DISPUTING THE ETHICS OF RESEARCH: THE CHALLENGE FROM BIOETHICS AND PATIENT ACTIVISM TO THE INTERPRETATION OF THE DECLARATION OF HELSINKI IN CLINICAL TRIALS

In this paper we argue that the consensus around normative standards for the ethics of research in clinical trials, strongly influenced by the Declaration of Helsinki, is perceived from various quarters as too conservative and potentially restrictive of research that is seen as urgent and necessary. We examine this problem from the perspective of various challengers who argue for alternative approaches to what ought or ought not to be permitted. Key themes within this analysis will examine these claims and argue they have implications for the interests of the research subject, research governance and regulation. Using our work with TREAT‐NMD, the neuromuscular clinical trials network, we posit that there is a place for advancing the discourse of moral rights and moral duties in the context of research, especially from the perspective of patients and their families, and for including the politics of patient activism and empowerment. At the same time we remain vigilant to the danger that the therapeutic misconception and other serious vulnerabilities for the patient population in clinical trials, are at risk of being overlooked.     

CAPACITY BUILDING OF ETHICS REVIEW COMMITTEES ACROSS AFRICA BASED ON THE RESULTS OF A COMPREHENSIVE NEEDS ASSESSMENT SURVEY

A needs assessment survey of ethics review committees (ERCs) across Africa was conducted in order to establish their major needs and areas of weaknesses in terms of ethical review capacity. The response rate was 84% (31 of 37 targeted committees), and committees surveyed were located in 18 African countries. The majority of the responding committees (61%) have been in existence between 5 and 10 years; approximately 74% of the respondents were institutional committees, with the remainder being either national (6/31) or regional (2/31).
In terms of the ethical review process, nine of the 31 committees that responded did not have standard operating procedures (SOPs), and seven of the 22 that did have SOPs had never revised them after their initial development (an average period of three years). Of the 31 committees, 10 operated without any ethical guidelines. Many of the committees (13/30) met once per month, and the number of proposals reviewed annually varied, ranging from five to over 100. All respondents relied on paper-based data management and archiving systems.
Overall, the survey identified the major constraints on ERCs as lack of office equipment, outdated or lack of SOPs, lack of electronic data management systems, inadequate resources, lack of or insufficient expertise on the committees, and poor recognition of the importance of the role of the committees. Consequently, the authors are addressing the identified needs and weaknesses through the Bill and Melinda Gates Foundation-funded capacity building project. The impact of the intervention project will be assessed during and at the end of the four-year longitudinal project.     

ETHICS OF MANDATORY PREMARITAL HIV TESTING IN AFRICA: THE CASE OF GOMA, DEMOCRATIC REPUBLIC OF CONGO

Despite decades of prevention efforts, millions of persons worldwide continue to become infected by the human immunodeficiency virus (HIV) every year. This urgent problem of global epidemic control has recently lead to significant changes in HIV testing policies. Provider-initiated approaches to HIV testing have been embraced by the Centers for Disease Control and Prevention and the World Health Organization, such as those that routinely inform persons that they will be tested for HIV unless they explicitly refuse ('opt out'). While these policies appear to increase uptake of testing, they raise a number of ethical concerns that have been debated in journals and at international AIDS conferences. However, one special form of 'provider-initiated' testing is being practiced and promoted in various parts of the world, and has advocates within international health agencies, but has received little attention in the bioethical literature: mandatory premarital HIV testing. This article analyses some of the key ethical issues related to mandatory premarital HIV testing in resource-poor settings with generalized HIV epidemics. We will first briefly mention some mandatory HIV premarital testing proposals, policies and practices worldwide, and offer a number of conceptual and factual distinctions to help distinguish different types of mandatory testing policies. Using premarital testing in Goma (Democratic Republic of Congo) as a point of departure, we will use influential public health ethics principles to evaluate different forms of mandatory testing. We conclude by making concrete recommendations concerning the place of mandatory premarital testing in the struggle against HIV/AIDS.     

