| 1. |
- Bjerregaard-Andersen, Morten, et al.
(författare)
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Tuberculosis burden in an urban population: a cross sectional tuberculosis survey from Guinea Bissau
- 2010
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known about the prevalence of pulmonary tuberculosis (TB) in low income countries. We conducted a cross sectional survey for pulmonary TB and TB symptoms in Bissau, Guinea-Bissau, in an urban cohort with known HIV prevalence. TB surveillance in the area is routinely based on passive case finding. Methods: Two cohorts were selected based on a previous HIV survey, but only 52.5% of those enrolled in the adult cohort had participated in the HIV survey. One cohort included all adults living in 384 randomly selected houses; in this cohort 8% (135/1687) were HIV infected. The other included individuals 50 years or older from all other houses in the study area; of these 11% (62/571) were HIV infected. Symptom screening was done through household visits using a standardised questionnaire. TB suspects were investigated with sputum smear microscopy and X-ray. Results: In the adult cohort, we found 4 cases among 2989 individuals screened, giving a total TB prevalence of 134/100,000 (95% CI 36-342/100,000). In the >50 years cohort, we found 4 cases among 571 individuals screened, giving a total prevalence of 701/100,000 (191-1784/100.000). Two of the eight detected TB cases were unknown by the TB program. Of the total TB cases five were HIV uninfected while three had unknown HIV status. The prevalence of TB symptoms was 2.1% (63/2989) and 10.3% (59/571) in the two cohorts respectively. Conclusions: In conclusion we found a moderately high prevalence of pulmonary TB and TB symptoms in the general population, higher among elderly individuals. By active case finding unknown cases were detected. Better awareness of TB and its symptoms needs to be promoted in low income settings.
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| 2. |
- Jelenkovic, Aline, et al.
(författare)
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Associations between birth size and later height from infancy through adulthood : An individual based pooled analysis of 28 twin cohorts participating in the CODATwins project
- 2018
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Ingår i: Early Human Development. - : Elsevier BV. - 0378-3782 .- 1872-6232. ; 120, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is evidence that birth size is positively associated with height in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. Aim: To analyze the associations of birth weight, length and ponderal index with height from infancy through adulthood within mono- and dizygotic twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods: This study is based on the data from 28 twin cohorts in 17 countries. The pooled data included 41,852 complete twin pairs (55% monozygotic and 45% same-sex dizygotic) with information on birth weight and a total of 112,409 paired height measurements at ages ranging from 1 to 69 years. Birth length was available for 19,881 complete twin pairs, with a total of 72,692 paired height measurements. The association between birth size and later height was analyzed at both the individual and within-pair level by linear regression analyses. Results: Within twin pairs, regression coefficients showed that a 1-kg increase in birth weight and a 1-cm increase in birth length were associated with 1.14–4.25 cm and 0.18–0.90 cm taller height, respectively. The magnitude of the associations was generally greater within dizygotic than within monozygotic twin pairs, and this difference between zygosities was more pronounced for birth length. Conclusion: Both genetic and individual-specific environmental factors play a role in the association between birth size and later height from infancy to adulthood, with a larger role for genetics in the association with birth length than with birth weight.
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| 3. |
- Jelenkovic, Aline, et al.
(författare)
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Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
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Tidskriftsartikel (refereegranskat)abstract
- A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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| 4. |
- Silventoinen, Karri, et al.
(författare)
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The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
- 2015
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
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Tidskriftsartikel (refereegranskat)abstract
- For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
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| 5. |
- Wagh, Rucha, et al.
(författare)
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Twins in Guinea-Bissau have a 'thin-fat' body composition compared to singletons
- 2022
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Ingår i: Journal of Developmental Origins of Health and Disease. - 2040-1744. ; 13:6, s. 787-793
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Tidskriftsartikel (refereegranskat)abstract
- The 'thrifty phenotype' hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country. Anthropometric data were available on 7-34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p = 0.055), weight (WAZ -0.73, p = 0.024) and BMI (BAZ -0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort. African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.
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| 6. |
- Yokoyama, Yoshie, et al.
(författare)
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Genetic and environmental factors affecting birth size variation : A pooled individual-based analysis of secular trends and global geographical differences using 26 twin cohorts
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 47:4, s. 1195-1206
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genetic architecture of birth size may differ geographically and over time. We examined differences in the genetic and environmental contributions to birthweight, length and ponderal index (PI) across geographical-cultural regions (Europe, North America and Australia, and East Asia) and across birth cohorts, and how gestational age modifies these effects. Methods: Data from 26 twin cohorts in 16 countries including 57 613 monozygotic and dizygotic twin pairs were pooled. Genetic and environmental variations of birth size were estimated using genetic structural equation modelling. Results: The variance of birthweight and length was predominantly explained by shared environmental factors, whereas the variance of PI was explained both by shared and unique environmental factors. Genetic variance contributing to birth size was small. Adjusting for gestational age decreased the proportions of shared environmental variance and increased the propositions of unique environmental variance. Genetic variance was similar in the geographical-cultural regions, but shared environmental variance was smaller in East Asia than in Europe and North America and Australia. The total variance and shared environmental variance of birth length and PI were greater from the birth cohort 1990-99 onwards compared with the birth cohorts from 1970-79 to 1980-89. Conclusions: The contribution of genetic factors to birth size is smaller than that of shared environmental factors, which is partly explained by gestational age. Shared environmental variances of birth length and PI were greater in the latest birth cohorts and differed also across geographical-cultural regions. Shared environmental factors are important when explaining differences in the variation of birth size globally and over time.
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| 7. |
- Kristensen, Nikolaj Pagh, et al.
(författare)
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Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma
- 2022
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Neoantigen-driven recognition and T cell–mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs). Yet how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS. Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic melanoma patients who received ACT. RESULTS. We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with increased survival and that neoepitope-specific CD8+ T cells shared with the infusion product in posttreatment blood samples were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS. These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING. NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation.
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| 8. |
- Schaltz-Buchholzer, Frederik, et al.
(författare)
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BCG skin reactions by 2 months of age are associated with better survival in infancy : A prospective observational study from Guinea-Bissau
- 2020
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Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Receiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ∼40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality. Methods Prospective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses. Results The BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30-0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51-0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2-12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26-0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions. Conclusion Among BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits.
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