Personalised Medicine in 2012: Editorial to the Special Issue of New Biotechnology on "MOLECULAR DIAGNOSTICS & PERSONALISED MEDICINE"

This special issue of New Biotechnology is focused on molecular diagnostics and personalised medicine and appears at an epochal moment in the development of the field. The practice of medicine is taking a significant and irrevocable turn towards personalisation, due to the great progress in areas such as genomics, pharmacogenomics and molecular diagnosis. It becomes increasingly apparent that to deliver the promise of personalised treatments, more and more novel medicines discovered today will be presented together with innovative companion diagnostics. The contributions to this volume touch on many disciplines, ranging from cell biology to genetics, immunology, molecular diagnostics, pharmaceutics and economic issues. The contributions of clinicians and basic scientists are synergistically presented to underline better the wide spectrum of studies that can contribute to the new field of personalised medicine. The promising perspectives of individualised treatments are related not only to higher effectiveness, but also to increased efficiency. This is relevant not only for the individual patient, but even more so for the general public, within a wider economical perspective where resources are limited and it becomes more and more mandatory to close the gap between social costs and benefits. This approach follows the steps of a stratified and individualised medicine and finds its final goal in an individualised healthcare.     

Herbal medicine use in the districts of Nakapiripirit, Pallisa, Kanungu, and Mukono in Uganda

ABSTRACT: BACKGROUND: Traditional medicine (TM) occupies a special place in the management of diseases in Uganda. Not with standing the many people relying on TM, indigenous knowledge (IK) related to TM is getting steadily eroded. To slow down this loss it is necessary to document and conserve as much of the knowledge as possible. This study was conducted to document the IK relevant to traditional medicine in the districts of Mukono, Nakapiripirit, Kanungu and Pallisa, in Uganda. METHODS: An ethnobotanical survey was conducted between October 2008 and February 2009 using techniques of key informant interviews and household interviews. RESULTS: The common diseases and conditions in the four districts include malaria, cough, headache, diarrhea, abdominal pain, flu, backache and eye diseases. Respondents stated that when they fall sick they self medicate using plant medicines or consult western-trained medicine practitioners. Self medication using herbal medicines was reported mostly by respondents of Nakapiripirit and Mukono. Respondents have knowledge to treat 78 ailments using herbal medicines. 44 species, mentioned by three or more respondents have been prioritized. The most frequently used part in herbal medicines is the leaf, followed by the stem and root. People sometime use animal parts, soil, salt and water from a grass roof, in traditional medicines. Herbal medicines are stored for short periods of time in bottles. The knowledge to treat ailments is acquired from parents and grandparents. Respondents' age and tribe appears to have a significant influence on knowledge of herbal medicine, while gender does not. CONCLUSION: This survey has indicated that IK associated with TM stills exists and that TM is still important in Uganda because many people use it as a first line of health care when they fall sick. Age and tribe influence the level of IK associated with herbal medicine, but gender does not.     

The Root Extract of the Medicinal Plant Pelargonium sidoides Is a Potent HIV-1 Attachment Inhibitor

Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.     

Health risk perception in Canada II: Worldviews,attitudes and opinions

In this article, we present the results of a national survey of 1500 Canadians on their attitudes and opinions about health risks. Ratings of perceived risk, sources of information on health risks and responsibility for risk management were also investigated, with findings reported separately. A high degree of concern about health risks was associated with industrial pollution and chemical products (with the exception of medicines), with almost complete agreement that the land, air and water are more contaminated than ever. In addition, there was widespread belief that a risk‐free environment was an achievable goal, and an unwillingness to accept some health risks to improve the economy. Lifestyle factors such as diet, exercise, and tobacco smoking were perceived to be important modifiers of health risk. On the other hand, many respondents endorsed the idea that they had little control over the risks to their health.     

Lessons from chimpanzee-based research on human disease: the implications of genetic differences

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98-99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus infection in the two species, the lack of correlation in the efficacy of vaccines and treatments between chimpanzees and humans, and the fact that chimpanzees are not useful for research on human cancer. The major molecular differences underlying these inter-species phenotypic disparities have been revealed by comparative genomics and molecular biology - there are key differences in all aspects of gene expression and protein function, from chromosome and chromatin structure to post-translational modification. The collective effects of these differences are striking, extensive and widespread, and they show that the superficial similarity between human and chimpanzee genetic sequences is of little consequence for biomedical research. The extrapolation of biomedical data from the chimpanzee to the human is therefore highly unreliable, and the use of the chimpanzee must be considered of little value, particularly given the breadth and potential of alternative methods of enquiry that are currently available to science.     

