Although clarity about HIV transmission biology and effective therapy should mean that an AIDS diagnosis is more socially acceptable today, for some groups the cultural stigma of HIV infection has changed little in the last 30 years. This paper will examine why representations of HIV-positive gay men suggest they pose a special civic risk and how these conceptualizations have harnessed cultural anxieties about racial and sexual minorities to shape public policy and behavior since the advent of Highly (...) class='Hi'>Active Antiretroviral Therapy (HAART) in 1996. (shrink)

Improvements in the health capital of citizens are central to the development of countries. By exploiting steep decreases in antiretroviral drug prices and the subsequent increases in antiretroviral therapy (ART) coverage, we test whether the resulting improvements in the health of the population are associated with the prevalence of entrepreneurial activity and whether entrepreneurial activity strengthens the relationship between ART coverage and a country’s development. Drawing on a sample of 87 low- and middle-income countries (2006–2019), we find (...) that a 1% increase in ART coverage is associated with a 1.5% increase in the number of newly registered limited liability firms; however, there is no significant relationship with (male or female) self-employment. Higher ART coverage is particularly associated with development—as proxied by gross domestic product (GDP) per capita and the Human Development Index—in countries with low levels of new business formation and high proportions of self-employment. (shrink)

Objectives: To test the range of beliefs regarding the ethics of testing, in resource poor settings, new therapies that are less efficacious but more affordable and feasible than the best current therapeutic standard. Design: Using a web-based survey, we presented a hypothetical scenario proposing to test a therapy for HIV disease ("therapeutic inoculation") known to be less efficacious than highly active antiretroviral therapy (HAART). Respondents evaluated various trial designs as ethical or unethical. Participants: 604 subscribers (...) to two listservs for individuals interested in international health research ethics. Main outcome measures: Proportion of respondents endorsing trials testing this "substandard" therapy, and proportion endorsing placebo-controlled trials. Results: There were 215 respondents from 47 countries. Forty-five percent of respondents were from low or middle income countries; 96% devoted at least some time to research activities; and 75% had "some" or "considerable" research experience in developing countries. Of respondents, 97% (95% CI 94.7 to 99.4) endorsed testing therapeutic inoculation, without HAART, in patients with HIV disease; 86% (95% CI 81.4% to 90.7%) endorsed testing against placebo. Sixty-eight percent explicitly endorsed principles where the standard of care for subjects in clinical trials is determined by local, not universal, standards. There were no differences in responses based on respondent education-level or the income-level of their country of citizenship. Conclusion: There was broad agreement that a therapy of potential local benefit may be tested, even when that therapy is known to be inferior to the standard of care in wealthy countries. Most agreed that a placebo control may be used in some circumstances. (shrink)

Effective therapies are now available that can stop the progression of HIV infection and significantly delay the onset of AIDS. The “highly active antiretroviral therapy” (HAART) is a combination of potent antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors, that has a variety of serious side effects, including lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance as well as fat wasting in face and limbs. (...) There is still an open debate that concerns the precise responsibility of HAART as well as metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. The similarities with multiple symmetric lipomatosis (MSL), in which mitochondria impairment plays a crucial role, lead to the hypothesis that drug-induced damages to mitochondrial DNA are able to alter mitochondria functionality to an extent that is similar to what occurs in MSL. In addition, several evidences indicate that HAART is also linked to a deregulated production of tumour necrosis factor-α, which uses mitochondria as intracellular targets. In this paper, we review data concerning the role of mitochondria in the pathogenesis of lipodystrophy, and advance a unifying hypothesis involving either direct or indirect effects of the drugs employed during HAART. BioEssays 23:1070–1080, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The discovery of a stable latent reservoir for HIV‐1 in resting memory CD4+ T cells provides a mechanism for lifelong persistence of HIV‐1. The long‐lived latently infected cells persist in spite of prolonged highly active antiretroviral therapy and present a major barrier to a cure of HIV‐1 infection. In this review, we discuss the current understanding of HIV‐1 persistence and latent viral infection in the context of effective antiretroviral therapy and the recent progress in (...) purging latent viral reservoirs. Recent studies demonstrate that reactivation of latent HIV‐1 is a promising strategy for the depletion of these viral reservoirs. A thorough evaluation of the anti‐latency activity of drug candidates should include the measurement of changes in intracellular viral RNA, plasma virus levels, and the size of latent viral reservoirs, as well as potential adverse effects. Currently, there are several technical barriers to the evaluation of anti‐latency drugs in vivo. We also discuss these challenging issues that remain unresolved. (shrink)

Zusammenfassung. Bisher fehlen Studien zur Einstellung und Praxis von Ärzten zur Beihilfe zum Suizid (”physician assisted suicide”: PAS) bei schwerkranken schwulen AIDS-Patienten nach Verbesserung der Behandlungsmöglichkeiten (”highly active antiretroviral therapies”: HAART). Von August 1999 bis Februar 2000 wurde in den Großräumen San Francisco und New York eine nicht repräsentative Stichprobe von Ärzten, Psychologen, Sozialarbeitern, Pflegepersonal und anderen Gesundheitsberufen (n=69) in semistrukturierten Interviews über ihre ethischen Bewertung des PAS bei AIDS-Patienten befragt. Die Mehrheit der Befragten kennt Gespräche über (...) PAS aus der professionellen Arbeit, ein Teil der befragten Ärzte hat selbst ärztliche Beihilfe zum Suizid geleistet. Durch HAART hat die Häufigkeit von Patientenwünschen nach PAS abgenommen, eine Ausweitung von PAS auf andere Patientengruppen wurde nicht beobachtet. In der Praxis bestehen weiterhin ungelöste Probleme bei der Suizidbegleitung, dem „richtigen Zeitpunkt”, der Arzt-Patient-Kommunikation und der Beurteilung der Selbstbestimmungsfähigkeit. Hinweise auf einen dammbruchartigen Missbrauch (”slippery slope”) wurden nicht gefunden. Trotz der hohen Akzeptanz bei AIDS-Kranken bewertet die Mehrzahl der Ärzte PAS weiterhin skeptisch. PAS findet nur auf expliziten Wunsch einer Untergruppe von AIDS- Patienten statt, hat aber den Stellenwert der Patientenselbstbestimmung in der Medizin generell erhöht. Weiterer Forschungsbedarf besteht bei der sicheren Feststellung von Selbstbestimmungsfähigkeit bei schwerkranken und sterbenden Patienten. (shrink)

Definition of the problem: Attitudes and practice of doctors regarding physician-assisted suicide (PAS) in patients with AIDS became considerably more liberal over the last 15 years in large U.S. cities. However, it remains an open question how the highly active antiretroviral therapies (HAART) have influenced the situation since the late 1990s. Methods and results: In 1999/2000 a nonrepresentative sample of medical doctors, psychologists, social workers, nurses and other health care professionals (n=69) in San Francisco und New York (...) gave semistructured interviews about the present situation of PAS in patients with AIDS. On the basis of written protocols a qualitative evaluation of the expert interviews has been performed. The majority of the health care professionals are familiar with PAS in their professional work. With HAART the requests for PAS in gay patients with AIDS dropped rapidly. PAS has not been noted in other subgroups of patients. However, unsolved problems exist in timing, execution and accompaniment of PAS and in competence assessment of PAS patients. No hints of a slippery slope abuse could be identified in the interviews. Conclusion: Although tolerated, the majority of the doctors still feel uncomfortable with PAS and regard PAS as alien to their professional ethos. In practice PAS takes place on request of a subgroup of AIDS patients only. However, the professional experience with PAS in patients with AIDS has changed the attitude of doctors toward a stronger acceptance of their patients autonomy and partnership with them. Open questions remain regarding the competence assessment of seriously ill and dying patients. (shrink)

