Enhanced response switching after negative feedback and novelty seeking in adolescence are associated with reduced representation of choice probability in medial frontal pole

Precisely charting the maturation of core neurocognitive functions such as reinforcement learning (RL) and flexible adaptation to changing action-outcome contingencies is key for developmental neuroscience. It can also help us understand how disruptions during development might contribute to the onset of psychopathology. However, research in this area is both sparse and conflicted, especially regarding potentially asymmetric development of learning for different motives (obtain wins vs avoid losses) and learning from valenced feedback (positive vs negative). In the current study, we investigated the development of RL from adolescence to adulthood, using a probabilistic reversal learning task modified to experimentally separate motivational context and feedback valence, in a sample of 95 healthy participants between 12 and 45. We show that adolescence is characterized by enhanced novelty seeking and response shifting after negative feedback, which leads to poorer returns when reward contingencies are stable. Computationally, this is accounted for by reduced impact of positive feedback on behavior. We also show, using fMRI, that activity of the medial frontopolar cortex reflecting choice probability is attenuated in adolescence. We argue that this can be interpreted as reflecting diminished confidence in upcoming choices. Interestingly, we find no age-related differences between learning in win and loss contexts

Cervicovaginal Microbiota Predicts Neisseria gonorrhoeae Clinical Presentation

Neisseria gonorrhoeae infection of the female lower genital tract can present with a spectrum of phenotypes ranging from asymptomatic carriage to symptomatic cervical inflammation, or cervicitis. The factors that contribute to the development of asymptomatic or symptomatic infections are largely uncharacterized. We conducted a pilot study to assess differences in the cervicovaginal microbial community of patients presenting with symptomatic vs. asymptomatic N. gonorrhoeae infections to a sexually transmitted infections (STI) clinic. DNA was isolated from cervicovaginal swab specimens from women who tested positive for N. gonorrhoeae infection using a clinical diagnostic nucleic acid amplification test. We performed deep sequencing of 16S ribosomal RNA gene amplicons, followed by microbiome analyses with QIIME, and species-specific real-time PCR to assess the composition of microbial communities cohabitating the lower genital tract with the infecting N. gonorrhoeae. Specimens collected from asymptomatic individuals with N. gonorrhoeae infection and no co-infection with Chlamydia trachomatis and/or Trichomonas vaginalis carried Lactobacillus-dominant microbial communities more frequently than symptomatic patients without co-infection. When compared to asymptomatic individuals, symptomatic women had microbial communities characterized by more diverse and heterogenous bacterial taxa, typically associated with bacterial vaginosis (BV) [Prevotella, Sneathia, Mycoplasma hominis, and Bacterial Vaginosis-Associated Bacterium-1 (BVAB1)/“Candidatus Lachnocurva vaginae”]. Both symptomatic and asymptomatic N. gonorrhoeae patients with additional STI co-infection displayed a BV-like microbial community. These findings suggest that Lactobacillus-dominant vaginal microbial community may protect individuals from developing symptoms during lower genital tract infection with N. gonorrhoeae

Reuse of malaria rapid diagnostic tests for amplicon deep sequencing to estimate Plasmodium falciparum transmission intensity in western Uganda

Molecular techniques are not routinely employed for malaria surveillance, while cross-sectional, community-based parasite surveys require significant resources. Here, we describe a novel use of malaria rapid diagnostic tests (RDTs) collected at a single facility as source material for sequencing to esimtate malaria transmission intensity across a relatively large catchment area. We extracted Plasmodium falciparum DNA from RDTs, then amplified and sequenced a region of the apical membrane antigen 1 (pfama1) using targeted amplicon deep sequencing. We determined the multiplicity of infection (MOI) for each sample and examined associations with demographic, clinical, and spatial factors. We successfully genotyped 223 of 287 (77.7%) of the samples. We demonstrated an inverse relationship between the MOI and elevation with individuals presenting from the highest elevation villages harboring infections approximately half as complex as those from the lowest (MOI 1.85 vs. 3.51, AOR 0.25, 95% CI 0.09-0.65, p = 0.004). This study demonstrates the feasibility and validity of using routinely-collected RDTs for molecular surveillance of malaria and has real-world utility, especially as the cost of high-throughpout sequencing continues to decline

