Linearized spectrum correlation analysis for thermal helium beam diagnostics.

We introduce a new correlation analysis technique for thermal helium beam (THB) diagnostics. Instead of directly evaluating line ratios from fluctuating time series, we apply arithmetic operations to all available He I lines and construct time series with desired dependencies on the plasma parameters. By cross-correlating those quantities and by evaluating ensemble averages, uncorrelated noise contributions can be removed. Through the synthetic data analysis, we demonstrate that the proposed analysis technique is capable of providing the power spectral densities of meaningful plasma parameters, such as the electron density and the electron temperature, even under low-photon-count conditions. In addition, we have applied this analysis technique to the experimental THB data obtained at the ASDEX Upgrade tokamak and successfully resolved the electron density and temperature fluctuations up to 90 kHz in a reactor relevant high power scenario.

Children as hematopoietic cell donors in research: when is it approvable?

With increasing frequency, allogeneic hematopoietic cell transplantation involving children is being performed in the research setting. Allogeneic hematopoietic cell transplantation, however, cannot be performed without a hematopoietic stem cell (HSC) donor. This donor is often a sibling of the recipient and may also be a child. In such circumstances, it is unclear whether or how the federal regulations for pediatric research apply to the minor donors. This introductory paper reviews the issues to be considered while evaluating studies that use HSCs obtained from minor donors and identifies areas where further research is needed. In the era of increasing applicability for donor-derived cellular therapies, we provide a suggested framework for determining when minor donors qualify as human research subjects and when their participation can be approved under the federal regulations.

Is it ethical to keep interim findings of randomised controlled trials confidential?

Data monitoring committees often are employed to review interim findings of randomised controlled trials. Interim findings are kept confidential until the data monitoring committee finds that they provide sufficiently compelling evidence regarding efficacy, typically because they have crossed the pre-defined statistical boundaries, or they raise serious concerns about safety. While this practice is vital to maintaining the scientific integrity of controlled trials and thereby ensuring their social value, it has been criticised as unethical. Commentators argue that withholding interim findings from research participants is deceptive, inconsistent with valid informed consent, and a violation of respect for participants' autonomy. The present article examines these arguments, focusing specifically on confidential data monitoring for efficacy. This practice need not be deceptive provided its use is disclosed to prospective research participants. In addition, confidential data monitoring does not make research participants worse off than they would be in the clinical setting and represents an acceptable limitation on the options available to prospective research participants. Taken together, these considerations suggest confidential data monitoring, subject to adequate safeguards, is ethically acceptable.

Assessing research risks systematically: the net risks test.

Dual-track assessment directs research ethics committees (RECs) to assess the risks of research interventions based on the unclear distinction between therapeutic and non-therapeutic interventions. The net risks test, in contrast, relies on the clinically familiar method of assessing the risks and benefits of interventions in comparison to the available alternatives and also focuses attention of the RECs on the central challenge of protecting research participants.

Assent in paediatric research: theoretical and practical considerations.

Guidelines around the world require children to provide assent for their participation in most research studies. Yet, little further guidance is provided on how review committees should implement this requirement, including which children are capable of providing assent and when the requirement for assent may be waived on the grounds that the research offers participating children the potential for important clinical benefit. The present paper argues that the assent requirement is supported by the importance of allowing children who are capable to make their own decisions. This suggests children are capable of assent when they become able to understand the research in question. While development varies across individual children, existing data suggest most children develop this ability by approximately age 14. Until instruments are developed to assess the assent capacity of individual children, this age should be used as the threshold for assent. In addition, the importance of protecting children from harm suggests that the sustained dissent of all children, including those who are unable to provide assent, should be respected. While the assent requirement may be waived when research participation offers the potential for important medical benefit that is unavailable outside the research context, analysis suggests that children's sustained dissent should be respected in all cases.

The standard of care debate: the Declaration of Helsinki versus the international consensus opinion.

The World Medical Association's revised Declaration of Helsinki endorses the view that all trial participants in every country are entitled to the worldwide best standard of care. In this paper the authors show that this requirement has been rejected by every national and international committee that has examined this issue. They argue that the consensus view now holds that it is ethically permissible, in some circumstances, to provide research participants less than the worldwide best care. Finally, the authors show that there is also consensus regarding the broad conditions under which this is acceptable.

