Quasi-normal modes, area spectra and multi-horizon spacetimes

We suggest an interpretation for the highly damped QNM frequencies of the spherically symmetric multi-horizon spacetimes (Reissner-Nordstrom, Schwarzschild-deSitter, Reissner-Nordstrom-deSitter) following Maggiore's proposal about the link between the asymptotic QNM frequencies and the black hole thermodynamics. We show that the behavior of the asymptotic frequencies is easy to understand if one assumes that all of the horizons have the same equispaced area spectra. The QNM analysis is then consistent with the choice of the area spectra to be the one originally proposed for the black hole's horizon by Bekenstein: A=8\pi n (in Planck units). The interpretation of the highly damped QNM frequencies in the multi-horizon case is based on the similar grounds as in the single horizon (Schwarzschild) case, but it has some new features that are discussed in the paper.Comment: 8 pages, v2: no physics changed, some references added, few sentences added in the discussion part

Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types.

Objective:  i) to describe the neuropsychiatric profile of elderly subjects with dementia by comparing vascular (VaD) and degenerative dementias, i.e. dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD); ii) to assess whether the severity and type of dementia are associated with clinically relevant neuropsychiatric symptoms (CR‐NPS). Method:  One hundred and thirty‐one out‐patients with VaD, 100 with DLB and 690 with AD were studied. NPS were evaluated by the neuropsychiatric inventory (NPI). Results:  Vascular dementia had lower total and domain‐specific NPI scores and a lower frequency of CR‐NPS than AD and DLB, for which frequency of CR‐NPS increased significantly with disease severity, particularly in AD. Logistic regression analysis showed that a higher CDR score and a diagnosis of degenerative dementia were independently associated with CR‐NPS. Conclusion:  Vascular dementia is associated less with CR‐NPS than AD and DLB. Frequency of CR‐NPS increases with disease severity in AD and, to a lesser extent, in DLB

Vitamin D and Risk of Neuroimaging Abnormalities.

Vitamin D deficiency has been linked with an increased risk of incident all-cause dementia and Alzheimer's disease. The aim of the current study was to explore the potential mechanisms underlying these associations by determining whether low vitamin D concentrations are associated with the development of incident cerebrovascular and neurodegenerative neuroimaging abnormalities. The population consisted of 1,658 participants aged ≥65 years from the US-based Cardiovascular Health Study who were free from prevalent cardiovascular disease, stroke and dementia at baseline in 1992-93. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected at baseline. The first MRI scan was conducted between 1991-1994 and the second MRI scan was conducted between 1997-1999. Change in white matter grade, ventricular grade and presence of infarcts between MRI scan one and two were used to define neuroimaging abnormalities. During a mean follow-up of 5.0 years, serum 25(OH)D status was not significantly associated with the development of any neuroimaging abnormalities. Using logistic regression models, the multivariate adjusted odds ratios (95% confidence interval) for worsening white matter grade in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (≥25-50 nmol/L) were 0.76 (0.35-1.66) and 1.09 (0.76-1.55) compared to participants with sufficient concentrations (≥50 nmol/L). The multivariate adjusted odds ratios for ventricular grade in participants who were severely 25(OH)D deficient and deficient were 0.49 (0.20-1.19) and 1.12 (0.79-1.59) compared to those sufficient. The multivariate adjusted odds ratios for incident infarcts in participants who were severely 25(OH)D deficient and deficient were 1.95 (0.84-4.54) and 0.73 (0.47-1.95) compared to those sufficient. Overall, serum vitamin D concentrations could not be shown to be associated with the development of cerebrovascular or neurodegenerative neuroimaging abnormalities in Cardiovascular Health Study participants.The Cardiovascular Health Study was supported by contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by AG023629, AG20098, AG15928 and HL084443 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at chs-nhlbi.org. Additional support was also provided by NIRG-11-200737 from the Alzheimer’s Association, the Mary Kinross Charitable Trust, the James Tudor Foundation, the Halpin Trust, the Age Related Diseases and Health Trust, and the Norman Family Charitable Trust (to D.J.L.). This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The National Institutes of Health was involved in the original design and conduct of the Cardiovascular Health Study and in the data collection methods

Question Answering on Scholarly Knowledge Graphs

Answering questions on scholarly knowledge comprising text and other artifacts is a vital part of any research life cycle. Querying scholarly knowledge and retrieving suitable answers is currently hardly possible due to the following primary reason: machine inactionable, ambiguous and unstructured content in publications. We present JarvisQA, a BERT based system to answer questions on tabular views of scholarly knowledge graphs. Such tables can be found in a variety of shapes in the scholarly literature (e.g., surveys, comparisons or results). Our system can retrieve direct answers to a variety of different questions asked on tabular data in articles. Furthermore, we present a preliminary dataset of related tables and a corresponding set of natural language questions. This dataset is used as a benchmark for our system and can be reused by others. Additionally, JarvisQA is evaluated on two datasets against other baselines and shows an improvement of two to three folds in performance compared to related methods.Comment: Pre-print for TPDL2020 accepted full paper, 14 page

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps

Intuitive visualization of data and results is very important in genomics, especially when many conditions are to be analyzed and compared. Heat-maps have proven very useful for the representation of biological data. Here we present Gitools (http://www.gitools.org), an open-source tool to perform analyses and visualize data and results as interactive heat-maps. Gitools contains data import systems from several sources (i.e. IntOGen, Biomart, KEGG, Gene Ontology), which facilitate the integration of novel data with previous knowledge

ADC Nonlinearity Correction for the Majorana Demonstrator

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy

The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or endosomes. In order to functionally evaluate endocytosis events resulted from pharmacological responses, we have developed an image analysis method -the Q-Endosomes algorithm- that specifically discriminates the fluorescent signal originated at endosomes from that one observed at the plasma membrane in images obtained from living cells by fluorescence microscopy. Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent protein (YFP) and permanently expressed in HEK293 cells was used as experimental model to validate this methodology. Time-course experiments performed with several agonists resulted in different sigmoid curves depending on the drug used to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by morphine plus serotonin was significantly different, in kinetics as well as in maximal response parameters, from the one caused by DAMGO, sufentanyl or methadone. Therefore, this analytical tool permits the pharmacological characterization of receptor endocytosis in living cells with functional and temporal resolution

Ecological conditions determine extinction risk in co-evolving bacteria-phage populations.

BACKGROUND: Antagonistic coevolution between bacteria and their viral parasites, phage, drives continual evolution of resistance and infectivity traits through recurrent cycles of adaptation and counter-adaptation. Both partners are vulnerable to extinction through failure of adaptation. Environmental conditions may impose unequal abiotic selection pressures on each partner, destabilising the coevolutionary relationship and increasing the extinction risk of one partner. In this study we explore how the degree of population mixing and resource supply affect coevolution-induced extinction risk by coevolving replicate populations of Pseudomonas fluorescens SBW25 with its associated lytic phage SBW25Ф2 under four treatment regimens incorporating low and high resource availability with mixed or static growth conditions. RESULTS: We observed an increased risk of phage extinction under population mixing, and in low resource conditions. High levels of evolved bacterial resistance promoted phage extinction at low resources under both mixed and static conditions, whereas phage populations could survive when phage susceptible bacterial genotypes rose to high frequency. CONCLUSIONS: These findings demonstrate that phage extinction risk is influenced by multiple abiotic conditions, which together act to destabilise the bacteria-phage coevolutionary relationship. The risk of coevolution-induced extinction is therefore dependent on the ecological context