Zusammenfassung. Bisher fehlen Studien zur Einstellung und Praxis von Ärzten zur Beihilfe zum Suizid (”physician assisted suicide”: PAS) bei schwerkranken schwulen AIDS-Patienten nach Verbesserung der Behandlungsmöglichkeiten (”highly active antiretroviral therapies”: HAART). Von August 1999 bis Februar 2000 wurde in den Großräumen San Francisco und New York eine nicht repräsentative Stichprobe von Ärzten, Psychologen, Sozialarbeitern, Pflegepersonal und anderen Gesundheitsberufen (n=69) in semistrukturierten Interviews über ihre ethischen Bewertung des PAS bei AIDS-Patienten befragt. Die Mehrheit der Befragten kennt Gespräche über (...) PAS aus der professionellen Arbeit, ein Teil der befragten Ärzte hat selbst ärztliche Beihilfe zum Suizid geleistet. Durch HAART hat die Häufigkeit von Patientenwünschen nach PAS abgenommen, eine Ausweitung von PAS auf andere Patientengruppen wurde nicht beobachtet. In der Praxis bestehen weiterhin ungelöste Probleme bei der Suizidbegleitung, dem „richtigen Zeitpunkt”, der Arzt-Patient-Kommunikation und der Beurteilung der Selbstbestimmungsfähigkeit. Hinweise auf einen dammbruchartigen Missbrauch (”slippery slope”) wurden nicht gefunden. Trotz der hohen Akzeptanz bei AIDS-Kranken bewertet die Mehrzahl der Ärzte PAS weiterhin skeptisch. PAS findet nur auf expliziten Wunsch einer Untergruppe von AIDS- Patienten statt, hat aber den Stellenwert der Patientenselbstbestimmung in der Medizin generell erhöht. Weiterer Forschungsbedarf besteht bei der sicheren Feststellung von Selbstbestimmungsfähigkeit bei schwerkranken und sterbenden Patienten. (shrink)

Enormous gaps between HIV burden and health care availability in low-income countries raise severe ethical problems. This article analyzes four HIV-priority dilemmas with interest across contexts and health systems. We explore principled distributive conflicts and use the Atkinson index to make explicit trade-offs between health maximization and equality in health. We find that societies need a relatively low aversion to inequality to favor treatment for children, even with large weights assigned to extending the lives of adults: higher inequality aversion is (...) needed to share resources equally between high-cost and low-cost treatment; higher inequality aversion is needed to favor treatment rather than prevention, and the highest inequality aversion is needed to favor sharing treatment between urban and rural regions rather than urban provision of treatment. This type of ethical sensitivity analysis may clarify the ethics of health policy choice. (shrink)

I defend a certain claim about rationing in the context of HIV/AIDS, namely, the 'priority thesis' that the state of a developing country with a high rate of HIV should provide highly active anti-retroviral treatment (HAART) to those who would die without it, even if doing so would require not treating most other life-threatening diseases. More specifically, I defend the priority thesis in a negative way, by refuting two influential and important arguments against it inspired by the Kantian (...) principle of respect for persons. The 'equality argument' more or less maintains that prioritizing treatment for HIV/AIDS would objectionably treat those who suffer from it as more important than those who do not. The 'responsibility argument' says, roughly, that to ration life-saving treatment by prioritizing those with HIV would wrongly fail to hold people responsible for their actions, since most people infected with HIV could have avoided the foreseeable harm of infection. While it appears that a Kantian must think that one of these two arguments is sound, I maintain that, in fact, respect for persons grounds neither the equality nor responsibility argument against prioritizing HAART and hence at least permits doing so. If this negative defence of the priority thesis succeeds, then conceptual space is opened up for the possibility that respect for persons requires prioritizing HAART, which argument I sketch in the conclusion as something to articulate and defend in future work. (shrink)

Independent on Sunday October 2nd One of the country's lead­ing philosophical counsellers, and chairman of the Society for Philosophy in Practice (SPP), Tim LeBon, said it typically took around six 50 ­minute sessions for a client to move from confusion to resolution. Mr LeBon, who has 'published a book on the subject, Wise Therapy, said philoso­phy was perfectly suited to this type of therapy, dealing as it does with timeless human issues such as love, purpose, happiness and emo­tional (...) challenges. `Wise Therapy, is part of a series aimed at promoting an integrative attitude as its ethos. Among all the many perspectives of psychotherapists and counselors, philosophy needs to take its place and needs to find its voice. Tim LeBon has provided an effective means by which counselors can bring philosophy into their work with clients' - APPA journal `Tim Le Bon's Wise Therapy is a comprehensible and well argued book dealing with the practical therapeutic applications of philosophical research that may well be of interest to philosophers but -- as the author himself intends -- will be of most obvious benefit to therapists and counselors, both by informing their dialogue with clients in new ways and by helping them become more informed about ways to resolve the ethical dilemmas arising within the context of their own work' - Metapsychology `A fascinating workshop for therapists and clients, backed up a thorough degree if philosophical acuity' - Journal of the Society for Existential Analysis `I strongly recommend the book for philosophers as well as practitioners, teachers, students and supervisors in counselling and psychotherapy' - Self and Society `Provides some additional and valuable arrows for the therapist's quiver' - Irvin Yalom, author of Love's Executioner `Like Aristotle, Tim LeBon examines what is said and extracts what is best from it…. There are many fascinating exercises designed to bring out and enlighten the client's values, conception of the good life, well-being, happiness, pleasure, and the proper place of reason in life…. Wise Therapy is well written and engaging. The case histories are illuminating examples of therapeutic techniques at work, the thought experiments are well designed, and the philosophical position adapted from the internal debates of the philosophers is level headed…. I recommend it highly to philosophers with an interest in counselling, and psychological counsellors with an interest in philosophy' - Jeff Mason, The Philosophers' Magazine `Tim LeBon has… authored a text which should become a staple on the philosophical counsellor's bookshelf…. Wise Therapy is a concise, well-written book…. His ability to relate philosophical concepts to counselling concerns is admirable and attests to the skill and knowledge he possesses as a working counsellor. But, by far the most important part of Tim LeBon's book to PC is the last chapter, "The Counsellor's Philosophical Toolbox"' - Craig Munns in The Examined Life ` Tim LeBon has done a good job of offering practical approaches to some of the most important and vexing issues that arise in counselling…. Tim LeBon's book contains helpful suggestions, practical information, and useful examples, and would make a good addition to the library of any counsellors willing to allow philosophy to turn mere client sessions into wise therapy' - Peter Raabe, Practical Philosophy Wise Therapy is an original and practical guide to how philosophy can benefit counselling and psychotherapy. Tim LeBon argues that therapy, informed by philosophy, can help clients make better decision and achieve emotional wisdom. He uses philosophical approaches to explore issues of right and wrong, the emotions and reasons, well-being and the meaning of life, and develops a 'counsellor's toolbox' of techniques that can help practitioners apply the wisdom of philosophy to good therapeutic practice. For counsellors who may find philosophical approaches to therapy useful, this work addresses key philosophical topics - the emotions, free will, the meaning of life and ethics. It is jargon-free where possible and assumes no previous philosophical training. From The Independent, 16th November 2004 Plato is my agony aunt It was the end of a love affair that broke her heart. Could the wisdom of the great philosophers show her how to be happy again? Claire Smith tries a novel form of therapy "The unexamined life is not worth living," Socrates said. Nor is the life you're left with after your boyfriend has left you for another woman - at least, that's how it felt in October last year when mine broke rank and went off with an art student from Cleveland, Ohio. We were over there for the opening of his new art exhibition. He'd flown over four days before me and had met her at a party. Supposedly, they "connected". The five months that followed were a roller-coaster of confusion, vitriol and despair. I knew there'd been problems in our relationship. We saw the world very differently; he delighted in the charm of the ordinary, I wanted maximum divinity. He walked; I galloped. He drank tea; I loathed the stuff. But, along the banks of the Thames, we'd made a promise to always stick together. Our love was something unique: "transcendental", I called it. And besides, we recycled. Surely a commitment to save the world would save our relationship? Alas, no. So there I was, a woman scorned. Hell truly hath no greater fury. And what made it worse was that I still believed in our transcendental love. If I wanted to change the way I was feeling, I needed to alter the way I was thinking. But how? A few bottles of wine and a sharp blow to the head might have done the trick. Fortunately, there's an older, more trusted way of turning your head on its head that counsellors are starting to use: philosophy. The idea of employing Plato as an agony aunt was begun in 1981 by the German philosopher Gerd Achenbach. Although philosophy spends a lot of its time asking real-life questions that affect real-life people - What is happiness? And is it always wrong to lie? - most of the debate goes on in ivory towers. What Achenbach and subsequent philosophers including Tim LeBon, the chairman of the UK's Society for Philosophy in Practice, wanted to do was "give practical application" to this gigantic library of great thoughts. So how does it work? Like most types of therapy, you sign up for a set of sessions. "Two would give you a new perspective on one issue; six would help you to make a major life-decision, like a career change; with 12 you can start to rethink your entire life philosophy," explains LeBon. Each session lasts 50 minutes and costs £50 - and, no, you don't have to have any previous knowledge of philosophy. "If you think of Friends, it would suit Ross and Chandler more than Joey," LeBon says. "It's for anyone who wants to make their emotions more intelligent. Or for those who have tried other kinds of therapy, and want something more cerebral." The first session begins with the patient venting off about whatever's troubling them. The rant over, the counsellor then picks out some key concepts that are crucial to the problem - in the case of heartbreak, it is love and happiness that come hurtling to the fore - and then gets the patient to define what they mean. So, what is love? What is happiness? To kick-start the patient's thinking, LeBon describes what a great philosopher had to say about it. In my case, he tells me what Plato wrote about love in his Symposium: that to stop man fighting the gods, Zeus decided to cut each human in two, so they would lose their strength. "This, then, is the source of our desire to love each other," Plato said. "Each of us is a 'matching half' of a human whole, because each was sliced like a flatfish, two out of one, and each of us is always seeking the half that matches him." This method of probing what we might think are "obvious" ideas, such as love and happiness, was devised by Socrates in the squares of Athens. "The only I thing I know is that I know nothing at all," he boasted. What Socrates showed was that although many of the thinkers of his time thought they knew what justice, happiness and goodness meant, their understanding was tied in to their personal agenda and world view, and, what's more, when pushed, their ideas often contradicted themselves. A bit like me on love. Whereas part of my understanding of love was something that gave life meaning, made it worth living and bound us together, I also believed that true love was "transcendental": that it was out of this world, and it didn't matter if the two people who loved each other couldn't get along in the day-to-day. Love was bigger than the mundane. But when it came to the next stage of the therapy, critical thinking - "to check out whether your assumptions stand up to examination" - I walked head first into a contradiction. If I think love's purpose is to make life worth living, but then say it's irrelevant to daily life, surely my two ideas of love are not compatible? As the cogs in my brain start to creak into motion, I feel myself taking a step back from my predicament: thinking about how I've been thinking. This idea I had of transcendental love might have started off as a romantic dream. But when the relationship stopped working, and I found myself feeling trapped and frustrated, I used it to justify the mechanics of a relationship that just didn't work in the daily grind. I used it to lie to myself. In the final stage, LeBon gets me to start thinking about how to go forward. "You can't change what has happened," he says. "You can't change that he's left you, or how you behaved in the relationship. So, as the Stoics did, let's work on controlling the controllables: the things that you can change." To work out what can be changed, he gets me to try out a thought experiment, a method often used in philosophy to imagine other worlds where people can have different codes of behaviour. Thought experiments shatter your preconceived ideas of how the world should be and let your imagination run wild to how the world could be. "I find Viktor Frankl very useful here, the Austrian psychiatrist and concentration-camp survivor who actually believed that everything in life happens for a purpose," LeBon says. "Suppose this break-up did happen for a reason that will work to your benefit," he suggests. "What might that be? The answer might be that you can now focus on something important that was denied in the relationship. Or - the Hollywood version - so you'll meet someone who is really right for you." Temporarily freed of any sense of responsibility for the relationship that was, and its sorry demise, the list came fast. I could now travel more; he didn't like me travelling on my own, but too often he didn't want to go anywhere, preferring to stay in his studio and make art. I'd love to meet someone with a similar sense of adventure to mine. For the first time in two years, I was being honest with myself about what I really wanted - listening to those voices that we all have inside our heads, and too often try to muzzle. So did philosophy save me? Well, I'm now dating a travel writer I have to run to keep up with. I still haven't got over the fact that my replacement came from Cleveland, Ohio. But I guess I never will. Tim LeBon can be reached by e-mail at [email protected] A FEW WORDS FROM THE WISE Compiled by Ed Caesar · "At the touch of love, everyone becomes a poet" - Plato · "There is always some madness in love. But there is also always some reason in madness" - Friedrich Nietzsche · "That man shall live as his own master and in happiness who can say each day 'I have lived'" - Horace · "The good of man is the active exercise of his soul's faculties in conformity with excellence or virtue... Moreover this activity must occupy a complete lifetime; for one swallow does not make spring, nor does one fine day; and similarly one day or a brief period of happiness does not make a man supremely blessed and happy" - Aristotle · "There is nothing on this earth more to be prized than friendship" - Thomas Aquinas · "Whatever you do... love those who love you" - Voltaire · "Happiness is not an ideal of reason but of imagination" - Immanuel Kant · "Happiness is a state of which you are unconscious. The moment you are aware that you are happy, you cease to be happy" - Jiddu Krishnamurti · "Love is an ideal thing. Marriage is a real thing" - Johann Wolfgang von Goethe I shrink, therefore I am Therapy has many answers, but some questions require the help of a philosopher, says Clint Witchalls Sunday November 21, 2004 The Observer Danny had worked in the City of London for 10 years. As a research analyst, stockbroker and fund manager, he'd made a lot of valuable contacts, earnt a lot of cash, and learnt some important business skills. However, as he approached his mid-thirties, he no longer felt good about himself or what he did for a living, and he found his colleagues cold and unfriendly. A chronic illness made him realise his mortality, and he began to reassess his priorities. Danny had been struggling with his career conundrum for nearly five years when he met David Arnaud, a philosophical counsellor. After a few soul-searching sessions, Danny arrived at a decision. Today, he teaches economics to sixth-formers, and he loves it. 'It's a much better lifestyle,' he says. Many people are turning to philosophical counsellors to get answers to questions such as: 'How do I make sense of myself?' 'What is important to me?' 'Where am I going?' These are perhaps not the sort of questions that require psychiatric intervention, but Arnaud, who recently completed the first empirical study of philosophical counselling in the UK, has found that within just five sessions the majority of clients, with important decisions to make, tend to move from a state of concern and confusion to a resolution. Modern philosophical counselling can be traced back to 1981, when the philosopher Gerd Achenbach opened the first practice near Cologne. Achenbach referred to the new discipline as 'therapy for the sane.' Today, there are hundreds of philosophical counsellors around the world, with the movement particularly strong in the US, Britain and the Netherlands. 'The dilemmas people face aren't always primarily psychological,' says Alex Howard, a philosophical counsellor from Newcastle. 'If people face problems that are social or economic, it doesn't make sense to define their problems in purely psychological terms.' Tim LeBon, a founder member of the Society for Philosophy in Practice (SPP) and author of Wise Therapy, adds: 'We are faced with far more life choices than our grandparents, yet have far fewer resources to deal with them. Our grandparents may have gone to a priest or to other family members for advice; most people don't trust these solutions any more and so want to make their own well-informed, well thought-out choices. Philosophical counselling can help these people - people in mid-life crises who are wondering how to make the most of the rest of their life. People who want to take stock of their values.' Where stressed executives might once have been prescribed a course of tranquillisers or antidepressants, they can now get a dose of Bertrand Russell instead: 'Success is too dearly purchased if all the other ingredients have been sacrificed to obtain it.' While some philosophical counsellors do recommend books for their clients to read, most sessions are about helping the client identify faulty thoughts. For example, a briefing in Aristotelian logic might show a client why their beliefs are erroneous. The person might infer that they're a screw-up because they've screwed up. The counsellor could point out that they're making an error called 'fallacy of composition' - that is, what's true of the part isn't necessarily true of the whole. In philosophical counselling, problems aren't pathologised as they are by the psychiatric profession, and the dialogue between client and counsellor is more like a meeting of equals, compared to many therapies where the client is treated like a patient and seen as someone who is, in some way, inadequate. 'Anybody can benefit from philosophical counselling,' says Howard. 'But it does require someone who is willing to take stock.' Lou Marinoff, author of international bestseller Plato Not Prozac! has done much to promote philosophical counselling. 'Some people who have stabilised their neurochemistry and validated their emotions now wish to examine or re-examine the criteria of their beliefs, the principles of their conduct, or the meaning of their lives,' he says. 'With whom shall they do this? Psychologists and psychiatrists can shed light on such issues - as can rabbis, priests, imams and gurus. Philosophers are now rejoining the ranks of helpers.' LeBon believes certain therapies (such as cognitive behavioural therapy) don't go far enough in helping their clients. 'For instance, if you are anxious about your relationship, a cognitive therapist would try to dispute your catastrophising and jump to conclusions to make you feel less anxious,' says LeBon. 'A philosophical counsellor would do this, but would also look for existential meaning in your anxiety - perhaps you really don't want to be in the relationship and that is what your anxiety is telling you.' LeBon also gives short shrift to psychoanalysts. 'There's very little evidence for the Freudian unconscious, and it's time to move on to more intellectually satisfying and helpful therapies,' he says. However, Alain de Botton, the man who popularised philosophy as self-help, isn't ready to bury psychologists and their ilk just yet. 'The truth is that psychoanalysis grew out of philosophy - it's not some completely new idea, and in fact, done properly, psychoanalysis is philosophical anyway. It may even be dangerous to the mental health of some people to suggest a philosopher rather than a properly trained analyst. The knowledge of analysts when it comes to many emotional problems is now much greater than that of most philosophers.' Guardian Unlimited © Guardian Newspapers Limited 2004. (shrink)

