Initial Clinical Experience with the Balloon-in-Basket Pulsed Field Ablation System: Acute Results of the VOLT CE Mark Feasibility Study.

BACKGROUND AND AIMS: Pulsed field ablation (PFA) for the treatment of atrial fibrillation (AF) potentially offers improved safety and procedural efficiencies compared to thermal ablation. Opportunities remain to improve effective circumferential lesion delivery, safety, and workflow of first generation PFA systems. Here we aim to evaluate the initial clinical experience with a balloon-in-basket, 3D integrated PFA system with a purpose-built form factor for pulmonary vein (PV) isolation. METHODS: The VOLT CE Mark Study is a premarket, prospective, multi-centre, single-arm study to evaluate the safety and effectiveness of the Volt™ PFA System for the treatment of paroxysmal (PAF) or persistent AF (PersAF). Feasibility sub-study subjects underwent phrenic nerve evaluation, endoscopy, chest CT, and cerebral MRI. Study endpoints were the rate of primary serious adverse event within 7-days and acute procedural effectiveness. RESULTS: A total of 32 subjects (age 61.6 ± 9.6 years, 65.6% male, 84.4% PAF) were enrolled and treated in the feasibility sub-study and completed 30-day follow-up. Acute effectiveness was achieved in 99.2% (127/128) of treated PVs (96.9% of subjects, 31/32) with 23.8 ± 4.2 PFA applications/subject. Procedure, fluoroscopy, LA dwell and transpired ablation times were 124.6 ± 28.1, 19.8 ± 8.9, 53.0 ± 21.0, and 48.0 ± 19.9 minutes respectively. Systematic assessments of initial safety revealed no phrenic nerve injury, pulmonary vein stenosis, or esophageal lesions causally related to the PFA system, and 3 subjects with silent cerebral lesions (9.4%). There were no primary serious adverse events. CONCLUSIONS: The initial clinical use of the Volt PFA System demonstrates acute safety and effectiveness in the treatment of symptomatic, drug refractory AF.

Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes.

Knowledge of locations and activities of cis -regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our V al i dated S ystematic I ntegrati on (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state Regulatory Potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbored distinctive transcription factor binding motifs that were similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we showed that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment.

Evaluation of a Computable Phenotype for Successful Cognitive Aging.

Objective: To establish, apply, and evaluate a computable phenotype for the recruitment of individuals with successful cognitive aging. Participants and Methods: Interviews with 10 aging experts identified electronic health record (EHR)-available variables representing successful aging among individuals aged 85 years and older. On the basis of the identified variables, we developed a rule-based computable phenotype algorithm composed of 17 eligibility criteria. Starting September 1, 2019, we applied the computable phenotype algorithm to all living persons aged 85 years and older at the University of Florida Health, which identified 24,024 individuals. This sample was comprised of 13,841 (58%) women, 13,906 (58%) Whites, and 16,557 (69%) non-Hispanics. A priori permission to be contacted for research had been obtained for 11,898 individuals, of whom 470 responded to study announcements and 333 consented to evaluation. Then, we contacted those who consented to evaluate whether their cognitive and functional status clinically met out successful cognitive aging criteria of a modified Telephone Interview for Cognitive Status score of more than 27 and Geriatric Depression Scale of less than 6. The study was completed on December 31, 2022. Results: Of the 45% of living persons aged 85 years and older included in the University of Florida Health EHR database identified by the computable phenotype as successfully aged, approximately 4% of these responded to study announcements and 333 consented, of which 218 (65%) met successful cognitive aging criteria through direct evaluation. Conclusion: The study evaluated a computable phenotype algorithm for the recruitment of individuals for a successful aging study using large-scale EHRs. Our study provides proof of concept of using big data and informatics as aids for the recruitment of individuals for prospective cohort studies.

Early prediction of Alzheimer's disease and related dementias using real-world electronic health records.

