The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

In lieu of an abstract, here is a brief excerpt of the content:Perceiving Particulars Blindly:Remarks on a Nyāya-Buddhist ControversyStephen H. PhillipsIntroductionThe discussion by Mark Siderits in this issue—"Perceiving Particulars"—and two pieces by Monima Chadha—the first her article "Perceptual Cognition: A Nyāya-Kantian Approach" (Chadha 2001) and the second her reply to Siderits in this issue—have taught me much.1 I have little to add beyond agreeing on the whole with Siderits and making a few tweaks concerning Nyāya. Chadha astutely captures the insight (...) of Gaṅgeśa, the fourteenth-century Naiyāyika cited by her (and by Siderits): indeterminate perception does not have a "particular as such" as its object (viṣaya), but only, as she says, a non-particular individual such as a universal or another qualifier that is in principle recurrent (recurrent out in the world), perceivable [End Page 389] again, and thus expressible by a (repeatable) word. Nevertheless, the holism of Wilfred Sellars and Kant and the attack on the "given" are not in the spirit of the Nyāya approach to epistemology, which is thoroughly externalist, as Siderits suggests. In several places (one presented below), Gaṅgeśa shows us controversy within Nyāya about indeterminate perception, including a rival Naiyāyika opinion that bare particulars are indeterminately grasped. This is not his own view, which is that positing indeterminate perception of qualifiers and not also of qualificanda is all that we need. But all in all the issue is not such a big deal, since perception does generate determinate knowledge of particulars, although these are always at least barely clothed.The notion of a "bare particular"—that is, the qualificandum thought about as distinct from all of its qualifiers—is an abstraction from what we directly perceive. We know it only by inference (specifically, by an inference of the sāmānyato dṘṣṭa type). Indeterminate perception is also known only by inference. Even in Navya Nyāya, the big deal is what is known determinately in perception, which is the principal way we know anything (the jyeṣṭa pramāṇa). And, clearly, determinate perceptual awareness is often of a particular—"The pot is blue" and "That's a pot," for instance. The particular known—indeed, the bare particular—is an intrinsic part of the viṣayatā, "intentionality," which is the relation between the knowing cognition and the world known.2Contrary to what Chadha says in her first article, "seeing as" does not require mental construction, according to Nyāya. The property bearer (dharmin = viśeṣya, "qualificandum") is grasped by the sense organ and is known directly in determinate perception as well as the qualifier and the qualificative relation. In two subtypes of perceptual awareness, (a) recurrent experience and (b) the recognition of something perceived previously, Chadha is right: the mind is operative, responsive to the firing of saṃskāra, "memory impressions," and fusing previous perceptual data into a current perceiving: (a) "A cow," "Another," "Another," and (b) "This is that Devadatta (I saw yesterday)." But hardly all cases of determinate perception require the mind (in Chadha's sense). The object known is minimally a complex of a property bearer (the particular as such), property, and an ontological relation tying them up, a-inherence-pothood (where "a" designates the pot as bare particular, "the subject of qualification"); the determinate perception, "That's a pot," makes that particular as qualified known.So, you say, I am agreeing with Chadha, whose argument is directed against the particular as such being known (either determinately or indeterminately) in perception. Yes, but the point is that the particular is known in perception; the particular-as-such is known in perception, although it would be fantasy to think it even possible that we could ever see her, this property bearer, well, not so much bare as disembodied. A rough analogy is seeing a door. We say we "see the door" when we see only one side of it, not the back. We see the thing as a door without grasping everything about the door that its being a door entails.Indeterminate perception of qualifiers is a controversial posit that does various work for Gaṅgeśa and other... (shrink)

One of the hallmarks of human cognition is the capacity to generalize over arbitrary constituents. Recently, Marcus (1998, 1998a, b; Cognition 66, p. 153; Cognitive Psychology 37, p. 243) argued that this capacity, called universal generalization (universality), is not supported by Connectionist models. Instead, universality is best explained by Classical symbol systems, with Connectionism as its implementation. Here it is argued that universality is also a problem for Classicism in that the syntax-sensitive rules that are supposed to provide causal explanations (...) of mental processes are either too strict, precluding possible generalizations; or too lax, providing no information as to the appropriate alternative. Consequently, universality is not explained by a Classical theory. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

