Wolbachia impacts microbiome diversity and fitness-associated traits for Drosophila melanogaster in a seasonally fluctuating environment.

The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but theory suggests that fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the impacts of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal environmental change with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, Wolbachia and a dominant member of the microbiome, Commensalibacter, were associated with differences in two higher-order fitness traits, starvation resistance and lifespan. Our work here suggests that the interplay between the abiotic context and microbe-microbe interactions may shape key host phenotypes that underlie adaptation to changing environments. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes that shape host-microbiome interactions.

Economic impact analysis of a minimally invasive temperature-controlled radiofrequency device versus nasal surgery for the treatment of nasal airway obstruction in the United States.

OBJECTIVE: To determine the economic impact of a minimally invasive temperature-controlled radiofrequency (TCRF) device for treating nasal airway obstruction (NAO). METHODS: A budget impact model was developed for two scenarios: a reference scenario of functional rhinoplasty surgery with concomitant septoplasty and inferior turbinate reduction (ITR) performed in the hospital outpatient department where TCRF is not an available treatment option and a new scenario consisting of in-office TCRF treatment of the nasal valve and ITR. A payor perspective was adopted with a hypothetical population plan size of one million members. Costs were estimated over a time horizon of 4 years. The eligible population included patients with severe/extreme NAO and nasal valve collapse (NVC) as the primary cause or significant contributor. Data inputs were sourced from targeted literature reviews. Uncertainty within the model structure and input parameters was assessed using one-way sensitivity analysis. RESULTS: The introduction of a TCRF device resulted in population-level cost savings of $20,015,123 and per-responder average cost savings of $3531 through a 4-year time horizon due to lower procedure costs and complication rates of the device relative to the surgical comparator. Results were robust when varying parameter values in sensitivity analyses, with cost savings being most sensitive to the prevalence of NAO and estimated response rates to functional rhinoplasty and TCRF. CONCLUSIONS: In patients with severe/extreme NAO, with NVC as the primary or major contributor, introducing TCRF with ITR as a treatment option demonstrates the potential for significant cost savings over functional rhinoplasty with septoplasty and ITR.

Nasal valve dysfunction is a common cause of nasal airway obstruction (NAO) that has a significant impact on heath and quality of life for affected individuals. Previously, patients were offered temporary measures or a type of surgery called functional rhinoplasty which is a highly complex surgery that can be costly, requires recovery time, and in rare cases, not be successful. Recently, a new minimally invasive treatment alternative for NAO called temperature-controlled radiofrequency (TCRF) that may be performed in a surgery center or a doctor's office has become available. This paper provides the results of budget impact analysis performed to assess whether adding the TCRF procedure in place of surgery as a choice for patients with NAO will result in cost savings to an insurance payer with 1 million covered individuals in the United States over a period of 4 years. Results show that TCRF may result in an average of 9,416 fewer rhinoplasty surgeries, provide an average 4-year cost-savings of $3,531 for every patient that responds to TCRF treatment, and a savings of $20,015,123 over 4 years for the insurance provider. These potential cost savings over 4 years would likely be due to reduced procedure costs and complication rates compared to surgery.

Capturing continuous, long timescale behavioral changes in Drosophila melanogaster postural data.

Animal behavior spans many timescales, from short, seconds-scale actions to circadian rhythms over many hours to life-long changes during aging. Most quantitative behavior studies have focused on short-timescale behaviors such as locomotion and grooming. Analysis of these data suggests there exists a hierarchy of timescales; however, the limited duration of these experiments prevents the investigation of the full temporal structure. To access longer timescales of behavior, we continuously recorded individual Drosophila melanogaster at 100 frames per second for up to 7 days at a time in featureless arenas on sucrose-agarose media. We use the deep learning framework SLEAP to produce a full-body postural data set for 47 individuals resulting in nearly 2 billion pose instances. We identify stereotyped behaviors such as grooming, proboscis extension, and locomotion and use the resulting ethograms to explore how the flies' behavior varies across time of day and days in the experiment. We find distinct circadian patterns in all of our stereotyped behavior and also see changes in behavior over the course of the experiment as the flies weaken and die.

