Search

Over the course of the last century, particle accelerators have emerged as a ubiquitous technology in experimental physics. Electron linear accelerators (linacs) have been particularly useful historically for light sources such as free electron lasers (FELs) and high energy physics experiments such as linear colliders. The most useful of these machines are significant undertakings often requiring the investment of nation states and kilometer footprints which reduce accessibility. In addition, newer applications of linacs for example in compact machines for medical purposes and imaging such as ultrafast electron diffraction (UED) have become popular. As a result, scale reduction without loss of beam performance has become a significant interest. Performance figures of merit such as beam energy, current, and brightness are commonly considered. Operating electron linear accelerators at cryogenic temperatures offers a promising venue for obtaining significant increases in beam brightness and consequently accelerator miniaturization. In the following dissertation, the general underpinnings for beam brightness as a figure of merit are explained and a derivation for the maximum achievable value for an ideal injector is described as introduction to the field. Relevant low temperature emission and surface physics are also introduced. We then draw specific attention to the brightness scaling of a cryogenic RF photogun and formulate this into expressions dependent on the cathode and accelerating cavity's low temperature behavior. We further use electromagnetic and beam dynamics simulations to augment this theory with analytic predictions. The general objective of this dissertation is not only to quantify the achievable beam brightness improvements from the cryogenic operation of a radio frequency photogun using a combination of theory, simulation, and experiment.The primary experiments involve the commissioning of a new lab facility for Multi-Objective Testing for High gradien

A set of universal quantum gates is a vital part of the theory of quantum computing, but is absent in the developing theory of Relativistic Quantum Information (RQI). Yet, the Unruh--DeWitt (UDW) detector formalism can be elevated to unitary gates between qubits and quantum fields and has allowed RQI applications in quantum Shannon theory, such as mutual information, coherent information, and quantum capacity in field-mediated quantum channels. Recently, experimental realizations of UDW-style qubits have been proposed in two-dimensional quantum materials, but their value as a quantum technology, including quantum communication and computation, is not yet clear, especially since fields introduce many avenues for decoherence. We introduce controlled-unitary UDW logic gates between qubit and field that are comparable to the two-qubit CNOT gate. We then extend this formalism to demonstrate Quantum State Transfer (QST) (two CNOT gates) and SWAP (three CNOT gates) channels. We illustrate the performance of these quantum operation gates with the diamond distance, a measure of distinguishability between quantum channels. Distinguishability measures like diamond distance allow for a rigorous comparison between field-mediated transduction through UDW detectors and local quantum mechanical operations and so quantify the performance of UDW detectors in quantum technological applications. Using the controlled-unitary qubit-field interactions we define an exact form of the CNOT gate. With this technique we also define quantum field-mediated single qubit operations associated with the Hadamard $H$, the $S$, and $T$ gates. Thus, UDW detectors in simple settings enable a collection of gates known to provide universal quantum computing., Comment: 17 pages, 11 figures, 4 tables

What is it for philosophy to make progress? While various putative forms of philosophical progress have been explored in some depth, this overarching question is rarely addressed explicitly, perhaps because it has been assumed to be intractable or unlikely to have a single, unified answer. In this paper, we aim to show that the question is tractable, that it does admit of a single, unified answer, and that one such answer is plausible. This answer is, roughly, that philosophical progress consists in putting people in a position to increase their understanding, where ‘increased understanding’ is a matter of better representing the network of dependence relations between phenomena. After identifying four desiderata for an account of philosophical progress, we argue that our account meets the desiderata in a particularly satisfying way. Among other things, the account explains how various other achievements, such as philosophical arguments, counterexamples, and distinctions, may contribute to progress. Finally, we consider the implications of our account for the pressing and contentious question of how much progress has been made in philosophy.

Vocal production learning (vocal learning) is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical, and neurophysiological data from the Egyptian fruit bat (Rousettus aegyptiacus) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.

