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Systemic sclerosis (SSc) is a rare, chronic autoimmune disorder associated with disability, diminished physical function, fatigue, pain, and mental health concerns. We assessed minimal detectable changes (MDCs) of the Health Assessment Questionnaire–Disability Index (HAQ‐DI), Patient‐Reported Outcomes Measurement Information System‐29 Profile version 2.0 (PROMIS‐29v2.0) domains, and Patient Health Questionnaire (PHQ)‐8 in people with SSc. Scleroderma Patient‐Centered Intervention Network Cohort participants completed the HAQ‐DI, PROMIS‐29v2.0 domains, and PHQ‐8 at baseline assessments from April 2014 until August 2023. We estimated MDC95 (smallest change that can be detected with 95% certainty) and MDC90 (smallest change that can be detected with 90% certainty) with 95% confidence intervals (CIs) generated via the percentile bootstrapping method resampling 1,000 times. We compared MDC estimates by age, sex, and SSc subtype. A total of 2,571 participants were included. Most were female (n = 2,241; 87%), and 38% (n = 976) had diffuse SSc. Mean (±SD) age was 54.9 (±12.7) years and duration since onset of first non‐Raynaud phenomenon symptom was 10.8 (±8.7) years. MDC95 estimate was 0.41 points (95% CI 0.40–0.42) for the HAQ‐DI, between 4.88 points (95% CI 4.72–5.05) and 9.02 points (95% CI 8.80–9.23) for the seven PROMIS‐29v2.0 domains, and 5.16 points (95% CI 5.06–5.26) for the PHQ‐8. MDC95 estimates were not materially different across subgroups. MDC95 and MDC90 estimates were precise and similar across age, sex, and SSc subtype groups. HAQ‐DI MDC95 and MDC90 were substantially larger than previous estimates of HAQ‐DI minimal important difference from several small studies. Minimally important differences of all measures should be evaluated in large studies using anchor‐based methods.

Dietary restriction (DR) and hypoxia (low oxygen) extend lifespan in Caenorhabditis elegansthrough the induction of a convergent downstream longevity gene, fmo-2. Flavin-containing monooxygenases (FMOs) are highly conserved xenobiotic-metabolizing enzymes with a clear role in promoting longevity in nematodes and a plausible similar role in mammals. This makes them an attractive potential target of small molecule drugs to stimulate the health-promoting effects of longevity pathways. Here, we utilize an fmo-2fluorescent transcriptional reporter in C. elegansto screen a set of 80 compounds previously shown to improve stress resistance in mouse fibroblasts. Our data show that 19 compounds significantly induce fmo-2, and 10 of the compounds induce fmo-2more than twofold. Interestingly, 9 of the 10 high fmo-2inducers also extend lifespan in C. elegans. Two of these drugs, mitochondrial respiration chain complex inhibitors, interact with the hypoxia pathway to induce fmo-2, whereas two dopamine receptor type 2 (DRD2) antagonists interact with the DR pathway to induce fmo-2, indicating that dopamine signaling is involved in DR-mediated fmo-2induction. Together, our data identify nine drugs that each (1) increase stress resistance in mouse fibroblasts, (2) induce fmo-2in C. elegans, and (3) extend nematode lifespan, some through known longevity pathways. These results define fmo-2induction as a viable approach to identifying and understanding mechanisms of putative longevity compounds.

The article discusses Walter Pater's analysis of an engraving by Alphonse Legros, emphasizing the interplay between form and content in art. It also explores Pietro Aretino's detailed description of the sky in Venice, drawing parallels between nature and art. The text delves into the philosophical implications of aesthetic experiences and the transition towards abstraction in art, highlighting the influence of Pater's ideas on abstract painting. The author, David Carrier, is a philosopher and art critic, known for his work on aesthetics and abstract art. [Extracted from the article]

The article discusses the differences between Venetian art and American art, highlighting how art in Venice often affirmed societal values, while American art tends to be politically critical. Venetian art was influenced by the Catholic state and supported the Republic's goals, while American art often critiques societal institutions. The article also explores the challenges of multicultural societies like the United States in finding unity through art, contrasting it with the more homogeneous Venetian Republic. Additionally, it delves into the philosophical implications of displaying art from monocultural societies in multicultural settings like museums. [Extracted from the article]