Suspended solids from industrial and municipal origins.

The origins of suspended solids are the effluents of municipal and industrial wastewater treatment plants and storm sewage treatment. This paper deals with the sources of industrial and municipal wastewater treatment and the single treatment of side streams. An overview of the common treatment processes is given and the main sinks for suspended solids are named and described. The food industry is based on the processing of organic matter (fruits, etc.). During the single processing steps three main fractions occur, inorganic material (e.g., from the washing step), organic residues (e.g., the peel), and suspended solids (SS) in the wastewater. Today higher rates of recycling (water and raw materials) can be found in all kinds of industrial processes. The principle is that avoidance should take precedence over utilization which should take precedence over disposal. Numerous possibilities of production-integrated measures exist, e.g., conveyance of production circuits, product recovery, and stepped cleaning. Despite and/or due to these efforts, huge amounts of residues occur. They are the main sink for suspended solids. Only seldom is landfilling used to treat these residues. Usually utilization as animal nourishment or biological (aerobic or anaerobic) or thermal (incineration) treatment methods are used. Huge capacities for a codigestion of agroindustrial residues (substrates) and wastewater sludge can be found in municipal digesters. As most of the food processing factories are indirect dischargers, the largest amount of the SS fraction in the wastewater is led to municipal wastewater treatment plants. Rarely, a connection between the SS concentrations in the influent and those in the effluent can be observed in conventional wastewater treatment. As a polishing step, filtration methods gain more and more importance with regard to suspended solids removal.

Core safeguards for clinical research with adults who are unable to consent.

The National Bioethics Advisory Commission has proposed new safeguards for clinical research with adults who are unable to consent. Three other major U.S. groups have also proposed additional safeguards for this population, and existing Canadian and European guidelines already include such safeguards. While these six guidelines agree on some safeguards, they disagree on others. To allow important research to proceed while protecting adults who are unable to consent, it will be crucial to resolve these differences. This paper uses a side-by-side comparison of these six guidelines to highlight their major points of consensus, analyze their significant differences, and distill six core safeguards.

The consent process for cadaveric organ procurement: how does it work? How can it be improved?

CONTEXT: Understanding the consent process that organ procurement organizations (OPOs) use is crucial to improving the process and thereby reducing the number of individuals who die each year for want of an organ transplant. However, no data exist on OPOs' current consent practices. OBJECTIVE: To assess whose wishes OPOs follow when procuring solid organs from deceased individuals and whether advance directives and computerized registries might improve the consent process for solid organ procurement. DESIGN, SETTING, AND PARTICIPANTS: Telephone survey conducted from June to August 1999 of all 61 active OPOs. MAIN OUTCOME MEASURES: Responses to the 49-question survey addressing consent practices in specific scenarios of deceased and next of kin wishes. RESULTS: Widespread divergence exists in OPOs' consent practices for cadaveric solid organ procurement. Regarding overall consent practices, 19 (31%) OPOs reported that they follow the deceased's wishes, 19 (31%) follow the next of kin's wishes, 13 (21%) procure organs if neither party objects, 8 (13%) procure organs if either party consents or neither objects, and 2 (3%) do not follow any of these 4 overall practices. These differences appear to be traceable to implicit ethical disagreements about whose wishes should be followed. A total of 29 (48%) OPOs reported having an official policy to address whether they follow the family's or deceased's wishes. Regarding factors that influence OPOs' choice of consent practice, 29 (48%) respondents ranked impact on the deceased's family as the most important factor, 13 (21%) ranked state law as most important, and 7 (11%) ranked the priority of the deceased's wishes as most important. Durable power of attorney appeared to have substantial weight in OPOs' decisions; for example, in the scenario in which the deceased supported organ donation and the next of kin opposed it, 34 (56%) OPOs reported they were likely to procure organs based on the consent of the holder of the deceased's durable power of attorney, whereas only 7 (11%) reported they were likely to procure organs based on a document of gift (a living will, donor card, or driver's license). CONCLUSIONS: Expanding the legal scope of living wills to cover individuals' organ donation preferences would likely have little impact on procurement rates. In contrast, expanding the legal scope of durable powers of attorney for health care may have a significant impact. A national discussion should take place addressing the underlying ethical issues that appear to account for much of the divergence among OPOs' consent practices for cadaveric solid organ procurement.

What makes clinical research ethical?

Many believe that informed consent makes clinical research ethical. However, informed consent is neither necessary nor sufficient for ethical clinical research. Drawing on the basic philosophies underlying major codes, declarations, and other documents relevant to research with human subjects, we propose 7 requirements that systematically elucidate a coherent framework for evaluating the ethics of clinical research studies: (1) value-enhancements of health or knowledge must be derived from the research; (2) scientific validity-the research must be methodologically rigorous; (3) fair subject selection-scientific objectives, not vulnerability or privilege, and the potential for and distribution of risks and benefits, should determine communities selected as study sites and the inclusion criteria for individual subjects; (4) favorable risk-benefit ratio-within the context of standard clinical practice and the research protocol, risks must be minimized, potential benefits enhanced, and the potential benefits to individuals and knowledge gained for society must outweigh the risks; (5) independent review-unaffiliated individuals must review the research and approve, amend, or terminate it; (6) informed consent-individuals should be informed about the research and provide their voluntary consent; and (7) respect for enrolled subjects-subjects should have their privacy protected, the opportunity to withdraw, and their well-being monitored. Fulfilling all 7 requirements is necessary and sufficient to make clinical research ethical. These requirements are universal, although they must be adapted to the health, economic, cultural, and technological conditions in which clinical research is conducted. JAMA. 2000;283:2701-2711.

Informed consent, exploitation and whether it is possible to conduct human subjects research without either one.

Clinical research with adults who are unable to provide informed consent has the potential to improve understanding and care of a number of devastating conditions. This research also has the potential to exploit some of society's most vulnerable members. Recently, a number of task forces and individual writers have proposed guidelines to ensure that such research is both possible and ethical. Yet, there is widespread disagreement over which safeguards should be adopted. In the present paper, I consider to what extent these disagreements can be resolved by appeal to a general account of the interests of subjects who are unable to consent and the conditions that must be satisfied for research enrollment to constitute exploitation of their inability to make their own decisions.

[Primary paraurethral malignant mixed tumor (carcinosarcoma) of the vagina. A case report]. / Primärer paraurethraler maligner Mischtumor (Karzinosarkom) der Vagina. Ein Fallbericht.

In total malignant mixed tumors (carcinosarcomas) represent a very rare gynecological neoplasm. In accordance with the embryological genesis primary localizations are with descending probability the uterus, the ovarians and finally the tubes. We report on a 55 year old female patient, with a paraurethral mass, which was primarily diagnosed in 1994. Histopathological evaluation of a transvaginal biopsy did not demonstrate evidence of malignancy at that time. After painful enlargement the paraurethral mass was resected surgically and histopathological evaluation revealed a primary paraurethral malignant mixed tumor (carcinosarcoma). Postoperatively, the patient underwent percutaneous (46.4 Gy) and intracavitary (2 x 6 Gy) radiation. Twelve months postoperatively there is no evidence of disease.

Immunohistochemical assessment of steroid hormone receptors in tissues of the anal canal. Implications for anal incontinence?

BACKGROUND: A prerequisite for a hormonal influence on anal continence in women is the presence of hormone receptors in the tissues of the anal canal. Using immunohistochemical techniques, we demonstrated and localized estrogen and progesterone receptors (ER, PR) in tissue sections of the anal canal. METHODS: Thirty-five specimens of the anorectal region from 21 patients (14 women, seven men) were examined histologically for smooth muscle (present in specimens from ten females and in seven males), striated muscle (present in three females and five males), and perimuscular connective tissue (present in 12 females and seven males). Immunostaining for ER and PR was then performed by incubating with primary anti-ER and anti-PR antibody and visualization of specific antibody binding by the ABC technique with DAB as chromogen. RESULTS: Positive staining for ER and PR was seen exclusively over cell nuclei. Estrogen receptors were found in the smooth muscle cells of the internal sphincter of all females (10/10) and in four of the seven males. Staining for ER was detected in the perimuscular connective tissue of all females (12/12) and in four of the seven males. No specific staining for ER or PR was found in the nuclei of striated muscle cells of the external sphincter in males or females (n = 8). In females, about 50% of the ER-positive tissues were also found to be positive for PR. Amongst the male patients, only one exhibited staining for PR, and this was confined to the smooth muscle. CONCLUSIONS: Expression of ER is a constitutional feature of the connective tissue and smooth muscle cells of the anal continence organ. Estrogen receptors and PR are not detectable in the striated muscle fibers of the external anal sphincter in either sex. The presence of ER in the stroma and smooth muscles of the anal canal suggests that these tissues are targets for estrogen. This constitutes a theoretical basis for the beneficial effects of estrogen and progestin replacement on anal continence in postmenopausal women.

Deception in medical and behavioral research: is it ever acceptable?

Ethicists argue that deception is unacceptable, whereas researchers regard it as a necessary part of (certain kinds of) research. This impasse could be resolved by establishing the specific conditions under which deception in medical and behavioral research can be tolerated. An approach based on a consideration of the "Ethical Principles of Psychologists and Code of Conduct," one of the few writings on this topic, would satisfy the needs of both parties. It takes the form of a requirement that subjects be informed of the use of deception before enrolling in a deceptive study. This "second order consent" approach to acceptable deception represents our best chance for reconciling respect for subjects with the occasional scientific need for deceptive research.

Tropheryma whippelii endocarditis confirmed by polymerase chain reaction.

This report concerns a patient with cardiac manifestation of Whipple's disease. For the first time, the gene that encodes the 16s rRNA of Tropheryma whippelii was identified in a native aortic valve by means of a polymerase chain reaction technique. DNA amplification gives evidence of Tropheryma whippelii as a causative organism in infective endocarditis.

Menstrual cycle exhibits no effect on postprandial lipemia.

Menstrual cycle effects on postprandial lipemia were investigated in 13 healthy women. They were monitored (dietary intake, basal body temperature) for a period of one cycle. Statistically significant follicular-luteal differences were neither observed between fasting triglyceride serum levels nor between areas under triglyceride response curves after a standardized oral fat load.

A controlled study of maternal serum concentrations of lipoproteins in pregnancy-induced hypertension.

Seventeen women with pregnancy-induced hypertension (PIH) and 17 controls with uncomplicated pregnancy who were matched for maternal and gestational age were investigated for lipid concentrations in whole serum and lipoprotein fractions. The triglyceride level in the low-density lipoprotein fraction was higher in PIH patients than in controls (P < 0.03). The differences between values of other parameters did not attain the level of statistical significance, although the tendency of the results was consistent with findings reported in other studies. The differences observed were small and the data exhibited wide variation. Therefore, it appears unlikely that serum lipid and lipoprotein concentrations could gain major clinical importance as diagnostic parameters in PIH.

Annulated gap junctions in the rat neural tube.

Annulated gap junctions have been studied electron microscopically in normal rat embryo neural tube on day 12 of gestation. Localization, size and content of annulated gap junctions were characterized. Like in other tissues annulated gap junctions are thought to be involved in a degradation cycle of gap junctions.

[Histochemical model investigations of the action mechanisms of lathyrogenic substances]. / Histochemische Modellversuche zum Wirkungsmechanismus lathyrogener Substanzen.

In histochemical model studies, aminoacetonitrile and 3-aminopropionitrile can form hydrolysis-stable azomethines (Schiff bases) with periodate-induced aldehyde groups of tissue slices. Both substances and triethylentetramine do not inhibit the histochemical monoaminoxidase activity, they even can act as substrates of this enzyme. These substances cause an inhibition of the histochemical aminopeptidase M activity, but this inhibition was recognized as a methodological error due to the formation of complexes between diazonium salts and aliphatic amines. The results indicate that the inhibition of the lysyl oxidase will not be the only mechanism of action of lathyrogenic substances.