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Urban climate adaptation through nature-based solutions (NBS) requires collective action that incorporates spatial justice considerations. Collective actions reveal new ways of thinking about urban green commons and spatial justice by reframing conventional understandings of NBS, space, and climate adaptation. Three urban green commons examined in Istanbul demonstrate how the grassroots-supported NBS must navigate complex land ownership arrangements, spatial justice, and opposing urban development priorities and socio-spatial reconfigurations spurred by local and national political elites. Using qualitative data collected from fieldwork carried out in 2019, we find critical relationships between activists, academics, professional organizations, and local residents collectively acting to promote urban green commons. NBS do not rely on the dominant techno-political processes that generate primarily infrastructure-based climate adaptation solutions in Istanbul. While spatial justice and collective action scholarship often pays attention to how disadvantaged communities gain recognition and involvement in decision making - such as establishing formal channels to access environmental goods and services - climate adaptation through NBS opens spaces of opportunity for these groups to promote justice and resist the dominant economic development paradigm. Further studies must pay attention to what extent collective actions create new socio-political identities that are harnessed to resist dominant techno-political processes, and when are these emergent identities co-opted by local and national governments. publishedVersion

We report QDπ-v1.0 for modeling the internal energy of drug molecules containing H, C, N, and O atoms. The QDπ model is in the form of a quantum mechanical/machine learning potential correction (QM/Δ-MLP) that uses a fast third order self-consistent density-functional tight-binding (DFTB3/ 3OB) model that is corrected to a quantitatively high-level of accuracy through a deep-learning potential (DeepPot-SE). The model has the advantage that it is able to properly treat electrostatic interactions and handle changes in charge/protonation states. The model is trained against reference data computed at the ωB97X/6-31G* level (as in the ANI-1x data set) and compared to several other approximate semiempirical and machine learning potentials (ANI-1x, ANI-2x, DFTB3, MNDO/d, AM1, PM6, GFN1-xTB, and GFN2-xTB). The QDπ model is demonstrated to be accurate for a wide range of intra-and intermolecular interactions (despite its intended use as an internal energy model) and has shown to perform exceptionally well for relative protonation/deprotonation energies and tautomers. An example application to model reactions involved in RNA strand cleavage catalyzed by protein and nucleic acid enzymes illustrates QDπ has average errors less than 0.5 kcal/mol, whereas the other models compared have errors over an order of magnitude greater. Taken together, this makes QDπ highly attractive as a potential force field model for drug discovery., This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © 2023 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jctc.2c01172

Supportive care with mechanical ventilation is the cornerstone of management for acute respiratory distress syndrome (ARDS). Positive end-expiratory pressure (PEEP) is often applied in mechanically ventilated patients with ARDS to improve oxygenation; however, determining the optimal PEEP level—the pressure that maximizes clinical benefit while minimizing risks of ventilator-induced lung injury and other harms—for each patient can be challenging. Recently, transthoracic lung ultrasonography (also called lung ultrasound) has been proposed as a tool to guide PEEP determination in patients with ARDS. This paper reviews the history of use of lung ultrasound as a method to guide PEEP determination and the four published studies which compared it to other techniques of PEEP determination, such as the oxygenation and PV-curve methods.

A methyltransferase ribozyme (MTR1) was selected in vitro to catalyze alkyl transfer from exogenous O6-methylguanine (O6mG) to a target adenine N1, and recently, high-resolution crystal structures have become available. We use a combination of classical molecular dynamics, ab initio quantum mechanical/molecular mechanical (QM/MM) and alchemical free energy (AFE) simulations to elucidate the atomic-level solution mechanism of MTR1. Simulations identify an active reactant state involving protonation of C10 that hydrogen bonds with O6mG:N1. The deduced mechanism involves a stepwise mechanism with two transition states corresponding to proton transfer from C10:N3 to O6mG:N1 and rate-controlling methyl transfer (19.4 kcal·mol−1 barrier). AFE simulations predict the pKa for C10 to be 6.3, close to the experimental apparent pKa of 6.2, further implicating it as a critical general acid. The intrinsic rate derived from QM/MM simulations, together with pKa calculations, enables us to predict an activity–pH profile that agrees well with experiment. The insights gained provide further support for a putative RNA world and establish new design principles for RNA-based biochemical tools.

This paper introduces a novel evaluation methodology for entity resolution algorithms. It is motivated by PatentsView.org, a U.S. Patents and Trademarks Office patent data exploration tool that disambiguates patent inventors using an entity resolution algorithm. We provide a data collection methodology and tailored performance estimators that account for sampling biases. Our approach is simple, practical and principled -- key characteristics that allow us to paint the first representative picture of PatentsView's disambiguation performance. This approach is used to inform PatentsView's users of the reliability of the data and to allow the comparison of competing disambiguation algorithms., 20 pages, 4 figures

PURPOSE: We aimed to understand how new diagnosis discussions are conducted in pediatric oncology, and the training provided for their conduct. METHODS: This mixed-methods study used a sequential exploratory design. Qualitative interviews (n = 20) were conducted with pediatric oncologists (n = 15) and fellows (n = 5) at a single institution, focusing on the process used to convey the diagnosis and treatment plan to the family. Accreditation Council for Graduate Medical Education–accredited pediatric oncology fellowship program directors (n = 38) and fellows (n = 70) were subsequently surveyed to confirm qualitative results and elucidate the training that fellows receive in conducting new diagnosis discussions. RESULTS: Our findings suggest that new diagnosis discussions in pediatric oncology are typically conducted in three stages: (1) concern for cancer; (2) confirmation of diagnosis; and (3) treatment plan/consent, and are fundamentally similar across settings; however, pediatric oncologists skillfully tailor their approach on the basis of clinical circumstances and parental needs. Decisions regarding inclusion of the child are primarily determined by parental preference, whereas inclusion of health care team members is driven by physician role (ie, trainee v program director) and health care organization–related factors. Physician preparation for discussions involves logistical, intellectual, and emotional components. Disclosure of prognosis is nuanced. There is variability across pediatric oncology fellowship programs in the provision of training for these discussions. CONCLUSION: We identified common practices of pediatric oncologists as they prepare for and lead new diagnosis discussions in pediatric oncology. We found variability in the training that pediatric oncology fellows receive regarding how to conduct these discussions, highlighting a need for standardized training curricula.

The accurate identification of mucinous pancreatic cystic lesions (PCLs) is paramount for cancer risk stratification. Cyst fluid carcinoembryonic antigen (CEA), the only routinely used test, requires high volumes and has low sensitivity. We aimed to compare the performance of two investigational small-volume biomarkers, glucose and the protease gastricsin, to CEA for PCL classification.We obtained cyst fluid samples from 81 patients with pathologically confirmed PCLs from four institutions between 2003 and 2016. Gastricsin activity was measured using an internally quenched fluorescent substrate. Glucose levels were measured with a standard glucometer. CEA levels were obtained from the medical record. Models using Classification and Regression Trees were created to predict mucinous status. Model performance was evaluated using nested cross-validation.Gastricsin activity, CEA, and glucose levels from patients with mucinous (n = 50) and nonmucinous (n = 31) PCLs were analyzed. Area under the curve (AUC) was similar for individual classifiers (gastricsin volume normalized [GVN] 0.88; gastricsin protein concentration normalized [GPN] 0.95; glucose 0.83; CEA 0.84). The combination of two classifiers did not significantly improve AUC, with CEA + GVN (0.88) performing similarly to CEA + GPN (0.95), GVN + glucose (0.87), GPN + glucose (0.95), and CEA + glucose (0.84). The three-analyte combination performed similarly to single and dual classifiers (GPN + glucose + CEA AUC 0.95; GVN + glucose + CEA AUC 0.87). After multiple comparison corrections, there were no significant differences between the individual, dual, and triple classifiers.Gastricsin and glucose performed similarly to CEA and required5% of the volume required for CEA; these classifiers may be useful in patients with limited cyst fluid. Future multicenter prospective studies are needed to validate and compare these novel small-volume biomarkers.

ispartof: EXPERT REVIEW OF VACCINES vol:22 issue:1 pages:518-519 ispartof: location:England status: accepted

ImportanceInternal medicine residents’ professional development preferences were discordant with their perceptions of cardiology in a survey circulated a decade ago; no contemporary data exist. This information is important for effective recruitment and retention of a highly talented and diverse future cardiology workforce.ObjectiveTo identify residents’ professional development preferences and cardiology perceptions, in relation to specialty choice, and compare the findings with those from a decade prior.Design, Setting, and ParticipantsThe original survey from the 2010 study was updated and sent to US internal medicine programs. Respondents (ie, internal medicine residents) rated 38 professional development preferences and 20 cardiology perceptions. Data were collected in 2020 and compared with survey results from the prior 2010 study. Multivariable models were created for specialty choice using scaled independent variables dichotomized using the top 2 options; categorical variables were recoded into binary variables for analysis.Main Outcomes and MeasuresMultivariable models were used to determine the association of demographic characterisitcs and survey responses with prospective career choice. Responses were examined by total group, by gender, by self-reported consideration of entering cardiology as a profession, and by comparison with a decade prior both as a group and by gender.ResultsA total of 840 residents (mean [SD] age, 29.24 [2.82] years; 49.8% male; 55.4% White) completed the survey. The survey incorporated a 5-point Likert scale of 1 (not important) to 5 (extremely important) for some of the questions, with additional questions on demographic characteristics. The most important professional development preferences by descending Likert score were as follows: positive role models (4.56), stimulating career (3.81), and family friendly (3.78). The cardiology perception statements with the highest agreement were as follows: interferes with family life during training (3.93) and having met positive role models or having positive views of cardiovascular disease as a topic (3.85). Multivariable analysis yielded a 22-element model predicting cardiology as career choice. Compared with the 2010 survey, the findings of this survey indicated increased importance of work-life balance components for both male and female residents, with a greater change in male residents. Contemporary residents were more likely than their predecessors to agree with negative perceptions of cardiology.Conclusions and RelevanceThis survey study found that both male and female residents place a high value on support for optimal work-life balance; these preferences have intensified over the past decade and factor into career choice. Negative perceptions of cardiology persist and, in some aspects, are worsening. Improving the culture of cardiology may make this specialty a more attractive career choice for all.

