BACKGROUND: A family history of premature coronary heart disease has long been thought to be a risk factor for coronary heart disease. Using data from 26 years of follow-up of 21,004 Swedish twins born between 1886 and 1925, we investigated this issue further by assessing the risk of death from coronary heart disease in pairs of monozygotic and dizygotic twins. METHODS: The study population consisted of 3298 monozygotic and 5964 dizygotic male twins and 4012 monozygotic and 7730 dizygotic female twins. The age at which one twin died of coronary heart disease was used as the primary independent variable to predict the risk of death from coronary heart disease in the other twin. Information about other risk factors was obtained from questionnaires administered in 1961 and 1963. Actuarial life-table analysis was used to estimate the cumulative probability of death from coronary heart disease. Relative-hazard estimates were obtained from a multivariate survival analysis. RESULTS: Among the men, the relative hazard of death from coronary heart disease when one's twin died of coronary heart disease before the age of 55 years, as compared with the hazard when one's twin did not die before 55, was 8.1 (95 percent confidence interval, 2.7 to 24.5) for monozygotic twins and 3.8 (1.4 to 10.5) for dizygotic twins. Among the women, when one's twin died of coronary heart disease before the age of 65 years, the relative hazard was 15.0 (95 percent confidence interval, 7.1 to 31.9) for monozygotic twins and 2.6 (1.0 to 7.1) for dizygotic twins. Among both the men and the women, whether monozygotic or dizygotic twins, the magnitude of the relative hazard decreased as the age at which one's twin died of coronary heart disease increased. The ratio of the relative-hazard estimate for the monozygotic twins to the estimate for the dizygotic twins approached 1 with increasing age. These relative hazards were little influenced by other risk factors for coronary heart disease. CONCLUSIONS: Our findings suggest that at younger ages, death from coronary heart disease is influenced by genetic factors in both women and men. The results also imply that the genetic effect decreases at older ages.
While there has been a recent growth of interest in the Digital Twin, a variety of definitions employed across industry and academia remain. There is a need to consolidate research such to maintain a common understanding of the topic and ensure future research efforts are to be based on solid foundations. Through a systematic literature review and a thematic analysis of 92 Digital Twin publications from the last ten years, this paper provides a characterisation of the Digital Twin, identification of gaps in knowledge, and required areas of future research. In characterising the Digital Twin, the state of the concept, key terminology, and associated processes are identified, discussed, and consolidated to produce 13 characteristics (Physical Entity/Twin; Virtual Entity/Twin; Physical Environment; Virtual Environment; State; Realisation; Metrology; Twinning; Twinning Rate; Physical-to-Virtual Connection/Twinning; Virtual-to-Physical Connection/Twinning; Physical Processes; and Virtual Processes) and a complete framework of the Digital Twin and its process of operation. Following this characterisation, seven knowledge gaps and topics for future research focus are identified: Perceived Benefits; Digital Twin across the Product Life-Cycle; Use-Cases; Technical Implementations; Levels of Fidelity; Data Ownership; and Integration between Virtual Entities; each of which are required to realise the Digital Twin.
BACKGROUND: Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments. METHODS: Pregnant women with severe twin-to-twin transfusion syndrome before 26 weeks of gestation were randomly assigned to laser therapy or amnioreduction. We assessed perinatal survival of at least one twin (a prespecified primary outcome), survival of at least one twin at six months of age, and survival without neurologic complications at six months of age on the basis of the number of pregnancies or the number of fetuses or infants, as appropriate. RESULTS: The study was concluded early, after 72 women had been assigned to the laser group and 70 to the amnioreduction group, because a planned interim analysis demonstrated a significant benefit in the laser group. As compared with the amnioreduction group, the laser group had a higher likelihood of the survival of at least one twin to 28 days of age (76 percent vs. 56 percent; relative risk of the death of both fetuses, 0.63; 95 percent confidence interval, 0.25 to 0.93; P=0.009) and 6 months of age (P=0.002). Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia (6 percent vs. 14 percent, P=0.02) and were more likely to be free of neurologic complications at six months of age (52 percent vs. 31 percent, P=0.003). CONCLUSIONS: Endoscopic laser coagulation of anastomoses is a more effective first-line treatment than serial amnioreduction for severe twin-to-twin transfusion syndrome diagnosed before 26 weeks of gestation.
