Migration to middle-income countries and tuberculosis-global policies for global economies.

International migration to middle-income countries is increasing and its health consequences, in particular increasing transmission rates of tuberculosis (TB), deserve consideration. Migration and TB are a matter of concern in high-income countries and targeted screening of migrants for active and latent TB infection is a main strategy to manage risk and minimize transmission. In this paper, we discuss some aspects of TB control and migration in the context of middle-income countries, together with the prospect of responding with equitable and comprehensive policies. TB rates in middle-income countries remain disproportionally high among the poorest and most vulnerable groups in large cities where most migrant populations are concentrated. Policies that tackle migrant TB in high-income countries may be inadequate for middle-income countries because of their different socio-economic and cultural scenarios. Strategies to control TB in these settings must take into account the characteristics of middle-income countries and the complexity of TB as a disease of poverty. Intersectoral policies of social protection such as cash-transfer programs help reducing poverty and improving health in vulnerable populations. We address the development of new approaches to improve well-established strategies including contact tracing and active and latent TB screening as an 'add on' to the existing health care guidelines of conditional cash transfer programs. In addition, we discuss how it might improve health and welfare among both poor migrants and locally-born populations. Authorities from middle-income countries should recognise that migrants are a vulnerable social group and promote cooperation efforts between sending and receiving countries for mitigation of poverty and prevention of disease in this group. Middle-income countries have long sent migrants overseas. However, the influx of large migrant populations into their societies is relatively new and a growing phenomenon and it is time to set comprehensive goals to improve health among these communities. Conditional cash transfer policies with TB screening and strengthening of DOTS are some strategies that deserve attention. Reduction of social and health inequality among migrants should be incorporated into concerted actions to meet TB control targets

Migration to middle-income countries and tuberculosis-global policies for global economies.

BACKGROUND: International migration to middle-income countries is increasing and its health consequences, in particular increasing transmission rates of tuberculosis (TB), deserve consideration. Migration and TB are a matter of concern in high-income countries and targeted screening of migrants for active and latent TB infection is a main strategy to manage risk and minimize transmission. In this paper, we discuss some aspects of TB control and migration in the context of middle-income countries, together with the prospect of responding with equitable and comprehensive policies. MAIN BODY: TB rates in middle-income countries remain disproportionally high among the poorest and most vulnerable groups in large cities where most migrant populations are concentrated. Policies that tackle migrant TB in high-income countries may be inadequate for middle-income countries because of their different socio-economic and cultural scenarios. Strategies to control TB in these settings must take into account the characteristics of middle-income countries and the complexity of TB as a disease of poverty. Intersectoral policies of social protection such as cash-transfer programs help reducing poverty and improving health in vulnerable populations. We address the development of new approaches to improve well-established strategies including contact tracing and active and latent TB screening as an 'add on' to the existing health care guidelines of conditional cash transfer programs. In addition, we discuss how it might improve health and welfare among both poor migrants and locally-born populations. Authorities from middle-income countries should recognise that migrants are a vulnerable social group and promote cooperation efforts between sending and receiving countries for mitigation of poverty and prevention of disease in this group. CONCLUSIONS: Middle-income countries have long sent migrants overseas. However, the influx of large migrant populations into their societies is relatively new and a growing phenomenon and it is time to set comprehensive goals to improve health among these communities. Conditional cash transfer policies with TB screening and strengthening of DOTS are some strategies that deserve attention. Reduction of social and health inequality among migrants should be incorporated into concerted actions to meet TB control targets

Migration and tuberculosis transmission in a middle-income country: a cross-sectional study in a central area of São Paulo, Brazil.

BACKGROUND: Little is known about the impact of growing migration on the pattern of tuberculosis (TB) transmission in middle-income countries. We estimated TB recent transmission and its associated factors and investigated the presence of cross-transmission between South American migrants and Brazilians. METHODS: We studied a convenient sample of cases of people with pulmonary TB in a central area of São Paulo, Brazil, diagnosed between 2013 and 2014. Cases with similar restriction fragment length polymorphism (IS6110-RFLP) patterns of their Mycobacterium tuberculosis complex isolates were grouped in clusters (recent transmission). Clusters with both Brazilian and South American migrants were considered mixed (cross-transmission). Risk factors for recent transmission were studied using logistic regression. RESULTS: Isolates from 347 cases were included, 76.7% from Brazilians and 23.3% from South American migrants. Fifty clusters were identified, which included 43% South American migrants and 60.2% Brazilians (odds ratio = 0.50, 95% confidence interval = 0.30-0.83). Twelve cross-transmission clusters were identified, involving 24.6% of all clustered cases and 13.8% of all genotyped cases, with migrants accounting for either an equal part or fewer cases in 11/12 mixed clusters. CONCLUSIONS: Our results suggest that TB disease following recent transmission is more common among Brazilians, especially among those belonging to high-risk groups, such as drug users. Cross-transmission between migrants and Brazilians was present, but we found limited contributions from migrants to Brazilians in central areas of São Paulo and vice versa

Researchers’ views on return of incidental genomic research results: qualitative and quantitative findings

Purpose: Comprehensive genomic analysis including exome and genome sequencing is increasingly being utilized in research studies, leading to the generation of incidental genetic findings. It is unclear how researchers plan to deal with incidental genetic findings. Methods: We conducted a survey of the practices and attitudes of 234 members of the US genetic research community and performed qualitative semistructured interviews with 28 genomic researchers to understand their views and experiences with incidental genetic research findings. Results: We found that 12% of the researchers had returned incidental genetic findings, and an additional 28% planned to do so. A large majority of researchers (95%) believe that incidental findings for highly penetrant disorders with immediate medical implications should be offered to research participants. However, there was no consensus on returning incidental results for other conditions varying in penetrance and medical actionability. Researchers raised concerns that the return of incidental findings would impose significant burdens on research and could potentially have deleterious effects on research participants if not performed well. Researchers identified assistance needed to enable effective, accurate return of incidental findings. Conclusion: The majority of the researchers believe that research participants should have the option to receive at least some incidental genetic research results

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4(+) enterocytes, microfold-like cells, and IL13RA2(+)IL11(+) inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and coregulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.Peer reviewe

Genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: Complement component C1q and Prnp polymorphisms

The genetic basis of susceptibility to chronic wasting disease (CWD) in free-ranging cervids is of great interest. Association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. We used an innovative matched case–control design and conditional logistic regression to evaluate associations between polymorphisms of complement C1q and prion protein (Prnp) genes and CWD infection in white-tailed deer from the CWD endemic area in southcentral Wisconsin. To reduce problems due to admixture or disease-risk confounding, we used neutral genetic (microsatellite) data to identify closely related CWD-positive (n = 68) and CWD-negative (n = 91) female deer to serve as matched cases and controls. Cases and controls were also matched on factors (sex, location, age) previously demonstrated to affect CWD infection risk. For Prnp, deer with at least one Serine (S) at amino acid 96 were significantly less likely to be CWD-positive relative to deer homozygous for Glycine (G). This is the first characterization of genes associated with the complement system in white-tailed deer. No tests for association between any C1q polymorphism and CWD infection were significant at p \u3c 0.05. After controlling for Prnp, we found weak support for an elevated risk of CWD infection in deer with at least one Glycine (G) at amino acid 56 of the C1qC gene. While we documented numerous amino acid polymorphisms in C1q genes none appear to be strongly associated with CWD susceptibility

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe