Page's “localist” code, a population code with occasional, maximally firing elements, does not seem to us usefully or testably different from sparse population coding. Some of the evidence adduced by Page for his proposal is not actually evidence for it, and coding by maximal firing is challenged by lower firing observed in neuronal responses to natural stimuli.

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in (...) placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampalanterior thalamic and the perirhinal–medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition. (shrink)

Schistosomes are parasitic blood flukes, responsible for significant human disease in tropical and developing nations. Here we review information on the organization of the cytoskeleton and associated motor proteins of schistosomes, with particular reference to the organization of the syncytial tegument, a unique cellular adaptation of these and other neodermatan flatworms. Extensive EST databases show that the molecular constituents of the cytoskeleton and associated molecular systems are likely to be similar to those of other eukaryotes, although there are potentially some (...) molecules unique to schistosomes and platyhelminths. The biology of some components, particular those contributing to host–parasite interactions as well as chemotherapy and immunotherapy are discussed. Unresolved questions in relation to the structure and function of the tegument relate to dynamic organization of the syncytial layer. BioEssays 26:752–765, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

ObjectiveTo increase knowledge of how doctors perceive futile treatments and scarcity of resources at the end of life. In particular, their perceptions about whether and how resource limitations influence end-of-life decision making. This study builds on previous work that found some doctors include resource limitations in their understanding of the concept of futility.SettingThree tertiary hospitals in metropolitan Brisbane, Australia.DesignQualitative study using in-depth, semistructured, face-to-face interviews. Ninety-six doctors were interviewed in 11 medical specialties. Transcripts of the interviews were analysed using thematic (...) analysis.ResultsDoctors’ perceptions of whether resource limitations were relevant to their practice varied, and doctors were more comfortable with explicit rather than implicit rationing. Several doctors incorporated resource limitations into their definition of futility. For some, availability of resources was one factor of many in assessing futility, secondary to patient considerations, but a few doctors indicated that the concept of futility concealed rationing. Doctors experienced moral distress due to the resource implications of providing futile treatment and the lack of administrative supports for bedside rationing.ConclusionsDoctors’ ability to distinguish between futility and rationing would be enhanced through regulatory support for explicit rationing and strategies to support doctors’ role in rationing at the bedside. Medical policies should address the distinction between resource limitations and futility to promote legitimacy in end-of-life decision making. (shrink)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

The goal of our target article was to review a number of emerging facts about the effects of limbic damage on memory in humans and animals, and about divisions within recognition memory in humans. We then argued that this information can be synthesized to produce a new view of the substrates of episodic memory. The key pathway in this system is from the hippocampus to the anterior thalamic nuclei. There seems to be a general agreement that the importance of this (...) pathway has previously been underestimated and that it warrants further study. At the same time, a number of key questions remain. These concern the relationship of this system to another temporal-lobe/diencephalic system that contributes to recognition, and the relationship of these systems to prefrontal cortex activity. (shrink)

For some time, the role of culture in language education within schools, universities and professional communication has received increasing attention. This article identifies two aporias in the discourse of intercultural communication : first, that it contains an unstated movement towards a universal consciousness; second, that its claims to truth are grounded in an implicit appeal to a transcendental moral signified.These features constitute IC discourse as ‘totality’, or as ‘metaphysics of presence’.The article draws on the work of Levinas ; and Derrida (...) to propose more considered ethical grounds for intercultural praxis. Contra a Hegelian impetus towards universal consciousness,we posit an irreducible distance and separation between the self and other. In so doing, not only are we able to supersede the field’s implicit appeal to the transcendental as a source of truth but also to counter perceptibly ‘exorbitant’ claims and actions of the intercultural other. In this vein, the article proposes a discourse ethics of responsibility by which it still becomes possible for a critical intercultural praxis to make value judgements and to take potentially transformative action vis-à-vis cultural acts that challenge the limits of intercultural tolerance and hospitality. (shrink)

Recent reports of CRISPR/Cas9 genome editing in parasitic helminths open up new avenues for research on these dangerous pathogens. However, the complex morphology and life cycles inherent to these parasites present obstacles for the efficient application of CRISPR/Cas9‐targeted mutagenesis. This is especially true with the trematode flukes where only modest levels of gene mutation efficiency have been achieved. Current major challenges in the application of CRISPR/Cas9 for study of parasitic worms thus lie in enhancing gene mutation efficiency and overcoming issues (...) involved in host passage so that mutated parasites survive. Strategies developed for CRISPR/Cas9 studies on Caenorhabditis elegans, protozoa and mammalian cells, including novel delivery methods, the choice of selectable markers, and refining mutation precision represent novel tactics whereby these impediments can be overcome. Furthermore, employing CRISPR/Cas9‐mediated gene drive to interfere with vector transmission represents a novel approach for the control of parasitic worms that is worthy of further exploration. (shrink)

Despite the known positive effects of acute exercise on cognition, the effects of a competitive team sport match are unknown. In a randomized crossover design, 20 female and 17 male field hockey players completed a battery of cognitive tests prior to, at half-time, and immediately following a competitive match ; with effect sizes presented as raw ES from mixed effect models. Blood samples were collected prior to and following the match and control trial, and analyzed for adrenaline, noradrenaline, brain derived (...) neurotrophic factor, cathepsin B, and cortisol. The match improved response times for a simple perception task at full-time and response times on the complex executive function task improved at half-time. Working memory declined at full-time on the match. The change in working memory was negatively correlated with increases in cortisol, as was the change in simple perception response time and the change in noradrenaline concentration. This study is the first to highlight the effects a competitive hockey match can have on cognition. These findings have implications for performance optimization, as understanding the influence on specific cognitive domains across a match allows for the investigation into strategies to improve these aspects. (shrink)

Objectives To determine the role played by law in medical specialists9 decision-making about withholding and withdrawing life-sustaining treatment from adults who lack capacity, and the extent to which legal knowledge affects whether law is followed. Design Cross-sectional postal survey of medical specialists. Setting The two largest Australian states by population. Participants 649 medical specialists from seven specialties most likely to be involved in end-of-life decision-making in the acute setting. Main outcome measures Compliance with law and the impact of legal knowledge (...) on compliance. Results 649 medical specialists (of 2104 potential participants) completed the survey (response rate 31%). Responses to a hypothetical scenario found a potential low rate of legal compliance, 32% (95% CI 28% to 36%). Knowledge of the law and legal compliance were associated: within compliers, 86% (95% CI 83% to 91%) had specific knowledge of the relevant aspect of the law, compared with 60% (95% CI 55% to 65%) within non-compliers. However, the reasons medical specialists gave for making decisions did not vary according to legal knowledge. Conclusions Medical specialists prioritise patient-related clinical factors over law when confronted with a scenario where legal compliance is inconsistent with what they believe is clinically indicated. Although legally knowledgeable specialists were more likely to comply with the law, compliance in the scenario was not motivated by an intention to follow law. Ethical considerations (which are different from, but often align with, law) are suggested as a more important influence in clinical decision-making. More education and training of doctors is needed to demonstrate the role, relevance and utility of law in end-of-life care. (shrink)

In resistance training, the use of predicting proximity to momentary task failure, and repetitions in reserve scales specifically, is a growing approach to monitoring and controlling effort. However, its validity is reliant upon accuracy in the ability to predict MF which may be affected by congruence of the perception of effort compared with the actual effort required. The present study examined participants with at least 1 year of resistance training experience predicting their proximity to MF in two different experiments using (...) a deception design. Within each experiment participants performed four trials of knee extensions with single sets to their self-determined repetition maximum and MF. For the first experiment participants used loads equal to 70% of a one repetition maximum performed in a separate baseline session. Aiming to minimize participants between day variability in repetition performances, in the second separate experiment they used loads equal to 70% of their daily isometric maximum voluntary contraction. Results suggested that participants typically under predicted the number of repetitions they could perform to MF with a meta-analytic estimate across experiments of 2.0 [95%CIs 0.0 to 4.0]. Participants with at least 1 year of resistance training experience are likely not adequately accurate at gauging effort in submaximal conditions. This suggests that perceptions of effort during resistance training task performance may not be congruent with the actual effort required. This has implications for controlling, programming, and manipulating the actual effort in resistance training and potentially on the magnitude of desired adaptations such as improvements in muscular hypertrophy and strength. (shrink)

ABSTRACT:A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on (...) rule following, the framework is designed to build researchers’ capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers’ intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework. (shrink)

A better understanding of how schistosomes exploit host nutrients, neuro‐endocrine hormones and signalling pathways for growth, development and maturation may provide new insights for improved interventions in the control of schistosomiasis. This paper describes recent advances in the identification and characterisation of schistosome tyrosine kinase and signalling pathways. It discusses the potential intervention value of insulin signalling, which may play an important role in glucose uptake and carbohydrate metabolism in schistosomes, providing the nutrients essential for parasite growth, development and, notably, (...) female fecundity. Significant progress has also been made in the characterisation of other schistosome growth factor receptors, such as transforming growth factor beta receptor and epidermal growth factor receptor, and in our understanding of their roles in the host‐parasite molecular dialogue and parasite development. The use of parasite signal transduction components as novel vaccine or drug targets may prove invaluable in prevention, treatment and control strategies to combat schistosomiasis. (shrink)

