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Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Epistemic decision theorists aim to justify Bayesian norms by arguing that these norms further the goal of epistemic accuracy—having beliefs that are as close as possible to the truth. The standard defense of Probabilism appeals to accuracy dominance: for every belief state that violates the probability calculus, there is some probabilistic belief state that is more accurate, come what may. The standard defense of Conditionalization, on the other hand, appeals to expected accuracy: before the evidence is in, one should expect to do better by conditionalizing than by following any other rule. We present a new argument for Conditionalization that appeals to accuracy‐dominance, rather than expected accuracy. Our argument suggests that Conditionalization is a rule of coherence: plans that conflict with Conditionalization don't just prescribe bad responses to the evidence; they also give rise to inconsistent attitudes.

Risk-weighted expected utility theory (REU theory for short) permits preferences which violate the Sure-Thing Principle (STP for short). But preferences that violate the STP can lead to bad decisions in sequential choice problems. In particular, they can lead decision-makers to adopt a strategy that is dominated – i.e. a strategy such that some available alternative leads to a better outcome in every possible state of the world.

We show that five important elements of the ‘nomological package’—laws, counterfactuals, chances, dispositions, and counterfactuals—needn’t be a problem for the Growing-Block view. We begin with the framework given in Briggs and Forbes (in The real truth about the unreal future. Oxford studies in metaphysics. Oxford University Press, Oxford, 2012), and, taking laws as primitive, we show that the Growing-Block view has the resources to provide an account of possibility, and a natural semantics for non-backtracking causal counterfactuals. We show how objective chances might ground a more fine-grained concept of feasibility, and furnished a places in the structure where causation and dispositions might fit. The Growing-Block view, thus understood, provides the resources to explain the close link between modality and tense, so that it predicts modal change as time passes. This account lets us capture not only what the future might hold for us, and also what might have been.

One of the standard approaches to the metaphysics of personal identity has some counter-intuitive ethical consequences when combined with maximising consequentialism and a plausible (though not uncontroversial) doctrine about aggregation of consequences. This metaphysical doctrine is the so-called ‘multiple occupancy’ approach to puzzles about fission and fusion. It gives rise to a new version of the ‘utility monster’ problem, particularly difficult problems about infinite utility, and a new version of a Parfit-style ‘repugnant conclusion’. While the article focuses on maximising consequentialism for simplicity, the problems demonstrated apply more widely to a range of ethical views, especially flavours of consequentialism. This article demonstrates how these problems arise, and discusses a number of options available in the light of these problems for a consequentialist tempted by a multiple occupancy metaphysics.

In this article, we consider two independently appealing theories—the Growing-Block view and Humean Supervenience—and argue that at least one is false. The Growing-Block view is a theory about the nature of time. It says that (a) past and present things exist, while future things do not, and (b) the passage of time consists in new things coming into existence. Humean Supervenience is a theory about the nature of entities like laws, nomological possibility, counterfactuals, dispositions, causation, and chance. It says that none of these entities are fundamental, since if there were, this would entail the existence of irreducible necessary connections between matters of fact. Instead, these entities supervene on a fundamental, nonnomological “Humean mosaic” of property instances at spacetime points. We will further explain and motivate the Growing-Block view and Humean Supervenience in sections 2 and 3, but first, we turn to our master argument.

To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss.Retrospective, multicenter cohort study.A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe.Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss.Yearly change in VA.The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P0.0001) per year overall, but the rate varied according to baseline VA: (1) eyes with baseline VA ≥20/25 (N = 53) declined at a rate of approximately 1.0 line per year; (2) eyes with VA between 20/25 and 20/70 (N = 65) declined at a rate of approximately 0.9 lines per year; (3) eyes with VA between 20/70 and 20/200 (N = 163) declined at a rate of 0.2 lines per year; and (4) eyes with VA worse than 20/200 (n = 49) improved at a rate of 0.5 lines per year. Older age of onset was associated with slower VA loss: Patients with onset age30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years.Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets.

