Nevin Manimala

Environ Monit Assess. 2021 Dec 10;194(1):21. doi: 10.1007/s10661-021-09671-1.

ABSTRACT

This study supplements previous research focused on environmental condition in the vicinity of waste ash material. The main aim of our study was the comparative analysis of lead levels in soil, plant, and animal organisms in the area of the tailings pond and surroundings, using x-ray. Findings confirm that the level of Pb in the top layer of soil is in the range of 20-135 ppm. Lead content in Calamagrostis plant tissues was confirmed only at the tailings pond area, with the highest lead concentrations measured in above-ground components; stems with blooms followed by roots and ground floor sheats. The livers, kidneys, and hearts of Apodemus flavicollis were examined, with findings of higher values in the tailings pond area than in the reference site, and average values of 14.5 ppm for livers, 16.0 ppm for kidneys, and 16.6 ppm for hearts. No significant differences were discovered based on sex and body length/body weight of A. flavicollis individuals. Values for Bombina variegata liver tissue reached an average of 12.3 ppm for individuals caught in a water reservoir without ash sediments, versus 15.7 ppm in those trapped by the edge of then tailings pond area. Females had lower concentrations of lead than males, but with no statistically significant differences found. Despite lower lead levels in soil and ash than expected, concentrations in mammalian and amphibian organs suggest a possible transition of this element into the food chain, and therefore further research in this area is recommended.

PMID:34893947 | DOI:10.1007/s10661-021-09671-1

AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.

ABSTRACT

We developed an integrated population pharmacokinetic model to investigate loncastuximab tesirine pharmacokinetics (PK) and exposure-response relationships for relapsed/refractory B cell non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL). The model, based on the recommended dosing schedule (150 µg/kg every 3 weeks [Q3W] for 2 cycles; 75 µg/kg Q3W thereafter) and drug concentrations in phase 1 and 2 studies (DLBCL [n = 284], non-DLBCL [n = 44]), was used to characterize loncastuximab tesirine PK and evaluate exposure covariates. Relationships between exposure (pyrrolobenzodiazepine-conjugated antibody [cAb] cycle 1 average concentration) and (1) efficacy (including overall response rate [ORR; primary endpoint] and overall survival [OS]) and (2) grade ≥ 2 treatment-emergent adverse events were explored. Statistical analyses included univariate and multivariate logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression. cAb and total Ab were best described by a two-compartment linear model with time-dependent clearance. The cAb steady-state half-life increased to 20.6 days by ~ 15 weeks. cAb exposure was lower for low albumin, mild/moderate hepatic impairment, non-DLBCL subtypes, and Eastern Cooperative Oncology Group scores > 1. Significant positive associations were reported between exposure and ORR (p = 3.21E-6), OS (p = 0.0016), grade ≥ 2 increased gamma-glutamyltransferase, liver function test abnormalities, pain, and skin/nail reactions (p < 0.05). Low albumin, bulky disease, and mild/moderate hepatic impairment had a significant negative effect on OS (p < 0.01). Modeling supports the recommended loncastuximab tesirine dosing schedule. Although reduced exposure and efficacy were predicted for specific covariates (e.g., low albumin, mild/moderate hepatic impairment), dose increases are not recommended. Trial registration: NCT02669017 and NCT03589469.

PMID:34893942 | DOI:10.1208/s12248-021-00660-3

Clin Oral Investig. 2021 Dec 10. doi: 10.1007/s00784-021-04338-0. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the effectiveness of different fiber post removal techniques and to correlate dentinal loss with microcrack formation.

MATERIALS AND METHODS: Forty-five extracted single-rooted teeth were root canal treated and fiber posts were adhesively luted. Specimens were divided into three groups (n = 15) according to the removal technique: long-shaft round bur (EndoTracer #08, Komet, Lemgo, Germany), SonicFlex Endo (KaVo, Biberach, Germany), DT Post Removal Kit (VDW, Munich, Germany). Roots were scanned before post cementation and after post removal using micro-computed tomography. Dentin loss, residual luting material, working time, and the induction of microcracks were assessed. Statistical analysis was performed by using multiple contrast tests (max-t tests, α = 0.05). Correlations between parameters dentin loss/new microcracks and dentin loss/residual material were calculated using Kendall’s tau.

RESULTS: Post removal with SonicFlex Endo resulted in the highest amount of removed dentin with significant differences to the round bur and the DT Post Removal Kit. No technique was found to completely remove the post and luting material. All techniques induced microcracks with the DT Post Removal Kit presenting the highest number of new defects. No correlation between dentin loss and new microcracks was observed. Deviations from the original root canal occurred in all groups, but no perforation was observed.