Incommensurable Worldviews? Is Public Use of Complementary and Alternative Medicines Incompatible with Support for Science and Conventional Medicine?

Proponents of controversial Complementary and Alternative Medicines, such as homeopathy, argue that these treatments can be used with great effect in addition to, and sometimes instead of, ‘conventional’ medicine. In doing so, they accept the idea that the scientific approach to the evaluation of treatment does not undermine use of and support for some of the more controversial CAM treatments. For those adhering to the scientific canon, however, such efficacy claims lack the requisite evidential basis from randomised controlled trials. It is not clear, however, whether such opposition characterises the views of the general public. In this paper we use data from the 2009 Wellcome Monitor survey to investigate public use of and beliefs about the efficacy of a prominent and controversial CAM within the United Kingdom, homeopathy. We proceed by using Latent Class Analysis to assess whether it is possible to identify a sub-group of the population who are at ease in combining support for science and conventional medicine with use of CAM treatments, and belief in the efficacy of homeopathy. Our results suggest that over 40% of the British public maintain positive evaluations of both homeopathy and conventional medicine simultaneously. Explanatory analyses reveal that simultaneous support for a controversial CAM treatment and conventional medicine is, in part, explained by a lack of scientific knowledge as well as concerns about the regulation of medical research.     

鹿茸在朝医药中的应用特点

朝医药是朝鲜民族在长期生活经验中总结出的抵抗病邪的智慧结晶,该医学的核心是四象理论,在治疗上倡导＂药乃局限于人＂的药性观。鹿茸是鹿科动物梅花鹿或马鹿等雄鹿头上长出的尚未骨化而带毛的幼角,在朝医药中归类于太阴人药,其功效有补肺、补肾阳、益精血等作用,主要用于太阴人的虚劳及气虚证。通过对鹿茸在临床上的应用以及其基础的研究,发现在药物的应用方面上,朝医药与中医药之间有着某些差异,如果探讨两者之差异的根源以及其中关联,那么对药物的基础研究一定会开辟更多的思路并对临床应用也提供更有效的方法。     

Potent anti-mycobacterial and immunomodulatory activity of some bioactive molecules of Indian ethnomedicinal plants that have the potential to enter in TB management

Tuberculosis (TB) is one of the deadliest infectious diseases of human civilization. Approximately one-third of global population is latently infected with the TB pathogen Mycobacterium tuberculosis (M.tb). The discovery of anti-TB antibiotics leads to decline in death rate of TB. However, the evolution of antibiotic-resistant M.tb-strain and the resurgence of different immune-compromised diseases re-escalated the death rate of TB. WHO has already cautioned about the chances of pandemic situation in TB endemic countries until the discovery of new anti-tubercular drugs, that is, the need of the hour. Analysing the pathogenesis of TB, it was found that M.tb evades the host by altering the balance of immune response and affects either by killing the cells or by creating inflammation. In the pre-antibiotic era, traditional medicines were only therapeutic measures for different infectious diseases including tuberculosis. The ancient literatures of India or ample Indian traditional knowledge and ethnomedicinal practices are evidence for the treatment of TB using different indigenous plants. However, in the light of modern scientific approach, anti-TB effects of those plants and their bioactive molecules were not established thoroughly. In this review, focus has been given on five bioactive molecules of different traditionally used Indian ethnomedicinal plants for treatment of TB or TB-like symptom. These compounds are also validated with proper identification and their mode of action with modern scientific approaches. The effectiveness of these molecules for sensitive or drug-resistant TB pathogen in clinical or preclinical studies was also evaluated. Thus, our specific aim is to highlight such scientifically validated bioactive compounds having anti-mycobacterial and immunomodulatory activity for future use as medicine or adjunct-therapeutic molecule for TB management.     

