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Abstract Questions about when early members of the genus Homo adapted to extreme environments like deserts and rainforests have traditionally focused on Homo sapiens. Here, we present multidisciplinary evidence from Engaji Nanyori in Tanzania’s Oldupai Gorge, revealing that Homo erectus thrived in hyperarid landscapes one million years ago. Using biogeochemical analyses, precise chronometric dating, palaeoclimate simulations, biome modeling, fire history reconstructions, palaeobotanical studies, faunal assemblages, and archeological evidence, we reconstruct an environment dominated by semidesert shrubland. Despite these challenges, Homo erectus repeatedly occupied fluvial landscapes, leveraging water sources and ecological focal points to mitigate risk. These findings suggest archaic humans possessed an ecological flexibility previously attributed only to later hominins. This adaptability likely facilitated the expansion of Homo erectus into the arid regions of Africa and Eurasia, redefining their role as ecological generalists thriving in some of the most challenging landscapes of the Middle Pleistocene.

IntroductionSecond language learning is a multifaceted task that benefits across numerous neurocognitive domains including central auditory processing. Existing cross-sectional and longitudinal data show that performance on tests of central auditory processing [central auditory tests (CATs)] worsens with HIV infection. Second language learning may modify this relationship. To explore the relationship between second language learning, central auditory processing, and its interaction with HIV, we assessed the effect of learning English as a second language on CATs among children both living with and without HIV (CLWH/CLWOH) in Dar es Salaam, Tanzania.MethodsThree hundred and seventy-two native Kiswahili speaking children aged 3-10 years old (196 CLWOH, 176 CLWH) were enrolled. Participants completed questionnaires about English language learning, socioeconomic status (SES), and health history. Three central auditory tests-the Triple Digit Test (TDT), the Staggered Spondaic Word Test (SSW), and the Hearing-In-Noise Test (HINT)-were used to assess each participant's central auditory processing abilities. Multivariate linear regression was used to assess the effect of written and spoken English language learning at home and in school on CATs with age, HIV-status, and SES included in each model.ResultsHIV status, age, and SES were all significant predictors of all three central auditory tests, with CLWH performing significantly worse on all three CATs than CLWOH. Children actively learning spoken and written English at home had significantly better central auditory processing abilities on the TDT compared to children not actively learning English at home (p < 0.01) independent of HIV status, age, and SES. Children learning spoken and written English at school performed significantly better on the HINT (p < 0.05) than those not actively learning English at school.DiscussionLearning English at home and learning English in school were associated with improved central auditory performance independent of HIV status, SES, and age. These findings also underscore the significance of second language acquisition as a potential mechanism of improving central auditory function within a Kiswahili-speaking cohort. This study found differences in central auditory processing between children exposed to English at home and in school, suggesting differences in language learning in both settings mediated by SES, and this benefit exists regardless of HIV status.

Abstract Background Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease. Methods In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment. Results At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 × 106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005). Conclusions In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity. Trial registration Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.

BackgroundProspective studies of interferon-gamma release assays (IGRA) on healthy subjects in tuberculosis-endemic regions have not examined the long-term variability of serial assays. This issue is relevant to the interpretation of tuberculosis (TB) vaccine trials based on prevention of infection.MethodsT-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis.Results3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (≥2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12).ConclusionsDefinitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.