Christian List and Philip Pettit (henceforth LP) argue that groups of people can be agents – beings that believe, desire and act. Their account combines a non-reductive realist view of group attitudes, on which groups literally have attitudes that cannot be analyzed in terms of the attitudes of their members, with methodological individualism, on which good explanations of group-level phenomena should not posit forces above individual attitudes and behaviors. I then discuss the main normative conclusion that LP draw from the claim that group agents exist: that we ought morally to grant legal rights and responsibilities to group agents, but that group rights should be more limited than individual rights. I argue that when it comes to the fitness of group agents to bear legal rights and responsibilities, LP can draw support from nonreductionist views elsewhere, particularly in the philosophy of mind. I raise some objections to LP's views about the value of granting legal rights and responsibilities to group agents.

A number of recent authors (Galles and Pearl, Found Sci 3 (1):151–182, 1998; Hiddleston, Nous 39 (4):232–257, 2005; Halpern, J Artif Intell Res 12:317–337, 2000) advocate a causal modeling semantics for counterfactuals. But the precise logical significance of the causal modeling semantics remains murky. Particularly important, yet particularly under-explored, is its relationship to the similarity-based semantics for counterfactuals developed by Lewis (Counterfactuals. Harvard University Press, 1973b). The causal modeling semantics is both an account of the truth conditions of counterfactuals, and an account of which inferences involving counterfactuals are valid. As an account of truth conditions, it is incomplete. While Lewis’s similarity semantics lets us evaluate counterfactuals with arbitrarily complex antecedents and consequents, the causal modeling semantics makes it hard to ascertain the truth conditions of all but a highly restricted class of counterfactuals. I explain how to extend the causal modeling language to encompass a wider range of sentences, and provide a sound and complete axiomatization for the extended language. Extending the truth conditions for counterfactuals has serious consequences concerning valid inference. The extended language is unlike any logic of Lewis’s: modus ponens is invalid, and classical logical equivalents cannot be freely substituted in the antecedents of conditionals.

We reply to recent papers by John Turri and Ben Bronner, who criticise the dispositionalised Nozickian tracking account we discuss in “Mad, Bad and Dangerous to Know.” We argue that the account we suggested can handle the problems raised by Turri and Bronner. In the course of responding to Turri and Bronner’s objections, we draw three general lessons for theories of epistemic dispositions: that epistemic dispositions are to some extent extrinsic, that epistemic dispositions can have manifestation conditions concerning circumstances where their bearers fail to exist, and that contrast is relevant to disposition attributions.

This article surveys several interrelated issues in the metaphysics of chance. First, what is the relationship between the probabilities associated with types of trials (for instance, the chance that a twenty-eight-year old develops diabetes before age thirty) and the probabilities associated with individual token trials (for instance, the chance that I develop diabetes before age thirty)? Second, which features of the the world fix the chances: are there objective chances at all, and if so, are there non-chancy facts on which they supervene? Third, can chance be reconciled with determinism, and if so, how?

It is a platitude among decision theorists that agents should choose their actions so as to maximize expected value. But exactly how to define expected value is contentious. Evidential decision theory (henceforth EDT), causal decision theory (henceforth CDT), and a theory proposed by Ralph Wedgwood that this essay will call benchmark theory (BT) all advise agents to maximize different types of expected value. Consequently, their verdicts sometimes conflict. In certain famous cases of conflict—medical Newcomb problems—CDT and BT seem to get things right, while EDT seems to get things wrong. In other cases of conflict, including some recent examples suggested by Andy Egan, EDT and BT seem to get things right, while CDT seems to get things wrong. In still other cases, EDT and CDT seems to get things right, while BT gets things wrong.It's no accident, this essay claims, that all three decision theories are subject to counterexamples. Decision rules can be reinterpreted as voting rules, where the voters are the agent's possible future selves. The problematic examples have the structure of voting paradoxes. Just as voting paradoxes show that no voting rule can do everything we want, decision-theoretic paradoxes show that no decision rule can do everything we want. Luckily, the so-called “tickle defense” establishes that EDT, CDT, and BT will do everything we want in a wide range of situations. Most decision situations, this essay argues, are analogues of voting situations in which the voters unanimously adopt the same set of preferences. In such situations, all plausible voting rules and all plausible decision rules agree.