The article discusses the birth of modernism in European art, contrasting it with the old master sacred tradition. It highlights the importance of secular subjects, art marketplaces, art critics, and industrial production in defining modernism. The author argues that the Venetian art world of the 18th century, exemplified by Canaletto's work, satisfies all the defining conditions of modernism, even though it was considered a premature innovation due to the lack of a lively art market economy in Venice. The text suggests reevaluating the origins of modernism, considering Venice as a potential birthplace alongside Paris and New York. [Extracted from the article]

The article from CounterPunch titled "Bill Beckley: A Perfect Friendship" by David Carrier reflects on the author's close relationship with conceptual artist Bill Beckley. Beckley, born in 1946, was a prominent figure in the New York art scene, known for his narrative art and aesthetic sensibilities. The article highlights Beckley's influence on the author's work, particularly in relation to a breakthrough in his book about Naples inspired by Beckley's exhibition in the city. The piece pays tribute to Beckley's legacy and impact on the author's life and work, emphasizing their shared love of art and Naples. [Extracted from the article]

Bridging Integrator 1 (BIN1) is the second most important Alzheimer’s disease (AD) risk gene, but its physiological roles in neurons and its contribution to brain pathology remain largely elusive. In this work, we show that BIN1plays a critical role in the regulation of calcium homeostasis, electrical activity, and gene expression of glutamatergic neurons. Using single-cell RNA-sequencing on cerebral organoids generated from isogenic BIN1wild type (WT), heterozygous (HET) and homozygous knockout (KO) human-induced pluripotent stem cells (hiPSCs), we show that BIN1is mainly expressed by oligodendrocytes and glutamatergic neurons, like in the human brain. Both BIN1HET and KO cerebral organoids show specific transcriptional alterations, mainly associated with ion transport and synapses in glutamatergic neurons. We then demonstrate that BIN1cell-autonomously regulates gene expression in glutamatergic neurons by using a novel protocol to generate pure culture of hiPSC-derived induced neurons (hiNs). Using this system, we also show that BIN1plays a key role in the regulation of neuronal calcium transients and electrical activity via its interaction with the L-type voltage-gated calcium channel Cav1.2. BIN1KO hiNs show reduced activity-dependent internalization and higher Cav1.2expression compared to WT hiNs. Pharmacological blocking of this channel with clinically relevant doses of nifedipine, a calcium channel blocker, partly rescues electrical and gene expression alterations in BIN1KO glutamatergic neurons. Further, we show that transcriptional alterations in BIN1KO hiNs that affect biological processes related to calcium homeostasis are also present in glutamatergic neurons of the human brain at late stages of AD pathology. Together, these findings suggest that BIN1-dependent alterations in neuronal properties could contribute to AD pathophysiology and that treatment with low doses of clinically approved calcium blockers should be considered as an option to slow disease-onset and progression.

The article discusses the development of new U.S. nuclear weapons and their implications. Topics include the construction of new plutonium pits for the W87-1 warhead, the planned deployment of this warhead on the Sentinel missile to replace older Minuteman III missiles, and the significant investment in the U.S. Nuclear Security Enterprise, reflecting a substantial commitment to modernizing the nation's nuclear arsenal.

The article reports on the continued protest in the U.S. for nuclear weapons freeze and disarmament. Focus is given on the Students for Nuclear Disarmament founded by high school student Rishi Gurudevan. A number of factors for nuclear silence are cited by historians and activists including the 1996 Comprehensive Test Ban Treaty and the 2010 New START Treaty. It highlights the growing awareness and activism that support the abolition of nuclear weapons.

ABSTRACTOcean models, such as the Navy Coastal Ocean Model (NCOM), rely on ocean observations through data assimilation to predict the evolution of ocean phenomena accurately. The accuracy is highly dependent on the type and quantity of observations available. This work attempts to examine the impact of spatially dense in-situ profile observations on the forecasts of mixed layer depth (MLD) and thermocline depth (TD), using a three-dimensional variational data assimilation algorithm. To do this, a twin data assimilation experiment is used to simulate the impact of float deployments on the forecast of MLD and TD in a specific area of interest (AOI) of the North Atlantic. It is found that during the northern hemisphere summer the model MLD is sensitive to the sea surface temperature (SST) observations rather than the profiling floats. TD is more strongly impacted by the assimilation of float observations, and the experiment with the most floats produces the best results. During the northern hemisphere winter the profiling floats have a greater impact on the model simulation of MLD. Finally, the overall lack of substantial improvement in the winter months for the highest density of profiling floats is determined to be due to the data assimilation methodology itself.

This article discusses the Museum of Modern Art (MoMA) in New York City and its role in the art world. The author acknowledges the strengths of MoMA's collection but also expresses ambivalence about its current overcrowded and expensive setting. They argue that the high admission prices and crowded galleries reflect the gentrification of New York City and the success of art education. The article also explores how MoMA is revising its modernist canon and responding to contemporary political and intellectual developments. The author praises MoMA for its efforts to display modernist and contemporary art from diverse perspectives, but also acknowledges the need for ongoing changes and revisions in the art world. [Extracted from the article]

This article, titled "In Praise of Editors: A Philosophical Argument," discusses the importance of editors in the writing process. The author argues that editors play a crucial role in improving the clarity and coherence of an author's thoughts. They bridge the gap between what the author intends to say and what is actually written, ensuring consistency and accuracy. The article also explores the idea that writing, like other creative activities, benefits from the participation of an audience. The author suggests that editors should be recognized and valued for their contributions, and highlights the gender dynamics in the field of editing. [Extracted from the article]

This article discusses the radical innovations of three artists: Caravaggio, Andy Warhol, and Keith Haring. Despite initial criticism, these artists created new works that challenged traditional notions of art. The article emphasizes the importance of understanding the cultural context in which these artists worked, as their entry points into the art world greatly influenced their success. Additionally, the article highlights the need for art critics to respond quickly to innovative work and prepare the public to understand it. [Extracted from the article]

We conducted a systematic review and network meta-analyses evaluating the effects of different intraoperative vasoactive drugs on acute kidney injury (AKI) and other perioperative outcomes in adult liver transplant recipients. We searched multiple electronic databases using words from the “liver transplantation” and “vasoactive drug” domains. We included all randomized controlled trials conducted in adult liver transplant recipients comparing 2 different intravenous vasoactive drugs or 1 against a standard of care that reported AKI, intraoperative blood loss, or any other postoperative outcome. We conducted 4 frequentist network meta-analyses using random effect models, based on the interventions’ mechanism of action, and evaluated the quality of evidence (QoE) using Grading of Recommendations, Assessment, Development, and Evaluations recommendations. We included 9 randomized controlled trials comparing different vasopressor drugs (vasoconstrictor or inotrope), 3 comparing a somatostatin infusion (or its analogues) to a standard of care, 11 comparing different vasodilator infusions together or against a standard of care, and 2 comparing vasoconstrictor boluses at graft reperfusion. Intravenous clonidine was associated with shorter duration of mechanical ventilation, intensive care unit, and hospital length of stay (very low QoE), and some vasodilators were associated with lower creatinine level 24 h after surgery (low to very low QoE). Phenylephrine and terlipressin were associated with less intraoperative blood loss when compared with norepinephrine (low and moderate QoE). None of the vasoactive drugs improve any other postoperative outcomes, including AKI. There is still important equipoise regarding the best vasoactive drug to use in liver transplantation for most outcomes. Further studies are required to better inform clinical practice.

ABSTRACTThe current study explores differences in transfer shock between veteran and non-veteran community college transfer students at a land grant institution in a rural state. Analysis includes institutional data for community college transfer students, including those who self-identified as veterans or used veteran tuition benefits from Fall 2015 to Spring 2022. Many of these students held marginalized identities in other categories such as nontraditional age. Overall, all community college transfer students in the sample experienced a decrease in mean GPA in their first university semester. Veteran and non-veteran community college transfer students did not experience significantly different levels of transfer shock. However, veteran community college transfer students showed little evidence of transfer shock overall and performed better on average than both their nontraditional and traditional nonveteran student counterparts after transferring.

