Awareness of Individual Daily Caloric Requirements and Food Energy Content and its Relation to Calorie Intake: A Multiple Baseline Design

The terms overweight and obesity are used to identify ranges of body weight that are linked to an increased risk for certain diseases and health problems such as cardiovascular disease, diabetes, sleep apnea, certain cancers, and others. Current estimates indicate that over two-thirds of American adults are overweight or obese while one-third of American children are overweight or obese. Therefore, this has become a significant public health issue. One strategy for combating overweight and obesity is to educate people about nutrition and the nutritional content of the food they consume. Nutrition labeling of prepackaged foods and calorie posting in restaurants are policies implemented to provide people with the needed information to make choices about food purchases. Through a multiple baseline design, this study analyzes the effects of caloric requirements knowledge and awareness of food energy content on calorie intake while self-monitoring in a college sample composed of Hispanic females

Atomic-Scale Interface Engineering of Majorana Edge Modes in a 2D Magnet-Superconductor Hybrid System

Topological superconductors are predicted to harbor exotic boundary states - Majorana zero-energy modes - whose non-Abelian braiding statistics present a new paradigm for the realization of topological quantum computing. Using low-temperature scanning tunneling spectroscopy (STS), we here report on the direct real-space visualization of chiral Majorana edge states in a monolayer topological superconductor, a prototypical magnet-superconductor hybrid system comprised of nano-scale Fe islands of monoatomic height on a Re(0001)-O(2$\times$1) surface. In particular, we demonstrate that interface engineering by an atomically thin oxide layer is crucial for driving the hybrid system into a topologically non-trivial state as confirmed by theoretical calculations of the topological invariant, the Chern number.Comment: 26 pages, 9 figure

A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor-positive/HER2-negative Advanced or Metastatic Breast Cancer

Fulvestrant; Breast cancerFulvestrant; Cáncer de mamaFulvestrant; Càncer de mamaPurpose: Endocrine-based therapy is the initial primary treatment option for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2− mBC. Patients and Methods: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2− breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor. Results: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8–20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73–4.83; P < 0.0001). Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study.This study was funded by GSK

Multi-Sensor Field Studies of Lightning and Implications for MTG-LI

Future geostationary satellite systems will offer a variety of improved observing capabilities which will be extremely useful for many applications like numerical weather forecasting, nowcasting of severe weather, climate research or hydrology. The planning for MTG (Meteosat Third Generation) includes an optical lightning imager (LI) as part of the payload. One requirement for a proper interpretation of these optical data is a better understanding of what components of a flash are to be seen from space and how these observations relate to ground based radio frequency observations. Therefore, the objectives of the present study concern the improvement of the understanding of the complex lightning process which then enables a proper interpretation of the optical data. For assessing the future performances and benefits of a geostationary lightning sensor this study takes advantage of the comprehensive lightning data sets obtained from the recent CHUVA field experiment performed in Brazil. (CHUVA - Cloud processes of tHe main precipitation systems in Brazil: A contribUtion to cloud resolVing modeling and to the GPM (GlobAl Precipitation Measurement)). During the rainy season of 2011-2012 a large number of ground based lightning detection systems was set up in the Sao Paulo area in Brazil. In the present study we look at the detailed radio frequency (RF) based observation from LINET (Lightning detection network operated by DLR, nowcast and USP) and observing strokes in the VLF/LF (very low and low frequency) range, the LMA (Lightning mapping array) from NASA observing RF sources in the VHF (very high frequency) range and the TRMM-LIS (Tropical Rainfall Measuring Mission-Lightning Imaging Sensor) optical space borne lightning imager. The LIS is used as a reference instrument for the future MTG-LI sensor as well as for the corresponding GLM sensor (Geostationary Lightning Mapper) on GOES-R. Thus it is possible to study the relations between the RF and optical signals from lightning in detail and to assess the performance of the future geostationary observations from a set of proxy satellite data generated from the ground based observations. In confirmation of previous studies, it was found that often a direct temporal coincidence of RF signals (LINET strokes) and optical pulses (LIS groups) exists. The short baseline configuration of LINET allowed to observe the strokes mapping the flash branches similar to LMA, but by locating the limited number of strong cloud strokes rather than a large number of weak source points from leader steps. An initial breakdown phase of vertically propagating sources can often be found in LINET and LMA data. The higher level LINET and LMA signals have higher probability to be optically detected. Lower level LINET and LMA signals are optically detected from above in case of missing high level precipitation as inferred from radar observations provided by USP. The new comprehensive data set allows for constructing proxy data for the future geostationary lightning mappers

Effectiveness of Feeding Therapy Approaches on Consumption and Dietary Variety in Children With Sensory-Based Feeding Challenges

This project was completed in collaboration with Hannah Michlmayer (OTR/L) at Therapy Services for Children in Seattle, Washington. The research team conducted a literature review to investigate the following question: For children ages 3-12 with sensory-based feeding challenges, what are the most effective interventions to improve dietary diversity and/or food acceptance? Evidence indicates that ABA-based interventions are the most studied, followed by video modeling and caregiver/parent training. These approaches demonstrate short-term increases in consumption and dietary variety. Most studies had small sample sizes with minimal long-term follow-up. There is a lack of research on group interventions, the SOS approach, and other sensory-based interventions (all used in OT practice). Further research in the following domains is strongly recommended: long-term follow-up studies, group feeding therapy approaches, sensory-based interventions, qualitative research, and higher level study designs. Knowledge translation (KT) activities focused on helping the collaborator improve service delivery of the SOS method and data collection on its effectiveness. Current caregiver/parent education materials were modified to increase accessibility for families to track their child’s progress at home, and a home documentation log was created to facilitate more robust progress tracking over time. Generalizable conclusions about the effectiveness of each KT activity cannot be drawn due to the small sample size of feedback providers. However, feedback received indicates the home documentation log was understandable and easy to use for caregivers/parents, and an effective progress monitoring tool for the collaborator. Collaborator feedback also indicated increased accessibility of caregiver/parent education materials. This suggests potential for home documentation and caregiver/parent education materials to facilitate increased progress tracking and understanding of the SOS feeding approach

Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood

IMPORTANCE: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes.OBJECTIVES: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood.DESIGN, SETTING, AND PARTICIPANTS: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024.EXPOSURES: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation.MAIN OUTCOMES AND MEASURES: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score.RESULTS: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years.CONCLUSIONS AND RELEVANCE: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.</p

Early neutrophil trajectory following clozapine may predict clozapine response - Results from an observational study using electronic health records

Background: Clozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. Aims: The current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. Methods: A retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. Results: Of the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31–3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03–2.49). Conclusions: Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.</p