Tag: nevin manimala

Acta Ophthalmol. 2021 Jul 7. doi: 10.1111/aos.14973. Online ahead of print.

ABSTRACT

PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets.

METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups.

RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2% when all three risk factors were present versus 4.4% when none were present (c-index = 0.737, 95% CI: 0.608, 0.865; p < 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475).

CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.

PMID:34233090 | DOI:10.1111/aos.14973

J Small Anim Pract. 2021 Jul 7. doi: 10.1111/jsap.13379. Online ahead of print.

ABSTRACT

OBJECTIVES: Activity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase is considered to be more pancreas specific than traditional lipase assays. The aim of this study was to evaluate the diagnostic performance of DGGR lipase activity for suspected acute pancreatitis in dogs and to assess its prognostic usefulness.

METHODS: Retrospective study of case records for suspected acute pancreatitis based on clinician-stated diagnosis, point-of-care and quantitative canine pancreas-specific lipase (cPL) results and consistent ultrasonographic features. Diagnostic performance of DGGR lipase was assessed by receiver-operating characteristic curve analysis, agreement by Cohen’s kappa (κ) and prognostic value by multiple regression analysis.

RESULTS: Median DGGR lipase activity was significantly (P < 0.001) higher in dogs with suspected acute pancreatitis [93.7 (range, 11.0-2853.0) U/L (n = 158)] compared to those with no evidence of pancreatitis [range, 20.9 (6.7-89.0) U/L (n = 356)]. A DGGR lipase activity >42.15 U/L had the best combined diagnostic sensitivity (81.0%) and specificity (92.1%). Previously established cut-offs (>130 and >80 U/L) had sensitivities of 40.5 and 43.0%, and specificities of 100 and 99.7%, respectively. There was near perfect (κ = 0.821) and substantial (κ = 0.751) agreement between DGGR lipase activity >42.15 U/L and quantitative cPL concentrations ≥200 and ≥400 μg/L, respectively. DGGR lipase activity but not quantitative cPL concentration was statistically (P = 0.043, odds ratio = 0.999) predictive of discharge but clinical utility is questionable.

CLINICAL SIGNIFICANCE: Using DGGR lipase at the lower cut-off could provide an additional test for supporting a diagnosis of acute pancreatitis in dogs particularly if cPL results are not available. Larger studies are required to more fully assess its value in prognostication.

PMID:34233038 | DOI:10.1111/jsap.13379

J Evol Biol. 2021 Jul 7. doi: 10.1111/jeb.13900. Online ahead of print.

ABSTRACT

Both assortment and plasticity can facilitate social evolution, as each may generate heritable associations between the phenotypes and fitness of individuals and their social partners. However, it currently remains difficult to empirically disentangle these distinct mechanisms in the wild, particularly for complex and environmentally responsive phenotypes subject to measurement error. To address this challenge, we extend the widely used animal model to facilitate unbiased estimation of plasticity, assortment, and selection on social traits, for both phenotypic and quantitative genetic analysis. Our social animal models (SAMs) estimate key evolutionary parameters for the latent reaction norms underlying repeatable patterns of phenotypic interaction across social environments. As a consequence of this approach, SAMs avoid inferential biases caused by various forms of measurement error in the raw phenotypic associations between social partners. We conducted a simulation study to demonstrate the application of SAMs and investigate their performance for both phenotypic and quantitative genetic analyses. With sufficient repeated measurements, we found desirably high power, low bias, and low uncertainty across model parameters using modest sample and effect sizes, leading to robust predictions of selection and adaptation. Our results suggest that SAMs will readily enhance social evolutionary research on a variety of phenotypes in the wild. We provide detailed coding tutorials and worked examples for implementing SAMs in the Stan statistical programming language.

PMID:34233047 | DOI:10.1111/jeb.13900

Nucleic Acids Res. 2021 Jul 7:gkab569. doi: 10.1093/nar/gkab569. Online ahead of print.

ABSTRACT

Microsatellite expansions are the cause of >20 neurological or developmental human disorders. Shortening expanded repeats using specific DNA endonucleases may be envisioned as a gene editing approach. Here, we measured the efficacy of several CRISPR-Cas nucleases to induce recombination within disease-related microsatellites, in Saccharomyces cerevisiae. Broad variations in nuclease performances were detected on all repeat tracts. Wild-type Streptococcus pyogenes Cas9 (SpCas9) was more efficient than Staphylococcus aureus Cas9 on all repeats tested, except (CAG)33. Cas12a (Cpf1) was the most efficient on GAA trinucleotide repeats, whereas GC-rich repeats were more efficiently cut by SpCas9. The main genetic factor underlying Cas efficacy was the propensity of the recognition part of the sgRNA to form a stable secondary structure, independently of its structural part. This suggests that such structures form in vivo and interfere with sgRNA metabolism. The yeast genome contains 221 natural CAG/CTG and GAA/CTT trinucleotide repeats. Deep sequencing after nuclease induction identified three of them as carrying statistically significant low frequency mutations, corresponding to SpCas9 off-target double-strand breaks.

