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Spatial concordance metrics and related risk factors of brain-peripheral barrier axes: unveiling distinct concordance patterns for mental and neurological axes.

Numerous studies have documented bidirectional interactions between the central nervous system and barrier organs (skin, gut, and lung). While genome-wide association studies have revealed shared genetic factors across brain-peripheral barrier axes, investigating these connections from an environmental perspective in large populations remains difficult. Using data from the Global Burden of Disease (GBD) 2023, I extracted annual incidence rates for 56 diseases related to brain-peripheral barrier axes and exposure rates for the 70 most detailed risk factors across 204 countries and territories. By categorizing regional incidence rates into four quartiles for each disease, I pinpointed regions with concordance of these axes and constructed a spatial atlas of disease concordance within the brain-peripheral barrier axis from a macro-epidemiologic view. Subsequently, I calculated global spatial concordance percentages for each axis, which allowed the comparatively assessment of concordance patterns across different axes, specific diseases, and their variations over time, across the lifespan, and by gender. Finally, I applied machine learning models and Shapley additive explanations to identify risk factors related to the spatial concordance of each axis. From 1990 to 2023, the overall trend for most brain-peripheral barrier axis pairs remained stable. Spatial concordance patterns showed dynamic fluctuations across the lifespan, followed by a convergence toward stability in older age. Several risk factors are related to most brain-peripheral barrier axes. Notably, the mental and neurological axes exhibited distinct concordance patterns. Compared with neurological axes, concordance within mental axes showed a broader and more dispersed geographic distribution, with greater variation across sexes and over time. Furthermore, concordance percentages of mental and neurological axes exhibited opposing age-related trends, contrasting disease spectra for peripheral conditions, and inverse relationships with alcohol and sodium consumption. Those divergences suggest distinct mechanisms underlying the brain-peripheral barrier axes in mental and neurological diseases. Related risk factors offer population-based hypotheses for further investigation in individual-level studies.

Humans

Cross-Platform Concordance in DNA Methylation Based Classification of CNS Tumors.

DNA methylation profiling enables precise classification of pediatric central nervous system (CNS) tumors. Oxford Nanopore Technologies (ONT) offers same-day, single-sample methylation readouts, but its concordance with Illumina EPIC arrays in routine diagnostic tasks remains incompletely defined. We profiled 23 pediatric tumors (18 CNS, 5 non-CNS) by EPIC arrays and ONT. Methylation profiles from both platforms were classified with crossNN (brain model or pan-cancer model); ONT data were additionally classified with Rapid-CNS2 and Sturgeon. We compared (i) classifier agreement with integrated histology (w/o NGS) at family/class levels, (ii) pass-rate above platform-specific score cutoffs, (iii) cross-platform concordance of copy-number variation (CNV), and MGMT promoter methylation status. In CNS cases, ONT and EPIC methylation profiles demonstrated strong correlation, except for a single outlier (P2), which was excluded from further analysis. Comparative assessment of the two platforms showed that: (a) Molecular classification of CNS tumors using the crossNN classifier was consistent with histology (w/o NGS) at the family level in all cases. (b) Copy-number profiles showed high concordance between platforms. (c) MGMT promoter methylation status matched in 94% of cases (16/17). When comparing ONT-specific analysis pipelines using the ONT data, the Rapid-CNS2 pipeline yielded the most reliable class level assignments with 94% (16/17) concordance with the histopathological diagnosis, which marginally exceeded the crossNN and sturgeon classifiers. In non-CNS tumors, the pan-cancer model produced low-confidence outputs with poor agreement with histology (w/o NGS) (only 1/5 concordant), indicating limited readiness for these entities. In conclusion, ONT enables same-day, clinically reliable family-level CNS tumor classification with high concordance to arrays, while EPIC retains a modest class-level edge. A key limitation of ONT is its reliance on fresh-frozen DNA and on classifiers originally built around array-derived CpG sites, rather than on models developed natively from ONT data.

DNA methylation

Concorde: ride quality and passenger reactions.

On four Concorde flights, recordings of environmental characteristics during flight were made and questionnaires were distributed to passengers to assess their reactions during and 24 h after their flight. The Concorde users were mostly traveling for business reasons. Most respondents were flying the Concorde for the first time. Passengers were satisfied with the Concorde, found it comfortable, and were able to perform a variety of activities in flight. On the day after their flight, respondents felt good, rested, and active. They reported less jet lag as a result of their Concorde flight than they had previously experienced on other transatlantic flights. Most respondents are likely to use the Concorde again.

Adult

Parents' Awareness of Their Adolescents' Sexual Behaviors and Experiences: A Concordance Analysis.

PURPOSE: Adolescence is a developmental period during which sexual exploration is normative. Parental awareness of adolescents' sexual behaviors can be protective during this stage; however, research suggests both parents and adolescents tend to avoid open conversations about these sensitive issues. This study aimed to examine concordance between parent proxy-reports and adolescent self-reports across three domains of adolescents' sexual behaviors and experiences. METHODS: Data were collected from a national sample of 522 parent-adolescent dyads (aged 15-17 years) from the AmeriSpeak panel (data collected May-September 2022). Prevalence-adjusted bias-adjusted kappa (PABAK) statistics were calculated to evaluate agreement. RESULTS: Findings revealed weak-to-moderate concordance regarding adolescents sending and receiving sexual photos (PABAKs = 0.54-0.79), whereas stronger concordance was observed for experiences related to nonconsensual sharing of sexual photos (PABAKs = 0.92-0.94), with high agreement largely driven by low reported prevalence of these experiences. Strong concordance regarding whether adolescents had ever had sex (PABAK = 0.80) was largely driven by both parents and adolescents reporting the adolescent had not had sex. Concordance regarding sexually transmitted infection and pregnancy prevention methods varied, ranging from weak to strong agreement across specific methods (or lack thereof; PABAKs = -0.07-0.79). DISCUSSION: Results highlight significant discrepancies in parents' knowledge about their adolescents' sexual behaviors and experiences. Interventions aimed at enhancing trust and open dialogue between parents and adolescents about sexuality-related topics, as well as ensuring adolescents have a variety of trusted sources to consult for sexual information, can help adolescents make informed sexual health decisions.

Humans

Physicians' concordance with consultants' recommendations for psychotropic medication.

Physicians' concordance with the recommendations of psychiatric consultants regarding the use of psychotropic medications in a general hospital was retrospectively examined in an outcome study. Using medical records in a series of 200 consecutive consultations, the authors found 68% of all psychotropic recommendations resulted in physician responses rated concordant and 24% nonconcordant. Resultant concordance ratings are presented according to category of recommendation (that is, start, adjust, continue, or discontinue) and drug groupings. The data suggest that drug group is not a critical variable in physician concordance. Responses did differ by category of recommendation. Further study of physician concordance is desirable. The work suggests both the potential of and need for outcome studies in consultation work.

Humans

Twin concordance. A more general model.

Estimation of the twin concordance rate for a disease often requires two stages. First, the disease is ascertained in a population or in a population sample, and such twins as are found with the disease become probands. Second, twin pairs with only one proband are further investigated and additional concordant pairs are thus discovered. A mathematical model is presented that allows for continuous variation in completeness of ascertainment in both stages, for correlation within pairs in the primary ascertainment process, and for correlation within pairs in occurrence of the disease. The concordance rate can be estimated by the proband method if secondary ascertainment is complete; other measures of concordance are accurate only if primary ascertainment is complete. A parameter analogous to the concordance rate but related to correlation in primary ascertainment can be estimated from the same data.

Age Factors

Concordance of SARS-CoV-2 Antibody Results during a Period of Low Prevalence.

Accurate, highly specific immunoassays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to evaluate seroprevalence. This study investigated the concordance of results across four immunoassays targeting different antigens for sera collected at the beginning of the SARS-CoV-2 pandemic in the United States. Specimens from All of Us participants contributed between January and March 2020 were tested using the Abbott Architect SARS-CoV-2 IgG (immunoglobulin G) assay (Abbott) and the EuroImmun SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) (EI). Participants with discordant results, participants with concordant positive results, and a subset of concordant negative results by Abbott and EI were also tested using the Roche Elecsys anti-SARS-CoV-2 (IgG) test (Roche) and the Ortho-Clinical Diagnostics Vitros anti-SARS-CoV-2 IgG test (Ortho). The agreement and 95% confidence intervals were estimated for paired assay combinations. SARS-CoV-2 antibody concentrations were quantified for specimens with at least two positive results across four immunoassays. Among the 24,079 participants, the percent agreement for the Abbott and EI assays was 98.8% (95% confidence interval, 98.7%, 99%). Of the 490 participants who were also tested by Ortho and Roche, the probability-weighted percentage of agreement (95% confidence interval) between Ortho and Roche was 98.4% (97.9%, 98.9%), that between EI and Ortho was 98.5% (92.9%, 99.9%), that between Abbott and Roche was 98.9% (90.3%, 100.0%), that between EI and Roche was 98.9% (98.6%, 100.0%), and that between Abbott and Ortho was 98.4% (91.2%, 100.0%). Among the 32 participants who were positive by at least 2 immunoassays, 21 had quantifiable anti-SARS-CoV-2 antibody concentrations by research assays. The results across immunoassays revealed concordance during a period of low prevalence. However, the frequency of false positivity during a period of low prevalence supports the use of two sequentially performed tests for unvaccinated individuals who are seropositive by the first test. IMPORTANCE What is the agreement of commercial SARS-CoV-2 immunoglobulin G (IgG) assays during a time of low coronavirus disease 2019 (COVID-19) prevalence and no vaccine availability? Serological tests produced concordant results in a time of low SARS-CoV-2 prevalence and no vaccine availability, driven largely by the proportion of samples that were negative by two immunoassays. The CDC recommends two sequential tests for positivity for future pandemic preparedness. In a subset analysis, quantified antinucleocapsid and antispike SARS-CoV-2 IgG antibodies do not suggest the need to specify the antigen targets of the sequential assays in the CDC's recommendation because false positivity varied as much between assays targeting the same antigen as it did between assays targeting different antigens.

Humans

Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma.

INTRODUCTION: In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing. METHODS: Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with &#x2265; 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index. RESULTS: Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson-Steiner grading and greater retention of CTNNB1, TP53, ARID1A, and KEAP1 mutations. The number of shared variants (median: 115 vs. 0, and p&#xa0;<&#xa0;0.001) and the Jaccard index (median: 0.44 vs. 0.00 and p&#xa0;<&#xa0;0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation. CONCLUSION: Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.

clonal relapse

Microbial signal profiles and organism-level concordance between plasma metagenomic sequencing and blood culture in suspected bloodstream infection.

Plasma metagenomic next-generation sequencing (mNGS) and blood culture detect different components of the microbial signal and frequently produce discordant organism reports. We characterized microbial signal class, report-derived burden, organism-level concordance, and independent clinical attribution in a retrospective, single-center, episode-level cohort. Among 329 episodes with evaluable plasma mNGS reports, 315 had blood culture performed; 232 were mNGS positive/culture negative and 53 were positive by both methods. In the 232 discordant episodes, the recorded routine-care diagnosis classified 124 as bloodstream infection (BSI) and 108 as non-BSI. Nonviral signals were present in 78.2% and 42.6%, respectively (P&#x2009;<&#x2009;0.001), and median maximum report-derived sequence counts were 98.5 and 11.5 (P&#x2009;<&#x2009;0.001). Two laboratory physicians then independently reviewed source records using structured criteria while masked to the recorded BSI label and mNGS organism and sequence-count information. Initial agreement for the five-category BSI assessment was 97.6% (Cohen's kappa, 0.960). Within the mNGS-positive/culture-negative subgroup, adjudicated BSI likelihood showed a modest ordinal association with report burden (Spearman rho&#x2009;=&#x2009;0.190; P&#x2009;=&#x2009;0.004), while mNGS organisms were considered supported in 1 episode, plausible in 158, unlikely or contaminant in 72, and unresolved in 1. Among 53 dual-positive episodes, 33 (62.3%) shared at least one species, but only 5 (9.4%) had complete species-set concordance. Plasma mNGS and blood culture therefore frequently generated non-equivalent organism sets. Signal class and report burden contributed graded contextual evidence, but organism-level attribution required clinical review and orthogonal microbiology rather than binary positivity alone.