Diachronic Dutch book arguments seem to support both conditionalization and Bas van Fraassen's Reflection principle. But the Reflection principle is vulnerable to numerous counterexamples. This essay addresses two questions: first, under what circumstances should an agent obey Reflection, and second, should the counterexamples to Reflection make us doubt the Dutch book for conditionalization?In response to the first question, this essay formulates a new “Qualified Reflection” principle, which states that an agent should obey Reflection only if he or she is certain that he or she will conditionalize on veridical evidence in the future. Qualified Reflection follows from the probability calculus together with a few idealizing assumptions. The essay then formulates a “Distorted Reflection” principle that approximates Reflection even in cases where the agent is not quite certain that he or she will conditionalize on veridical evidence.In response to the second question, the essay argues that contrary to a common misconception, not all Dutch books dramatize incoherence—some dramatize a less blameworthy sort of epistemic frailty that the essay calls “self-doubt.” The distinction between Dutch books that dramatize incoherence and those that dramatize self-doubt cross-cuts the distinction between synchronic and diachronic Dutch books. The essay explains why the Dutch book for conditionalization reveals true incoherence, whereas the Dutch book for Reflection reveals only self-doubt.

David Lewis’s ‘Humean Supervenience’ (henceforth ‘HS’) combines realism about laws, chances, and dispositions with a sparse ontology according to which everything supervenes on the overall spatiotemporal distribution of non-dispositional properties (Lewis 1986a, Philosophical papers: Volume II, pp. ix–xvii, New York: Oxford Univesity Press, 1994, Mind 103:473–490). HS faces a serious problem—a “big bad bug” (Lewis 1986a, p. xiv): it contradicts the Principal Principle, a seemingly obvious norm of rational credence. Two authors have tried to rescue Lewis’s ontology from the ‘big bad bug’ (henceforth ‘the Bug’) by rejecting realism about laws, chances, and dispositions (Halpin 1994, Aust J Phil 72:317–338, 1998, Phil Sci 65:349–360; Ward 2005, Phil Sci 71:241–261). I will argue that this strategy cannot possibly work: it is the ontology, not the realist thesis, that lies at the root of the problem.

David Lewis claimed that deterministic chance was impossible. But deterministic chance seems ubiquitous in casinos, in statistical mechanics, and in evolutionary theory. It would be best for Lewis's metaphysics if, in spite of what he says, we could reconcile his core views with deterministic chance. In this chapter, the author briefly rebuts two Lewisian objections to deterministic chance. The first is that our world is indeterministic at the quantum level, and this lower‐level indeterminism translates to indeterminism at higher levels. The chapter explains how deterministic chances are possible on a broadly Lewisian theory. It also explains how there can be deterministic chances that function as nomological magnitudes, guide credence, and arise in objectively chancy situations. It is true that the author's deterministic chances are not time‐indexed. It is also true that they do not exactly satisfy principles, proposed by Lewis and others in a broadly Lewisian tradition, that presuppose time‐indexing.

A common objective for quantum control is to force a quantum system, initially in an unknown state, into a particular target subspace. We show that if the subspace is required to be a decoherence-free subspace of dimension greater than 1, then such control must be decoherent. That is, it will take almost any pure state to a mixed state. We make no assumptions about the control mechanism, but our result implies that for this purpose coherent control offers no advantage, in principle, over the obvious measurement-based feedback protocol., Comment: 3 pages. To be published in Quantum Measurements & Quantum Metrology http://versita.com/qm/

Recent times have been very much focussed on the future. The election of Barack Obama in America was accompanied by a wave of optimism. The Global Financial Crisis and the challenge of Climate Change cause many to descend into pessimism. It is not whether our glass is half-empty or half-full that we worry about, but whether it will be empty or full. As philosophers, naturally, we want to illuminate such concerns, so that we might understand them better and subject them to rational scrutiny. According to the Growing-Block view of time, most famously put forward by C.D. Broad [1923], the flow of time consists in events coming into existence, so that past things and events are real, while future things and events are not. While the Growing-Block view is often considered intuitively appealing, some are concerned it has little to say about the future it denies the existence of. We show how Growing-Block theorists can assign meaningful, mind-independent truth conditions to sentences about the future.