Experimental observation of nonclassical effects on single-photon detection rates

It is often asserted that quantum effects can be observed in coincidence detection rates or other correlations, but never in the rate of single-photon detection. We observe nonclassical interference in a singles rate, thanks to the intrinsic nonlinearity of photon counters. This is due to a dependence of the effective detection efficiency on the quantum statistics of the light beam. Such measurements of detector response to photon pairs promise to shed light on the microscopic aspects of silicon photodetectors, and on general issues of quantum measurement and decoherence.Comment: 8 pages, 4 figure

Computational Characterization and Prediction of Estrogen Receptor Coactivator Binding Site Inhibitors

Many carcinogens have been shown to cause tissue specific tumors in animal models. The mechanism for this specificity has not been fully elucidated and is usually attributed to differences in organ metabolism. For heterocyclic amines, potent carcinogens that are formed in well-done meat, the ability to either bind to the estrogen receptor and activate or inhibit an estrogenic response will have a major impact on carcinogenicity. Here we describe our work with the human estrogen receptor alpha (hERa) and the mutagenic/carcinogenic heterocyclic amines PhIP, MeIQx, IFP, and the hydroxylated metabolite of PhIP, N2-hydroxy-PhIP. We found that PhIP, in contrast to the other heterocyclic amines, increased cell-proliferation in MCF-7 human breast cancer cells and activated the hERa receptor. We show mechanistic data supporting this activation both computationally by homology modeling and docking, and by NMR confirmation that PhIP binds with the ligand binding domain (LBD). This binding competes with estradiol (E2) in the native E2 binding cavity of the receptor. We also find that other heterocyclic amines and N2-hydroxy-PhIP inhibit ER activation presumably by binding into another cavity on the LBD. Moreover, molecular dynamics simulations of inhibitory heterocyclic amines reveal a disruption of the surface of the receptor protein involved with protein-protein signaling. We therefore propose that the mechanism for the tissue specific carcinogenicity seen in the rat breast tumors and the presumptive human breast cancer associated with the consumption of well-done meat maybe mediated by this receptor activation

A Cauchy-Dirac delta function

The Dirac delta function has solid roots in 19th century work in Fourier analysis and singular integrals by Cauchy and others, anticipating Dirac's discovery by over a century, and illuminating the nature of Cauchy's infinitesimals and his infinitesimal definition of delta.Comment: 24 pages, 2 figures; Foundations of Science, 201

A multi-centre qualitative study exploring the experiences of UK South Asian and White Diabetic Patients referred for renal care

Background An exploration of renal complications of diabetes from the patient perspective is important for developing quality care through the diabetic renal disease care pathway. Methods Newly referred South Asian and White diabetic renal patients over 16 years were recruited from nephrology outpatient clinics in three UK centres - Luton, West London and Leicester – and their experiences of the diabetes and renal care recorded. A semi-structured qualitative interview was conducted with 48 patients. Interview transcripts were analysed thematically and comparisons made between the White and South Asian groups. Results 23 South Asian patients and 25 White patients were interviewed. Patient experience of diabetes ranged from a few months to 35 years with a mean time since diagnosis of 12.1 years and 17.1 years for the South Asian and White patients respectively. Confusion emerged as a response to referral shared by both groups. This sense of confusion was associated with reported lack of information at the time of referral, but also before referral. Language barriers exacerbated confusion for South Asian patients. Conclusions The diabetic renal patients who have been referred for specialist renal care and found the referral process confusing have poor of awareness of kidney complications of diabetes. Healthcare providers should be more aware of the ongoing information needs of long term diabetics as well as the context of any information exchange including language barriers

The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process

Objectives: The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies’ decisions and enhance the case for additional research funding. Design: Prospective survey with support from the James Lind Alliance. Setting: UK-wide National Health Service (NHS) and non-NHS. Participants: Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio). Outcome measure: People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops. Results: 2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category. Conclusions: The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Stevin numbers and reality

We explore the potential of Simon Stevin's numbers, obscured by shifting foundational biases and by 19th century developments in the arithmetisation of analysis.Comment: 22 pages, 4 figures. arXiv admin note: text overlap with arXiv:1104.0375, arXiv:1108.2885, arXiv:1108.420

