Twin Individuals Research Articles

A novel loss-of-function KCNB1 gene variant in a twin with global developmental delay and seizures.

Human voltage-gated potassium (Kv) channels are expressed by a 40-member gene family that is essential for normal electrical activity and is closely linked to various excitability disorders. Function-altering sequence variants in the KCNB1 gene, which encodes the neuronally expressed Kv2.1 channel, are associated with neurodevelopmental disorders including developmental delay with or without epileptic activity. In this study, we describe a 40-month-old fraternal twin who presented with severe neurodevelopmental delay. Electroencephalogram recordings at 19 months of age revealed poor sleep architecture and the presence of multifocal epileptiform discharges. The individual's fraternal twin was neurotypical, and there was no family history of neurodevelopmental delay or seizures. Whole genome sequencing at 33 months of age for the proband revealed a de novo variant in KCNB1 [c.1154C > T/p.Pro385Leu], encoding a proline-to-leucine substitution at residue 385, in the extracellular region immediately preceding Kv2.1 transmembrane segment 6 (S6). Cellular electrophysiological analysis of the effects of the gene variant in heterologously expressed Kv2.1 demonstrated that homozygous Kv2.1-P385L channels were completely non-functional. Channels generated by a 50/50 expression of wild-type Kv2.1 and Kv2.1-P385L, designed to mimic the proband's heterozygous status, revealed a partially dominant-negative effect, resulting in an 81% reduction in current magnitude. The dramatic loss of function in Kv2.1 is the most likely cause of the severe developmental delay and seizure activity in the proband, further enriching our phenotypic understanding of KCNB1 developmental encephalopathies.

Does Camouflaging Cause Reduced Quality of Life? A Co-Twin Control Study.

Camouflaging has been proposed to have a detrimental effect on quality of life, yet previous research has not accounted sufficiently for potential confounding by genetic and shared environmental factors. The current study utilized a co-twin control design providing stringent control for a range of confounders to investigate the hypothesis that camouflaging autistic traits has a negative impact on quality of life. The sample included 140 individual twins from 42 monozygotic (MZ) and 28 dizygotic (DZ) twin-pairs, enriched for participants with neurodevelopmental conditions including 22 autistic participants. All twins provided self-reports of camouflaging and quality of life. Autistic participants and specifically autistic females displayed increased camouflaging behaviors compared to non-autistic participants. Across the sample, higher levels of camouflaging were associated with reduced quality of life, surviving adjustment for confounding effects of autistic traits, ADHD, sex, and age. Within DZ- as well as MZ-pairs, which provide the highest level of control for unmeasured confounders, twins who camouflaged more reported lower quality of life compared to their co-twins, consistent with a causal influence of camouflaging on quality of life. Our results strengthen previous claims purporting camouflaging behaviors as a risk factor for reduced quality of life.

Is cancer associated with frailty? Results from a longitudinal study of old Danish twins

Abstract Background While age is an important risk factor for both cancer and frailty, it is unclear whether cancer itself increases the risk of frailty. We aimed to assess the association between cancer and frailty in a longitudinal cohort of older Danish twins, taking familial effect into account. Methods Using the Danish Cancer Registry, cancer cases were identified among participants aged 70 and over in the Longitudinal Study of Aging Danish Twins (LSADT). Frailty was evaluated over 10 years of follow-up using the frailty index (FI) and defined as FI > 0.21. Stratified Cox regressions were performed on discordant twin pairs (pairs where one twin had incident cancer and the other was cancer-free), and on all LSADT individual twins (twin pairs and singletons) with no history of cancer. Results Among the 72 discordant pairs (n=144, median age at inclusion=75) included in the study, the median FI at inclusion was 0.08 for both cancer twins and cancer-free co-twins. From the stratified Cox regression, twins with cancer had an increased hazard of developing frailty (HR=3.67, 95%CI=1.02,13.14) compared to their cancer-free co-twins. The analyses on individual twins (n=4,027) provided similar results, showing an increased hazard of frailty in individuals with cancer (HR=2.57, 95%CI= 1.77,3.74) compared to those without cancer. Conclusions We showed a higher risk of becoming frail following a cancer diagnosis in both discordant twin pairs and individual twins. These findings support the importance of monitoring of frailty in older adults with cancer through geriatric assessments and implementation of frailty interventions.

