We describe a broad class of problems, called “uncompromising problems,” which are characterized by the requirement that solutions must perform optimally on each of many test cases. Many of the problems that have long motivated genetic programming research, including the automation of many traditional programming tasks, are uncompromising. We describe and analyze the recently proposed “lexicase” parent selection algorithm and show that it can facilitate the solution of uncompromising problems by genetic programming. Unlike most traditional parent selection techniques, lexicase selection (...) does not base selection on a fitness value that is aggregated over all test cases; rather, it considers test cases one at a time in random order. We present results comparing lexicase selection to more traditional parent selection methods, including standard tournament selection and implicit fitness sharing, on four uncompromising problems: 1) finding terms in finite algebras; 2) designing digital multipliers; 3) counting words in files; and 4) performing symbolic regression of the factorial function. We provide evidence that lexicase selection maintains higher levels of population diversity than other selection methods, which may partially explain its utility as a parent selection algorithm in the context of uncompromising problems. (shrink)

Consistent application of dialectical materialism leads Marxism-Leninism to the assertion that matter is infinite in its properties. However, the history of physics shows that the various levels of matter possess geometric dimensions that originate at the lowest level and continue through the others. The search for absolute natural constants -- which Planck called the most pleasant task of physics -- shows the conviction of the physicists that there is a limit to the parameters, a limit beyond which matter is no (...) longer divisible. (shrink)

A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients’ perception of material risks, by trained interviewers. Patients’ demographics were obtained. Mann–Whitney U (...) test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education, being employed and younger age group are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea, Drowsiness and Surgical Wound Pain. Patients ranked Heart Attack, Death and Stroke as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist, instead of letting the doctor decide or deciding for themselves. Discussion with the anaesthetist is the preferred medium of communication compared to reading a pamphlet or watching a video. Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship. (shrink)

We propose a new approach for tracing value change. Value change may lead to a mismatch between current value priorities in society and the values for which technologies were designed in the past, such as energy technologies based on fossil fuels, which were developed when sustainability was not considered a very important value. Better anticipating value change is essential to avoid a lack of social acceptance and moral acceptability of technologies. While value change can be studied historically and qualitatively, we (...) propose a more quantitative approach that uses large text corpora. It uses probabilistic topic models, which allow us to trace values that are latent. We demonstrate the approach for five types of value change in technology. Our approach is useful for testing hypotheses about value change, such as verifying whether value change has occurred and identifying patterns of value change. The approach can be used to trace value change for various technologies and text corpora, including scientific articles, newspaper articles, and policy documents. (shrink)

What if human joy went on endlessly? Suppose, for example, that each human generation were followed by another, or that the Western religions are right when they teach that each human being lives eternally after death. If any such possibility is true in the actual world, then an agent might sometimes be so situated that more than one course of action would produce an infinite amount of utility. Deciding whether to have a child born this year rather than next is (...) a situation wherein an agent may face several alternatives whose effects could well ramify endlessly on such suppositions, for the child born this year would be a different person—one who preferred different things, performed different actions, and had different descendants—from a child born next year. It has recently been suggested that traditional utilitarianism stumbles on such cases of infinite utility. Specifically, utilitarianism seems to require, for its application, that all experience of pleasure and pain cease at some time in the future or asymptotically approach zero.2 If neither of these conditions holds, then the utility produced by each of two alternative actions may turn out to be infinite, and utilitarianism thus loses its ability to discriminate morally between them. (shrink)

Amyotrophic lateral sclerosis (ALS; also called motor neuron disease) is a devastating medical condition that progressively robs patients of their ability to move, speak and eventually breathe. At present, many physicians are hesitant to propose tracheostomy and respiratory support in the terminal phase of ALS. In accordance with the principle of patient autonomy, physicians should respect the right of the ALS patient to accept or refuse any treatment, including mechanical ventilation. Also, in environments where euthanasia or physician-assisted death is legal, (...) such requests can be acceptable. At least two conditions are necessary for full autonomy. To have a claim on full autonomy, people need to have intact cognitive abilities, and to exercise this right they must be able to communicate. In the past, the first condition was in doubt (indeed, overlap with other neurodegenerative diseases is sometimes suspected and some patients with ALS are thought to have associated frontotemporal dementia) and the second was severely compromised in patients with devastating motor impairment (communication being limited to the twitch of a finger or the blink of an eye). In this issue of J Neurol Neurosurg Psychiatry, Lakerveld and colleagues1 investigated cognition in 11 patients with late stage ALS (see page 25). They showed preserved cognitive functioning (ie, language, executive function, intelligence, learning and long term memory) compared with healthy controls. Assessments were exclusively based on a ‘‘yes–no’’ response mode. Because of the absence of verbal and motor communication, the neuropsychological assessment of these patients is complicated, and adapted testing is needed. By using a ‘‘yes–no’’ response mode based on the remaining motor abilities of the patient, this study proves the possibility of assessing patients with minimal motor capacities. (shrink)

BackgroundCentral to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson’s disease, since potential subjects will be Parkinson’s patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses.MethodAs part of an expanded informed consent process (...) for a pilot Phase I study of deep brain stimulation in early stage Parkinson’s disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation.ResultsWhile the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as potential benefit from enrolling. However, 91 percent also indicated helping other Parkinson’s patients as motivation when considering whether or not to enroll.ConclusionsThis combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects’ preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson’s sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed. (shrink)

Background Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent. Objectives To explore what people want in a surrogate decision-maker whom they themselves select and to test the assumption that people want their chosen surrogate to make only a substituted judgement. Methods 30 undergraduate students were recruited. They were presented with a hypothetical scenario about their expected loss of mental capacity in (...) the future and asked to answer some questions about their choice of surrogate. These data were analysed qualitatively using thematic content analysis. Results Most respondents talked about choosing someone who was caring and competent in certain ways, giving interesting evidence for their judgements. Surprisingly few highlighted how well they thought their chosen surrogate knew their preferences and would be able to make a substituted judgement. Moreover, few specified that their chosen surrogate had similar attitudes and values to their own and so would make a similar decision to theirs in the circumstances presented. Some respondents also referred to the social role of their chosen surrogate or the social dynamics of their situation which influenced their choices, as well as to ideas of reciprocity and characteristics of honesty and loyalty. Conclusion In the event that they lose mental capacity, many people will not select a surrogate to decide about medical treatments on their behalf solely on the basis that they expect their surrogate to make a substituted judgement. (shrink)

It will be noticed that, in the stemma above, no line of descent is marked from the first generation registered therein to the following generations. The genealogy of the Emperor Nerva is customarily traced back to the consul of 36 b.c., M. Cocceius Nerva. This short note will underline the ancient testimony found amongst the Pseudacroniana tracing his descent from the latter's brother, the consummate diplomat. There are ramifications. Amongst the items of interest will be the light shone upon what (...) Dio and Eutropius understood to be Nerva's standing at the time of his accession. Before passing on to Pseudacron's datum, it might be worthwhile pausing on that point, as well as briefly contemplating the factors that actually bore upon the emperor's ancestral training. (shrink)

La doctrine d’Afriean Spir. Les objets d’expérience ne coïncident pas avec la norme logique. La méthode de réflexion. L’évident de fait et la certitude rationnelle. La nature et l’origine du concept a priori. Son unité. Jugement identique et jugement synthétique. Le principe d’identité comme principe de toute connaissance. Les applications de la pensée fondamentale de Spir dans le domaine de la morale et de la religion. L’importance historique de cette pensée.

After gene duplication, mutations cause the gene copies to diverge. The classical model predicts that these mutations will generally lead to the loss of function of one gene copy; rarely, new functions will be created and both duplicate genes are conserved. In contrast, under the subfunctionalization model both duplicates are preserved due to the partition of different functions between the duplicates. A recent study(1) provides support for the subfunctionalization model, identifying several expressed gene duplicates common to humans and mice that (...) contain regions conserved in one duplicate but variable in the other (and vice versa). We discuss both the methodology used in this study and also how gene phylogeny may lead to additional evidence for the importance of subfunctionalization in the evolution of new genes. BioEssays 23:873–876, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

A gas in a box is perhaps the most important model system studied in thermodynamics and statistical mechanics. Usually, studies focus on the gas, whereas the box merely serves as an idealized confinement. The present article focuses on the box as the central object and develops a thermodynamic theory by treating the geometric degrees of freedom of the box as the degrees of freedom of a thermodynamic system. Applying standard mathematical methods to the thermody- namics of an empty box allows (...) equations with the same structure as those of cosmology and classical and quantum mechanics to be derived. The simple model system of an empty box is shown to have interesting connections to classical mechanics, special relativity, and quantum field theory. (shrink)

On Kratzer’s canonical account, modal expressions (like “might” and “must”) are represented semantically as quantifiers over possibilities. Such expressions are themselves neutral; they make a single contribution to determining the propositions expressed across a wide range of uses. What modulates the modality of the proposition expressed—as bouletic, epistemic, deontic, etc.—is context.2 This ain’t the canon for nothing. Its power lies in its ability to figure in a simple and highly unified explanation of a fairly wide range of language use. Recently, (...) though, the canon’s neat story has come under attack. The challenge cases involve the epistemic use of a modal sentence for which no single resolution of the contextual parameter appears capable of accommodating all our intuitions.3 According to these revisionaries, such cases show that the canonical story needs to be amended in some way that makes multiple bodies of information relevant to the assessment of such statements. Here I show that how the right canonical, flexibly contextualist account of modals can accommodate the full range of challenge cases. The key will be to extend Kratzer’s formal semantic account with an account of how context selects values for a modal’s.. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

What considerations place genuine constraints on an adequate semantics for normative and evaluative expressions? Linguists recognize facts about ordinary uses of such expressions and competent speakers’ judgments about which uses are appropriate. The contemporary literature reflects the widespread assumption that linguists don’t rely upon an additional source of data—competent speakers’ judgments about possible disagreement with hypothetical speech communities. We have several good reasons to think that such judgments are not probative for semantic theorizing. Therefore, we should accord these judgments no (...) probative value for the development of a semantics for our moral terms. Such judgments can no longer be presumed to put pressure on theories according to which our moral expressions share a semantics with ordinary, descriptive terms. Many rivals to pure, Descriptivist theories count among their advantages the ability to accommodate these judgments. If these judgments have no probative value, such theories lose an important source of support. (shrink)