The dome: An unexpectedly simple failure of determinism

Newton's equations of motion tell us that a mass at rest at the apex of a dome with the shape specified here can spontaneously move. It has been suggested that this indeterminism should be discounted since it draws on an incomplete rendering of Newtonian physics, or it is "unphysical," or it employs illicit idealizations. I analyze and reject each of these reasons. Copyright 2008 by the Philosophy of Science Association. All rights reserved

There are no universal rules for induction

In a material theory of induction, inductive inferences are warranted by facts that prevail locally. This approach, it is urged, is preferable to formal theories of induction in which the good inductive inferences are delineated as those conforming to universal schemas. An inductive inference problem concerning indeterministic, nonprobabilistic systems in physics is posed, and it is argued that Bayesians cannot responsibly analyze it, thereby demonstrating that the probability calculus is not the universal logic of induction. Copyright 2010 by the Philosophy of Science Association.All right reserved

Observationally Indistinguishable Spacetimes: A Challenge for Any Inductivist

Results on the observational indistinguishability of spacetimes demonstrate the impossibility of determining by deductive inference which is our spacetime, no matter how extensive a portion of the spacetime is observed. These results do not illustrate an underdetermination of theory by evidence, since they make no decision between competing theories and they make little contact with the inductive considerations that must ground such a decision. Rather, these results express a variety of indeterminism in which a specification of the observable past always fails to fix the remainder of a spacetime. This form of indeterminism is more troubling than the familiar indeterminism of quantum theory. The inductive inferences that can discriminate among the different spacetime extensions of the observed past are here called "opaque," which means that we cannot readily see the warrant that lies behind them

Ignorance and indifference

The epistemic state of complete ignorance is not a probability distribution. In it, we assign the same, unique, ignorance degree of belief to any contingent outcome and each of its contingent, disjunctive parts. That this is the appropriate way to represent complete ignorance is established by two instruments, each individually strong enough to identify this state. They are the principle of indifference (PI) and the notion that ignorance is invariant under certain redescriptions of the outcome space, here developed into the 'principle of invariance of ignorance' (PII). Both instruments are so innocuous as almost to be platitudes. Yet the literature in probabilistic epistemology has misdiagnosed them as paradoxical or defective since they generate inconsistencies when conjoined with the assumption that an epistemic state must be a probability distribution. To underscore the need to drop this assumption, I express PII in its most defensible form as relating symmetric descriptions and show that paradoxes still arise if we assume the ignorance state to be a probability distribution. Copyright 2008 by the Philosophy of Science Association. All rights reserved

Why constructive relativity fails

Constructivists, such as Harvey Brown, urge that the geometries of Newtonian and special relativistic spacetimes result from the properties of matter. Whatever this may mean, it commits constructivists to the claim that these spacetime geometries can be inferred from the properties of matter without recourse to spatiotemporal presumptions or with few of them. I argue that the construction project only succeeds if constructivists antecedently presume the essential commitments of a realist conception of spacetime. These commitments can be avoided only by adopting an extreme form of operationalism

Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease.

Background: Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Methods: Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the `GenePattern' suite of computational tools (Broad Institute, MIT, USA). Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR) test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, `leave-one-out' cross-validation method. Results: 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P <= 0.01, false discovery rate <= 0.05). Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100\% sensitivity and specificity (95\% confidence interval: 67.9-99.2\%). Supervised prediction using `leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = < 0.001; receiver-operator characteristics - ROC - error, 0.171); disease recurrence was correctly predicted in 5/6 cases and disease-free survival (median follow-up time, 25 months) was correctly predicted in 22/23 cases (P = < 0.001; ROC error, 0.105). A similar analysis of normal mucosa spectra correctly predicted 11/14 patients with, and 15/19 patients without lymph node involvement (P = 0.001; ROC error, 0.212). Conclusions: Protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value in studies aimed at improved molecular classification of this disease. Further studies, with longer follow-up times and larger patient cohorts, that would permit independent validation of supervised classification models, would be required to confirm the predictive value of tumour spectra for disease recurrence/patient survival

Analysis of post-operative changes in serum protein expression profiles from colorectal cancer patients by MALDI-TOF mass spectrometry: a pilot methodological study.

Background: Mass spectrometry-based protein expression profiling of blood sera can be used to discriminate colorectal cancer (CRC) patients from unaffected individuals. In a pilot methodological study, we have evaluated the changes in protein expression profiles of sera from CRC patients that occur following surgery to establish the potential of this approach for monitoring post-surgical response and possible early prediction of disease recurrence. Methods: In this initial pilot study, serum specimens from 11 cancer patients taken immediately prior to surgery and at approximately 6 weeks following surgery were analysed alongside 10 normal control sera by matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS). Using a two-sided t-test the top 20 ranked protein peaks that discriminate normal from pre-operative sera were identified. These were used to classify postoperative sera by hierarchical clustering analysis (Spearman's Rank correlation) and, as an independent `test' dataset, by k-nearest neighbour and weighted voting supervised learning algorithms. Results: Hierarchical cluster analysis classified post-operative sera from all six early Dukes' stage (A and B) patients as normal. The remaining five post-operative sera from more advanced Dukes' stages (C1 and C2) were classified as cancer. Analysis by supervised learning algorithms similarly grouped all advanced Dukes' stages as cancer, with four of the six post-operative sera from early Dukes' stages being classified as normal (P = 0.045; Fisher's exact test). Conclusions: The results of this pilot methodological study illustrate the proof-of-concept of using protein expression profiling of post-surgical blood sera from individual patients to monitor disease course. Further validation on a larger patient cohort and using an independent post-operative sera dataset would be required to evaluate the potential clinical relevance of this approach. Prospective data, including follow-up on patient survival, could in the future, then be evaluated to inform decisions on individualised treatment modalities

Nonminimal Couplings in the Early Universe: Multifield Models of Inflation and the Latest Observations

Models of cosmic inflation suggest that our universe underwent an early phase of accelerated expansion, driven by the dynamics of one or more scalar fields. Inflationary models make specific, quantitative predictions for several observable quantities, including particular patterns of temperature anistropies in the cosmic microwave background radiation. Realistic models of high-energy physics include many scalar fields at high energies. Moreover, we may expect these fields to have nonminimal couplings to the spacetime curvature. Such couplings are quite generic, arising as renormalization counterterms when quantizing scalar fields in curved spacetime. In this chapter I review recent research on a general class of multifield inflationary models with nonminimal couplings. Models in this class exhibit a strong attractor behavior: across a wide range of couplings and initial conditions, the fields evolve along a single-field trajectory for most of inflation. Across large regions of phase space and parameter space, therefore, models in this general class yield robust predictions for observable quantities that fall squarely within the "sweet spot" of recent observations.Comment: 17pp, 2 figs. References added to match the published version. Published in {\it At the Frontier of Spacetime: Scalar-Tensor Theory, Bell's Inequality, Mach's Principle, Exotic Smoothness}, ed. T. Asselmeyer-Maluga (Springer, 2016), pp. 41-57, in honor of Carl Brans's 80th birthda

Deductively Definable Logics of Induction

A broad class of inductive logics that includes the probability calculus is defined by the conditions that the inductive strengths [A{pipe}B] are defined fully in terms of deductive relations in preferred partitions and that they are asymptotically stable. Inductive independence is shown to be generic for propositions in such logics; a notion of a scale-free inductive logic is identified; and a limit theorem is derived. If the presence of preferred partitions is not presumed, no inductive logic is definable. This no-go result precludes many possible inductive logics, including versions of hypothetico-deductivism. © 2010 Springer Science+Business Media B.V