A generalized quantum microcanonical ensemble

We discuss a generalized quantum microcanonical ensemble. It describes isolated systems that are not necessarily in an eigenstate of the Hamilton operator. Statistical averages are obtained by a combination of a time average and a maximum entropy argument to resolve the lack of knowledge about initial conditions. As a result, statistical averages of linear observables coincide with values obtained in the canonical ensemble. Non-canonical averages can be obtained by taking into account conserved quantities which are non-linear functions of the microstate.Comment: improved version, new titl

A guide to evaluating linkage quality for the analysis of linked data.

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Brain Microvascular Injury and White Matter Disease Provoked by Diabetes-Associated Hyperamylinemia

OBJECTIVE: The brain blood vessels of patients with type 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin. It is not known whether vascular amylin deposition is a consequence or a trigger of vascular injury. We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins. METHODS: Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with aggregated amylin were used for in vivo phenotyping. We also carried out biochemical analyses of human brain tissues and studied the effects of the aggregated amylin on endothelial cells ex vivo. RESULTS: Amylin deposition in brain blood vessels is associated with vessel wall disruption and abnormal surrounding neuropil in patients with type 2 diabetes and dementia, in HIP rats, and in AKO rats infused with aggregated amylin. HIP rats have brain microhemorrhages, white matter injury, and neurologic deficits. Vascular amylin deposition provokes loss of endothelial cell coverage and tight junctions. Intravenous infusion in AKO rats of human amylin, or combined human amylin and apolipoprotein E4, showed that amylin binds to plasma apolipoproteins. The intravenous infusion of apolipoprotein E4 exacerbated the brain accumulation of aggregated amylin and vascular pathology in HIP rats. INTERPRETATION: These data identify vascular amylin deposition as a trigger of brain endothelial dysfunction that is modulated by plasma apolipoproteins and represents a potential therapeutic target in diabetes-associated dementia and stroke. Ann Neurol 2017;82:208-222

Decoupling in an expanding universe: boundary RG-flow affects initial conditions for inflation

We study decoupling in FRW spacetimes, emphasizing a Lagrangian description throughout. To account for the vacuum choice ambiguity in cosmological settings, we introduce an arbitrary boundary action representing the initial conditions. RG flow in these spacetimes naturally affects the boundary interactions. As a consequence the boundary conditions are sensitive to high-energy physics through irrelevant terms in the boundary action. Using scalar field theory as an example, we derive the leading dimension four irrelevant boundary operators. We discuss how the known vacuum choices, e.g. the Bunch-Davies vacuum, appear in the Lagrangian description and square with decoupling. For all choices of boundary conditions encoded by relevant boundary operators, of which the known ones are a subset, backreaction is under control. All, moreover, will generically feel the influence of high-energy physics through irrelevant (dimension four) boundary corrections. Having established a coherent effective field theory framework including the vacuum choice ambiguity, we derive an explicit expression for the power spectrum of inflationary density perturbations including the leading high energy corrections. In accordance with the dimensionality of the leading irrelevant operators, the effect of high energy physics is linearly proportional to the Hubble radius H and the scale of new physics L= 1/M.Comment: LaTeX plus axodraw figures. v2: minor corrections; refs added. JHEP style: 34 pages + 18 pages appendi

First-order flows and stabilisation equations for non-BPS extremal black holes

We derive a generalised form of flow equations for extremal static and rotating non-BPS black holes in four-dimensional ungauged N = 2 supergravity coupled to vector multiplets. For particular charge vectors, we give stabilisation equations for the scalars, analogous to the BPS case, describing full known solutions. Based on this, we propose a generic ansatz for the stabilisation equations, which surprisingly includes ratios of harmonic functions.Comment: 27 pages; v2: presentation improved and references added as in the published versio

First-order flow equations for extremal and non-extremal black holes

We derive a general form of first-order flow equations for extremal and non-extremal, static, spherically symmetric black holes in theories with massless scalars and vectors coupled to gravity. By rewriting the action as a sum of squares a la Bogomol'nyi, we identify the function governing the first-order gradient flow, the `generalised superpotential', which reduces to the `fake superpotential' for non-supersymmetric extremal black holes and to the central charge for supersymmetric black holes. For theories whose scalar manifold is a symmetric space after a timelike dimensional reduction, we present the condition for the existence of a generalised superpotential. We provide examples to illustrate the formalism in four and five spacetime dimensions.Comment: 27 pages, v2: small changes, referencing and misprints corrected, v3: text updated and a reference added to match the JHEP versio