Melissa Alcaraz, Hayley Pierce, Natalie D Eggum, Bertha Lidia Nuño-Gutiérrez, Dirgha Ghimire
A cross-cultural examination of adverse childhood experiences in low-and middle-income countries and their relation with adolescent educational aspirations
Child abuse & neglect
bacterial diversity could contribute diversity tuberculosis infection treatment outcomes observed clinically biological basis association poorly understood aim study identify associations phenogenomic variation mycobacterium tuberculosis tuberculosis clinical features developed highthroughput platform define phenotypegenotype relationships tuberculosis clinical isolates tested set 158 drugsensitive tuberculosis strains sampled large tuberculosis clinical study ho chi minh city viet nam tagged strains unique genetic barcodes multiplicate allowing us pool strains invitro competitive fitness assays across 16 hostrelevant antibiotic metabolic conditions relative fitness quantified deep sequencing enumerating output barcode read counts relative input normalised values performed genomewide association study identify phylogenetically linked monogenic mutations associated invitro fitness phenotypes genetic determinants associated relevant clinical outcomes cavitary disease treatment failure calculating odds ratios ors binomial logistic regressions also assessed populationlevel transmission strains associated cavitary disease treatment failure using terminal branch length analysis phylogenetic data tuberculosis clinical strains diverse growth characteristics hostlike metabolic drug conditions fitness phenotypes highly heritable identified monogenic phylogenetically linked variants associated fitness phenotypes data enabled us define two genetic features associated clinical outcomes first mutations rv1339 phosphodiesterase associated slow growth glycerol associated treatment failure 534 95 ci 1212358 p0027 second identified phenotypically distinct slowgrowing subclade lineage 1 strains l1111 associated cavitary disease 249 111559 p0027 treatment failure 476 1531478 p00069 shorter terminal branch lengths phylogenetic tree suggesting increased transmission slow growth various antibiotic metabolic conditions served invitro intermediate phenotypes underlying association tuberculosis monogenic phylogenetically linked mutations outcomes cavitary disease treatment failure transmission potential data suggest tuberculosis growth regulation adaptive advantage bacterial success human populations least circumstances data suggest markers underlying bacterial processes contribute clinical outcomes national health medical research councilastar national institutes allergy infectious diseases national institute child health human development wellcome trust fellowship public health tropical medicine