1-Nitronaphthalene, a non-OD, non-MDO polytype

Abstract Crystals of 1-nitronaphthalene were grown by evaporation of a methanol solution. The structure [P21/c, a = 13.2780(13) Å, b = 3.8131(3)° Å, c = 31.851(3) Å, β = 91.173(8), V = 1,612.3 Å3] was solved from a crystal twinned by twofold rotation about [100]. Twinning is explained by the polytype character: layers with (idealized) p2111 symmetry can connect via either 1‾ or 21 operations, leading to geometrically distinct pairs of layers. In the twin individuals, the two kinds of contacts alternate, at the composition plane two subsequent contacts of the same type are realized.

Identifying a Birth Cohort of Twins from Linked Data – Challenges and Opportunities

ObjectiveIn the absence of accurate perinatal records, identifying and differentiating twins in administrative records is difficult because of their similarity; they share surnames, dates of birth, and residences. In administrative databases, events within twin pairs are often incorrectly identified as being from one individual, representing a threat to data accuracy. An inability to identify twins in administrative data precludes applying powerful twin-based causal inference methods to understand health and social well-being. ApproachWe developed an algorithm using linked administrative birth, perinatal, emergency department, and hospital records in Victoria, Australia from 1 January 1993 to 31 December 2023. We probabilistically linked a sample of 1,434 ‘known’ twin pairs from the Australian Twin Registry to validate the sensitivity of our algorithm. We calculated specificity using a sample of non-twins derived from linked data. ResultsOur algorithm identified 37,900 twin pairs, 75,800 twin individuals, in the Victorian linked dataset. The accuracy of our ascertainment of twins by key characteristics will be presented and discussed. ConclusionsThe birth cohort we have generated is one of the largest twin cohorts in the world with unprecedented granularity in longitudinal health and social data. ImplicationsOur algorithm improves the accuracy of administrative data repositories and linkage, providing novel information on where errors in previous linkages have occurred due to limited familial or intergenerational information. Our large population-based birth cohort of twins can be used to investigate the familial and non-familial determinants of health using advanced causal inference which leverages the natural similarity between twins.

Rate-independent mechanism of deformation twinning in single crystal magnesium

The dynamics of {101‾2}〈101‾1〉 extension twins in a single crystal of pure magnesium are studied through uniaxial compression experiments coupled with direct optical imaging. The experiments covered a seven orders of magnitude strain rate, between 10−5−102s−1, covering all rates of engineering applications of magnesium and its alloys. Under uniaxial compression along a direction perpendicular to prismatic planes, only two variants of extension twins are activated, facilitating in-situ tracking of individual twin boundaries throughout the deformation process. Across the entire strain rate range, the twinning transformation evolves in a self-similar pattern of twin nucleation and thickening. Deformation fronts initiate at the edges of the sample and propagate toward the center, creating parallel twins with characteristic thicknesses and distances from each other. The velocity of the deformation fronts scales linearly with the imposed external strain rate and a nearly uniform resolved shear stress is measured over the entire strain rate range. We show that this unique process is attributed to the constant ratio between the nucleation rate and sideways velocity of individual twin boundaries, where both processes are proportional to the imposed strain rate. These findings indicate that, within the large strain rate range investigated in this study, the evolution mechanism of extension twinning is practically rate-independent.

Differential etiologic associations of heroin use and prescription opioid misuse with psychopathology.

Patterns of association with externalizing and internalizing features differ across heroin use and prescription opioid misuse (POM). The present study examined whether heroin use and POM display differential etiologic overlap with symptoms of conduct disorder (CD), adult antisocial behavior (AAB), and major depressive episodes (MDEs), how aggregating heroin use and POM into a single phenotype may bias results, and explored potential sex differences. Seven thousand one hundred and sixty-four individual twins from the Australian Twin Registry (ATR; 59.81% female; Mage = 30.58 years) reported lifetime heroin use, POM, CD symptoms, AABs, and MDE symptoms within a semi-structured interview. Biometric models decomposed phenotypic variance and covariance into additive genetic, common environmental, and unique environmental effects. The proportion of variance in heroin use attributable to factors shared with CD, AAB, and MDE, respectively, was 41%, 41%, and 0% for men and 26%, 19%, and 42% for women; for POM, the proportions were 33%, 35%, and 20% for men and 15%, 9%, and 13% for women. CD and AAB were more strongly genetically correlated with heroin use among women and with POM among men. MDE was more strongly genetically correlated with POM than with heroin use among men, but more strongly genetically correlated with heroin use than with POM among women. Analyses using an aggregate opioid (mis)use variable were biased toward POM, which was the more prevalent phenotype. Magnitude and source of etiologic influence may differ across forms of opioid (mis)use and sex. Disaggregating heroin use and POM in future opioid research may be warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Risk factors for bronchopulmonary dysplasia in twin preterm infants: a multicenter study

To investigate the risk factors for bronchopulmonary dysplasia (BPD) in twin preterm infants with a gestational age of <34 weeks, and to provide a basis for early identification of BPD in twin preterm infants in clinical practice. A retrospective analysis was performed for the twin preterm infants with a gestational age of <34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020. According to their conditions, they were divided into group A (both twins had BPD), group B (only one twin had BPD), and group C (neither twin had BPD). The risk factors for BPD in twin preterm infants were analyzed. Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins. A total of 904 pairs of twins with a gestational age of <34 weeks were included in this study. The multivariate logistic regression analysis showed that compared with group C, birth weight discordance of >25% between the twins was an independent risk factor for BPD in one of the twins (OR=3.370, 95%CI: 1.500-7.568, P<0.05), and high gestational age at birth was a protective factor against BPD (P<0.05). The conditional logistic regression analysis of group B showed that small-for-gestational-age (SGA) birth was an independent risk factor for BPD in individual twins (OR=5.017, 95%CI: 1.040-24.190, P<0.05). The development of BPD in twin preterm infants is associated with gestational age, birth weight discordance between the twins, and SGA birth.

The role of familial factors and neuroticism in the association between exposure to offensive behaviors at work and long-term sickness absence due to common mental disorders - a prospective twin study

ObjectivesThe aim of this study was to investigate associations between exposure to work-related violence/threats and harassment, and future sickness absence (SA) due to common mental disorders (CMDs), taking familial factors (shared genetics and early-life environment) and neuroticism into account.MethodsThe study sample included 8795 twin individuals from the Swedish Twin Project of Disability Pension and Sickness Absence (STODS), including survey data from the Study of Twin Adults: Genes and Environment (STAGE). Self-reported work-related violence and/or threats as well as work-related harassment (including bullying) and national register data on SA due to CMDs were analyzed using standard logistic regression, and conditional logistic regression among complete twin pairs discordant on exposures. Individuals were followed for a maximum of 13 years. Interactions between neuroticism and exposures were assessed using both multiplicative and additive interaction analyses.ResultsExposure to work-related violence/threats was associated with higher odds of SA due to CMDs when adjusting for age, sex, marital status, children, education, type of living area, work characteristics, and symptoms of depression and burnout (OR 2.11, 95% CI 1.52–2.95). Higher odds of SA due to CMDs were also found for exposure to harassment (OR 1.52, 95% CI 1.10–2.11) and a combined indicator of exposure to violence/threats and/or harassment (OR 1.98, 95% CI 1.52–2.59), compared with the unexposed. Analyses of twins discordant on exposure, using the unexposed co-twin as reference, showed reduced ORs. These ORs were still elevated but no longer statistically significant, potentially due to a lack of statistical power. No multiplicative interaction was found between neuroticism and exposure to work-related violence/threats, or harassment. However, a statistically significant additive interaction was found between neuroticism and exposure to violence/threats, indicating higher odds of SA due to CMDs in the group scoring lower on neuroticism.ConclusionsExposure to work-related offensive behaviors was associated with SA due to CMDs. However, the results indicated that these associations may be partly confounded by familial factors. In addition, an interaction between exposure and neuroticism was suggested. Thus, when possible, future studies investigating associations and causality between offensive behaviors at work and mental health-related outcomes, should consider familial factors and neuroticism.

Hydrogen-enhanced densified deformation twins in 304L austenitic stainless steel fabricated by selective laser melting

Twin boundaries are the preferred site for crack nucleation and propagation in a hydrogen-rich environment. The relationship among hydrogen, cellular structure, and deformation twins is significant in further enhancing the resistance to hydrogen embrittlement of austenitic stainless steels produced by SLM. It has been demonstrated that cellular structures with high dislocation densities play a positive role in increasing stress above a critical level for deformation twin formation. The cellular structure affects the distribution of hydrogen, with hydrogen presence at cellular boundaries reducing its accumulation at grain boundaries. Hydrogen increases the density of deformation twins and reduces the thickness of individual deformation twins. This phenomenon can be attributed to an increase in nucleation sites for the deformation twin, which is closely related to the decrease in stacking fault energy and the increase in dislocation density caused by hydrogen. Both cellular structure and deformation twins play a positive role in improving the hydrogen embrittlement resistance of austenitic stainless steels.

Genetic and Environmental Influences on Perceived Stress in South Korean Twins.

Researchers have proposed that culture significantly influences perceived stress (PS). To date, however, twin studies on PS have been conducted mostly in western, individualistic cultures, which demonstrate that PS due to controllable (personal) life events is more heritable than PS due to uncontrollable (network) life events. This study aimed to investigate genetic and environmental influences on PS in South Korean twins. South Korea practices a dominant collectivist culture. In total, 1372 twin individuals (mean age = 22.4 ± 2.5 years) completed an online survey on PS, which consisted of the scales, Friendship, Academic Stress, Future Career, Family Conflicts, and Family Financial Difficulties (FFD). Friendship, Academic Stress, and Future Career can be considered PS due to personal life events, and Family Conflict and FFD, PS due to network life events. The general sex-limitation model-fitting analysis revealed the absence of qualitative or quantitative sex differences in genetic and environmental influences. Specifically, additive genetic influences were predominant for Friendship (63%), Academic Stress (67%), and Future Career (57%) for both sexes, with the remaining variance attributable to nonshared environmental influences. In contrast, shared environmental influences were largest for Family Conflict (47% for both genders) and FFD (64% for males, 63% for females) with no significant genetic effects. Despite known cultural differences in the means and variances of PS, South Korean twins exhibited significant genetic effects in PS due to personal life events and large shared environmental effects in PS due to network life events, which is similar to western samples.

Association of cancer with functional decline at old age: a longitudinal study in Danish twins.

There is evidence that older adults with cancer have a higher risk of functional decline than cancer-free older adults. However, few studies are longitudinal, and none are twin studies. Thus, we aimed to investigate the relationship between cancer and functional decline in older adult (aged 70+ years) twins. Cancer cases in the Longitudinal Study of Aging Danish Twins were identified through the Danish Cancer Registry. Functional status was assessed using hand grip strength (6 years follow-up), and self-reported questions on mobility (10 years follow-up), and cut-offs were defined to assess functional decline. Cox regression models were performed for all the individual twins. In addition, we extended the analysis to discordant twin pairs (twin pairs with one having cancer and the other being cancer-free), to control to a certain extent for (unmeasured) shared confounders (genetic and environmental factors). The analysis based on individual twins showed that individual twins with cancer are at increased hazard of worsening hand grip strength (hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.04, 1.80) than cancer-free twins. Among the discordant twin pairs, twins with cancer had a higher hazard of worsening hand grip strength (HR 3.50, 95% CI 1.15, 10.63) than cancer-free cotwins. In contrast, there was no evidence of a difference between the hazard of experiencing mobility decline for twins with cancer compared with cancer-free twins, in both individual twins and discordant twin pairs analyses. Cancer was associated with hand grip strength functional decline in old individual twins and discordant pairs. Our results strengthen the importance of comprehensive geriatric assessment in older adults with cancer, as well as the importance of routine assessment of functional status. Promoting physical activity through exercise training programmes could enable the prevention of functional decline in older adults with cancer.

The Population-Based Hungarian Twin Registry: An Update.

Between 2006 and 2021, the Hungarian Twin Registry (HTR) operated a volunteer twin registry of all age groups (50% monozygotic [MZ], 50% dizygotic [DZ], 70% female, average age 34 ± 22 years), including 1044 twin pairs, 24 triplets and one quadruplet set. In 2021, the HTR transformed from a volunteer registry into a population-based one, and it was established in the Medical Imaging Centre of Semmelweis University in Budapest. Semmelweis University's innovation fund supported the development of information technology, a phone bank and voicemail infrastructure, administrative materials, and a new website was established where twins and their relatives (parent, foster parent or caregiver) can register. The HTR's biobank was also established: 157,751 individuals with a likely twin-sibling living in Hungary (77,042 twins, 1194 triplets, 20 quadruplets, and one quintuplet) were contacted between February and March of 2021 via sealed letters. Until November 20, 2022, 12,001 twin individuals and their parents or guardians (6724 adult twins, 3009 parents/guardians and 5277 minor twins) registered, mostly online. Based on simple self-reports, 37.6% of the registered adults were MZ twins and 56.8% were DZ; 1.12% were triplets and 4.5% were unidentified. Of the registered children, 22.3% were MZ, 72.7% were DZ, 1.93% were triplets, and 3.05% were unidentified. Of the registered twins, 59.9% were female (including both the adult and minor twins). The registration questionnaire consists of eight parts, including socio-demographic and anthropometric data, smoking habits and medical questions (diseases, operations, therapies). Hungary's twin registry has become the sole and largest population-based twin registry in Central Eastern Europe. This new resource will facilitate performing world-class modern genetic research.

In Situ Pure Shear Tests on Textured Magnesium AZ31B Sheets

Pure shear tests of textured magnesium AZ31B sheet samples were carried out using a 5 kN Kammrath &amp; Weiss in situ tension-compression stage in a scanning electron microscope in combination with real-time electron backscatter diffraction lattice orientation mapping. The sample design was optimized to produce a pure shear stress in the central gauge zone. Distributions of the deformation twins were correlated with finite element simulations using a linear-elastic constitutive law considering large deformations to show that twins form in areas where the principal compressive stress σ3* is a maximum and that they form normal to the trajectories of that minor principal stress. Mappings of the same area at different load values revealed the formation and growth of individual twins and their relationship to the internal elastic strain of individual grains as indicated by the internal grain disorientation. All twins observed were of the extension type, with an 86.3° disorientation with respect to the parent grains. A more detailed study was conducted using transmission electron microscopy to correlate with the EBSD observations and to further elucidate the twin structures within samples.

A Genetically Informed Study of the Association Between Perceived Stress and Loneliness

Although research shows a strong positive association between perceived stress and loneliness, the genetic and environmental etiology underlying their association remains unknown. People with a genetic predisposition to perceived stress, for example, may be more prone to feeling lonely and vice versa. Conversely, unique factors in people’s lives may explain differences in perceived stress levels that, in turn, affect feelings of loneliness. We tested whether genetic factors, environmental factors, or both account for the association between perceived stress and loneliness. Participants were 3,066 individual twins (nFemale = 2,154, 70.3%) from the Washington State Twin Registry who completed a survey during April–May, 2020. Structural equation modeling was used to analyze the item-level perceived stress and loneliness measures. The correlation between latent perceived stress and latent loneliness was .68. Genetic and nonshared environmental variance components underlying perceived stress accounted for 3.71% and 23.26% of the total variance in loneliness, respectively. The genetic correlation between loneliness and perceived stress was .45 and did not differ significantly between men and women. The nonshared environmental correlation was .54 and also did not differ between men and women. Findings suggest that holding constant the strong genetic association between perceived stress and loneliness, unique life experiences underlying people’s perceived stress account for individual differences in loneliness.

Virtual Commissioning of Linked Cells Using Digital Models in an Industrial Metaverse

Various software environments have been developed in the past to create digital twins of single cells or a digital twin of a factory. Each environment has its own strengths and weaknesses and has been designed with a specific focus. The environments that are able to holistically simulate complete factories are limited in terms of the modelling details required for the analysis of single manufacturing cells (e.g., manufacturer-independence of the individual digital twins) and their ability for virtual commissioning. This paper presents three options for realising a virtual commissioning of linked cells using a 3D integration platform with NVIDIA Omniverse, consisting of two different digital models fused into a combined model, also representing material flow. First, with a source/sink solution and unidirectional connector controlled by OPC UA; secondly, with a bidirectional connector, developed in the course of this elaboration, and an extension of the 3D integration platform controlled by Apache Kafka; thirdly, with a bidirectional connector and using only an extension of the 3D integration platform. The research demonstrates that virtually commissioning multiple linked digital twins from different manufacturers in a 3D platform with material flow makes a significant contribution to the industrial metaverse.

Automated Manufacturing Toolchain using Skill-based Digital Twins

Digital twins with a skill-based description are increasingly finding their way into industrial production. Their models link properties of a product with available process capabilities that are realized by resource skills. A matchmaking derives capable resources, e.g. for modular assembly systems. For capability-based planning in manufacturing, integration with computer-aided design (CAD) and computer-aided manufacturing (CAM) programs is missing. This paper presents an automated toolchain with focus on subtractive manufacturing using skill-based digital twins. Product-Process-Resource (PPR) models are used and enriched with subtractive manufacturing information and further relations. A configurator allows the design of the individual digital product twin, which can synchronously be generated as a 3D model using a CAD service. Necessary subtractive manufacturing steps including capable resources are then determined in a planning environment and fed into the CAM system. This allows an individual generation of machining code based on PPR information, which can be validated on a simulation model. The result is an automated tool chain of different software services, which are composed by a common description of the PPR model and the software services themselves. By defined models and interfaces the toolchain is not restricted to subtractive manufacturing but enables the integration of computer-aided everything (CAx) services.

Associations between executive functions assessed in different contexts in a genetically informative sample.

Executive functions (EFs) are cognitive functions that help direct goal-related behavior. EFs are usually measured via behavioral tasks assessed in highly controlled laboratory settings under the supervision of a research assistant. Online versions of EF tasks are an increasingly popular alternative to in-lab testing. However, researchers do not have the same control over the testing environment during online EF assessments. To assess the extent to which EFs assessed in-lab and online are related, we used data from the Colorado Online Twin Study (CoTwins; 887 individual twins aged 13.98-19.05) and constructed an Lab Common EF factor and an Online Common EF factor from four EF tasks assessed in-lab and online. The Lab Common and Online Common EF factors were genetically identical (rA = 1.00) but phenotypically separable (r = .77, 95% confidence interval [0.59, 0.94]) indicating that these EF factors have the same genetic underpinnings but may be differentially influenced by environmental factors. We examined phenotypic, genetic, and environmental correlations between the EF factors and a general cognitive ability factor (g) assessed in the lab and found similar relationships between Lab Common EF and g and Online Common EF and g. Overall, these results suggest that Common EF factors assessed in different contexts are highly related to each other and similarly related to other cognitive outcomes. These findings indicate that online task-based EF assessments could be a viable strategy for increasing sample sizes in large-scale studies, particularly genetically informed studies. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

In Situ Uniaxial Compression of Textured Magnesium AZ31B

Strain-controlled uniaxial compression tests on textured magnesium AZ31B sheet samples were carried out using a 5 kN Kammrath &amp; Weiss tension–compression in situ stage using a scanning electron microscope in combination with real-time electron backscatter diffraction lattice orientation mapping. The distribution of deformation twins in the samples was studied and correlated with the results of finite element simulation of the elastic strain to show that bands of twinned grains formed in areas where the principal compressive stress (σ3) was a maximum, and they formed normal to the trajectory of the principal direction of σ3. This was correlated with maps of lattice disorientation within the grains, which showed the inclination for twins to grow in alignment with local and larger-scale distributions of elastic strain. Mappings of the same area at different values of strain were made to examine the formation and growth of individual twins within the macroscopic bands of twinned grains. All the twins observed were consistent with the extension-type twin, with 86.3° disorientation with respect to the parent grain. Mappings of the grain internal disorientation were related to the elastic strain, and it was found that twin formation and growth followed the contours of the highest elastic strain within and across grains. The maximum angular disorientation found within the grains was approximately 10°, suggesting that this might correspond to a threshold of elastic strain required to initiate twinning.

Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.

Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.