The role of vergence in the perception of distance: a fair test of Bishop Berkeley's claim

Binocular eye movements were measured while subjects perceived the wallpaper illusion in order to test the claim made by Bishop Berkeley in 1709 that we perceive the distance of nearby objects by evaluating the vergence angles of our eyes. Four subjects looked through a nearby fronto-parallel array of vertical rods (28-35 cm away) as they binocularly fixated a point about 1 meter away. The wallpaper illusion was perceived under these conditions, i.e. the rods appeared farther away than their physical location. We found that although binocular fixation at an appropriate distance was needed to begin perceiving the wallpaper illusion (at least for naive observers), once established, the illusion was quite robust in the sense that it was not affected by changing vergence. No connection between the apparent localization of the rods and vergence was observed. We conclude that it is unlikely that vergence, itself, is responsible for the perceived distance shift in the wallpaper illusion, making it unlikely that vergence contributes to the perception of distance as Bishop Berkeley suggested. We found this to be true even when vergence angles were relatively large (more than 2 deg), the region in which the control of vergence eye movements has been shown to be both fast and effective.     

Local adaptation to salinity in the three‐spined stickleback?

Different lines of evidence suggest that the occurrence and extent of local adaptation in high gene flow marine environments – even in mobile and long‐lived vertebrates with complex life cycles – may be more widespread than earlier thought. We conducted a common garden experiment to test for local adaptation to salinity in Baltic Sea sticklebacks (Gasterosteus aculeatus). Fish from three different native salinity regimes (high, mid and low) were subjected to three salinity treatments (high, mid and low) in a full‐factorial experimental design. Irrespective of their origin, fish subjected to low (and mid) salinity treatments exhibited higher juvenile survival, grew to largest sizes and were in better condition than fish subjected to the high salinity treatment. However, a significant interaction between native and treatment salinities – resulting mainly from the poor performance of fish native to low salinity in the high salinity treatment – provided clear cut evidence for adaptation to local variation in salinity. Additional support for this inference was provided by the fact that the results concur with an earlier demonstration of significant differentiation in a number of genes with osmoregulatory functions across the same populations and that the population‐specific responses to salinity treatments exceeded that to be expected by random genetic drift.     

Revisiting the Relationship between Individual Differences in Analytic Thinking and Religious Belief: Evidence That Measurement Order Moderates Their Inverse Correlation

Prior research has found that persons who favor more analytic modes of thought are less religious. We propose that individual differences in analytic thought are associated with reduced religious beliefs particularly when analytic thought is measured (hence, primed) first. The current study provides a direct replication of prior evidence that individual differences in analytic thinking are negatively related to religious beliefs when analytic thought is measured before religious beliefs. When religious belief is measured before analytic thinking, however, the negative relationship is reduced to non-significance, suggesting that the link between analytic thought and religious belief is more tenuous than previously reported. The current study suggests that whereas inducing analytic processing may reduce religious belief, more analytic thinkers are not necessarily less religious. The potential for measurement order to inflate the inverse correlation between analytic thinking and religious beliefs deserves additional consideration.     

What is clinical effectiveness?

Clinical trials and other forms of evaluation of medical treatment are held to give an objective assessment of the ‘clinical effectiveness’ of the medical treatments under evaluation. This kind of evaluation is central to the evidence-based medicine movement, as it provides a basis for the rational selection of treatment. The ethical status of randomised clinical trials is widely agreed to depend crucially upon the state of equipoise regarding which of two (or more) treatments is more (or most) effective in a defined population. However, the meaning and nature of ‘clinical effectiveness’ are unclear. in this paper, I discuss the proposals to define clinical effectiveness as a relational property and as an intrinsic property, and the way effectiveness may supervene upon more fundamental physical properties of treatments. I discuss whether effectiveness is a single property or a family of properties; the types of outcome which can be explained by effectiveness properties; and the relationship between ‘objective’ and ‘preference’ outcomes. This paper suggests that while it may be possible to put clinical effectiveness on a proper metaphysical footing, in practice the language of clinical effectiveness is more properly a topic of the human sciences than of the natural sciences.     