Introduction: Second language learning is a multifaceted task that benefits across numerous neurocognitive domains including central auditory processing. Existing cross-sectional and longitudinal data show that performance on tests of central auditory processing [central auditory tests (CATs)] worsens with HIV infection. Second language learning may modify this relationship. To explore the relationship between second language learning, central auditory processing, and its interaction with HIV, we assessed the effect of learning English as a second language on CATs among children both living with and without HIV (CLWH/CLWOH) in Dar es Salaam, Tanzania. Methods: Three hundred and seventy-two native Kiswahili speaking children aged 3-10 years old (196 CLWOH, 176 CLWH) were enrolled. Participants completed questionnaires about English language learning, socioeconomic status (SES), and health history. Three central auditory tests-the Triple Digit Test (TDT), the Staggered Spondaic Word Test (SSW), and the Hearing-In-Noise Test (HINT)-were used to assess each participant's central auditory processing abilities. Multivariate linear regression was used to assess the effect of written and spoken English language learning at home and in school on CATs with age, HIV-status, and SES included in each model. Results: HIV status, age, and SES were all significant predictors of all three central auditory tests, with CLWH performing significantly worse on all three CATs than CLWOH. Children actively learning spoken and written English at home had significantly better central auditory processing abilities on the TDT compared to children not actively learning English at home (p < 0.01) independent of HIV status, age, and SES. Children learning spoken and written English at school performed significantly better on the HINT (p < 0.05) than those not actively learning English at school. Discussion: Learning English at home and learning English in school were associated with improved central auditory performance independent of HIV status, SES, and age. These findings also underscore the significance of second language acquisition as a potential mechanism of improving central auditory function within a Kiswahili-speaking cohort. This study found differences in central auditory processing between children exposed to English at home and in school, suggesting differences in language learning in both settings mediated by SES, and this benefit exists regardless of HIV status. [ABSTRACT FROM AUTHOR]

Objective: Tests requiring central auditory processing, such as speech perception-in-noise, are simple, time efficient, and correlate with cognitive processing. These tests may be useful for tracking brain function. Doing this effectively requires information on which tests correlate with overall cognitive function and specific cognitive domains. This study evaluated the relationship between selected central auditory focused tests and cognitive domains in a cohort of normal hearing adults living with HIV and HIV– controls. The long-term aim is determining the relationships between auditory processing and neurocognitive domains and applying this to analyzing cognitive function in HIV and other neurocognitive disorders longitudinally.Method: Subjects were recruited from an ongoing study in Dar es Salaam, Tanzania. Central auditory measures included the Gap Detection Test (Gap), Hearing in Noise Test (HINT), and Triple Digit Test (TDT). Cognitive measures included variables from the Test of Variables of Attention (TOVA), Cogstate neurocognitive battery, and Kiswahili Montreal Cognitive Assessment (MoCA). The measures represented three cognitive domains: processing speed, learning, and working memory. Bootstrap resampling was used to calculate the mean and standard deviation of the proportion of variance explained by the individual central auditory tests for each cognitive measure. The association of cognitive measures with central auditory variables taking HIV status and age into account was determined using regression models.Results: Hearing in Noise Tests and TDT were significantly associated with Cogstate learning and working memory tests. Gap was not significantly associated with any cognitive measure with age in the model. TDT explained the largest mean proportion of variance and had the strongest relationship to the MoCA and Cogstate tasks. With age in the model, HIV status did not affect the relationship between central auditory tests and cognitive measures. Age was strongly associated with multiple cognitive tests.Conclusion: Central auditory tests were associated with measures of learning and working memory. Compared to the other central auditory tests, TDT was most strongly related to cognitive function. These findings expand on the association between auditory processing and cognitive domains seen in other studies and support evaluating these tests for tracking brain health in HIV and other neurocognitive disorders.

# Background A unique syndrome affecting young adults of unexplained hearing loss often associated with uncorrectable poor visual acuity and lower extremity numbness is endemic in Dar es Salaam. This study characterised the hearing loss, associated it with other symptoms, and gathered information on potential causes. # Methods Forty-seven patients (23 men, 24 women) \

BackgroundThe development of neurocognitive deficits in people infected with HIV is a significant public health problem. Previous cross-sectional studies have shown that performance on central auditory tests (CATs) correlates with cognitive test results in those with HIV, but no longitudinal data exist for confirmation. We have been performing longitudinal assessments of central auditory and cognitive function on a cohort of HIV-positive and HIV-negative individuals in Dar es Salaam, Tanzania to understand how the central auditory system could be used to study and track the progress of central nervous system dysfunction. ObjectiveThe goal of the project was to determine if CATs can track the trajectory of cognitive function over time in people diagnosed with HIV. MethodsTests of peripheral and central auditory function as well as cognitive performance were performed on 382 individuals over the course of 3.5 years. Visits were scheduled every 6 months. CATs included tests of auditory temporal processing (gap detection) and speech perception in noise (Hearing in Noise Test and Triple Digit Test). Cognitive tests included the Montreal Cognitive Assessment (MoCA), Test of Variables of Attention (TOVA), and subtests from the Cogstate battery. HIV-positive subjects were divided into groups based on their CAT results at their final visit (bottom 20%, top 20%, middle 60%). Primary analyses focused on the comparison between HIV-positive individuals that performed worse on CATs (bottom 20%) and the overall HIV-positive group (middle 60%). Data were analyzed using linear mixed-effect models with time as the main fixed effect. ResultsThe group with the worst (bottom 20%) CAT performance showed a difference in trajectory for the MoCA (P=.003), TOVA (P

