Hepatitis B virus infects about 200 million people worldwide yearly. The consequences of the infection range from mild, self‐limiting hepatitis with full recovery and immunity to chronic infection with liver disease of varying severity, including fulminant hepatitis and death. Alternatively, individuals may become healthy carriers of the virus and thus serve as a reservoir of infection. In addition, all chronic carriers of the virus are also at risk for development of primary hepatocellular carcinoma later in life. Efforts (...) to combat this disease on a global scale require an inexpensive vaccine. Studies of the hepatitis B viral coat protein (HBsAg) have permitted the development of two generations of vaccine to date, and detailed structural studies of its antigenic sites may eventually allow the development of a completely synthetic (and therefore inexpensive) vaccine in the future. (shrink)

This article investigates the question of how forensic toxicologists established the credibility of chemical analytical methods in poisoning lawsuits in the nineteenth century. After encountering the problem of laypersons in court, forensic toxicologists attempted to find strategies to make their evidence compelling to an untrained audience. Three of these strategies are discussed here: redundancy, standard methods, and intuitive comprehensibility. Whereas redundancy was not very practical and legally prescribed standard methods were not very popular with most forensic toxicologists, intuitive comprehensibility proved (...) effective and popular. This strategy relied on employing methods which did not require chemical knowledge to be understandable. The methods aimed to generate a visual aid and to be obvious in their results. Two forms of this strategy are discussed here: the presentation of the actual material and explicit comparison. I argue that this shift towards presenting forensic toxicology expertise as evident represents an important step in the history of forensic expertise. (shrink)

ZusammenfassungDieser Artikel beschäftigt sich mit Geschlechterstereotypen in psychiatrischen Gerichtsgutachten während des Deutschen Kaiserreichs 1871–1914. Wie gezeigt werden wird, lassen sich in diesen Gutachten vier auf das Geschlecht bezogene Narrative identifizieren. Einerseits wurden Frauen und Männer beschrieben, die den Geschlechterstereotypen der Zeit nicht entsprachen. Für diese nonkonformen Angeklagten wurde in den hier betrachteten Gutachten die Erklärung zur Unzurechnungsfähigkeit empfohlen. Andererseits wurden aber auch Männer und Frauen beschrieben, die sich konform zu den entsprechenden Stereotypen verhielten. Allerdings wurden in diesen Fällen „weibliche“ Frauen (...) weiterhin tendenziell für unzurechnungsfähig erklärt, während „männliche“ Männer der Simulation einer Geisteskrankheit bezichtigt wurden, um einer Strafe zu entgehen. Ich werde argumentieren, dass diese Ergebnisse Grundannahmen der Feministischen Epistemologie stärken: sie zeigen erstens, dass psychiatrische Vorstellungen von Zurechnungsfähigkeit eng verbunden waren mit der der Norm des „männlichen“ Mannes, und zweitens, dass ein doppelter Standard bei der Beurteilung des Geisteszustands von Männern und Frauen angelegt wurde. (shrink)

Currently, any dentist in the UK who is HIV-seropositive must stop treating patients. This is despite the fact that hepatitis B-infected dentists with a low viral load can continue to practise, and the fact that HIV is 100 times less infectious than hepatitis B. Dentists are obliged to treat HIV-positive patients, but are obliged not to treat any patients if they themselves are HIV-positive. Furthermore, prospective dental students are now screened for hepatitis B and C and HIV, (...) and are not allowed to enrol on Bachelor of Dental Surgery degrees if they are infectious carriers of these diseases. -/- This paper will argue that: (i) the current restriction on HIV-positive dentists is unethical, and unfair; (ii) dentists are more likely to contract HIV from patients than vice versa, and this is not reflected by the current system; (iii) the screening of dental students for HIV is also unethical; (iv) the fact that dentists can continue to practise despite hepatitis B infection, but infected prospective students are denied matriculation, is unethical; and (v) that the current Department of Health protocols, as well as being intrinsically unfair, have further unethical effects, such as the waste of valuable resources on ‘lookback’ exercises and the even more damaging loss of present and future dentists. Regulation in this area seems to have been driven by institutional fear of public fear of infection, rather than any scientific evidence or ethical reasoning. (shrink)