Hindgut microbiota in laboratory-reared and wild Triatoma infestans

Triatomine vectors transmit Trypanosoma cruzi, the etiological agent of Chagas disease in humans. Transmission to humans typically occurs when contaminated triatomine feces come in contact with the bite site or mucosal membranes. In the Southern Cone of South America, where the highest burden of disease exists, Triatoma infestans is the principal vector for T. cruzi. Recent studies of other vector-borne illnesses have shown that arthropod microbiota influences the ability of infectious agents to colonize the insect vector and transmit to the human host. This has garnered attention as a potential control strategy against T. cruzi, as vector control is the main tool of Chagas disease prevention. Here we characterized the microbiota in T. infestans feces of both wild-caught and laboratory-reared insects and examined the relationship between microbial composition and T. cruzi infection using highly sensitive high-throughput sequencing technology to sequence the V3-V4 region of the 16S ribosomal RNA gene on the MiSeq Illumina platform. We collected 59 wild (9 with T. cruzi infection) and 10 lab-reared T. infestans (4 with T. cruzi infection) from the endemic area of Arequipa, Perú. Wild T. infestans had greater hindgut bacterial diversity than laboratory-reared bugs. Microbiota of lab insects comprised a subset of those identified in their wild counterparts, with 96 of the total 124 genera also observed in laboratory-reared insects. Among wild insects, variation in bacterial composition was observed, but time and location of collection and development stage did not explain this variation. T. cruzi infection in lab insects did not affect α-or β-diversity; however, we did find that the β-diversity of wild insects differed if they were infected with T. cruzi and identified 10 specific taxa that had significantly different relative abundances in infected vs. uninfected wild T. infestans (Bosea, Mesorhizo-bium, Dietzia, and Cupriavidus were underrepresented in infected bugs; Sporosarcina, an unclassified genus of Porphyromonadaceae, Nestenrenkonia, Alkalibacterium, Peptoniphi-lus, Marinilactibacillus were overrepresented in infected bugs). Our findings suggest that T. cruzi infection is associated with the microbiota of T. infestans and that inferring the microbiota of wild T. infestans may not be possible through sampling of T. infestans reared in the insectary

Measuring self-regulation in everyday life: reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one’s goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test–retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures’ construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

Measuring self-regulation in everyday life: Reliability and validity of smartphone-based experiments in alcohol use disorder

Self-regulation, the ability to guide behavior according to one's goals, plays an integral role in understanding loss of control over unwanted behaviors, for example in alcohol use disorder (AUD). Yet, experimental tasks that measure processes underlying self-regulation are not easy to deploy in contexts where such behaviors usually occur, namely outside the laboratory, and in clinical populations such as people with AUD. Moreover, lab-based tasks have been criticized for poor test-retest reliability and lack of construct validity. Smartphones can be used to deploy tasks in the field, but often require shorter versions of tasks, which may further decrease reliability. Here, we show that combining smartphone-based tasks with joint hierarchical modeling of longitudinal data can overcome at least some of these shortcomings. We test four short smartphone-based tasks outside the laboratory in a large sample (N = 488) of participants with AUD. Although task measures indeed have low reliability when data are analyzed traditionally by modeling each session separately, joint modeling of longitudinal data increases reliability to good and oftentimes excellent levels. We next test the measures' construct validity and show that extracted latent factors are indeed in line with theoretical accounts of cognitive control and decision-making. Finally, we demonstrate that a resulting cognitive control factor relates to a real-life measure of drinking behavior and yields stronger correlations than single measures based on traditional analyses. Our findings demonstrate how short, smartphone-based task measures, when analyzed with joint hierarchical modeling and latent factor analysis, can overcome frequently reported shortcomings of experimental tasks

The epidemiology of Plasmodium vivax among adults in the Democratic Republic of the Congo

Reports of P. vivax infections among Duffy-negative hosts have accumulated throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa have been performed. To overcome this gap in knowledge, we screened over 17,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Overall, we found a 2.97% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Infections were associated with few risk-factors and demonstrated a relatively flat distribution of prevalence across space with focal regions of relatively higher prevalence in the north and northeast. Mitochondrial genomes suggested that DRC P. vivax were distinct from circulating non-human ape strains and an ancestral European P. vivax strain, and instead may be part of a separate contemporary clade. Our findings suggest P. vivax is diffusely spread across the DRC at a low prevalence, which may be associated with long-term carriage of low parasitemia, frequent relapses, or a general pool of infections with limited forward propagation