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Summary: Background: Development of a non-sputum test using readily-obtainable biospecimens remains a global priority for tuberculosis (TB) control. We quantified lipoarabinomannan (LAM) concentrations, a pathogen biomarker for Mycobacterium tuberculosis, in urine, plasma and serum for real-world diagnostic accuracy of pulmonary TB among people living with and without HIV. Methods: We conducted a prospective diagnostic study among adults with TB symptoms in South Africa. We measured LAM concentrations in time-matched urine, plasma and serum with an electrochemiluminescence immunoassay using two capture antibodies (FIND 28 and S4–20). From the completed cohort, we randomly selected 210 participants (2 cases: 1 control) based on sensitivity estimates, and we compared diagnostic accuracy of LAM measurements against the microbiological reference standard. Findings: Urine and blood specimens from 210 of 684 adults enrolled were tested for LAM. Among 138 TB-positive adults (41% female), median urine LAM was 137 pg/mL and 52 pg/mL by FIND 28 and S4–20, respectively. Average LAM concentrations were highest in HIV-positive participants with CD4+ T cells

Summary: DNA elements act across long genomic distances to regulate gene expression. During transvection in Drosophila, DNA elements on one allele of a gene act between chromosomes to regulate expression of the other allele. Little is known about the biological roles and developmental regulation of transvection. Here, we study the stochastic expression of spineless (ss) in photoreceptors in the fly eye to understand transvection. We determine a biological role for transvection in regulating expression of naturally occurring ss alleles. We identify DNA elements required for activating and repressing transvection. Different enhancers participate in transvection at different times during development to promote gene expression and specify cell fates. Bringing a silencer element on a heterologous chromosome into proximity with the ss locus “reconstitutes” the gene, leading to repression. Our studies show that transvection regulates gene expression via distinct DNA elements at specific timepoints in development, with implications for genome organization and architecture.

Background: Dysphagia affects over half of adults after stroke. Dysphagia rehabilitation aims to improve swallowing and reduce negative outcomes for these adults. However, significant variability exists in dysphagia rehabilitation. Research is needed to explore the underlying clinician-specific and workplace factors that contribute to variability in dysphagia rehabilitation after stroke. Aim: To explore factors influencing speech pathology practice in dysphagia rehabilitation after stroke. Methods & Procedures: We used a phenomenological approach with an interpretivist perspective. Twenty speech pathologists working in dysphagia rehabilitation participated from different workplace settings around Australia. Five semi-structured focus groups were conducted online. Data were inductively analysed using thematic analysis with a coding reliability method. Outcomes & Results: Four themes were discussed within focus groups: (1) relationship between experienced and less experienced clinicians: 'Following what other people have done', (2) need for collaborative learning: 'A safe space to share and train', (3) variation between settings impacts on continuity of care: 'There's a difference between community and acute', and (4) working effectively with multidisciplinary teams (MDT): 'An MDT which can listen to the voice of speech pathology'. Conclusions & Implications: Relationships between senior and junior speech pathologists, within speech pathology and MDT, and across inpatient and community settings influenced speech pathology practice. Flattened hierarchies in speech pathology, collaborative learning in workplaces, mutual respect within teams and connection across inpatient and community settings could improve the quality and consistency of dysphagia rehabilitation after stroke.

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic on/off expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss that lowers the ratio of SsON to SsOFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of SsON to SsOFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic expression, setting the ratio of alternative fates and ultimately determining color preference.

BACKGROUND:We aimed to evaluate the antibody in lymphocyte supernatant (ALS) assay as a biomarker to diagnose tuberculosis among adults from Tanzania with and without HIV. METHODS:Adults admitted with suspicion for tuberculosis had sputa obtained for GeneXpert MTB/RIF, acid-fast bacilli smear and mycobacterial culture; blood was obtained prior to treatment initiation and after 4 weeks. Adults hospitalized with non-infectious conditions served as controls. Peripheral blood mononuclear cells were cultured unstimulated for 72 hours. Anti-mycobacterial antibodies were measured from culture supernatants by ELISA, using BCG vaccine as the coating antigen. Median ALS responses were compared between cases and controls at baseline and between cases over time. RESULTS:Of 97 TB cases, 85 were microbiologically confirmed and 12 were clinically diagnosed. Median ALS responses from TB cases (0.366 OD from confirmed cases and 0.285 from clinical cases) were higher compared to controls (0.085, p