Newton-Krylov continuation of amplitude-modulated rotating waves in sheared annular electroconvection.

We present an approach for studying the primary, secondary, and tertiary flow transitions in sheared annular electroconvection. In particular, we describe a Newton-Krylov method based on time integration for the computation of rotating waves and amplitude-modulated rotating waves, and for the continuation of these flows as a parameter of the system is varied. The method exploits the rotational nature of the flows and requires only a time-stepping code of the model differential equations, i.e., it does not require an explicit code for the discretization of the linearized equations. The linear stability of the solutions is computed to identify the parameter values at which the transitions occur. We apply the method to a model of electroconvection that simulates the flow of a liquid crystal film in the smectic A phase suspended between two annular electrodes and subjected to an electric potential difference and a radial shear. Due to the layered structure of the smectic A phase, the fluid can be treated as two-dimensional (2D) and is modeled using the 2D incompressible Navier-Stokes equations coupled with an equation for charge continuity. The system is a close analog to laboratory-scale geophysical fluid experiments and thus represents an ideal system in which to apply the method before its application to these other systems that exhibit similar flow transitions. In the model for electroconvection, we identify the parameter values at which the primary transition from steady axisymmetric flow to rotating waves occurs, as well as at which the secondary transition from the rotating waves to amplitude-modulated rotating waves occurs. In addition, we locate the tertiary transition, which corresponds to a transition from the amplitude-modulated waves to a three-frequency flow. Of particular interest is that the method also finds a period-doubling bifurcation from the amplitude-modulated rotating waves and a subsequent transition from the flow resulting from this bifurcation.

Hidden species diversity in an iconic living fossil vertebrate.

Ancient, species-poor lineages persistently occur across the Tree of life. These lineages are likely to contain unrecognized species diversity masked by the low rates of morphological evolution that characterize living fossils. Halecomorphi is a lineage of ray-finned fishes that diverged from its closest relatives before 200 Ma and is represented by only one living species in eastern North America, the bowfin, Amia calva Linnaeus. Here, we use double digest restriction-site-associated DNA sequencing and morphology to illuminate recent speciation in bowfins. Our results support the delimitation of a second living species of Amia, with the timing of diversification dating to the Plio-Pleistocene. This delimitation expands the species diversity of an ancient lineage that is integral to studies of vertebrate genomics and development, yet is facing growing conservation threats driven by the caviar fishery.

Massive Perivillous Fibrin Deposition and Chronic Histiocytic Intervillositis a Complication of SARS-CoV-2 Infection.

An emerging complication of COVID-19 (SARS-CoV-2) infection is reported. A 23-year-old patient presented with high temperature and reduced fetal movements at 25 + 5/40 weeks of gestation. RT-PCR proved maternal COVID-19 infection. Ultrasound examination confirmed intrauterine death. Placenta histology showed necrosis of the villous trophoblast, associated with Chronic Histiocytic Intervillositis (CHI) and Massive Perivillous Fibrin Deposition (MPFD) with up to 90% - of the intervillous spaces being involved. Immunohistochemistry showed CD68 positive histiocytes in the intervillous spaces and the villous trophoblast was positive for the COVID-19 spike protein. RNA scope signal was indicative of the presence of the viral genome and active viral replication in the villous trophoblastic cells, respectively. MPFD is a gradually developing end-stage disease with various etiology, including autoimmune and alloimmune maternal response to antigens expressed at the feto-maternal interface and frequently accompanies chronic alloimmune villitis or histiocytic intervillositis. Covid-19 infection is associated with similar pattern of histological changes of the placenta leading to placental insufficiency and fetal death. This case report supports maternal- fetal vertical transmission of SARS-CoV-2 virus leading to placental insufficiency and fetal demise. MPFD and CHI appear to be the typical placental histology for SARS-CoV-2 virus infection associated fetal demise.

Statins in survivors of traumatic brain injury: a propensity score-matched analysis.

BACKGROUND: Several in-vitro and animal studies suggest that statins may have beneficial effects on clinical outcomes of traumatic brain injury (TBI), however, clinical data are scarce. OBJECTIVES: To examine the association of statin use with TBI clinical outcomes among patients with TBI. METHODS: A retrospective cohort study of Tricare beneficiaries who had a TBI diagnosis, as defined by the Barbell injury diagnosis matrix. Outcomes were defined using ICD-9 codes and included: post-concussion syndrome, neurological disorders, substance dependence or abuse, and psychiatric disorders. Statin-users and non-users were propensity score (PS)-matched using 103 baseline characteristics. RESULTS: Out of 1187 adult patients with a TBI diagnosis (172 statin-users and 1015 nonusers), we PS-matched 70 statin-users to 70 non-users. There were no statistically significant differences in the PS-matched cohort of statin-users in comparison to nonusers for post-concussion syndrome (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.03-2.20), neurological disorders (OR: 0.60, CI: 0.31-1.16); substance dependence or abuse (OR: 0.80, CI: 0.40-1.60), or psychiatric disorders (OR 0.80, CI: 0.41-1.55). CONCLUSION: This study did not show benefit or harm for statins among survivors of TBI. Our findings do not support the evidence from some animal studies and small randomized controlled trials. Further studies utilizing larger sample sizes are warranted.

Prevalence of hearing loss and tinnitus in Iraq and Afghanistan Veterans: A Chronic Effects of Neurotrauma Consortium study.

The purpose of this study was to describe the prevalence of hearing loss and tinnitus in a cohort of Iraq and Afghanistan Veterans (IAV) with common post-deployment conditions, including traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and other typical post-concussive conditions such as headaches and vertigo/dizziness. This retrospective observational study used data from the national Veterans Health Administration (VA) data repository from fiscal years 2001-2014. Veteran data was included if there were at least three years of VA care, with one or more years of care in 2007 or after. We identified comorbidities that may be associated with post-deployment hearing loss or tinnitus including TBI, PTSD, depression, and common post-concussive symptoms using International Classification of Diseases, 9th Revision, Clinical Modification codes. A multinomial logistic regression analysis was used to examine conditions associated with hearing loss or tinnitus. Among IAV, 570,332 were included in the final analysis. Of these, 7.78% of these were diagnosed with hearing loss alone, 6.54% with tinnitus alone, and 6.24% with both hearing loss and tinnitus. Comorbid TBI, PTSD, and depression were significantly associated with increased rates of hearing loss, tinnitus, or both conditions together. Older individuals, males, and those with TBI, PTSD, or vertigo/dizziness were significantly more likely to have hearing loss, tinnitus, or both. In order to provide more holistic post-deployment support, this myriad of conditions should be carefully considered in the planning of clinical care and beyond.

Hearing testing in the U.S. Department of Defense: Potential impact on Veterans Affairs hearing loss disability awards.

Hearing loss is the second most common disability awarded by the U.S. Department of Veterans Affairs (VA) to former members of the U.S. uniformed services. Hearing readiness and conservation practices differ among the four largest uniformed military services (Air Force, Army, Marine Corps, and Navy). Utilizing a data set consisting of all hearing loss claims submitted to the VA from fiscal years 2003-2013, we examined characteristics of veterans submitting claims within one year of separation from military service. Our results indicate that having a hearing loss disability claim granted was significantly more likely for men, individuals over the age of 26 years at the time of the claim, individuals most recently serving in the U.S. Army, and those with at least one hearing loss diagnosis. Importantly, individuals with at least one test record in the Defense Occupational and Environmental Health Readiness System-Hearing Conservation (DOEHRS-HC) system were significantly less likely to have a hearing loss disability claim granted by the VA. Within the DOEHRS-HC cohort, those with at least one threshold shift or clinical hearing loss diagnosis while on active duty were more than two and three times more likely to have a hearing loss disability claim granted, respectively. These findings indicate that an established history of reduced hearing ability while on active duty was associated with a significantly increased likelihood of an approved hearing loss disability claim relative to VA claims without such a history. Further, our results show a persistent decreased rate of hearing loss disability awards overall. These findings support increased inclusion of personnel in DoD hearing readiness and conservation programs to reduce VA hearing loss disability awards.