INTRODUCTION: This study aims to explore machine learning (ML) methods for early prediction of Alzheimer's disease (AD) and related dementias (ADRD) using the real-world electronic health records (EHRs). METHODS: A total of 23,835 ADRD and 1,038,643 control patients were identified from the OneFlorida+ Research Consortium. Two ML methods were used to develop the prediction models. Both knowledge-driven and data-driven approaches were explored. Four computable phenotyping algorithms were tested. RESULTS: The gradient boosting tree (GBT) models trained with the data-driven approach achieved the best area under the curve (AUC) scores of 0.939, 0.906, 0.884, and 0.854 for early prediction of ADRD 0, 1, 3, or 5 years before diagnosis, respectively. A number of important clinical and sociodemographic factors were identified. DISCUSSION: We tested various settings and showed the predictive ability of using ML approaches for early prediction of ADRD with EHRs. The models can help identify high-risk individuals for early informed preventive or prognostic clinical decisions.

Contact force catheter ablation for the treatment of persistent atrial fibrillation: Results from the PERSIST-END study.

INTRODUCTION: Use of a novel magnetic sensor enabled optical contact force ablation catheter has been established to be safe and effective for treatment of symptomatic drug-refractory paroxysmal atrial fibrillation (AF) but has yet to be demonstrated in the persistent AF (PersAF) population. METHODS: PERSIST-END was a multicenter, prospective, nonrandomized, investigational study designed to demonstrate the safety and effectiveness of TactiCath™ Ablation Catheter, Sensor Enabled™(SE) (TactiCath SE) for use in the treatment of subjects with documented PersAF refractory or intolerant to at least one Class I/III AAD. The ablation strategy included pulmonary vein isolation and additional targets at physician discretion. Follow-up through 15-months, including a 3-month blanking period and 3-month therapy consolidation period, was performed with cardiac event and Holter monitoring. Primary safety, primary effectiveness, clinical success, and quality of life (QOL) endpoints were analyzed. RESULTS: Of 224 subjects enrolled at 21 investigational sites in the United States and Australia, 223 underwent ablation with the investigational catheter. The primary safety event rate was 3.1% (seven events in seven subjects). The Kaplan-Meier estimate of freedom from AF/atrial flutter/atrial tachycardia recurrence at 15-months was 61.6% and clinical success at 15 months was 89.8%. Subject QOL significantly improved following ablation as assessed via AFEQT (31.6 point increase, p < .0001) and EQ-5D-5L (10.7 point increase, p < .0001) and was met with a 53% reduction in all cause cardiovascular healthcare utilization. CONCLUSION: The sensor-enabled force-sensing catheter is safe and effective for the treatment of drug refractory recurrent symptomatic PersAF, reducing arrhythmia recurrence while improving QOL and healthcare utilization.

Collaborative development of an innovative virtual research recruitment strategy through an academic/clinical partnership.

PURPOSE: Recruitment for research studies is the crucial first step and often the most challenging one. A major shift in recruitment methods for research was necessitated by the onset of the COVID-19 pandemic. Our goal is to describe lessons learned and the success rate of virtual research recruitment compared with other research recruitment strategies employed by our Academic/Clinical Partnership research team. METHODS: A descriptive design was employed to assess the success of in-person, mailed introductory letters with follow-up telephone calls and virtual recruitment strategies. The potential participants (N = 144) were parents caring for technology-dependent children (e.g., mechanical ventilation, feeding tubes) at home. To meet recruitment goals the Academic/Clinical Partnership research team (academic project team, hospital-based research nurses) collaboratively developed creative recruitment strategies and a framework to assess recruitment strategy success; percentage who agreed to be contacted by the academic partner, total time for recruitment visit, efficiency, and adherence to ethical recruitment principles. RESULTS: Virtual recruitment via telehealth visits was highly successful meeting all recruitment strategy benchmarks. Importantly, 91.7 % of potential participants that were approached agreed to be contacted for enrollment in a time efficient manner while adhering to ethical recruitment principles. Best practices and lessons learned were identified. CONCLUSIONS: The transition to virtual study recruitment due to the pandemic was an innovative and successful strategy. An Academic/Clinical Partnership research team benefits both partners: (1) enhances study recruitment by increasing research capacity at the clinical site; and (2) provides mentoring by nurse scientists to facilitate nurse research scholar knowledge and skills.