Characterizing the landscape of gene expression variance in humans.

Gene expression variance has been linked to organismal function and fitness but remains a commonly neglected aspect of molecular research. As a result, we lack a comprehensive understanding of the patterns of transcriptional variance across genes, and how this variance is linked to context-specific gene regulation and gene function. Here, we use 57 large publicly available RNA-seq data sets to investigate the landscape of gene expression variance. These studies cover a wide range of tissues and allowed us to assess if there are consistently more or less variable genes across tissues and data sets and what mechanisms drive these patterns. We show that gene expression variance is broadly similar across tissues and studies, indicating that the pattern of transcriptional variance is consistent. We use this similarity to create both global and within-tissue rankings of variation, which we use to show that function, sequence variation, and gene regulatory signatures contribute to gene expression variance. Low-variance genes are associated with fundamental cell processes and have lower levels of genetic polymorphisms, have higher gene-gene connectivity, and tend to be associated with chromatin states associated with transcription. In contrast, high-variance genes are enriched for genes involved in immune response, environmentally responsive genes, immediate early genes, and are associated with higher levels of polymorphisms. These results show that the pattern of transcriptional variance is not noise. Instead, it is a consistent gene trait that seems to be functionally constrained in human populations. Furthermore, this commonly neglected aspect of molecular phenotypic variation harbors important information to understand complex traits and disease.

From GWAS to signal validation: An approach for estimating genetic effects while preserving genomic context.

Validating associations between genotypic and phenotypic variation remains a challenge, despite advancements in association studies. Common approaches for signal validation rely on gene-level perturbations, such as loss-of-function mutations or RNAi, which test the effect of genetic modifications usually not observed in nature. CRISPR-based methods can validate associations at the SNP level, but have significant drawbacks, including resulting off-target effects and being both time-consuming and expensive. Both approaches usually modify the genome of a single genetic background, limiting the generalizability of experiments. To address these challenges, we present a simple, low-cost experimental scheme for validating genetic associations at the SNP level in outbred populations. The approach involves genotyping live outbred individuals at a focal SNP, crossing homozygous individuals with the same genotype at that locus, and contrasting phenotypes across resulting synthetic outbred populations. We tested this method in Drosophila melanogaster, measuring the longevity effects of a polymorphism at a naturally-segregating cis-eQTL for the midway gene. Our results demonstrate the utility of this method in SNP-level validation of naturally occurring genetic variation regulating complex traits. This method provides a bridge between the statistical discovery of genotype-phenotype associations and their validation in the natural context of heterogeneous genomic contexts.

NAPS: Integrating pose estimation and tag-based tracking.

1. Significant advances in computational ethology have allowed the quantification of behaviour in unprecedented detail. Tracking animals in social groups, however, remains challenging as most existing methods can either capture pose or robustly retain individual identity over time but not both. 2. To capture finely resolved behaviours while maintaining individual identity, we built NAPS (NAPS is ArUco Plus SLEAP), a hybrid tracking framework that combines state-of-the-art, deep learning-based methods for pose estimation (SLEAP) with unique markers for identity persistence (ArUco). We show that this framework allows the exploration of the social dynamics of the common eastern bumblebee (Bombus impatiens). 3. We provide a stand-alone Python package for implementing this framework along with detailed documentation to allow for easy utilization and expansion. We show that NAPS can scale to long timescale experiments at a high frame rate and that it enables the investigation of detailed behavioural variation within individuals in a group. 4. Expanding the toolkit for capturing the constituent behaviours of social groups is essential for understanding the structure and dynamics of social networks. NAPS provides a key tool for capturing these behaviours and can provide critical data for understanding how individual variation influences collective dynamics.

Dabigatran Reversal With Idarucizumab in 2 Patients With Portal Vein Thrombosis Undergoing Orthotopic Liver Transplantation.

