Mosquito Microbiomes of Rwanda: Characterizing Mosquito Host and Microbial Communities in the Land of a Thousand Hills.

Mosquitoes are a complex nuisance around the world and tropical countries bear the brunt of the burden of mosquito-borne diseases. Rwanda has had success in reducing malaria and some arboviral diseases over the last few years, but still faces challenges to elimination. By building our understanding of in situ mosquito communities in Rwanda at a disturbed, human-occupied site and at a natural, preserved site, we can build our understanding of natural mosquito microbiomes toward the goal of implementing novel microbial control methods. Here, we examined the composition of collected mosquitoes and their microbiomes at two diverse sites using Cytochrome c Oxidase I sequencing and 16S V4 high-throughput sequencing. The majority (36 of 40 species) of mosquitoes captured and characterized in this study are the first-known record of their species for Rwanda but have been characterized in other nations in East Africa. We found significant differences among mosquito genera and among species, but not between mosquito sexes or catch method. Bacteria of interest for arbovirus control, Asaia, Serratia, and Wolbachia, were found in abundance at both sites and varied greatly by species.

Component-specific developmental trajectories of ERP indices of cognitive control in early childhood.

Early childhood is characterized by robust developmental changes in cognitive control. However, our understanding of intra-individual change in neural indices of cognitive control during this period remains limited. Here, we examined developmental changes in event-related potential (ERP) indices of cognitive control from preschool through first grade, in a large and diverse sample of children (N = 257). We recorded ERPs during a visual Go/No-Go task. N2 and P3b mean amplitudes were extracted from the observed waveforms (Go and No-Go) and the difference wave (No-Go minus Go, or ∆). Latent growth curve modeling revealed that while N2 Go and No-Go amplitudes showed no linear change, P3b Go and No-Go amplitudes displayed linear decreases in magnitude (became less positive) over time. ∆N2 amplitude demonstrated a linear increase in magnitude (became more negative) over time whereas ∆P3b amplitude was more positive in kindergarten compared to preschool. Younger age in preschool predicted greater rates of change in ∆N2 amplitude, and higher maternal education predicted larger initial P3b Go and No-Go amplitudes in preschool. Our findings suggest that observed waveforms and difference waves are not interchangeable for indexing neurodevelopment, and the developmental trajectories of different ERP indices of cognitive control are component-specific in early childhood.

Telehealth medication management and health care spending in a Medicare Accountable Care Organization.

BACKGROUND: Value-based care is an opportunity for medication optimization services to improve medication management and reduce health care spending. The reach of these services may be extended through telehealth. However, as health care systems and payers grapple with the long-term financing of telehealth, real-world assessments are needed to evaluate the potential economic impact of pharmacy-driven telehealth services. OBJECTIVE: To evaluate the impact of a scalable pharmacist-driven telehealth intervention to improve medication management on health care spending for clinically complex patients who were enrolled in a Medicare Next Generation Accountable Care Organization. METHODS: Data for this pretest-posttest nonequivalent group design study came from Medicare claims from 2015 to 2020 and linked pharmacist care activity data derived from the electronic medical record. Patients in the intervention group were identified as those who received the telehealth medication management service. Patients in the control group were offered the service and refused or could not be contacted. The primary outcome was total medical spending over a 6-month period, and impact was assessed using a covariate-adjusted difference-in-difference model. RESULTS: There were 581 patients who received the intervention and 1,765 who served as controls. The telehealth intervention reduced total medical spending by $2,331.85 per patient over the first 6 months of the service ($388.50 per month; P = 0.0261). Across a range of estimates for the cost of service delivery, we find a return on investment of 3.6:1 to 5.2:1. CONCLUSIONS: The $388.50 monthly savings found in this study represent a substantial reduction in health care spending and emphasize the opportunity for telehealth delivery of medication management services to improve value as a part of alternative payment models. DISCLOSURES: This study was funded by the UNC Health Care Department of Pharmacy. Dr Urick has received personal fees from Pharmacy Quality Solutions and Cardinal Health. Drs Peters, Vest, Colmenares, Foushee, and DeFalco are employees of UNC Health Care Department of Pharmacy. Mr Easter received a Co-PI grant from NACDS Foundation to implement Community-based Value Care Initiative (CVCI) in a community pharmacy setting. He also received a grant to Eshelman School of Pharmacy. He has an individual consulting agreement with digital health company Truentity Health to provide go to market strategy for medication management services. He also has stock options from Truentity Health as a component of the consulting agreement. Dr Foushee has a leadership or fiduciary role at Member-At-Large and the Ambulatory Care Academy of the North Carolina Association of Pharmacists. At the time this work was conducted, Dr Urick, Dr Pathak, and Dr Blanchard were all employees of the UNC Eshelman School of Pharmacy.