Purpose Recognising that there is increasing urgency to equip graduates to become future leaders in delivering the SDGs, we present a critical analysis of a whole-institution approach to embedding Education for Sustainable Development (ESD) in curricula. We explore the wider reach of adopting a similar approach within varied professional practices and institutional settings. Approach Our approach is mixed-methods action research framed within a revised institutional strategy. We place this in the wider context of ESD in Higher Education. Findings Embedding ESD in curricula and recognition of its relevance across all disciplines were important to stakeholders. These outcomes translated into strategic commitments. Within the first year of the strategy, Carbon Literacy was embedded in almost 20% of courses and in progress in a further 25%; ESD was embedded in 42% of courses and in progress in a further 7%; and over 80% of students agreed with the statement ‘My course provides me with the opportunities to gain knowledge and skills relating to sustainable development’. Originality This work demonstrates effective measures that can be amplified across the sector, framed by two overarching principles that are effective regardless of context: (1) demonstration that sustainability adds value to academic activities and (2) consultation and co-creation to build a shared vision and support for change.

Objectives: To map and summarise the sports coaches’ and support staff's perspectives on athlete monitoring to explore the breadth of literature, identify knowledge gaps and inform future research. Design: Scoping review based on the Joanna Briggs Institute (JBI) methodology. Methods: SPORTDiscus, MEDLINE, APA PsycInfo, and Embase databases were searched in English until 6 September 2022. The inclusion criteria were (1) coach(es) and/or support staff were explicitly questioned about their knowledge, perceptions, understanding, opinions, and/or applied practice of athlete monitoring; (2) results could be directly attributed to coach(es) and/or support staff; (3) primary research projects that are available as full-text. Exclusion criteria were applied for grey literature. The data were extracted into a custom-made data charting spreadsheet. Results: From the 4381 identified records, 42 met the eligibility criteria. Almost all the studies were conducted within the Anglosphere and at the national or international level. The main reasons for coaches and support staff to implement athlete monitoring were to reduce injury and illness, inform the training program, and improve or maintain performance. While training load monitoring is generally seen as valuable the coaches and support staff acknowledged that there was no perfect scientific approach to monitoring athletes and believed it should be part of the bigger picture, emphasising communication. Conclusions: There has been a recent surge in research demonstrating that athlete monitoring extends beyond quantitative information and encompasses non-quantified subjective information. This further substantiates that coaches and support staff will remain central to athlete monitoring, even amidst the anticipated technological progress.

Background: Community acquired pneumonia (CAP) is a life-threatening lung infection and the most common reason for hospital admission. Both COVID-19 and non-COVID-19 CAP trigger inflammatory and thrombotic host responses driving morbidity and mortality. In non-critically ill patients hospitalized for COVID-19, therapeutic-dose heparin improves survival and reduces intensive care unit (ICU)-level organ support. Antiplatelet agents may also favorably modulate host responses; however, their role in COVID-19 and non-COVID-19 CAP remains uncertain. Objectives: The overall objective was to evaluate the treatment effects and safety of antiplatelet agents and their interactions with therapeutic-dose heparin in CAP. Specifically, we aimed to meta- analyze the effect of antiplatelet agents in non-COVID-19 CAP, and to evaluate the effect of combination antiplatelet agents with therapeutic-dose heparin in COVID-19 CAP. Methods: We conducted a systematic review/meta-analysis of observational studies and randomized controlled trials (RCTs) of hospitalized patients with non-COVID-19 CAP evaluating the effect of antiplatelet agents (ASA or P2Y12 inhibitors) on mortality. We conducted a secondary analysis of the multiplatform trial (mpRCT) to evaluate the effect of combination antiplatelet agents with therapeutic-dose heparin compared to therapeutic-dose heparin alone in COVID-19. Results: We meta-analyzed 13 observational studies and 2 RCTs in our systematic review. In observational studies reporting hazard ratio (HR), antiplatelet agents were associated with lower mortality (HR 0.65, 95% CI 0.46-0.91; I2 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio (aOR), antiplatelet agents were associated with reduced odds of mortality (aOR 0.67, 95% CI 0.45 – 1.00, I2 0%; 2 studies, 24,899 patients). Among RCTs there was a non- significant association with mortality (risk ratio 0.66, 95% CI 0.20 – 2.25; I2 54%, 2 studies, 225 patients). In our secondary analysis of