Objective In adherence to the American Educational Research Association (AERA) guidelines on culturally informed testing practices, this paper aims to review a suggested battery of tests that is linguistically and culturally appropriate for Arabic-speaking patients and to inform the reader of the varied characteristics of the Arab world to aid in providing a culturally informed neuropsychological evaluation. Method Test instruments in Arabic were identified through systematic searches of PubMed and Google Scholar, U.S.-based website searches in Arabic and French, and in consultation with Arabic-speaking cultural brokers. Results A battery assessing cognitive domains and mood was assembled using core measures that were developed using appropriate translations, cultural adaptations, and include normative data of Arabic-speaking individuals. Supplemental measures that can be administered using translated instructions and English normative data are also identified. The rationale for test selection and clinical utility, including strengths and limitations of the proposed measures is presented. Conclusions Given the large number of Arab Americans residing in the United States combined with the dearth of Arabic speaking neuropsychologists, it is essential that non-Arabic speaking neuropsychologists educate themselves regarding culturally informed practices to better service this growing community.

Objective Asians of Chinese origin are the largest single Asian origin group in the United States and are also the third largest group in Harris County, TX (i.e., the Houston metropolitan area). Mandarin speakers constitute the majority of the group. The linguistic gaps between Chinese (Mandarin) and English make it essential to use appropriate tests and normative data when working with the Mandarin-speaking population. Although it is ideal to develop original tests and/or normative data for Mandarin-speaking patients residing in the United States, the process can be lengthy. Although these indigenous tests are being developed, a neuropsychological battery with tests validated in Mandarin-speaking regions (e.g., Mainland China, Taiwan, and Singapore) can provide valuable information for Mandarin-speaking patients who identify with their home culture/country/region. Methods A systematic review of two electronic databases (PubMed and PsycInfo) was conducted. Results A neuropsychological battery to assess cognitive domains, including global intellectual function, attention/processing speed, executive function, visuospatial/visuoconstruction, language, learning and memory, and emotion, was developed. Cognitive screeners and performance validity measures were also included. The battery consists of core and supplementary measures validated in the Mandarin-speaking population. A case illustration is provided. Conclusion Strengths and limitations of the battery and the role of interpretation in service delivery are discussed. The battery is recommended to clinicians for the evaluation of Mandarin-speaking older adults residing in the United States and other non-Mandarin-speaking regions where local norms are not available.

Objective To serve the over 1.82 million people of Korean descent who reside in the United States, we assembled a core and supplemental battery of culturally and linguistically appropriate neuropsychological measures for differential diagnosis of dementia for Korean-speaking patients. Method Test instruments in Korean were identified through systematic searches of PubMed and Google Scholar, US-based website searches in Korean, and in consultation with Korean-speaking cultural brokers, residing in the United States and Korea. Results A battery assessing cognitive domains and mood was assembled using core measures developed specifically for Korean-speaking individuals within the United States and supplemental English measures that can be administered using translated instructions and English normative data. The rationale for test selection and clinical utility, including strengths and limitations of the proposed measures, is presented. Additionally, a case illustration using the proposed battery is included. Conclusions Given the large and aging population of Korean-speaking residents in the United States, it is imperative to utilize appropriately designed and normed instruments to provide culturally competent assessments to better serve the Korean community.

Objectives To assemble a core battery of culturally and linguistically appropriate neuropsychological measures that can be administered to Vietnamese-speaking patients with suspected dementia. Methods Test instruments in Vietnamese were identified through systematic searches of PubMed, PsychInfo, and Google Scholar, and in consultation with two Vietnamese-speaking cultural brokers. Results A battery assessing the domains of attention, executive function, verbal and visual episodic memory, basic language abilities, visuospatial/visuoconstruction abilities, and mood/anxiety was assembled that included core measures developed either specifically for a Vietnamese-speaking population, or were validated/normed with a Vietnamese-speaking sample either in Vietnam or Vietnamese-speaking persons in the U.S. Supplemental measures were selected that can be administered using translated instructions with U.S. English normative data. The rationale for test selection and caveats for their clinical use are presented. Conclusions The number of neuropsychological measures identified in Vietnamese and/or with Vietnamese normative data was sparse. Given the large and growing population of Vietnamese-speaking residents in the U.S. and the aging of these communities, it is imperative to develop additional, appropriately designed and normed instruments to provide culturally competent assessments to better serve these individuals.

Objective Becoming culturally competent healthcare providers depends on the ability of practitioners to acquire knowledge, awareness, and skills related to other cultures. In building these areas of competence, it is essential to consider geopolitical factors that may influence health and health-seeking behaviors, particularly when working with immigrant populations. When care is sought, they are likely to experience significant barriers to effective care, including lack of providers who speak their language and failure of practitioners to integrate cultural beliefs into treatment plans. This is further complicated by the presence of geopolitical issues, including immigration status, war/conflict in the patient’s country of origin, and/or human rights violations. Method The current study uses a sample case of a Burmese-speaking, Myanmar national to illustrate a culturally informed approach to the assessment of neurobehavioral changes within complex geopolitical circumstances. The sample represents an amalgam of several patients, designed to represent common presentations, sociodemographic situations, and concerns that arise during the neuropsychological assessment process. Results Description of relevant case information including background, clinical observations, and performance on testing is provided. Discussion Awareness of the impact of these life experiences not only has the potential to deepen our understanding of our patients but also results in a more holistic, accurate, and culturally competent conceptualization of their physical and mental health needs.

Objective As the third largest immigrant population in Houston, Texas, Brazilians represent a large bloc of the community in need of culturally and linguistically informed healthcare. In particular, the number of older adults within this population is rapidly growing, emphasizing the increased need to develop socially responsible neuropsychological assessment practices that can meet the needs of this demographic. Additionally, early symptoms of cognitive decline in Brazilian older adults can be culturally perceived as normal aging and may be masked by cultural and lifestyle practices (i.e., scaffolding by family members) that result in lack of appreciation for cognitive and functional decrements. With increased knowledge and awareness of Brazilian culture and customs, we can better understand and assess brain–behavior relationships, provide tailored assessment services, and determine the clinical implications for this population. Methods Test instruments in Portuguese were identified through systematic literature searches, and in consultation with clinicians serving the Portuguese community in the United States, and cultural brokers involved in Brazilian-based neuropsychology. Results A multidomain neuropsychological battery with accompanying normative data for use with adults from this community is presented. A case illustration is utilized to highlight limitations and strengths of the proposed battery, which includes core and supplemental measures. Conclusion Neuropsychologists are encouraged to familiarize themselves with the proposed protocol, understand the psychometric limitations of the available tools, and make an earnest attempt toward providing socially responsible neuropsychological care via the appropriate use of culturally and linguistically tailored instruments and clinical practices.

Objective To assemble a comprehensive neuropsychological battery appropriate for differential diagnosis of dementia in Farsi-speaking Iranian adults in the United States. Method Systematic searches of PubMed, PsychInfo, and Google Scholar databases were conducted to obtain test instruments relevant to Farsi speakers in consultation with a Farsi-speaking cultural broker. Results A proposed battery assessing the domains of attention, executive function, verbal and visual episodic memory, language, visuospatial/visuoconstruction abilities, and mood/anxiety was assembled that includes core measures developed, either specifically for a Farsi-speaking Iranian population or validated/normed with a Farsi-speaking Iranian sample. Though not ideal, additional measures were selected that can be administered using translated instructions with English normative data to supplement the limited tests available for use in this population. The rationale for test selection and caveats for their clinical use are presented along with a case study. Conclusions The number of neuropsychological measures available in Farsi and/or with normative data for Farsi speakers is extremely limited. Cognitive tests either developed for or validated with a bilingual Farsi-English sample also represent a significant gap in the literature. Appropriate measures for these populations are urgently needed to provide a culturally competent assessment of a growing older adult segment of an underserved community.

Introdução: O envelhecimento biológico é um processo de declínio progressivo na aptidão do organismo e na função celular, que contribui para o desenvolvimento de doenças relacionadas com a idade e eventual morte. O estresse psicológico é mencionado como fator significativo do envelhecimento da pele, bem como fator de várias doenças de pele. Pesquisas recentes confirmaram a pele tanto como um receptor imediato de estresse quanto como alvo de respostas ao estresse. Objetivo: Descrever os aspectos gerais do estresse, assim como sua importância durante o processo de senescência cutâneo. Métodos: Este estudo configura-se como uma revisão integrativa realizada por meio de levantamento bibliográfico nos diretórios: Google Scholar e Scientific Eletronic LibraryOn-line (SciELO). Desta busca, foram encontrados 21 artigos, posteriormente submetidos aos critérios de seleção. Os critérios de inclusão foram: artigos publicados entre os anos de 2005 e 2022, excetuando-se um que foi publicado em 1997, todos nas línguas portuguesa, inglesa e espanhola, que abordavam a temática da relação entre os aspectos psicossociais e o envelhecimento cutâneo precoce. Os critérios de exclusão foram: resumos em eventos, artigos que não cumpriam os critérios de inclusão supracitados e artigos duplicados. Com isso, a seleção resultou em 6 artigos que foram submetidos à análise seletiva, exploratória e interpretativa para os dados para este estudo. Conclusão: Portanto, o aumento no nível de fatores de estresse leva a um aumento de processos inflamatórios, inclusive na pele, causando o envelhecimento acelerado da pele, o qual aumenta a liberação de fatores de estresse.

Background: Brugada syndrome (BrS) is an inherited arrhythmia syndrome caused by loss-of-function variants in the cardiac sodium channel gene SCN5A (sodium voltage-gated channel alpha subunit 5) in ≈20% of subjects. We identified a family with 4 individuals diagnosed with BrS harboring the rare G145R missense variant in the cardiac transcription factor TBX5 (T-box transcription factor 5) and no SCN5A variant. Methods: We generated induced pluripotent stem cells (iPSCs) from 2 members of a family carrying TBX5-G145R and diagnosed with Brugada syndrome. After differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), electrophysiologic characteristics were assessed by voltage- and current-clamp experiments (n=9 to 21 cells per group) and transcriptional differences by RNA sequencing (n=3 samples per group), and compared with iPSC-CMs in which G145R was corrected by CRISPR/Cas9 approaches. The role of platelet-derived growth factor (PDGF)/phosphoinositide 3-kinase (PI3K) pathway was elucidated by small molecule perturbation. The rate-corrected QT (QTc) interval association with serum PDGF was tested in the Framingham Heart Study cohort (n=1893 individuals). Results: TBX5-G145R reduced transcriptional activity and caused multiple electrophysiologic abnormalities, including decreased peak and enhanced “late” cardiac sodium current (I Na ), which were entirely corrected by editing G145R to wild-type. Transcriptional profiling and functional assays in genome-unedited and -edited iPSC-CMs showed direct SCN5A down-regulation caused decreased peak I Na , and that reduced PDGF receptor ( PDGFRA [platelet-derived growth factor receptor α]) expression and blunted signal transduction to PI3K was implicated in enhanced late I Na . Tbx5 regulation of the PDGF axis increased arrhythmia risk due to disruption of PDGF signaling and was conserved in murine model systems. PDGF receptor blockade markedly prolonged normal iPSC-CM action potentials and plasma levels of PDGF in the Framingham Heart Study were inversely correlated with the QTc interval ( P Conclusions: These results not only establish decreased SCN5A transcription by the TBX5 variant as a cause of BrS, but also reveal a new general transcriptional mechanism of arrhythmogenesis of enhanced late sodium current caused by reduced PDGF receptor–mediated PI3K signaling.

A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function.Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates.There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73mThe use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease.

Tracey G Simon,1,2 Sebastian Schneeweiss,2 Richard Wyss,2 Zhigang Lu,2 Lily G Bessette,2 Cassandra York,2 Kueiyu Joshua Lin1,2 1Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 2Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Kueiyu Joshua Lin, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St. Suite 3030, Boston, MA, 02120, USA, Tel +1 617 278-0930, Fax +1 617 232-8602, Email jklin@bwh.harvard.eduBackground: The Model for End-Stage Liver Disease (MELD) score predicts disease severity and mortality in cirrhosis. To improve cirrhosis phenotyping in administrative databases lacking laboratory data, we aimed to develop and externally validate claims-based MELD prediction models, using claims data linked to electronic health records (EHR).Methods: We included adults with established cirrhosis in two Medicare-linked EHR networks (training and internal validation; 2007– 2017), and a Medicaid-linked EHR network (external validation; 2000– 2014). Using least absolute shrinkage and selection operator (LASSO) with 5-fold cross-validation, we selected among 146 investigator-specified variables to develop models for predicting continuous MELD and relevant MELD categories (MELD< 10, MELD≥ 15 and MELD≥ 20), with observed MELD calculated from laboratory data. Regression coefficients for each model were applied to the validation sets to predict patient-level MELD and assess model performance.Results: We identified 4501 patients in the Medicare training set (mean age 75.1 years, 18.5% female, mean MELD=13.0), and 2435 patients in the Medicare validation set (mean age: 74.3 years, 31.7% female, mean MELD=12.3). Our final model for predicting continuous MELD included 112 variables, explaining 58% of observed MELD variability; in the Medicare validation set, the area-under-the-receiver operating characteristic curves (AUC) for MELD< 10 and MELD≥ 15 were 0.84 and 0.90, respectively; the AUC for the model predicting MELD≥ 20 (using 27 variables) was 0.93. Overall, these models correctly classified 77% of patients with MELD< 10 (95% CI=0.75– 0.78), 85% of patients with MELD≥ 15 (95% CI=0.84– 0.87), and 87% of patients with MELD≥ 20 (95% CI=0.86– 0.88). Results were consistent in the external validation set (n=2240).Conclusion: Our MELD prediction tools can be used to improve cirrhosis phenotyping in administrative datasets lacking laboratory data.Keywords: cirrhosis, phenotyping, administrative data, claims

The anticipation, inclusion, responsiveness, and reflexivity (AIRR) framework (Stilgoe et al., 2013) is a novel framework that has helped those in science and technology fields shift their focus from products to the processes used to create those products. However, the framework has not been known to be applied to the development and implementation of data analytics in higher education. In a case study of creating an early-alert retention system at James Madison University, a working group of ~20 faculty, staff, and students creatively utilized the AIRR framework. The present study discusses how the AIRR framework was utilized to observe and enhance group processes, and the outcomes of those enhanced processes.

Some human settlements endure for millennia, while others are founded and abandoned within a few decades or centuries. The reasons for variation in the duration of site occupation, however, are rarely addressed. Here, the authors introduce a new approach for the analysis of settlement longevity or persistence. Using seven regional case studies comprising both survey and excavation data, they demonstrate how the median persistence of individual settlements varies widely within and among regions. In turn, this variability is linked to the effects of environmental potential. In seeking to identify the drivers of settlement persistence in the past, it is suggested that archaeologists can contribute to understanding of the sustainability and resilience of contemporary cities.

