNS may affect the treatment response, which may cause a different evolution of viral drug resistance in the 2 compartments. Although HIV-1 resistance testing in CSF is not recommended for the routine management of patients with virological failure, treatment decisions in patients with neurological disorders may require knowledge of the resistance profile of the virus in the CSF.

人类免疫缺陷病毒1型(HIV-1)对中枢神经系统(CNS)的倾向在感染过程中早期发展。强有力的抗逆转录病毒疗法已被证明可有效控制HIV-1在脑脊液(CSF)中的复制,尽管已观察到脑脊液与血浆中的反应不同。在脑脊液中发现了不同浓度的抗逆转录病毒药物,并且认为需要使用穿透血脑屏障的抗逆转录病毒药物来控制晚期患者的中枢神经系统感染,特别是那些患有神经系统疾病的患者。HIV-1感染在中枢神经系统中的区室化可能影响治疗反应,这可能导致病毒在两个区室中产生不同的耐药进化。尽管不建议对病毒学失败的患者进行脑脊液HIV-1耐药检测,但神经系统疾病患者的治疗决策可能需要了解脑脊液中病毒的耐药情况。
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引用次数: 26
Too early or too late: a never-ending dilemma with new technologies. 太早或太晚:新技术的一个永无止境的困境。
Pub Date : 2003-01-01 DOI: 10.1080/03008870310016247
Giuseppe Biondi
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引用次数: 1
期刊
Scandinavian journal of infectious diseases. Supplementum
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