Les lésions hautes du nerf médian sont connues pour leurs difficultés de récupération motrice distale, en particulier au niveau des muscles thénariens responsables de l’opposition et de l’antépulsion du pouce. Le palmaris brevis (PB) est un muscle peaucier de l’éminence hypothénar innervé par le nerf ulnaire. Les branches motrices du PB sont le plus souvent issues du nerf digital ulnaire du cinquième doigt. Le but de cette étude est d’évaluer la faisabilité du transfert de la branche motrice du PB (PBMB) sur la branche récurrente thénarienne du nerf médian (TMB) pour la réanimation précoce de l’opposition et de l’antépulsion du pouce dans les lésions hautes du nerf médian, par une étude préliminaire cadavérique.

This article, written by David Carrier, reflects on his collaboration with art historian Mark Roskill and the importance of collaboration in academia. Carrier describes how he reached out to Roskill for guidance and how their friendship and collaboration developed over time. He highlights Roskill's generosity, open-mindedness, and intellectual flexibility, which made him an ideal collaborator. Carrier also discusses his later collaborations with other individuals and emphasizes the value of collaboration in producing unique and fruitful results. The article concludes by emphasizing the importance of recognizing and praising the contributions of individuals and their work in our culture. [Extracted from the article]

Cancer and atrial fibrillation (AF) are common concurrent disorders. Direct oral anticoagulants (DOACs) are prescribed to prevent stroke in patients with AF. Patients with cancer often undergo invasive procedures for diagnostic or therapeutic purposes, necessitating interruption of anticoagulation. There are limited data to guide best periprocedural anticoagulation management practices in the setting of active cancer.

Patients with cancer commonly require a central venous catheter, which is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear.

The article discusses whether charitable donations should be tax deductible. The argument against tax deductions for charitable donations is that they largely benefit wealthy individuals and corporations, reducing money that could go to public coffers and support effective policies. Additionally, research shows that monetary rewards can have negative effects on people's motivation to donate. On the other hand, the argument in favor of tax deductions is that they incentivize donations and increase the amount of charity. The tax credit is shown to be treasury-efficient and benefits are largely passed on to charities. The article also addresses concerns about relying on charities to provide goods and services that the government should provide. Ultimately, the decision on whether to support donations through the tax system depends on perspectives on equity, government intervention, and the effectiveness of incentives. [Extracted from the article]

The article discusses the importance of art museums in understanding society and cultural continuity. It highlights how art museums have expanded their canons to include a diverse range of artworks from different cultures and time periods. The author argues that canonical artworks have permanent value and serve as stabilizing institutions in a changing world. The article also mentions recent revisions to the permanent European collection at the Metropolitan Museum of Art, which incorporate works from the colonies of Spain and depict Black people in European artworks. The author acknowledges that change can be disconcerting but emphasizes the importance of embracing radical change in order to maintain cultural relevance. [Extracted from the article]

The article discusses the role of public intellectuals in academia and their impact on society. It highlights the work of philosophers such as John Dewey, Jean-Paul Sartre, Simone de Beauvoir, Jacques Derrida, and Michel Foucault, who made claims that were relevant to diverse social and political concerns. The author also explores the idea of philosophy as an impersonal activity, with philosophers like Descartes, Kant, and Danto presenting arguments that are universally valid. However, Alexander Nehamas challenges this view by examining the philosophical tradition concerned with the art of living, as exemplified by Socrates, Montaigne, Nietzsche, and Foucault. The article concludes by suggesting that Nehamas' books may have the potential to change readers' lives. [Extracted from the article]

ABSTRACTCommunity colleges often employ measures to determine student course placement. Though much research has examined the predictive validity of placement measures such as ACT or high-school GPA, little research examines the effects of students’ traditional and non-traditional status. Using data from a rural state community college, we examined the predictability of high-school GPA and ACT scores on college GPA and passing math and English courses. The results confirm previous research that finds high-school GPA to predict better than other placement measures. The results from the analyses of traditional and non-traditional students add to the placement literature by suggesting that the number of years between high-school graduation and community college attendance also affects overall success. This signifies that the number of years since a student graduated high school should be factored into placement decisions.

ABSTRACTA combination of nesting and data assimilation setups is explored for lowering analysis and forecast errors in a regional operational ocean model. Original downscaling from the global model and applying 3dVar to a regional model produce unacceptably high errors. The latter are reduced by the introduction of an intermediate assimilative nest with 3dVar and 4dVar assimilations, and by the use of 4dVar assimilation in the regional model. It is found that if only 3dVar assimilation is available, then the intermediate assimilative nest is necessary for lowering errors in the regional model. Alternatively, 4dVar assimilation can be used directly in the regional model or in the intermediate nest. Errors in the regional 3dVar nested in the intermediate 4dVar assimilative nest are comparable to regional 4dVar. Although the latter has lowest errors, there is value in the former, because the intermediate nest could encompass several regional models.

ABSTRACTeSports is an increasingly visible part of our popular culture and is becoming both a financial and technological force. In higher education, community colleges are rapidly developing eSports programs for a variety of reasons, including increasing student engagement to developing alumni relationships. Although some discussion exists in sports management, economics, psychology and legal literature, there appears to be little work dedicated to eSports in the literature of community college studies. This study draws upon the small base of literature on eSports beyond community college studies and presents an example of a recently emerging eSports program at one rural community college in the mountain western U.S. A look forward on eSports is provided by noting breaking issues, trends, and proposals for a research agenda for scholars and practitioners in community college studies.

Purpose: While there is limited patient-centred evidence (i.e., evidence that is important for patients and end-users) to inform the use of pharmacologic opioid minimization strategies (i.e., the use of opioid alternatives) for adult surgical patients requiring general anesthesia, such strategies are increasingly being adopted into practice. Our objectives were to describe anesthesiologists’ beliefs regarding intraoperative opioid minimizing strategies use and utility, and to explore important clinical decision-making factors. Methods: We conducted a pan-Canadian web-based survey of anesthesiologists that was distributed using a modified Dillman technique. Our multidisciplinary team, including a patient partners panel, participated in the process of domains and items generation, items reduction, formatting, and composition. Our sampling frames were members of the Canadian Anesthesiologists’ Society and members of the Association des Anesthésiologistes du Québec. We used the newsletters of each organization to distribute our survey, which was available in English and French and housed on the LimeSurvey (LimeSurvey GmbH, Hamburg, Germany) platform. Results: From our eligible sampling frame, 18% completed the survey (356 respondents out of 2,008 eligible participants). Most of the respondents believed that using opioid minimization strategies during general anesthesia could improve postoperative clinical outcomes, including pain control (84% agree or strongly agree, n= 344/409). Reported use of pharmacologic opioid minimization strategies was variable; however, most respondents believed that nonsteroidal anti-inflammatory drugs, acetaminophen, N-methyl-D-aspartate receptor antagonists (ketamine), α2-adrenoceptor agonists (dexmedetomidine), corticosteroids, and intravenous lidocaine improve prostoperative clinical outcomes. The primary factors guiding decision-making regarding the use of opioid minimization strategies were postoperative acute pain intensity, the impact of acute pain on functioning, patient well-being (i.e., quality of recovery) and patient satisfaction with care. A lack of evidence was the most important barrier limiting the use of opioid minimization strategies. Conclusion: In our survey of Canadian anesthesiologists, several opioid minimization strategies were believed to be effective complements to general anesthesia, although there was substantial variation in their reported use. Future randomized controlled trials and systematic reviews evaluating the effectiveness of opioid minimization strategies should prioritize patient-centred outcome measures assessment such as the quality of recovery or the impact of acute pain on functioning.

Exosomes have emerged as a promising tool for the delivery of drugs and genetic materials, owing to their biocompatibility and non-immunogenic nature. However, challenges persist in achieving successful oral delivery due to their susceptibility to degradation in the harsh gastrointestinal (GI) environment and impeded transport across the mucus-epithelium barrier. To overcome these challenges, we have developed high-purity bovine milk exosomes (mExo) as a scalable and efficient oral drug delivery system, which can be customized by incorporating hydrophilic and zwitterionic motifs on their surface. In our study, we observed significantly improved transport rates by 2.5–4.5-fold in native porcine intestinal mucus after the introduction of hydrophilic and zwitterionic surface modifications, as demonstrated by transwell setup and fluorescence recovery after photobleaching (FRAP) analysis. Remarkably, mExo functionalized by a block peptide (BP), consisting of cationic and anionic amino acids arranged in blocks at the two ends, demonstrated superior tolerability in the acidic gastric environment (with a protein recovery rate of 84.8 ± 7.7%) and exhibited a 2.5-fold increase in uptake by intestinal epithelial cells. Furthermore, both mExo and mExo-BP demonstrated successful intracellular delivery of functional siRNA, resulting in up to 65% suppression of the target green fluorescence protein (GFP) gene expression at a low dose of siRNA (5 pmol) without causing significant toxicity. These findings highlight the immense potential of modifying mExo with hydrophilic and zwitterionic motifs for effective oral delivery of siRNA therapies.