The Impact of Spatial Incongruence on an Auditory-Visual Illusion

Background

The sound-induced flash illusion is an auditory-visual illusion – when a single flash is presented along with two or more beeps, observers report seeing two or more flashes. Previous research has shown that the illusion gradually disappears as the temporal delay between auditory and visual stimuli increases, suggesting that the illusion is consistent with existing temporal rules of neural activation in the superior colliculus to multisensory stimuli. However little is known about the effect of spatial incongruence, and whether the illusion follows the corresponding spatial rule. If the illusion occurs less strongly when auditory and visual stimuli are separated, then integrative processes supporting the illusion must be strongly dependant on spatial congruence. In this case, the illusion would be consistent with both the spatial and temporal rules describing response properties of multisensory neurons in the superior colliculus.

Methodology/Principal Findings

The main aim of this study was to investigate the importance of spatial congruence in the flash-beep illusion. Selected combinations of one to four short flashes and zero to four short 3.5 KHz tones were presented. Observers were asked to count the number of flashes they saw. After replication of the basic illusion using centrally-presented stimuli, the auditory and visual components of the illusion stimuli were presented either both 10 degrees to the left or right of fixation (spatially congruent) or on opposite (spatially incongruent) sides, for a total separation of 20 degrees.

Conclusions/Significance

The sound-induced flash fission illusion was successfully replicated. However, when the sources of the auditory and visual stimuli were spatially separated, perception of the illusion was unaffected, suggesting that the “spatial rule” does not extend to describing behavioural responses in this illusion. We also find no evidence for an associated “fusion” illusion reportedly occurring when multiple flashes are accompanied by a single beep.     

Subjective figures and texture perception

A texture discrimination task using the Ehrenstein illusion demonstrates that subjective brightness effects can play an essential role in early vision. The subjectively bright regions of the Ehrenstein can be organized either as discs or as stripes, depending on orientation. The accuracy of discrimination between variants of the Ehrenstein and control patterns was a direct function of the presence of the illusory brightness stripes, being high when they were present and low otherwise. It is argued that neither receptive field structure nor spatial-frequency content can adequately account for these results. We suggest that the subjective brightness illusions, rather than being a high-level, cognitive aspect of vision, are in fact the result of an early visual process.     

Questionable Gate-keeping: Scientific Evidence for Complementary and Alternative Medicines (CAM): Response to Malcolm Parker

The more popular complementary and alternative medicine (CAM) has become, the more often it is demanded that the integration of CAM should be limited to those approaches that are scientifically proven to be effective. This paper argues that this demand is ethically and philosophically questionable. The clinical legitimacy being gained by CAM and its increasing informal integration should instead caution against upholding the biomedical framework and evidence-based medicine as conditions of acceptance. Patients’ positive experiences with CAM deserve a truly scientific exploration of non-biomedical conceptualizations of health and illness. It is also problematic to request scientific evidence when there is proven resistance against CAM in research institutions, under-funding and a lack of suitable research methodologies. This is even more so, when much conventional medicine is not practiced with the same level of evidence as demanded from CAM.     

