Category: Nevin Manimala

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

J Spinal Cord Med. 2021 Jul 7:1-9. doi: 10.1080/10790268.2021.1940794. Online ahead of print.

ABSTRACT

CONTEXT: The implantation of commercially available phrenic nerve/diaphragm pacers has been available for more than 40 years and has enabled thousands of patients in over 40 countries to achieve freedom from invasive mechanical ventilation.

OBJECTIVE: The cervical approach to implantation of these pacers is described, as are the pros and cons of using this technique compared to intrathoracic and sub-diaphragmatic.

METHODS: Study design was a retrospective review of 1,522 subjects from the Avery Biomedical Devices (ABD) database who were implanted with the Avery diaphragm pacer. Long term statistics from patients implanted with diaphragm pacers are presented as well.

RESULTS: 17% of cervically placed electrodes required at least one replacement compared to 18% of electrodes placed thoracically. Devices implanted cervically show no significant difference in their longevity than those implanted using the thoracic approach (P value of 0.9382 using Two-Sample t-Test). The mean longevity for both approaches was found to be 6.4 years. The majority of electrodes implanted have never required replacement. A majority of CCHS patients were implanted using the thoracic approach and only find it necessary to use the device during sleeping hours. Most of the cervically implanted patients are found to be older at the time of implantation and implanted for diagnoses that require longer daily use of the device.

CONCLUSION: The cervical approach for the implantation of phrenic nerve/diaphragm pacers is the most minimally invasive, but underutilized, technique that allows for the use of local or monitored anesthesia, does not require entering any body cavities, and keeps incision size small.

PMID:34232840 | DOI:10.1080/10790268.2021.1940794

Disabil Rehabil. 2021 Jul 7:1-11. doi: 10.1080/09638288.2021.1942242. Online ahead of print.

ABSTRACT

PURPOSE: To identify the short-term effects of robotic-assisted gait training (RAGT) on walking distance, gait speed and functionality of cerebral palsy (CP) patients, and to verify if the effects of RAGT are maintained in the long term.

METHODS: A systematic literature review was performed in PubMed, PEDro, CINAHL, and LILACS databases. Studies were included considering: (1) population (CP individuals); (2) study design (experimental studies); (3) type of intervention (RAGT); (4) outcome (gait parameters and function); and (5) period (short and long term).

RESULTS: This systematic review included seven articles in meta-analysis. Only walking distance, thru six minutes walking test, increased statistically after RAGT. However, RAGT demonstrated large clinical effects differences (minimal clinically important difference – MCID) in gait speed and Gross Motor Function Measure score (dimensions D and E), for CP population. After RAGT intervention, differences in short term (comparison 1) were maintained in long term (comparison 2) for all outcomes. Gait speed results were not significant.

CONCLUSIONS: Evidence from the present study demonstrated that RAGT can be an important intervention to improve gait parameters and functionality, in children with CP, that are maintained over long-term.Implications for RehabilitationRobotic-assisted gait training (RAGT) is a beneficial treatment for children with cerebral palsy (CP).RAGT improvements in walking distance are maintained over the long-term in children with CP.RAGT demonstrated large clinical effect differences in gait speed and functionality in CP population.

PMID:34232847 | DOI:10.1080/09638288.2021.1942242

Stat Methods Med Res. 2021 Jul 7:9622802211009257. doi: 10.1177/09622802211009257. Online ahead of print.

ABSTRACT

By collecting multiple sets per subject in microarray data, gene sets analysis requires characterize intra-subject variation using gene expression profiling. For each subject, the data can be written as a matrix with the different subsets of gene expressions (e.g. multiple tumor types) indexing the rows and the genes indexing the columns. To test the assumption of intra-subject (tumor) variation, we present and perform tests of multi-set sphericity and multi-set identity of covariance structures across subjects (tumor types). We demonstrate by both theoretical and empirical studies that the tests have good properties. We applied the proposed tests on The Cancer Genome Atlas (TCGA) and tested covariance structures for the gene expressions across several tumor types.

PMID:34232835 | DOI:10.1177/09622802211009257

Stat Methods Med Res. 2021 Jul 7:9622802211023543. doi: 10.1177/09622802211023543. Online ahead of print.

ABSTRACT

We conducted this study to determine whether fallopian tube anatomy can predict the likelihood of pregnancy and pregnancy outcomes after tubal sterilization reversal. We built a flexible, non-parametric, multivariate model via generalized additive models to assess the effects of the following tubal parameters observed during tubal reparative surgery: tubal lengths; differences in tubal segment location and diameters at the anastomosis sites; and fibrosis of the tubal muscularis. In this study, population, age, and tubal length-in that order-were the primary factors predicting the likelihood of pregnancy. For pregnancy outcomes, tubal length was the most influential predictor of birth and ectopic pregnancy, while age was the primary predictor of miscarriage. Segment location and diameters contributed slightly to the odds of miscarriage and ectopic pregnancy. Tubal muscularis fibrosis had little apparent effect. This study is the first to show that a statistical learning predictive model based on fallopian tube anatomy can predict pregnancy and pregnancy outcome probabilities after tubal reversal surgery.

PMID:34232836 | DOI:10.1177/09622802211023543