Tag: nevin manimala

Biom J. 2021 Jul 16. doi: 10.1002/bimj.202100046. Online ahead of print.

ABSTRACT

We analyze data from a clinical trial investigating the effect of an on-demand drug for women with low sexual desire. These data consist of a varying number of measurements/events across patients of when the drug was taken, including data on a patient-reported outcome consisting of five items measuring an unobserved construct (latent variable). Traditionally, these data are aggregated prior to analysis by composing one sum score per event and averaging this sum score over all observed events. In this paper, we explain the drawbacks of this aggregating approach. One drawback is that these averages have different standard errors because the variance of the underlying events differs between patients and because the number of events per patient differs. Another drawback is the implicit assumption that all items have equal weight in relation to the latent variable being measured. We propose a multilevel structural equation model, treating the events (level 1) as nested observations within patients (level 2), as alternative analysis method to overcome these drawbacks. The model we apply includes a factor model measuring a latent variable at the level of the event and at the level of the patient. Then, in the same model, the latent variables are regressed on covariates to assess the drug effect. We discuss the inferences obtained about the efficacy of the on-demand drug using our proposed model. We further illustrate how to test for measurement invariance across grouping covariates and levels using the same model.

PMID:34270801 | DOI:10.1002/bimj.202100046

Biom J. 2021 Jul 16. doi: 10.1002/bimj.202100089. Online ahead of print.

ABSTRACT

Our paper differs from previous literature in two ways: 1.We think in terms of clinical consequences, what benefits patients, what harms patients. Our main message is: using a not logic-respecting efficacy measure can potentially harm patients in a randomized controlled trial (RCT), as we prove analytically, and demonstrate with the OAK blood-based tumor mutational burden (bTMB) study. 2.We follow nature, which mixes effects within each treatment arm. Our secondary message is that following nature to mix within each treatment arm first before calculating any efficacy measure between treatments resolves issues. For example, following natural mixing to prove ratio of time is logic-respecting avoids the issue that weights of efficacy measures are implicit solution to an equation that depends on the unknown prognostic effect. More importantly, coding subgroup mixable estimation (SEM) by mixing within each treatment arm first and then calculating efficacy will make marginal and conditional efficacy agree, for logic-respecting efficacy measures (be it a ratio or a difference), no matter the outcome is continuous, binary, or time-to-event. One does not have to choose between marginal and conditional.

PMID:34270810 | DOI:10.1002/bimj.202100089

Radiat Res. 2021 Jul 16. doi: 10.1667/RADE-21-00079.1. Online ahead of print.

ABSTRACT

This commentary considers research needs for radiofrequency (RF) energy above 6 GHz, including in the “high band” of 5G New Radio (NR) communications systems that exists just beneath the mm-wave band (30-300 GHz). As of late 2020, approximately 100 RF bioeffects studies have been published involving exposures above 6 GHz, encompassing a wide range of exposure levels and frequencies. A majority of these studies report statistically significant effects of exposure, many at exposures within international safety limits. This commentary examines 31 genetic damage studies involving RF exposures above 6 GHz in the context of two sets of quality-assessment criteria: 1. “Risk of bias” (RoB) criteria used for systematic reviews of health-related studies; and 2. a broader set of criteria for research quality from a different scholarly approach (metascience). The 31 studies report several statistically significant effects of exposure on different markers for genetic damage. These effects, if real, would have great potential significance for carcinogen risk assessment. However, the studies as a group have significant technical weaknesses, including small size, failure to meet multiple RoB criteria, naïve use of statistics, and lack of prespecified hypotheses and methods of analysis, all of which increase the chances of false discovery. Here we propose a “carrot” (adequate funding to support high-quality research) and a “stick” (more stringent review of bioeffects manuscripts, including explicit instructions to reviewers to assess study quality) approach to increase the reliability of RF bioeffects studies to facilitate health agency reviews of this socially controversial topic.

PMID:34270779 | DOI:10.1667/RADE-21-00079.1

Int J Cancer. 2021 Jul 16. doi: 10.1002/ijc.33740. Online ahead of print.