Modern antiretroviral therapies are capable of suppressing HIV in the bloodstream to undetectable levels. Nonetheless, people living with HIV must maintain lifelong adherence to ART to avoid the re-emergence of the infection. So despite the existence and efficacy of ART, there is still substantial interest in development of a cure. But HIV cure trials can be risky, their success is as of yet unlikely, and the medical gain of being cured is limited against a baseline of ART access. The (...) medical prospect associated with participation in cure research thus look poor. Are the risks and burdens that HIV cure research places on participants so high that it is unethical, at present, to conduct it? In this paper, I answer ‘no’. I start my argument by describing a foundational way of thinking about the ethical justification for regulatory limits on research risk; I then apply this way of thinking to HIV cure trials. In offering this analysis, I confine my attention to studies enrolling competent adults and I also do not consider risks research may pose to third parties or society. Rather, my concern is to engage with the thought that some trials are so risky that performing them is an ethically unacceptable way to treat the participants themselves. I reject this thought and instead argue that there is no level of risk, no matter how high, that inherently mistreats a participant. (shrink)

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption, involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal (...) decision-making study nested in a Thai acute HIV research cohort. In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks. These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach. (shrink)

: In 1998, 39 pharmaceutical manufacturers sued the government of South Africa to prevent the implementation of a law designed to facilitate access to AIDS drugs at low cost. The companies accused South Africa, the country with the largest population of individuals living with HIV/AIDS in the world, of circumventing patent protections guaranteed by intellectual property rules that were included in the latest round of world trade agreements. The pharmaceutical companies dropped their lawsuit in the spring of 2001 after an (...) avalanche of negative publicity. Yet, despite the government's victory, AIDS drugs remain very expensive in South Africa, and the government still refuses to provide antiretroviral therapy to adults. These events have shone a spotlight, not only on the possibilities for coordinated political activism in the era of instant global communications, but also on the tangled social, economic, and political dimensions of AIDS treatment in poor countries. (shrink)

The DNA hypomethylating agents (HMA) azacitidine (AZA) and decitabine (DAC) improve survival and transfusion independence in myelodysplastic syndrome (MDS) and enable a low intensity cytotoxic treatment for aged AML patients unsuitable for intensive chemotherapy, particularly in combination with novel agents. The proposed mechanism of AZA and DAC relies on active DNA replication and therefore patient responses are only observed after multiple cycles of treatment. Although extended dosing may provide the optimal scheduling, the reliance of injectable formulation of the drug (...) limits it to intermittent treatment. Recently, an oral formulation of AZA demonstrated significantly improved patient relapse free survival (RFS) and overall survival (OS) when used as maintenance after chemotherapy for AML. In addition, both DAC and AZA were found to be highly effective to improve survival in elderly patients with AML through combination with other drugs. These recent exciting results have changed the therapeutic paradigm for elderly patients with AML. In light of this, we review current knowledge on HMA mechanism of action, clinical trials exploring dosing and scheduling, and recent HMA combination therapies to enhance efficacy. (shrink)

In his paper “The Catholic Church, the American Military, and Homosexual Reorientation Therapy,” David W. Lutz ultimately concludes that it is “appropriate, and highly ethical” for the American military to offer reorientation therapy to help homosexuals overcome “the vice of sodomy.” The major thrust of his paper, however, is to call for abandonment of the “Don’t Ask/Don’t Tell” policy currently in place in the military. Lutz’s paper covers much ground, and this review begins by examining whether such (...) a wide view is necessary for the ultimate conclusions. It goes on to ask whether Lutz has omitted to mention important considerations bearing on this issue, and whether Lutz’s call for the introduction of reorientation therapy is a serious call or a symbolic response to homosexual activities. Lutz fails to address essential issues such as the actual experiences of other nations having homosexuals in the military, and issues regarding what constitutes “reorientation therapy,” the latter leading to questions about how such a therapy would actually be implemented. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex (...) 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

Exposure Therapy (ET) has demonstrated its efficacy in the treatment of phobias, anxiety and Post-traumatic Stress Disorder (PTSD), however, it suffers a high drop-out rate because of too low or too high patient engagement in treatment. Virtual Reality Exposure Therapy (VRET) is comparably effective regarding symptom reduction and offers an alternative tool to facilitate engagement for avoidant participants. Neuroimaging studies have demonstrated that both ET and VRET normalize brain activity within a fear circuit. However, previous studies have employed (...) brain imaging technology which restricts people’s movement and hides their body, surroundings and therapist from view. This is at odds with the way engagement is typically controlled. We used a novel combination of neural imaging and VR technology—Functional Near-Infrared Spectroscopy (fNIRS) and Immersive Projection Technology (IPT), to avoid these limitations. Although there are a few studies that have investigated the effect of VRET on a brain function after the treatment, the present study utilized technologies which promote ecological validity to measure brain changes after VRET treatment. Furthermore, there are no studies that have measured brain activity within VRET session. In this study brain activity within the prefrontal cortex (PFC) was measured during three consecutive exposure sessions. N = 13 acrophobic volunteers were asked to walk on a virtual plank with a 6 m drop below. Changes in oxygenated (HbO) hemogl... (shrink)

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the (...) dramatic increase in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action. Methods: We conducted a thorough systematic search of studies published until October 2017, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning. Results: Seventy-five studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analysed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy. Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EDMR therapy are still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions. (shrink)

Published data show that new HIV prevention strategies including treatment‐as‐prevention and pre‐exposure prophylaxis (PrEP) using oral antiretroviral drugs (ARVs) are highly, but not completely, effective if regimens are taken as directed. Consequently, their implementation may challenge norms around HIV prevention. Specific concerns include the potential for ARV‐based prevention to reframe responsibility, erode beneficial sexual norms and waste resources. This paper explores what rights claims uninfected people can make for access to ARVs for prevention, and whether moral claims justify (...) the provision of ARV therapy to those who do not yet clinically require treatment as a way of reducing HIV transmission risk. An ethical analysis was conducted of the two strategies, PrEP and treatment‐as‐prevention, using a public health stewardship model developed by the Nuffield Bioethics Council to consider and compare the application of PrEP and treatment‐as‐prevention strategies. We found that treating the person with HIV rather than the uninfected person offers advantages in settings where there are limited opportunities to access care. A treatment‐as‐prevention strategy that places all the emphasis upon the positive person's adherence however carries a disproportionate burden of responsibility. PrEP remains an important option for receptive partners who face increased biological vulnerability. We conclude that the use of ARV for prevention is ethically justified, despite imperfect global to drugs for those in clinical need. The determination of which ARV‐based HIV prevention strategy is ethically preferable is complex and must take into account both public health and interpersonal considerations. (shrink)

BackgroundThe therapeutic effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) is related to the modulation of pathological neural activities, particularly the synchronization in the β band (13–35 Hz). However, whether the local β activity in the STN region can directly predict the stimulation outcome remains unclear.ObjectiveWe tested the hypothesis that low-β (13–20 Hz) and/or high-β (20–35 Hz) band activities recorded from the STN region can predict DBS efficacy.MethodsLocal field potentials (LFPs) were recorded in (...) 26 patients undergoing deep brain stimulation surgery in the subthalamic nucleus area. Recordings were made after the implantation of the DBS electrode prior to its connection to a stimulator. The maximum normalized powers in the theta (4–7 Hz), alpha (7–13 Hz), low-β (13–20 Hz), high-β (20–35 Hz), and low-γ (40–55 Hz) subbands in the postoperatively recorded LFP were correlated with the stimulation-induced improvement in contralateral tremor or bradykinesia–rigidity. The distance between the contact selected for stimulation and the contact with the maximum subband power was correlated with the stimulation efficacy. Following the identification of the potential predictors by the significant correlations, a multiple regression analysis was performed to evaluate their effect on the outcome.ResultsThe maximum high-β power was positively correlated with bradykinesia–rigidity improvement (rs = 0.549, p < 0.0001). The distance to the contact with maximum high-β power was negatively correlated with bradykinesia–rigidity improvement (rs = −0.452, p < 0.001). No significant correlation was observed with low-β power. The maximum high-β power and the distance to the contact with maximum high-β power were both significant predictors for bradykinesia–rigidity improvement in the multiple regression analysis, explaining 37.4% of the variance altogether. Tremor improvement was not significantly correlated with any frequency.ConclusionHigh-β oscillations, but not low-β oscillations, recorded from the STN region with the DBS lead can inform stimulation-induced improvement in contralateral bradykinesia–rigidity in patients with PD. High-β oscillations can help refine electrode targeting and inform contact selection for DBS therapy. (shrink)

