Search

GHOST is a novel, compact shortwave-infrared grating spectrometer, designed for remote sensing of tropospheric columns of greenhouse gases (GHGs) from an airborne platform. It observes solar radiation at medium to high spectral resolution (better than 0.3 nm), which has been reflected by the Earth's surface using similar methods to those used by polar-orbiting satellites such as the JAXA GOSAT mission, NASA's OCO-2, and the Copernicus Sentinel-5 Precursor. By using an original design comprising optical fibre inputs along with a single diffraction grating and detector array, GHOST is able to observe CO2 absorption bands centred around 1.61 and 2.06 µm (the same wavelength regions used by OCO-2 and GOSAT) whilst simultaneously measuring CH4 absorption at 1.65 µm (also observed by GOSAT) and CH4 and CO at 2.30 µm (observed by Sentinel-5P). With emissions expected to become more concentrated towards city sources as the global population residing in urban areas increases, there emerges a clear requirement to bridge the spatial scale gap between small-scale urban emission sources and global-scale GHG variations. In addition to the benefits achieved in spatial coverage through being able to remotely sense GHG tropospheric columns from an aircraft, the overlapping spectral ranges and comparable spectral resolutions mean that GHOST has unique potential for providing validation opportunities for these platforms, particularly over the ocean, where ground-based validation measurements are not available. In this paper we provide an overview of the GHOST instrument, calibration, and data processing, demonstrating the instrument's performance and suitability for GHG remote sensing. We also report on the first GHG observations made by GHOST during its maiden science flights on board the NASA Global Hawk unmanned aerial vehicle, which took place over the eastern Pacific Ocean in March 2015 as part of the CAST/ATTREX joint Global Hawk flight campaign.

The compact linear accelerator for research and applications (CLARA) is an ultrabright electron beam test facility being developed at STFC Daresbury Laboratory. The ultimate aim of CLARA is to test advanced free electron laser (FEL) schemes that can later be implemented on existing and future short-wavelength FELs. In addition, CLARA is a unique facility to provide a high-quality electron beam to test novel concepts and ideas in a wide range of disciplines and to function as a technology demonstrator for a future United Kingdom x-ray FEL facility. CLARA is being built in three phases; the first phase, or front end (FE), comprises an S-band rf photoinjector, a linac, and an S-bend merging with the existing versatile electron linear accelerator beam line; the second phase will complete the acceleration to full beam energy of 250 MeV and also incorporate a separate beam line for use of electrons at 250 MeV; and the third phase will include the FEL section. The CLARA FE was commissioned during 2018, and the facility was later made available for user experiments. Significant advancements have been made in developing high-level software and a simulation framework for start-to-end simulations. The high-level software has been successfully used for unmanned rf conditioning and for characterization of the electron beam. This paper describes the design of the CLARA FE, performance of technical systems, high-level software developments, preliminary results of measured beam parameters, and plans for improvements and upgrades.

The purpose of this study was to determine if participation in the Community Action Poverty Simulation (CAPS) had an impact on rural educator candidates' and practicing rural educators' attitudes toward poverty (ATP). The group of rural educator candidates are students pursuing an undergraduate degree in education at a small, rural university in Alabama. Practicing educators who participated in the research were from a rural school in west Alabama. The CAPS is a one-hour simulation made up of four 15-minute weeks. Each 15-minute time segment simulates one week in poverty. In each week, participants have various tasks to complete in the allotted time. Participants in the simulation take on the roles of individuals living in poverty. Data was examined from two different simulation groups, rural educator candidates and practicing rural educators. All participants completed a demographic information sheet and the Pretest before participation in the CAPS. Following the simulation, all participants are involved in the debrief session. This session, led by the facilitator, allows participants to discuss the range of feelings they experienced during the simulation. After the debrief portion of the simulation, participants completed the Posttest. Statistical analysis using SPSS was conducted. Data were analyzed using a paired samples t-test. The results indicated an increased (more positive) ATP score (M[subscript 1] = 3.65, M[subscript 2] = 3.68) for rural educator candidates, but there was not a statistically significant difference (p=0.578). However, the data for practicing rural educators indicated an increase in the ATP score (M[subscript 1] = 3.51, M[subscript 2] = 3.68) and a statistically significant difference (p=0.000). Based on the data analysis, it was concluded that participation in the CAPS has a greater impact on practicing educators versus undergraduate education majors. Rural school leaders grapple with ways to ensure students living in poverty have the same learning opportunities as other students to thrive academically. Often school accountability is focused on high-stakes testing results. Across the nation, there is an increase of children from homes of poverty, who have unique educational needs. Rural schools are faced with barriers such as funding, isolation, and community support. School leaders must ensure faculty and staff have a clear understanding of poverty and how poverty can affect a student's educational journey; hence, the need to provide poverty simulation training.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic "rebound" effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

ABSTRACT: Objective: To evaluate the impact of the COVID-19 pandemic on the psychosocial functioning of individuals with cleft lip and/or palate (CL/P). Methods: Patients with CL/P ≥ 6 years old were prospectively recruited from the Cleft and Craniofacial Clinic of a tertiary children's hospital. From July-October 2021, eligible patients (or their parent/guardian) were sent a survey regarding their psychosocial functioning before and after the start of the pandemic. Main Outcome Measure: The difference between prepandemic and intrapandemic patient-reported outcome scores. Results: Thirty-six patients (20 female, age: 15.9 ± 9.8 years) responded. Most had cleft lip and palate (77.8%), responded online (69.4%), interacted remotely via both voice- and video-conferencing (62.9%), and wore masks routinely (77.1%). Similar numbers of patients responded independently (27.8%), responded with the help of a parent/guardian (36.1%), or had a parent/guardian respond on their behalf (36.1%). General social-emotional well-being (p = 0.004, rrb = 0.659) and satisfaction with facial appearance (p = 0.044, rrb = 0.610) significantly improved after the start of the pandemic. Compared to their general intrapandemic social-emotional well-being scores, patients reported higher scores while wearing a mask (rrb = 0.827) and lower scores while interacting remotely (rrb = 0.605), although all were still significantly improved compared to their prepandemic scores (p ≤ 0.010). Patients also reported significant improvement in social functioning while wearing a mask (p = 0.036, rrb = 0.519), whereas they did not when considering their general intrapandemic feelings/experiences (p = 0.269, rrb = 0.211). Conclusion: Patients with CL/P demonstrated significant improvement in overall social-emotional well-being, satisfaction with facial appearance, and social functioning after the start of the COVID-19 pandemic, particularly when wearing a mask.

There is abundant literature about interviewer effects on the survey process, but studies of interviewer training are quite limited. Previous research has produced mixed findings on how training affects interviewer performance. Trainings are often conducted in person despite the mixed findings. There has been no research that examines the use of videoconferencing as a medium for training field survey interviewers. We conducted an interviewer training experiment with the Medical Expenditure Panel Survey (MEPS). We randomly assigned 242 field interviewers into three training modes: in person, videoconference (i.e., WebEx), and self-administered training. Each interviewer's performance was observed before and after the training. As post-hoc analysis, we observed improvement for higher performed interviewers trained in videoconference. Interviewers trained in videoconference rated their experiences similar to their counterparts trained in person.

In this study, we analyzed student participation and success in a college-level Calculus I course that utilized standards-based grading. By measuring the level to which students participate in this class structure, we were able to use a clustering algorithm that revealed multiple groupings of students that were distinct based on activity throughout the semester. Additionally, we analyzed student progress, defined as the number of graded activities successfully completed each week. We found that students who progressed steadily throughout the semester, and thus had lower variability in the number of completed activities per week, tended to receive a higher overall grade. Students whose progress was less consistent, and thus exhibited higher variability in weekly activities completed, tended to receive a lower grade. Overall, this shows a relationship between understanding the expectations in standards-based grading and succeeding in a course.

Obesity, defined by excessive body fat, is a highly complex condition affecting numerous physiological processes, such as metabolism, proliferation, and cellular homeostasis. These multifaceted effects impact cells and tissues throughout the host, including immune cells as well as cancer biology. Because of the multifaceted nature of obesity, common parameters used to define it (such as body mass index in humans) can be problematic, and more nuanced methods are needed to characterize the pleiotropic metabolic effects of obesity. Obesity is well-accepted as an overall negative prognostic factor for cancer incidence, progression, and outcome. This is in part due to the meta-inflammatory and immunosuppressive effects of obesity. Immunotherapy is increasingly used in cancer therapy, and there are many different types of immunotherapy approaches. The effects of obesity on immunotherapy have only recently been studied with the demonstration of an obesity paradox, in which some immune therapies have been demonstrated to result in greater efficacy in obese subjects despite the direct adverse effects of obesity and excess body fat acting on the cancer itself. The multifactorial characteristics that influence the effects of obesity (age, sex, lean muscle mass, underlying metabolic conditions and drugs) further confound interpretation of clinical data and necessitate the use of more relevant preclinical models mirroring these variables in the human scenario. Such models will allow for more nuanced mechanistic assessment of how obesity can impact, both positively and negatively, cancer biology, host metabolism, immune regulation, and how these intersecting processes impact the delivery and outcome of cancer immunotherapy.

Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non-antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1- populations in vitro. Higher activation and proliferative responses were also observed in the PD-1- memory population in both mice and patients with cancer receiving high-dose IL-2, mirroring the in vitro phenotypes. This inhibitory effect of PD-1 could be reversed by PD-1 blockade in vivo or observed using memory T cells from PD-1-/- mice. Interestingly, increased activation through abrogation of PD-1 signaling in bystander-activated T cells also resulted in increased apoptosis due to activation-induced cell death (AICD) and eventual T cell loss in vivo. These results demonstrate that the PD-1/PD-Ligand 1 (PD-L1) pathway inhibited bystander-activated memory T cell responses but also protected cells from AICD.

The neurophysiological mechanisms in the human amygdala that underlie post-traumatic stress disorder (PTSD) remain poorly understood. In a first-of-its-kind pilot study, we recorded intracranial electroencephalographic data longitudinally (over one year) in two male individuals with amygdala electrodes implanted for the management of treatment-resistant PTSD (TR-PTSD) under clinical trial NCT04152993. To determine electrophysiological signatures related to emotionally aversive and clinically relevant states (trial primary endpoint), we characterized neural activity during unpleasant portions of three separate paradigms (negative emotional image viewing, listening to recordings of participant-specific trauma-related memories, and at-home-periods of symptom exacerbation). We found selective increases in amygdala theta (5-9 Hz) bandpower across all three negative experiences. Subsequent use of elevations in low-frequency amygdala bandpower as a trigger for closed-loop neuromodulation led to significant reductions in TR-PTSD symptoms (trial secondary endpoint) following one year of treatment as well as reductions in aversive-related amygdala theta activity. Altogether, our findings provide early evidence that elevated amygdala theta activity across a range of negative-related behavioral states may be a promising target for future closed-loop neuromodulation therapies in PTSD.

Psychoneuroimmunology (PNI) researchers can advance their careers and increase their scientific impact by prioritizing their writing skills. In addition to Dr. Kiecolt-Glaser's landmark research that inspired this special issue, her legacy is reflected in her prolific writing. Dr. Kiecolt-Glaser has the unique ability to convey her innovative research clearly and to diverse audiences. She also made writing mentorship a critical part of the training experience in her lab. In these ways, Dr. Kiecolt-Glaser's writing skills and mentorship have shaped both the PNI field and her trainees' careers. In this paper, I distill lessons learned about writing from Dr. Kiecolt-Glaser during my time as a graduate student in her Stress and Health Lab in the 2010s. I reflect on Dr. Kiecolt-Glaser's influence on her trainees' writing habits, summarize “writing pearls” inspired by her feedback/revisions, and provide observations on her writing mentorship habits. These tips are intended to help PNI trainees to clearly communicate their work and to help mentors reflect on ways they can prioritize and advance their trainees' writing skills. Finally, I reflect on how Dr. Kiecolt-Glaser's mentorship and scientific accomplishments had a tremendous impact on my own career development.

The Brazilian Cerrado is considered a hotspot for biodiversity conservation. However, in recent decades, the intensification of human activities, directly influencing changes in use and coverage, has caused severe environmental problems. Thus, this study proposed a dynamic environmental zoning model for the Pântano River watershed (PRW) based on the CA-Markov model and Multicriteria Analysis. The methodological procedures were based on predictive modeling of land use and land cover, analysis of environmental fragility, and estimation of soil losses and sediment delivery rate from the InVEST model for the years 1984, 2007, 2013, 2020, 2030, and 2050. The results showed that over the time analyzed and projected, in the category of Legal Restrictions Zone, there was a slight decrease in the extension of Permanent Preservation Areas, while the Natural Vegetation cover increased considerably, indicating possible changes in the environmental patterns of the region. The areas classified as Plains maintained minimal variations throughout the period studied. With regard to the Rural Productive Zone, there was a notable increase in areas with Low Restriction, suggesting an expansion of less restrictive agricultural and land use activities. On the other hand, the areas with Medium and High Restrictions showed decreasing trends, signaling possible improvements in environmental management and conservation of natural resources. Also noteworthy is the significant reduction in areas classified as High Restriction, associated with the high rate of soil loss. This trend is particularly relevant as it indicates practical efforts to mitigate adverse environmental impacts and promote sustainable soil management practices. Finally, the areas designated as Special Protection Zones, including Incongruities and Reservoirs, remained stable throughout the period analyzed, demonstrating the importance of preserving these areas to conservation of biodiversity and water resources. In conclusion, the results obtained in this study contribute to guiding public policies and environmental management practices in the PRW region. The observed trends indicate a positive evolution towards the conservation and sustainable use of natural resources, underscoring the importance of continuous measures to ensure the health and resilience of local ecosystems.

The thymus is the central organ involved with T-cell development and the production of naïve T cells. During normal aging, the thymus undergoes marked involution, reducing naïve T-cell output and resulting in a predominance of long-lived memory T cells in the periphery. Outside of aging, systemic stress responses that induce corticosteroids (CS), or other insults such as radiation exposure, induce thymocyte apoptosis, resulting in a transient acute thymic involution with subsequent recovery occurring after cessation of the stimulus. Despite the increasing utilization of immunostimulatory regimens in cancer, effects on the thymus and naïve T cell output have not been well characterized. Using both mouse and human systems, the thymic effects of systemic immunostimulatory regimens, such as high dose IL-2 (HD IL-2) with or without agonistic anti-CD40 mAbs and acute primary viral infection, were investigated. These regimens produced a marked acute thymic involution in mice, which correlated with elevated serum glucocorticoid levels and a diminishment of naïve T cells in the periphery. This effect was transient and followed with a rapid thymic “rebound” effect, in which an even greater quantity of thymocytes was observed compared to controls. Similar results were observed in humans, as patients receiving HD IL-2 treatment for cancer demonstrated significantly increased cortisol levels, accompanied by decreased peripheral blood naïve T cells and reduced T-cell receptor excision circles (TRECs), a marker indicative of recent thymic emigrants. Mice adrenalectomized prior to receiving immunotherapy or viral infection demonstrated protection from this glucocorticoid-mediated thymic involution, despite experiencing a substantially higher inflammatory cytokine response and increased immunopathology. Investigation into the effects of immunostimulation on middle aged (7-12 months) and advance aged (22-24 months) mice, which had already undergone significant thymic involution and had a diminished naïve T cell population in the periphery at baseline, revealed that even further involution was incurred. Thymic rebound hyperplasia, however, only occurred in young and middle-aged recipients, while advance aged not only lacked this rebound hyperplasia, but were entirely absent of any indication of thymic restoration. This coincided with prolonged deficits in naïve T cell numbers in advanced aged recipients, further skewing the already memory dominant T cell pool. These results demonstrate that, in both mice and humans, systemic immunostimulatory cancer therapies, as well as immune challenges like subacute viral infections, have the potential to induce profound, but transient, glucocorticoid-mediated thymic involution and substantially reduced thymic output, resulting in the reduction of peripheral naive T cells. This can then be followed by a marked rebound effect with naïve T cell restoration, events that were shown not to occur in advanced-aged mice.

Os conflitos e a discordância entre porta-vozes na pandemia da covid-19 centralizaram o debate sobre a desconfiança da vacina da covid-19 no Brasil. O status de desconfiança intensificou a problemática da hesitação vacinal para o Programa Nacional de Imunizações. Este ensaio propõe a aproximação entre uma perspectiva metodológica, alicerçada na Teoria Ator-Rede, e a temática, sugerindo a cartografia da controvérsia como ferramenta para investigação. A discussão centrou-se no complexo fenômeno da hesitação vacinal, ressaltando que ele não se supera com o ato de se vacinar, e exige da política pública de saúde a recuperação da confiança na vacinação, especialmente diante de possíveis novos estados de emergência em saúde pública. Nesse sentido, o ensaio ressalta as ligações entre atores da hesitação vacinal e suas ações e sugere o desenho de uma rede para a proliferação da hesitação vacinal entre os anos 2021 e 2022.

Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.

IntroductionThe incidence of obesity, a condition characterized by systemic chronic inflammation, has reached pandemic proportions and is a poor prognostic factor in many pathologic states. However, its role on immune parameters has been diverse and at times contradictory. We have previously demonstrated that obesity can result in what has been called the "obesity paradox" which results in increased T cell exhaustion, but also greater efficacy of immune checkpoint blockade in cancer treatment.MethodsThe role of obesity, particularly in the context of aging, has not been robustly explored using preclinical models. We therefore evaluated how age impacts the immune environment on T cell development and function using diet-induced obese (DIO) mice.ResultsWe observed that DIO mice initially displayed greater thymopoiesis but then developed greater thymic involution over time compared to their lean counterparts. Both aging and obesity resulted in increased T cell memory conversion combined with increased expression of T cell exhaustion markers and Treg expansion. This increased T cell immunosuppression with age then resulted in a loss of anti-tumor efficacy by immune checkpoint inhibitors (ICIs) in older DIO mice compared to the younger DIO counterparts.DiscussionThese results suggest that both aging and obesity contribute to T cell dysfunction resulting in increased thymic involution. This combined with increased T cell exhaustion and immunosuppressive parameters affects immunotherapy efficacy reducing the advantage of obesity in cancer immunotherapy responses.

The video essay is an opportunity for students to record their words and combine other visual elements to complete the typical requirements of a standard written paper. Applicable across disciplines and pedagogically aligned with an honors ethos of self-directed learning, video essays allow for individual and collaborative forms of expression while providing unique approaches to compositional assessment on an array of subjects.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as “unhealthy macrophages”. Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system–active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs. Here, we report a case of successful rechallenge of dose-reduced lorlatinib after recovery of grade IV psychosis in a patient with ALK-positive NSCLC.