There are limited data to guide the use of anticoagulation in cirrhotic patients prior to liver transplantation especially when using direct oral anticoagulants. In this article, we present 2 cases. The first is a 42-year-old male with cirrhosis complicated by portal vein thrombosis (PVT) treated with dabigatran who underwent orthotopic liver transplantation without complication. The second case is a 65-year-old man with alcoholic cirrhosis complicated by PVT treated with dabigatran who underwent orthotopic liver transplantation and required reoperation for surgical bleeding. Both patients were treated with dabigatran's reversal agent idarucizumab prior to incision. In this case series, we discuss the treatment of cirrhotic patients with various anticoagulants, considerations for anticoagulant selection and reversal prior to liver transplant, and questions for future investigation.

Introducing the GASP scale: a new measure of guilt and shame proneness.

Although scholars agree that moral emotions are critical for deterring unethical and antisocial behavior, there is disagreement about how 2 prototypical moral emotions--guilt and shame--should be defined, differentiated, and measured. We addressed these issues by developing a new assessment--the Guilt and Shame Proneness scale (GASP)--that measures individual differences in the propensity to experience guilt and shame across a range of personal transgressions. The GASP contains 2 guilt subscales that assess negative behavior-evaluations and repair action tendencies following private transgressions and 2 shame subscales that assess negative self-evaluations (NSEs) and withdrawal action tendencies following publically exposed transgressions. Both guilt subscales were highly correlated with one another and negatively correlated with unethical decision making. Although both shame subscales were associated with relatively poor psychological functioning (e.g., neuroticism, personal distress, low self-esteem), they were only weakly correlated with one another, and their relationships with unethical decision making diverged. Whereas shame-NSE constrained unethical decision making, shame-withdraw did not. Our findings suggest that differentiating the tendency to make NSEs following publically exposed transgressions from the tendency to hide or withdraw from public view is critically important for understanding and measuring dispositional shame proneness. The GASP's ability to distinguish these 2 classes of responses represents an important advantage of the scale over existing assessments. Although further validation research is required, the present studies are promising in that they suggest the GASP has the potential to be an important measurement tool for detecting individuals susceptible to corruption and unethical behavior.

Development and Implementation of a Culturally Tailored Diabetes Intervention in Primary Care.

Diabetes education for ethnic minorities should address variations in values underlying motivations, preferences, and behaviors of individuals within an ethnic group. This paper describes the development and implementation of a culturally tailored diabetes intervention for Puerto Rican Americans that can be delivered by a health care paraprofessional and implemented in routine clinical care. We describe a formative process, including interviews with providers, focus groups with patients and a series of multidisciplinary collaborative workshops used to inform intervention content. We highlight the intervention components and link them to a well-validated health behavior change model. Finally, we present support for the intervention's clinical effects, feasibility, and acceptability and conclude with implications and recommendations for practice. Lessons learned from this process should guide future educational efforts in routine clinical care.

A brief culturally tailored intervention for Puerto Ricans with type 2 diabetes.

UNLABELLED: The information-motivation-behavioral skills (IMB) model of health behavior change informed the design of a brief, culturally tailored diabetes self-care intervention for Puerto Ricans with type 2 diabetes. Participants (n = 118) were recruited from an outpatient, primary care clinic at an urban hospital in the northeast United States. ANCOVA models evaluated intervention effects on food label reading, diet adherence, physical activity, and glycemic control (HbA1c). At follow-up, the intervention group was reading food labels and adhering to diet recommendations significantly more than the control group. Although the mean HbA1c values decreased in both groups ( INTERVENTION: 0.48% vs. CONTROL: 0.27% absolute decrease), only the intervention group showed a significant improvement from baseline to follow-up (p < .008), corroborating improvements in diabetes self-care behaviors. Findings support the use of the IMB model to culturally tailor diabetes interventions and to enhance patients' knowledge, motivation, and behavior skills needed for self-care.

Impact of disease management on utilization and adherence with drugs and tests: the case of diabetes treatment in the Florida: a Healthy State (FAHS) program.

OBJECTIVE: The purpose of this study was to evaluate the effect of telephonic care management within a diabetes disease management program on adherence to treatment with hypoglycemic agents, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and recommended laboratory tests in a Medicaid population. RESEARCH DESIGN AND METHODS: A total of 2,598 patients with diabetes enrolled for at least 2 years in Florida: A Healthy State (FAHS), a large Medicaid disease management program, who received individualized telephonic care management were selected if they were eligible for at least 12 months before and 12 months after beginning care management. Patients were matched one-to-one on all baseline characteristics to 2,598 control patients. The impact of care management on utilization and adherence rates for diabetes-related medications and tests was analyzed with the difference-in-difference estimator. RESULTS: Changes in utilization were evaluated separately for those who were characterized as adherent to treatment at baseline ("users") and those who were not ("nonusers"). Both groups achieved significant improvement in adherence between baseline and follow-up. Nonusers increased their overall hypoglycemic use by 0.7 script (P < 0.001), by 0.7 script for ACEIs and statins (both P < 0.001), by 0.8 test for A1C (P < 0.001), and by 0.7 test for lipids (P < 0.001). Users increased hypoglycemic use by 1.5 scripts (P < 0.001) and insulin use by 0.9 script (P < 0.001). CONCLUSIONS: The FAHS telephonic care management intervention effectively induced Medicaid patients with diabetes to begin treatment and improved adherence to oral hypoglycemic agents and recommended tests. It also substantially improved adherence among baseline insulin users.

Interindividual-intergroup discontinuity in the domain of correspondent outcomes: the roles of relativistic concern, perceived categorization, and the doctrine of mutual assured destruction.

Most prior research on the tendency for groups to be less cooperative than individuals (the interindividual-intergroup discontinuity effect) has used the Prisoner's Dilemma Game (PDG). Experiment 1 examined the discontinuity effect with 3 additional matrices: Chicken, Leader, and Battle of the Sexes (BOS). Unlike the PDG, these matrices are characterized by correspondence of outcomes. The discontinuity effect was significant for the PDG and Chicken matrices only. With the BOS and Leader matrices, both individuals and groups pursued outcome maximization through coordinated turn taking. Despite the lesser competitiveness, sets of interacting participants in the BOS and Leader conditions did perceive that they were 2 groups. Experiment 2 examined the discontinuity effect in 2 Chicken matrices with varying outcomes associated with mutual competition. Consistent with the doctrine of mutual assured destruction, the discontinuity effect was eliminated for the matrix in which mutual competition was associated with very low outcomes. Although concern for relative in-group standing gave rise to intergroup competition even in the domain of correspondent outcomes, such concern was constrained to the extent that it interfered with outcome maximization.

Reduction of interindividual-intergroup discontinuity: the role of leader accountability and proneness to guilt.

Two experiments contrasted interactions between group leaders with interactions between individuals in a mixed-motive setting. Consistent with the idea that being accountable to the in-group implies normative pressure to benefit the in-group, Experiment 1 found that accountable leaders were more competitive than individuals. Consistent with the idea that being unaccountable to the in-group implies normative pressure to be cooperative and that high guilt proneness provides motivation to be moral, Experiment 2 found that when guilt proneness was high, unaccountable leaders were less competitive than accountable leaders and did not differ significantly from individuals. In other words, the robust interindividual-intergroup discontinuity effect was eliminated when groups had unaccountable leaders who were high in guilt proneness.

Population volume kinetics predicts retention of 0.9% saline infused in awake and isoflurane-anesthetized volunteers.