大气CO_2浓度升高对植物的直接影响——国外十余年来模拟实验研究之主要手段及基本结论

本文针对国外近十几年来在ＣＯ２浓度升高对植物的直接影响方面所开展的生理生态学研究方法、动态、基本结论、存在问题等内容做了简要的介绍。大气ＣＯ２浓度在过去２００年内已增加了８０μｍｏｌ·ｍｏｌ－１,生长在高ＣＯ２环境下的植物,其生理生态、形态及化学成分等方面将会发生相应的变化。表现在光合作用速率出现不同程度的提高;呼吸作用受抑制;气孔密度减少,水分利用效率增加;生物量及产量增加;一些关键蛋白质及酶、非结构性碳水化合物含量增加;组织中的氮、硫等元素含量降低;根系及花的发育也随ＣＯ２浓度的升高而提前等。不同光合途径（Ｃ３、Ｃ４及ＣＡＭ）及不同植被类型（自然植被、栽培植被）的植物随ＣＯ２浓度发生的上述指标的变化在长期反应与短期反应方面具有很大的差异。另外,实验控制条件如温度、光照、水分、养分甚至实验装置（如花盆）的大小对预测结果也有很大的影响。     

FROM MEDICAL RATIONING TO RATIONALIZING THE USE OF HUMAN RESOURCES FOR AIDS CARE AND TREATMENT IN AFRICA: A CASE FOR TASK SHIFTING

With a global commitment to scaling up AIDS care and treatment in resource‐poor settings for some of the most HIV‐affected countries in Africa, availability of antiretroviral treatment is no longer the principal obstacle to expanding access to treatment. A shortage of trained healthcare personnel to initiate treatment and manage patients represents a more challenging barrier to offering life‐saving treatment to all patients in need. Physician‐centered treatment policies accentuate this challenge. Despite evidence that task shifting for nurse‐centered AIDS patient care is effective and can alleviate severe physician shortages that currently obstruct treatment scale‐up, political commitment and policy action to support task shifting models of care has been slow to absent. In this paper we review the evidence in support of task shifting for AIDS treatment in Africa and argue that continued policy inaction amounts to unwarranted healthcare rationing and as such is ethically untenable.     

INITIATION AND ONTOGENY OF THE MICROSPORANGIATE CONE IN CUPRESSUS ARIZONICA IN RESPONSE TO GIBBERELLIN

Cupressus arizonica, a member of the Cupressaceae, was induced to produce pollen cones in response to gibberellin treatment. All apices remained vegetative during the first 17 days of treatment. At this time many lateral vegetative apices began to undergo a transition to the reproductive state. The transition was marked by changes in apical zonation characterized by increased mitotic activity primarily in the subapical mother-cell and peripheral zones. Also, precocious initiation of branch meristems occurred much higher on the shoot apex than before the transition period. About 22 days after the initial treatment, most apices became distinctly reproductive. The reproductive apex has a zonation pattern similar to the branching apex but is shorter and wider and quite distinct from the vegetative apex. The small subapical mother cells and cells of the peripheral zone form a continuous mantle of mitotically active cells with prominent nucleoli. This mantle encloses a very broad pith region which differentiates nearly to the summit of the apex. Microsporophyll and leaf initiation are similar and the protoderm of the apex remains discrete and does not contribute to deeper tissues. Sporangia do not originate from superficial cells of the microsporophyll. After all microsporophylls are initiated the reproductive apex becomes inactive. A discussion concerns the morphological implication in the origin of the foliar structures and of the similarity of C. arizonica to many angiosperms in the transition of the apex from vegetative to reproductive.     

水生维管束植物对水体铅污染的反应、抗性和净化作用

重金属铅污染环境的一个主要方面是对水体的污染。主要的污染源是某些矿山(如铅锌矿等)、有色金属冶炼厂、铅制品加工厂等的废水和废气以及汽车尾气等。按金属的生物效应来分类,铅为有毒金属。大量的铅直接或者通过食物链的富集进入人体会造成严重的危害。目前,国内外对于铅污染的环境对陆生植物的影响以及陆生植物对铅污染的反应开展了一些     

ON THE DIFFERENTIAL RESPONSE OF SARCOPLASM AND MYOPLASM TO DENERVATION IN FROG MUSCLE

Electron microscopic evidence is presented that the early response to denervation ("simple atrophy") of the semitendinosus m. of the frog is characterized by a greater prominence of the sarcoplasmic reticulum and by the presence, in the interfibrillar spaces, of mitochondria which are more numerous and smaller than in normal muscle. In contrast with the dynamic changes of the sarcoplasmic structural components, the myofibrils showed a progressive decrease in diameter after denervation and throughout the period studied. By carrying out tissue fractionation experiments, the yield of microsome-protein was found significantly greater in the denervated muscles, as compared with the contralateral controls, in this initial stage. Under the conditions attending the overdevelopment of the sarcoplasmic reticulum (SR), denervated semitendinosus m. incorporated valine-C¹⁴ into proteins more actively than the control pairs. The denervated muscles also showed an increase in the number of freely scattered and membrane-bound ribosomes and of polyribosomes, suggesting a more active synthesis of the SR membranes. Pronounced atrophy of the myofibrils, disorganization of the SR, and an increased number of ribonucleoprotein particles lying in the enlarged interfibrillar spaces were the main ultrastructural features of "degenerative atrophy" in frog muscle in the late periods after denervation. The probably adaptive character of the early changes occurring on denervation of frog muscle is discussed.     