Humans

Definitions of schizophrenia: concordance and prediction of outcome.

The study reports a comparison of 10 definitions of schizophrenia (Feighner's, Taylor's, Schneider's, Longfeldt's, Spitzer's, Carpenter's, Astrachan's, 2 from Forrest & Hay and Catego) in respect of their reliability, concordance and prediction of outcome. Some (including Feighner's) proved too strict, and others (including Schneider's) were weak predictors of clinical and social state. Four definitions (Spitzer's, Langfeldt's, Carpenter's and Catego) emerged as relatively effective and these also had a somewhat more satisfactory mutual concordance.

Employment

Monozygotic twins with concordance for Down's syndrome and congenital heart disease.

Cytogenetic, clinical, and other findings are presented on a pair of same-sex, monochorial MZ twins concordant for both trisomy 21 and congenital heart disease. The literature on Down's syndrome in twins and on congenital heart disease in twins is reviewed and the exceptional occurrence of concordant congenital heart disease in MZ twins is stressed.

Abnormalities, Multiple

Twin growth: initial deficit, recovery, and trends in concordance from birth to nine years.

Height and weight measurements for a large sample of twins from birth to nine years were used to construct growth curves for this period. Compared to singletons, twins were substantially smaller at birth, particularly for weight (30% deficit), but the latter showed a dramatic recovery in the first 3 months, then smaller increments until finally reaching the singleton norms at 8 years. Height, while less depressed at birth (17% deficit), was also slower to recover during the first year, then moved in comparable increments with weight until reaching parity with singletons. Prenatal influences on birth size were largely dissipated as each twin converged on his/her genetic growth curve. Monozygotic twins became progressively more concordant with age (R = 0.94 for height), while dizygotic twins became less concordant (R = 0.49). Ten monozygotic pairs with large birth-weight differences (greater than 750 g) were examined at 6 years; the smaller twin was still significantly lighter (P less than 0.01), marginally shorter (P less than 0.10), but not significantly lower in IQ. The results suggested a high degree of buffering for intelligence against the effects of nutritional deficit in the prenatal period. Some factors in addition to placental anastomosis are suggested as a possible basis for long-term size differences in monozygotic pairs.

Birth Weight

Sex differences in concordance rates for schizophrenia in twins.

In response to my discussion of sex differences in concordance rates for schizophrenia in twins, Lewine (1979) noted that male schizophrenics are hospitalized earlier than females. He questioned whether females had been followed through the risk period. To clarify, I calculated the age at followup of discordant twins in three studies. In Gottesman and Shields' (1972) study, the majority of both male and female co-twins were still under the age of 45. In contrast, all but a few of Kringlen's (1967a, 1967b, 1968) and Fischer's (1973) co-twins were 45 or over. Their findings support the conclusion that recent twin studies show no significant sex differences in concordance.

Diseases in Twins

Monozygotic twins concordant for tracheo-esophageal fistula and discordant for the VATER association.

Monozygotic female twins were concordant for tracheo-esophageal fistula (TEF); and one twin also manifested other anomalies in the VATER association, including agenesis of the female reproductive tract. Review of the literature discloses a familial tendency for recurrence of TEF and a high concordance rate in monozygotic twins, indicating a significant genetic influence for the isolated anomaly. In the case of the VATER association, the sporadic occurrence of affected individuals and discordance in twins implicates the effect of non-genetic factors.

Abnormalities, Multiple

An integrated proteomics and transcriptomics analysis highlights concordance between protein turnover and carbohydrate transport and metabolism as key functional categories during the growth of Trichophyton rubrum.

Dermatophytes are a class of keratinophilic skin fungi that invade host skin, hair, and nails to acquire nutrients. An integrated multi-omics approach utilizing liquid chromatography-tandem mass spectrometry and RNA-seq after growth in a protein-rich soy medium was employed to capture the major subset of secreted protein families of Trichophyton rubrum. The secretome consisted mainly of proteases and cell wall-degrading enzymes, with subtilisins (Sub6 and Sub7), metallopeptidase (LAP2), and chitinase having the most abundant peptides. Transcriptional profiling indicated fungal adaptation in protein-rich media to process the protein nutrients through modulation of metabolism and general cellular function pathways. Correlation analysis between proteomics and transcriptomics data using functional KOG categories shows high concordance of KOG categories O (posttranslational modification, protein turnover, and chaperones), P (inorganic ion transport and metabolism), and G (carbohydrate transport and metabolism), as per cosine similarity analysis.IMPORTANCEDermatophytes are keratinophilic skin fungal pathogens that invade host skin, hair, and nails to acquire nutrients. There is an epidemic-like increase in infections, as well as an increase in antimicrobial resistance among dermatophytes, as witnessed over the last decade. There is hence a need to understand the key pathways and virulence factors required during growth and infection. We present an integrated multi-omics analysis (proteomics and transcriptomics data) using a vector-based similarity approach to show high concordance of KOG functional categories belonging to posttranslational modification, protein turnover, carbohydrate transport, and metabolism.

Proteomics

A criss-cross heart with concordant atrioventriculo-arterial connections. Report of a case.

A distinctive angiographic appearance is described in a case of "criss-cross" heart with concordant atrioventriculo-arterial connections. The atrial situs was normal, and the morphological right ventricle was superior to the left ventricle, and the ventricular septum was horizontal in position. Both ventricleswere connected by a small ventricular septal defect. The aorta was situated anteriorly and to the right of the pulmonary artery. Although the cardiac segment was the apparent [S,L,D] type, the heart had conconrdant atrioventriculo-arterial connections. The ventricular rotation of the solitus heart about the longitudinal and the anteroposterior axis affected the atrioventricular flows, the plane of the ventricular septum, the inflow and outflow tracts of the ventricles, the interrelationship of the great arteries, and the course of the left coronary artery. Using the recent definition of criss-cross heart, we classified the heart as solitus-concordant (l-rotated) -normal.

Arteries

[Monozygotic and dizygotic twins concordant with regard to schizophrenia].

The paper deals with a clinical study of schizophrenia in 30 pairs of concordant twins among which 10 were monozygotic, 5 pairs of a doubtful zygoticy and 16 dizygotic. Concordance to manifest schizophrenia was found in 62.5% of monozygotic twins and 25.5% in dizygotic. Both in monozygotic and in dizygotic pairs a constant coinciding sign, except the nozological belonging, was only the form of development in schizophrenia. The level of postive and negative disorders, the frequency of attacks and duration of remissions differes in monozygotic pairs insignificantly, in dizygotic-somewhat more. However, even in dizygotic pairs the similarities prevail over differences. It was possible to distinguish correlations between the traits of premorbid personality and the severity of the subsequent disease.

Diseases in Twins

The Concorde and cosmic rays.

In 1976, Air France's Concordes operated 2,642 h of flight time during 772 commercial flights to Rio de Janeiro, Caracas, and Washington. The cosmic radiation dose equivalent rate was measured during each of these flights. The average amount recorded was 0.99 mrems/h. A distinction must be made between the high latitudes (Washington route), on which an average dose equivalent rate of 1.49 mrem/h was recorded, and low latitudes (Rio de Janeiro and Caracas routes), on which the average dose equivalent rate was only 0.78 mrems/h. These figures show that 1976 Concorde passengers and crews were exposed to very low quantities of radiation--very much lower than the maximum value recommended for the general public, which is 500 mrems per year.

Aerospace Medicine