According to non-doxastic theories of propositional faith, belief that p is not necessary for faith that p. Rather, propositional faith merely requires a ‘positive cognitive attitude’. This broad condition, however, can be satisfied by several pragmatic approaches to a domain, including fictionalism. This paper shows precisely how fictionalists can have faith given non-doxastic theory, and explains why this is problematic. It then explores one means of separating the two theories, in virtue of the fact that the truth of the propositions (...) in a discourse is of little consequence for fictionalists, whereas their truth matters deeply for the faithful. Although promising, this approach incurs several theoretical costs, hence providing a compelling reason to favour a purely doxastic account of faith. (shrink)

According to the seventh-century C.E. philosopher Kumārila Bhat.t.a, epistemic agents are warranted in taking their world-presenting experiences as veridical, if they lack defeaters. For him, these experiences are defeasibly sources of knowledge without the agent reflecting on their content or investigating their causal origins. This position is known as svatah prāmāṇya in Sanskrit (henceforth the SP principle). -/- As explicated by the eleventh-century commentator, Pārthasārathi Misŕa, this position entails that epistemic agents know things without simultaneously knowing that they know them, (...) or being in a position to know that they know. In contrast, some contemporary Anglo-analytic philosophers argue for the “knows-knows principle” (KK principle), in which if someone knows that p, then that person also knows that they know that p, or that person is in a position to know that they know p. Despite some apparent similarities, the SP principle is not a version of the KK principle, nor would Pārthasārathi’s Kumārila have held the KK principle. -/- Recently, Daniel Immerman (2018) has argued that the SP principle is a position-to-know version of the “knows-knows principle” (KK-pos principle). By examining Kumārila’s response to his Buddhist opponent, who challenges the veracity of Vedic testimony, we will see that Kumārila understands higher-order knowing as involving an independent check on one’s epistemic processes, through an epistemic instrument known as postulation (arthāpatti). This precludes him from holding the KK-pos principle. (shrink)

In making his distinction between revisionary and descriptive metaphysics, P.F. Strawson wrote that the former has some value provided that its "partial vision" is at the service of the latter, "which needs no justification at all beyond that of inquiry in general." (Individuals, p. 9) Perhaps we feel no need to ask what justification there is for inquiry in general. But if we do recognize any such need, then we discover that inquiry is self-justifying. The more I put it into (...) question, the more I bring the theme of my inquiry to light in my performance of inquiring. Questioning is the business of philosophers. They are now content to leave the search for detailed information to experts in the various disciplines that have won their independence from philosophy. The questioning a philosopher conducts is of the 'second-order'. He asks about the status of various sorts of questions, the types of knowledge they yield and of con fusion into which they lead. (shrink)

This collection of essays by leading patristic scholars of the U.K. and Germany illuminates aspects of the relation between Christian faith and Greek philosophy.

The psychological work environment is composed of both stressful and motivational work conditions at different levels of analysis. However, most relevant theory and research lack an integrative conceptualization and appropriate instrumentation to account for this work context structure. These limitations are particularly present in non-mainstream populations, such as the Spanish community of researchers and practitioners. In this study, based on the job demands–resources model, we present an updated conceptualization in which stressful and motivational psychosocial factors are integrated and defined at (...) the job, the group, and the organizational level of analysis into a single conceptualization. Furthermore, derived from this conceptualization, we present a study of the development and validation of a questionnaire to account for the psychosocial work environment in Spanish, labeled Psychosocial Factors Questionnaire 75, which provides measures for 23 different psychosocial factors. The results of this study supported the questionnaire’s construct, convergent, divergent, and predictive validity, together with its reliability. Thus, this conceptualization and questionnaire provides researchers and partitioners with a more comprehensive approach to the assessment of the psychosocial work environment and promises benefits for interventions in the workplace. (shrink)