The Effect of Various Supportive Housing Models on ART Adherence Among Persons Living With HIV in Supportive Housing.

BACKGROUND: Providing permanent supportive housing to chronically homeless persons living with human immunodeficiency virus (PLH) contributes to improved human immunodeficiency virus (HIV) outcomes, including adherence to antiretroviral therapy (ART). This study seeks to understand whether certain components of housing, namely intensity of case management and specialized HIV housing programs, affects ART adherence for PLH in supportive housing. METHODS: From 2015 to 2019 we conducted quantitative assessments with 157 PLH in supportive housing at baseline, 6-, 12-, and 18-month postbaseline to identify factors associated with ART adherence. General Estimating Equations for repeated measures were performed to assess bivariate and multivariate measures. RESULTS: Two thirds of PLH in supportive housing reported 95% or greater adherence to ART. Multivariate analyses indicate that neither intensity of case management services nor specialized housing for PLH were associated with greater ART adherence. Greater time since diagnosis was positively associated with ART adherence. Greater depressive symptoms and African American race were negatively associated with ART adherence. CONCLUSIONS: Study findings reveal that although prior research has established the importance of receipt of housing for homeless PLH, the type or intensity of case management services associated with that housing may not be as important as simply being housed. Our results highlight the importance of considering mental health and more recent HIV diagnosis when developing treatment and case management plans to enhance residents' ART adherence.

Batrachochytrium salamandrivorans ELICITS ACUTE STRESS RESPONSE IN SPOTTED SALAMANDERS BUT NOT INFECTION OR MORTALITY.

The emerging fungal pathogen Batrachochytrium salamandrivorans (Bsal) is a major threat to amphibian species worldwide with potential to infect many species if it invades salamander biodiversity hotspots in the Americas. Bsal can cause the disease chytridiomycosis, and it is important to assess the risk of Bsal-induced chytridiomycosis to species in North America. We evaluated the susceptibility to Bsal of the common and widespread spotted salamander, Ambystoma maculatum, across life history stages and monitored the effect of Bsal exposure on growth rate and response of the stress hormone, corticosterone. We conclude that spotted salamanders appear resistant to Bsal because they showed no indication of disease or infection, and experienced minor effects on growth upon exposure. While we focused on a single population for this study, results were consistent across conditions of exposure including high or repeated doses of Bsal, life-stage at exposure, environmental conditions including two temperatures and two substrates, and promoting pathogen infectivity by conditioning Bsal cultures with thyroid hormone. Exposure to high levels of Bsal elicited an acute but not chronic increase in corticosterone in spotted salamanders, and reduced growth. We hypothesize that the early acute increase in corticosterone facilitated mounting an immune response to the pathogen, perhaps through immunoredistribution to the skin, but further study is needed to determine immune responses to Bsal. These results will contribute to development of appropriate Bsal management plans to conserve species at risk of emerging disease.

Publisher Correction: Host-associated microbiomes are predicted by immune system complexity and climate.

Following publication of the original paper [1], it was reported that an error in the processing of Fig. 8 occurred. In the online HTML version of the article, Fig. 8 was presented as a duplication of Fig. 7. The original article [1] has been corrected.

Host-associated microbiomes are predicted by immune system complexity and climate.

BACKGROUND: Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function. It is possible that host surface-associated (external) microbiomes respond more strongly to variations in environmental factors, whereas internal microbiomes are more tightly linked to host factors. RESULTS: Here, we use the dataset from the Earth Microbiome Project and accumulate data from 50 additional studies totaling 654 host species and over 15,000 samples to examine global-scale patterns of bacterial diversity and function. We analyze microbiomes from non-captive hosts sampled from natural habitats and find patterns with bioclimate and geophysical factors, as well as land use, host phylogeny, and trophic level/diet. Specifically, external microbiomes are best explained by variations in mean daily temperature range and precipitation seasonality. In contrast, internal microbiomes are best explained by host factors such as phylogeny/immune complexity and trophic level/diet, plus climate. CONCLUSIONS: Internal microbiomes are predominantly associated with top-down effects, while climatic factors are stronger determinants of microbiomes on host external surfaces. Host immunity may act on microbiome diversity through top-down regulation analogous to predators in non-microbial ecosystems. Noting gaps in geographic and host sampling, this combined dataset represents a global baseline available for interrogation by future microbial ecology studies.

