Isolation drives increased diversification rates in freshwater amphipods.

Vicariance and dispersal events affect current biodiversity patterns in desert springs. Whether major diversification events are due to environmental changes leading to radiation or due to isolation resulting in relict species is largely unknown. We seek to understand whether the Gammarus pecos species complex underwent major diversification events due to environmental changes in the area leading either to radiation into novel habitats, or formation of relicts due to isolation. Specifically, we tested the hypothesis that Gammarus in the northern Chihuahuan Desert of New Mexico and Texas, USA are descendants of an ancient marine lineage now containing multiple undescribed species. We sequenced a nuclear (28S) and two mitochondrial (16S, COI) genes from gammarid amphipods representing 16 desert springs in the northern Chihuahuan Desert. We estimated phylogenetic relationships, divergence times, and diversification rates of the Gammarus pecos complex. Our results revealed that the region contained two evolutionarily independent lineages: a younger Freshwater Lineage that shared a most-recent-common-ancestor with an older Saline Lineage ∼66.3  MYA (95.6-42.4  MYA). Each spring system generally formed a monophyletic clade based on the concatenated dataset. Freshwater Lineage diversification rates were 2.0-9.8 times higher than rates of the Saline Lineage. A series of post-Cretaceous colonizations by ancestral Gammarus taxa was likely followed by isolation. Paleo-geological, hydrological, and climatic events in the Neogene-to-Quaternary periods (23.03  MYA - present) in western North America promoted allopatric speciation of both lineages. We suggest that Saline Lineage populations include two undescribed Gammarus species, while the Freshwater Lineage shows repetition of fine-scale genetic structure in all major clades suggesting incipient speciation. Such ongoing speciation suggests that this region will continue to be a biodiversity hotspot for amphipods and other freshwater taxa.

Noninferiority Clinical Trial of Adapted START NOW Psychotherapy for Outpatient Opioid Treatment.

Background: Medications for opioid use disorder (MOUD) such as buprenorphine is effective for treating opioid use disorder (OUD). START NOW (SN) is a manualized, skills-based group psychotherapy originally developed and validated for the correctional population and has been shown to result in reduced risk of disciplinary infractions and future psychiatric inpatient days with a dose response effect. We investigate whether adapted START NOW is effective for treating OUD in a MOUD office-based opioid treatment (OBOT) setting in this non-inferiority clinical trial. Methods: Patients enrolled in once weekly buprenorphine/suboxone MOUD OBOT were eligible for enrollment in this study. Participants were cluster-randomized, individually-randomized, or not randomized into either START NOW psychotherapy or treatment-as-usual (TAU) for 32 weeks of therapy. Treatment effectiveness was measured as the number of groups attended, treatment duration, intensity of attendance, and overall drug use as determined by drug screens. Results: 137 participants were quasi-randomized to participate in SN (n = 79) or TAU (n = 58). Participants receiving START NOW psychotherapy, when compared to TAU, had comparable number of groups attended (16.5 vs. 16.7, p = 0.80), treatment duration in weeks (24.1 vs. 23.8, p = 0.62), and intensity defined by number of groups attended divided by the number of weeks to last group (0.71 vs. 0.71, p = 0.90). SN compared to TAU also had similar rates of any positive drug screen result (81.0% vs. 91.4%, p = 0.16). This suggests that adapted START NOW is noninferior to TAU, or the standard of care at our institution, for treating opioid use disorder. Conclusion: Adapted START NOW is an effective psychotherapy for treating OUD when paired with buprenorphine/naloxone in the outpatient group therapy setting. Always free and publicly available, START NOW psychotherapy, along with its clinician manual and training materials, are easily accessible and distributable and may be especially useful for low-resource settings in need of evidence-based psychotherapy.

A randomized controlled trial to test the effectiveness of two technology-enhanced diabetes prevention programs in primary care: The DiaBEAT-it study.

