Altered Gating of K\u3csub\u3ev\u3c/sub\u3e1.4 in the Nucleus Accumbens Suppresses Motivation for Reward

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine signaling genes. Functionally, motivation was inversely related to excitability of NAc principal neurons. Furthermore, neuronal and behavioral outputs associated with low motivation were linked to faster inactivation of a voltage-gated potassium channel, Kv1.4. These results raise the prospect of targeting Kv1.4 gating in psychiatric conditions associated with motivational dysfunction

Linking variation in planktonic primary production to coral reef fish growth and condition

Within low-nutrient tropical oceans, islands and atolls with higher primary production support higher fish biomass and reef organism abundance. External energy subsidies can be delivered onto reefs via a range of physical mechanisms. However, the influence of spatial variation in primary production on reef fish growth and condition is largely unknown. It is not yet dear how energy subsidies interact with reef depth and slope. Here we test the hypothesis that with increased proximity to deep-water oceanic nutrient sources, or at sites with shallower reef slopes, parameters of fish growth and condition will be higher. Contrary to expectations, we found no association between fish growth rate and sites with higher mean chlorophyll-a values. There were no differences in fish delta N-15 or delta C-13 values between depths. The relationship between fish condition and primary production was influenced by depth, driven by increased fish condition at shallow depths within a primary production 'hotspot' site. Carbon delta C-13 was depleted with increasing primary production, and interacted with reef slope. Our results indicate that variable primary production did not influence growth rates in planktivorous Chromis fieldi within 10-17.5 m depth, but show site-specific variation in reef physical characteristics influencing fish carbon isotopic composition

Using in-cylinder gas internal energy balance to calibrate cylinder pressure data and estimate residual gas amount in gasoline homogeneous charge compression ignition combustion

HCCI engines are likely to become one of the future alternatives to SI engines due to their ability to deliver high efficiency and low NOx emissions. There are, however, problems with the control of the ignition and heat release rate over the entire load and the speed range, which limits the practical application of this technology. In order to investigate the combustion parameters of both SI and HCCI gasoline engines, a widely used and powerful diagnostic tool is the analysis of the in-cylinder pressure time history as derived from in-cylinder pressure transducers. Such information has particular application in HCCI engines for control of TRG levels, valve timing, misfire and knock detection. Unfortunately, although the use of in-cylinder pressure transducers for that purpose has been an invaluable research tool, it is not without problems. In the case of HCCI combustion, the violent rates of heat release make the signal derived from pressure transducers more prone to thermal shock. In addition, in HCCI research, it is often necessary to establish the TRG amount as accurately as possible. However, TRG presence also complicates pegging techniques. Since the pressure transducer signal can be compromised by these calibration issues, it is prudent to try to address these issues when dealing with pressure signals derived during HCCI operation. The present article presents an algorithm aiming to account for these calibration issues surrounding the use of pressure transducers in HCCI research. Results for the TRG amount and initial mixture composition and temperature on a cycle-to-cycle basis are also derived

Light Curves and Period Changes of Type II Cepheids in the Globular Clusters M3 and M5

Light curves in the B, V, and I_c passbands have been obtained for the type II Cepheids V154 in M3 and V42 and V84 in M5. Alternating cycle behavior, similar to that seen among RV Tauri variables, is confirmed for V84. Old and new observations, spanning more than a century, show that V154 has increased in period while V42 has decreased in period. V84, on the other hand, has shown large, erratic changes in period that do not appear to reflect the long term evolution of V84 through the HR diagram.Comment: 28 pages, 12 figure

Will opposites attract? Similarities and differences in students' perceptions of the stereotype profiles of other health and social care professional groups

The extent to which health and social care (HSC) students hold stereotypical views of other HSC professional groups is of great potential importance to team working in health care. This paper explores students' perceptions of different HSC professional groups at the beginning of their university programmes. Findings are presented from an analysis of baseline data collected as part of the New Generation Project longitudinal cohort study which is assessing the impact of interprofessional education over time on a range of variables including stereotyping. Questionnaires were administered to a cohort of over 1200 students from 10 different HSC professional groups entering their first year of university. Stereotypes were measured using a tool adapted from Barnes et al. (2000) designed to elicit stereotype ratings on a range of nine characteristics. The findings confirm that students arrive at university with an established and consistent set of stereotypes about other health and social care professional groups. Stereotypical profiles were compiled for each professional group indicating the distinctive characteristics of the groups as well as the similarities and differences between groups. Midwives, social workers and nurses were rated most highly on interpersonal skills and on being a team player whilst doctors were rated most highly on academic ability. Doctors, midwives and social workers were perceived as having the strongest leadership role, whilst doctors were also rated most highly on decision making. All professions were rated highly on confidence and professional competence and, with the exception of social workers, on practical skills. A comparison of profiles for each professional group reveals that, for example, pharmacists and doctors were perceived as having very similar characteristics as were social workers, midwives and nurses. However, the profiles of nurses and doctors were perceived to be very different. The implications of these similarities and differences are discussed in terms of their potential impact on interprofessional interactions, role boundaries and team working

A Tool for Interactive Data Visualization: Application to Over 10,000 Brain Imaging and Phantom MRI Data Sets

In this paper we propose a web-based approach for quick visualization of big data from brain magnetic resonance imaging (MRI) scans using a combination of an automated image capture and processing system, nonlinear embedding, and interactive data visualization tools. We draw upon thousands of MRI scans captured via the COllaborative Imaging and Neuroinformatics Suite (COINS). We then interface the output of several analysis pipelines based on structural and functional data to a t-distributed stochastic neighbor embedding (t-SNE) algorithm which reduces the number of dimensions for each scan in the input data set to two dimensions while preserving the local structure of data sets. Finally, we interactively display the output of this approach via a web-page, based on data driven documents (D3) JavaScript library. Two distinct approaches were used to visualize the data. In the first approach, we computed multiple quality control (QC) values from pre-processed data, which were used as inputs to the t-SNE algorithm. This approach helps in assessing the quality of each data set relative to others. In the second case, computed variables of interest (e.g., brain volume or voxel values from segmented gray matter images) were used as inputs to the t-SNE algorithm. This approach helps in identifying interesting patterns in the data sets. We demonstrate these approaches using multiple examples from over 10,000 data sets including (1) quality control measures calculated from phantom data over time, (2) quality control data from human functional MRI data across various studies, scanners, sites, (3) volumetric and density measures from human structural MRI data across various studies, scanners and sites. Results from (1) and (2) show the potential of our approach to combine t-SNE data reduction with interactive color coding of variables of interest to quickly identify visually unique clusters of data (i.e., data sets with poor QC, clustering of data by site) quickly. Results from (3) demonstrate interesting patterns of gray matter and volume, and evaluate how they map onto variables including scanners, age, and gender. In sum, the proposed approach allows researchers to rapidly identify and extract meaningful information from big data sets. Such tools are becoming increasingly important as datasets grow larger

Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer

Purpose: Giredestrant is an investigational next-generation, oral, selective estrogen receptor antagonist and degrader for the treatment of estrogen receptor-positive (ER+) breast cancer. We present the primary analysis results of the phase Ia/b GO39932 study (NCT03332797).Patients and Methods: Patients with ER+, HER2-negative locally advanced/metastatic breast cancer previously treated with endocrine therapy received single-agent giredestrant (10, 30, 90, or 250 mg), or giredestrant (100 mg) +/- palbociclib 125 mg +/- luteinizing hormone-releasing hormone (LHRH) agonist. Detailed cardiovascular assessment was conducted with giredestrant 100 mg. Endpoints included safety (primary), pharmacokinetics, pharmacodynamics, and efficacy.Results: As of January 28, 2021, with 175 patients enrolled, no dose-limiting toxicity was observed, and the MTD was not reached. Adverse events (AE) related to giredestrant occurred in 64.9% and 59.4% of patients in the single-agent +/- LHRH agonist and giredestrant + palbociclib +/- LHRH agonist cohorts, respectively (giredestrant-only-related grade 3/4 AEs were reported in 4.5% of patients across the single-agent cohorts and 3.1% of those with giredestrant + palbociclib). Dose-dependent asymptomatic bradycardia was observed, but no clinically significant changes in cardiac-related outcomes: heart rate, blood pressure, or exercise duration. Clinical benefit was observed in all cohorts (48.6% of patients in the single-agent cohort and 81.3% in the giredestrant + palbociclib +/- LHRH agonist cohort), with no clear dose relationship, including in patients with ESR1-mutated tumors.Conclusions: Giredestrant was well tolerated and clinically active in patients who progressed on prior endocrine therapy. Results warrant further evaluation of giredestrant in randomized trials in early- and late-stage ER+ breast cancer

Habits of Mind: Designing Courses for Student Success

Although content knowledge remains at the heart of college teaching and learning, forward-thinking instructors recognize that we must also provide 21st-century college students with transferable skills (sometimes called portable intellectual abilities) to prepare them for their futures (Vazquez, 2020; Ritchhart, 2015; Venezia & Jaeger, 2013; Hazard, 2012). To “grow their capacity as efficacious thinkers to navigate and thrive in the face of unprecedented change” (Costa et al., 2023), students must learn and improve important study skills and academic dispositions throughout their educational careers. If we do not focus on skills-building in college courses, students will not be prepared for the challenges that await them after they leave institutions of higher education. If students are not prepared for these postsecondary education challenges, then it is fair to say that college faculty have failed them