The Goldilocks principle: Finding the balance between water volume and nutrients for ovipositing Culex mosquitoes (Diptera: Culicidae).

Females of container-breeding mosquito species use visual and chemical cues to determine suitable habitats to oviposit their eggs. Female Culex mosquitoes oviposit single egg rafts containing hundreds of eggs on the surface of water in container habitats. In this project, the effects of water volume and nutrient concentration were studied using three semi-controlled field assays to determine the role these parameters play on female Culex mosquito oviposition preference. The results of this study suggest female Culex prefer to oviposit in larger volumes of water and higher concentrations of nutrients separately, but chose intermediate conditions when presented with a combination of these two variables, which follows the Goldilocks principle. This choice may provide their offspring with optimal conditions for development by reducing intraspecific competition, thereby maximizing the biological fitness of the ovipositing Culex females.

Examination of Early CNS Symptoms and Severe Coronavirus Disease 2019: A Multicenter Observational Case Series.

To determine if early CNS symptoms are associated with severe coronavirus disease 2019. DESIGN: A retrospective, observational case series study design. SETTING: Electronic health records were reviewed for patients from five healthcare systems across the state of Florida, United States. PATIENTS: A clinical sample (n = 36,615) of patients with confirmed diagnosis of coronavirus disease 2019 were included. Twelve percent (n = 4,417) of the sample developed severe coronavirus disease 2019, defined as requiring critical care, mechanical ventilation, or diagnosis of acute respiratory distress syndrome, sepsis, or severe inflammatory response syndrome. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We reviewed the electronic health record for diagnosis of early CNS symptoms (encephalopathy, headache, ageusia, anosmia, dizziness, acute cerebrovascular disease) between 14 days before the diagnosis of coronavirus disease 2019 and 8 days after the diagnosis of coronavirus disease 2019, or before the date of severe coronavirus disease 2019 diagnosis, whichever came first. Hierarchal logistic regression models were used to examine the odds of developing severe coronavirus disease 2019 based on diagnosis of early CNS symptoms. Severe coronavirus disease 2019 patients were significantly more likely to have early CNS symptoms (32.8%) compared with nonsevere patients (6.11%; χ2[1] = 3,266.08, p < 0.0001, φ = 0.29). After adjusting for demographic variables and pertinent comorbidities, early CNS symptoms were significantly associated with severe coronavirus disease 2019 (odds ratio = 3.21). Diagnosis of encephalopathy (odds ratio = 14.38) was associated with greater odds of severe coronavirus disease 2019; whereas diagnosis of anosmia (odds ratio = 0.45), ageusia (odds ratio = 0.46), and headache (odds ratio = 0.63) were associated with reduced odds of severe coronavirus disease 2019. CONCLUSIONS: Early CNS symptoms, and specifically encephalopathy, are differentially associated with risk of severe coronavirus disease 2019 and may serve as an early marker for differences in clinical disease course. Therapies for early coronavirus disease 2019 are scarce, and further identification of subgroups at risk may help to advance understanding of the severity trajectories and enable focused treatment.

Effects of sheared chromatin length on ChIP-seq quality and sensitivity.