A finite volume method and experimental study of a stator of a piezoelectric traveling wave rotary ultrasonic motor.

Piezoelectric traveling wave rotary ultrasonic motors are motors that generate torque by using the friction force between a piezoelectric composite ring (or disk-shaped stator) and a metallic ring (or disk-shaped rotor) when a traveling wave is excited in the stator. The motor speed is proportional to the amplitude of the traveling wave and, in order to obtain large amplitudes, the stator is excited at frequencies close to its resonance frequency. This paper presents a non-empirical partial differential equations model for the stator, which is discretized using the finite volume method. The fundamental frequency of the discretized model is computed and compared to the experimentally-measured operating frequency of the stator of Shinsei USR60 piezoelectric motor.

Validating a natural language processing tool to exclude psychogenic nonepileptic seizures in electronic medical record-based epilepsy research.

RATIONALE: As electronic health record (EHR) systems become more available, they will serve as an important resource for collecting epidemiologic data in epilepsy research. However, since clinicians do not have a systematic method for coding psychogenic nonepileptic seizures (PNES), patients with PNES are often misclassified as having epilepsy, leading to sampling error. This study validates a natural language processing (NLP) tool that uses linguistic information to help identify patients with PNES. METHODS: Using the VA national clinical database, 2200 notes of Iraq and Afghanistan veterans who completed video electroencephalograph (VEEG) monitoring were reviewed manually, and the veterans were identified as having documented PNES or not. Reviewers identified PNES-related vocabulary to inform a NLP tool called Yale cTakes Extension (YTEX). Using NLP techniques, YTEX annotates syntactic constructs, named entities, and their negation context in the EHR. These annotations are passed to a classifier to detect patients without PNES. The classifier was evaluated by calculating positive predictive values (PPVs), sensitivity, and F-score. RESULTS: Of the 742 Iraq and Afghanistan veterans who received a diagnosis of epilepsy or seizure disorder by VEEG, 44 had documented events on VEEG: 22 veterans (3.0%) had definite PNES only, 20 (2.7%) had probable PNES, and 2 (0.3%) had both PNES and epilepsy documented. The remaining 698 veterans did not have events captured during the VEEG admission and/or did not have a definitive diagnosis. Our classifier achieved a PPV of 93%, a sensitivity of 99%, and a F-score of 96%. CONCLUSION: Our study demonstrates that the YTEX NLP tool and classifier is highly accurate in excluding PNES, diagnosed with VEEG, in EHR systems. The tool may be very valuable in preventing false positive identification of patients with epilepsy in EHR-based epidemiologic research.

Validation of self-reported epilepsy for purposes of community surveillance.

We evaluated the validity of questions designed to identify lifetime and active epilepsy, medication use, and seizure occurrence on population-based surveys. Subjects were interviewed by telephone, and responses were compared with information in their medical records. Prevalence, sensitivity, specificity, and positive predictive value (PPV) were calculated. The prevalence of ever having been diagnosed with epilepsy was 3.1% by self-report and 2.7% by medical record review. Sensitivity was 84.2%, specificity was 99.2%, and PPV was 73.5% for self-reported lifetime epilepsy, and values were similar for active epilepsy. By comparison, sensitivity was higher and specificity was lower for epilepsy medication use and seizure occurrence. The PPV for seizure occurrence was substantially higher for a recall period of 12 months than for 3 months. These results compare favorably with results for other chronic conditions, such as diabetes and arthritis, and indicate that questionnaires can be used to identify epilepsy at a population level.

Guideline-concordant therapy and outcomes in healthcare-associated pneumonia.