This paper is taken from a long section of the _Tattva-cintā-maṇi_ by Gaṅgeśa that is devoted to proving the existence of—to use an inadequate word—“God” in a somewhat minimalist sense. The _īśvara_, the “Lord,” is for Gaṅgeśa, following Nyāya predecessors, a divine agent, a self, responsible for much, not all, of the order in the world. Unseen Force, _adṛṣṭa_, which is in effect _karman_ made by human action, is also a powerful agent as well as things’ intrinsic natures. Moreover, ordinary (...) selves, atoms, ether, and universals are uncreated. But the _īśvara_ brings about just desert in reincarnation in actualizing Unseen Force, and is responsible for a broad swathe of what some see as accidental arrangements as well as the forming of the macro elements from eternal, naturally _dis_joined atoms. Thus the cosmos in its general existence and structure is viewed in Nyāya as the work of the Lord. Gaṅgeśa’s argument runs: Earth and the like [_a_ (_pakṣa_) = earth and the like (_kṣity-ādi_)] have a conscious agent as a cause [S (_sādhya_) = having an agential cause (_sakartṛkatva_) (S_a_)], _since_ they are effects [H (_sādhana_) = being an effect [(_kāryatva_) (H_a_)], like a pot [_b_ (_dṛṣṭānta_) = a pot (H_b_,S_b_)]. And so the _vyāpti_ rule is: [H → S (_vyāpti_)] Whatever is an effect has an agential cause. For earth and the like, it is reasoned that only an omniscient _īśvara_ could be that cause. The argument was a target of Buddhists who pointed to counterexamples such as growing grass. Growing grass exhibits the prover property, being-an-effect, but not the property to be proved, having-an-agential-cause. The long section is dominated by Gaṅgeśa’s rebutting this and other potential defeaters, in particular, the _upādhi_, having-a-living-body (God does not have a living body but all the agential causes with which we are familiar do), along with a counterinference (_sat-pratipakṣa_), I_a_ & (x)(Ix → ¬Sx), where I = not-produced-by-an-agent-with-a-body. (shrink)

Introduction -- Wittgenstein's early conception of value -- An outline of tractarian ontology -- Value, the self, and the mystical -- The lecture on ethics -- Language-games, the private language argument and aspect psychology -- Language-games -- The private language argument -- Aspect psychology -- The soul and attitudes towards the living -- Wittgenstein's general conception of the soul -- Ilham Dilman on the soul and seeing-as -- Religious contexts -- J.B. Watson and the denial of the soul -- Attitudes (...) towards other minds and forms of life -- The soul and the face -- Aspect blindness and dawning -- Particularism, rule-following, and evaluations -- David McNaughton on the property of humanity and particularism -- John McDowell on rule-following and values -- Peter Winch on moral particularism -- The meaning and value of the religious point of view -- Wittgenstein on Frazer's golden bough -- Truth in religion -- Wittgenstein on art : reactions and causes -- Aesthetics, causes, and natural history -- A contemporary evolutionary account of aesthetic value -- Neuro-scientific accounts -- Aesthetic realism and the definition of art -- Aesthetic historicism and relativism -- Institutional and historical theories of art -- Forms of life, moral truth, and justification -- Cora Diamond on forms on seeing-as theory and imagination -- Paul Johnston on moral justification and truth -- D.Z. Phillips and H.O. Mounce on the justification of morality -- Doubt and certainty : framework beliefs and core values -- An overview of certainty -- Avrum Stroll, Anthony O'Hear , and Cyril Barrett on certainty and value -- Cultural relativism and institutional embodiment -- Peter Winch on cultural relativism -- Sabina Lovibond on moral facts and institutional embodiment -- Cyril Barrett on cultural relativism -- Conclusion: How to do things with Wittgenstein. (shrink)

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