CONCLUSIONS: All techniques resulted in dentin loss, residual luting material, and the formation of microcracks. However, no correlation between dentin loss and the induction of microcracks was observed.

CLINICAL RELEVANCE: As all techniques resulted in microcrack formation and dentin loss, this study emphasizes the risk of iatrogenic damage due to post removal procedures.

PMID:34893941 | DOI:10.1007/s00784-021-04338-0

Arch Osteoporos. 2021 Dec 10;17(1):4. doi: 10.1007/s11657-021-01046-w.

ABSTRACT

PURPOSE: To investigate the time and effort needed to perform vertebral morphometry, as well as inter-observer agreement for identification of vertebral fractures on vertebral fracture assessment (VFA) images.

METHODS: Ninety-six images were retrospectively selected, and three radiographers independently performed semi-automatic 6-point morphometry. Fractures were identified and graded using the Genant classification. Time needed to annotate each image was recorded, and reader fatigue was assessed using a modified Simulator Sickness Questionnaire (SSQ). Inter-observer agreement was assessed per-patient and per-vertebra for detecting fractures of all grades (grades 1-3) and for grade 2 and 3 fractures using the kappa statistic. Variability in measured vertebral height was evaluated using the intraclass correlation coefficient (ICC).

RESULTS: Per-patient agreement was 0.59 for grades 1-3 fracture detection, and 0.65 for grades 2-3 only. Agreement for per-vertebra fracture classification was 0.92. Vertebral height measurements had an ICC of 0.96. Time needed to annotate VFA images ranged between 91 and 540 s, with a mean annotation time of 259 s. Mean SSQ scores were significantly lower at the start of a reading session (1.29; 95% CI: 0.81-1.77) compared to the end of a session (3.25; 95% CI: 2.60-3.90; p < 0.001).

CONCLUSION: Agreement for detection of patients with vertebral fractures was only moderate, and vertebral morphometry requires substantial time investment. This indicates that there is a potential benefit for automating VFA, both in improving inter-observer agreement and in decreasing reading time and burden on readers.

PMID:34893935 | DOI:10.1007/s11657-021-01046-w

Eur Arch Otorhinolaryngol. 2021 Dec 10. doi: 10.1007/s00405-021-07209-2. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of the study was to determine the influence of oral, oropharyngeal, laryngeal and hypopharyngeal dysplasia and cancer diagnosis on motivation to smoking cessation in patients. Consecutively, we assessed the competence of ENT specialists in counseling anti-smoking therapies.

METHODS: Questionnaire of expected support, Schneider motivation test and Fagerström Test for Nicotine Dependence (FTND) were administered to 50 smoking patients. The online survey was collected from 152 ENT doctors.

RESULTS: Mean FTND score was 4.58 and Heaviness of Smoking Index (HSI) was 3.1. Patients with oral cavity and oropharyngeal cancer showed the greatest dependence to nicotine 7.67 and 5.25, respectively, and with hypopharyngeal cancer had the lowest 3.5, (p = 0.039). The ranges of HSI were significantly higher for younger patients (p = 0.036). 35 patients were adequately motivated to quit smoking, and their mean age was statistically higher (p = 0.05). Self-reported motivation to smoking cessation was 76%. Of 152 surveyed doctors, only 39% declared knowledge of the diagnostic and therapeutic cessation interventions. 75% showed interest in the training programs.

PMID:34893934 | DOI:10.1007/s00405-021-07209-2

Sci Rep. 2021 Dec 10;11(1):23801. doi: 10.1038/s41598-021-03207-w.

ABSTRACT

In this study, we used 10 healthy sheep, which gave birth to healthy twins. Stool samples were collected from mothers and their offspring 3 times during the study (0, 28 and 56 day postpartum). Milk samples were taken from the mothers at the same time. RT PCR analysis of faeces and milk was performed in order to assess the level of bacteria from the Firmicutes and Bacteroidetes phyla including the family Lactobacillaceae (phylum Firmicutes). The composition of mother’s milk was also analyzed and their BCS. The data were compiled statistically. The obtained results showed that the level of the studied groups of bacteria may change due to the change of diet. Additionally, there were significant differences between lambs and mothers in the levels of the studied groups of bacteria. Analysis also shown that in the digestive system of mothers was a smaller disproportion in the level of the studied bacterial phyla than in lambs. The results also indicated the occurrence of differences in the bacterial composition at the individual level, both in ewes and their offspring. Additionally, in the conducted experiment, there were differences in the level of Firmicutes and Bacteroidetes groups depending on the sex.

PMID:34893656 | DOI:10.1038/s41598-021-03207-w

Sci Rep. 2021 Dec 10;11(1):23824. doi: 10.1038/s41598-021-02623-2.

