Transcutaneous immunisation assisted by low-frequency ultrasound.

Low-frequency ultrasound application is known to increase the skin's permeability to large molecules such as vaccines, and to enable transcutaneous immunisation. Sodium dodecyl sulphate (SDS) - a skin irritant - is often included in the coupling medium at 1% (w/v), as this has been found to enhance skin permeability. In this paper we show, for the first time, the feasibility of low-frequency ultrasound-assisted transcutaneous immunisation in the absence of SDS. Antibody titres were strongly influenced by experimental conditions. SDS presence in the coupling medium increased antibody titres, though a lower concentration of 0.5% (w/v) generated much higher titres than the commonly used 1% (w/v), despite causing less skin damage. A lower ultrasound duty cycle of 10% generated higher antibody titres than a duty cycle of 20%, also despite causing lower skin damage. Such lack of correlation between skin damage and immune responses indicates that enhancement of skin permeability to topically applied antigen (as indicated by changes in skin integrity) was not the main mechanism of low-frequency ultrasound-assisted skin immunisation

Use of horseradish peroxidase for gene-directed enzyme prodrug therapy with paracetamol

Gene therapy is a potential method of treating cancer with a greater degree of targeting than conventional therapies. In addition, therapy can be directed towards cells within the tumour population that are traditionally resistant to current treatment schedules. Horseradish peroxidase (HRP) can oxidise paracetamol to N-acetyl-p-benzoquinoneimine via a one-electron pathway. Incubation of human cells expressing HRP with 0.5–10 mm paracetamol reduced clonogenic survival, but had little effect on control cells. A small increase in apoptosis was seen and a decrease in the number of cells undergoing mitosis, consistent with reports in hepatocytes using higher paracetamol concentrations. The cytotoxicity was also seen under conditions of severe hypoxia (catalyst induced anoxia), indicating that the HRP/paracetamol combination may be suitable for hypoxia-targeted gene therapy

