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The most commonly encountered and most serious objection against consequentialist theories of punishment is that they could sometimes endorse punishing innocent people. Two-level consequentialists can resist this objection. Because of how deterrence works, a system of social protection would clearly need to be careful, most of the time, to pick out only the guilty for punishment. What about exceptional cases? Any institution empowered to secretly frame innocent people would pose a grave danger to democracy, a danger that could prove lethal under only moderately unusual conditions. Meanwhile, individual consequentialists working within the criminal justice system should fear that their own views could be distorted by confirmation bias and other cognitive errors. These officials should normally trust any moderately well-functioning adversarial trial process more than they trust their own judgment of who needs to be punished. They should use extra-legal discretion only in cases where both their confidence an...

Countermeasures against potential biothreat agents remain important to US Homeland Security, and many of these pharmaceuticals could have dual use in the improvement of global public health. Junin virus, the causative agent of Argentine hemorrhagic fever (AHF), is an arenavirus identified as a category A high-priority agent. There are no Food and Drug Administration (FDA) approved drugs available for preventing or treating AHF, and the current treatment option is limited to administration of immune plasma. Whereas immune plasma demonstrates the feasibility of passive immunotherapy, it is limited in quantity, variable in quality, and poses safety risks such as transmission of transfusion-borne diseases. In an effort to develop a monoclonal antibody (mAb)-based alternative to plasma, three previously described neutralizing murine mAbs were expressed as mouse-human chimeric antibodies and evaluated in the guinea pig model of AHF. These mAbs provided 100% protection against lethal challenge when administered 2 d after infection (dpi), and one of them (J199) was capable of providing 100% protection when treatment was initiated 6 dpi and 92% protection when initiated 7 dpi. The efficacy of J199 is superior to that previously described for all other evaluated drugs, and its high potency suggests that mAbs like J199 offer an economical alternative to immune plasma and an effective dual use (bioterrorism/public health) therapeutic.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10(6) PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a human anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment.

Traditional Buddhist views of karma as a cosmic force that makes the universe fair have little credibility in contemporary philosophy. However, a naturalized account of karma, understanding it as a psychological process, could easily turn out to be true. If we read between the lines of Śāntideva’s classic Training Anthology, there is reason to believe that some of his sources already had such a psychological view in mind. A modernized account of karma would have important implications for the theoretical structure of Buddhist ethics, the prospects for a Buddhist political philosophy, and the practice of Engaged Buddhism in contemporary society.

As observed during the 2013–2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus–infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings.

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use. A new treatment, containing an optimized cocktail of three monoclonal antibodies against Ebola virus, provided full protection and disease reversal in rhesus monkeys when given under conditions in which controls succumbed by day 8; this new therapy may be a good candidate for treating Ebola virus infection in human patients. This study shows that ZMapp, an optimized cocktail of three monoclonal antibodies that has been pressed into clinical use in response to the current Ebola virus disease epidemic, was able to rescue all of 18 rhesus macaques when treatment was initiated up to five days post-infection. All three controls had died by day eight.

Does the decision to relax by taking a drive rather than by taking a walk cause harm? In particular, do the additional carbon emissions caused by such a decision make anyone worse off? Recently several philosophers have argued that the answer is no, and on this basis have gone on to claim that act-consequentialism cannot provide a moral reason for individuals to voluntarily reduce their emissions. The reasoning typically consists of two steps. First, the effect of individual emissions on the weather is miniscule: the planet’s meteorological system is so large, and the size of individual emissions so tiny, that whatever impact an individual emission has on the weather must be vanishingly small. Second, vanishingly small impacts aren’t morally relevant because no one could possibly tell the difference between such an impact occurring and it not occurring. In this paper, we show why both steps are mistaken, and hence why act-consequentialism implies that each of us has an individual obligation to do what we can to stop damaging the climate, including by refraining from, or perhaps by purchasing offsets against, our own individual luxury carbon emissions.

Respiratory syncytial virus (RSV) can cause devastating lower respiratory tract infections in preterm infants or when other serious health problems are present. Immunoprophylaxis with palivizumab (Synagis), a humanized IgG1 mAb, is the current standard of care for preventing RSV infection in at-risk neonates. We have explored the contribution of effector function to palivizumab efficacy using a plant-based expression system to produce palivizumab N-glycan structure variants with high homogeneity on different antibody isotypes. We compared these isotype and N-glycoform variants with commercially available palivizumab with respect to both in vitro receptor and C1q binding and in vivo efficacy. Whereas the affinity for antigen and neutralization activity of each variant were indistinguishable from those of palivizumab, their Fcγ receptor binding profiles were very different, which was reflected in either a reduced or enhanced ability to influence the RSV lung titer in challenged cotton rats. Enhanced Fcγ receptor binding was associated with reduced viral lung titers compared with palivizumab, whereas abrogation of receptor binding led to a drastic reduction in efficacy. The results support the hypotheses that classic antibody neutralization is a minor component of efficacy by palivizumab in the cotton rat and that antibody-dependent cell-mediated cytotoxicity activity can significantly enhance the efficacy of this antiviral mAb.

Recent incidents in the United States and abroad have heightened concerns about the use of ricin toxin as a bioterrorism agent. In this study, we produced, using a robust plant-based platform, four chimeric toxin-neutralizing monoclonal antibodies that were then evaluated for the ability to passively protect mice from a lethal-dose ricin challenge. The most effective antibody, c-PB10, was further evaluated in mice as a therapeutic following ricin exposure by injection and inhalation.

Owen Flanagan's important book The Bodhisattva's Brain presents a naturalized interpretation of Buddhist philosophy. Although the overall approach of the book is very promising, certain aspects of its presentation could benefit from further reflection. Traditional teachings about reincarnation do not contradict the doctrine of no self, as Flanagan seems to suggest; however, they are empirically rather implausible. Flanagan's proposed “tame” interpretation of karma is too thin; we can do better at fitting karma into a scientific worldview. The relationship between eudaimonist and utilitarian strands in Buddhist ethics is more complex than the book suggests. Flanagan is right to criticize incautious and imprecise claims that Buddhism will make practitioners happy. We can make progress by distinguishing between happiness in the sense of a Buddhist version of eudaimonia, and happiness in the sense of attitudinal pleasure. Doing so might result in an interpretation of Buddhist views about happiness that was simultaneously philosophically interesting, historically credible, and psychologically testable.

Of all the Buddhist teachers whose writings have come down to us, only Śāntideva has yet been shown to have engaged in sustained, general theoretical reflection about ethics. Śāntideva offers a radical critique of the rationality of most emotions, similar in some ways to that of the Stoics. His overall view has important similarities with utilitarianism; and he offers philosophical arguments for a distinctively utilitarian form of impartiality. Śāntideva quotes scriptures that make hyperbolic and implausible claims about the relative value of different practices; it may be possible to interpret these passages in terms of the lexical priority of some values over others. He also tells us that the various Buddhist virtues reinforce and sustain each other. These claims could be used to construct a homeostatic cluster view of well-being.

Albahari, Miri, Analytical Buddhism: The Two-Tiered Illusion of Self, Basingstoke & New York: Palgrave Macmillan, 2006, pp. xiv + 235, £45.00 (cloth). Analytical Buddhism is a valuable and highly o...

In defending the teaching of emptiness, Bhāvaviveka offers some very strange arguments, which initially may appear so weak that we may be hard pressed to understand how anyone could endorse them. To make sense of these passages, it is helpful to compare them to an argument found in the writings of the Naiyāyika Uddyotakara. These arguments have a certain formal feature which makes them count as valid from the point of view of the rules and norms of some forms of Indian logic. Once we understand the logical structure of the arguments offered by Uddyotakara and Bhāvaviveka, we will not only have a better grasp on their philosophical views, but we will also be in a better position to understand how and why those views were rejected by later figures in the Indian tradition, such as Dharmakīrti and Śāntarak⋅ita.

We have found heat inactivation of leukocyte 4-methylumbelliferyl-beta-D-glucosidase to be useful in identifying heterozygotes for adult (chronic) Gaucher's disease. The overlap between high heterozygote values and low normal values is reduced by the heat inactivation step, compared to assays without heating; that is from an overlap of 23% to 6%. Although preliminary, our results indicate that this procedure may be useful in families with adult (chronic) Gaucher's disease.

might be enriched by the ideas of the other. However, such a dialogue will be very difficult unless we Westerners can find some way of understanding, in our terms, what kind of ethical theory Buddhism might involve. Damien Keown's influential work on this topic has convinced many scholars that Buddhist ethical views are not very similar to utilitarianism. Keown holds that these views should be understood through analogies with Aristotelian virtue ethics. However, if we draw on current debates in Western ethics to clarify the range of theories available for comparison, Keown's position becomes less plausible. Though a case could be made that no form of Buddhist ethics is as similar to Aristotelianism as Keown claims, I focus here on Mah?y?na Buddhism. There are several Indian Mah?y?na texts that express an ethical perspective that has many features in common with the various versions of universalist consequentialism. Of these versions, the one that seems most promising as a basis of comparison with Mah?y?na views has sometimes been called "?deal Utilitarianism" or "perfectionist consequentialism." Consequentialism is a broad and diverse family of ethical theories. Each of these theories gives consequences some kind of decisive role in deciding how we should behave. Thus, an act-consequential ist ethical theory says that actions should be eval uated with reference only to their consequences. Meanwhile, a rule-consequentialist theory says that we should follow a set of rules whose acceptance would, under some specified circumstances, bring about the best consequences. Various rule consequentialist theories involve endorsing rules that would produce the best conse quences if everybody followed them; or merely if everybody tried to follow them; or perhaps if enough people tried to follow them. And there are additional forms of consequentialism that trace the rightness of actions to consequences in some other indirect way, such as through the motives of the agent. The consequentialist theories that I want to put forward as models of Mah?y?na ethics are universalist: they take into account consequences for all sentient beings over the entire future history of the universe. I will be ignoring those consequentialist theories that are not welfarist, in that they assign intrinsic value to states of affairs that have nothing to do with the goodness of the lives of sentient beings. I shall take it as obvious that the beauty of rock formations and the balance of ecosystems, for exam ple, are not the sorts of matters with which Indian Buddhist ethical thinkers were pri marily concerned.1

Most modern analytic philosophers have ignored works of Indian philosophy such as Vasubandhu's ‘Treasury of Metaphysics’. This neglect is unjustified. The account of the nature of the physical world given in the ‘Treasury’ is a one-category ontology of dharmas, which are simple, momentary tropes. They include bade physical tropes, the most fundamental level of the physical world, as well as higher-level tropes, including sensible properties such as colours, which are known as derived form. I argue that the relationship between the basic physical tropes and derived form is one of supervenience. Vasubandhu's theory is a powerful and flexible one, which can be adapted so as to be consistent with modern science.

Due to the fast-acting nature of ricin, staphylococcal enterotoxin B (SEB), and Clostridium perfringens epsilon toxin (ETX), it is necessary that therapeutic interventions following a bioterrorism incident by one of these toxins occur as soon as possible after intoxication. Moreover, because the clinical manifestations of intoxication by these agents are likely to be indistinguishable from each other, especially following aerosol exposure, we have developed a cocktail of chimeric monoclonal antibodies that is capable of neutralizing all three toxins. The efficacy of this cocktail was demonstrated in mouse models of lethal dose toxin challenge.

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, is among the most lethal toxins known. ETX is a potential bioterrorism threat that was listed as a Category B agent by the U.S. Centers for Disease Control until 2012 and it still remains a toxin of interest for several government agencies. We produced a monoclonal antibody (MAb) against ETX (ETX MAb c4D7) in Nicotiana benthamiana and characterized its preventive and therapeutic efficacy in mice. The ETX preparation used was highly lethal for mice (LD50=1.6μg/kg) and resulted in a mean time from inoculation to death of 18 and 180min when administered intravenously or intraperitoneally, respectively. High lethal challenge resulted in dramatic increases of a variety of pro-inflammatory cytokines in serum, while lower, but still lethal doses, did not elicit such responses. ETX MAb c4D7 was highly effective prophylactically (ED50=0.3mg/kg; ED100=0.8mg/kg) and also provided protection when delivered 15-30min post-ETX intoxication. These data suggest that ETX MAb c4D7 may have use as a pre- and post-exposure treatment for ETX intoxication.

This paper describes a system for minimizing NOx emissions in gas turbines. The system uses an optimization technique implemented on a portable computer. No hardware changes are necessary in the combustion system. The system was developed for an LM6000 Dry Low Emissions (DLE) engine. However, it can be applied across the board on any LM series DLE engine manufactured by the Industrial Aero-derivatives (IAD) division of GE Power Systems (GEPS).Copyright © 2000 by ASME