Chromatin immunoprecipitation followed by massively parallel, high throughput sequencing (ChIP-seq) is the method of choice for genome-wide identification of DNA segments bound by specific transcription factors or in chromatin with particular histone modifications. However, the quality of ChIP-seq datasets varies widely, with a substantial fraction being of intermediate to poor quality. Thus, it is important to discern and control the factors that contribute to variation in ChIP-seq. In this study, we focused on sonication, a user-controlled variable, to produce sheared chromatin. We systematically varied the amount of shearing of fixed chromatin from a mouse erythroid cell line, carefully measuring the distribution of resultant fragment lengths prior to ChIP-seq. This systematic study was complemented with a retrospective analysis of additional experiments. We found that the level of sonication had a pronounced impact on the quality of ChIP-seq signals. Over-sonication consistently reduced quality, while the impact of under-sonication differed among transcription factors, with no impact on sites bound by CTCF but frequently leading to the loss of sites occupied by TAL1 or bound by POL2. The bound sites not observed in low-quality datasets were inferred to be a mix of both direct and indirect binding. We leveraged these findings to produce a set of CTCF ChIP-seq datasets in rare, primary hematopoietic progenitor cells. Our observation that the amount of chromatin sonication is a key variable in success of ChIP-seq experiments indicates that monitoring the level of sonication can improve ChIP-seq quality and reproducibility and facilitate ChIP-seq in rare cell types.

Ventricular Assist Device Implantation and Bariatric Surgery: A Route to Transplantation in Morbidly Obese Patients with End-Stage Heart Failure.

We reviewed our experience of morbidly obese patients with end-stage heart failure that underwent left ventricular assist device (LVAD) implantation. From January 1, 2008 to January 1, 2018, 240 adult LVADs were implanted at our center. We reviewed the cases of patients presenting with end-stage heart failure and morbid obesity (preoperative body mass index [BMI] ≥ 35 kg/m2) who underwent LVAD-alone, and compared that to a group that underwent LVAD and bariatric surgery (laparoscopic sleeve gastrectomy [LSG]) as a means for weight reduction. Demographic characteristics, perioperative details, BMI, and status of transplant candidacy were recorded. Statistical analysis was performed (SPSS version 25) with χ2 analysis, Kaplan-Meier survival analysis, regression analysis, and Student's t-test. Twenty-nine patients met criteria and underwent LVAD implantation. Fifteen patients underwent LVAD-alone. Fourteen patients underwent LVAD + LSG. Both groups showed good survival outcomes, LVAD-alone (88.9 ± 5.9 months) versus LVAD +LSG (96.1 ± 12.4 months) but were not significantly different. However, we did note that more patients in the LVAD + LSG group were bridged to heart transplantation (p < 0.001). LVAD-alone and/or LVAD + LSG are both technically feasible and effective treatment options for the long-term survival of morbidly obese patients with end-stage heart failure. Combining LVAD + LSG can help bridge patients to heart transplantation.

Mesospheric Bore Evolution and Instability Dynamics Observed in PMC Turbo Imaging and Rayleigh Lidar Profiling Over Northeastern Canada on 13 July 2018.

Two successive mesospheric bores were observed over northeastern Canada on 13 July 2018 in high-resolution imaging and Rayleigh lidar profiling of polar mesospheric clouds (PMCs) performed aboard the PMC Turbo long-duration balloon experiment. Four wide field-of-view cameras spanning an area of ~75 × 150 km at PMC altitudes captured the two evolutions occurring over ~2 hr and resolved bore and associated instability features as small as ~100 m. The Rayleigh lidar provided PMC backscatter profiling that revealed vertical displacements, evolving brightness distributions, evidence of instability character and depths, and insights into bore formation, ducting, and dissipation. Both bores exhibited variable structure along their phases, suggesting variable gravity wave (GW) source and bore propagation conditions. Both bores also exhibited small-scale instability dynamics at their leading and trailing edges. Those at the leading edges comprised apparent Kelvin-Helmholtz instabilities that were advected downward and rearward beneath the bore descending phases extending into an apparently intensified shear layer. Instabilities at the trailing edges exhibited alignments approximately orthogonal to the bore phases that resembled those seen to accompany GW breaking or intrusions arising in high-resolution modeling of GW instability dynamics. Collectively, PMC Turbo bore imaging and lidar profiling enabled enhanced definition of bore dynamics relative to what has been possible by previous ground-based observations, and a potential to guide new, three-dimensional modeling of bore dynamics. The observed bore evolutions suggest potentially important roles for bores in the deposition of energy and momentum transported into the mesosphere and to higher altitudes by high-frequency GWs achieving large amplitudes.

Impact of an automated hand hygiene monitoring system combined with a performance improvement intervention on hospital-acquired infections.

OBJECTIVE: Hand hygiene adherence has been associated with reductions in nosocomial infection. We assessed the effect of improvements in electronically measured hand hygiene adherence on the incidence of hospital-acquired infections. METHODS: This quasi-experimental study was conducted in a 555-bed urban safety-net level I trauma center. The preintervention period was January 2015 through June 2016. Baseline electronic hand hygiene data collection took place from April through June 2016. The intervention period was July 2016 through December 2017. An electronic hand hygiene system was installed in 4 locations in our hospital. Performance improvement strategies were implemented that included education, troubleshooting, data dissemination, and feedback. Adherence rates were tracked over time. Rates of hospital-acquired infections were evaluated in the intervention units and in control units selected for comparison. The intervention period was subdivided into the initial and subsequent 9-month periods and were compared to the baseline period. RESULTS: Electronically measured hand hygiene rates improved significantly from baseline to intervention, from 47% 77% adherence. Rates >70% continued to be measured 18 months after the intervention. Interrupted time series analysis indicated a significant effect of hand hygiene on healthcare facility-onset Clostridioides difficile infection rates during the first 9 months of the intervention. This trend continued during the final 9 months of the intervention but was nonsignificant. No effects were observed for other hospital-acquired infection rates. CONCLUSIONS: Implementation of electronic hand hygiene monitoring and performance improvement interventions resulted in reductions in hospital-onset Clostridioides difficile infection rates.

Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma.

Oncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly (P < 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.

An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis.

Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By using IDEAS as our integrative and discriminative epigenome annotation system, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of more than 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website to aid research in genomics and hematopoiesis.

APOBEC3B-mediated corruption of the tumor cell immunopeptidome induces heteroclitic neoepitopes for cancer immunotherapy.

APOBEC3B, an anti-viral cytidine deaminase which induces DNA mutations, has been implicated as a mediator of cancer evolution and therapeutic resistance. Mutational plasticity also drives generation of neoepitopes, which prime anti-tumor T cells. Here, we show that overexpression of APOBEC3B in tumors increases resistance to chemotherapy, but simultaneously heightens sensitivity to immune checkpoint blockade in a murine model of melanoma. However, in the vaccine setting, APOBEC3B-mediated mutations reproducibly generate heteroclitic neoepitopes in vaccine cells which activate de novo T cell responses. These cross react against parental, unmodified tumors and lead to a high rate of cures in both subcutaneous and intra-cranial tumor models. Heteroclitic Epitope Activated Therapy (HEAT) dispenses with the need to identify patient specific neoepitopes and tumor reactive T cells ex vivo. Thus, actively driving a high mutational load in tumor cell vaccines increases their immunogenicity to drive anti-tumor therapy in combination with immune checkpoint blockade.

The PMC Turbo Balloon Mission to Measure Gravity Waves and Turbulence in Polar Mesospheric Clouds: Camera, Telemetry, and Software Performance.

The Polar Mesospheric Cloud Turbulence (PMC Turbo) instrument consists of a balloon-borne platform which hosts seven cameras and a Rayleigh lidar. During a 6-day flight in July 2018, the cameras captured images of Polar Mesospheric Clouds (PMCs) with a sensitivity to spatial scales from ~20 m to 100 km at a ~2-s cadence and a full field of view (FOV) of hundreds of kilometers. We developed software optimized for imaging of PMCs, controlling multiple independent cameras, compressing and storing images, and for choosing telemetry communication channels. We give an overview of the PMC Turbo design focusing on the flight software and telemetry functions. We describe the performance of the system during its first flight in July 2018.