Thirteen follies and fallacies about alternative medicine

Thirteen common misunderstandings about alternative medicine and the consequences for health.The use of alternative medicine (AM)—treatments such as herbs or massage therapy—has long been a part of healthcare in many regions of the world “to complement mainstream medicine by contributing to a common whole, by satisfying a demand not met by orthodoxy or by diversifying the conceptual frameworks of medicine” [1]. What AM cannot do is replace conventional treatment, particularly when it comes to serious or even life-threatening conditions. Nevertheless, many AM apologists insist that it can do so, that it is an alternative rather than a complement. This assumption can confuse patients and even endanger their lives. In this Opinion article, I explore some of the most common fallacies used to support, justify or promote AM.1. Since many people believe in or practise AM, it is tempting to assume that it is useful. According to this argumentum ad populum, millions cannot all be wrong. However, belief can be wrong, practice can be misguided, and popularity is not a reliable indicator for effectiveness; after all, medicine is no popularity contest. The history of medicine is littered with examples that demonstrate how misleading this fallacy can be. Bloodletting was believed to be effective, was widely practised and highly popular, yet it certainly killed more patients than it ever helped.2. The classic post hoc, ergo propter hoc fallacy—‘it worked for me (my aunt, my cat etc)''—is firmly engrained into the human mind. If a patient receives a treatment and then gets better, what could be more logical than to assume that the treatment was the cause of the improvement? This conclusion seems as obvious to patients—and many clinicians—as it is fallacious. Proponents of AM employ this fallacy incessantly to convince us that ineffective treatments are, in fact, effective.Apart from the treatment per se, a whole range of phenomena exists that can cause or contribute to improvement: the placebo effect, the natural history of the illness, the regression towards the mean and so on. It means that patients can get better after administering useless or even mildly harmful remedies; subsequently is not the same as consequently. Causal inferences based on anecdotes are therefore highly problematic and certainly no sound basis for robust conclusions about the efficacy of therapeutic interventions.Most apologists for AM argue that it is of secondary importance how a given type of AM works. Even if it were a pure placebo, they say, it would still help suffering patients through a placebo response, and surely that must be a good thing. In other words, the mechanism of the effect is of little practical relevance and what counts most is to help the patient.This fallacy ignores several important issues. The administration of placebos in clinical routine can be unethical and dangerous, but is also not necessary to produce a placebo response. If a clinician administers an effective therapy with empathy and compassion, he or she generates a placebo effect in addition to the specific therapeutic effect. Exclusively relying on placebos therefore deprives the patient of the latter.3. Apologists for AM like to cite statistics that show how a sizeable percentage of all conventional treatments is not supported by sound evidence. Thus, they argue, it is unfair to insist on AM being solidly evidence-based. Unquestionably, many conventional therapies are currently not evidence-based. Yet, this is hardly a reasonable justification for using unproven or disproven forms of AM. Unreliable railways do not get more acceptable because thousands of people get stuck in traffic jams on the roads.4. The adverse effects of conventional medicine are argued to be so serious and frequent that those of AM are negligible. While it is true that the risks of some conventional treatments are greater than those of some forms of AM, this is beside the point. The real value of a treatment is not determined by its absolute risk but by the balance between risk and benefit. If a treatment is potentially life-saving, substantial risks can be tolerated. If a therapy has no benefit, even a small risk would weigh heavily and the risk–benefit balance would not be positive.5. Whenever scientific investigations fail to show what they had hoped for, apologists for AM claim that science cannot be meaningfully applied to their field. Their type of AM, they insist, is holistic, individualized, complex, relies on subtle, unquantifiable energies and so on, and these circumstances prevent it from being squeezed into the straight jacket of reductionist science. After all, there are many things “between heaven and earth” that science will never be able to capture.Science certainly has its limits. Yet, when it comes to testing therapeutic claims, it provides us with fairly adequate tools to assess them. Even if the claim is that a particular holistic, individualised and complex form of energy healing makes you feel better, live longer or experience life more wholesomely, the hypothesis is scientifically testable. Even if no validated outcome measure exists for a particular claim, scientists should be able to develop one. The notion that “a therapy defies scientific testing” merely discloses a lack of understanding of what science can achieve.6. Most people would probably agree that many AM practitioners are well intentioned. There is also evidence that they are capable of building up a good therapeutic relationship with their patients [3]. To extrapolate from such data that AM is useful would, however, be erroneous. Compassion, empathy and good interactions with patients are certainly important, but they are not a monopoly of AM. In fact, these qualities are among the hallmarks of any good healthcare. To imply that only AM practitioners possess them is wrong and an insult to the many clinicians