Rapid Detection of Botulinum Neurotoxins—A Review

A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent

Are moral norms rooted in instincts? The sibling incest taboo as a case study

1. Are Moral Norms Rooted in Instincts? The Sibling Incest Taboo as a Case Study According to Westermarck's widely accepted explanation of the incest taboo, cultural prohibitions on sibling sex are rooted in an evolved biological disposition to feel sexual aversion toward our childhood coresidents. Bernard Williams posed the "representation problem" for Westermarck's theory: the content of the hypothesized instinct (avoid sex with childhood coresidents) is different from the content of the incest taboo (avoid sex with siblings)—thus the former cannot be causally responsible for the latter. Arthur Wolf posed the related "moralization problem": the instinct concerns personal behavior whereas the prohibition concerns everyone. This paper reviews possible ways of defending Westermarck's theory from the representation and moralization problems, and concludes that the theory is untenable. A recent study purports to support Westermarck's account by showing that unrelated children raised in the same peer groups on kibbutzim feel sexual aversion toward each other and morally oppose third-party intra-peer-group sex, but this study has been misinterpreted. I argue that the representation and moralization problems are general problems that could potentially undermine many popular evolutionary explanations of social/moral norms. The cultural evolution of morality is not tightly constrained by our biological endowment in the way some philosophers and evolutionary psychologists believe. 2. Power in Cultural Evolution and the Spread of Prosocial Norms According to cultural evolutionary theory in the tradition of Boyd and Richerson, cultural evolution is driven by individuals' learning biases, natural selection, and random forces. Learning biases lead people to preferentially acquire cultural variants with certain contents or in certain contexts. Natural selection favors individuals or groups with fitness-promoting variants. Durham (1991) argued that Boyd and Richerson's approach is based on a "radical individualism" that fails to recognize that cultural variants are often "imposed" on people regardless of their individual decisions. Fracchia and Lewontin (2005) raised a similar challenge, suggesting that the success of a variant is often determined by the degree of power backing it. With power, a ruler can impose beliefs or practices on a whole population by diktat, rendering all of the forces represented in cultural evolutionary models irrelevant. It is argued here, based on work by Boehm (1999, 2012), that, from at least the time of the early Middle Paleolithic, human bands were controlled by powerful coalitions of the majority that deliberately guided the development of moral norms to promote the common good. Cultural evolutionary models of the evolution of morality have been based on false premises. However, Durham (1991) and Fracchia and Lewontin's (2005) challenge does not undermine cultural evolutionary modeling in nonmoral domains. 3. A Debunking Explanation for Moral Progress According to "debunking arguments," our moral beliefs are explained by evolutionary and cultural processes that do not track objective, mind-independent moral truth. Therefore (the debunkers say) we ought to be skeptics about moral realism. Huemer counters that "moral progress"—the cross-cultural convergence on liberalism—cannot be explained by debunking arguments. According to him, the best explanation for this phenomenon is that people have come to recognize the objective correctness of liberalism. Although Huemer may be the first philosopher to make this explicit empirical argument for moral realism, the idea that societies will eventually converge on the same moral beliefs is a notable theme in realist thinking. Antirealists, on the other hand, often point to seemingly intractable cross-cultural moral disagreement as evidence against realism (the "argument from disagreement"). This paper argues that the trend toward liberalism is susceptible to a debunking explanation, being driven by two related non-truth-tracking processes. First, large numbers of people gravitate to liberal values for reasons of self-interest. Second, as societies become more prosperous and advanced, they become more effective at suppressing violence, and they create conditions where people are more likely to empathize with others, which encourages liberalism. The latter process is not truth tracking (or so this paper argues) because empathy-based moral beliefs are themselves susceptible to an evolutionary debunking argument. Cross-cultural convergence on liberalism per se does not support either realism or antirealism. 4. Realist Social Selection: How Gene–Culture Coevolution Can (but Probably Did Not) Track Mind-Independent Moral Truth Standard evolutionary debunking arguments (EDAs) in metaethics target moral beliefs by attributing them to natural selection. According to the debunkers, natural selection does not track mind-independent moral truth, so the discovery that our moral beliefs (realistically construed) were caused by natural selection renders them unjustified. I argue that our innate moral faculty is likely not the product of natural selection, but rather social selection. Social selection is a kind of gene–culture coevolution driven by the enforcement of collectively agreed-upon rules. Unlike natural selection, social selection is teleological and could potentially track mind-independent moral truth by a process that I term realist social selection: early humans could have acquired moral knowledge via reason and enforced rules based on that knowledge, thereby creating selection pressures that drove the evolution of our innate moral faculty. Given anthropological evidence that early humans designed rules with the conscious aim of preserving individual autonomy and advancing their collective interests, realist social selection appears to be an attractive theory for moral realists. However, I propose a new EDA to show that realist social selection is unlikely to have occurred. 5. A Debunking How-Possibly Explanation for the Principle of Universal Benevolence According to Street's evolutionary debunking argument (EDA), evolutionary biology provides "powerful" explanations of our "basic evaluative judgements." The discovery that our moral beliefs (realistically construed) are "saturated with evolutionary influence" renders them unjustified, since natural selection does not track mind-independent moral truth. De Lazari-Radek and Singer agree that most of our commonsense moral beliefs are debunked in the way Street claims, but they argue that belief in Sidgwick's principle of universal benevolence cannot be explained by natural selection and is therefore immune from EDAs. I argue that Street oversold the power of her evolutionary explanations, thus leaving an opening for realists to claim that moral beliefs with less powerful evolutionary explanations can escape debunking. In fact, all naturalistic theories of morality—including those invoked by Street and de Lazari-Radek and Singer—are speculative "how-possibly" explanations. If how-possibly explanations are not debunking, then both Street's (global) and de Lazari-Radek and Singer's (selective) debunking arguments fail. If how-possibly explanations are debunking, then selective debunkers must show that there is no plausible way that naturalistic forces could have produced the beliefs they want to defend. I argue that naturalistic how-possibly explanations can debunk moral beliefs by appealing to ontological parsimony, and provide a debunking how-possibly explanation for belief in the principle of universal benevolence

Culture or Biology? If this sounds interesting, you might be confused

Culture or Biology? The question can seem deep and important. Yet, I argue in this chapter, if you are enthralled by questions about our biological differences, then you are probably confused. My goal is to diagnose the confusion. In debates about the role of biology in the social world it is easy to ask the wrong questions, and it is easy to misinterpret the scientific research. We are intuitively attracted to what is called psychological essentialism, and therefore interpret what is biological as what can be traced to “essences”. On this interpretation, it would be deep and important to know what about, say, the differences between the genders is biological: it would correspond to what is essential to being a man or being a woman, and be opposed to what is a mere accidental feature that some women or some men have. Yet, the psychological essentialist understanding of ‘biological differences’ is deeply mistaken about biology. It has the wrong conception of biological kinds, of biological heritability, and of how genes and hormones work. Those who argue for an important role of ‘biology’ in the explanation of human differences often see ‘the science’ on their side. But this is false – on the interpretation of ‘biological differences’ that is most intuitive and that makes the question appear to be most interesting. Defenders of ‘biology’ often have the science against them. What is often called ‘biology’ is a myth: a myth created by an intuitive tendency that grotesquely distorts real biological research

A review of the international issues surrounding the availability and demand for diphtheria antitoxin for therapeutic use.

Diphtheria treatment requires early administration of diphtheria antitoxin (DAT), an immunoglobulin preparation that neutralises circulating diphtheria toxin. Here, we review issues relating to the supply and use of DAT and assess its availability by means of an international survey. Results showed that several countries do not currently hold DAT stockpiles due to low prevalence, and hence perceived risk of diphtheria, and/or difficulties in obtaining DAT supplies. The potential for importation of cases into any country exists globally, since diphtheria remains endemic in many regions. It is therefore important that DAT be readily available - particularly since waning diphtheria immunity has been observed among adult populations in countries with good vaccination coverage. Options for diphtheria therapy are discussed