Uniform Time Average Consistency of Monte Carlo Particle Filters

We prove that bootstrap type Monte Carlo particle filters approximate the optimal nonlinear filter in a time average sense uniformly with respect to the time horizon when the signal is ergodic and the particle system satisfies a tightness property. The latter is satisfied without further assumptions when the signal state space is compact, as well as in the noncompact setting when the signal is geometrically ergodic and the observations satisfy additional regularity assumptions.Comment: 21 pages, 1 figur

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

A Simulation Approach to Optimal Stopping Under Partial Information

We study the numerical solution of nonlinear partially observed optimal stopping problems. The system state is taken to be a multi-dimensional diffusion and drives the drift of the observation process, which is another multi-dimensional diffusion with correlated noise. Such models where the controller is not fully aware of her environment are of interest in applied probability and financial mathematics. We propose a new approximate numerical algorithm based on the particle filtering and regression Monte Carlo methods. The algorithm maintains a continuous state-space and yields an integrated approach to the filtering and control sub-problems. Our approach is entirely simulation-based and therefore allows for a robust implementation with respect to model specification. We carry out the error analysis of our scheme and illustrate with several computational examples. An extension to discretely observed stochastic volatility models is also considered

Brain diffusivity in patients with neuropsychiatric systemic lupus erythematosus with new acute neurological symptoms

Purpose To investigate the source of significant difference in apparent diffusion coefficient (ADC) between patients with acute symptoms of neuropsychiatric (NP) systematic lupus erythematosus (SLE) (NPSLE) and normal controls. Materials and Methods Diffusion-weighted echo-planar imaging was performed on 1.5-T scanners in 17 female and four male NPSLE patients with acute neurological symptoms (23–76 years, mean = 42.7 years), and in 21 aged-matched healthy controls (16 female, five male, 26–63 years, mean = 41.1 years). ADC histograms were calculated for whole brain, gray matter tissue, and white matter tissue. Results Of the 17 NPSLE patients, 13 (72%) had abnormal findings on MR imaging. The NPSLE patients had a mean ADC value of (1105.1 ± 23.6) × 10 —6 mm 2 /second and the control had a mean ADC value of (1012.5 ± 9.4) × 10 −6 mm 2 /second ( P ≤ 0.0012). Significant differences were also found in white matter ( P ≤ 0.0020) and gray matter ( P ≤ 0.0022). Conclusion ADC histogram analysis demonstrated increased general diffusivity in the brain in NPSLE patients with acute symptoms compared with healthy normal controls. This finding suggests that in the brain parenchyma of NPSLE patients a loss of tissue integrity occurs facilitating motility of free-water protons. J. Magn. Reson. Imaging 2007;26:541–551. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56148/1/21036_ftp.pd

Supernova / Acceleration Probe: A Satellite Experiment to Study the Nature of the Dark Energy

The Supernova / Acceleration Probe (SNAP) is a proposed space-based experiment designed to study the dark energy and alternative explanations of the acceleration of the Universe's expansion by performing a series of complementary systematics-controlled measurements. We describe a self-consistent reference mission design for building a Type Ia supernova Hubble diagram and for performing a wide-area weak gravitational lensing study. A 2-m wide-field telescope feeds a focal plane consisting of a 0.7 square-degree imager tiled with equal areas of optical CCDs and near infrared sensors, and a high-efficiency low-resolution integral field spectrograph. The SNAP mission will obtain high-signal-to-noise calibrated light-curves and spectra for several thousand supernovae at redshifts between z=0.1 and 1.7. A wide-field survey covering one thousand square degrees resolves ~100 galaxies per square arcminute. If we assume we live in a cosmological-constant-dominated Universe, the matter density, dark energy density, and flatness of space can all be measured with SNAP supernova and weak-lensing measurements to a systematics-limited accuracy of 1%. For a flat universe, the density-to-pressure ratio of dark energy can be similarly measured to 5% for the present value w0 and ~0.1 for the time variation w'. The large survey area, depth, spatial resolution, time-sampling, and nine-band optical to NIR photometry will support additional independent and/or complementary dark-energy measurement approaches as well as a broad range of auxiliary science programs. (Abridged)Comment: 40 pages, 18 figures, submitted to PASP, http://snap.lbl.go

Treatment of hemangiomas in children using a Nd:YAG laser in conjunction with ice cooling of the epidermis: techniques and results