who are doing their best to implement patient-centred care, often under difficult circumstances.7. Many forms of AM are said to have long histories that must surely count for something; any treatment that has stood the test of time must be useful. Some practitioners of AM even insist that the “test of time” is more relevant than that of science. A long tradition of use can, of course, be an indicator of the safety and efficacy of a treatment, but it can never be proof. On the contrary, a long history might just indicate that the origins of that therapy reach back to a time when anatomy and physiology, among other things, were not well understood. This, in turn, might lessen the chances that any such intervention is plausible or effective. Treatments such as bloodletting or purging again provide apt examples.8. Enthusiasts of AM tend to appeal to authority in various ways. They may state that a government organization endorses particular modalities, that respectable pharmacies sell AM preparations, that the royal family uses them, that Nobel-prize winners support them and so on. These claims may well be true, but to infer that such endorsements render AM valuable would be fallacious. Endorsements of this kind might merely show that even well-educated, authoritative people or institutions can sometimes commit silly mistakes.9. An entire industry has developed around the notion that AM is natural and therefore cannot do any harm. The implication is that conventional treatments are based on unnatural chemicals, which are potentially harmful. Nature, by contrast, is benign and natural remedies are to be preferred. This argument is as effective for marketing purposes as it is fallacious. Firstly, by no means are all forms of AM natural. For instance, there is nothing natural in sticking needles into a patient''s body (as in acupuncture) or endlessly diluting and shaking a medicine (as in homeopathy). Secondly, Nature is not necessarily benign. Even herbal extracts from natural sources are not necessarily safe [2]—think of hemlock.10. Many AM enthusiasts seem to believe that powerful intrigues aim at suppressing the knowledge of AM about how to heal the sick. The pharmaceutical industry is often cited in this context. The underlying assumption is that the pharmaceutical sector would lose substantial amounts of revenue if the true value of this or that form of AM became general knowledge. I have never seen any evidence to suggest that this notion is true or that those who make such claims can produce good evidence for it. In my experience, the pharmaceutical industry is barely aware of AM or, when it is, it has found ways of profiting from it by marketing ‘natural'' supplements.11. If ‘big pharma'' is not in the frame, other institutions or professionals might be. Oncologists, for instance, are said to disregard and suppress alternative methods claimed to be cancer cures. Yet I have never met a single oncologist who would not be delighted to see an effective cancer cure emerge or who would care one iota whether it originates from the field of AM or from any other source.12. Absence of evidence is not evidence of absence of effect. If, for a given form of AM, we have no or no good evidence for its effectiveness, we cannot assume that it is ineffective. The principle is, of course, entirely correct. We have not identified life on other planets, for instance, but we cannot be sure that no extraterrestrial life exists. However, the conclusion some AM apologists draw from this principle is grossly misleading. They argue that it is reasonable to use the treatment in question until evidence emerges that proves it to be ineffective. In healthcare, it is unwise and arguably unethical to give the benefit of the doubt to under-researched therapies. In the interest of our patients, we should use treatments that are supported by sound evidence for effectiveness, while those that do not fall into this category should be avoided.13. AM is dominated by strong beliefs rather than sound evidence. Thus, it is perhaps unsurprising that some believers resort to ad hominem attacks, particularly when they have run out of rational arguments against their critics. During the past 20 years of researching AM, I have received my fair share of such personal attacks that attempt to undermine my authority and integrity. For instance, it has been claimed that I am not qualified to do the work that I do, that I am guilty of scientific misconduct, that I am on the payroll of ‘big pharma'', or that I have personal reasons to be biased. The aim of ad hominem attacks is to discredit an opponent and, for some fanatic believers, this aim seems to justify even the most drastic means.AM is plagued by fallacies that confuse or mislead the public and thus prevent many patients from making the right therapeutic decisions. A good example is the attitude of many AM apologists regarding immunization [2]. They tend to combine several of the above-listed fallacies into a series of grossly misleading arguments: vaccinations are not as effective as they are made out to be, and infection rates actually declined because of better hygiene; vaccinations frequently cause serious problems, such as autism; famous and intelligent people have refused to vaccinate their children; vaccinations are unnatural, while the alternative options are natural and safe; vaccinations are pushed by ‘big pharma'' to enrich their shareholders; just because there is no evidence for the alternatives, this does not mean they are not effective; and the experts who speak out in favour of vaccinations are corrupt.This example highlights the fact that much harm can be done by falling for the plethora of fallacies that dominate the field of AM. It is therefore important to discuss these arguments openly and disclose them for what they truly are: often seemingly plausible notions that are actually misleading to the point of endangering public health.     

Perception,Price and Preference: Consumption and Protection of Wild Animals Used in Traditional Medicine

A wide array of wildlife species, including many animals, are used in traditional medicines across many medicinal systems, including in Traditional Chinese Medicine (TCM). Due to over-exploitation and habitat loss, the populations of many animals commonly used in TCM have declined and are unable to meet market demand. A number of measures have been taken to try to reduce the impact that this large and growing market for TCM may have on wild animal species. Consumer preferences and behavior are known to play an important role in the consumption and protection of wild animals used in traditional medicine, and thus are likely to be an important factor in the success of many of these mechanisms—particularly given the significant percentage of TCMs that are over-the-counter products (access to which is not mediated by practitioners). In this study we conducted questionnaires and designed stated preference experiments embodying different simulation scenarios using a random sample of the population in Beijing to elicit individuals’ knowledge, perceptions and preferences toward wild or farmed animal materials and their substitutes used in traditional Chinese medicine. We found that respondents had a stated preference for wild materials over farm-raised and other alternatives because they believe that the effectiveness of wild-sourced materials is more credible than that of other sources. However, we also found that, although respondents used TCM products, they had a poor understanding of the function or composition of either traditional Chinese medicines or proprietary Chinese medicines (PCM), and paid little attention to the composition of products when making purchasing decisions. Furthermore, awareness of the need for species protection, or “conservation consciousness” was found to play an important role in willingness to accept substitutions for wild animal materials, while traditional animal medicinal materials (TAMs) derived from well-known endangered species, such as bear bile and tiger bone, show relatively higher substitutability. These results suggest that there is still hope for conservation measures which seek to promote a transition to farmed animal, plant and synthetic ingredients and provide clear directions for future social marketing, education and engagement efforts.     

The medium of signs: nominalism, language and the philosophy of mind in the early thought of Dugald Stewart

In 1792 Dugald Stewart published Elements of the philosophy of the human mind. In its section on abstraction he declared himself to be a nominalist. Although a few scholars have made brief reference to this position, no sustained attention has been given to the central role that it played within Stewart's early philosophy of mind. It is therefore the purpose of this essay to unpack Stewart's nominalism and the intellectual context that fostered it. In the first three sections I aver that his nominalism emanated from his belief that objects of the mind--qualities, ideas and words--were signs that bore no necessary relation to the external objects that they were meant to represent. More specifically, it was these signs that were arranged into systems of thought by the 'operations of the mind'. The next three sections suggest that his treatment of words as signs most probably originated in his views on language and medicine and that his nominalistic philosophy of mind could also be extended to systems that sought to classify the natural world. I conclude by suggesting several avenues of enquiry that could be pursued by future scholars interested in excavating Stewart's thought.     

WHO Essential Medicines Policies and Use in Developing and Transitional Countries: An Analysis of Reported Policy Implementation and Medicines Use Surveys

Background

Suboptimal medicine use is a global public health problem. For 35 years the World Health Organization (WHO) has promoted essential medicines policies to improve quality use of medicines (QUM), but evidence of their effectiveness is lacking, and uptake by countries remains low. Our objective was to determine whether WHO essential medicines policies are associated with better QUM.

Methods and Findings

We compared results from independently conducted medicines use surveys in countries that did versus did not report implementation of WHO essential medicines policies. We extracted survey data on ten validated QUM indicators and 36 self-reported policy implementation variables from WHO databases for 2002–2008. We calculated the average difference (as percent) for the QUM indicators between countries reporting versus not reporting implementation of specific policies. Policies associated with positive effects were included in a regression of a composite QUM score on total numbers of implemented policies. Data were available for 56 countries. Twenty-seven policies were associated with better use of at least two percentage points. Eighteen policies were associated with significantly better use (unadjusted p<0.05), of which four were associated with positive differences of 10% or more: undergraduate training of doctors in standard treatment guidelines, undergraduate training of nurses in standard treatment guidelines, the ministry of health having a unit promoting rational use of medicines, and provision of essential medicines free at point of care to all patients. In regression analyses national wealth was positively associated with the composite QUM score and the number of policies reported as being implemented in that country. There was a positive correlation between the number of policies (out of the 27 policies with an effect size of 2% or more) that countries reported implementing and the composite QUM score (r = 0.39, 95% CI 0.14 to 0.59, p = 0.003). This correlation weakened but remained significant after inclusion of national wealth in multiple linear regression analyses. Multiple policies were more strongly associated with the QUM score in the 28 countries with gross national income per capita below the median value (US$2,333) (r = 0.43, 95% CI 0.06 to 0.69, p = 0.023) than in the 28 countries with values above the median (r = 0.22, 95% CI −0.15 to 0.56, p = 0.261). The main limitations of the study are the reliance on self-report of policy implementation and measures of medicine use from small surveys. While the data can be used to explore the association of essential medicines policies with medicine use, they cannot be used to compare or benchmark individual country performance.

Conclusions

WHO essential medicines policies are associated with improved QUM, particularly in low-income countries. Please see later in the article for the Editors'' Summary