CONTEXT: The cause of Parkinson disease (PD) is unknown. Genetic linkages have been identified in families with PD, but whether most PD is inherited has not been determined. OBJECTIVE: To assess genetic inheritance of PD by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. DESIGN: Twin study comparing concordance rates of PD in MZ and DZ twin pairs. SETTING AND PARTICIPANTS: A total of 19842 white male twins enrolled in the National Academy of Sciences/National Research Council World War II Veteran Twins Registry were screened for PD and standard diagnostic criteria for PD were applied. Zygosity was determined by polymerase chain reaction or questionnaire. MAIN OUTCOME MEASURE: Parkinson disease concordance in twin pairs, stratified by zygosity and age at diagnosis. RESULTS: Of 268 twins with suspected parkinsonism and 250 presumed unaffected twin brothers, 193 twins with PD were identified (concordance-adjusted prevalence, 8.67/1000). In 71 MZ and 90 DZ pairs with complete diagnoses, pairwise concordance was similar (0.129 overall, 0.155 MZ, 0.111 DZ; relative risk, 1.39; 95% confidence interval, 0.63-3.1). In 16 pairs with diagnosis at or before age 50 years in at least 1 twin, MZ concordance was 1.0 (4 pairs), and DZ was 0.167 (relative risk, 6.0; 95% confidence interval, 1.69-21.26). CONCLUSIONS: The similarity in concordance overall indicates that genetic factors do not play a major role in causing typical PD. No genetic component is evident when the disease begins after age 50 years. However, genetic factors appear to be important when disease begins at or before age 50 years.
CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. DESIGN, SETTING, AND PARTICIPANTS: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services. MAIN OUTCOME MEASURES: Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD). CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.
To assess the relative importance of genetic and environmental effects on the body-mass index (weight in kilograms divided by the square of the height in meters), we studied samples of identical and fraternal twins, reared apart or reared together. The samples consisted of 93 pairs of identical twins reared apart, 154 pairs of identical twins reared together, 218 pairs of fraternal twins reared apart, and 208 pairs of fraternal twins reared together. The intrapair correlation coefficients of the values for body-mass index of identical twins reared apart were 0.70 for men and 0.66 for women. These are the most direct estimates of the relative importance of genetic influences (heritability) on the body-mass index, and they were only slightly lower than those for twins reared together in this and earlier studies. Similar estimates were derived from maximum-likelihood model-fitting analyses--0.74 for men and 0.69 for women. Nonadditive genetic variance made a significant contribution to the estimates of heritability, particularly among men. Of the potential environmental influences, only those unique to the individual and not those shared by family members were important, contributing about 30 percent of the variance. Sharing the same childhood environment did not contribute to the similarity of the body-mass index of twins later in life. We conclude that genetic influences on body-mass index are substantial, whereas the childhood environment has little or no influence. These findings corroborate and extend the results of earlier studies of twins and adoptees.
BACKGROUND: The etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD. METHODS: A PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins. RESULTS: The meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability. CONCLUSIONS: We demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.
BACKGROUND: The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. METHODS: We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. RESULTS: At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 percent; 95 percent confidence interval, 10 to 48 percent), and breast cancer (27 percent; 95 percent confidence interval, 4 to 41 percent). CONCLUSIONS: Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms. This finding indicates that the environment has the principal role in causing sporadic cancer. The relatively large effect of heritability in cancer at a few sites suggests major gaps in our knowledge of the genetics of cancer.
Since 1979, a continuing study of monozygotic and dizygotic twins, separated in infancy and reared apart, has subjected more than 100 sets of reared-apart twins or triplets to a week of intensive psychological and physiological assessment. Like the prior, smaller studies of monozygotic twins reared apart, about 70% of the variance in IQ was found to be associated with genetic variation. On multiple measures of personality and temperament, occupational and leisure-time interests, and social attitudes, monozygotic twins reared apart are about as similar as are monozygotic twins reared together. These findings extend and support those from numerous other twin, family, and adoption studies. It is a plausible hypothesis that genetic differences affect psychological differences largely indirectly, by influencing the effective environment of the developing child. This evidence for the strong heritability of most psychological traits, sensibly construed, does not detract from the value or importance of parenting, education, and other propaedeutic interventions.
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
Digital Twin technology is an emerging concept that has become the centre of attention for industry and, in more recent years, academia. The advancements in industry 4.0 concepts have facilitated its growth, particularly in the manufacturing industry. The Digital Twin is defined extensively but is best described as the effortless integration of data between a physical and virtual machine in either direction. The challenges, applications, and enabling technologies for Artificial Intelligence, Internet of Things (IoT) and Digital Twins are presented. A review of publications relating to Digital Twins is performed, producing a categorical review of recent papers. The review has categorised them by research areas: manufacturing, healthcare and smart cities, discussing a range of papers that reflect these areas and the current state of research. The paper provides an assessment of the enabling technologies, challenges and open research for Digital Twins.
Digital twin can be defined as a virtual representation of a physical asset enabled through data and simulators for real-time prediction, optimization, monitoring, controlling, and improved decision making. Recent advances in computational pipelines, multiphysics solvers, artificial intelligence, big data cybernetics, data processing and management tools bring the promise of digital twins and their impact on society closer to reality. Digital twinning is now an important and emerging trend in many applications. Also referred to as a computational megamodel, device shadow, mirrored system, avatar or a synchronized virtual prototype, there can be no doubt that a digital twin plays a transformative role not only in how we design and operate cyber-physical intelligent systems, but also in how we advance the modularity of multi-disciplinary systems to tackle fundamental barriers not addressed by the current, evolutionary modeling practices. In this work, we review the recent status of methodologies and techniques related to the construction of digital twins mostly from a modeling perspective. Our aim is to provide a detailed coverage of the current challenges and enabling technologies along with recommendations and reflections for various stakeholders.
With the advances in new-generation information technologies, especially big data and digital twin, smart manufacturing is becoming the focus of global manufacturing transformation and upgrading. Intelligence comes from data. Integrated analysis for the manufacturing big data is beneficial to all aspects of manufacturing. Besides, the digital twin paves a way for the cyber-physical integration of manufacturing, which is an important bottleneck to achieve smart manufacturing. In this paper, the big data and digital twin in manufacturing are reviewed, including their concept as well as their applications in product design, production planning, manufacturing, and predictive maintenance. On this basis, the similarities and differences between big data and digital twin are compared from the general and data perspectives. Since the big data and digital twin can be complementary, how they can be integrated to promote smart manufacturing are discussed.
The many 'friendly' microbes that inhabit the human gut have been implicated in numerous health-related issues, in particular those involving digestion and susceptibility to infection. A study of the faecal microbial communities of pairs of adult female twins, selected to include 'lean' and 'obese' individuals, reveals some similarities between the human gut microbiomes among family members, but each person's gut microbial community varies in the specific bacterial lineages present. There was a wide array of shared microbial genes among individuals, comprising an identifiable 'core microbiome' at the gene, rather than at the microbial species level. This core includes many novel genes for carbohydrate metabolism, and deviations from this core are associated with the obese versus lean state. The human microbiota has been implicated in many health-related issues. In this study, the microbiota composition of monozygotic and dizygotic twins and their mothers is examined. Although a core microbiome could not be defined on a phylogenetic level, the data suggests that core functions are conserved. The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides1,2,3,4,5,6. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes6,7,8, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored3,4,5. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person’s gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable ‘core microbiome’ at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
Height, weight, and body mass index (BMI) were assessed in a sample of 1974 monozygotic and 2097 dizygotic male twin pairs. Concordance rates for different degrees of overweight were twice as high for monozygotic twins as for dizygotic twins. Classic twin methods estimated a high heritability for height, weight, and BMI, both at age 20 years (.80, .78, and .77, respectively) and at a 25-year follow-up (.80, .81, and .84, respectively). Height, weight, and BMI were highly correlated across time, and a path analysis suggested that the major part of that covariation was genetic. These results are similar to those of other twin studies of these measures and suggest that human fatness is under substantial genetic control.
We propose Twin SVM, a binary SVM classifier that determines two nonparallel planes by solving two related SVM-type problems, each of which is smaller than in a conventional SVM. The Twin SVM formulation is in the spirit of proximal SVMs via generalized eigenvalues. On several benchmark data sets, Twin SVM is not only fast, but shows good generalization. Twin SVM is also useful for automatically discovering two-dimensional projections of the data.
Injection molding industry has evolved over decades and became the most common method to manufacture plastic parts. Monitoring and improvement in the injection molding industry are usually performed separately in each stage, i.e. mold design, mold making and injection molding process. However, in order to make a breakthrough and survive in the industrial revolution, all the stages in injection molding need to be linked and communicated witheachother.Anychangesinonestagewillcauseacertaineffectinotherstagebecausethere is a correlation between each other. Hence, the simulation should not only based on the input of historical data, but it also needs to include the current condition of equipment and prediction of future events in other stages to make the responsive decision. This can be achieved by implementing the concept of Digital Twin that models the entire process as a virtual model and enables bidirectional control with the physical process. This paper presented types of data and technology required to build the Digital Twin for the injection molding industry. The concept includes Digital Twin of each stage and integration of these Digital Twin model as a thoroughgoing model of the injection molding industry.
Digital Twin (DT) refers to the virtual copy or model of any physical entity (physical twin) both of which are interconnected via exchange of data in real time. Conceptually, a DT mimics the state of its physical twin in real time and vice versa. Application of DT includes real-time monitoring, designing/planning, optimization, maintenance, remote access, etc. Its implementation is expected to grow exponentially in the coming decades. The advent of Industry 4.0 has brought complex industrial systems that are more autonomous, smart, and highly interconnected. These systems generate considerable amounts of data useful for several applications such as improving performance, predictive maintenance, training, etc. A sudden influx in the number of publications related to ‘Digital Twin’ has led to confusion between different terminologies related to the digitalization of industries. Another problem that has arisen due to the growing popularity of DT is a lack of consensus on the description of DT as well as so many different types of DT, which adds to the confusion. This paper intends to consolidate the different types of DT and different definitions of DT throughout the literature for easy identification of DT from the rest of the complimentary terms such as ‘product avatar’, ‘digital thread’, ‘digital model’, and ‘digital shadow’. The paper looks at the concept of DT since its inception to its predicted future to realize the value it can bring to certain sectors. Understanding the characteristics and types of DT while weighing its pros and cons is essential for any researcher, business, or sector before investing in the technology.
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.