Decidability of strong equivalence for subschemas of a class of linear, free, near-liberal program schemas

The article attached is a preprint version of the final published article which can be accessed at the link below. The article title has been changed. For referencing purposes please use the published details. Copyright © 2010 Elsevier B.V. All rights reserved.A program schema defines a class of programs, all of which have identical statement structure, but whose functions and predicates may differ. A schema thus defines an entire class of programs according to how its symbols are interpreted. Two schemas are strongly equivalent if they always define the same function from initial states to final states for every interpretation. A subschema of a schema is obtained from a schema by deleting some of its statements. A schema S is liberal if there exists an initial state in the Herbrand domain such that the same term is not generated more than once along any executable path through S. In this paper, we introduce near-liberal schemas, in which this non-repeating condition applies only to terms not having the form g() for a constant function symbol g. Given a schema S that is linear (no function or predicate symbol occurs more than once in S) and a variable v, we compute a set of function and predicate symbols in S which is a subset of those defined by Weiser's slicing algorithm and prove that if for every while predicate q in S and every constant assignment w:=g(); lying in the body of q, no other assignment to w also lies in the body of q, our smaller symbol set defines a correct subschema of S with respect to the final value of v after execution. We also prove that if S is also free (every path through S is executable) and near-liberal, it is decidable which of its subschemas are strongly equivalent to S. For the class of pairs of schemas in which one schema is a subschema of the other, this generalises a recent result in which S was required to be linear, free and liberal.This work was supported by a grant from the Engineering and Physical Sciences Research Council, Grant EP/E002919/1

Characterizing minimal semantics-preserving slices of predicate-linear, free, liberal program schemas

This is a preprint version of the article - Copyright @ 2011 ElsevierA program schema defines a class of programs, all of which have identical statement structure, but whose functions and predicates may differ. A schema thus defines an entire class of programs according to how its symbols are interpreted. A subschema of a schema is obtained from a schema by deleting some of its statements. We prove that given a schema S which is predicate-linear, free and liberal, such that the true and false parts of every if predicate satisfy a simple additional condition, and a slicing criterion defined by the final value of a given variable after execution of any program defined by S, the minimal subschema of S which respects this slicing criterion contains all the function and predicate symbols ‘needed’ by the variable according to the data dependence and control dependence relations used in program slicing, which is the symbol set given by Weiser’s static slicing algorithm. Thus this algorithm gives predicate-minimal slices for classes of programs represented by schemas satisfying our set of conditions. We also give an example to show that the corresponding result with respect to the slicing criterion defined by termination behaviour is incorrect. This complements a result by the authors in which S was required to be function-linear, instead of predicate-linear.This work was supported by a grant from the Engineering and Physical Sciences Research Council, Grant EP/E002919/1

Rate of infarct-edema growth on CT predicts need for surgical intervention and clinical outcome in patients with cerebellar infarction

BACKGROUND: Up to 20% of patients with cerebellar infarcts will develop malignant edema and deteriorate clinically. Radiologic measures, such as initial infarct size, aid in identifying individuals at risk. Studies of anterior circulation stroke suggest that mapping early edema formation improves the ability to predict deterioration; however, the kinetics of edema in the posterior fossa have not been well characterized. We hypothesized that faster edema growth within the first hours after acute cerebellar stroke would be an indicator for individuals requiring surgical intervention and those with worse neurological outcomes. METHODS: Consecutive patients admitted to the neurological intensive care unit with acute cerebellar infarction were retrospectively identified. Hypodense regions of infarct and associated edema, infarct-edema , were delineated by using ABC/2 for all computed tomography (CT) scans up to 14 days from last known well. To examine how rate of infarct-edema growth varied across clinical variables and surgical intervention status, nonlinear and linear mixed-effect models were performed over 2 weeks and 2 days, respectively. In patients with at least two CT scans, multivariable logistic regression examined clinical and radiological predictors of surgical intervention (defined as extraventricular drainage and/or posterior fossa decompression) and poor clinical outcome (discharge to skilled nursing facility, long-term acute care facility, hospice, or morgue). RESULTS: Of 150 patients with acute cerebellar infarction, 38 (25%) received surgical intervention and 45 (30%) had poor clinical outcome. Age, admission National Institutes of Health Stroke Scale (NIHSS) score, and baseline infarct-edema volume did not differ, but bilateral/multiple vascular territory involvement was more frequent (87% vs. 50%, p \u3c 0.001) in the surgical group than that in the medical intervention group. On 410 serial CTs, infarct-edema volume progressed rapidly over the first 2 days, followed by a subsequent plateau. Of 112 patients who presented within two days, infarct-edema growth rate was greater in the surgical group (20.1 ml/day vs. 8.01 ml/day, p = 0.002). Of 67 patients with at least two scans, after adjusting for baseline infarct-edema volume, vascular territory, and NIHSS, infarct-edema growth rate over the first 2 days (odds ratio 2.55; 95% confidence interval 1.40-4.65) was an independent, and the strongest, predictor of surgical intervention. Further, early infarct-edema growth rate predicted poor clinical outcome (odds ratio 2.20; 95% confidence interval 1.30-3.71), independent of baseline infarct-edema volume, brainstem infarct, and NIHSS. CONCLUSIONS: Early infarct-edema growth rate, measured via ABC/2, is a promising biomarker for identifying the need for surgical intervention in patients with acute cerebellar infarction. Additionally, it may be used to facilitate discussions regarding patient prognosis