Objective: To evaluate the effectiveness of two technology-enhanced interventions for diabetes prevention among adults at risk for developing diabetes in a primary care setting. Methods: The DiaBEAT-it study employed a hybrid 2-group preference (Choice) and 3-group randomized controlled (RCT) design. This paper presents weight related primary outcomes of the RCT arm. Patients from Southwest Virginia were identified through the Carilion Clinic electronic health records. Eligible participants (18 and older, BMI ≥ 25, no Type 2 Diabetes) were randomized to either Choice (n = 264) or RCT (n = 334). RCT individuals were further randomized to one of three groups: (1) a 2-h small group class to help patients develop a personal action plan to prevent diabetes (SC, n = 117); (2) a 2-h small group class plus automated telephone calls using an interactive voice response system (IVR) to help participants initiate weight loss through a healthful diet and regular physical activity (Class/IVR, n = 110); or (3) a DVD with same content as the class plus the same IVR calls over a period of 12 months (DVD/IVR, n = 107). Results: Of the 334 participants that were randomized, 232 (69%) had study measured weights at 6 months, 221 (66%) at 12 months, and 208 (62%) at 18 months. Class/IVR participants were less likely to complete weight measures than SC or DVD/IVR. Intention to treat analyses, controlling for gender, race, age and baseline BMI, showed that DVD/IVR and Class/IVR led to reductions in BMI at 6 (DVD/IVR -0.94, p < 0.001; Class/IVR -0.70, p < 0.01), 12 (DVD/IVR -0.88, p < 0.001; Class/IVR-0.82, p < 0.001) and 18 (DVD/IVR -0.78, p < 0.001; Class/IVR -0.58, p < 0.01) months. All three groups showed a significant number of participants losing at least 5% of their body weight at 12 months (DVD/IVR 26.87%; Class/IVR 21.62%; SC 16.85%). When comparing groups, DVD/IVR were significantly more likely to decrease BMI at 6 months (p < 0.05) and maintain the reduction at 18 months (p < 0.05) when compared to SC. There were no differences between the other groups. Conclusions: The DiaBEAT-it interventions show promise in responding to the need for scalable, effective methods to manage obesity and prevent diabetes in primary care settings that do not over burden primary care clinics and providers. Registration: https://clinicaltrials.gov/ct2/show/NCT02162901, identifier: NCT02162901.

Examining Ways to Improve Weight Control Programs' Population Reach and Representativeness: A Discrete Choice Experiment of Financial Incentives.

BACKGROUND: Both theoretical and empirical evidence supports the potential of modest financial incentives to increase the reach of evidence-based weight control programs. However, few studies exist that examine the best incentive design for achieving the highest reach and representativeness at the lowest cost and whether or not incentive designs may be valued differentially by subgroups that experience obesity-related health disparities. METHODS: A discrete choice experiment was conducted (n = 1232 participants; over 90% of them were overweight/obese) to collect stated preference towards different financial incentive attributes, including reward amount, program location, reward contingency, and payment form and frequency. Mixed logit and conditional logit models were used to determine overall and subgroup preference ranking of attributes. Using the National Health and Nutrition Examination Survey data sample weights and the estimated models, we predicted US nationally representative participation rates by subgroups and examined the effect of offering more than one incentive design. External validity was checked by using a completed cluster randomized control trial. RESULTS: There were significant subgroup differences in preference toward incentive attributes. There was also a sizable negative response to larger incentive amounts among African Americans, suggesting that higher amounts would reduce participation from this population. We also find that offering participants a menu of incentive designs to choose from would increase reach more than offering higher reward amounts. CONCLUSIONS: We confirmed the existence of preference heterogeneity and the importance of subgroup-targeted incentive designs in any evidence-based weight control program to maximize population reach and reduce health disparities.

Phase 2: a dose-escalation study of OncoGel (ReGel/paclitaxel), a controlled-release formulation of paclitaxel, as adjunctive local therapy to external-beam radiation in patients with inoperable esophageal cancer.

OncoGel, a novel injectable formulation of paclitaxel in a biocompatible biodegradable gel (ReGel), provides controlled release of paclitaxel at the injection site, resulting in high intralesional paclitaxel concentrations and continuous radiosensitization without attendant systemic toxicities. This dose-escalation study evaluated the toxicity, pharmacokinetics, and preliminary antitumor activity of OncoGel injected intralesionally in patients with inoperable esophageal cancer who were candidates for palliative external-beam radiotherapy (RT). Eleven patients with inoperable advanced esophageal cancer received a single administration of OncoGel into the primary tumor using conventional endoscopic techniques. Three cohorts received approximately one-third of the tumor volume with increasing paclitaxel concentrations to achieve 0.48, 1.0, and 2.0 mg paclitaxel/cm tumor volume. Subsequent to injection, RT was initiated (50.4 Gy in 1.8 Gy fractions). Pharmacokinetic sampling was performed. All patients completed the study. No dose-limiting toxicities were reported. Dysphagia improved and tumor size decreased in most patients. Biopsies were negative for carcinoma in 4 of 11 patients. Peak paclitaxel plasma concentrations were low (0.53-2.73 ng/ml) and directly related to the absolute amount of paclitaxel administered. Paclitaxel was detectable in plasma for 24 h in all patients and for 3 weeks in six patients. OncoGel given as an adjunct to RT was well tolerated in patients with inoperable esophageal cancer and provided prolonged paclitaxel release with minimal systemic exposure. OncoGel plus RT seemed to reduce tumor burden as evidenced by dysphagia improvement, tumor size reduction, and negative esophageal biopsies. The addition of OncoGel to combined modality therapy merits continued clinical development.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator.

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention.

Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans.

BACKGROUND: Mitochondrial alterations have been observed in subjects with metabolic disorders such as obesity and diabetes. Studies on animal models and cell cultures suggest aberrant glucose and lipid levels, and impaired insulin signaling might lead to mitochondrial changes. However, the molecular mechanism underlying mitochondrial aberrance remains largely unexplored in human subjects. RESULTS: Here we show that the mitochondrial DNA copy number (mtDNAn) was significantly reduced (6.9-fold lower, p < 0.001) in the leukocytes from obese humans (BMI >30). The reduction of mtDNAn was strongly associated with insulin resistance (HOMA-IR: -0.703, p < 0.05; fasting insulin level: -0.015, p < 0.05); by contrast, the correlation between fasting glucose or lipid levels and mtDNAn was not significant. Epigenetic study of the displacement loop (D-loop) region of mitochondrial genome, which controls the replication and transcription of the mitochondrial DNA as well as organization of the mitochondrial nucleoid, revealed a dramatic increase of DNA methylation in obese (5.2-fold higher vs. lean subjects, p < 0.05) and insulin-resistant (4.6-fold higher vs. insulin-sensitive subjects, p < 0.05) individuals. CONCLUSIONS: The reduction of mtDNAn in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation, suggesting an insulin signaling-epigenetic-genetic axis in mitochondrial regulation.

Agreement between telepsychiatry assessment and face-to-face assessment for Emergency Department psychiatry patients.

We compared psychiatrists' evaluations of Emergency Department (ED) mental health patients made face-to-face or by telemedicine. In a 39-month study, 73 patients presenting in the ED were enrolled after initial screening. Patients were interviewed by a psychiatrist either face-to-face in the ED or remotely by video. A second psychiatrist, acting as an observer, was in the room with the patient and independently completed the assessment. Based on the primary diagnosis of the interviewer, 48% of patients had a depressive disorder, 18% a substance use disorder, 14% a bipolar disorder, 11% a psychotic disorder, 6% an anxiety disorder and 4% other disorders. The raw agreement between the psychiatrists about disposition when both used face-to-face assessment was 84% and it was 86% when one used telemedicine. Using Cohen's kappa to evaluate agreement, there were no significant differences for disposition recommendation, strength of recommendation, diagnosis or the HCR-20 dangerousness scale. There was no significant difference for the intraclass correlation coefficients for the suicide scale. The results provide preliminary support for the safe use of telepsychiatry in the ED to determine the need for admission to inpatient care.