Since the 1970s, new therapeutic practices, involving the interaction between humans and dolphins - Tursiops truncatus in particular, have developed. Such practices are known as dolphin-assisted therapies (DAT), a specific case of a more heterogeneous set of experiences with dolphins called dolphin-assisted activities (DAA): these include programmes of dolphin watching and swimming in high seas, as well as shows in dolphinariums and marine parks. DAT has grown rapidly as a highly attractive form of therapy, due to the well-liked (...) animals used in an aquatic, and often exotic, environment. This kind of co-therapy seems to testify the enchantement that dolphins - in myths and chronicles often reported in rescue at sea, perceived as especially charismatic - exert on people; the human attempt of bonding with them, possibly in response to the need of building a human-animal bodily intersubjectivity. (shrink)

Psychedelic treatments, particularly 3,4-methylenedioxymethamphetamine (MDMA)-assisted and psilocybin-assisted therapies, have recently seen renewed interest in their clinical potential to treat various mental health conditions. Clinical trials for both MDMA-assisted and psilocybin-assisted therapies have shown to be highly efficacious for post-traumatic stress disorder and major depression. Recent research trials for psychedelic-assisted therapies (PAT) have demonstrated that although they are resource-intensive, their effects are rapid-acting, durable and cost-effective. These results have generated enthusiasm among researchers seeking to investigate psychedelic therapies in active-duty (...) service members of the US military, particularly those with treatment refractory mental health conditions. At the same time, psychedelics remain in early stages of clinical investigation, have not yet achieved regulatory approval for general clinical use and may confer unique psychological and neurobiological effects that could raise novel ethical considerations when treating active-duty service members. Should psychedelics achieve regulatory approval, military relevant considerations may include issues of access to these treatments, appropriate procedures for informed consent, confidentiality standards, and possible unanticipated mental health risks and other psychological sequelae. A service member’s deployability, as well as their ability to return to full military duty following PAT, may also be of unique concern. The authors argue that MDMA-assisted therapy currently represents a promising treatment that should be more rapidly investigated as a clinical therapy for service members while still taking a measured approach that accounts for the many military-specific uncertainties that remain. (shrink)

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth (...) in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)

Considerable heterogeneity among pediatric chronic pain patients may at least partially explain the variability seen in the response to behavioral therapies. The current study tested whether autistic traits and attention-deficit/hyperactivity disorder symptoms in a clinical sample of children and adolescents with chronic pain are associated with socioemotional and functional impairments and response to acceptance and commitment therapy treatment, which has increased psychological flexibility as its core target for coping with pain and pain-related distress. Children and adolescents aged 8–18 years (...) were recruited. Patients and their parents completed questionnaires pre- and post-ACT of 17 sessions. Correlational analyses and mixed-effects models were used to assess the role of autistic traits and ADHD symptoms in pretreatment functioning and ACT-treatment response. Outcome variables were degree to which pain interfered with daily activities, socioemotional functioning, psychological inflexibility, and pain intensity. Autistic traits and ADHD symptoms, pain frequency, and pain duration were measured at pretreatment only. Higher autistic traits were associated with greater pain interference, higher depression, and greater psychological inflexibility. Higher ADHD symptomatology was associated with greater pretreatment pain interference, lower emotional functioning, greater depression, and longer duration of pain. Across patients, all outcome variables, except for sleep disturbances and school functioning, significantly improved from pre- to post-ACT. Higher autistic traits were associated with greater pre- to post-ACT improvements in emotional functioning and sleep disturbance and non-significant improvements in pain interference. ADHD symptomatology was not associated with treatment outcome. The current results showed that neuropsychiatric symptoms in pediatric chronic pain patients are associated with lower functioning, particularly pain interfering with daily life and lower socioemotional functioning. The results suggest that not only pediatric chronic pain patients low in neuropsychiatric symptoms may benefit from ACT, but also those high in autism traits and ADHD symptoms. With the present results in mind, pediatric chronic pain patients higher in autistic traits may actually derive extra benefit from ACT. Future research could assess whether increased psychological flexibility, the core focus of ACT, enabled those higher in autism traits to cope relatively better with pain-related distress and thus to gain more from the treatment, as compared to those lower in autism traits. Moreover, to address specific effects of ACT, inclusion of an appropriate control group is key. (shrink)

BackgroundBurnout is a major societal issue adversely affecting employees’ health and performance, which over time results in high sick leave costs for organizations. Traditional rehabilitation therapies show suboptimal effects on reducing burnout and the return-to-work process. Based on the health-promoting effects of nature, taking clients outdoors into nature is increasingly being used as a complementary approach to traditional therapies, and evidence of their effectiveness is growing. Theories explaining how the combination of general psychological support and outdoor-specific elements can trigger the (...) rehabilitation process in outdoor therapy are often lacking, however, impeding its systematic research.AimThe study aims to develop an intervention and evaluation model for outdoor therapy to understand and empirically evaluate whether and how such an outdoor intervention may work for rehabilitation after burnout.Methodological ApproachWe build on the exemplary case of an outdoor intervention for rehabilitation after burnout, developed by outdoor clinical psychologists in Netherlands. We combined the generic context, process, and outcome evaluation model and the burnout recovery model as an overarching deductive frame. We then inductively specified the intervention and evaluation model of outdoor therapy, building on the following qualitative data: semi-structured interviews with outdoor clinical psychologists and former clients; a content analysis of the intervention protocol; and reflective meetings with the intervention developers and health promotion experts.ResultsWe identified six key outdoor intervention elements: physical activity; reconnecting body and mind; nature metaphors; creating relationships; observing natural interactions; and experiential learning. The results further showed that the implementation of these elements may facilitate the rehabilitation process after burnout in which proximal, intermediate, and distal outcomes emerge. Finally, the results suggested that this implementation process depends on the context of the therapist, therapy, and of the clients.ConclusionThe intervention and evaluation model for outdoor therapy shows how key outdoor intervention elements may contribute to the rehabilitation process after burnout. However, our model needs to be further tested among a larger group of clients to empirically evaluate whether and how outdoor therapy can support rehabilitation. (shrink)

Trials with highly unfavourable risk–benefit ratios for participants, like HIV cure trials, raise questions about the quality of the consent of research participants. Why, it may be asked, would a person with HIV who is doing well on antiretroviral therapy be willing to jeopardise his health by enrolling in such a trial? We distinguish three concerns: first, how information is communicated to potential participants; second, participants’ motivations for enrolling in potentially high risk research with no prospect of (...) direct benefit; and third, participants’ understanding of the details of the trials in which they enrol. We argue that the communication concern is relevant to the validity of informed consent and the quality of decision making, that the motivation concern does not identify a genuine problem with either the validity of consent or the quality of decision making and that the understanding concern may not be relevant to the validity of consent but is relevant to the quality of decision making. In doing so, we derive guidance points for researchers recruiting and enrolling participants into their HIV cure trials, as well as the research ethics committees reviewing proposed studies. (shrink)

Published data show that new HIV prevention strategies including treatment-as-prevention and pre-exposure prophylaxis (PrEP) using oral antiretroviral drugs (ARVs) are highly, but not completely, effective if regimens are taken as directed. Consequently, their implementation may challenge norms around HIV prevention. Specific concerns include the potential for ARV-based prevention to reframe responsibility, erode beneficial sexual norms and waste resources. This paper explores what rights claims uninfected people can make for access to ARVs for prevention, and whether moral claims justify (...) the provision of ARV therapy to those who do not yet clinically require treatment as a way of reducing HIV transmission risk. An ethical analysis was conducted of the two strategies, PrEP and treatment-as-prevention, using a public health stewardship model developed by the Nuffield Bioethics Council to consider and compare the application of PrEP and treatment-as-prevention strategies. We found that treating the person with HIV rather than the uninfected person offers advantages in settings where there are limited opportunities to access care. A treatment-as-prevention strategy that places all the emphasis upon the positive person's adherence however carries a disproportionate burden of responsibility. PrEP remains an important option for receptive partners who face increased biological vulnerability. We conclude that the use of ARV for prevention is ethically justified, despite imperfect global to drugs for those in clinical need. The determination of which ARV-based HIV prevention strategy is ethically preferable is complex and must take into account both public health and interpersonal considerations. (shrink)

Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 and few other proteins encoded by Herpesviridae, Nef, E1A, NS5A, PB2, HN, L83L, (...) MC155R, other Poxviridae proteins, and some bacteriophages of human associated bacteria. If confirmed experimentally, these findings may aid in dissection of molecular functions of uncharacterized viral proteins and provide a novel rationale for statin and FT/GGT1-based inhibition of viral infections. Prenylation of bacteriophage proteins may aid in moderation of microbial infections. Many human viruses, including HCV, HIV1, ASFV, and a number of Adeno-, Pox-, and herpesviruses, including CMV, encode the substrates for mammalian prenylation enzymes. Prenylation is advantageous for viral infection; its suppression by FT/GGT and FPPS inhibitors has antiviral effects. In bacteriophages, prenylation may aid in moderation of microbial infections. (shrink)

This paper reflects on the meanings of ‘post-AIDS’ in the Global North and South. I bring together contemporary arguments to suggest that the notion of ‘post-AIDS’ is, at best, misplaced, not least because its starting point remains a biotechnical one. Drawing on aspects of the sub-Saharan African experience, this essay suggests that, despite significant shifts in access to antiretroviral therapy, HIV continues to be fundamentally shaped by economic determinants and social and cultural practices. In this essay, I question (...) the certainty of the discourse of ‘positive progress’, which underpins the ‘post-AIDS’ narrative, and suggest that living with HIV and AIDS in our contemporary global context is a life lived with ongoing complexity, stigma and chronicity. I suggest that HIV in the Global North shares many characteristics with HIV in the Global South yet differs in significant ways, not least in the fact that a resource-rich context generates an environment where health and social care support is possible, and, mostly, usual. In both contexts, however, the experience of living with a highly stigmatized illness with no cure in both the Global South and North suggests that this is a point of shared experience. (shrink)

Intracellular bacteria were recently shown to employ eukaryotic prenylation system for modifying activity and ensuring proper intracellular localization of their own proteins. Following the same logic, the proteins of viruses may also serve as prenylation substrates. Using extensively validated high-confidence prenylation predictions by PrePS with a cut-off for experimentally confirmed farnesylation of hepatitis delta virus antigen, we compiled in silico evidence for several new prenylation candidates, including IRL9 and few other proteins encoded by Herpesviridae, Nef, E1A, NS5A, PB2, HN, L83L, (...) MC155R, other Poxviridae proteins, and some bacteriophages of human associated bacteria. If confirmed experimentally, these findings may aid in dissection of molecular functions of uncharacterized viral proteins and provide a novel rationale for statin and FT/GGT1-based inhibition of viral infections. Prenylation of bacteriophage proteins may aid in moderation of microbial infections. Many human viruses, including HCV, HIV1, ASFV, and a number of Adeno-, Pox-, and herpesviruses, including CMV, encode the substrates for mammalian prenylation enzymes. Prenylation is advantageous for viral infection; its suppression by FT/GGT and FPPS inhibitors has antiviral effects. In bacteriophages, prenylation may aid in moderation of microbial infections. (shrink)

BackgroundFreezing of gait is a disabling burden for Parkinson’s disease patients with poor response to conventional therapies. Combined deep brain stimulation of the subthalamic nucleus and substantia nigra moved into focus as a potential therapeutic option to treat the parkinsonian gait disorder and refractory FoG. The mechanisms of action of DBS within the cortical-subcortical-basal ganglia network on gait, particularly at the cortical level, remain unclear.MethodsTwelve patients with idiopathic PD and chronically-implanted DBS electrodes were assessed on their regular dopaminergic medication in (...) a standardized stepping in place paradigm. Patients executed the task with DBS switched off, conventional STN DBS and combined STN+SN DBS and were compared to healthy matched controls. Simultaneous high-density EEG and kinematic measurements were recorded during resting-state, effective stepping, and freezing episodes.ResultsClinically, STN+SN DBS was superior to conventional STN DBS in improving temporal stepping variability of the more affected leg. During resting-state and effective stepping, the cortical activity of PD patients in STIM OFF was characterized by excessive over-synchronization in the theta, alpha, and high-beta band compared to healthy controls. Both active DBS settings similarly decreased resting-state alpha power and reduced pathologically enhanced high-beta activity during resting-state and effective stepping compared to STIM OFF. Freezing episodes during STN DBS and STN+SN DBS showed spectrally and spatially distinct cortical activity patterns when compared to effective stepping. During STN DBS, FoG was associated with an increase in cortical alpha and low-beta activity over central cortical areas, while with STN+SN DBS, an increase in high-beta was prominent over more frontal areas.ConclusionsSTN+SN DBS improved temporal aspects of parkinsonian gait impairment compared to conventional STN DBS and differentially affected cortical oscillatory patterns during regular locomotion and freezing suggesting a potential modulatory effect on dysfunctional cortical-subcortical communication in PD. (shrink)

Over the past two decades we have seen dramatic improvements in the efficacy, safety and availibity of antiretroviral therapy (ART). In the USA and Europe, life expectancy in people living with HIV disease approaches that of the HIV-uninfected.1 Even in regions hardest hit by the HIV epidemic, effective HIV therapy has reversed more than a decade of HIV-related decreased survival. Despite these advances in ART, motivations to pursue HIV cure remain strong due to the toxicity, adherence challenges, (...) cost and access to care issues associated with HIV therapy, as well as the persistant stigma associated with having HIV infection. Further and renewed motivation comes from a single case of HIV cure after stem cell transplantation for acute leukaemia. Given the tremendous improvements in ART, it is important to assess how effective and safe an HIV cure would need to be in order to be a viable option compared to ART. We argue that this should be done prior to the availability of a cure to provide realistic goals for researchers and policy makers. One methodology that has been increasingly popular over the past decade is the use of mathematical simulation modelling to assess the clinical impact, cost-effectiveness and clinical role of different treatment strategies in HIV disease, as well as in medicine broadly.2 Such models provide a framework and approach for using the best available data at any point in time, and assessing the potential impact of emerging innovations. Further, unlike individual trials focused on a single endpoint, these models can integrate multiple data sources to project beyond the timeline or outcomes of individual studies and project long-term outcomes in many domains, including virologic, immunologic, clinical and cost.3 Mathematical models have particular value in their ability to assess uncertainty in clinical care. Examples include parameters determined in …. (shrink)

Background: “Therapeutic misconception” arises when human subjects interpret a clinical trial as aimed primarily at therapy rather than producing knowledge. Therapeutic misconceptions may be more prevalent in trials enrolling gravely ill subjects or involving novel and well publicised investigational agents.Objective: To examine the extent to which investigators express therapeutic optimism in phase 1 human gene transfer consent documents, whether highly active gene transfer researchers are more prone to expressing therapeutic optimism, and whether consent forms have grown more (...) optimistic in their descriptions of personal benefit over the last decade.Design: Content analysis was performed on 277 consent documents to measure the number of sentences describing possibility of benefit, terminology used for experimental agents, the proportion of statements describing personal versus societal benefits, and whether investigators attempted to thwart therapeutic misconceptions.Results: Consent forms generally used therapeutic terminology to describe study agents, devoted more sentences to describing possible personal benefits than to describing benefits to society, and infrequently explained that a particular benefit was unlikely. Consent documents used by highly active gene transfer researchers tended to portray significantly greater optimism about personal benefit than less active investigators, though they were also significantly more cautious with agent terminology. Finally, therapeutic optimism expressed in consent forms has declined over the past decade.Conclusions: Consent documents used in phase 1 gene transfer trials, although increasingly attentive to possible therapeutic misconceptions, are inappropriately optimistic about direct benefits of trial participation. Such optimism is expressed more emphatically in trials involving highly active gene transfer researchers as principal investigators. (shrink)

Franz Anton Mesmer (1734–1815), a physician who graduated from the University of Vienna, invented a therapy based on the concept of a universal fluid, similar to electricity, that flowed through all living things. By restoring the circulation of this fluid in the nerves of human bodies, he believed he could cure illness without resorting to medication. Few medical theories have enjoyed as great success as Mesmer's, first among French high society and then in Germany, Switzerland, the Netherlands, Italy, Sweden, (...) Russia, Britain, and the US. Mesmerism was the circulatory phenomenon par excellence. Its success was founded not only on the hypothesis of the circulation of a fluid common to human physiology and the entire universe, but also on the scientific practices of the time—correspondence, translations, and periodicals—and some ardent and highly active supporters who ensured its spread. However, far from functioning along the lines of direct exportation–importation from one country to another, or a centre to the periphery, mesmerism's dissemination was the work of diffuse institutions and individual mobilities influenced by the modalities of communication. In seeking to reconstitute the wellsprings of these circulations, the first sources that come to mind are printed matter: the many pamphlets and especially the articles and reviews that appeared in periodicals, as well as the Romantic literature that flourished after 1810. Such documents are foundational for authoritative studies of mesmerism in Germany, which proceed from the thesis of successive “waves” of reception. Such sources, however, are somewhat misleading. Rather than taking them as our starting point, it would be better to reconstitute the channels of information by using many sources, both printed and handwritten. The complexity of the circulation of knowledge generated by mesmerism is implicitly testament to the difficulties arising from the institutionalization of this current. (shrink)