ABSTRACT

Loess presents very unique collapsible behaviour due to its special under-compactness, weak cementation and porousness. Many environmental issues and geological hazards including subgrade subsidences, slope collapses or failures, building cracking and so on are directly caused by the collapsible deformation of loess. Such collapsible behaviour may also severe accidents due to sinkholes, underground caves or loess gullies. Moreover, with the increasing demand of construction and development in the loess areas, an in-depth research towards effective evaluation of loess collapsibility is urged. Currently no studies have made attempts to explore a rather complete and representative area of Loess Plateau. This paper thus provides a novel approach on spatial modelling over Jin-Shan Loess Plateau as an extension to experimental studies. The in-lab experiment results have shown that shown that the porosity ratio and collapsibility follow a Gaussian distribution and a Gamma distribution respectively for both sampling areas: Yan’an and Lv Liang. This establishes the prior intuition towards spatial modelling which provides insights of potential influential factors on loess collapsibility and further sets a potential direction of the loess studies by considering an extra dimension of spatial correlation. Such modelling allows robust predictions taken into account of longitudinal information as well as structural parameters and basic physical properties. Water contents, dry densities, pressure levels and elevations of samples are determined to be statistically significant factors which affect the loess collapsibility. All regions in Lv Liang area are at risk of high collapsibility with average around 0.03, out of which roughly a third of them are predicted to be at high risk. Clear spatial patterns of higher expected collapsibility in the southwest comparing to the northeast are shown adjusting for influential covariates. On reference guidelines for potential policy makings, county-level regions with the highest expected loess collapsibility are also identified.

PMID:34893645 | DOI:10.1038/s41598-021-02623-2

Nat Commun. 2021 Dec 10;12(1):7223. doi: 10.1038/s41467-021-27568-y.

ABSTRACT

The pedestrian-induced instability of the London Millennium Bridge is a widely used example of Kuramoto synchronisation. Yet, reviewing observational, experimental, and modelling evidence, we argue that increased coherence of pedestrians’ foot placement is a consequence of, not a cause of the instability. Instead, uncorrelated pedestrians produce positive feedback, through negative damping on average, that can initiate significant lateral bridge vibration over a wide range of natural frequencies. We present a simple general formula that quantifies this effect, and illustrate it through simulation of three mathematical models, including one with strong propensity for synchronisation. Despite subtle effects of gait strategies in determining precise instability thresholds, our results show that average negative damping is always the trigger. More broadly, we describe an alternative to Kuramoto theory for emergence of coherent oscillations in nature; collective contributions from incoherent agents need not cancel, but can provide positive feedback on average, leading to global limit-cycle motion.

PMID:34893627 | DOI:10.1038/s41467-021-27568-y

Sci Rep. 2021 Dec 10;11(1):23773. doi: 10.1038/s41598-021-02666-5.

ABSTRACT

Previous molecular characterization studies conducted in Canadian wheat cultivars shed some light on the impact of plant breeding on genetic diversity, but the number of varieties and markers used was small. Here, we used 28,798 markers of the wheat 90K single nucleotide polymorphisms to (a) assess the extent of genetic diversity, relationship, population structure, and divergence among 174 historical and modern Canadian spring wheat varieties registered from 1905 to 2018 and 22 unregistered lines (hereinafter referred to as cultivars), and (b) identify genomic regions that had undergone selection. About 91% of the pairs of cultivars differed by 20-40% of the scored alleles, but only 7% of the pairs had kinship coefficients of < 0.250, suggesting the presence of a high proportion of redundancy in allelic composition. Although the 196 cultivars represented eight wheat classes, our results from phylogenetic, principal component, and the model-based population structure analyses revealed three groups, with no clear structure among most wheat classes, breeding programs, and breeding periods. F_ST statistics computed among different categorical variables showed little genetic differentiation (< 0.05) among breeding periods and breeding programs, but a diverse level of genetic differentiation among wheat classes and predicted groups. Diversity indices were the highest and lowest among cultivars registered from 1970 to 1980 and from 2011 to 2018, respectively. Using two outlier detection methods, we identified from 524 to 2314 SNPs and 41 selective sweeps of which some are close to genes with known phenotype, including plant height, photoperiodism, vernalization, gluten strength, and disease resistance.

PMID:34893626 | DOI:10.1038/s41598-021-02666-5

Nat Commun. 2021 Dec 10;12(1):7217. doi: 10.1038/s41467-021-27410-5.

ABSTRACT

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50-89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14-35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65-84 days) compared with those vaccinated with a standard (19-29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14-35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.

PMID:34893611 | DOI:10.1038/s41467-021-27410-5