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Renal reactivity to angiotensin II (ANG II) is mediated by superoxide signaling produced by NADPH oxidase (NOX)A1/NOX1. Acute vasoconstriction of renal arteries by ANG was blunted in Noxa1−/− compared with wild-type mice. NOXA1/NOX1/O2•− signaling was also observed in ANG II stimulation of vascular smooth muscle cells and isolated mesenteric resistance arteries, indicating that it contributes to ANG II-induced hypertension. A NOXA1/NOX1 assembly inhibitor (C25) has been characterized that inhibits superoxide production and ameliorates the effects of ANG II.

Purpose To determine the effect of prolonged exercise on moderate-to-heavy intensity transition power output and heart rate. Methods Fourteen endurance-trained cyclists and triathletes took part in the present investigation (13 males, 1 female, V·O2peak 59.9 ± 6.8 mL.kg−1.min−1). Following a characterisation trial, participants undertook a five-stage incremental step test to determine the power output and heart rate at the moderate-to-heavy intensity transition before and after two hours of cycling at 90% of the estimated power output at first ventilatory threshold (VT1). Results Power output at the moderate-to-heavy intensity transition significantly decreased following acute prolonged exercise when determined using expired gases (VT1, 217 ± 42 W vs. 196 ± 42 W, P P = 0.004). This was attributable to loss of efficiency (VT1, -8 ± 10 W; LoglogLT, − 7 ± 9 W) and rates of metabolic energy expenditure at the transition (VT1, − 14 ± 11 W; LoglogLT, − 15 ± 22 W). The heart rate associated with the moderate-to-heavy intensity transition increased following acute prolonged exercise (VT1, 142 ± 9 beats.min−1 vs. 151 ± 12 beats.min−1, P .min−1 vs. 150 ± 15 beats.min−1, P = 0.006). Conclusion These results demonstrate the external work output at the moderate-to-heavy intensity transition decreases during prolonged exercise due to decreased efficiency and rates of metabolic energy expenditure, but the associated heart rate increases. Therefore, individual assessments of athlete ‘durability’ are warranted.

PurposeResidency programs must ensure resident competence for independent practice. The coronavirus disease-19 (COVID-19) pandemic disrupted health care delivery, impacting pediatric residencies. This study examines the impact on pediatric resident education.MethodsThe authors conducted a mixed methods national survey of pediatric residency program directors (PDs) from May 2020 to July 2020. Data analysis included descriptive statistics, chi-square, and Wilcoxon rank sum tests. Multivariable modeling identified factors associated with resident preparation for more senior roles. Thematic analysis was performed on open-ended questions about PD COVID-19 pandemic recommendations to peers, Accreditation Council for Graduate Medical Education and American Board of Pediatrics.ResultsResponse rate was 55% (110/199). PDs reported the COVID-19 pandemic negatively affected inpatient (n=86, 78.2%), and outpatient education (n=104, 94.5%), procedural competence (n=64; 58.2%), and resident preparation for more senior roles (n=50, 45.5%). In bivariate analyses, increasingly negative impacts on inpatient and outpatient education were associated with an increasingly negative impact on resident preparation for more senior roles (P=.03, P=.008), these relationships held true in multivariable analysis. Qualitative analysis identified 4 themes from PD recommendations: 1) Clear communication from governing bodies and other leaders; 2) Flexibility within programs and from governing bodies; 3) Clinical exposure is key for competency development; 4) Online platforms are important for education, communication, and support.ConclusionsThe COVID-19 pandemic negatively impacted inpatient and outpatient education. When these were more negatively impacted, resident preparation for more senior roles was worse, highlighting the importance of competency based medical education to tailor experiences ensuring each resident is competent for independent practice.