In May 2011, the Brazilian Ministry of Health announced the distribution of the first batch of locally produced generic tenofovir disoproxil fumarate (TDF) to support its program of universal and free access for the treatment of HIV/AIDS. The inclusion of TDF in the public health program illustrates what has been considered the ‘Brazilian model’ of HIV/AIDS response, as it illustrates the current phase of the Brazilian pharmaceutical economy. Brazil is known for having managed to control the expansion of HIV/AIDS through (...) a unique initiative combining the public health and the industrial production of generics. But, if at first local manufacturers could freely copy ARVs and produce cheaper generic versions that were delivered to the Ministry of Health, since the country started to grant patents on drugs in 1996, the sustainability of this policy has been challenged by the high cost of patented second-line HIV/AIDS treatments. In order to assure continuity of the local production of ARVs, and keep the program of public health alive, Brazilians are now forced to deal with conflicts of drugs' intellectual property rights in order to open the path to generic production. This article aims to describe the experiences surrounding TDF in Brazil and the unprecedented conflicts and challenges it has brought for our different interviewees. Blurring the frontier between the public and the private, the TDF case was driven at the same time by an ethic of drug access and regulation of drug quality, which has inspired Brazilians to intervene and transform the world they live in. (shrink)

BackgroundAdolescents living with human immunodeficiency virus (HIV) experience challenges, including lack of involvement in their care as well nondisclosure of HIV status, which leads to poor adherence to antiretroviral therapy (ART). Parents have authority over their children, but during adolescence there is an increasing desire for independence. The aim of the study was to explore adolescents’ experience of challenges identified by adolescents ages 10–19 years attending HIV care and treatment at Temeke Regional Referral Hospital in Tanzania. MethodsAn exploratory (...) descriptive qualitative design was employed in the HIV Care and Treatment Centre (CTC) in the Out-Patient Department at the Temeke Regional Referral Hospital in Tanzania with adolescents living with HIV who were 10–19 years of age. A total of 22 adolescents participated in semi-structured face-to-face interviews after parental consent and adolescent assent were obtained. Participants were interviewed about their participation in decisions to be tested for HIV and enrolled in the CTC, concerns surrounding disclosure of their HIV status to the adolescent or to others, stigma and discrimination, and the effect of these challenges on their adherence to medication. All interviews were audio-taped, transcribed verbatim in Swahili, and back-translated to English. Data analysis included both inductive and deductive thematic analysis.ResultsQualitative themes identified included lack of participation in decisions about HIV testing, challenges to enrollment in care and treatment; issues around disclosure of HIV status, such as delays in disclosure to the adolescent and disclosure to other persons and benefits and harms of such disclosures; and factors supporting and interfering with adherence to ART, such as parental support, organizational (clinic) support and problems, and self-stigmatization and shame.ConclusionLack of adolescents’ involvement in their care decision making and delayed disclosure of HIV status to the adolescent were identified concerns, leading to poor adherence to ART among adolescents. Disclosure to others, especially teachers, helped adolescents at school to take their medication properly. Disclosure to others led to stigma and discrimination for some adolescents. More research is needed to better understand the role of disclosure and its benefits and challenges for HIV-positive adolescents in Tanzania. (shrink)

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV-based pre-exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at-risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother-to-child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive (...) measures. In this sense, it represents a new bio-technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries’ struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource-poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections. (shrink)

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV‐based pre‐exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at‐risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother‐to‐child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive (...) measures. In this sense, it represents a new bio‐technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries’ struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource‐poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections. (shrink)

BackgroundWhereas many adolescents and young people with HIV require the transfer of care from paediatric/adolescent clinics to adult ART clinics, this transition is beset with a multitude of factors that have the potential to hinder or facilitate the process, thereby raising ethical challenges of the transition process. Decisions made regarding therapy, such as when and how to transition to adult HIV care, should consider ethical benefits and risks. Understanding and addressing ethical challenges in the healthcare transition could ensure a (...) smooth and successful transition. The purpose of this study was to analyze the ethical challenges of transitioning HIV care for adolescents into adult HIV clinics.MethodsData presented were derived from 191 adolescents attending nine different health facilities in Uganda, who constituted 18 focus group discussions. In the discussions, facilitators and barriers regarding adolescents transitioning to adult HIV clinics were explored. Guided by the Silences Framework for data interpretation, thematic data analysis was used to analyze the data. The principles of bioethics and the four-boxes ethics framework for clinical care (patient autonomy, medical indications, the context of care, and quality of life) were used to analyze the ethical issues surrounding the transition from adolescent to adult HIV care.ResultsThe key emerging ethical issues were: reduced patient autonomy; increased risk of harm from stigma and loss of privacy and confidentiality; unfriendly adult clinics induce disengagement and disruption of the care continuum; patient preference to transition as a cohort, and contextual factors are critical to a successful transition.ConclusionThe priority outcomes of the healthcare transition for adolescents should address ethical challenges of the healthcare transition such as loss of autonomy, stigma, loss of privacy, and discontinuity of care to ensure retention in HIV care, facilitate long-term self-care, offer ongoing all-inclusive healthcare, promote adolescent health and wellbeing and foster trust in the healthcare system. Identifying and addressing the ethical issues related to what hinders or facilitates successful transitions with targeted interventions for the transition process may ensure adolescents and young people with HIV infection remain healthy across the healthcare transition. (shrink)

Our understanding of the neurochemical bases of human love and attachment, as well as of the genetic, epigenetic, hormonal, and experiential factors that conspire to shape an individual's sexual orientation, is increasing exponentially. This research raises the vexing possibility that we may one day be equipped to modify such variables directly, allowing for the creation of “high-tech” conversion therapies or other suspect interventions. In this article, we discuss the ethics surrounding such a possibility, and call for the development of legal (...) and procedural safeguards for protecting vulnerable children from the application of such technology. We also consider the more difficult case of voluntary, adult “conversion” and argue that in rare cases, such attempts might be permissible under strict conditions. (shrink)

In recent years, precise high flow oxygen therapy as a new type of oxygen therapy machine has gradually attracted people’s attention and has been widely used in hospital emergency and clinical treatment of respiratory diseases; especially in recent years, severe coronavirus disease has played an important role in the treatment of patients. This paper presents a new type of precise high flow oxygen therapy machine with electromagnetic pneumatic flow valve as the core control element. A sliding mode (...) control strategy based on the system is proposed to realize the accurate control of oxygen concentration and output flow of oxygen therapy mixture. The physical equipment of the precision high flow system is established, and its working performance is verified through the test platform. The optimization design goal of the precision high flow equipment is achieved. (shrink)

The ‘born this way’ movement for sexual orientation minority rights is premised on the view that sexual orientation is something that can neither be chosen nor changed. Indeed, current sexual orientation change efforts appear to be both harmful and ineffective. But what if ‘high-tech conversion therapies’ are invented in the future that are effective at changing sexual orientation? The conceptual basis for the movement would collapse. In this chapter, we argue that the threat of HCT should be taken seriously, motivating (...) a change in tactics for proponents of sexual orientation minority rights. We also discuss some of the practical-ethical and public-policy issues surrounding HCT, in case the technology is one day developed. (shrink)

Background: The new human coronavirus that leads to COVID-19 has spread rapidly around the world and has a high degree of lethality. In more severe cases, patients remain hospitalized for several days under treatment of the health team. Thus, it is important to develop and use technologies with the aim to strengthen conventional therapy by encouraging movement, physical activity, and improving cardiorespiratory fitness for patients. In this sense, therapies for exposure to virtual reality are promising and have been shown (...) to be an adequate and equivalent alternative to conventional exercise programs.Aim: This is a study protocol with the aim of comparing the conventional physical therapy intervention with the use of a non-immersive VR software during COVID-19 hospitalization.Methods: Fifty patients hospitalized with confirmed diagnosis of COVID-19 will be divided in two groups under physiotherapy treatment using conventional or VR intervention: Group A: participants with COVID-19 will start the first day of the protocol with VR tasks in the morning and then in the second period, in the afternoon, will perform the conventional exercises and Group B: participants with COVID-19 will start the first day with conventional exercises in the morning and in the second period, in the afternoon, will perform activity with VR. All participants will be evaluated with different motor and physiologic scales before and after the treatment to measure improvements.Conclusion: Considering the importance of benefits from physical activity during hospitalization, VR software shows promise as a potential mechanism for improving physical activity. The results of this study may provide new insights into hospital rehabilitation.Trial Registration:ClinicalTrials.gov, identifier: NCT04537858. Registered on 01 September 2020. (shrink)

