Tag: nevin manimala

Infancy. 2022 Apr 11. doi: 10.1111/infa.12467. Online ahead of print.

ABSTRACT

Interaction with unfamiliar partners is a component of social life from infancy onward. Yet little is known about preverbal communication with strangers. This study compared the development of infant communication with strangers to communication with mothers and fathers and examined the contribution of temperament to partner-specific communication patterns. A sample of 58 infants was observed at four and eight months during separate home-based face-to-face interactions with three partners (mother, father, and stranger). Infant visual, facial, and vocal communication behaviors were coded microanalytically. Each parent reported on infant temperament at both ages. Multilevel regression analyses indicated that infants gazed longer at strangers than at fathers, exhibited less smiling to strangers than to mothers, and produced fewer vocalizations with strangers than with either parent. Both age and temperament moderated these differences. Vocal communication with fathers became more frequent at eight months; smiling to mothers was accentuated among infants with higher levels of temperamental surgency. Importantly, levels of communication behaviors with strangers were concurrently and longitudinally associated with those with mothers and fathers. Overall, findings suggest that infant emotional communication patterns are modulated by individual temperamental differences and are reproduced in and over time, though at different levels, when interacting with novel partners.

PMID:35403337 | DOI:10.1111/infa.12467

Transbound Emerg Dis. 2022 Apr 10. doi: 10.1111/tbed.14556. Online ahead of print.

ABSTRACT

Porcine reproductive and respiratory syndrome (PRRS) is among the most devastating diseases affecting the pig industry. Despite vaccines having been available for decades, the remarkable genetic variability of this virus, leading to poor cross-protection, has limited their efficacy and other measures must be adopted to effectively control the viral circulation. Some recent studies have investigated the factors involved in viral spreading and persistence, at least at local level. However, despite the topic’s relevance, no statistically grounded evidence is currently available evaluating the variables more involved in PRRSV epidemiological success at a broader scale, like the European one. In the present study, an extensive phylodynamic and phylogeographic analysis was performed on more than one thousand ORF5 sequences to investigate the history, dynamics and spreading patterns of PRRSV within European borders. Moreover, several potential predictors, representative of swine population features and trade, human population, economy and geographic characteristics, were evaluated through a specifically designed generalized linear model (GLM) to assess their weight on viral migration rate between countries over time. Although pig stock density, mean PRRSV strains genetic diversity, investments in agriculture (including a likely role of vaccination) and farmer education were involved to a certain extent, the major determinant was proven to be by far the live pig trade. Providing a robust depiction of PRRSV European molecular epidemiology patterns and determinants, the present study could contribute to a more rational allocation of limited resources based on an effective prioritization of control measures This article is protected by copyright. All rights reserved.

PMID:35403349 | DOI:10.1111/tbed.14556

J Clin Lab Anal. 2022 Apr 11:e24429. doi: 10.1002/jcla.24429. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the diagnostic value of peripheral blood neutrophil-to-lymphocyte ratio (NLR) combined with the thyroid imaging reporting and data system (TIRADS) for benign and malignant thyroid nodules.

METHODS: A total of 585 adults were enrolled in the study. The receiver operating characteristic curves were used to determine the optimal cut-off values for NLR and Kwak TIRADS (K-TIRADS) grades, which were 1.87 and 4a, respectively. Thyroid nodules were scored as follows: NLR-K-TIRADS score is 2 (both elevated K-TIRADS grade and NLR), NLR-K-TIRADS score is 1 (one of these was elevated) and NLR-k-TIRADS score is 0 (neither were elevated).

RESULTS: The proportions of malignant nodules with NLR-K-TIRADS scores of 2, 1 and 0 were 98.59%, 69.62% and 10.19%, and the difference was statistically significant (p < 0.001). In terms of the sensitivity of diagnosis of malignant nodules, NLR-K-TIRADS 1 tends to increase relative to K-TIRADS grades ≥ 4a; in terms of specificity and positive predictive value for the diagnosis of malignant nodules, NLR-K-TIRADS 2 was significantly higher than K-TIRADS grades ≥ 4a (all p < 0.05).

CONCLUSIONS: NLR combined with K-TIRADS grades may be a novel method for screening benign and malignant thyroid nodules.

PMID:35403307 | DOI:10.1002/jcla.24429

Stat Med. 2022 Apr 30;41(9):1728-1732. doi: 10.1002/sim.9123.

NO ABSTRACT

PMID:35403287 | DOI:10.1002/sim.9123

Proteins. 2022 Apr 10. doi: 10.1002/prot.26343. Online ahead of print.

ABSTRACT

The startling diversity in αβ T cell receptor (TCR) sequences and structures complicates molecular-level analyses of the specificity and sensitivity determining T cell immunogenicity. A number of 3D structures are now available of ternary complexes between TCRs and peptide:major histocompatibility complexes (pMHC). Here, to glean molecular-level insights we analyze structures of TCRs bound to human class I nonamer peptide-MHC complexes. Residues at peptide positions 4 to 8 are found to be particularly important for TCR binding. About 90% of the TCRs hydrogen bond with one or both of the peptide residues at positions 4 and 8 presented by MHC allele HLA-A2, and this number is still ~79% for peptides presented by other MHC alleles. Residue 8, which lies outside the previously-identified central peptide region, is crucial for TCR recognition of class I MHC-presented nonamer peptides. The statistics of the interactions also sheds light on the MHC residues important for TCR binding. The present analysis will aid in the structural modeling of TCR:pMHC complexes and has implications for the rational design of peptide-based vaccines and T cell-based immunotherapies.

PMID:35403257 | DOI:10.1002/prot.26343

J Clin Pharmacol. 2022 Apr 10. doi: 10.1002/jcph.2061. Online ahead of print.