Ten Misconceptions from the History of Analysis and Their Debunking

The widespread idea that infinitesimals were "eliminated" by the "great triumvirate" of Cantor, Dedekind, and Weierstrass is refuted by an uninterrupted chain of work on infinitesimal-enriched number systems. The elimination claim is an oversimplification created by triumvirate followers, who tend to view the history of analysis as a pre-ordained march toward the radiant future of Weierstrassian epsilontics. In the present text, we document distortions of the history of analysis stemming from the triumvirate ideology of ontological minimalism, which identified the continuum with a single number system. Such anachronistic distortions characterize the received interpretation of Stevin, Leibniz, d'Alembert, Cauchy, and others.Comment: 46 pages, 4 figures; Foundations of Science (2012). arXiv admin note: text overlap with arXiv:1108.2885 and arXiv:1110.545

A Burgessian critique of nominalistic tendencies in contemporary mathematics and its historiography

We analyze the developments in mathematical rigor from the viewpoint of a Burgessian critique of nominalistic reconstructions. We apply such a critique to the reconstruction of infinitesimal analysis accomplished through the efforts of Cantor, Dedekind, and Weierstrass; to the reconstruction of Cauchy's foundational work associated with the work of Boyer and Grabiner; and to Bishop's constructivist reconstruction of classical analysis. We examine the effects of a nominalist disposition on historiography, teaching, and research.Comment: 57 pages; 3 figures. Corrected misprint

Leibniz's Infinitesimals: Their Fictionality, Their Modern Implementations, And Their Foes From Berkeley To Russell And Beyond

Many historians of the calculus deny significant continuity between infinitesimal calculus of the 17th century and 20th century developments such as Robinson's theory. Robinson's hyperreals, while providing a consistent theory of infinitesimals, require the resources of modern logic; thus many commentators are comfortable denying a historical continuity. A notable exception is Robinson himself, whose identification with the Leibnizian tradition inspired Lakatos, Laugwitz, and others to consider the history of the infinitesimal in a more favorable light. Inspite of his Leibnizian sympathies, Robinson regards Berkeley's criticisms of the infinitesimal calculus as aptly demonstrating the inconsistency of reasoning with historical infinitesimal magnitudes. We argue that Robinson, among others, overestimates the force of Berkeley's criticisms, by underestimating the mathematical and philosophical resources available to Leibniz. Leibniz's infinitesimals are fictions, not logical fictions, as Ishiguro proposed, but rather pure fictions, like imaginaries, which are not eliminable by some syncategorematic paraphrase. We argue that Leibniz's defense of infinitesimals is more firmly grounded than Berkeley's criticism thereof. We show, moreover, that Leibniz's system for differential calculus was free of logical fallacies. Our argument strengthens the conception of modern infinitesimals as a development of Leibniz's strategy of relating inassignable to assignable quantities by means of his transcendental law of homogeneity.Comment: 69 pages, 3 figure

Patient and Caregiver Priorities for Outcomes in CKD: A Multinational Nominal Group Technique Study

RATIONALE & OBJECTIVE: Patients with chronic kidney disease (CKD) are at an increased risk for premature death, cardiovascular disease, and burdensome symptoms that impair quality of life. We aimed to identify patient and caregiver priorities for outcomes in CKD. STUDY DESIGN: Focus groups with nominal group technique. SETTING & PARTICIPANTS: Adult patients with CKD (all stages) and caregivers in the United States, Australia, and United Kingdom. ANALYTICAL APPROACH: Participants identified, ranked, and discussed outcomes that were important during the stages of CKD before kidney replacement therapy. For each outcome, we calculated a mean importance score (scale, 0-1). Qualitative data were analyzed using thematic analysis. RESULTS: 67 (54 patients, 13 caregivers) participated in 10 groups and identified 36 outcomes. The 5 top-ranked outcomes for patients were kidney function (importance score, 0.42), end-stage kidney disease (0.29), fatigue (0.26), mortality (0.25), and life participation (0.20); and for caregivers, the top 5 outcomes were life participation (importance score, 0.38), kidney function (0.37), mortality (0.23), fatigue (0.21), and anxiety (0.20). Blood pressure, cognition, and depression were consistently ranked in the top 10 outcomes across role (patient/caregiver), country, and treatment stage. Five themes were identified: re-evaluating and reframing life, intensified kidney consciousness, battling unrelenting and debilitating burdens, dreading upheaval and constraints, and taboo and unspoken concerns. LIMITATIONS: Only English-speaking participants were included. CONCLUSIONS: Patients and caregivers gave highest priority to kidney function, mortality, fatigue, life participation, anxiety, and depression. Consistent reporting of these outcomes in research may inform shared decision making based on patient and caregiver priorities in CKD