Reduction in overt and silent stroke recurrence rate following cerebral revascularization surgery in children with sickle cell disease and severe cerebral vasculopathy

Background Children with sickle cell disease (SCD) and moyamoya may benefit from indirect cerebral revascularization surgery in addition to chronic blood transfusion therapy for infarct prevention. We sought to compare overt and silent infarct recurrence rates in children with SCD undergoing revascularization. Methods This was a retrospective cohort study of all children with SCD and moyamoya treated at two children’s hospitals. Clinical events and imaging studies were reviewed. Results Twenty-seven children with SCD and confirmed moyamoya receiving chronic transfusion therapy were identified, of whom 12 underwent indirect cerebral revascularization. Two subjects had post-operative transient ischemic attacks and another had a subarachnoid blood collection, none of which caused permanent consequences. Two subjects had surgical wound infections. Among these 12 children, the rate of overt and silent infarct recurrence decreased from 13.4 infarcts/100 patient-years before revascularization to 0 infarcts/100 patient-years after revascularization (p=0.0057); the post-revascularization infarct recurrence rate was also significantly lower than the overall infarct recurrence of 8.87 infarcts/100 patient-years in 15 children without cerebral revascularization (p=0.025). Conclusion The rate of overt and silent infarct recurrence was significantly lower following indirect cerebral revascularization. A prospective study of cerebral revascularization in children with SCD is needed

Neuroinflammation and amyloid deposition in the progression of mixed Alzheimer and vascular dementia

BACKGROUND: Alzheimer\u27s disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies coexist in patients with cognitive impairment. Abnormal amyloid beta (Aβ) deposition is the hallmark pathologic biomarker for AD. Neuroinflammation may be a pathophysiological mechanism in both AD and VCID. In this study, we aimed to understand the role of neuroinflammation and Aβ deposition in white matter hyperintensities (WMH) progression and cognitive decline over a decade in patients with mixed AD and VCID pathologies. METHODS: Twenty-four elderly participants (median [interquartile range] age 78 [64.8, 83] years old, 14 female) were recruited from the Knight Alzheimer Disease Research Center. RESULTS: Fifteen participants (62.5%) had mixed AD (positive PiB) and VCID (at least one vascular risk factor) pathologies. Elevated CONCLUSIONS: Neuroinflammation and Aβ deposition may represent two distinct pathophysiological pathways, and both independently contributed to the progression of cognitive impairment in mixed AD and VCID pathologies. Neuroinflammation, but not Aβ deposition, contributed to WMH volume and progression

Loss of lag-response curvilinearity of indices of heart rate variability in congestive heart failure

BACKGROUND: Heart rate variability (HRV) is known to be impaired in patients with congestive heart failure (CHF). Time-domain analysis of ECG signals traditionally relies heavily on linear indices of an essentially non-linear phenomenon. Poincaré plots are commonly used to study non-linear behavior of physiologic signals. Lagged Poincaré plots incorporate autocovariance information and analysis of Poincaré plots for various lags can provide interesting insights into the autonomic control of the heart. METHODS: Using Poincaré plot analysis, we assessed whether the relation of the lag between heart beats and HRV is altered in CHF. We studied the influence of lag on estimates of Poincaré plot indices for various lengths of beat sequence in a public domain data set (PhysioNet) of 29 subjects with CHF and 54 subjects with normal sinus rhythm. RESULTS: A curvilinear association was observed between lag and Poincaré plot indices (SD1, SD2, SDLD and SD1/SD2 ratio) in normal subjects even for a small sequence of 50 beats (p value for quadratic term 3 × 10(-5), 0.002, 3.5 × 10(-5 )and 0.0003, respectively). This curvilinearity was lost in patients with CHF even after exploring sequences up to 50,000 beats (p values for quadratic term > 0.5). CONCLUSION: Since lagged Poincaré plots incorporate autocovariance information, these analyses provide insights into the autonomic control of heart rate that is influenced by the non-linearity of the signal. The differences in lag-response in CHF patients and normal subjects exist even in the face of the treatment received by the CHF patients

Nuggets, Pearls, and Vignettes of Master Heart Failure Clinicians

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73696/1/j.1527-5299.2001.00307.x.pd

Dysfunction in the βII Spectrin-Dependent Cytoskeleton Underlies Human Arrhythmia.

Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked with cardiac pathologies including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction in cardiac electrical activity is not well understood, and often overlooked in the cardiac arrhythmia field. Methods and Results: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the post-translational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electrical and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes that include the Na/Ca exchanger, RyR2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin-deficient mice. Conclusions: Our findings identify βII spectrin as critical for normal myocyte electrical activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology