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The question of how people develop extreme, radical or even terrorist ideas and behaviors is one which is attracting more and more scientific attention. There are many factors that contribute to such extremist attitudes. This book focuses on one specific contributor which has received only little attention in the past: social exclusion. Recent research shows that being kept apart from others, physically or emotionally, is a powerful event in people's lives. The chapters provide an overview of the existing body of research for the first time and explore the exclusion-extremism link in depth by gathering together a seminal collection of essays, written by leading social psychologists. Timely, novel, and highly instructive, this volume delivers an expert understanding of psychological underpinnings of such behavior and offer inspiration for future research.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.
To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.
This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Understanding parents’ communication preferences and how parental and child characteristics impact satisfaction with communication is vital to mitigate communication challenges in the cardiac ICU.
This cross-sectional survey was conducted from January 2019 to March 2020 in a paediatric cardiac ICU with parents of patients admitted for at least two weeks. Family satisfaction with communication with the medical team was measured using the Communication Assessment Tool for Team settings. Clinical characteristics were collected via Epic, Pediatric Cardiac Critical Care Consortium local entry and Society for Thoracic Surgeons Congenital Heart Surgery Databases. Associations between communication score and parental mood, stress, perceptions of clinical care, and demographic characteristics along with patient demographic and clinical characteristics were examined. Multivariable ordinal models were conducted with characteristics significant in bivariate analysis.
In total, 93 parents of 84 patients (86% of approached) completed surveys. Parents were 63% female and 70% White. Seventy per cent of patients were <6 months old at admission, 25% had an extracardiac abnormality, and 80% had a cardiac surgery this admission. Parents of children with higher pre-surgical risk of mortality scores (OR 2.875; 95%CI 1.076–7.678), presence of surgical complications (72 [63.0, 75.0] vs. 64 [95%CI 54.6, 73] (p = 0.0247)), and greater satisfaction with care in the ICU (r = 0.93922; p < 0.0001) had significantly higher communication scores.
These findings can prepare providers for scenarios with higher risk for communication challenges and demonstrate the need for further investigation into interventions that reduce parental anxiety and improve communication for patients with unexpected clinical trajectories
Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.
We present new data from the debris-rich basal ice layers of the NEEM ice core (NW Greenland). Using mineralogical observations, SEM imagery, geochemical data from silicates (meteoric 10Be, εNd, 87Sr/86Sr) and organic material (C/N, δ13C), we characterize the source material, succession of previous glaciations and deglaciations and the paleoecological conditions during ice-free episodes. Meteoric 10Be data and grain features indicate that the ice sheet interacted with paleosols and eroded fresh bedrock, leading to mixing in these debris-rich ice layers. Our analysis also identifies four successive stages in NW Greenland: (1) initial preglacial conditions, (2) glacial advance 1, (3) glacial retreat and interglacial conditions and (4) glacial advance 2 (current ice-sheet development). C/N and δ13C data suggest that deglacial environments favored the development of tundra and taiga ecosystems. These two successive glacial fluctuations observed at NEEM are consistent with those identified from the Camp Century core basal sediments over the last 3 Ma. Further inland, GRIP and GISP2 summit sites have remained glaciated more continuously than the western margin, with less intense ice-substratum interactions than those observed at NEEM.
Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.
OBJECTIVES/GOALS: The effect of immunosuppressive metabolites on anti-tumor immunity in human papillomavirus (HPV)-associated vs carcinogen-driven head and neck cancer is unknown. The objective of this study is to define the extent to which metabolites impair this response and identify novel metabolic targets for enhancing anti-tumor immunity. METHODS/STUDY POPULATION: HPV-associated and carcinogen-driven head and neck squamous cell carcinoma specimens were frozen following surgical excision, and tumor sections were cut onto glass slides. Slides were coated in alpha-cyano-4-hydroxy-cinnamic acid (CHCA) matrix and subjected to mass spectrometry imaging using matrix-assisted laser desorption ionization (MALDI) on a Bruker SolariX XR 12T Hybrid QqFT-ICR mass spectrometer run in positive mode. Slides were then stained for immunohistochemistry (IHC) using markers of CD8 T cells, macrophages (CD163), B cells (CD20), and tumor cells (panCK). Mass spectrometry imaging and IHC spatially resolved data will be co-registered and metabolite intensity in regions of interest (cell types) quantified. RESULTS/ANTICIPATED RESULTS: A total of seven HPV-associated (three metastatic lymph nodes and four primary tumors) and six carcinogen-driven (primary tumors) HNSC specimens were subjected to MALDI and IHC. Metabolites significantly enriched in HPV-associated HNSC relative to carcinogen-driven HNSC include 2,3-diphosphoglyceric acid, xanthine, 2,3,5-Trichloromaleylacetate, and indole-3-carboxyaldehyde. Metabolites significantly enriched in carcinogen-driven HNSC relative to HPV-associated HNSC include hesperetin 3'-O-sulfate, hypoxanthine, phosphorylcholine, and L-homocysteine sulfonic acid. In ongoing analyses, we anticipate identifying a relationship between CD8+ T cell enriched vs depleted regions and immunosuppressive metabolites (e.g., kynurenine, adenosine monophosphate). DISCUSSION/SIGNIFICANCE: Defining the extent to which CD8+ T cells interact with the metabolic milieu of the microenvironment will provide a foundation for metabolic Precision Medicine. Strategically targeting metabolic pathways to enhance the anti-tumor immune response will be leveraged for the design and implementation of immune modulatory metabolic therapy.
On 3–4 October 2022, the Memorial Sloan Kettering Cancer Center Supportive Care Service and Department of Psychiatry and Behavioral Sciences hosted the Third Annual United States (US) Celebration of World Hospice and Palliative Care Day (WHPCD). The purpose of this article is to reflect on the event within the broader context of the international WHPCD theme: “healing hearts and communities.” We describe lessons learned in anticipation of the fourth annual conference to be held on 3–4 October 2023.
Description of the third annual event, conference planning team reflection, and attendee evaluation responses.
The Worldwide Hospice Palliative Care Alliance launched WHPCD in 2005 as an annual unified day of action to celebrate and support hospice and palliative care globally. Since 2020, the conference has attracted an increasing number of attendees from around the world. Two primary aims continue to guide the event: community building and wisdom sharing. Fifty-two interprofessional palliative care experts, advocates, patients, and caregivers provided 13 unique interactive sessions. Four hundred and fifty-eight multidisciplinary registrants from at least 17 countries joined the program. Free registration for colleagues in low- and middle-income countries, students and trainees, and individuals experiencing financial hardship remains a cornerstone of inclusion and equitable access to the event.
Significance of results
The US WHPCD celebration provides a virtual platform that offers opportunities for scientific dissemination and collective reflection on hospice and palliative care delivery amid significant local and global changes in clinical practice, research, policy and advocacy, and population health. We remain committed to ensuring an internationally relevant, culturally diverse, and multidisciplinary agenda that will continue to draw increased participation worldwide during future annual events.
The University of Illinois at Chicago (UIC), along with many academic institutions worldwide, made significant efforts to address the many challenges presented during the COVID-19 pandemic by developing clinical staging and predictive models. Data from patients with a clinical encounter at UIC from July 1, 2019 to March 30, 2022 were abstracted from the electronic health record and stored in the UIC Center for Clinical and Translational Science Clinical Research Data Warehouse, prior to data analysis. While we saw some success, there were many failures along the way. For this paper, we wanted to discuss some of these obstacles and many of the lessons learned from the journey.
Principle investigators, research staff, and other project team members were invited to complete an anonymous Qualtrics survey to reflect on the project. The survey included open-ended questions centering on participants’ opinions about the project, including whether project goals were met, project successes, project failures, and areas that could have been improved. We then identified themes among the results.
Nine project team members (out of 30 members contacted) completed the survey. The responders were anonymous. The survey responses were grouped into four key themes: Collaboration, Infrastructure, Data Acquisition/Validation, and Model Building.
Through our COVID-19 research efforts, the team learned about our strengths and deficiencies. We continue to work to improve our research and data translation capabilities.
Although post-error slowing and the “hot hand” (streaks of good performance) are both types of sequential dependencies arising from the differential influence of success and failure, they have not previously been studied together. We bring together these two streams of research in a task where difficulty can be controlled by participants delaying their decisions, and where responses required a degree deliberation, and so are relatively slow. We compared performance of unpaid participants against paid participants who were rewarded differentially, with higher reward for better performance. In contrast to most previous results, we found no post-error slowing for paid or unpaid participants. For the unpaid group, we found post-error speeding and a hot hand, even though the hot hand is typically considered a fallacy. Our results suggest that the effect of success and failure on subsequent performance may differ substantially with task characteristics and demands. We also found payment affected post-error performance; financially rewarding successful performance led to a more cautious approach following errors, whereas unrewarded performance led to recklessness following errors.
Scholarship on “stealth democracy” finds that many citizens want to avoid the debate and conflict that often come with democratic governance. This scholarship has argued that citizens adopt this posture because they are uncomfortable with disagreement and desire a more expedient political process that enables leaders to make decisions without discussion or compromise. We revisit this argument in light of recent political developments that suggest another reason why citizens may desire a more expedient political process. We examine the possibility that some citizens are not merely uncomfortable with disagreement but also want leaders who will aggressively protect them and champion their interests. Using a nationally representative survey, we ask citizens about their preferences for stealth democracy. We also ask questions that tap into their willingness to support leaders who would “bend the rules for supporters” and take aggressive action against political opponents. We find that a substantial component of the electorate continues to prefer a stealth version of democracy. However, we also find that many “stealth democrats” are willing to support leadership practices that would threaten or even undermine democratic norms. We argue that this evidence indicates that, in recent years, many citizens who appear to desire “stealth democracy” pose a threat to democracy itself.
The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology.
A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the “final” Residual Lesion Score.
The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the “final” Residual Lesion Score.
Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network’s Residual Lesion Score study.
Using 14 proxy human population time series from around the North Pacific (Alaska, Hokkaido and the Kuril Islands), we evaluate the possibility that the North Pacific climate and marine ecosystem includes a millennial-scale regime shift cycle affecting subsistence and migration. We develop both visual and statistical methods for addressing questions about relative population growth and movement in the past. We introduce and explore the use of a Time Iterative Moran I (TIMI) spatial autocorrelation method to compare time series trends quantitatively – a method that could prove useful in other paleoecological analyses. Results reveal considerable population dynamism around the North Pacific in the last 5000 years and strengthen a previously reported inverse correlation between Northeast and Northwest Pacific proxy population indices. Visual and TIMI analyses suggest multiple, overlapping explanations for the variability, including the potential that oscillating ecological regime shifts affect the North Pacific basin. These results provide an opening for coordinated research to unpack the interrelated social, cultural and environmental dynamics around the subarctic and arctic North Pacific at different spatial and temporal scales by international teams of archaeologists, historians, paleoecologists, paleoceanographers, paleoclimatologists, modelers and data management specialists.
This paper provides a large-scale, per Major League Baseball (MLB) game analysis of foul ball (FB) injury data and provides estimates of injury frequency and severity.
This study’s goal was to quantify and describe the rate and type of FB injuries at MLB games.
This was a retrospective review of medical care reports for patients evaluated by on-site health care providers (HCPs) over a non-contiguous 11-year period (2005-2016). Data were obtained using Freedom of Information Act (FOIA) requests.
Data were received from three US-based MLB stadiums.
The review reported 0.42-0.55 FB injuries per game that were serious enough to warrant presentation at a first aid center. This translated to a patients per 10,000 fans rate (PPTT) of 0.13-0.23. The transport to hospital rate (TTHR) was 0.02-0.39. Frequently, FB injuries required analgesics but were overwhelmingly minor and occurred less often than non-FB traumatic injuries (5.2% versus 42%-49%). However, FB injured fans were more likely to need higher levels of care and transport to hospital (TH) as compared to people suffering other traumatic injuries at the ballpark. Contusions or head injuries were common. Finally, FB injured fans were often hit in the abdomen, upper extremity, face, or head. It was found that FB injuries appeared to increase with time, and this increase in injuries aligns with the sudden increase in popularity of smartphones in the United States.
Conclusions and Relevance:
These data suggest that in roughly every two or three MLB games, a foul ball causes a serious enough injury that a fan seeks medical attention. This rate is high enough to warrant attention, but is comparable in frequency to other diagnostic categories. Assessing the risk to fans from FBs remains difficult, but with access to uniform data, researchers could answer persistent questions that would lead to actionable changes and help guide public policy towards safer stadiums.