Experienced physician descriptions of intuition in clinical reasoning: a typology.

Background Diagnostic intuition is a rapid, non-analytic, unconscious mode of reasoning. A small body of evidence points to the ubiquity of intuition, and its usefulness in generating diagnostic hypotheses and ascertaining severity of illness. Little is known about how experienced physicians understand this phenomenon, and how they work with it in clinical practice. Methods Descriptions of how experienced physicians perceive their use of diagnostic intuition in clinical practice were elicited through interviews conducted with 30 physicians in emergency, internal and family medicine. Each participant was asked to share stories of diagnostic intuition, including times when intuition was both correct and incorrect. Multiple coders conducted descriptive analysis to analyze the salient aspects of these stories. Results Physicians provided descriptions of what diagnostic intuition is, when it occurs and what type of activity it prompts. From stories of correct intuition, a typology of four different types of intuition was identified: Sick/Not Sick, Something Not Right, Frame-shifting and Abduction. Most physician accounts of diagnostic intuition linked this phenomenon to non-analytic reasoning and emphasized the importance of experience in developing a trustworthy sense of intuition that can be used to effectively engage analytic reasoning to evaluate clinical evidence. Conclusions The participants recounted myriad stories of diagnostic intuition that alerted them to unusual diagnoses, previous diagnostic error or deleterious trajectories. While this qualitative study can offer no conclusions about the representativeness of these stories, it suggests that physicians perceive clinical intuition as beneficial for correcting and advancing diagnoses of both common and rare conditions.

Reasons For Lack of Follow-up Colonoscopy Among Persons With A Positive Fecal Occult Blood Test Result: A Qualitative Study.

OBJECTIVES: Follow-up colonoscopy rates among persons with positive fecal occult blood test results (FOBT + ) remain suboptimal in many jurisdictions. In Ontario, Canada, primary care providers (PCPs) are responsible for arranging follow-up colonoscopies. The objectives were to understand the reasons for a lack of follow-up colonoscopy and any action plans to address follow-up. METHODS: Semi-structured interviews were conducted with 30 FOBT+ persons and 30 PCPs in Ontario. Eligible FOBT+ persons were identified through administrative databases and included those aged 50-74, with a 6-12 month old FOBT+, no follow-up colonoscopy, and no prior colorectal cancer diagnosis or colectomy. Eligible PCPs had ≥1 rostered FOBT+ person without follow-up colonoscopy. Transcripts were analyzed inductively using Nvivo 11 (QSR International Pty Ltd., 2015). RESULTS: Reasons for lack of follow-up colonoscopy were: person and/or provider believed the FOBT + was a false positive; person was afraid of colonoscopy; person had other health issues; and breakdown in communication of FOBT+ results or colonoscopy appointments. PCPs who initially recommended follow-up colonoscopy did not change the minds of the persons who dismissed the FOBT+ as a false positive and/or who were afraid of the procedure. These FOBT+ persons negotiated an alternative follow-up action plan including repeating the FOBT or not following-up. CONCLUSIONS: PCPs may not adequately counsel FOBT+ persons who believe the FOBT+ is a false positive and/or fear colonoscopy. PCPs may lack fail-safe systems to communicate FOBT+ results and colonoscopy appointments. Using navigators may help address these barriers and increase follow-up rates.

Amplitude by Peak Interaction but No Evidence of Auditory Mismatch Response Deficits to Frequency Change in Preschool-Aged Children with Fetal Alcohol Spectrum Disorders.

BACKGROUND: Prior studies indicate that the auditory mismatch response is sensitive to early alterations in brain development in multiple developmental disorders. Prenatal alcohol exposure is known to impact early auditory processing. The current study hypothesized alterations in the mismatch response in young children with fetal alcohol spectrum disorders (FASD). METHODS: Participants in this study were 9 children with a FASD and 17 control children (Control) aged 3 to 6 years. Participants underwent magnetoencephalography and structural magnetic resonance imaging scans separately. We compared groups on neurophysiological mismatch negativity (MMN) responses to auditory stimuli measured using the auditory oddball paradigm. Frequent (1,000 Hz) and rare (1,200 Hz) tones were presented at 72 dB. RESULTS: There was no significant group difference in MMN response latency or amplitude represented by the peak located ~200 ms after stimulus presentation in the difference time course between frequent and infrequent tones. Examining the time courses to the frequent and infrequent tones separately, repeated measures analysis of variance with condition (frequent vs. rare), peak (N100m and N200m), and hemisphere as within-subject factors and diagnosis and sex as the between-subject factors showed a significant interaction of peak by diagnosis (p = 0.001), with a pattern of decreased amplitude from N100m to N200m in Control children and the opposite pattern in children with FASD. However, no significant difference was found with the simple effects comparisons. No group differences were found in the response latencies of the rare auditory evoked fields. CONCLUSIONS: The results indicate that there was no detectable effect of alcohol exposure on the amplitude or latency of the MMNm response to simple tones modulated by frequency change in preschool-aged children with FASD. However, while discrimination abilities to simple tones may be intact, early auditory sensory processing revealed by the interaction between N100m and N200m amplitude indicates that auditory sensory processing may be altered in children with FASD.

Development of Auditory Evoked Responses in Normally Developing Preschool Children and Children with Autism Spectrum Disorder.

The cortical responses to auditory stimuli undergo rapid and dramatic changes during the first 3 years of life in normally developing (ND) children, with decreases in latency and changes in amplitude in the primary peaks. However, most previous studies have focused on children >3 years of age. The analysis of data from the early stages of development is challenging because the temporal pattern of the evoked responses changes with age (e.g., additional peaks emerge with increasing age) and peak latency decreases with age. This study used the topography of the auditory evoked magnetic field (AEF) to identify the auditory components in ND children between 6 and 68 months (n = 48). The latencies of the peaks in the AEF produced by a tone burst (ISI 2 ± 0.2 s) during sleep decreased with age, consistent with previous reports in awake children. The peak latencies of the AEFs in ND children and children with autism spectrum disorder (ASD) were compared. Previous studies indicate that the latencies of the initial components of the auditory evoked potential (AEP) and the AEF are delayed in children with ASD when compared to age-matched ND children >4 years of age. We speculated whether the AEF latencies decrease with age in children diagnosed with ASD as in ND children, but with uniformly longer latencies before the age of about 4 years. Contrary to this hypothesis, the peak latencies did not decrease with age in the ASD group (24-62 months, n = 16) during sleep (unlike in the age-matched controls), although the mean latencies were longer in the ASD group as in previous studies. These results are consistent with previous studies indicating delays in auditory latencies, and they indicate a different maturational pattern in ASD children and ND children. Longitudinal studies are needed to confirm whether the AEF latencies diverge with age, starting at around 3 years, in these 2 groups of children.

Examining the Influence of Context and Professional Culture on Clinical Reasoning Through Rhetorical-Narrative Analysis.

According to the dual process model of reasoning, physicians make diagnostic decisions using two mental systems: System 1, which is rapid, unconscious, and intuitive, and System 2, which is slow, rational, and analytical. Currently, little is known about physicians' use of System 1 or intuitive reasoning in practice. In a qualitative study of clinical reasoning, physicians were asked to tell stories about times when they used intuitive reasoning while working up an acutely unwell patient, and we combine socio-narratology and rhetorical theory to analyze physicians' stories. Our analysis reveals that in describing their work, physicians draw on two competing narrative structures: one that is aligned with an evidence-based medicine approach valuing System 2 and one that is aligned with cooperative decision making involving others in the clinical environment valuing System 1. Our findings support an understanding of clinical reasoning as distributed, contextual, and influenced by professional culture.

New Frontiers for Conditional Release: Applying Lessons Learned from Other Offenders with Mental Illness.

There is relatively little research in the literature on insanity acquittees as compared with the large number of studies focused on the supervision and treatment of probationers and parolees with mental illness. Ideally, the latter literature could be successfully applied to insanity acquittees discharged from an inpatient hospital on "conditional release." This article describes the challenges faced by persons on conditional release as well as the gaps in extant conditional release literature. Then, five evidence-based models for the supervision and/or treatment of probationers and parolees with mental illness are applied to a theoretical conditionally released population (mental health courts, forensic assertive community treatment teams, the risk-need-responsivity model, informed supervision practices, and HOPE probation). Benefits and limitations are noted, and recommendations for such crossover are given. Copyright © 2016 John Wiley & Sons, Ltd.

Delays in auditory processing identified in preschool children with FASD.