Prepping for Prevention: An Intervention to Optimize Skin Antisepsis and Peri-Operative Antibiotic Prophylaxis.

Background: The U.S. Centers for Disease Control and Prevention recommend bathing prior to surgery, surgical skin antisepsis, peri-operative antibiotic administration, normothermia throughout the procedure, serum glucose concentration <200 mg/dL throughout the procedure, and hyperoxygenation in the immediate post-operative period to prevent surgical site infection (SSI). We developed interventions to standardize skin antisepsis and peri-operative antibiotic administration at our institution. Methods: This is a cross-sectional evaluation of surgical skin antisepsis and antibiotic administration before and after a series of interventions designed to standardize the processes. Results: One hundred twenty-four surgical skin antisepsis opportunities were observed; significant improvement was seen in hand hygiene prior to performing skin antisepsis (compliance changing from 1% to 48%; p < 0.001), sleeves being worn during skin antisepsis (1% versus 67%; p < 0.001), use of the correct cleansing time (47% versus 85%; p < 0.001), allowance for adequate drying time (67% versus 87%; p = 0.02), and use of a cleansing motion from the incision to the periphery (78% versus 95%; p = 0.004). Pre-operative antibiotic order placement, correct antibiotic selection, and optimal antibiotic dose were evaluated in 466 surgical procedures. Significant improvement was seen in both peri-operative order placement (59% versus 70%; p = 0.02) and correct antibiotic selection (52% versus 95%; p < 0.001). Conclusion: An intervention to standardize skin antisepsis and to encourage early ordering of peri-operative antibiotics was successful.

Effects of d-amphetamine and MK-801 on impulsive choice: Modulation by schedule of reinforcement and delay length.

Procedural modifications can modulate drug effects in delay discounting, such as signaling the delay to reinforcement and altering the order in which delays are presented. Although the schedule of reinforcement can alter the rate at which animals discount a reinforcer, research has not determined if animals trained on different schedules of reinforcement are differentially affected by pharmacological manipulations. Similarly, research has not determined if using different delays to reinforcement can modulate drug effects in delay discounting. Male Sprague Dawley rats (n = 36) were split into four groups and were trained in a delay-discounting procedure. The schedule of reinforcement (fixed ratio [FR] 1 vs. FR 10) and delays to reinforcement (0, 5, 10, 20, and 50 s vs. 0, 10, 30, 60, 100 s) were manipulated for each group. Following behavioral training, rats were treated with d-amphetamine (0, 0.25, 0.5, and 1.0 mg/kg) and MK-801 (0, 0.03, and 0.06 mg/kg). Results showed that amphetamine decreased impulsive choice when a FR 1 schedule was used, but only when the short delay sequence was used. Conversely, amphetamine decreased impulsive choice when a FR 10 schedule was used, but only when rats were trained on the long delay sequence. MK-801 decreased impulsive choice in rats trained on a FR 1 schedule, regardless of delay sequence, but did not alter choice in rats trained on a FR 10 schedule. These results show that schedule of reinforcement and delay length can modulate drug effects in delay discounting.

Cooperative predation in the social amoebae Dictyostelium discoideum.

The eukaryotic amoeba Dictyostelium discoideum is commonly used to study sociality. The amoebae cooperate during development, exhibiting altruism, cheating, and kin-discrimination, but growth while preying on bacteria has been considered asocial. Here we show that Dictyostelium are cooperative predators. Using mutants that grow poorly on Gram-negative bacteria but grow well on Gram-positive bacteria, we show that growth depends on cell-density and on prey type. We also found synergy, by showing that pairwise mixes of different mutants grow well on live Gram-negative bacteria. Moreover, wild-type amoebae produce diffusible factors that facilitate mutant growth and some mutants exploit the wild type in mixed cultures. Finding cooperative predation in D. discoideum should facilitate studies of this fascinating phenomenon, which has not been amenable to genetic analysis before.