急性低氧时的Starling效应及心包的影响

为确定 Starling效应在心泵急性低氧反应中的地位,以及心包对此反应的影响,把17条雄狗,分别在心包切开(A 组)和缝合(B 组)条件下进行实验。在连续、依次吸入空气、氧分压为89、70和55mmHg 的常压氧-氮混合气各30min,并最后吸入氮气时,分别记录不同低氧状况下的左室前后径超声图、左室压力,dp/dt,右室压力或主动脉压力和第二导联心电图。结果表明,重度低氧时,左室舒张期末直径显著增大,A组由对照值3.88±0.15cm(M±SE)增大至4.22±0.18cm(P<0.01);B组由3.53±0.13cm增至3.67±0.12cm(P<0.01),并伴以每搏直径变化的明显增大(A 组由对照值的4.4±0.2mm增至4.9±0.2mm P<0.05;B 组由3.2±0.1mm 增至3.8±0.2mm P<0.01)。左室压力-直径环在重度低氧时显著右移,环体面积不缩小。说明重度低氧时,Starling 效应对心脏搏血功能的调节具有重要作用。在严重低氧导致左室收缩压进行性降低时,迅速切开心包可有利于心泵功能的改善,提示,心包对 Starling 效应的充分发挥有限制作用。     

FLOWERING OF DICHONDRA IN RESPONSE TO TEMPERATURE AND DAYLENGTH

Experiments using controlled environment facilities showed that flowering of Dichondra repens was promoted by chilling plants at 10 C or below. Optimum length of the chilling period was 5–6 weeks. Unchilled plants did not flower. The flowering stimulus resulting from chilling was destroyed by temperatures above 21 C. Rate of flowering was increased by short days during chilling, but short days could not substitute for the chilling requirement. Optimum daylength for flower initiation following chilling was approximately 14 hr and the optimum temperature was approximately 15 C. Flower buds developed in leaf axils of primary stems and laterals, but stem apices remained vegetative. When the chilling requirement was met flowering continued indefinitely as the plants grew.     

RELEVANCE OF REGRESSION TO THE MEAN TO EPIDEMIOLOGICAL AND CLINCAL STUDIES: A REVIEW OF THE LITERATURE

Investigation of the relative heights of pairs of fathers and sons led the famous 19th century scientist, Sir Francis Galton, to the concept known as "regression to the mean." Gallon observed that sons of extremely tall or extremely short fathers tended to be less extremely tall or short. The concept has since been - found to apply to virtually any experiment requiring a test-retest design. On the average, the bottom group on the first test will tend to increase, and the top group will on average decrease on the retest. For example, a clinical study requiring an initially high blood pressure baseline value (screening value), might decrease as a group on a subsequent retest, perhaps merely due to a regression effect. One way to account for possible bias due to regression effects is by using an appropriate control group. In the absence of a control group, James (1973) has developed some useful formulas for estimating the expected regression effect, when a truncated population is being sampled. Choice of an appropriate baseline value should also be guided by consideration of the potential effects of regression.     

THE IMPORTANCE OF MOSQUITO BEHAVIOURAL ADAPTATIONS TO MALARIA CONTROL IN AFRICA

Over the past decade the use of long‐lasting insecticidal nets (LLINs), in combination with improved drug therapies, indoor residual spraying (IRS), and better health infrastructure, has helped reduce malaria in many African countries for the first time in a generation. However, insecticide resistance in the vector is an evolving threat to these gains. We review emerging and historical data on behavioral resistance in response to LLINs and IRS. Overall the current literature suggests behavioral and species changes may be emerging, but the data are sparse and, at times unconvincing. However, preliminary modeling has demonstrated that behavioral resistance could have significant impacts on the effectiveness of malaria control. We propose seven recommendations to improve understanding of resistance in malaria vectors. Determining the public health impact of physiological and behavioral insecticide resistance is an urgent priority if we are to maintain the significant gains made in reducing malaria morbidity and mortality.