In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti‐parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms. Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological (...) information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Comments on “Moral Complicity in Induced Pluripotent Stem Cell Research”W. Malcolm Byrnes, Ph.D. and Edward J. FurtonIn his article titled “Moral Complicity in Induced Pluripotent Stem Cell Research,” Mark T. Brown (2009) unfortunately mischaracterizes my ethical analysis of the use of induced pluripotent stem (iPS) cells for replacement therapies, or treatments (Byrnes 2008). In my paper, which Brown cites, I argue that, just as it is ethically acceptable (...) for parents to allow their children and themselves to be immunized using vaccines produced by cell lines derived from human fetuses aborted in the past, it is also acceptable for persons in the future to benefit from treatments that use iPS cells validated using human embryonic stem (ES) cell lines [End Page 202] derived in the past. The assumption I make is that iPS cells would have to be shown to be functionally equivalent to human ES cells—i.e., validated—before they could be used for cell replacement treatments. (If it turns out that this assumption is incorrect, and primate or even mouse ES cells can be used for the validation, then all residual ethical problems will disappear and there will be no ethical problems whatsoever associated with iPS cells.) I wrote:... [I]n both cases, the origin of the treatment is in a one-time event: either the one-time use of aborted fetuses to obtain cell lines (e.g., MRC-5 and WI- 38) to grow weakened virus strains for vaccine production, or the one-time destruction of human embryos to validate iPS cells, which then effectively replace embryonic stem cells. In the latter case, if no additional embryonic stem cell lines are derived, then derivation of the existing lines could be considered a “one-time” event in the past, albeit an event that extended over a several-year period(Byrnes 2008, p. 287, emphasis added).Note the phrase “if no additional embryonic stem cell lines are derived.” The derivation of ES cell lines inherently involves destruction of embryos; indeed, that is why many people, including me, are opposed to human ES cell research. In my article, I am arguing that, if no additional ES cell lines are derived, then no additional human embryos will be destroyed, and the destruction of human embryos will lie in the past. In this case, embryo destruction could be considered a past event, just as the abortion of a human fetus from which vaccine-producing cell lines were derived is a past, albeit tragic, event.In the process of building his argument that proponents of iPS cell research are morally complicit in embryo destruction, Brown (2009, p. 15) casts me as being in favor of the “derivation of new embryonic stem [cell lines].” This is the exact opposite of my position. In fact, I am opposed to further destruction of human embryos. I believe that the hundreds of ES cell lines already in existence are more than sufficient to validate iPS cells and so no additional lines need to be derived. This means that no additional human embryos will need to be destroyed.Apparently based on the misperception that I support future destruction of human embryos, Brown concludes that “Byrnes’s endorsement of ongoing iPSC validation studies would seem to implicate him and those who follow his lead in formal and material complicity in what they perceive as moral evil” (p. 16). He writes that “explicit formal complicity would attach because he [Byrnes] knowingly and intentionally recommends that embryos be killed in order to facilitate a transition to a future in which no more embryos need be destroyed” (p. 16). Additionally, my “followers” and I would be guilty of “proximate material complicity” as well as “remote material complicity” (p. 16). Unfortunately, this broad condemnation is based on a misconception of my actual position.An additional problem involves Brown’s use of a quotation he attributes to me: [End Page 203]Once embryonic stem cells are used to successfully validate iPS cells, they will no longer be needed and their association with iPS cells will lie in the past. Is there not an element of sadness and resignation in accepting something (iPS cells) associated with an unjust act (destruction of an... (shrink)

Deductive logic is about the validity of arguments. An argument is valid when its conclusion follows deductively from its premises. Here’s an example: If Alice is guilty then Bob is guilty, and Alice is guilty. Therefore, Bob is guilty. The validity of the argument has nothing to do with what the argument is about. It has nothing to do with the meaning, or content, of the argument beyond the meaning of logical phrases such as if…then. Thus, any argument of the (...) following form (called modus ponens) is valid: If P then Q, and P, therefore Q. Any claims substituted for P and Q lead to an argument that is valid. Probability theory is also content-free in the same sense. This is why deductive logic and probability theory have traditionally been the main technical tools in philosophy of science. (shrink)

Although in every inductive inference, an act of invention is requisite, the act soon slips out of notice. Although we bind together facts by superinducing upon them a new Conception, this Conception, once introduced and applied, is looked upon as inseparably connected with the facts, and necessarily implied in them. Having once had the phenomena bound together in their minds in virtue of the Conception men can no longer easily restore them back to the detached and incoherent condition in which (...) they were before they were thus combined. The pearls once strung, they seem to form a chain by their nature. Induction has given them unity which it is so far from costing us an effort to preserve, that it requires an effort to imagine it dissolved — William Whewell, 1858. (Quoted from Butts (ed.), 1989, p. 143). (shrink)

Deductive logic is about the property of arguments called validity. An argument has this property when its conclusion follows deductively from its premises. Here’s an example: If Alice is guilty then Bob is guilty, and Alice is guilty. Therefore, Bob is guilty. The important point is that the validity of this argument has nothing to do with the content of the argument. Any argument of the following form (called modus ponens) is valid: If P then Q, and P, therefore Q. (...) Any claims substituted for P and Q lead to an argument that is valid. Probability theory is also content-free. This is why deductive logic and probability theory have traditionally been the main tools in philosophy of science. (shrink)

What is induction? John Stuart Mill (1874, p. 208) defined induction as the operation of discovering and proving general propositions. William Whewell (in Butts, 1989, p. 266) agrees with Mill’s definition as far as it goes. Is Whewell therefore assenting to the standard concept of induction, which talks of inferring a generalization of the form “All As are Bs” from the premise that “All observed As are Bs”? Does Whewell agree, to use Mill’s example, that inferring “All humans are mortal” (...) from the premise that “John, Peter and Paul, etc., are mortal” is an example of induction? The surprising answer is “no”. How can this be? (shrink)