ABSTRACT

Evidence for the human health effects of pesticides is needed to inform risk assessment. We studied the relationship between occupational insecticide use and risk of non-Hodgkin lymphoma (NHL) by pooling data from nine case-control studies participating in the InterLymph Consortium, including 7909 cases and 8644 controls from North America, the European Union, and Australia. Insecticide use was coded using self-report or expert assessment, for insecticide groups (e.g., organophosphates, pyrethroids) and active ingredients (e.g., malathion, permethrin). Associations with insecticides were estimated using logistic regression to produce odds ratios (ORs) and 95% confidence intervals (CI) for all NHL and NHL subtypes, with adjustment for study site, demographic factors, and use of other pesticides. Occupational insecticide use, overall, was not associated with risk of NHL. Use of organophosphate insecticides was associated with increased risk of all NHL and the subtype follicular lymphoma, and an association was found with diazinon, in particular (ever use: OR=2.05, 95% CI: 1.24-3.37). The carbamate insecticide, carbaryl, was associated with risk of all NHL, and the strongest associations were found with T-cell NHL for ever-use (OR=2.44, 95% CI: 1.13-5.28) and longer duration (>8 years vs. never: OR=2.90, 95% CI: 1.02-8.25). There was no association of NHL with other broad groups of insecticides, including organochlorine and pyrethroids, and some inverse associations were estimated in relation to historical DDT use. Our findings contribute to the totality of evidence available to help inform risk decisions by public health and regulatory agencies – of importance given continued, widespread use of organophosphate and carbamate insecticides. This article is protected by copyright. All rights reserved.

PMID:34270795 | DOI:10.1002/ijc.33740

Angle Orthod. 2021 Jul 16. doi: 10.2319/012121-62.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the root resorption resulting from miniscrew-supported maxillary posterior dentoalveolar intrusion using two different force magnitudes.

MATERIALS AND: Methods: Adult patients with skeletal open bite, indicated for maxillary posterior dentoalveolar intrusion, were recruited and randomly assigned to the comparison or intervention groups. The comparison group involved applying 200 g of intrusive force per segment, which measured 20 g per root, while this force was 400 g per segment in the intervention group, measuring 40 g per root.

RESULTS: Twenty participants were included in the final analysis after 2 patients dropped out, 1 in each group, to end up with 10 subjects (200 roots) per group. There was statistically significant root resorption of 0.84 ± 0.96 mm and 0.93 ± 1.00 mm in the comparison and the intervention groups, respectively. However, there was no statistically significant difference between the groups.

CONCLUSIONS: Root resorption inevitably took place in association with orthodontic intrusion. However, increasing the magnitude of the intrusive force did not increase the amount of root resorption, either statistically or clinically.

PMID:34270689 | DOI:10.2319/012121-62.1

J Parasitol. 2021 Jul 1;107(4):554-561. doi: 10.1645/21-28.

ABSTRACT

Parasite infection pressure is suggested to be a strong driver of transmission within ecosystems. We tested if infection pressure drives seroprevalence in intermediate host species for Toxoplasma gondii. We defined Toxoplasma infection pressure to intermediate host species as the combined influence of cat abundance, environmental conditions, and its prevalence in the cat population. We sampled and tested 2 species of rodent and collated information on Toxoplasma seroprevalence in koalas, wallabies, kangaroos, and sheep. All species were sampled using equivalent methods, within a 2-yr period, and from adjacent regions of low and high Toxoplasma infection pressure. The seroprevalence of Toxoplasma in kangaroos scaled with infection pressure, but we observed no statistical difference in seroprevalence for any other species between these 2 regions. Within the region of low infection pressure, Toxoplasma seroprevalence did not differ between species. However, within the region of high Toxoplasma infection pressure, we observed large variation in seroprevalence between species. Our results demonstrate that infection pressure is not sufficient by itself, but merely necessary, to drive Toxoplasma seroprevalence in intermediate host species. Where Toxoplasma seroprevalence in an intermediate host species is already low, further reducing infection pressure will not necessarily further decrease seroprevalence in those species. This has important ramifications for the mitigation of parasite infections and suggests that reductions in Toxoplasma infection pressure, intended to reduce infections, may be most effective and applicable to species that are known to experience high rates of infection.

PMID:34270758 | DOI:10.1645/21-28

Phys Ther. 2021 Jul 16:pzab177. doi: 10.1093/ptj/pzab177. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the static balance of children with sensorineural hearing loss (SNHL) according to the degrees of SNHL and the function of the vestibular system.

METHODS: This cross-sectional study was conducted in public schools located in Caruaru, Pernambuco state, Brazil, with 130 children (65 with normal hearing and 65 with SNHL as documented by air and bone conduction audiometry) of both sexes and between 7 and 11 years old. Static balance was assessed by a stabilometric analysis using a force platform consisting of the circular area of center-of-pressure (COP) displacement of the children, evaluated in 3 positions: bipedal support with feet together and parallel (PF), tandem feet (TF), and 1 foot (OF), carried out under 2 sensory conditions each, with eyes open and eyes closed. After balance assessments, the children with SNHL received examinations of auditory and vestibular functions-through audiometry and computerized vectoelectronystagmography, respectively-to compose the groups according to degrees of SNHL and vestibular function.

RESULTS: The children with severe and profound SNHL demonstrated more static balance instabilities than the children with normal hearing in 5 positions assessed with eyes open (PF, TF, and OF) and eyes closed (PF and TF). The same phenomenon occurred in children with SNHL and associated vestibular dysfunction in all of the positions assessed with eyes open and eyes closed (PF, TF, and OF).

