Hepatic periportal fibrosis, which affects 5–10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p ≤ 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-γ levels were associated with a marked reduction of the risk of fibrosis (p = 0.01; OR, 0.1); in contrast, high TNF-α levels were associated with an increased risk (p = 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-γ production. These results with observations in experimental models strongly suggest that IFN-γ plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-α may aggravate the disease.

Lethal disease due to hepatic periportal fibrosis occurs in 2%-10% of subjects infected by Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development. Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with.16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the IFN-gammaR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-gamma. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the IFN-gammaR1 gene could determine severe hepatic disease due to S. mansoni infection and that the IFN-gammaR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.

Selection and recruitment into healthcare education and practice is a major area of endeavor for health professional educators. Key insights have emerged to guide further inquiry and influence future policy and practice since the last Ottawa consensus statement on selection (Prideaux et al., 2011). However, much remains to be done, not only in refining the science of selection, but also in considering the opportunities and challenges of translating current research understandings into established practice. This updated consensus statement is based on strong theoretical research evidence and was developed using a multi-stage process. First, a group of international researchers with expertise in selection and recruitment, assessment, curriculum, and educational theory was specially convened to critically appraise the literature and develop a draft consensus statement. Second, the group shared the draft statement with the wider community via a workshop and symposium at the 2018 Ottawa-ICME Joint Conference on the Assessment of Competence in Medicine and the Healthcare Professions, and at the Second International Conference of Selection into the Health Professions. Colleagues from diverse countries and regions actively engaged with these activities face-to-face and through social media. Finally, the statement was refined on the basis of feedback, questions and comments, sent for independent peer review, and further revised. Reflecting the state of the science at the time, the previous consensus (Prideaux et al., 2011) characterised selection as an assessment system and focussed on the quality of different selection methods. In this updated statement, we present the latest research findings on selection methods and, reflecting progression within the field, we also consider potentially more complex issues including: selection policies; methodological concerns (beyond psychometric issues); social accountability, diversity and fairness, workforce shortages in some specialities (e.g. General Practice and Psychiatry) and in certain contexts (e.g. remote and rural working, and emerging countries), globalisation issues, developments in theory, and evaluation frameworks. We conclude with a synthesis of the key issues and a series of recommendations to guide future research and practice and encourage debate between colleagues across the globe. Our findings are

Behaviors and conditions known to persist into adulthood and result in morbidity and premature mortality are prevalent among adolescents in Saudi Arabia. Preventive measures and local health policies are urgently needed and can impact adolescents and future adults. Establishing adolescent health surveillance is necessary to monitor trends and impacts of such measures.

Lethal disease in Schistosoma mansoni infections is mostly due to portal hypertension caused by hepatic periportal fibrosis. To evaluate the factors that may determine severe disease, livers and spleens were examined by ultrasound in a Sudanese population living in a village where S. mansoni is endemic. Early (FI), moderate (FII), or advanced (FIII) fibrosis was observed in 58%, 9%, and 3% of the population, respectively. Although FI affected 50%-70% of the children and adolescents, FII prevalence was low in subjects