Meeting the challenge of cancer survivorship in public health: results from the evaluation of the chronic disease self-management program for cancer survivors.

INTRODUCTION: Self-management has been identified as an important opportunity to improve health outcomes among cancer survivors. However, few evidence-based interventions are available to meet this need. METHODS: The effectiveness of an adapted version of the Chronic Disease Self-Management Program for cancer survivors called Cancer Thriving and Surviving was evaluated in a randomized trial. Outcomes were assessed at baseline and 6-months post program via written survey among 244 participants in Colorado. Repeated measures analysis was used to analyze pre/post program change. RESULTS: Statistically significant improvement was observed among those in the intervention in the following outcomes: Provider communication (+16.7% change); depression (-19.1%); energy (+13.8%); sleep (-24.9%) and stress-related problems (-19.2%); change over time was also observed in the controls for energy, sleep, and stress-related outcomes though to a lesser degree. Effect sizes of the difference in change over time observed indicate a net beneficial effect for provider communication (0.23); and decreases in depression (-0.18); pain (-0.19); problems related to stress (-0.17); and sleep (-0.20). CONCLUSION: Study data suggest that the self-management support from adaptation of the CDSMP can reach and appeal to cancer survivors, improves common concerns in this population, and can fill an important gap in meeting the ongoing need for management of post-diagnosis issues in this growing segment of the U.S. population.

Beginning a patient-centered approach in the design of a diabetes prevention program.

OBJECTIVE: The purpose of this study was to identify patient preferences for different components of a local diabetes prevention program that would improve reach. A secondary purpose was to determine if patient characteristics were related to program preferences. METHODS: Participants were identified through electronic medical records from two family medicine clinics in Virginia. Participants completed a mailed survey addressing demographics, economic status, risk factors for diabetes, and preferences regarding diabetes prevention interventions-delivery mode, program length, and duration. RESULTS: Twenty-nine percent of eligible participants responded (n = 142); 83% of participants were at risk for diabetes and 82% had a household income <$20,000. When presented with the choice between a class-based vs. a technology-based program, 83% preferred a technology-based program. Whites were less likely to choose the technology-based program, with no significant differences based on age, education, income, or gender. CONCLUSIONS: Contrary to beliefs that lower income individuals may not use technology-based interventions, lower socioeconomic patients indicated a preference for a technology- and telephone-supported diabetes prevention program over in-person class approaches. Findings provide formative data to support the design of a patient-centered, technology-enhanced diabetes prevention program in a real-world setting, thereby increasing potential participation and reach.

Design and methods of "diaBEAT-it!": a hybrid preference/randomized control trial design using the RE-AIM framework.

BACKGROUND: Diabetes prevention is a public health priority that is dependent upon the reach, effectiveness, and cost of intervention strategies. However, understanding each of these outcomes within the context of randomized controlled trials is problematic. PURPOSE: To describe the methods and design of a hybrid preference/randomized control trial using the RE-AIM framework. METHODS: The trial, which was developed using the RE-AIM framework, will contrast the effects of 3 interventions: (1) a standard care, small group, diabetes prevention education class (SG), (2) the small group intervention plus 12 months of interactive voice response telephone follow-up (SG-IVR), and (3) a DVD version of the small group intervention with the same IVR follow-up (DVD-IVR). Each intervention includes personal action planning with a focus on key elements of the lifestyle intervention from the Diabetes Prevention Program (DPP). Adult patients at risk for diabetes will be randomly assigned to either choice or RCT. Those assigned to choice (n=240) will have the opportunity to choose between SG-IVR and DVD-IVR. Those assigned to RCT group (n=360) will be randomly assigned to SG, SG-IVR, or DVD-IRV. Assessment of primary (weight loss, reach, & cost) and secondary (physical activity, & dietary intake) outcomes will occur at baseline, 6, 12, and 18 months. CONCLUSION: This will be the first diabetes prevention trial that will allow the research team to determine the relationships between reach, effectiveness, and cost of different interventions.