Healthcare-associated pneumonia (HCAP) guidelines were first proposed in 2005 but have not yet been validated. The objective of this study was to compare 30-day mortality in HCAP patients treated with either guideline-concordant (GC)-HCAP therapy or GC community-acquired pneumonia (CAP) therapy. We performed a population-based cohort study of >150 hospitals in the US Veterans Health Administration. Patients were included if they had one or more HCAP risk factors and received antibiotic therapy within 48 h of admission. Critically ill patients were excluded. Independent risk factors for 30-day mortality were determined in a generalised linear mixed-effect model, with admitting hospital as a random effect. Propensity scores for the probability of receiving GC-HCAP therapy were calculated and incorporated into a second logistic regression model. A total of 15,071 patients met study criteria and received GC-HCAP therapy (8.0%), GC-CAP therapy (75.7%) or non-GC therapy (16.3%). The strongest predictors of 30-day mortality were recent hospital admission (OR 2.49, 95% CI 2.12-2.94) and GC-HCAP therapy (OR 2.18, 95% CI 1.86-2.55). GC-HCAP therapy remained an independent risk factor for 30-day mortality (OR 2.12, 95% CI 1.82-2.48) in the propensity score analysis. In nonsevere HCAP patients, GC-HCAP therapy is not associated with improved survival compared with GC-CAP therapy.

Risk of adverse events on epilepsy monitoring units: a survey of epilepsy professionals.

In 2008 a workgroup of health care professionals from the American Epilepsy Society (AES) was convened to address the lack of consensus regarding patient care in epilepsy monitoring units (EMUs). The group developed a questionnaire designed to identify the extent to which selected adverse events occurred in EMUs, and it was sent via email to all members of the AES. We asked that only one representative from each center report. Seventy responses were received. The number of centers reporting the following adverse events included: falls by 69%, status epilepticus by 63%, and postictal psychosis by 54%. Infrequent events with serious consequences were also reported including pneumonia by 10%, cardiac arrest by 7%, fractures by 6%, and death by 3% (N=2). Of the 58 respondents who reported using intracranial electrodes, 37.9% (N=22) reported that patients pulled out or dislodged electrodes. This study highlights the need for EMUs to identify and address potential safety risks in their environment, patient population, and system of care.

Metabolic and hormonal derangements in pulmonary hypertension: from mouse to man.

Pulmonary arterial hypertension (PAH) is a complex disease with significant morbidity and mortality. Recent animal and human studies have highlighted abnormalities in regulation and metabolism of insulin, sex hormones, adipokines and lipids that may play a role in disease development. Mouse studies suggest features of the metabolic syndrome (MS) including insulin resistance, deficiencies in peroxisome proliferator-activated receptor γ and apolipoprotein E, and low adiponectin are linked to development of PAH. In humans, insulin resistance, the MS and low levels of high-density lipoprotein have been associated with PAH. In addition, abnormal metabolism of oestrogens has been demonstrated in human and animal models of PAH, suggesting an important relationship of sex hormones and pulmonary vascular disease. Improved understanding of how metabolic and hormonal derangements relate to development and progression of pulmonary hypertension may lead to better disease therapies and understanding of potential risk factors. This review will focus on the animal and human data regarding metabolic and sex hormone derangements in PAH.

Inhaled corticosteroid use is associated with lower mortality for subjects with COPD and hospitalised with pneumonia.

Recent studies suggest that use of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) may be associated with a higher incidence of pneumonia. However, it is unclear whether COPD subjects on ICS who develop pneumonia have worse outcomes. Therefore, our aim was to examine the association of prior outpatient ICS therapy with mortality in hospitalised COPD subjects with pneumonia. We included subjects ≥64 yrs of age, hospitalised with pneumonia in US Veterans Affairs hospitals, and assessed the association of ICS exposure with mortality for hospitalised COPD subjects with pneumonia in a covariate-adjusted regression model. We identified 6,353 subjects with a diagnosis of pneumonia and prior COPD, of whom 38% were on ICS. Mortality was 9% at 30 days and 16% at 90 days. In regression analyses, outpatient ICS therapy was associated with lower mortality at both 30 days (OR 0.76, 95% CI 0.70-0.83), and 90 days (OR 0.80, 95% CI 0.75-0.86). Outpatient therapy with ICS was associated with a significantly lower 30- and 90-day mortality in hospitalised COPD patients with pneumonia.