Background: By organizing and activating our passions with both hormones and experiences, the heart and mind of sexual behavior, sexual motivation, and sexual preference is the brain, the organ of learning. Despite decades of progress, this incontrovertible truth is somehow lost in the far-too-often biologically deterministic interpretation of genetic, hormonal, and anatomical scientific research into the biological origins of sexual motivation. Simplistic and polarized arguments are used in the media by both sides of the seemingly endless debate over sexual orientation, (...) equality, and human rights with such catch phrases as ‘‘born gay’’ contrasted against attempts of ‘‘reparative therapy’’ or ‘‘pray the gay away’’. Though long abandoned in practically every other area of psychology, this remnant of the nature-nurture controversy remains despite its generally acknowledged insufficiency in explaining any adult aspect of the human condition within the scientific community. Methods: This theoretical review article identifies three factors: 1) good intentions with regard to the argument from immutability; 2) false dichotomies limiting intellectual progress by oversimplification of theory and thus hypothesis, and most dangerously, interpretation and; 3) Tradition: a historical separation of the disciplines of biology and psychology, which, to this day, interferes with the effective translation of well-conducted science into good public understanding and policy. Results: Studies clearly demonstrate that progress toward sexual-orientation equality is being made, if slowly, despite the apparent irrelevance of the ‘‘born gay’’ argument from immutability. Evidence is further provided supporting the inadequacy of polarized, dichotic theories of sexual development, particularly those pitting ‘‘blank slate learning’’ against a fated, deterministic biological perspective. Results of this review suggest that an emerging interactionist perspective will promote both better scientific progress and better public understanding, hopefully contributing to progress toward nondiscriminatory public policy. Conclusion: Accepting that the brain is a highly plastic, modularly dimorphic, developmentally biased organ of learning, one which is organized and activated by both hormones and experiences across the lifespan, is essential for doing ‘‘good science’’ well. Interactionist theories of psychosexual development provide an empirically sound, strong, yet modifiable foundation for testable hypotheses exploring biologically biased sexual learning. Keywords: Brain; conditioning; controversy; dichotomy; differentiation; discrimination; equality; sex; sexual; orientation; learning; learned sexuality; born gay; hedonic evaluation; immutability; imprinting; incentive motivation; interactionism; predispositions; theory; therapy (Published: 15 March 2012) Citation: Socioaffective Neuroscience & Psychology 2012, 2 : 17334 - DOI: 10.3402/snp.v2i0.17334. (shrink)

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size — by far, the largest for a gene therapy — poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

In lieu of an abstract, here is a brief excerpt of the content:Promoting Health and Social Progress by Accepting and Depathologizing Benign Intersex TraitsHida ViloriaI was born with ambiguous genitalia and it was a doctor who, by honoring my bodily integrity and not “fixing” me, gave me the greatest gift I’ve ever received. Because my body and its sexual traits are a positive, fundamental part of my experience and identity as a human being, I know that having my genitals removed (...) or altered according to someone else’s vision would have deeply damaged me, both physically and psychologically.The doctor who protected my autonomy was, unsurprisingly, my father. I say “unsurprisingly” because in my experience parents are typically more protective of their children than doctors are of their patients. Also, doctors do not discuss cases with other doctors in the same way they do with laypeople, as doctors know more about medical issues such as the risks involved in infant genital surgery.Other than having clitoromegaly (a large clitoris), my reproductive anatomy is typically female, and so I was assigned female and raised as such without incident. My parents didn’t discuss my intersex traits with me, and I grew up thinking of myself and being accepted as, a girl.When I began menstruating, my father told me I’d need to take pills to “grow taller.” I thought this unusual, as I wasn’t short, and later overheard my mother arguing with him, saying that the pills were “experimental”. I was reminded of this discussion years later, when she told me that the pills had actually been hormones to make my breasts grow. I never took them though as she convinced my father not to make me.Article 7 of The International Covenant on Civil and Political Rights states that, “No one shall be subjected without his free consent to medical or scientific experimentation,” and I’m grateful to both my parents for protecting my civil rights as they protected my health.Due to my Catholic upbringing and schooling, I had no opportunity to compare my genitals to other girls’, and it wasn’t until the age of twelve that I realized, while perusing magazines with friends, that I have atypical sex anatomy. Contrary to common speculation however, this awareness didn’t make me question being female. I simply assumed there must be some genital variation in humans.I feel my parents made the wisest decision possible by registering me as one of the two accepted, available genders but allowing me to live, physically and behaviorally, as who I am. Despite not having developed a stereotypically curvaceous female figure, I was popular and excelled in typically feminine social activities, as well as sports and academics. For example, I was one of four girls selected out of one hundred twenty–five that competed for a spot on my high school cheerleading [End Page 114] squad when I tried out to help a friend who needed a tryout partner.Other than escaping IGM (Intersex Genital Mutilation) and estrogen therapy, I’ve had only a few experiences pertaining to my medical care around being intersex. These experiences fall into two categories: seeing medical doctors who treated me the same after discovering that I have ambiguous genitalia, and seeing ones who didn’t. I feel incredibly blessed that my experiences in the former category vastly outweigh the latter.My first experience came at the age of twenty, when a gynecologist asked me if my clitoris had always been as large as it is. I responded that it had, and she said, while looking at me disapprovingly, that she’d like to do some tests. When I asked her what they were for though, she wouldn’t respond directly. She said I’d reported having some upper lip hair, and acne, on my intake forms. I replied that neither were above average, and asked if there were health issues I should be concerned about. She reluctantly said no. I asked what reason there was then for undergoing tests because of the size of my clitoris.She finally responded, “It’s just not normal.”Fortunately, I’d had positive reactions to my sex traits from the people I’d dated. For example, the first... (shrink)

Background With the huge number of patients who suffer from chronic and incurable diseases, medical scientists continue to search for new curative methods for patients in dire need of treatment. Interest in stem cells is growing, generating high expectations in terms of the possible benefits that could be derived from stem cell research and therapy. However, regardless of the hope of stem cells changing and improving lives, there are many ethical, religious, and political challenges and controversies that affect the (...) research, and mandated to establish ethical guidelines and regulations. In Saudi Arabia, key stakeholders play an active role in discussing the ethics of stem cell research and therapy. The focus of the study was to explore professionals’ perceptions related to the ethical challenges of using stem cells in research and treatment in Saudi Arabia. Results A qualitative research study was conducted to explore and describe the perceptions of 25 professionals employed at different tertiary hospitals in the various regions of Saudi. A thematic analysis was performed to search for and identify the most significant perceptions shared by the participants. Four themes were generated based on the ethical challenges of four areas related to stem cell use, including forbidden and permitted sources of stem cells, informed consent, beneficence, and ethical regulations and guidelines. Conclusion The study identified that there is a growing need to advance the knowledge, education, and awareness related to stem cell research and treatment in Saudi Arabia. (shrink)

Rudolf Steiner, the often undervalued, multifaceted genius of modern times, contributed much to the regeneration of culture. In addition to his philosophical teachings, he provided ideas for the development of many practical activities including education--both general and special--agriculture, medicine, economics, architecture, science, religion, and the arts. Today there are thousands of schools, clinics, farms, and many other organizations based on his ideas. Steiner's original contribution to human knowledge was based on his ability to conduct spiritual research, the investigation of metaphysical (...) dimensions of existence. With his scientific and philosophical training, he brought a new systematic discipline to the field, allowing for conscious methods and comprehensive results. A natural seer from childhood, he cultivated his spiritual vision to a high degree, enabling him to speak with authority on previously veiled mysteries of life. Topics include: true human nature as a basis for medical practice; the science of knowing; the mission of reverence; the four temperaments; the bridge between universal spirituality and the physical; the constellation of the supersensible bodies; the invisible human within us: the pathology underlying therapy; cancer and mistletoe, and aspects of psychiatry; case history questions: diagnosis and therapy; anthroposophic medicine in practice: and three case histories. (shrink)