ABSTRACT

BROCADE3 is a Phase 3 study, evaluating veliparib in combination with carboplatin/paclitaxel with continuation as monotherapy if carboplatin/paclitaxel is discontinued in patients with germline BRCA1/2 mutation-associated, advanced HER2-negative breast cancer. The objective of the current analysis was to characterize the veliparib exposure-response relationships for efficacy (progression-free survival; PFS) and safety in this study. Exposure-efficacy analyses of PFS were conducted using Kaplan-Meier plots and Cox Proportional Hazards (CPH) models using treatment alone or both treatment and exposure as time-dependent predictors to estimate the effect of veliparib in combination with carboplatin/paclitaxel and as monotherapy. The CPH model with only treatment as the time-varying predictor estimated a statistically significant benefit of veliparib monotherapy compared to placebo monotherapy (HR = 0.49 [95% CI, 0.33-0.73]) and a modest, non-statistically significant benefit (HR = 0.81 [95% CI, 0.62-1.05]) of adding veliparib to carboplatin/paclitaxel. Inclusion of exposure as an additional time-varying predictor in the CPH model indicated a flat exposure-response relationship between the veliparib exposure and PFS when veliparib was administered in combination with carboplatin/paclitaxel or as monotherapy. The exposure-safety analysis did not reveal any meaningful exposure-dependent trend in the incidence of adverse events of interest. These analyses support the dose regimen of veliparib (120 mg twice daily) in combination with carboplatin/paclitaxel and continuation of veliparib (300 to 400 mg twice daily) as monotherapy if carboplatin/paclitaxel were discontinued before disease progression in this patient population. This study is registered with ClinicalTrials.gov with a registration ID: NCT02163694. This article is protected by copyright. All rights reserved.

PMID:35403245 | DOI:10.1002/jcph.2061

Stat Med. 2022 Apr 10. doi: 10.1002/sim.9397. Online ahead of print.

ABSTRACT

We propose a test for multisample comparison studies that can be applied without strict assumptions, especially when the underlying population distributions are far from normal. The new test can detect differences not only in location or scale but also in shape parameters among parent population distributions. We are motivated by numerous medical studies, where the variables are not normally distributed and may present in the various groups more complex differences than simple differences in a particular aspect of underlying distributions, such as location or scale. In these situations, traditional ANOVA and Kruskal-Wallis tests are unreliable since the underlying assumptions are not valid. The proposed procedure also allows the researcher to determine which aspects are more responsible for a significant result. This is an important practical advantage over procedures that test for general differences among the distribution functions but cannot identify which aspects lead to significant results. The asymptotic distribution of the test statistic is analyzed along with its small sample behavior against several competing tests. The practical advantages of the proposed procedure are illustrated with a multisample comparison study of a biomarker for liver damage in patients with hepatitis C.

PMID:35403240 | DOI:10.1002/sim.9397

Stat Med. 2022 Apr 10. doi: 10.1002/sim.9393. Online ahead of print.

ABSTRACT

The development of a new diagnostic test ideally follows a sequence of stages which, among other aims, evaluate technical performance. This includes an analytical validity study, a diagnostic accuracy study, and an interventional clinical utility study. In this article, we propose a novel Bayesian approach to sample size determination for the diagnostic accuracy study, which takes advantage of information available from the analytical validity stage. We utilize assurance to calculate the required sample size based on the target width of a posterior probability interval and can choose to use or disregard the data from the analytical validity study when subsequently inferring measures of test accuracy. Sensitivity analyses are performed to assess the robustness of the proposed sample size to the choice of prior, and prior-data conflict is evaluated by comparing the data to the prior predictive distributions. We illustrate the proposed approach using a motivating real-life application involving a diagnostic test for ventilator associated pneumonia. Finally, we compare the properties of the approach against commonly used alternatives. The results show that, when suitable prior information is available, the assurance-based approach can reduce the required sample size when compared to alternative approaches.

PMID:35403239 | DOI:10.1002/sim.9393

Prenat Diagn. 2022 Apr 11. doi: 10.1002/pd.6143. Online ahead of print.

ABSTRACT

OBJECTIVE: Viral infections during pregnancy are a major health concern to mother and fetus. By repurposing cell-free Non Invasive Prenatal Testing (NIPT) sequencing data, we investigated prevalence and abundance of viral DNA in a cohort of 108,349 pregnant women.

METHOD: Cell-free DNA sequencing reads that did not map to any of the human chromosomes or mitochondrial DNA of the human reference genome build GRCh38 were aligned to 224 DNA viruses selected from the NCBI refseq viral database.

RESULTS: In total 443,665 reads of viral origin were detected across 42,273 samples representing 165 viral species. Several are known to be potentially harmful during pregnancy and/or childbirth, including Cytomegalovirus, Parvovirus B19 and Hepatitis B. Viral sequences were mostly detected at very low abundance. However, several cases had exceptionally high viral loads for Parvovirus B19, Hepatitis B and others. We found statistically significant associations between presence of viral DNA and gestational age, maternal age, fetal fraction, cfDNA concentration and others.

CONCLUSION: We demonstrate the feasibility to detect viral DNA from typical genome-wide NIPT cfDNA sequencing and describe the main characteristics of the viral DNA in our cohort. Our dataset of detected viral sequence reads is made publicly available to guide future clinical implementations. This article is protected by copyright. All rights reserved.

PMID:35403226 | DOI:10.1002/pd.6143

Clin Exp Metastasis. 2022 Apr 11. doi: 10.1007/s10585-022-10161-y. Online ahead of print.

NO ABSTRACT

PMID:35403206 | DOI:10.1007/s10585-022-10161-y