BACKGROUND: In previous work, extravascular expansion was observed to be enhanced by isoflurane anesthesia in sheep when a crystalloid bolus was administered. The aim of the current study was to further elaborate these investigations to humans and to explore the use of population kinetics in the analysis of fluid shifts. METHODS: Eleven healthy volunteers participated in two experiments each, either awake or isoflurane anesthetized, during which they received 25 ml/kg saline, 0.9%, intravenously over 20 min. Plasma dilution data were derived from repeated sampling of hemoglobin concentration, and population pharmacokinetic analysis was conducted using the WinNonMix 2.0.1 software (Pharsight Corporation, Mountain View, CA). Plasma hormones were measured, and hemodynamic values were monitored. RESULTS: Fluid infusion during isoflurane anesthesia was followed by a higher cardiac output, lower arterial pressure, and lower urinary excretion as compared with the awake protocol (P < 0.05). Albumin dilution was greater than hemoglobin concentration-derived plasma dilution, which indicates a transcapillary leak of albumin. A two-compartment model with an isoflurane-depressed, intercompartmental distribution parameter predicted that more than 50% of the infused volume was retained in the peripheral compartment at 180 min in both protocols. Isoflurane markedly increased the plasma levels of renin and aldosterone, whereas vasopressin was mostly unchanged. CONCLUSION: Fluid retention after rapid infusion of 0.9% saline was prominent in both awake and isoflurane-anesthetized subjects. Altered kinetics of infused 0.9% saline during isoflurane anesthesia was expressed as reduced clearance and a slower distribution, resulting in a small but significant increase in fluid accumulation in the body fluid compartments. These changes may be due to the associated decreasing of mean arterial pressure and increased release of renin and aldosterone.

Discharge patterns of patients with asthma from the emergency department: a retrospective review.

BACKGROUND: Despite evidence that specific therapies improve outcomes in patients with asthma, they are often not used. Combining several evidence-based therapies into a treatment "bundle" to be offered at the time of discharge from the emergency department, might reduce variation and potentially optimize clinical outcomes. OBJECTIVE: To assess the utilization of four evidence-based therapies for asthma by analyzing the visits of patients with acute exacerbations of asthma discharged from the emergency department. DESIGN: A retrospective chart review. SETTING: Single 650-bed inner-city hospital emergency department. PATIENTS: Two hundred and twenty six patients discharged from the emergency department after 500 acute exacerbations of asthma. MEASUREMENTS: All visits were reviewed for the presence of the four evidence-based components of asthma treatment upon discharge: follow-up referral, oral steroids, asthma education, and inhaled corticosteroids. Visits were also assessed for medications prescribed upon discharge, medication history, and patient's asthma severity based on national guidelines. RESULTS: The four components of asthma treatment were documented as follows: follow-up referral (86.2%), oral steroids (67.8%), asthma education (19.6%), and inhaled corticosteroids (16.2%). Only 3.4% of visits documented all four components in the aggregate. Twenty-three distinct combinations of medication were prescribed upon discharge. The majority of visits failed to document asthma severity. CONCLUSIONS: This retrospective chart review reveals significant variation in the discharge management of patients with asthma, specifically regarding medications prescribed. While follow-up referral was sufficiently documented, the remaining three components were not. With only 3.4% of visits containing all four components, implementing an asthma "bundle" may present an opportunity to improve outcomes in asthma management.

An assessment of Hispanic health status.

The health-care systems in urban communities are facing major challenges. They are being forced to reduce costs while maintaining and improving quality. Compounding these systems issues are the inequalities in health access and barriers that persist within certain segments of the population. Hispanic Americans make up a significant and growing segment of American society; one particularly important issue for Hispanics is staying healthy. Lack of health insurance, environmental stressors, limited access to provider services, and language barrier are a few of the social inequalities that add to the difficulty in receiving health care. To reduce the inequalities and improve access to quality health care, an assessment may be necessary. An investigation into the trends in the health status, beliefs, and practices of Hispanics would be appropriate in order to address their health needs. These inquiries must go beyond having knowledge of different countries of familial origin to include knowledge of differing cultures, socioeconomic status, and experiences within the health-care system.