The impact of social protection and poverty elimination on global tuberculosis incidence: a statistical modelling analysis of Sustainable Development Goal 1.

BACKGROUND: The End TB Strategy and the Sustainable Development Goals (SDGs) are intimately linked by their common targets and approaches. SDG 1 aims to end extreme poverty and expand social protection coverage by 2030. Achievement of SDG 1 is likely to affect the tuberculosis epidemic through a range of pathways. We estimate the reduction in global tuberculosis incidence that could be obtained by reaching SDG 1. METHODS: We developed a conceptual framework linking key indicators of SDG 1 progress to tuberculosis incidence via well described risk factor pathways and populated it with data from the SDG data repository and the WHO tuberculosis database for 192 countries. Correlations and mediation analyses informed the strength of the association between the SDG 1 subtargets and tuberculosis incidence, resulting in a simplified framework for modelling. The simplified framework linked key indicators for SDG 1 directly to tuberculosis incidence. We applied an exponential decay model based on linear associations between SDG 1 indicators and tuberculosis incidence to estimate tuberculosis incidence in 2035. FINDINGS: Ending extreme poverty resulted in a reduction in global incidence of tuberculosis of 33·4% (95% credible interval 15·5-44·5) by 2035 and expanding social protection coverage resulted in a reduction in incidence of 76·1% (45·2-89·9) by 2035; both pathways together resulted in a reduction in incidence of 84·3% (54·7-94·9). INTERPRETATION: Full achievement of SDG 1 could have a substantial effect on the global burden of tuberculosis. Cross-sectoral approaches that promote poverty reduction and social protection expansion will be crucial complements to health interventions, accelerating progress towards the End TB targets. FUNDING: World Health Organization

The First α Helix of Interleukin (Il)-2 Folds as a Homotetramer, Acts as an Agonist of the IL-2 Receptor β Chain, and Induces Lymphokine-Activated Killer Cells

Interleukin (IL)-2 interacts with two types of functional receptors (IL-2Rαβγ and IL-2Rβγ) and acts on a broad range of target cells involved in inflammatory reactions and immune responses. For the first time, we show that a chemically synthesized fragment of the IL-2 sequence can fold into a molecule mimicking the quaternary structure of a hemopoietin. Indeed, peptide p1–30 (containing amino acids 1–30, covering the entire α helix A of IL-2) spontaneously folds into an α-helical homotetramer and stimulates the growth of T cell lines expressing human IL-2Rβ, whereas shorter versions of the peptide lack helical structure and are inactive. We also demonstrate that this neocytokine interacts with a previously undescribed dimeric form of IL-2Rβ. In agreement with its binding to IL-2Rβ, p1–30 activates Shc and p56lck but unlike IL-2, fails to activate Janus kinase (Jak)1, Jak3, and signal transducer and activator of transcription 5 (STAT5). Unexpectedly, we also show that p1–30 activates Tyk2, thus suggesting that IL-2Rβ may bind to different Jaks depending on its oligomerization. At the cellular level, p1–30 induces lymphokine-activated killer (LAK) cells and preferentially activates CD8low lymphocytes and natural killer cells, which constitutively express IL-2Rβ. A significant interferon γ production is also detected after p1–30 stimulation. A mutant form of p1–30 (Asp20→Lys), which is likely unable to induce vascular leak syndrome, remains capable of generating LAK cells, like the original p1–30 peptide. Altogether, our data suggest that p1–30 has therapeutic potential

Decoding information in the human hippocampus: a user's guide

Multi-voxel pattern analysis (MVPA), or 'decoding', of fMRI activity has gained popularity in the neuroimaging community in recent years. MVPA differs from standard fMRI analyses by focusing on whether information relating to specific stimuli is encoded in patterns of activity across multiple voxels. If a stimulus can be predicted, or decoded, solely from the pattern of fMRI activity, it must mean there is information about that stimulus represented in the brain region where the pattern across voxels was identified. This ability to examine the representation of information relating to specific stimuli (e.g., memories) in particular brain areas makes MVPA an especially suitable method for investigating memory representations in brain structures such as the hippocampus. This approach could open up new opportunities to examine hippocampal representations in terms of their content, and how they might change over time, with aging, and pathology. Here we consider published MVPA studies that specifically focused on the hippocampus, and use them to illustrate the kinds of novel questions that can be addressed using MVPA. We then discuss some of the conceptual and methodological challenges that can arise when implementing MVPA in this context. Overall, we hope to highlight the potential utility of MVPA, when appropriately deployed, and provide some initial guidance to those considering MVPA as a means to investigate the hippocampus

Catastrophic costs potentially averted by tuberculosis control in India and South Africa: a modelling study.

BACKGROUND: The economic burden on households affected by tuberculosis through costs to patients can be catastrophic. WHO's End TB Strategy recognises and aims to eliminate these potentially devastating economic effects. We assessed whether aggressive expansion of tuberculosis services might reduce catastrophic costs. METHODS: We estimated the reduction in tuberculosis-related catastrophic costs with an aggressive expansion of tuberculosis services in India and South Africa from 2016 to 2035, in line with the End TB Strategy. Using modelled incidence and mortality for tuberculosis and patient-incurred cost estimates, we investigated three intervention scenarios: improved treatment of drug-sensitive tuberculosis; improved treatment of multidrug-resistant tuberculosis; and expansion of access to tuberculosis care through intensified case finding (South Africa only). We defined tuberculosis-related catastrophic costs as the sum of direct medical, direct non-medical, and indirect costs to patients exceeding 20% of total annual household income. Intervention effects were quantified as changes in the number of households incurring catastrophic costs and were assessed by quintiles of household income. FINDINGS: In India and South Africa, improvements in treatment for drug-sensitive and multidrug-resistant tuberculosis could reduce the number of households incurring tuberculosis-related catastrophic costs by 6-19%. The benefits would be greatest for the poorest households. In South Africa, expanded access to care could decrease household tuberculosis-related catastrophic costs by 5-20%, but gains would be seen largely after 5-10 years. INTERPRETATION: Aggressive expansion of tuberculosis services in India and South Africa could lessen, although not eliminate, the catastrophic financial burden on affected households. FUNDING: Bill & Melinda Gates Foundation

Translational research for tuberculosis elimination: priorities, challenges, and actions

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035

Economic Support to Patients in HIV and TB Grants in Rounds 7 and 10 from the Global Fund to Fight AIDS, Tuberculosis and Malaria.

People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p

Antisemitism and anti-Zionism in Iran: the effects of identity, threat, and political trust

Antisemitism and anti-Zionism constitute two important ideological building blocks of the Islamic Republic of Iran. This article is the first to present quantitative empirical survey data elucidating attitudes towards Jews and Israel among an opportunity sample of Iranians. This study examines the correlates of antisemitism and anti-Zionism in Iran with particular attention to the effects of identity, threat, and political trust. Consistent with emerging research into antisemitism and anti-Zionism, there was a positive association between both forms of prejudice, suggesting social psychological overlap between the constructs. Given the pervasiveness of antisemitic and anti-Zionist representations in Iran, there were no significant differences in levels of anti-Zionism or antisemitism on the basis of gender and educational orientations. Political conservatives did manifest greater antisemitism and anti-Zionism than political reformists, although both groups scored high on these scales. There was a significant interaction effect of Iranian national identity and political trust on anti-Zionism, and a significant interaction effect of Muslim religious identity and political trust on antisemitism. Political trust was by far the most powerful predictor of both forms of prejudice, followed by the perception of identity threat. These observations are considered through the lenses of Social Identity Theory and Identity Process Theory from social psychology

Alteridad, etnicidad y racismo en la búsqueda de orígenes de personas adoptadas. El caso de España

En España, la búsqueda de orígenes de las personas adoptadas, motivada por la necesidad de comunicar la historia previa a los/las menores provenientes principalmente de China, Rusia, Etiopía y Vietnam, transita entre lo biológico y lo cultural. Las adopciones internacionales introducen en el contexto de la adopción un replanteamiento de las nociones origen e identidad e incorporan las de etnicidad y raza. En este artículo, mediante el análisis crítico de discurso de un trabajo etnográfico, se subraya la importancia de repensar qué se está entendiendo por “orígenes”, tanto institucional como académicamente, y cuáles son las consecuencias —tanto teóricas como metodológicas y prácticas— de esta conceptualización en la construcción de otredad y diferencia en las personas adoptadas, en función de su procedenciaIn Spain, the search for the origins of adopted people, driven by the need to communicate the prior history of minors coming mainly from China, Russia, Ethiopia and Vietnam, moves between the biological and the cultural. International adoptions introduce a rethinking of the notions of origin and identity and incorporate those of ethnicity and race into the context of adoption. In this article, through the critical discourse analysis of an ethnographic paper, we highlight the importance of rethinking what is being understood as “origins”, both institutionally as well as academically, and what are the consequences —both theoretically as well as methodologically and practically— of this conceptualization in the construction of otherness and difference in adopted people, based on their provenance.El presente artículo se inscribe en el Proyecto I+D+i, “Menores migrantes en el arco mediterráneo: movilidad, sistemas de acogida e integración” (DER2017-89623-R), financiado por el Ministerio de Economía, Industria y Competitividad del Gobierno de España

Management of latent Mycobacterium tuberculosis infection:WHO guidelines for low tuberculosis burden countries

ABSTRACT Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of &lt;100 per 100000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing an