A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation

Deep brain stimulation (DBS) is an established therapy for Parkinson's Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian state-space methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms.National Institutes of Health (U.S.)(R01 MH-071847)National Institutes of Health (U.S.) (DP1 OD003646)National Institutes of Health (U.S.)(NS02172)IntElect Medical (Firm

Sum-over-histories origin of the composition laws of relativistic quantum mechanics and quantum cosmology

The scope of the paper has been broadened to include a more complete discussion of the following topics: The derivation of composition laws in quantum cosmology. The connection between the existence of a composition law in the sum over histories approach to relativistic quantum mechanics and quantum cosmology, and the existence of a canonical formulation.Comment: 36 page

Evidence-based decision support for pediatric rheumatology reduces diagnostic errors.

BACKGROUND: The number of trained specialists world-wide is insufficient to serve all children with pediatric rheumatologic disorders, even in the countries with robust medical resources. We evaluated the potential of diagnostic decision support software (DDSS) to alleviate this shortage by assessing the ability of such software to improve the diagnostic accuracy of non-specialists. METHODS: Using vignettes of actual clinical cases, clinician testers generated a differential diagnosis before and after using diagnostic decision support software. The evaluation used the SimulConsult® DDSS tool, based on Bayesian pattern matching with temporal onset of each finding in each disease. The tool covered 5405 diseases (averaging 22 findings per disease). Rheumatology content in the database was developed using both primary references and textbooks. The frequency, timing, age of onset and age of disappearance of findings, as well as their incidence, treatability, and heritability were taken into account in order to guide diagnostic decision making. These capabilities allowed key information such as pertinent negatives and evolution over time to be used in the computations. Efficacy was measured by comparing whether the correct condition was included in the differential diagnosis generated by clinicians before using the software ( unaided ), versus after use of the DDSS ( aided ). RESULTS: The 26 clinicians demonstrated a significant reduction in diagnostic errors following introduction of the software, from 28% errors while unaided to 15% using decision support (p \u3c 0.0001). Improvement was greatest for emergency medicine physicians (p = 0.013) and clinicians in practice for less than 10 years (p = 0.012). This error reduction occurred despite the fact that testers employed an open book approach to generate their initial lists of potential diagnoses, spending an average of 8.6 min using printed and electronic sources of medical information before using the diagnostic software. CONCLUSIONS: These findings suggest that decision support can reduce diagnostic errors and improve use of relevant information by generalists. Such assistance could potentially help relieve the shortage of experts in pediatric rheumatology and similarly underserved specialties by improving generalists\u27 ability to evaluate and diagnose patients presenting with musculoskeletal complaints. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02205086

Diagnosis of patients with heart failure with preserved ejection fraction in primary care : Cohort study

Aims Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure (HF), but low awareness and diagnostic challenges hinder identification in primary care. Our aims were to evaluate the recruitment and diagnostic strategy in the Optimise HFpEF cohort and compare with recent recommendations for diagnosing HFpEF. Methods and results Patients were recruited from 30 primary care practices in two regions in England using an electronic screening algorithm and two secondary care sites. Baseline assessment collected clinical and patient-reported data and diagnosis by history, assessment, and trans-thoracic echocardiogram (TTE). A retrospective evaluation compared study diagnosis with H2FPEF score and HFA-PEFF diagnostic algorithm. A total of 152 patients (86% primary care, mean age 78.5, 40% female) were enrolled; 93 (61%) had HFpEF confirmed. Most participants had clinical features of HFpEF, but those with confirmed HFpEF were more likely female, obese, functionally impaired, and symptomatic. Some echocardiographic findings were diagnostic for HFpEF, but no difference in natriuretic peptide levels were observed. The H2FPEF and HFA-PEFF scores were not significantly different by group, although confirmed HFpEF cases were more likely to have scores indicating high probability of HFpEF. Conclusions Patients with HFpEF in primary care are difficult to identify, and greater awareness of the condition, with clear diagnostic pathways and specialist support, are needed. Use of diagnostic algorithms and scores can provide systematic approaches to diagnosis but may be challenging to apply in older multi-morbid patients. Where diagnostic uncertainty remains, pragmatic decisions are needed regarding the value of additional testing versus management of presumptive HFpEF

Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study

Background & AimsPatients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward.MethodsIn a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child–Turcotte–Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation.ResultsSixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%).ConclusionsAdministration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844

Dementias show differential physiological responses to salient sounds.

Abnormal responsiveness to salient sensory signals is often a prominent feature of dementia diseases, particularly the frontotemporal lobar degenerations, but has been little studied. Here we assessed processing of one important class of salient signals, looming sounds, in canonical dementia syndromes. We manipulated tones using intensity cues to create percepts of salient approaching ("looming") or less salient withdrawing sounds. Pupil dilatation responses and behavioral rating responses to these stimuli were compared in patients fulfilling consensus criteria for dementia syndromes (semantic dementia, n = 10; behavioral variant frontotemporal dementia, n = 16, progressive nonfluent aphasia, n = 12; amnestic Alzheimer's disease, n = 10) and a cohort of 26 healthy age-matched individuals. Approaching sounds were rated as more salient than withdrawing sounds by healthy older individuals but this behavioral response to salience did not differentiate healthy individuals from patients with dementia syndromes. Pupil responses to approaching sounds were greater than responses to withdrawing sounds in healthy older individuals and in patients with semantic dementia: this differential pupil response was reduced in patients with progressive nonfluent aphasia and Alzheimer's disease relative both to the healthy control and semantic dementia groups, and did not correlate with nonverbal auditory semantic function. Autonomic responses to auditory salience are differentially affected by dementias and may constitute a novel biomarker of these diseases

Diagnosis of patients with heart failure with preserved ejection fraction in primary care: cohort study

Funder: NIHR Cambridge Clinical Research FacilityAbstract: Aims: Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure (HF), but low awareness and diagnostic challenges hinder identification in primary care. Our aims were to evaluate the recruitment and diagnostic strategy in the Optimise HFpEF cohort and compare with recent recommendations for diagnosing HFpEF. Methods and results: Patients were recruited from 30 primary care practices in two regions in England using an electronic screening algorithm and two secondary care sites. Baseline assessment collected clinical and patient‐reported data and diagnosis by history, assessment, and trans‐thoracic echocardiogram (TTE). A retrospective evaluation compared study diagnosis with H2FPEF score and HFA‐PEFF diagnostic algorithm. A total of 152 patients (86% primary care, mean age 78.5, 40% female) were enrolled; 93 (61%) had HFpEF confirmed. Most participants had clinical features of HFpEF, but those with confirmed HFpEF were more likely female, obese, functionally impaired, and symptomatic. Some echocardiographic findings were diagnostic for HFpEF, but no difference in natriuretic peptide levels were observed. The H2FPEF and HFA‐PEFF scores were not significantly different by group, although confirmed HFpEF cases were more likely to have scores indicating high probability of HFpEF. Conclusions: Patients with HFpEF in primary care are difficult to identify, and greater awareness of the condition, with clear diagnostic pathways and specialist support, are needed. Use of diagnostic algorithms and scores can provide systematic approaches to diagnosis but may be challenging to apply in older multi‐morbid patients. Where diagnostic uncertainty remains, pragmatic decisions are needed regarding the value of additional testing versus management of presumptive HFpEF

Physics Laws of Social Science

Economics, and other fields of social science are often criticized as unscientific for their apparent failures to formulate universal laws governing human societies. Whether economics is truly a science is one of the oldest questions. This paper attempts to create such universal laws, and asserts that economics is a branch of quantum physics just like chemistry. Choice is a central concept in economics and other fields of social science, yet there is no corresponding concept of choice in modern physics. This article suggests that by introducing the concept of choice to the existing framework of physics, one can formulate five new physics laws, which establishes a common physics foundation for all fields of social and natural science. Applications in economics, biology, history, and finance prove that these new laws remove the invisible wall, which has been artificially separating social science from natural science. One implication of this article is that to establish a sound scientific foundation for social science requires not only advances in psychology and neurobiology but also a new interpretation of quantum mechanics