OBJECTIVE:To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. DESIGN:Randomized, controlled trial. SETTING:Dar es Salaam, Tanzania. SUBJECTS, PARTICIPANTS:Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. INTERVENTION:Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. MAIN OUTCOME MEASURE(S):Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. RESULTS:PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388-719 Kcal); and increases in daily protein intake (range of differences: +22-33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). CONCLUSIONS:In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. TRIAL REGISTRATION:Clinical Trials.Gov NCT01461863.

One in three people has been infected with Mycobacterium tuberculosis (MTB), and the risk for MTB infection in HIV-infected individuals is even higher. We hypothesized that HIV-positive individuals living in tuberculosis-endemic regions who do not get infected by Mycobacterium tuberculosis are genetically resistant. Using an "experiment of nature" design that proved successful in our previous work, we performed a genome-wide association study of tuberculin skin test positivity using 469 HIV-positive patients from prospective study cohorts of tuberculosis from Tanzania and Uganda to identify genetic loci associated with MTB infection in the context of HIV-infection. Among these individuals, 244 tested were tuberculin skin test (TST) positive either at enrollment or during the >8 year follow up, while 225 were not. We identified a genome-wide significant association between a dominant model of rs877356 and binary TST status in the combined cohort (Odds ratio = 0.2671, p = 1.22x10-8). Association was replicated with similar significance when examining TST induration as a continuous trait. The variant lies in the 5q31.1 region, 57kb downstream from IL9. Two-locus analyses of association of variants near rs877356 showed a haplotype comprised of rs877356 and an IL9 missense variant, rs2069885, had the most significant association (p = 1.59x10-12). We also replicated previously linked loci on chromosomes 2, 5, and 11. IL9 is a cytokine produced by mast cells and TH2 cells during inflammatory responses, providing a possible link between airway inflammation and protection from MTB infection. Our results indicate that studying uninfected, HIV-positive participants with extensive exposure increases the power to detect associations in complex infectious disease.

Objective: Little is known about peripheral auditory function in young adults with HIV, who might be expected to show early evidence of hearing loss if HIV infection or treatment does affect peripheral function. The goal of this study was to compare peripheral auditory function in 2 age- and gender-matched groups of young adults with clinically normal hearing with and without HIV. Study Design: Matched cohort study with repeated measures. Setting: Infectious disease center in Dar es Salaam, Tanzania. Methods: Participants included HIV-positive (n = 38) and HIV-negative (n = 38) adults aged 20 to 30 years who had clinically normal hearing, defined as type A tympanograms, air conduction thresholds ≤25 dB HL bilaterally from 0.5 to 8 kHz, and distortion product otoacoustic emissions (DPOAEs) >6 dB above the noise floor bilaterally from 1.5 to 8 kHz. Participants were tested multiple times over 6-month intervals (average, 2.7 sessions/participant) for a total of 208 observations. Primary outcome measures included tympanograms, air conduction audiograms, DPOAEs, and click-evoked auditory brainstem responses. Results: HIV groups did not significantly differ in age, static immittance, or air conduction thresholds. HIV-positive status was independently associated with approximately 3.7-dB lower DPOAE amplitudes from 2 to 8 kHz (95% CI, 1.01-6.82) in both ears and 0.04-µV lower (95% CI, 0.003-0.076) auditory brainstem response wave I amplitudes in the right ear. Conclusion: Young adults living with HIV have slightly but reliably smaller DPOAEs and auditory brainstem response wave I amplitudes than matched HIV-negative controls. The magnitude of these differences is small, but these results support measuring peripheral auditory function in HIV-positive individuals as they age. [ABSTRACT FROM AUTHOR]