In the decade following hepatitis B vaccine’s 1981 approval, U.S. health officials issued evolving guidelines on who should receive the vaccine: first, gay men, injection drug users, and healthcare workers; later, hepatitis B-positive women’s children; and later still, all newborns. States laws that mandated the vaccine for all children were quietly accepted in the 1990s; in the 2000s, however, popular anti-vaccine sentiment targeted the shot as an emblem of immunization policy excesses. Shifting attitudes toward the vaccine in this (...) period were informed by hepatitis B’s changing popular image, legible in textual and visual representations of the infection from the 1980s through the 1990s. Notably, the outbreak of AIDS, the advent of genetically engineered pharmaceuticals, and a Democratic push for health reform shaped and reshaped hepatitis B’s public image. Hepatitis B thus became, in turn, an AIDS-like scourge; proof of a new era of pharmaceuticals; a threat from which all American children had a right to be protected; and a cancer-causing infection spread by teenage lifestyles. The metamorphosis of the infection’s image was reflected in evolving policy recommendations regarding who should receive the vaccine in the 1980s, and was key to securing broad uptake of the vaccine in the 1990s. (shrink)

A simplified model using kinetic logic is proposed to approach the problem after Hepatitis B viral (HBV) infection. It accounts for several stable regimes or attractors corresponding to the essential dynamic behaviour of the replication of the Hepatitis B virus. Infection with the virus can result in viral clearance, fulminant hepatic failure and death, or chronic transmissible infection, that is multistationarity corresponding to the existence of the positive feedback circuit in our modelling. Another implication of this model is (...) the existence of oscillations or homeostatic mechanisms, sometimes observed in the viral cycle, consistent with the existence of the negative feedback circuit. Thus, this report shows how a simple model of kinetic logic may be used to account for the variety of manifestations of HBV infection. This model implies the presence of the Hepatitis B e antigen, whose conservation suggests that it plays an important role in the life cycle of hepadnaviruses. Its function in the viral cycle is still unknown, but our model suggests that this antigen could explain the passage from one state of the viral infection (acute or latent) to another, as well as the oscillatory behavior which may account for the intermittent symptoms of hepatitis observed in some patients. Furthermore, this model shows a virgin state. This state is also reached after recovery. The model proposed demonstrates that starting from a viral acute infection, the host's immune response, depending on the immunological status of the patient, can lead to viral clearance, or to periodic spontaneous reactivation. (shrink)

Background The potential for transmission of blood-borne pathogens such as hepatitis B virus from infected healthcare workers to patients is an important and difficult issue facing healthcare policymakers internationally. Law and policy on the subject is still in its infancy, and subject to a great degree of uncertainty and controversy. Policymakers have made few recommendations regarding the specifics of practice restriction for health care workers who are hepatitis B seropositive. Generally, they have deferred this work to vaguely defined (...) "expert panels" which will have the power to dictate the conditions under which infected health care workers may continue to practice. Discussion In this paper we use recent Canadian policy statements as a critical departure point to propose more specific recommendations regarding disclosure of transmission risks in a way that minimizes practice restriction of hepatitis B seropositive health care workers without compromising patient safety. The range of arguments proposed in the literature are critically examined from the perspective of ethical analysis. Summary A process for considering the ethical implications of the disclosure of the sero-status of health care workers is advanced that considers the varied perspectives of different stakeholders. (shrink)

We investigate and analyze the dynamics of hepatitis B with various infection phases and multiple routes of transmission. We formulate the model and then fractionalize it using the concept of fractional calculus. For the purpose of fractionalizing, we use the Caputo–Fabrizio operator. Once we develop the model under consideration, existence and uniqueness analysis will be discussed. We use fixed point theory for the existence and uniqueness analysis. We also prove that the model under consideration possesses a bounded and positive (...) solution. We then find the basic reproductive number to perform the steady-state analysis and to show that the fractional-order epidemiological model is locally and globally asymptotically stable under certain conditions. For the local and global analysis, we use linearization, mean value theorem, and fractional Barbalat’s lemma, respectively. Finally, we perform some numerical findings to support the analytical work with the help of graphical representations. (shrink)

This paper examines the ethical issues faced by health workers managing a fictional case of a female sex worker who is hepatitis B positive with a high level of virus but is asymptomatic. According to guidelines she does not require treatment herself, but is potentially highly infectious to others. Recent legal cases in the UK show it can be criminal to pass on HIV or hepatitis B infection sexually if the risk is known and the partner has not (...) been informed. However, there is no statute or case law showing that health workers are required to intervene to prevent such a potential ‘crime’, particularly when the partners are unknown, as in this case. The health workers could respond in various ways. They could do nothing, thus making further infection probable. They could advise the sex worker to use condoms and to inform her clients. They could treat the sex worker to reduce her level of infectivity, although there is no benefit to her. They could disclose the sex worker's status, although breaking confidentiality is a serious matter ethically and may be of no benefit to the unknown client group. Regulating prostitution might help; but sex workers with infection may work off licence. This paper discusses the clinical, moral and ethical issues associated with such a scenario and concludes that the most beneficial course is to target clients, through health education, to recognise the potential risks of infection from a sex worker and to take suitable precautions including immunisation against hepatitis B. (shrink)

Aim: To evaluate health-related quality of life of chronic hepatitis B and hepatitis B virus related cirrhosis patients and analyzed specific differences in all dimensions of HRQoL.Methods: A total of 349 patients met selection criteria were enrolled. The 36-Item Short-Form Health Survey was adopted.Results: Results showed that the physiological HRQoL of the cirrhotic group was significantly lower than that of the non-cirrhotic group, the psychological HRQoL was also lower. HRQoL was significantly negatively correlated with liver stiffness. We further (...) evaluated the risk factors associated with poor HRQoL in HBV-related cirrhosis patients. Results showed that positive HBV DNA viral load and HCC family history were independent factors associated with HRQoL in HBV-related cirrhosis. For better risk stratification of patients, multivariable analyses were conducted to explore the independent factors that affected specific physiological and psychological HRQoL. In specific physiological HRQoL, results show that marital status, positive HBV DNA viral load and antiviral drugs were independent factors associated with physiological HRQoL in cirrhosis patients. In psychological HRQoL, only HCC family history was independent risk factors associated with psychological HRQoL.Conclusion: We found that the impaired HRQoL dimensions of HBV related cirrhosis patients differ between the various subpopulations. According to our results, risk stratification, medical decision making and personalizing interventions could be made. (shrink)

Bd. 1. A-B -- Bd. 2. C-F -- Bd. 3. G-Inn -- Bd. 4. Ins-Loc.

Die »Enzyklopädie Philosophie- und Wissenschaftstheorie«, das größte allgemeine Nachschlagewerk zur Philosophie im deutschsprachigen Raum, wurde 1980 begonnen und 1996 mit dem vierten Band abgeschlossen. Sie erschien 2005 bis 2018 in einer komplett aktualisierten und erweiterten 8-bändigen Neuauflage, die hiermit nun in einer kartonierten Sonderausgabe vorliegt. Die »Enzyklopädie« umfasst in Sach- und Personenartikeln nicht nur den klassischen Bestand des philosophischen Wissens, sondern auch die neuere Entwicklung der Philosophie, insbesondere in den Bereichen Logik, Erkenntnis- und Wissenschaftstheorie sowie Sprachphilosophie. Zugleich finden Grundlagenreflexionen in (...) den Wissenschaften und deren Geschichte ausführliche Berücksichtigung. Die umfassenden Bibliographien und Werkverzeichnisse wurden für die 2. Auflage in allen Artikeln auf den neuesten Stand gebracht. Der Herausgeber Jürgen Mittelstraß, Professor em. für Philosophie und Wissenschaftstheorie an der Universität Konstanz, ist einer der international renommiertesten deutschen Philosophen. 1989 erhielt er den Leibniz-Preis der Deutschen Forschungsgemeinschaft (DFG) und seitdem zahlreiche weitere Wissenschaftspreise sowie Ehrendoktorwürden. Er ist Direktor des Konstanzer Wissenschaftsforums, war Präsident der Academia Europaea (2002-2008) und Vorsitzender des Österreichischen Wissenschaftsrates (2005-2015). Band 1: A-B | Band 2: C-F | Band 3: G-Inn | Band 4: Ins-Loc | Band 5: Log-N | Band 6: O-Ra | Band 7: Re-Te | Band 8: Th-Z. (shrink)

The International Institute for the Study of Man has promoted a research theme charged with a project of reforestation of the Atlas Mountains to be proposed to the E.C.The Atlas Project relies on three fundamental assumptions: a. there is the need to build CO2 sinks that, at the same time, are a source of energy and income in regions from which, due to the lack of both, vast migratory flows start. The state members of the European Community are not able (...) to absorb the quantity of CO2 produced by industrial combustion, the heating system and cars, and they still do not follow the international agreement on pollution control;b. a regular stream of air from Northern Europe discharges its humidity on the Atlas Mountains, before it re-ascends over Europe. This stream of air could be a natural carrier for conveying and immobilising the CO2 produced in the industrial regions of Europe through its fixation in timber on the Atlas Mountains before it re-ascends over the European continent;c. the Moroccan area, and North Africa in general, are the source of a large number of immigrants into Europe due to the high population pressure and the lack of employment. (shrink)

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, (...) NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USA: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity. (shrink)

Alzheimer's disease is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-beta peptide . The rate-limiting step in the production of Abeta is the processing of Abeta precursor protein by beta-site APP-cleaving enzyme . Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Abeta within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was (...) suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of beta-galactoside alpha-2,6-sialyltransferase I . In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future. (shrink)

In recent years, as newborn screening has expanded to include conditions for which treatment is questionable, new rationales for screening have proliferated. One such rationale is the potential reproductive benefit to parents from the detection of a genetic condition or carrier status in infants. An unanticipated consequence of invoking knowledge of reproductive risk as a major benefit of screening has been to open newborn screening to the charge that it constitutes state‐sanctioned eugenics. Thus, an endeavor that had been viewed (...) as the converse of state programs of selective breeding has come to be seen in some quarters as yet another of its incarnations. The result has been serious and self‐inflected harm to the reputation of newborn screening programs. (shrink)

From the Christian perspective, creation exists through the Word of God. The Word of God does not create God again but brings forth the absolute “otherness” of God: creation. The nature of God is to exist. God is existence as unity in the diversity of God the Father, the Son, and the Holy Spirit. The gift of created existence reflects the triune nature of the Word of God. It is synthesis of diversity into unity that creates. Nature brings forth new (...) existence by unifying what it already brought forth previously. Therefore, the creative process of nature is self‐similar and nonlinear: self‐similar because at all levels it is synthesis that brings forth novelty; nonlinear because the properties of the new unities are not present in their (isolated) elements. The new properties of the wholes, however, do not destroy the properties of the parts. Rather, the elements integrated into new wholes become creatively transformed. This is because the parts become carriers of the whole, which transforms the parts through its presence. The parts become and express the qualities of the whole, qualities that the parts do not possess in isolation. Synthesis, therefore, transforms the parts creatively, because synthesis is creative. The qualities of the parts become “elevated” because the whole becomes present in and through the parts. The understanding of creation as the result of sequential, creative transformations offers a glance into the mystery of the Word of God present in the Eucharist. Here, too, the elements of bread and wine are not destroyed but elevated, creatively transformed into the Word of God. The elements (bread and wine) become the carrier of a transcendent “quality,” the Word of God. From this perspective, creation and the sacrament of the Eucharist illuminate each other. This is because the Word of God that creates the otherness of creation and the Word of God present in the Eucharist is the same. (shrink)

Most metazoan organisms have evolved a mildly acidified and calcium diminished sorting hub in the early secretory pathway commonly referred to as the Endoplasmic Reticulum‐Golgi intermediate compartment (ERGIC). These membranous vesicular‐tubular clusters are found tightly juxtaposed to ER subdomains that are competent for the production of COPII‐coated transport carriers. In contrast to many unicellular systems, metazoan COPII carriers largely transit just a few hundred nanometers to the ERGIC, prior to COPI‐dependent transport on to the cis‐Golgi. The mechanisms underlying formation and (...) maintenance of ERGIC membranes are poorly defined. However, recent evidence suggests an important role for Trk‐fused gene (TFG) in regulating the integrity of the ER/ERGIC interface. Moreover, in the absence of cytoskeletal elements to scaffold tracks on which COPII carriers might move, TFG appears to promote anterograde cargo transport by locally tethering COPII carriers adjacent to ERGIC membranes. This action, regulated in part by the intrinsically disordered domain of TFG, provides sufficient time for COPII coat disassembly prior to heterotypic membrane fusion and cargo delivery to the ERGIC. -/- . (shrink)

Variant Creutzfeldt–Jakob disease is a fatal, transmissible, neurodegenerative disorder for which there is currently no effective treatment. vCJD arose from the zoonotic spread of bovine spongiform encephalopathy. There is now compelling evidence for human to human transmission through blood transfusions from presymptomatic carriers and experts are warning that the real epidemic may be yet to come. Imperatives exist for the development of reliable, non-invasive presymptomatic diagnostic tests. Research into such tests is well advanced. In this article the ethical implications of (...) the availability of these tests are elaborated and comparisons drawn with predictive genetic testing for Huntington’s disease and screening for HIV. Paramount to considerations is the issue of whom to test, weighing up respect for personal autonomy against obligations to benefit and protect society. A paradigm is proposed similar to that used for HIV screening but with unique features: compulsory testing of all blood/organ donors and individuals undergoing surgery or invasive procedures who have a significant risk of disease transmission. (shrink)

On the 50th anniversary of the Willowbrook experiment's inception, in which Dr. Saul Krugman intentionally infected cognitively disabled children with hepatitis, it is worth reflecting on how our attitude toward research ethics of the past informs our current practices. In examining ethical violations in postwar medicine, we frequently turn to examples that shock and appall, thereby offering concomitant comfort as we measure their safe distance from our own medical context. And yet, which modern medical student has not heard a (...) variation of the phrase "This study would never have passed an ethics committee today" in reference to a classic experiment or a professor's very own work? Even with Nuremburg fresh in the .. (shrink)

Background: Expanded newborn screening generates incidental results, notably carrier results. Yet newborn screening programmes typically restrict parental choice regarding receipt of this non-health serving genetic information. Healthcare providers play a key role in educating families or caring for screened infants and have strong beliefs about the management of incidental results. Methods: To inform policy on disclosure of infant sickle cell disorder (SCD) carrier results, a mixed-methods study of healthcare providers was conducted in Ontario, Canada, to understand attitudes regarding (...) result management using a cross-sectional survey (N = 1615) and semistructured interviews (N = 42). Results: Agreement to reasons favouring disclosure of SCD carrier results was high (65.1%–92.7%) and to reasons opposing disclosure was low (4.1%–18.1%). Genetics professionals expressed less support for arguments favouring disclosure (35.3%–78.8%), and more agreement with arguments opposing disclosure (15.7%–51.9%). A slim majority of genetics professionals (51.9%) agreed that a reason to avoid disclosure was the importance of allowing the child to decide to receive results. Qualitatively, there was a perceived “duty” to disclose, that if the clinician possessed the information, the clinician could not withhold it. Discussion: While a majority of respondents perceived a duty to disclose the incidental results of newborn screening, the policy implications of these attitudes are not obvious. In particular, policy must balance descriptive ethics (ie, what providers believe) and normative ethics (ie, what duty-based principles oblige), address dissenting opinion and consider the relevance of moral principles grounded in clinical obligations for public health initiatives. (shrink)

The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological (...) data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. (...) The clinical features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

Citrate, an organic trivalent anion, is a major substrate for generation of energy in most cells. It is produced in mitochondria and used either in the Krebs' cycle or released into cytoplasm through a specific mitochondrial carriers. Citrate can also be taken up from blood through different plasma membrane transporters. In the cytoplasm, citrate can be used ultimately for fatty acid synthesis, which is increased in cancer cells. Here, we review the ways in which citrate can be transported and discuss (...) the changes in transport and metabolism that occur in cancer cells. The primary focus is on the prostate gland, which is known to produce and release large amounts of citrate during its normal secretory function. The significant changes that occur in citrate‐related metabolism and transport in prostate cancer are the second focus. This review strives to relate these mechanisms to molecular biology on the one hand and to clinical applications on the other. (shrink)

Few, if any, scientific inquiries are conducted against a background of complete knowledge, a background in which inquirers are in possession of the ‘full facts’ that relate to a particular question or issue. More often than not, scientists are compelled to conduct their deliberations in contexts of epistemic uncertainty, in which partial knowledge or even a total absence of knowledge characterise inquiry. Nowhere is this epistemic uncertainty more evident, or indeed more successfully controlled, than in the branch of scientific inquiry (...) called epidemiology. In this paper, I examine how epidemiologists overcome the unique challenges to inquiry that are posed by epistemic uncertainty. In specific terms, I contend that epidemiologists employ analogical reasoning strategies in an attempt to advance their inquiries in situations that are epistemically uncertain. The context for my claims will be the early inquiries that were conducted into the emergence of HIV/AIDS in the United States. I argue that early scientific work in relation to HIV/AIDS was directly premised upon epidemiological investigations in which analogical reasoning with hepatitis B had featured significantly. I conclude that epidemiological investigations of AIDS exemplify the capacity of analogical reasoning to advance inquiry under conditions of epistemic uncertainty. To this extent, analogical reasoning should be a concern both to those who address practical problems of uncertainty management and to those who pursue theoretical debates within argumentation studies and epistemology. (shrink)

Introduction Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. Methods Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. Results 123 youth completed the questionnaire (mean (...) age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. Conclusions Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking. (shrink)