CONCLUSION: The larger the degree of SNHL, the greater the balance instability of the children. The children with SNHL and associated vestibular dysfunction showed the highest balance instabilities in this study.

IMPACT: Children with larger degrees of SNHL and associated vestibular dysfunction might require prolonged periods to rehabilitate their balance.

PMID:34270771 | DOI:10.1093/ptj/pzab177

Bioinformatics. 2021 Jul 16:btab531. doi: 10.1093/bioinformatics/btab531. Online ahead of print.

ABSTRACT

MOTIVATION: The rise in the number of genotyped ancient individuals provides an opportunity to estimate population admixture models for many populations. However, in models describing modern populations as mixtures of ancient ones, it is typically difficult to estimate the model mixing coefficients and to evaluate its fit to the data.

RESULTS: We present LINADMIX, designed to tackle this problem by solving a constrained linear model when both the ancient and the modern genotypes are represented in a low-dimensional space. LINADMIX estimates the mixing coefficients and their standard errors, and computes a p-value for testing the model fit to the data. We quantified the performance of LINADMIX using an extensive set of simulated studies. We show that LINADMIX can accurately estimate admixture coefficients, and is robust to factors such as population size, genetic drift, proportion of missing data, and various types of model misspecification.

AVAILABILITY: LINADMIX is available as a python code at https://github.com/swidler/linadmix.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34270685 | DOI:10.1093/bioinformatics/btab531

Anesthesiology. 2021 Jul 16. doi: 10.1097/ALN.0000000000003883. Online ahead of print.

ABSTRACT

BACKGROUND: Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia.

METHODS: Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin-dependent protein kinase 2α-positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg-1 · min-1 for 45 min, eight rats; high dose: 4.5 µg · kg-1 · min-1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg-1 · min-1 for 30 min, seven rats; high dose: 4 mg · kg-1 · min-1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed.

RESULTS: Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide – saline] during dexmedetomidine infusion = -6.06 [99% CI = -12.36 to -1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [-1.93, -0.87] dB, 99% CI = [-4.16 to -0.56, -1.62 to -0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [-20.06 to 14.14, -20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: -3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016).

CONCLUSIONS: These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic’s molecular target.

PMID:34270686 | DOI:10.1097/ALN.0000000000003883

PLoS One. 2021 Jul 16;16(7):e0254579. doi: 10.1371/journal.pone.0254579. eCollection 2021.

ABSTRACT

BACKGROUND: Although Diabetes Self-Management Education (DSME) programs are recommended to help reduce the burden of diabetes and diabetes-related complications, Florida is one of the states with the lowest DSME participation rates. Moreover, there is evidence of geographic disparities of not only DSME participation rates but the burden of diabetes as well. Understanding these disparities is critical for guiding control programs geared at improving participation rates and diabetes outcomes. Therefore, the objectives of this study were to: (a) investigate geographic disparities of diabetes prevalence and DSME participation rates; and (b) identify predictors of the observed disparities in DSME participation rates.

METHODS: Behavioral Risk Factor Surveillance System (BRFSS) data for 2007 and 2010 were obtained from the Florida Department of Health. Age-adjusted diabetes prevalence and DSME participation rates were computed at the county level and their geographic distributions visualized using choropleth maps. Significant changes in diabetes prevalence and DSME participation rates between 2007 and 2010 were assessed and counties showing significant changes were mapped. Clusters of high diabetes prevalence before and after adjusting for common risk factors and DSME participation rates were identified, using Tango’s flexible spatial scan statistics, and their geographic distribution displayed in maps. Determinants of the geographic distribution of DSME participation rates and predictors of the identified high rate clusters were identified using ordinary least squares and logistic regression models, respectively.

RESULTS: County level age-adjusted diabetes prevalence varied from 4.7% to 17.8% while DSME participation rates varied from 26.6% to 81.2%. There were significant (p≤0.05) increases in both overall age-adjusted diabetes prevalence and DSME participation rates from 2007 to 2010 with diabetes prevalence increasing from 7.7% in 2007 to 8.6% in 2010 while DSME participation rates increased from 51.4% in 2007 to 55.1% in 2010. Generally, DSME participation rates decreased in rural areas while they increased in urban areas. High prevalence clusters of diabetes (both adjusted and unadjusted) were identified in northern and central Florida, while clusters of high DSME participation rates were identified in central Florida. Rural counties and those with high proportion of Hispanics tended to have low DSME participation rates.

CONCLUSIONS: The findings confirm that geographic disparities in both diabetes prevalence and DSME participation rates exist. Specific attention is required to address these disparities especially in areas that have high diabetes prevalence but low DSME participation rates. Study findings are useful for guiding resource allocation geared at reducing disparities and improving diabetes outcomes.

PMID:34270601 | DOI:10.1371/journal.pone.0254579