Trends in antiepileptic drug prescribing for older patients with new-onset epilepsy: 2000-2004.

BACKGROUND: Newer antiepileptic drugs (AEDs) have been shown to be equally efficacious as older seizure medications but with fewer neurotoxic and systemic side effects in the elderly. A growing body of clinical recommendations based on systematic literature review and expert opinion advocate the use of the newer agents and avoidance of phenobarbital and phenytoin. This study sought to determine if changes in practice occurred between 2000 and 2004--a time during which evidence and recommendations became increasingly available. METHODS: National data from the Veterans Health Administration (VA; inpatient, outpatient, pharmacy) from 1998 to 2004 and Medicare data (1999-2004) were used to identify patients 66 years and older with new-onset epilepsy. Initial AED was the first AED received from the VA. AEDs were categorized into four groups: phenobarbital, phenytoin, standard (carbamazepine, valproate), and new (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate). RESULTS: We found a small reduction in use of phenytoin (70.6% to 66.1%) and phenobarbital (3.2% to 1.9%). Use of new AEDs increased significantly from 12.9% to 19.8%, due primarily to use of lamotrigine, levetiracetam, and topiramate. CONCLUSIONS: Despite a growing list of clinical recommendations and guidelines, phenytoin was the most commonly used antiepileptic drug, and there was little change in its use for elderly patients over 5 years. Research further exploring physician and health care system factors associated with change (or lack thereof) will provide better insight into the impact of clinical recommendations on practice.

Impact of statins and angiotensin-converting enzyme inhibitors on mortality of subjects hospitalised with pneumonia.

Recent studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for some types of infections. The present study aimed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged >65 yrs and hospitalised with community-acquired pneumonia. A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged >/=65 yrs hospitalised with community-acquired pneumonia, and having >/=1 yr of prior Veterans Affairs outpatient care. In total, 8,652 subjects were identified with a mean age of 75 yrs, 98.6% were male, and 9.9% of subjects died within 30 days of presentation. In this cohort, 18.1% of subjects were using statins and 33.9% were using ACE inhibitors. After adjusting for potential confounders, current statin use (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.42-0.70) and ACE inhibitor use (OR 0.80, 95% CI 0.68-0.89) were significantly associated with decreased 30-day mortality. Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia. Randomised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial.

What constitutes high quality of care for adults with epilepsy?

BACKGROUND: Providers are increasingly being held accountable for the quality of care provided. While quality indicators have been used to benchmark the quality of care for a number of other disease states, no such measures are available for evaluating the quality of care provided to adults with epilepsy. In order to assess and improve quality of care, it is critical to develop valid quality indicators. Our objective is to describe the development of quality indicators for evaluating care of adults with epilepsy. As most care is provided in primary and general neurology care, we focused our assessment of quality on care within primary care and general neurology clinics. METHODS: We reviewed existing national clinical guidelines and systematic reviews of the literature to develop an initial list of quality indicators; supplemented the list with indicators derived from patient focus groups; and convened a 10-member expert panel to rate the appropriateness, reliability, and necessity of each quality indicator. RESULTS: From the original 37 evidence-based and 10 patient-based quality indicators, the panel identified 24 evidence-based and 5 patient-based indicators as appropriate indicators of quality. Of these, the panel identified 9 that were not necessary for high quality care. CONCLUSION: There is, at best, a poor understanding of the quality of care provided for adults with epilepsy. These indicators, developed based on published evidence, expert opinion, and patient perceptions, provide a basis to assess and improve the quality of care for this population.

A finite locus effect diffusion model for the evolution of a quantitative trait.

A diffusion model is constructed for the joint distribution of absolute locus effect sizes and allele frequencies for loci contributing to an additive quantitative trait under selection in a haploid, panmictic population. The model is designed to approximate a discrete model exactly in the limit as both population size and the number of loci affecting the trait tend to infinity. For the case when all loci have the same absolute effect size, formal multiple-timescale asymptotics are used to predict the long-time response of the population trait mean to selection. For the case where loci can take on either of two distinct effect sizes, not necessarily with equal probability, numerical solutions of the system indicate that response to selection of a quantitative trait is insensitive to the variability of the distribution of effect sizes when mutation is negligible.

Pharmacological and clinical aspects of antiepileptic drug use in the elderly.

In this article, epidemiological and clinical aspects related to the use of antiepileptic drugs (AEDs) in the elderly are highlighted. Studies have shown that people with epilepsy receiving AED treatment show important deficits in physical and social functioning compared with age-matched people without epilepsy. To what extent these deficits can be ascribed to epilepsy per se or to the consequences of AED treatment remains to be clarified. The importance of characterizing the effects of AEDs in an elderly population is highlighted by epidemiological surveys indicating that the prevalence of AED use is increased in elderly people, particularly in those living in nursing homes. Both the pharmacokinetics and the pharmacodynamics of AEDs may be altered in old age, which may contribute to the observation that AEDs are among the drug classes most commonly implicated as causing adverse drug reactions in an aged population. Age alone is one of several contributors to alterations in AED response in the elderly; other factors include physical frailty, co-morbidities, dietary influences, and drug interactions. Individualization of dosage, avoidance of unnecessary polypharmacy, and careful observation of clinical response are essential for an effective and safe utilization of AEDs in an elderly population.

Quality of care for NSAID users: development of an assessment tool.

OBJECTIVE: Assessments of NSAID use based on authoritative guidelines typically overlook patients' views and nuances of medical history. Our objective was to develop an assessment tool that incorporates these aspects, and technical items, for quality of care assessments in NSAID users. METHODS: Patients newly referred to a university hospital were interviewed by a nurse using an agreed template. A multidisciplinary group of rheumatologists, nurse specialists, primary care physicians and a pharmacist reviewed current guidance and systematic reviews on NSAID use, and a series of interview transcripts. The group agreed, by informal consensus, important determinants of effective and safe NSAID use. Technical aspects of medical care and items that reflected interpersonal care were included in an index for assessing quality of care for individual patients. Interview transcripts of 100 patients were scored by panel members and reliability of scores was tested by calculating weighted percentage agreement and the kappa statistic. RESULTS: Our final index had five domains: medical risk factors; steps taken to reduce risk; knowledge of adverse effects; NSAID dose; and cost efficiency. Each item was scored 0, 1 or 2. Scores were summed, giving a maximum of 10 (low scores indicating low quality). Intra-rater agreement was >90%; kappa was 0.47-0.87 for individual domains and 0.59 for overall score. Inter-rater agreement for overall score was 95%; kappa was 0.25-0.78 for domains and 0.48 for overall score. Patients with especially low scores were identified using the mode of scores for five assessors; obvious clinical concerns were identified, supporting index face validity. CONCLUSIONS: A simple index to evaluate quality of care for NSAID users based on a patient interview is described. This may be used by one or more assessors to examine care standards and highlight deficiencies in relation to NSAID use in practice.

Determination of E2 for nitride ceramics using FE-SEM and the Duane-Hunt limit procedure.

This work demonstrates the possibility of using the Duane-Hunt limit of the bremsstrahlung to determine E2 values of Si3N4 and AlN ceramics. The E(DHL) versus E0 graph demonstrates that for conductive materials, the experimental curve is parallel to the theoretical (E(DHL) = E0), but both curves cross in the case of insulators. The intersection points (E2 value), are 3.01 keV for Si3N4 and 2.67 keV for AlN. Imaging of ceramic grain structure at high magnification was performed to demonstrate the validity of the calculated E2 values.