A synthetic gene drive that targets haplolethal genes on the X chromosome can skew the sex ratio toward males. Like an "X-shredder," it does not involve "homing," and that has advantages including the reduction of gene drive resistance allele formation. We examine this "X-poisoning" strategy by targeting 4 of the 11 known X-linked haplolethal/haplosterile genes of Drosophila melanogaster with CRISPR/Cas9. We find that targeting the wupA gene during spermatogenesis skews the sex ratio so fewer than 14% of progeny are daughters. That is unless we cross the mutagenic males to X^XY female flies that bear attached-X chromosomes, which reverses the inheritance of the poisoned X chromosome so that sons inherit it from their father, in which case only 2% of the progeny are sons. These sex ratio biases suggest that most of the CRISPR/Cas9 mutants we induced in the wupA gene are haplolethal but some are recessive lethal. The males generating wupA mutants do not suffer from reduced fertility; rather, the haplolethal mutants arrest development in the late stages of embryogenesis well after fertilized eggs have been laid. This provides a distinct advantage over genetic manipulation strategies involving sterility which can be countered by the remating of females. We also find that wupA mutants that destroy the nuclear localization signal of shorter isoforms are not haplolethal as long as the open reading frame remains intact. Like D. melanogaster, wupA orthologs of Drosophila suzukii and Anopheles mosquitos are found on X chromosomes making wupA a viable X-poisoning target in multiple species.

On 8 April 2024, tens of millions of people across North America will be able to view a total solar eclipse. Such astronomical events have been important throughout history, but with nearly 10,000 satellites in orbit, we question whether total eclipses will now reveal a sky full of satellites, fundamentally changing this experience for humanity. Using the current population of Starlink satellites, we find that the brightest satellites would be naked-eye visible in dark skies, but the high sky brightness during totality will make them undetectable to the unaided eye. Our model does not take into account the effects of chance reflections from large, flat surfaces like solar panels, which we expect will cause glints and flares that could be visible from large satellites and abandoned rocket bodies. Time-lapse all-sky imaging might reveal satellites during the eclipse., Comment: submitted to RNAAS

Medical errors in clinical text pose significant risks to patient safety. The MEDIQA-CORR 2024 shared task focuses on detecting and correcting these errors across three subtasks: identifying the presence of an error, extracting the erroneous sentence, and generating a corrected sentence. In this paper, we present our approach that achieved top performance in all three subtasks. For the MS dataset, which contains subtle errors, we developed a retrieval-based system leveraging external medical question-answering datasets. For the UW dataset, reflecting more realistic clinical notes, we created a pipeline of modules to detect, localize, and correct errors. Both approaches utilized the DSPy framework for optimizing prompts and few-shot examples in large language model (LLM) based programs. Our results demonstrate the effectiveness of LLM based programs for medical error correction. However, our approach has limitations in addressing the full diversity of potential errors in medical documentation. We discuss the implications of our work and highlight future research directions to advance the robustness and applicability of medical error detection and correction systems.

“Problems of Life and Mind in Late Victorian Speculative Fiction” contributes to the thriving study of literature and science in the Victorian period by presenting three case studies in non-realist literature’s mediation of scientific debates at the end of the nineteenth century. In Arthur Machen’s early Weird tale “The Inmost Light” (1984), H. G. Wells’ science fiction novels The Time Machine (1895) and The Island of Doctor Moreau (1896), and Vernon Lee’s ghost story “Oke of Okehurst” (1884), we find answers to interdisciplinary questions about agency and purpose in human action, biological classification, and our ability to perceive and understand other people. In the second half of the nineteenth century, the emerging sciences of neurology, psychology, and evolution made human bodies newly problematic. These bodies were increasingly understood to be made of atoms and meat, shaped by evolutionary biology and their own histories of sensory experience, and subject to laws of physics and physiology. The texts in this dissertation respond to these limits by imagining alternative realities. Rather than being reconcilable with known natural laws, the worlds of these speculative texts go beyond them: they prompt an imagining of other configurations of natural law, possibilities rather than facts, carrying readers beyond what could be supported or countenanced in scientific discourse. In this way, these texts prompt readers to imagine the shape of solutions for problems that feel irresolvable in consensus reality. In calling these texts “speculative fiction”—rather than the more usual term “Gothic fiction”—I hope to draw attention to their cognitive work. Against a critical tendency to read these genres as ‘anxious’ responses to contemporary science, I argue that they offer creative and critical thought about the structure of the world, the body, and the human mind.

Perception is influenced by predictions about the sensory environment. These predictions are informed by past experience and can be shaped by exposure to recurring patterns of sensory stimulation. Predictions can enhance perception of a predicted stimulus, but they can also suppress it by favoring novel and unexpected sensory information that is inconsistent with the predictions. Here we employed statistical learning to assess the effects of exposure to consistent sequences of oriented gratings on subsequent visual perceptual selection, as measured with binocular rivalry. Following statistical learning, the first portion of a learned sequence of stimulus orientations was presented to both eyes, followed by simultaneous presentation of the next grating in the sequence to one eye and an orthogonal unexpected orientation to the other eye. We found that subjects were more likely to perceive the grating that matched the orientation that was consistent with the predictive context. That is, observers were more likely to see what they expected to see, compared to the likelihood of perceiving the unexpected stimulus. Some other studies in the literature have reported the opposite effect of prediction on visual perceptual selection, and we suggest that these inconsistencies may be due to differences across studies in the level of the visual processing hierarchy at which competing perceptual interpretations are resolved.

This report presents information obtained from three questions on the U.S. Census 2000 long form about coresident grandparents, focusing on data from people over age 29 years. Results indicated that the percentage of coresident grandparents varied sharply by race and Hispanic origin. More than half of American Indian and Alaska Native coresident grandparents and black coresident grandparents were responsible for their grandchildren. Younger grandparents were more likely to be responsible for their grandchildren. The west had the highest percentage of coresident grandparents. Counties in the midwest had some of the lowest coresident grandparent percentages. At the state level, Hawaii had the highest percentage of grandparents living with grandchildren, and North Dakota had the lowest. For many grandparent caregivers, this responsibility was a long-term commitment. San Diego, California, had the lowest percentage of coresident grandparents among the 10 largest cities in the United States. Of the 5.8 million coresident grandparents in 2000, 64 percent were women. Nearly all of grandparent caregivers were either the householder or the spouse of the householder. Nearly 20 percent of grandparent caregivers had incomes below the poverty level. (SM)

This book discusses several types of parent-teacher conferences and issues relevant to parent-teacher conferences in 10 chapters. Chapter 1 outlines a working model for successful parent-teacher conferences. Research on parent attitudes and relationships with teachers is summarized in chapter 2. Chapter 3 discusses communication topics, including listening skills, ways to respond to parents, ways to clarify messages, and body language. Chapter 4 examines the changing structure of the family. Chapters 5 through 7 describe characteristics of conferences that relate to academic performance, referrals for handicapped children, and discipline problems. Conflicts between parents and teachers are examined in chapter 8. Chapter 9 considers unsuccessful conferences and conferences without planned agendas. The final chapter promotes the development of partnerships between parents and teachers. Many of the issues raised in the 10 chapters are illustrated with vignettes. Appendixes include a conference evaluation checklist, a vignette of a conference dealing with a discipline problem, a set of role-playing activities, and a list of suggestions for facilitating conflict resolution. A 68-item bibliography and a 31-item resource list are provided. (BC)

This book is designed to provide a foundation in adult learning theory, a knowledge base that will increase understanding of what works and what does not work with the adult learner. It is written for practitioners who work with adults in nearly any setting. The book is both theoretical and practical. It provides a foundation in adult learning ideas and strategies based on research and personal experience, along with practical strategies for implementation. Chapter 1 discusses the purposes of educating adults and the underlying philosophies of adult education. Chapter 2 examines the various and diverse attributes of adult participants. How adults learn is explored in Chapter 3. Chapter 4 discusses theories of adult development. The last two chapters on facilitating adult learning and putting it all together provide important strategies and guidelines for effective practice. Within each chapter are found theoretical information, steps to review one's own experience, and implementation strategies that can be adapted to unique educational settings. Exercises are provided at the end of the chapters to enable readers to explore their own experiences. Appendixes include lists of 30 references, 5 needs assessment resources, and 5 learning styles resources; 9 principles of adult education; and a form to evaluate this book. (YLB)