Background: Parents of children newly diagnosed with cancer require specialized knowledge and skills in order to safely care for their children at home. The Children's Oncology Group (COG) developed expert consensus recommendations to guide new diagnosis education; however, these recommendations have not been empirically tested. Methods: We used a sequential two-cohort study design to test a nurse-led Structured Discharge Teaching Intervention (SDTI) that operationalizes the COG expert recommendations in the setting of a tertiary children's hospital. Outcomes included parent Readiness for Hospital Discharge Scale (RHDS); Quality of Discharge Teaching Scale (QDTS); Post-Discharge Coping Difficulty (PDCD); Nurse Satisfaction; and post-discharge unplanned healthcare utilization. Results: The process for discharge education changed significantly before and after implementation of the SDTI, with significantly fewer instances of one-day discharge teaching, and higher involvement of staff nurses in teaching. Overall, parental RHDS, QDTS, and PDCD scores were similar in the unintervened and intervened cohorts. Almost 60% of patients had unplanned healthcare encounters during the first 30 days following their initial hospital discharge. Overall nurse satisfaction with the quality and process of discharge education significantly increased post-intervention. Discussion: Although the structure for and process of delivering discharge education changed significantly with implementation of the SDTI, parent RHDS and QDTS scores remained uniformly high and PDCD scores and non-preventable unplanned healthcare utilization remained similar, while nurse satisfaction with the quality and process of discharge education significantly improved, suggesting that further testing of the SDTI across diverse pediatric oncology settings is warranted.

We develop a framework for the design of optimized alchemical transformation pathways in free energy simulations using nonlinear mixing and a new functional form for so-called "softcore" potentials. We describe the implementation and testing of this framework in the GPU-accelerated AMBER software suite. The new optimized alchemical transformation pathways integrate a number of important features, including (1) the use of smoothstep functions to stabilize behavior near the transformation end points, (2) consistent power scaling of Coulomb and Lennard-Jones (LJ) interactions with unitless control parameters to maintain balance of electrostatic attractions and exchange repulsions, (3) pairwise form based on the LJ contact radius for the effective interaction distance with separation-shifted scaling, and (4) rigorous smoothing of the potential at the nonbonded cutoff boundary. The new softcore potential form is combined with smoothly transforming nonlinear λ weights for mixing specific potential energy terms, along with flexible λ-scheduling features, to enable robust and stable alchemical transformation pathways. The resulting pathways are demonstrated and tested, and shown to be superior to the traditional methods in terms of numerical stability and minimal variance of the free energy estimates for all cases considered. The framework presented here can be used to design new alchemical enhanced sampling methods, and leveraged in robust free energy workflows for large ligand data sets.

Co3O4 nanoparticles were supported on different TiO2 polymorphs, namely, rutile, anatase, and a 15 : 85 mixture of rutile and anatase (also known as P25), via incipient wetness impregnation. The Co3O4/TiO2 catalysts were evaluated in the preferential oxidation of CO (CO-PrOx) in a H2-rich gas environment and characterised in situ using PXRD and magnetometry. Our results show that supporting Co3O4 on P25 resulted in better catalytic performance, that is, a higher maximum CO conversion to CO2 of 72.7% at 200 °C was achieved than on rutile (60.7%) and anatase (51.5%). However, the degree of reduction (DoR) of Co3O4 to Co0 was highest on P25 (91.9% at 450 °C), with no CoTiO3 detected in the spent catalyst. The DoR of Co3O4 was lowest on anatase (76.4%), with the presence of TixOy-encapsulated CoOx nanoparticles and bulk CoTiO3 (13.8%) also confirmed in the spent catalyst. Relatively low amounts of CoTiO3 (8.9%) were detected in the spent rutile-supported catalyst, while a higher DoR (85.9%) was reached under reaction conditions. The Co0 nanoparticles formed on P25 and rutile existed in the fcc and hcp crystal phases, while only fcc Co0 was detected on anatase. Furthermore, undesired CH4 formation took place over the Co0 present in the P25- and rutile-supported catalysts, while CH4 was not formed over the Co0 on anatase possibly due to encapsulation by TixOy species. For the first time, this study revealed the influence of different TiO2 polymorphs (used as catalyst supports) on the chemical and crystal phase transformations of Co3O4, which in turn affect its activity and selectivity during CO-PrOx.

Medical and surgical treatment for musculoskeletal sarcoma (MSS) place survivors at risk for impairments in muscle properties including muscle strength, muscle size, and neuromuscular activation. The purpose of this study was to explore muscle properties, gross motor performance, and quality of life (QoL) and the changes in response to a 6-week functional strengthening intervention (PT-STRONG) in MSS survivors of childhood cancer (CCS).Eight lower extremity MSS CCS (13-23 years old) performed baseline testing and three completed PT-STRONG. Participants completed measurements of knee extension strength using handheld dynamometry, vastus lateralis (VL) and rectus femoris (RF) muscle thickness using ultrasonography at rest, and neuromuscular activation using electromyography during strength testing and a step-up task. Participants also completed gross motor and QoL assessments.Compared with the non-surgical limb, MSS CCS had lower surgical limb knee extension strength, VL muscle thickness, and RF step-up muscle rate of activation (RoA). Compared with normative values, MSS CCS had decreased bilateral knee extension strength, gross motor performance, and physical QoL. Positive correlations among muscle strength, muscle thickness, and gross motor performance were identified. After PT-STRONG, MSS CCS had improvements in VL muscle thickness, VL and RF RoA duing step-up, gross motor performance, and physical QoL.Positive association between larger muscle thickness with greater knee extension strength, and higher knee extension strength with better gross motor performance indicate that comprehensive physical therapy assessment and interventions that identify and target impairments in muscle properties to guide clinical decision making should be considered for MSS CCS into survivorship.

The rule of law and democracy in the European Union (EU) are under great pressure. Indices measuring the rule of law show that attacks on it are on the rise. In the meantime, the EU has developed numerous instruments to defend the rule of law, but so far these have only been able to sanction, but not to prevent the dismantling of the rule of law. What both approaches have in common: they are more reactive than preventive. They can detect deterioration and sanction violations, but not anticipate them. In order to mitigate this shortcoming, we propose a new approach. It adds a preventive dimension to the debate on the rule of law in the EU: resilience. To this end, we identify factors that make the rule of law resilient to attacks and argue that this depends above all on its political, social and economic environment.

What is this? An example of informal LLP between a teacher (or, possibly, a parent with a high level of gaming literacy and interest in their child) and their son. Why did you make it? To showcase an example of the rich literacy skills that may emerge when players take time to engage with and consider a game. Who is it for? Mothers, fathers, game players, games-in-education advocates, skeptics, and the curious. ⭐ BONUS: A lesson plan is provided in the Appendix which may be utilized in L1 and L2 teaching contexts for young learners, teens, and beyond. The lesson is designed to show how this interaction between teacher-parent and son may be implemented in the classroom.

Little is understood about dental student perspectives providing care to people with serious mental illness (SMI), a population with significant oral health disparities. This study explored student perceptions, questions and beliefs about people with SMI using the Social Ecological Model as a framework to better understand perspectives and identify potential educational needs in dental medicine curricula for providing care to this population.Survey data was collected in spring of 2021 from predoctoral dental students (n = 126) enrolled in a required course at a mid-Atlantic university. Ninety-nine percent of the students completed the survey. The IRB approved qualitative study examined student responses to a six question survey using content analysis. An iterative coding process was used and included reflexivity memos, data dictionaries and consensus building among the four coding researchers to identify recurring concepts and ultimately identify themes.Four primary themes were identified: Concerns and Stereotypes; Uncertainties; Professional Role and Responsibilities; and Learning Preferences. Participants expressed fear and discomfort in working with people with SMI. They also noted multiple questions about providing clinical care, referrals and the interaction of oral health and mental health. Lastly, they offered ideas about educational strategies to improve learning on the topic.Pre-doctoral dental students have concerns about providing care to people with SMI and limited understanding of dental professional role and responsibilities about care for this vulnerable population. Predoctoral dental curriculum should be expanded to address professional roles when working with this population to improve student competency and comfort, and ultimately improve care to people with SMI.

KATP channel gain- (GOF) and loss-of-function (LOF) mutations in SUR1 or Kir6.2 underlie human neonatal diabetes mellitus (NDM) and congenital hyperinsulinism (CHI), respectively. Genetically modified mice with transgenic overexpression of GOF mutations recapitulate many features of human NDM and transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, although complete KATP knockout mice do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis in zebrafish are regulated by identical KATP channels to those in mammals, and to explore the possibility of using zebrafish for modeling CHI, we have examined SUR1 truncation mutation (K499X) introduced into the abcc8 gene. Patch-clamp analysis confirmed complete absence of channel activity in β-cells from K499X (SUR1-/-) fish. No difference in random blood glucose was detected in heterozygous SUR1+/- fish, nor in homozygous SUR1-/- fish, mimicking findings in SUR1 knockout mice. Mutant fish also demonstrated impaired glucose tolerance, similar to LOF mouse models. In paralleling features of mammalian hyperinsulinism resulting from loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP LOF driven-dependent pancreatic disease.Key PointsLoss-of function in the Kir6.2 (KCNJ11) and SUR1 (ABCC8)-encoded pancreatic islet β-cell KATP channels underlie congenital hyperinsulinism. Mouse models reiterate key features, but zebrafish models could provide a powerful model for further analysis and therapy testing.An early nonsense mutation in exon 10 of SUR1 was generated by ENU mutagenesis.Patch-clamp analysis revealed an absence of β-cells of SUR1 truncation mutants.Ca imaging demonstrated elevated basal [Ca]i in β-cells with SUR1 truncation.Homozygous SUR1 truncation mutants had normal fasting glucose but impaired glucose tolerance as adults, mimicking findings in mouse SUR1 knockouts.In paralleling features of mammalian diabetes and hyperinsulinism resulting from equivalent loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP -LOF dependent pancreatic diseases.

What is the central question of this study? Skeletal muscle extracellular vesicles likely act as pro-angiogenic signalling factors: does overexpression of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) alter skeletal muscle myotube extracellular vesicle release, contents and angiogenic potential? What is the main finding and its importance? Overexpression of PGC-1α results in secretion of extracellular vesicles that elevate measures of angiogenesis and protect against acute oxidative stress in vitro. Skeletal muscle with high levels of PGC-1α expression, commonly associated with exercise induced angiogenesis and high basal capillarization, may secrete extracellular vesicles that support capillary growth and maintenance.Skeletal muscle capillarization is proportional to muscle fibre mitochondrial content and oxidative capacity. Skeletal muscle cells secrete many factors that regulate neighbouring capillary endothelial cells (ECs), including extracellular vesicles (SkM-EVs). Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) regulates mitochondrial biogenesis and the oxidative phenotype in skeletal muscle. Skeletal muscle PGC-1α also regulates secretion of multiple angiogenic factors, but it is unknown whether PGC-1α regulates SkM-EV release, contents and angiogenic signalling potential. PGC-1α was overexpressed via adenovirus in primary human myotubes. EVs were collected from PGC-1α-overexpressing myotubes (PGC-EVs) as well as from green fluorescent protein-overexpressing myotubes (GFP-EVs), and from untreated myotubes. EV release and select mRNA contents were measured from EVs. Additionally, ECs were treated with EVs to measure angiogenic potential of EVs in normal conditions and following an oxidative stress challenge. PGC-1α overexpression did not impact EV release but did elevate EV content of mRNAs for several antioxidant proteins (nuclear factor erythroid 2-related factor 2, superoxide dismutase 2, glutathione peroxidase). PGC-EV treatment of cultured human umbilical vein endothelial cells (HUVECs) increased their proliferation (+36.6%), tube formation (length: +28.1%; number: +25.7%) and cellular viability (+52.9%), and reduced reactive oxygen species levels (-41%) compared to GFP-EVs. Additionally, PGC-EV treatment protected against tube formation impairments and induction of cellular senescence following acute oxidative stress. Overexpression of PGC-1α in human myotubes increases the angiogenic potential of SkM-EVs. These angiogenic benefits coincided with increased anti-oxidative capacity of recipient HUVECs. High PGC-1α expression in skeletal muscle may prompt the release of SkM-EVs that support vascular redox homeostasis and angiogenesis.

The radiocephalic arteriovenous fistula (AVF), first introduced by Dr Kenneth Charles Appell, allowed for the provision of hemodialysis for patients with chronic kidney disease (CKD) and remains a reliable method for vascular access today. The purpose of this study is to review the contributions that led to the development of the AVF. We describe the work of Dr Appell, whose procedure bypassed the need for repeated cannulation in achieving vascular access, transforming the management of patients with dialysis-dependent CKD.A literature search was conducted by searching "arteriovenous fistula," "history of surgery," "hemodialysis," "vascular access," "chronic kidney disease," "repeated cannulation," and "Kenneth Charles Appell" on PubMed, Embase, and Web of Science. Only articles written in English were considered.Before the arteriovenous fistula, glass cannulae were used for vascular access, beginning with Abel's "vividiffusion" apparatus in animals and Haas's experimental dialysis on humans. The use of glass cannulae was continued by Kolff, who transitioned from venipuncture needles to glass cannulae. However, these attempts were complicated by thrombosis, excessive bleeding related to heparin use, and damage to vascular access sites from repeated cannulation. Arteriovenous shunts, using polytetrafluoroethylene tubing, were an improvement from previous attempts at vascular access, but were prone to local bleeding, shunt occlusion, phlebitis, cellulitis, and rarely lasted more than a few months. To address these challenges, Dr Appell created an upper extremity AVF, allowing for the provision of maintenance dialysis without externalized devices, repeated cannulation, and extensive anticoagulant administration. Despite Dr Appell's vision and pioneering contributions to vascular surgery, he has received little credit for his work.The enormous contribution by Dr Appell in the development of the AVF that transformed the modern management of patients with CKD is recognized in this review of the history of vascular access surgery for hemodialysis.

Recent STEAM programs have made accomplishments in recruiting K-12 girl students to participate in STEAM activities. Educational researchers have called for studies of how STEM programs engage girls. However, little research has embedded STEM education with girl education such as their emotional needs, identity, and self-expression. This study examined how crochet that was embedded in a STEM summer camp impacted their sense of belonging, creativity, well-being, and STEAM learning. For this qualitative study, surveys were conducted with 37 student participants and Discord was used as part of the data sources. Findings indicated that crocheting enhanced students’ sense of belonging, creativity, well-being, as well as STEM learning. This study contributes to the STEM learning program design for girls in secondary schools with two closely related theories: constructivist learning environment theory and sense of belonging theory. This study added new knowledge to the research of crochet in girl education and STEM program design.