BACKGROUND: Both sensory and cognitive deficits have been associated with prenatal exposure to alcohol; however, very few studies have focused on sensory deficits in preschool-aged children. As sensory skills develop early, characterization of sensory deficits using novel imaging methods may reveal important neural markers of prenatal alcohol exposure. METHODS: Participants in this study were 10 children with a fetal alcohol spectrum disorder (FASD) and 15 healthy control (HC) children aged 3 to 6 years. All participants had normal hearing as determined by clinical screens. We measured their neurophysiological responses to auditory stimuli (1,000 Hz, 72 dB tone) using magnetoencephalography (MEG). We used a multidipole spatio-temporal modeling technique to identify the location and timecourse of cortical activity in response to the auditory tones. The timing and amplitude of the left and right superior temporal gyrus sources associated with activation of left and right primary/secondary auditory cortices were compared across groups. RESULTS: There was a significant delay in M100 and M200 latencies for the FASD children relative to the HC children (p = 0.01), when including age as a covariate. The within-subjects effect of hemisphere was not significant. A comparable delay in M100 and M200 latencies was observed in children across the FASD subtypes. CONCLUSIONS: Auditory delay revealed by MEG in children with FASDs may prove to be a useful neural marker of information processing difficulties in young children with prenatal alcohol exposure. The fact that delayed auditory responses were observed across the FASD spectrum suggests that it may be a sensitive measure of alcohol-induced brain damage. Therefore, this measure in conjunction with other clinical tools may prove useful for early identification of alcohol affected children, particularly those without dysmorphia.

Evaluation of artery visualizations for heart disease diagnosis.

Heart disease is the number one killer in the United States, and finding indicators of the disease at an early stage is critical for treatment and prevention. In this paper we evaluate visualization techniques that enable the diagnosis of coronary artery disease. A key physical quantity of medical interest is endothelial shear stress (ESS). Low ESS has been associated with sites of lesion formation and rapid progression of disease in the coronary arteries. Having effective visualizations of a patient's ESS data is vital for the quick and thorough non-invasive evaluation by a cardiologist. We present a task taxonomy for hemodynamics based on a formative user study with domain experts. Based on the results of this study we developed HemoVis, an interactive visualization application for heart disease diagnosis that uses a novel 2D tree diagram representation of coronary artery trees. We present the results of a formal quantitative user study with domain experts that evaluates the effect of 2D versus 3D artery representations and of color maps on identifying regions of low ESS. We show statistically significant results demonstrating that our 2D visualizations are more accurate and efficient than 3D representations, and that a perceptually appropriate color map leads to fewer diagnostic mistakes than a rainbow color map.

Drug discovery using very large numbers of patents: general strategy with extensive use of match and edit operations.

A patent data base of 6.7 million compounds generated by a very high performance computer (Blue Gene) requires new techniques for exploitation when extensive use of chemical similarity is involved. Such exploitation includes the taxonomic classification of chemical themes, and data mining to assess mutual information between themes and companies. Importantly, we also launch candidates that evolve by "natural selection" as failure of partial match against the patent data base and their ability to bind to the protein target appropriately, by simulation on Blue Gene. An unusual feature of our method is that algorithms and workflows rely on dynamic interaction between match-and-edit instructions, which in practice are regular expressions. Similarity testing by these uses SMILES strings and, less frequently, graph or connectivity representations. Examining how this performs in high throughput, we note that chemical similarity and novelty are human concepts that largely have meaning by utility in specific contexts. For some purposes, mutual information involving chemical themes might be a better concept.

No evidence for parental imprinting of mouse 22q11 gene orthologs.

Non-Mendelian factors may influence central nervous system (CNS) phenotypes in patients with 22q11 Deletion Syndrome (22q11DS, also known as DiGeorge or Velocardiofacial Syndrome), and similar mechanisms may operate in mice carrying a deletion of one or more 22q11 gene orthologs. Accordingly, we examined the influence of parent of origin on expression of 25 murine 22q11 orthologs in the developing and mature CNS using single nucleotide polymorphism (SNP)-based analysis in interspecific crosses and quantification of mRNA in a murine model of 22q11DS. We found no evidence for absolute genomic imprinting or silencing. All 25 genes are biallelically expressed in the developing and adult brains. Furthermore, if more subtle forms of allelic biasing are present, they are very small in magnitude and most likely beyond the resolution of currently available quantitative approaches. Given the high degree of similarity of human 22q11 and the orthologous region of mmChr16, genomic imprinting most likely cannot explain apparent parent-of-origin effects in 22q11DS.