PMID:34233005 | DOI:10.1093/nar/gkab569

Bioelectromagnetics. 2021 Jul 7. doi: 10.1002/bem.22359. Online ahead of print.

ABSTRACT

In magnetobiology, it is difficult to reproduce the nonspecific (not associated with specialized receptors) biological effects of weak magnetic fields. This means that some important characteristic of the data may be missed in standard statistical processing, where the set of measurements to be averaged belongs to the same population so that the contribution of fluctuations decreases according to the Central Limit Theorem. It has been shown that a series of measurements of a nonspecific magnetic effect contains not only the usual scatter of data around the mean but also a significant random component in the mean itself. This random component indicates that measurements belong to different statistical populations, which requires special processing. This component, otherwise called heterogeneity, is an additional characteristic that is typically overlooked, and which reduces reproducibility. The current method for studying and summarizing highly heterogeneous data is the random-effect meta-analysis of absolute values, i.e., of magnitudes, rather than the values themselves. However, this estimator-the average of absolute values-has a significant positive bias when it comes to the small effects that are characteristic of magnetobiology. To solve this problem, an improved estimator based on the folded normal distribution that gives several times less bias is proposed. We used this improved estimator to analyze the nonspecific effect of the hypomagnetic field in the Stroop test in 40 subjects and found a statistically significant meta-effect with a standardized average of magnitudes of about 0.1. It has been shown that the proposed approach can also be applied to a single study. © 2021 Bioelectromagnetics Society.

PMID:34233018 | DOI:10.1002/bem.22359

Acta Paediatr. 2021 Jul 7. doi: 10.1111/apa.16025. Online ahead of print.

ABSTRACT

AIM: Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used.

METHODS: All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012-2016 were included. Vancomycin trough levels were registered. Student t-test, Wilcoxon test and regression models were used for statistical analysis.

RESULTS: A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p=0.09).

CONCLUSIONS: In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.

PMID:34233034 | DOI:10.1111/apa.16025

IEEE J Biomed Health Inform. 2021 Jul 7;PP. doi: 10.1109/JBHI.2021.3095415. Online ahead of print.

ABSTRACT

This study investigated the brain functional connectivity (FC) patterns related to lie detection (LD) tasks with the purpose of analyzing the underlying cognitive processes and mechanisms in deception. Using the guilty knowledge test protocol, 30 subjects were divided randomly into guilty and innocent groups, and their electroencephalogram (EEG) signals were recorded on 32 electrodes. Phase synchrony of EEG was analyzed between different brain regions. A few-trials-based relative phase synchrony (FTRPS) measure was proposed to avoid the false synchronization that occurs due to volume conduction. FTRPS values with a significantly statistical difference between two groups were employed to construct FC patterns of deception, and the FTRPS values from the FC networks were extracted as the features for the training and testing of the support vector machine. Finally, four more intuitive brain fingerprinting graphs (BFG) on delta, theta, alpha and beta bands were respectively proposed. The experimental results reveal that deceptive responses elicited greater oscillatory synchronization than truthful responses between different brain regions, which plays an important role in executing lying tasks. The functional connectivity in the BFG are mainly implicated in the visuo-spatial imagery, bottom-top attention and memory systems, work memory and episodic encoding, and top-down attention and inhibition processing. These may, in part, underlie the mechanism of communication between different brain cortices during lying. High classification accuracy demonstrates the validation of BFG to identify deception behavior, and suggests that the proposed FTRPS could be a sensitive measure for LD in the real application.

PMID:34232900 | DOI:10.1109/JBHI.2021.3095415

PLoS Comput Biol. 2021 Jul 7;17(7):e1009099. doi: 10.1371/journal.pcbi.1009099. Online ahead of print.

ABSTRACT

Electrodermal activity (EDA) is a direct read-out of sweat-induced changes in the skin’s electrical conductance. Sympathetically-mediated pulsatile changes in skin sweat measured as EDA resemble an integrate-and-fire process, which yields an inverse Gaussian model as the inter-pulse interval distribution. We have previously showed that the inter-pulse intervals in EDA follow an inverse Gaussian distribution. However, the statistical structure of EDA pulse amplitudes has not yet been characterized based on the physiology. Expanding upon the integrate-and-fire nature of sweat glands, we hypothesized that the amplitude of an EDA pulse is proportional to the excess volume of sweat produced compared to what is required to just reach the surface of the skin. We modeled this as the difference of two inverse Gaussian models for each pulse, one which represents the time required to produce just enough sweat to rise to the surface of the skin and one which represents the time requires to produce the actual volume of sweat. We proposed and tested a series of four simplifications of our hypothesis, ranging from a single difference of inverse Gaussians to a single simple inverse Gaussian. We also tested four additional models for comparison, including the lognormal and gamma distributions. All models were tested on EDA data from two subject cohorts, 11 healthy volunteers during 1 hour of quiet wakefulness and a different set of 11 healthy volunteers during approximately 3 hours of controlled propofol sedation. All four models represent simplifications of our hypothesis outperformed other models across all 22 subjects, as measured by Akaike’s Information Criterion (AIC), as well as mean and maximum distance from the diagonal on a quantile-quantile plot. Our broader model set of four simplifications offered a useful framework to enhance further statistical descriptions of EDA pulse amplitudes. Some of the simplifications prioritize fit near the mode of the distribution, while others prioritize fit near the tail. With this new insight, we can summarize the physiologically-relevant amplitude information in EDA with at most four parameters. Our findings establish that physiologically based probability models provide parsimonious and accurate description of temporal and amplitude characteristics in EDA.

PMID:34232965 | DOI:10.1371/journal.pcbi.1009099

Arch Pathol Lab Med. 2021 Jul 7. doi: 10.5858/arpa.2020-0376-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: RET gene fusions are oncogenic drivers in nonsmall cell lung cancer and nonmedullary thyroid cancer. Selpercatinib (RETEVMO), a targeted inhibitor of RET, was approved by the US Food and Drug Administration for the treatment of RET fusion-positive nonsmall cell lung cancer and nonmedullary thyroid cancer emphasizing the need for rapid and accurate diagnosis of RET fusions. Fluorescence in situ hybridization (FISH) has been used to detect gene rearrangements, but its performance detecting RET rearrangements is understudied.

OBJECTIVE.—: To validate and describe the performance of Abbott Molecular RET break-apart FISH probes for detecting RET rearrangements.

DESIGN.—: A training set with RET fusion-positive (13) and RET fusion-negative nonsmall cell lung cancer and nonmedullary thyroid cancer samples (12) was used to establish criteria for FISH scoring. The scoring criteria was then applied to a larger validation set of samples (96).

RESULTS.—: A cutoff of 19% or more positive nuclei by FISH was established in the training set and determined by the mean ±3 SD. The validation set was tested using Abbott Molecular RET break-apart FISH compared with sequencing. With this cutoff, a sensitivity of 86% (12 of 14) and specificity of 99% (81 of 82) was achieved. Bootstrapping showed sensitivity could be optimized by using a greater than 13% cutoff with indeterminate samples of 13% to 18% abnormal nuclei requiring confirmation by an orthogonal method. Using this 3-tier scoring system sensitivity increased to 100% (14 of 14) and specificity was 96% (79 of 82).

CONCLUSIONS.—: Abbott Molecular break-apart FISH probes can be used to detect RET fusions. Laboratories can optimize cutoffs and/or testing algorithms to maximize sensitivity and specificity to ensure appropriate patients receive effective, timely therapy.

PMID:34232984 | DOI:10.5858/arpa.2020-0376-OA

Stat Methods Med Res. 2021 Jul 7:9622802211017592. doi: 10.1177/09622802211017592. Online ahead of print.

ABSTRACT

Clinical trials with survival endpoints are typically designed to enroll patients for a specified number of years, (usually 2-3 years) with another specified duration of follow-up (usually 2-3 years). Under this scheme, patients who are alive or free of the event of interest at the termination of the study are censored. Consequently, a patient may be censored due to insufficient follow-up duration or due to being lost to follow-up. Potentially, this process could lead to unequal censoring in the treatment arms and lead to inaccurate and adverse conclusions about treatment effects. In this article, using extensive simulation studies, we assess the impact of such censorings on statistical procedures (the generalized logrank tests) for comparing two survival distributions and illustrate our observations by revisiting Mukherjee et al.’s¹ findings of cardiovascular events in patients who took Rofecoxib (Vioxx).

PMID:34232837 | DOI:10.1177/09622802211017592