BACKGROUND: Hemangiomas are the most common type of congenital anomaly in childhood. Although many resolve spontaneously, intervention is required when their growth could damage vital adjacent structures. Various therapeutic approaches to childhood hemangiomas with different types of laser have been described previously. The objective of this study was to determine whether the cooling of the epidermis during irradiation of hemangiomas with a Nd:YAG laser prevents thermal damage and decreases the number of sessions required to treat these lesions. METHODS: Between 1993 and 2001, 110 patients aged 3 months to 4 years, with cutaneous hemangiomas were treated with a Nd:YAG laser. The lesion was cooled with ice prior to, during, and after the irradiation. During each session the laser beam passed through the pieces of ice. The laser power was between 35–45 W with a pulse length of 2–10 seconds. RESULTS: After 6 months of follow-up, from the first session of laser treatment, total resolution was obtained in 72 (65.5%) patients. A second or third session followed in 30 out of 38 patients in which, the initial results were good, moderate, or poor. The parents of the remaining eight children refused this second session and these patients excluded from the study Complications were seen in nine (8.8%) patients. One patient had postoperative bleeding which stopped spontaneously, while atrophic scars occurred in six (5.8%) patients, and hypertrophic scars in two (1.9%) patients. CONCLUSIONS: Nd:YAG laser irradiation in conjunction with ice protection of the epidermis produces good cosmetic results for the treatment of cutaneous hemangiomas in children, and decreases the number of sessions for treatment of these lesions

Sequence-Specific Binding of Recombinant Zbed4 to DNA: Insights into Zbed4 Participation in Gene Transcription and Its Association with Other Proteins

Zbed4, a member of the BED subclass of Zinc-finger proteins, is expressed in cone photoreceptors and glial Müller cells of human retina whereas it is only present in Müller cells of mouse retina. To characterize structural and functional properties of Zbed4, enough amounts of purified protein were needed. Thus, recombinant Zbed4 was expressed in E. coli and its refolding conditions optimized for the production of homogenous and functionally active protein. Zbed4’s secondary structure, determined by circular dichroism spectroscopy, showed that this protein contains 32% α-helices, 18% β-sheets, 20% turns and 30% unordered structures. CASTing was used to identify the target sites of Zbed4 in DNA. The majority of the DNA fragments obtained contained poly-Gs and some of them had, in addition, the core signature of GC boxes; a few clones had only GC-boxes. With electrophoretic mobility shift assays we demonstrated that Zbed4 binds both not only to DNA and but also to RNA oligonucleotides with very high affinity, interacting with poly-G tracts that have a minimum of 5 Gs; its binding to and GC-box consensus sequences. However, the latter binding depends on the GC-box flanking nucleotides. We also found that Zbed4 interacts in Y79 retinoblastoma cells with nuclear and cytoplasmic proteins Scaffold Attachment Factor B1 (SAFB1), estrogen receptor alpha (ERα), and cellular myosin 9 (MYH9), as shown with immunoprecipitation and mass spectrometry studies as well as gel overlay assays. In addition, immunostaining corroborated the co-localization of Zbed4 with these proteins. Most importantly, in vitro experiments using constructs containing promoters of genes directing expression of the luciferase gene, showed that Zbed4 transactivates the transcription of those promoters with poly-G tracts

GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin

Background: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. Methods: We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. Results: There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). Conclusions: In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did. © Schiariti et al

Primary care nurses struggle with lifestyle counseling in diabetes care: a qualitative analysis

Contains fulltext : 89605.pdf (publisher's version ) (Open Access)BACKGROUND: Patient outcomes are poorly affected by lifestyle advice in general practice. Promoting lifestyle behavior change require that nurses shift from simple advice giving to a more counseling-based approach. The current study examines which barriers nurses encounter in lifestyle counseling to patients with type 2 diabetes. Based on this information we will develop an implementation strategy to improve lifestyle behavior change in general practice. METHOD: In a qualitative semi-structured study, twelve in-depth interviews took place with nurses in Dutch general practices involved in diabetes care. Specific barriers in counseling patients with type 2 diabetes about diet, physical activity, and smoking cessation were addressed. The nurses were invited to reflect on barriers at the patient and practice levels, but mainly on their own roles as counselors. All interviews were audio-recorded and transcribed. The data were analyzed with the aid of a predetermined framework. RESULTS: Nurses felt most barriers on the level of the patient; patients had limited knowledge of a healthy lifestyle and limited insight into their own behavior, and they lacked the motivation to modify their lifestyles or the discipline to maintain an improved lifestyle. Furthermore, nurses reported lack of counseling skills and insufficient time as barriers in effective lifestyle counseling. CONCLUSIONS: The traditional health education approach is still predominant in primary care of patients with type 2 diabetes. An implementation strategy based on motivational interviewing can help to overcome 'jumping ahead of the patient' and promotes skills in lifestyle behavioral change. We will train our nurses in agenda setting to structure the consultation based on prioritizing the behavior change and will help them to develop social maps that contain information on local exercise programs