Abstract.In asymptomatic multiple-concussion athletes, studies evidenced long-term impairments in psychomotor speed, motor sequence learning, and cognitive control processes, as indexed by the Error Negativity (Ne), also commonly referred to as the Error-related Negativity (ERN). In healthy controls, motor sequence learning during a Serial Reaction Time (SRT) task is associated with an increase in Ne/ERN amplitude. The objective of this paper is to investigate whether concussion effects on cognitive control are associated with sequence learning changes in asymptomatic multi-concussion athletes. Thirty-seven athletes (18 nonconcussed; 19 concussed) completed a SRT task during which continuous electroencephalographic (EEG) activity was recorded. Ne/ERN amplitude modulation from early to late learning blocks of the task was measured. Median reaction times (RTs) were computed to assess psychomotor speed and motor sequence learning. Psychomotor speed was significantly reduced in concussed athletes. Accentuated Ne/ERN amplitude from early to late learning blocks significantly correlated with motor sequence learning in nonconcussed athletes. In contrast, Ne/ERN amplitude was found to decrease significantly with task progression in concussed athletes who nonetheless achieved normal motor sequence learning. Multiple concussions detrimentally affect psychomotor speed. Unlike nonconcussed athletes, motor sequence learning in multi-concussion athletes was not associated with Ne/ERN amplitude modulation, indicating that cognitive control processes do not centrally contribute to learning of a motor sequence after repeated concussions.

This article describes the results of the Spring of 2021 New England Shelf Break Acoustics (NESBA) Signals and Noise experiment as they pertain to the optimization of a field of passive receivers versus an environmentally aware source with end-state goals. A discrete optimization has been designed and used to demonstrate providing an acoustic system operator with actionable guidance relating to optimally distributed receiver locations and depths and likely mean source detection times and associated uncertainties as a function of source and receiver levels of environmental awareness. The uncertainties considered here are those due to the imperfect spatial and temporal sensing of the water column, ambient noise (AN), and the seabed, and the impact this has on ocean forecasting and acoustic performance prediction accuracy. As a part of the NESBA experiment, high-resolution (1 km spatial) regional Navy Coastal Ocean Model ensemble forecasts were generated to capture oceanographic variability and uncertainty. Passive AN-based seabed measurements were conducted to estimate seabed properties including variability and uncertainty. Extensive AN and conductivity, temperature, and depth measurements were also conducted. In this article, operationally relevant metrics are employed to estimate the potential value-added of optimal receiver location and depth placements as a function of source end-state goals and assumed level of environmental awareness. A concept for generating stochastic acoustic prediction metrics and associated optimally distributed receiver locations and depths in an operational environment is proposed.

AbstractMealtimes in long-term care (LTC) can reinforce relationships between staff and residents through relationship-centred care (RCC) practices; however, meals are often task-focused (TF). This cross-sectional study explores multi-level contextual factors that contribute to RCC and TF mealtime practices. Secondary data from residents in 32 Canadian LTC homes were analyzed (n= 634; mean age 86.7 ± 7.8; 31.1% male). Data included resident health record review, standardized mealtime observation tools, and valid questionnaires. A higher average number of RCC (9.6 ± 1.4) than TF (5.6 ± 2.1) practices per meal were observed. Multi-level regression revealed that a significant proportion of variation in the RCC and TF scores was explained at the resident- (intraclass correlation coefficient [ICC]RCC= 0.736; ICCTF= 0.482), dining room- (ICCRCC= 0.210; ICCTF= 0.162), and home- (ICCRCC= 0.054; ICCTF= 0.356) levels. For-profit status and home size modified the associations between functional dependency and practices. Addressing multi-level factors can reinforce RCC practices and reduce TF practices.