Numerical methods for the TSD equation in conservation law form

The Transonic Small Disturbance (TSD) Equation is a common model equation for describing subsonic and supersonic flow close to the local speed of sound (transonic). In transonic flow there is an embedded region of locally supersonic flow inside an otherwise subsonic flow. The supersonic region is usually terminated by a shock discontinuity. The success of a numerical scheme for transonic flow prediction depends on its capability of capturing all the flow details and non-linearities including sharp shock profiles without oscillations near the shock. Most of the important phenomena in the TSD equation occur in the stream-wise direction. The nonlinearity and changes in the region of influence depend only on the stream-wise derivation. A suitable one-dimensional model equation derived from the TSD Equation is used. The one-dimensional equation is written in conservation law form. This nonlinear system of equations models the transition from supersonic to subsonic flow. In the numerical calculations the discretised problem is treated as a series of Riemann problems. We will investigate various techniques for solving these Riemann problems. It will be shown that the techniques do not allow non-physical expansion shocks to develop and that the techniques smooth out expansion shocks when these non-physical shocks are present in the initial velocity profile. A comparison will be made between the schemes based on the sharpness of the resulting shock profiles

Transonic flow calculations using a dimensional splitting method

The time-dependent Transonic Small Disturbance equation, will be reformulated in Hyperbolic Conservation Law form. In Hyperbolic Conservation Law form, with dimensional splitting the equations can be discretized and treated as a series of Riemann problems. Steady subsonic and transonic flow calculations will be presented for a suitable test configuration and where possible comparisons will be made with analytic solutions

Buffered Versus Non-Buffered Lidocaine With Epinephrine for Mandibular Nerve Block: Clinical Outcomes

Outcomes for peak blood levels were assessed for buffered 2% lidocaine with 1:100,000 epinephrine compared with non-buffered 2% lidocaine with 1:100,000 epinephrine. In this institutional review board-approved prospective, randomized, double-blinded, crossover trial, the clinical impact of buffered 2% lidocaine with 1:100,000 epinephrine (Anutra Medical, Research Triangle Park, Cary, NC) was compared with the non-buffered drug. Venous blood samples for lidocaine were obtained 30 minutes after a mandibular nerve block with 80 mg of the buffered or unbuffered drug. Two weeks later, the same subjects were tested with the alternate drug combinations. Subjects also reported on pain on injection with a 10-point Likert-type scale and time to lower lip numbness. The explanatory variable was the drug formulation. Outcome variables were subjects' peak blood lidocaine levels, subjective responses to pain on injection, and time to lower lip numbness. Serum lidocaine levels were analyzed with liquid chromatography-mass spectrometry. Statistical analyses were performed using Proc TTEST (SAS 9.3; SAS Institute, Cary, NC), with the crossover option for a 2-period crossover design, to analyze the normally distributed outcome for pain. For non-normally distributed outcomes of blood lidocaine levels and time to lower lip numbness, an assessment of treatment difference was performed using Wilcoxon rank-sum tests with Proc NPAR1WAY (SAS 9.3). Statistical significance was set at a P value less than .05 for all outcomes. Forty-eight percent of subjects were women, half were Caucasian, 22% were African American, and 13% were Asian. Median age was 21 years (interquartile range [IQR], 20-22 yr), and median body weight was 147 lb (IQR, 130-170 lb). Median blood levels (44 blood samples) at 30 minutes were 1.19 μg/L per kilogram of body weight. Mean blood level differences of lidocaine for each patient were significantly lower after nerve block with the buffered drug compared with the non-buffered agent (P < .01). Mean score for pain on injection for nerve block (n = 46 scores) was 3.3 (standard deviation, 0.9). Seventy-eight percent of subjects reported lower or the same pain scores with the buffered drug; 61% of subjects reported a shorter time to lower lip numbness with the buffered drug. Buffering 2% lidocaine with epinephrine can produce clinical outcomes favorable for subjects and clinicians without clinically detrimental peak blood lidocaine levels

A Newly Identified Impairment in Both Vision and Hearing Increases the Risk of Deterioration in Both Communication and Cognitive Performance

Vision and hearing impairments are highly prevalent in adults 65 years of age and older. There is a need to understand their association with multiple health-related outcomes. We analyzed data from the Resident Assessment Instrument for Home Care (RAI-HC). Home care clients were followed for up to 5 years and categorized into seven unique cohorts based on whether or not they developed new vision and/or hearing impairments. An absolute standardized difference (stdiff) of at least 0.2 was considered statistically meaningful. Most clients (at least 60%) were female and 34.9 per cent developed a new sensory impairment. Those with a new concurrent vison and hearing impairment were more likely than those with no sensory impairments to experience a deterioration in receptive communication (stdiff = 0.68) and in cognitive performance (stdiff = 0.49). After multivariate adjustment, they had a twofold increased odds (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI]:1,87, 2.35) of deterioration in cognitive performance. Changes in sensory functioning are common and have important effects on multiple health-related outcomes

DNA cytosine hydroxymethylation levels are distinct among non-overlapping classes of peripheral blood leukocytes

AbstractBackgroundPeripheral blood leukocytes are the most commonly used surrogates to study epigenome-induced risk and epigenomic response to disease-related stress. We considered the hypothesis that the various classes of peripheral leukocytes differentially regulate the synthesis of 5-methylcytosine (5mCG) and its removal via Ten-Eleven Translocation (TET) dioxygenase catalyzed hydroxymethylation to 5-hydroxymethylcytosine (5hmCG), reflecting their responsiveness to environment. Although it is known that reductions in TET1 and/or TET2 activity lead to the over-proliferation of various leukocyte precursors in bone marrow and in development of chronic myelomonocytic leukemia and myeloproliferative neoplasms, the role of 5mCG hydroxymethylation in peripheral blood is less well studied.ResultsWe developed simplified protocols to rapidly and reiteratively isolate non-overlapping leukocyte populations from a single small sample of fresh or frozen whole blood. Among peripheral leukocyte types we found extreme variation in the levels of transcripts encoding proteins involved in cytosine methylation (DNMT1, 3A, 3B), the turnover of 5mC by demethylation (TET1, 2, 3), and DNA repair (GADD45A, B, G) and in the global and gene-region-specific levels of DNA 5hmCG (CD4+ T cells≫CD14+ monocytes>CD16+ neutrophils>CD19+ B cells>CD56+ NK cells>Siglec8+ eosinophils>CD8+ T cells).ConclusionsOur data taken together suggest a potential hierarchy of responsiveness among classes of leukocytes with CD4+, CD8+ T cells and CD14+ monocytes being the most distinctly poised for a rapid methylome response to physiological stress and disease

Structural brain differences between monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve

Two independent lines of research provide evidence that speaking more than one language may 1) contribute to increased grey matter in healthy younger and older adults and 2) delay cognitive symptoms in mild cognitive impairment (MCI) or Alzheimer disease (AD). We examined cortical thickness and tissue density in monolingual and multilingual MCI and AD patients matched (within Diagnosis Groups) on demographic and cognitive variables. In medial temporal disease-related (DR) areas, we found higher tissue density in multilingual MCIs versus monolingual MCIs, but similar or lower tissue density in multilingual AD versus monolingual AD, a pattern consistent with cognitive reserve in AD. In areas related to language and cognitive control (LCC), both multilingual MCI and AD patients had thicker cortex than the monolinguals. Results were largely replicated in our native-born Canadian MCI participants, ruling out immigration as a potential confound. Finally, multilingual patients showed a correlation between cortical thickness in LCC regions and performance on episodic memory tasks. Given that multilinguals and monolinguals were matched on memory functioning, this suggests that increased gray matter in these regions may provide support to memory functioning. Our results suggest that being multilingual may contribute to increased gray matter in LCC areas and may also delay the cognitive effects of disease-related atrophy

Early diagnosis of mild cognitive impairment and Alzheimer’s with event-related potentials and event-related desynchronization in N-back working memory tasks

Background and Objective: In this study we investigate whether or not event-related potentials (ERP) and/or event-related (de)synchronization (ERD/ERS) can be used to differentiate between 27 healthy elderly (HE), 21 subjects diagnosed with mild cognitive impairment (MCI) and 15 mild Alzheimer’s disease (AD) patients. Methods: Using 32-channel EEG recordings, we measured ERP responses to a three-level (N-back, N = 0,1,2) visual working memory task. We also performed ERD analysis over the same EEG data, dividing the full-band signal into the well-known delta, theta, alpha, beta and gamma bands. Both ERP and ERD analyses were followed by cluster analysis with correction for multicomparisons whenever significant differences were found between groups. Results: Regarding ERP (full-band analysis), our findings have shown both patient groups (MCI and AD) with reduced P450 amplitude (compared to HE controls) in the execution of the non-match 1-back task at many scalp electrodes, chiefly at parietal and centro-parietal areas. However, no significant differences were found between MCI and AD in ERP analysis whatever was the task. As for sub-band analyses, ERD/ERS measures revealed that HE subjects elicited consistently greater alpha ERD responses than MCI and AD patients during the 1-back task in the match condition, with all differences located at frontal, central and occipital regions. Moreover, in the non-match condition, it was possible to distinguish between MCI and AD patients when they were performing the 0-back task, with MCI presenting more desynchronization than AD on the theta band at temporal and fronto-temporal areas. In summary, ERD analyses have revealed themselves more valuable than ERP, since they showed significant differences in all three group comparisons: HE vs. MCI, HE vs. AD, and MCI vs. AD. Conclusions: Based on these findings, we conclude that ERD responses to working memory (N-back) tasks could be useful not only for early MCI diagnosis or for improved AD diagnosis, but probably also for assessing the likelihood o

Combined Impairments in Vision, Hearing and Cognition are Associated with Greater Levels of Functional and Communication Difficulties Than Cognitive Impairment Alone: Analysis of interRAI Data for Home Care and Long-Term Care Recipients in Ontario

Objectives: The objective of the current study was to understand the added effects of having a sensory impairment (vision and/or hearing impairment) in combination with cognitive impairment with respect to health-related outcomes among older adults (65+ years old) receiving home care or residing in a long-term care (LTC) facility in Ontario, Canada. Methods: Cross-sectional analyses were conducted using existing data collected with one of two interRAI assessments, one for home care (n = 291,824) and one for LTC (n = 110,578). Items in the assessments were used to identify clients with single sensory impairments (e.g., vision only [VI], hearing only [HI]), dual sensory impairment (DSI; i.e., vision and hearing) and those with cognitive impairment (CI). We defined seven mutually exclusive groups based on the presence of single or combined impairments. Results: The rate of people having all three impairments (i.e., CI+DSI) was 21.3% in home care and 29.2% in LTC. Across the seven groups, individuals with all three impairments were the most likely to report loneliness, to have a reduction in social engagement, and to experience reduced independence in their activities of daily living (ADLs) and instrumental ADLs (IADLs). Communication challenges were highly prevalent in this group, at 38.0% in home care and 49.2% in LTC. In both care settings, communication difficulties were more common in the CI+DSI group versus the CI-alone group. Conclusions: The presence of combined sensory and cognitive impairments is high among older adults in these two care settings and having all three impairments is associated with higher rates of negative outcomes than the rates for those having CI alone. There is a rising imperative for all health care professionals to recognize the potential presence of hearing, vision and cognitive impairments in those for whom they provide care, to ensure that basic screening occurs and to use those results to inform care plans

HtrA, fatty acids, and membrane protein interplay in Chlamydia trachomatis to impact stress response and trigger early cellular exit

UNLABELLED: Chlamydia trachomatis is an intracellular bacterial pathogen that undergoes a biphasic developmental cycle, consisting of intracellular reticulate bodies and extracellular infectious elementary bodies. A conserved bacterial protease, HtrA, was shown previously to be essential for Chlamydia during the reticulate body phase, using a novel inhibitor (JO146). In this study, isolates selected for the survival of JO146 treatment were found to have polymorphisms in the acyl-acyl carrier protein synthetase gene (aasC). AasC encodes the enzyme responsible for activating fatty acids from the host cell or synthesis to be incorporated into lipid bilayers. The isolates had distinct lipidomes with varied fatty acid compositions. A reduction in the lipid compositions that HtrA prefers to bind to was detected, yet HtrA and MOMP (a key outer membrane protein) were present at higher levels in the variants. Reduced progeny production and an earlier cellular exit were observed. Transcriptome analysis identified that multiple genes were downregulated in the variants especially stress and DNA processing factors. Here, we have shown that the fatty acid composition of chlamydial lipids, HtrA, and membrane proteins interplay and, when disrupted, impact chlamydial stress response that could trigger early cellular exit.IMPORTANCE: Chlamydia trachomatis is an important obligate intracellular pathogen that has a unique biphasic developmental cycle. HtrA is an essential stress or virulence protease in many bacteria, with many different functions. Previously, we demonstrated that HtrA is critical for Chlamydia using a novel inhibitor. In the present study, we characterized genetic variants of Chlamydia trachomatis with reduced susceptibility to the HtrA inhibitor. The variants were changed in membrane fatty acid composition, outer membrane proteins, and transcription of stress genes. Earlier and more synchronous cellular exit was observed. Combined, this links stress response to fatty acids, membrane proteins, and HtrA interplay with the outcome of disrupted timing of chlamydial cellular exit.</p