Between 1989 and 2004, Noah Purifoy constructed over one hundred large-scale sculptures that intersect earth art, assemblage, and architecture spread out across a ten-acre parcel of land in Joshua Tree, California. His works are primarily made from locally discarded and repurposed industrial materials that create a site-specific dialogue with their environment. Across space and time, these constructions have culminated in his Outdoor Desert Art Museum. For several decades, he worked as an artist, educator, and administrator throughout Southern California until the rising cost of living prompted him to relocate to the high desert at 72 years old until his death. In effect, scholars have located Purifoy within the discourses of Black Art, socially engaged art, and the postwar Los Angeles art scene regarding his early bodies of work made in the aftermath of the 1965 Watts Rebellion; however, few have written in-depth about his late works. Perhaps this is because his site is not easily categorizable- his constructions sprawl out across the vast desert floor, decentered into various pockets of experiences. Some works recall Purifoy’s past, while others suggest references to modernist art and design, the African diaspora, and African American identities; other works play with commercial graphics and language, defunct technology, labor, and consumerist surplus. Because of the plurality of meanings that emanate from his works, this project examines how Purifoy’s site operates as a re-spatialization of personal and collective narratives through the juxtaposition of material objects to realize potential futures. Furthermore, this project focuses on three particular works: Bessemer Steel, No Contest (bicycles), and Adrian’s Little Theater, as exemplary case studies to examine the real-life implications of space, place, and perspective through compositional forms. In the wake of the current weaponization of critical race theory and education, oppressive policymaking, racialized

Aim: After environmental disasters, species with large population losses may need urgent protection to prevent extinction and support recovery. Following the 2019–2020 Australian megafires, we estimated population losses and recovery in fire-affected fauna, to inform conservation status assessments and management. Location: Temperate and subtropical Australia. Time period: 2019–2030 and beyond. Major taxa: Australian terrestrial and freshwater vertebrates; one invertebrate group. Methods: From > 1,050 fire-affected taxa, we selected 173 whose distributions substantially overlapped the fire extent. We estimated the proportion of each taxon’s distribution affected by fires, using fire severity and aquatic impact mapping, and new distribution mapping. Using expert elicitation informed by evidence of responses to previous wildfires, we estimated local population responses to fires of varying severity. We combined the spatial and elicitation data to estimate overall population loss and recovery trajectories, and thus indicate potential eligibility for listing as threatened, or uplisting, under Australian legislation. Results: We estimate that the 2019–2020 Australian megafires caused, or contributed to, population declines that make 70–82 taxa eligible for listing as threatened; and another 21–27 taxa eligible for uplisting. If so-listed, this represents a 22–26% increase in Australian statutory lists of threatened terrestrial and freshwater vertebrates and spiny crayfish, and uplisting for 8–10% of threatened taxa. Such changes would cause an abrupt worsening of underlying trajectories in vertebrates, as measured by Red List Indices. We predict that 54–88% of 173 assessed taxa will not recover to pre-fire population size within 10 years/three generations. Main conclusions: We suggest the 2019–2020 Australian megafires have worsened the conservation prospects for many species. Of the 91 taxa recommended for listing/uplisting consideration, 84 are now under formal review

Aim After environmental disasters, species with large population losses may need urgent protection to prevent extinction and support recovery. Following the 2019–2020 Australian megafires, we estimated population losses and recovery in fire-affected fauna, to inform conservation status assessments and management. Location Temperate and subtropical Australia. Time period 2019–2030 and beyond. Major taxa Australian terrestrial and freshwater vertebrates; one invertebrate group. Methods From > 1,050 fire-affected taxa, we selected 173 whose distributions substantially overlapped the fire extent. We estimated the proportion of each taxon’s distribution affected by fires, using fire severity and aquatic impact mapping, and new distribution mapping. Using expert elicitation informed by evidence of responses to previous wildfires, we estimated local population responses to fires of varying severity. We combined the spatial and elicitation data to estimate overall population loss and recovery trajectories, and thus indicate potential eligibility for listing as threatened, or uplisting, under Australian legislation. Results We estimate that the 2019–2020 Australian megafires caused, or contributed to, population declines that make 70–82 taxa eligible for listing as threatened; and another 21–27 taxa eligible for uplisting. If so-listed, this represents a 22–26% increase in Australian statutory lists of threatened terrestrial and freshwater vertebrates and spiny crayfish, and uplisting for 8–10% of threatened taxa. Such changes would cause an abrupt worsening of underlying trajectories in vertebrates, as measured by Red List Indices. We predict that 54–88% of 173 assessed taxa will not recover to pre-fire population size within 10 years/three generations. Main conclusions We suggest the 2019–2020 Australian megafires have worsened the conservation prospects for many species. Of the 91 taxa recommended for listing/uplisting consideration, 84 a

Unruh--DeWitt (UDW) detectors implemented as UDW quantum gates provide a framework for evaluating quantum Shannon theory properties of qubit-field systems. UDW quantum channels consist of qubits encoding/decoding quantum information onto/off of quantum fields. With the controlled unitary structure of UDW gates, the encoding/decoding process happens on the diagonals of the coherent state density matrix describing the field. However, given the non-orthogonality of coherent states the output of UDW channels consists of unwanted states and unwanted mixing of states that lower the channel capacity. In idealized models, these appear in the off-diagonals and diagonals of the field's density matrix in the coherent state basis. For this reason, we show that UDW quantum channels have an unexpected representation as certain bosonic dephasing channels with dephasing parameters captured by a combination of the coupling, smearing, and switching functions of the UDW detector model. We demonstrate the unexpected consequence that a larger dephasing parameter results in higher channel capacity and helps alleviate unwanted state mixing. We illustrate these properties through two examples: inserting an additional ideal dephasing channel into the quantum channel and inserting cross-talk noise via a third UDW gate. Remarkably, the cross-talk noise channel qualitatively improves a lower bound on the quantum capacity suggesting UDW gates will have unexpected performance improvements if realized in condensed matter experiments., Comment: 8 pages, 3 figures

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues. Applying TACIT to associate motor cortex and parvalbumin-positive interneuron enhancers with neurological phenotypes revealed dozens of enhancer-phenotype associations, including brain size-associated enhancers that interact with genes implicated in microcephaly or macrocephaly. TACIT provides a foundation for identifying enhancers associated with the evolution of any convergently evolved phenotype in any large group of species with aligned genomes.

BACKGROUND: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated. OBJECTIVES: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured. RESULTS: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017). CONCLUSIONS: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care.

Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06

The paper presents a detailed analysis of employment relations in the NHS, as the Service emerges from the pandemic and into a ‘new normal’. Working with the Healthcare People Management Association and CMP Solutions, the study is based on 229 survey responses and 22 in-depth interviews with HR leaders, senior practitioners and union representatives. In assessing the potential efficacy of a culture change, key findings include concern over: the capability and capacity of line managers; the key role of HR; staff wellbeing; ways of more effectively managing conflict, where relationship and personal issues figure high as significant reasons for workplace disputes

Item does not contain fulltext, IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital surv

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Pesticides with novel modes of action including neonicotinoids and anthranilic diamides are increasingly detected in global surface waters. Little is known about how these pesticides of concern interact in mixtures at environmentally relevant concentrations, a common exposure scenario in waterways impacted by pesticide pollution. We examined effects of chlorantraniliprole (CHL) and imidacloprid (IMI) on the sensitive invertebrate, Daphnia magna. Exposures were first performed using surface waters known to be contaminated by agricultural runoff. To evaluate the seasonal variation in chemical concentration and composition of surface waters, we tested surface water samples taken at two time points: during an extended dry period and after a first flush storm event. In surface waters, the concentrations of CHL, IMI, and other pesticides of concern increased after first flush, resulting in hypoactivity and dose-dependent photomotor responses. We then examined mortality and behavior following single and binary chemical mixtures of CHL and IMI. We detected inverse photomotor responses and some evidence of synergistic effects in binary mixture exposures. Taken together, this research demonstrates that CHL, IMI, and contaminated surface waters all cause abnormal swimming behavior in D. magna. Invertebrate swimming behavior is a sensitive endpoint for measuring the biological effects of environmental pesticides of concern.

DNA-encoded libraries (DELs) provide the means to make and screen millions of diverse compounds against a target of interest in a single experiment. However, despite producing large volumes of binding data at a relatively low cost, the DEL selection process is susceptible to noise, necessitating computational follow-up to increase signal-to-noise ratios. In this work, we present a set of informatics tools to employ data from prior DEL screen(s) to gain information about which building blocks are most likely to be productive when designing new DELs for the same target. We demonstrate that similar building blocks have similar probabilities of forming compounds that bind. We then build a model from the inference that the combined behavior of individual building blocks is predictive of whether an overall compound binds. We illustrate our approach on a set of three-cycle OpenDEL libraries screened against soluble epoxide hydrolase (sEH) and report performance of more than an order of magnitude greater than random guessing on a holdout set, demonstrating that our model can serve as a baseline for comparison against other machine learning models on DEL data. Lastly, we provide a discussion on how we believe this informatics workflow could be applied to benefit researchers in their specific DEL campaigns.

Fouling of polyamide membranes during reverse osmosis (RO) is a major challenge for adopting membrane technologies to treat highly contaminated waters, especially those containing organic foulants (e.g., natural organic matter (NOM), polysaccharides) and dominant cations (e.g., sodium, magnesium, calcium). This work combines bench-scale membrane fouling experiments with detailed characterization of feedwater chemistry and fouling layer composition/morphology to reveal fundamental mechanisms of (in)organic fouling during RO. Divalent cations are shown to promote fouling by hydrophobic NOM containing aromatic and carboxyl groups, while NOM fouling in the presence of a monovalent cation, sodium, occurs by smaller fulvic acids containing larger fractions of carboxyl groups and other oxygen-rich moieties. Calcium-carboxyl bridging occurs in solution and near the membrane surface to induce NOM aggregation on nanometer length scales. In complex waters containing foulant mixtures, co-fouling by calcium-carboxyl bridging and CaCO3 precipitation influence membrane performance at longer timeframes. However, the flux decline observed for the co-fouling mechanism was less significant than the sum of its parts, suggesting both synergistic and antagonistic fouling mechanisms should be considered in membrane design/operation. These results encourage the design of pretreatment processes to reduce concentrations of multivalent ions and hydrophobic NOM in RO feedwaters, and of membrane materials to limit attachment/deposition of aggregates to/on polyamide surfaces.

Thousands of genomic regions have been associated with heritable human diseases, but attempts to elucidate biological mechanisms are impeded by an inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function, agnostic to cell type or disease mechanism. Single-base phyloP scores from 240 mammals identified 3.3% of the human genome as significantly constrained and likely functional. We compared phyloP scores to genome annotation, association studies, copy-number variation, clinical genetics findings, and cancer data. Constrained positions are enriched for variants that explain common disease heritability more than other functional annotations. Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues. Applying TACIT to associate motor cortex and parvalbumin-positive interneuron enhancers with neurological phenotypes revealed dozens of enhancer-phenotype associations, including brain size-associated enhancers that interact with genes implicated in microcephaly or macrocephaly. TACIT provides a foundation for identifying enhancers associated with the evolution of any convergently evolved phenotype in any large group of species with aligned genomes.

RationaleMitigating the spread of COVID-19 requires that people understand the need for and engage in protective behaviors. Given the complexity and rapid progression of media information about the pandemic, health literacy could be essential to acquiring the accurate beliefs, concern for societal risks, and appreciation of restrictive policies needed to motivate these behaviors. Yet with the increasingly politicized nature of COVID-related issues in the United States, health literacy could be an asset for those with more liberal views but less so for those with more conservative views.ObjectiveThis study tested a hypothesized model proposing that political views moderate the associations of health literacy with COVID-19 protective behaviors as well as the mediational roles of accurate and inaccurate COVID-19 beliefs, concern for society, and governmental control attitudes.MethodsWe surveyed residents in three diverse regions of California in June 2020 (N = 669) and February 2021 (N = 611). Participants completed measures of health literacy, political views, and COVID-19 beliefs and behaviors.ResultsModerated mediational analyses largely supported the proposed model with both samples. Health literacy was associated with more accurate COVID-19 beliefs, less inaccurate COVID-19 beliefs, greater concern for societal risks, more positive attitudes regarding restrictive government control, more protective behavior, less risky behavior, and stronger vaccine intentions; beliefs, concern for society, and governmental control attitudes mediated the health literacy-behavior relationships. As predicted, however, these associations of health literacy with adaptive beliefs, attitudes, and behaviors varied according to political views. The direct and mediated relationships were held for participants with more liberal views and, to a lesser extent, for those with moderate views, but they were weaker or absent for participants with more conservative views.Conclu

The purpose of this qualitative study was to explore the experiences adults have with forgiveness in healing from interpersonal childhood trauma. Forgiveness is a phenomenon often talked about in research and healing modalities. This study utilized a qualitative interview approach to explore how adult survivors of interpersonal trauma in childhood think about and integrate forgiveness into their healing journey. Research participants included 15 individuals who are between 25 and 45 years of age and self-identified as having experienced interpersonal trauma during their childhood. In-depth interviews were conducted to explore how each individual feels about forgiveness and how they might have integrated forgiveness into their healing from the trauma they experienced as children. Further, this study explored how the experience of forgiveness in their healing journey has impacted or changed the experience of trauma symptoms in their lives. The themes derived from the data collected in interviews included letting go, actualized forgiveness, and self-compassion. Findings presented a better understanding of the impact of the definition of forgiveness an individual internalizes, implications for practice, and the need for future research to follow up on this study and potentially focus on male perspectives.

Through our work to examine mathematical and computational learning in authentic and convivial contexts that requires creativity, imagination, reasoning, and discourse, we have theorized an experiential learning cycle that attends to the development of voice, agency, and identity needed in young people for an earned insurgency—the right to demand change. Our work underscores how the current situation that many students face in classrooms amounts to a type of cognitive segregation that denies these students access to authentic and empowering intellectual agency. By facilitating a process whereby students, using their own creative and imaginative means, intentionally develop a type of ownership over the exploration and application of the mathematical concepts they are being taught, we help students move from simple surface level, syntactic understandings, to deeper semantic learning that is more personally significant and meaningful., Através do nosso trabalho para examinar a aprendizagem matemática e computacional em contextos autênticos e conviviais que requerem criatividade, imaginação, raciocínio e discurso, teorizamos um ciclo de aprendizagem experiencial que atende ao desenvolvimento da voz, agência e identidade necessários nos jovens para uma insurgência conquistada—o direito de exigir mudanças. Nosso trabalho ressalta como a situação atual que muitos alunos enfrentam nas salas de aula equivale a um tipo de segregação cognitiva que nega a esses alunos o acesso a uma agência intelectual autêntica e capacitadora. Ao facilitar um processo pelo qual os alunos, usando seus próprios meios criativos e imaginativos, desenvolvem intencionalmente um tipo de propriedade sobre a exploração e aplicação dos conceitos matemáticos que estão sendo ensinados, ajudamos os alunos a passar de um nível de superfície simples, entendimentos sintáticos, para um entendimento semântico mais profundo. aprendizagem que é mais pessoalmente significativa., A través de nuestro trabajo para examinar el aprendizaje matemático y computacional en contextos auténticos y agradables que requieren creatividad, imaginación, razonamiento y discurso, hemos teorizado un ciclo de aprendizaje experiencial que atiende al desarrollo de la voz, la agencia y la identidad necesarias en los jóvenes para un insurgencia ganada—el derecho a exigir cambios. Nuestro trabajo subraya cómo la situación actual que enfrentan muchos estudiantes en las aulas equivale a un tipo de segregación cognitiva que niega a estos estudiantes el acceso a una agencia intelectual auténtica y empoderadora. Al facilitar un proceso mediante el cual los estudiantes, usando sus propios medios creativos e imaginativos, desarrollan intencionalmente un tipo de propiedad sobre la exploración y aplicación de los conceptos matemáticos que se les están enseñando, ayudamos a los estudiantes a pasar de un nivel superficial simple, comprensión sintáctica, a una comprensión semántica más profunda. aprendizaje que es más personalmente significativo y significativo.

The Near-Earth Object (NEO) Surveyor mission is a NASA observatory designed to discover and characterize near-Earth asteroids and comets. The mission's primary objective is to find the majority of objects large enough to cause severe regional impact damage ($>$140 m in effective spherical diameter) within its five-year baseline survey. Operating at the Sun-Earth L1 Lagrange point, the mission will survey to within 45 degrees of the Sun in an effort to find the objects in the most Earth-like orbits. The survey cadence is optimized to provide observational arcs long enough to reliably distinguish near-Earth objects from more distant small bodies that cannot pose an impact hazard. Over the course of its survey, NEO Surveyor will discover $\sim$200,000 - 300,000 new NEOs down to sizes as small as $\sim$10 m and thousands of comets, significantly improving our understanding of the probability of an Earth impact over the next century., Comment: accepted to PSJ