ObjectiveDetermine extent of impact of coronavirus disease 2019 (COVID-19) pandemic on career choice and employment of pediatricians entering pediatric workforce.MethodsA national, cross-sectional electronic survey of pediatricians registering for the 2021 American Board of Pediatrics initial general certifying examination on the impact of the COVID-19 pandemic on 3 aspects of career (career choice, employment search, employment offers) was performed. Data were analyzed using descriptive statistics and multivariate logistic regression to determine factors associated with the pandemic's impact on career. Thematic analysis was used to generate themes for open-ended survey questions.ResultsOver half (52.3%, 1767 of 3380) of pediatricians responded. Overall, 29.1% reported that the pandemic impacted their career (career choice [10.4%], employment search [15.6%], or employment offers [19.0%]); applicants to general pediatrics (GP) (52.9%) or pediatric hospitalist (PH) positions (49.3%) were most affected. Multivariate logistic regression modeling found those applying to GP (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 2.22-6.60), PH (OR: 9.02, 95% CI: 5.60-14.52), and International Medical Graduates (IMGs) (OR: 1.90; 95% CI: 1.39-2.59) most likely to experience any career impact.ConclusionsAlmost one third of pediatricians registering for the initial general pediatrics certifying examination reported their careers were impacted by the COVID-19 pandemic, with 10% of respondents reporting the pandemic impacted their career choice. Half of new pediatricians seeking employment reported being impacted by the pandemic, particularly IMGs. As the pandemic evolves, career advising will continue to be critical to support trainees in their career choices and employment.

Understanding the type and frequency of current neonatal intensive care unit (NICU) therapy services and predictors of referral for therapy services is a crucial first step to supporting positive long-term outcomes in very preterm infants. This study enrolled 83 very preterm infants (

To evaluate the impact of the series 13Reasons Why on depression and suicidal behaviors in children and adolescents.Data from the 2016 to 2018 Nationwide Inpatient Sample (NIS) and the Nationwide Emergency Department Sample (NEDS) of the Healthcare Cost and Utilization Project (HCUP) from 2016 to 2018 was used to determine the presentation in both settings for depression and suicidal thoughts and behavior. This was compared to predictive modeling for presentations in the same time frame.Following the release of 13 Reasons Why both hospital admissions and presentations to the Emergency Department (ED) increased for complaints of worsening depression or suicidal thoughts and behavior. This was more pronounced for youth aged 10-17 years, Black race, and female sex. There were no significant findings, overall, for females 6-9 years, but in-patient visits for depression increased in May 2017 for Black females 6-9 years. Males 6-9 years had higher rates of ED visits for depression and both ED and in-patient visits for suicidal behaviors.Secondary data analyses have known limitations including inability to track over time, inclusion of only visit-level data, and failure to collect variables of interest.The series 13 Reasons Why was likely associated with exacerbations of both depressive illnesses and suicidal behavior in youth, particularly for female and Black youth from 10 to 17 years. This study adds to known concerns regarding the role of media in influencing suicidal behavioral in vulnerable children and has important implications for youth monitoring and parent and youth education. More research is needed to identify specific targets for prevention.

PURPOSE. The purpose of this executive summary is to review the process and outcomes of the Academy of Pediatric Physical Therapy Research Summit V, “Optimizing transitions from infancy to young adulthood in children with neuromotor disabilities: biological and environmental factors to support functional independence.” SUMMARY OF KEY POINTS. An interdisciplinary group of researchers, representatives from funding agencies, and individuals with neuromotor disabilities and their parents participated in an intensive 2.5-day summit to determine research priorities to optimize life transitions for children with neuromotor disabilities. Recommended priorities for research included: (1) Promoting self-determination and self-efficacy of individuals with neuromotor disabilities and their families, (2) Best care at the right time: evidence-based best practice care, led and navigated by families seamlessly across the lifespan, (3) Strengthening connections between developmental domains to enhance function and participation, and (4) Optimal dosing and timing to support adaptive bone, muscle, and brain plasticity across the lifespan.

Background and objectives: Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis.\ud \ud \ud \ud Design, setting, participants, & measurements: A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: “complete response,” “partial response,” and “active disease” defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active–Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan–Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored.\ud \ud \ud \ud Results: In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year.\ud \ud \ud \ud Conclusions: Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

The giant Kuparuk Field (Figure 1), the second largest oil field on the Alaska North Slope and one of the largest oil fields in the United States, has been on production for 41 years. The field, a legacy asset in the ConocoPhillips portfolio, contains more than 7.5 Bstb OOIP with 2.5 Bstb in the C Sands and 5.0 Bstb in the A Sands. Production commenced in December 1981 and has cumulated to date more than 2.5 Bstb oil through water-flooding, immiscible water-alternating gas (IWAG) and miscible water-alternating-gas (MWAG) injection. Currently, the field produces about 60,000 stb/d oil, 515,000 bbl/d water and 105 MMscf/d gas, and injects 625,000 bbl/d water and 80 MMscf/d gas through 3 central processing facilities (CPF1, CPF2, and CPF3, located as shown in Figure 1), 45 drillsites, and about 700 active wells. Although the Kuparuk Field is mature, recent studies highlight the potential to optimize the oil recovery. Static and dynamic data along with benchmark studies indicate that the underlying Kuparuk A Sands are of lower maturity than the overlying Kuparuk C Sands. Significant A Sands recovery improvement is possible with strategic reservoir management practices. Several activities were undertaken to understand relative immaturities across the field and investigate methods to improve the performance of Kuparuk A Sands. These include: identifying geologically controlled reservoir performance regions, developing a state-of-the-art full field reservoir model, testing pattern realignment that combines infill drilling with reconfiguration of existing wellbores, and conducting injectivity treatments in various parts of the field. The analysis of available data shows the benefits of increasing the throughput in the Kuparuk A Sands through voidage balancing, improved produced water and gas handling strategies, waterflood pattern realignment, continued in-fill drilling, and increased injectivity. Kuparuk reservoir management has been revised to focus future activities around these core strategies tailored to specific reservoir regions. The intent of this paper is to document strategies that can be implemented to revitalize mature waterflood fields, specifically those that have been developed with commingled reservoirs.

Chondrosarcoma (CS) is the second most common primary malignant bone tumour and, in the absence of reliable chemotherapy and radiotherapy, is effectively a surgical disease. Overall disease specific survival (DSS) is affected by tumour grade, whilst resection margin contributes to local recurrence free survival (LRFS). The aim of this study was to investigate factors that affect the local and systemic prognoses for conventional central CSs arising from the proximal humerus. A multi-centre, retrospective study from three international collaborative sarcoma centres identified 110 patients between 1995 and 2020 undergoing treatment for a conventional central CS of the proximal humerus; 58 patients (53%) had a grade 1 tumour, 36 (33%) had a grade 2 tumour, and 16 patients (13%) had a grade 3 CS. The mean age of patients was 50 years (range 10–85). The incidence of local recurrence (LR) was 9/110 (8.2%), and the disease specific mortality was 6/110 (5.5%). The grade was a statistically significant factor for LRFS (p < 0.001). None of the grade 1 tumours developed LR. The DSS was affected by the grade (p < 0.001) but not by the LR (p = 0.4). Only one patient with a grade 2 tumour died from the disease. The proximal humeral grade 1 CS behaved as a benign tumour, having no cases of LR nor death due to disease. Grade 2 CSs of the proximal humerus behaved in a more indolent way when compared with comparable grade tumours elsewhere in the appendicular skeleton, being locally aggressive with a higher LR rate than grade 1 CSs but still having very low mortality and a high rate of DSS. The LR in grade 2 CSs did not affect the DSS; therefore, surgical management in proximal humeral grade 2 CSs should have a greater emphasis on preserving function whilst maintaining an adequate margin for resection. The proximal humeral grade 3 CS was, as elsewhere in the skeleton, an aggressive, high-grade tumour. Therefore, surgical management should include en bloc resection with clear margins to avoid LR.

Einstenium-254 (Z = 99, N = 155), can be prepared as a target for research into nuclear reaction studies. This work presents structure and reaction calculations of Es-254 and Ca-48 (Z = 20, N = 28), using the Skyrme-(Time-Dependent)-Energy-Density-Functional formalism. The reaction calculations show the initial parts of the heavy-ion reaction between the nuclei which, depending on the interaction parameters, can lead to capture to a compound nucleus of element 119. For collisions with the spherical 48Ca impinging on the tip of the prolate 254Es no fusion events are found. For collisions where the calcium approaches the belly of the einsteinium, capture occurs with the compound nucleus outlasting the lifetime of the calculation, indicating a possible fusion candidate. For a sample center-of-mass collision energy of 220 MeV, slightly non-central collisions, up to an impact parameter of 1 fm, also form long-lived compound nuclei.

Circular economy for lithium-ion batteries and photovoltaic modules—status, challenges, and opportunities

Engineered products have economic, environmental, and social impacts, which comprise the major dimensions of sustainability. This paper seeks to determine the interaction between design parameters when the social impacts are incorporated into the design process. Social impact evaluation is increasing in importance similar to what has happened with environmental impact consideration in recent years in the design of engineered products. Concurrently, research into new airship design has increased, however airships have yet to be reintroduced at a large scale and for a range of applications in society. Although airships have the potential for positive environmental and economic impacts, the social impacts are still rarely considered. This paper presents a case study of the hypothetical introduction of airships in the Amazon to help local farmers transport their produce to market. It explores the design space in terms of the airship's social impacts connected to the design parameters. The social impacts are found to be dependent not only on the social factors and airship design parameters, but also on the farmer-airship system, suggesting that socio-technical systems design will benefit from integrated social impact metric analysis.

OBJECTIVE: Evaluate longitudinal changes in brain microstructure and volumes in very preterm during the first year of life with and without intervention. DESIGN: Descriptive pilot study METHODS: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care. Brain structural and diffusion MRI’s were acquired within 72 hours after neonatal intensive care unit discharge (n=5), three months post-baseline (n=5), and six months post-baseline (n=3). Fractional anisotropy (FA), Mean diffusivity (MD), and volume metrics were computed for five brain regions. RESULTS: More than 60% of eligible participants completed 100% of the scheduled MRIs. FA and volume increased from baseline to six months across all brain regions. Rate of white matter volume change from baseline to six months was highest in SPEEDI Early. CONCLUSIONS: Non-sedated longitudinal MRI is feasible in very preterm infants and appears to demonstrate longitudinal changes in brain structure and connectivity.

Objective:To explore and provide contextual meaning around issues surrounding food insecurity, namely factors influencing food access, as one domain of food security.Design:A community-based, qualitative inquiry using semi-structured face-to-face interviews was conducted as part of a larger sequential mixed-methods study.Setting:Cayo District, Belize, May 2019–August 2019.Participants:Thirty English-speaking individuals (eight males, twenty-two females) between the ages of 18–70, with varying family composition residing within the Cayo District.Results:Participants describe a complex interconnectedness between family- and individual-level barriers to food access. Specifically, family composition, income, education and employment influence individuals’ ability to afford and access food for themselves or their families. Participants also cite challenges with transportation and distance to food sources and educational opportunities as barriers to accessing food.Conclusion:These findings provide insight around food security and food access barriers in a middle-income country and provide avenues for further study and potential interventions. Increased and sustained investment in primary and secondary education, including programmes to support enrollment, should be a priority to decreasing food insecurity. Attention to building public infrastructure may also ease burdens around accessing foods.

Objective:To describe healthcare provider, veteran, and organizational barriers to, challenges to, and facilitators of implementation of the oral care Hospital-Acquired Pneumonia Prevention by Engaging Nurses (HAPPEN) initiative to prevent non–ventilator-associated hospital-acquired pneumonia (NV-HAP).Design:Concurrent mixed methods. Qualitative interviews of staff and patients were conducted in addition to a larger survey of VA employees regarding implementation.Setting:Medical surgical or extended care units in 6 high-complexity (01a–c) VA hospitals.Participants:Between January 2020 and February 2021, we interviewed 7 staff and 7 veterans, and we received survey responses from 91 staff.Intervention:Provide education, support, and oral care supplies to prevent NV-HAP.Results:Barriers to HAPPEN implementation and tracking at the pilot sites included maintaining oral care supplies and completion of oral care documentation. Facilitators for HAPPEN implementation included development of supportive formal and informal nurse leaders, staff engagement, and shared beliefs in the importance of care quality and infection prevention. Nurses worked together as a team to provide consistent oral care. Oral care was viewed as an essential infection control practice (not just “a task”) and was considered part of the “culture” and “mission” in caring for veterans.Conclusions:Nurse leaders and direct-care staff were engaged throughout HAPPEN implementation, and most reported feeling supported and well prepared as they walked through the steps. Veterans reported positive experiences and increased knowledge about prevention of pneumonia. Lessons learned included building a community of practice and sharing expertise, which led to the successful replication of the HAPPEN initiative nationwide, improving patient safety and care quality and influencing health policy.

Diastolic dysfunction (DD) underlies heart failure with preserved ejection fraction (HFpEF), a clinical syndrome associated with aging that is becoming more prevalent. Despite extensive clinical studies, no effective treatment exists for HFpEF. Recent findings suggest that oxidative stress contributes to the pathophysiology of DD, but molecular mechanisms underpinning redox-sensitive cardiac remodeling in DD remain obscure. Using transgenic mice with mitochondria-targeted NOX4 overexpression (Nox4TG618) as a model, we demonstrate that NOX4-dependent mitochondrial oxidative stress induces DD in mice as measured by increased E/E', isovolumic relaxation time, Tau Glantz and reduced dP/dt

Aims: this study compared the patient and microbiological profile of prosthetic joint infection (PJI) for patients treated with two-stage revision for knee arthroplasty with that of lower-limb endoprostheses for oncological resection. Patient and methods: a total of 118 patients were treated with two-stage revision surgery for infected knee arthroplasty and lower-limb endoprostheses between 1999 and 2019. A total of 74 patients had two-stage revision for PJI of knee arthroplasty, and 44 had two-stage revision of oncology knee endoprostheses. There were 68 men and 50 women. The mean ages of the arthroplasty and oncology cohorts were 70.2 years (range of 50–89) and 36.1 years (range of 12–78) respectively (p.01). Patient host and extremity criteria were categorized according to the Musculoskeletal Infection Society (MSIS) host and extremity staging system. The patient microbiological culture, the incidence of polymicrobial infection, and multidrug resistance (MDR) were analysed and recorded. Results: polymicrobial infection was reported in 16 % (12 patients) of knee arthroplasty PJI cases and in 14.5 % (8 patients) of endoprostheses PJI cases (p=0.783). There was a significantly higher incidence of MDR in endoprostheses PJI, isolated in 36.4 % of cultures, compared with knee arthroplasty PJI (17.2 %, p=0.01). Gram-positive organisms were isolated in more than 80 % of cultures from both cohorts. Coagulase-negative Staphylococcus (CoNS) was the most common Gram-positive organism, and Escherichia coli was the most common Gram-negative organism in both groups. According to the MSIS staging system, the host and extremity grades of the oncology PJI cohort were significantly worse than those for the arthroplasty PJI cohort (p.05). Conclusion: empirical antibiotic prophylaxis against PJI in orthopaedic oncology is based upon PJI in arthroplasty, despite oncology patients presenting with worse host and extremity staging. CoNS was the most common infective organism in both groups; however, pathogens showing MDR were significantly more prevalent in oncological PJI of the knee. Therefore, empirical broad-spectrum treatment is recommended in oncological patients following revision surgery.

Residency programs must ensure resident competence for independent practice. The COVID-19 pandemic disrupted healthcare delivery, impacting pediatric residencies. This study examines the impact on pediatric resident education.The authors conducted a mixed methods national survey of pediatric residency program directors (PDs) from May- July 2020. Data analysis included descriptive statistics, χResponse rate was 55% (110/199). PDs reported the COVID-19 pandemic negatively affected inpatient (n= 86, 78.2%), and outpatient education (n=104, 94.5%), procedural competence (n=64; 58.2%), and resident preparation for more senior roles (n= 50, 45.5%). In bivariate analyses, increasingly negative impacts on inpatient and outpatient education were associated with an increasingly negative impact on resident preparation for more senior roles (p=0.03, p=0.008), these relationships held true in multivariable analysis. Qualitative analysis identified 4 themes from PD recommendations: 1) Clear communication from governing bodies and other leaders; 2) Flexibility within programs and from governing bodies; 3) Clinical exposure is key for competency development; 4) Online platforms are important for education, communication, and support.The COVID-19 pandemic negatively impacted inpatient and outpatient education. When these were more negatively impacted, resident preparation for more senior roles was worse. Highlighting the importance of competency based medical education to tailor experiences ensuring each resident is competent for independent practice.The COVID-19 pandemic negatively impacted inpatient and outpatient clinical education which negatively impacted resident preparation for more senior roles. This highlights the importance of competency based medical education to ensure each graduating resident is competent for independent practice.

Background: Disparities in outcomes for children with type 1 diabetes (T1DM) are associated with poverty and race. However, little is known regarding the impact of systemic racism. Objective: This aim of this study is to determine if neighborhood concentrated disadvantage index (NCDI) or Childhood Opportunity Index (COI) are associated with HbA1c and diabetes ketoacidosis (DKA) in children ≤ 18 years of age with type 1 diabetes. Methods: The retrospective secondary data analysis included data from children ≤ 18 years of age with a diagnosis of T1DM for ≥ 6 months seen in 2017 who reside in Kentucky (n=675) . NCDI scores were calculated based on the NIH PhenX Toolkit protocol. The tool was developed from a principal components analysis of six variables at the census tract level. COI was obtained from diversitydatakids.org. Univariate analyses were performed using Kruskal-Wallis test or Pearson’s correlation. Multiple linear regression analysis was conducted to to evaluate HbA1C and multivariate Poisson model was used for DKA. Results: Prior to controlling for age, race, and insurance type, NCDI (p Conclusions: This study identified NCDI and COI as predictors of HbA1c in children and adolescents with T1DM only in univariate analysis. While NCDI and COI have been shown to correlate with structural racism, these findings suggest that more research is needed in larger and more diverse samples to disentangle the complex relationships among race, racism, and poverty. Understanding the mechanisms through which racism impacts outcomes for children with T1DM is essential to improving health equity. Disclosure M.B.Coriell: None. K.S.Jawad: None. Y.B.Feygin: None. S.Watson: None. M.D.Stevenson: None. B.A.Wattles: Research Support; Merck & Co., Inc. V.F.Jones: None. J.Porter: None. D.W.Davis: None.

Drawing on newspaper and archival sources, this article examines post-war Canadian attitudes towards Dwight D. Eisenhower, particularly during his time in office as the United States President from 1953 to 1961. Eisenhower emerged from the Second World War as a trusted figure for many Canadians due to his inspiring leadership of the Allied cause. Once in the White House, however, his reputation began to suffer, and public opinion in Canada increasingly questioned core elements of the traditional Canada–United States relationship and America's ability to lead the Western alliance during a period of heightening Cold War tensions.

White dwarfs, with masses just above the Chandrasekhar limit (1.4 solar masses), can violently collapse into small (104 km radius) and very dense (ρ = 1017 kg/m3) magnetars that can produce B-field...

Nutrition indicators suggest that Belize faces broad food challenges; however, there are little data on factors influencing perceived food access. This study, based in the Cayo District, Belize, ex...

Objective The aim of this project is to study the effect of a physical therapist intervention provided in the first months of life on developmental outcomes of infants born very preterm. Secondary aims are to investigate the impact of intervention timing on the efficacy and impact of the intervention on infants with and without cerebral palsy. Methods This study is a multisite longitudinal controlled trial comparing developmental outcomes from infants in the Supporting Play, Exploration, and Early Development Intervention (SPEEDI)_Late or SPEEDI_Early group to a usual care group. Settings are urban Urban and rural areas surrounding 2 academic medical centers. There will be 90 preterm infants enrolled in this study born at Impact More than 270,000 infants are born very preterm in the United States each year, 50% of whom will have neurological dysfunction that limits their ability to keep pace with peers who are typically developing. This study is a step toward understanding the impact that intensive developmental intervention could have in this population in the first months of life.

While Jupiter's massive gas envelope consists mainly of hydrogen and helium, the key to understanding Jupiter's formation and evolution lies in the distribution of the remaining (heavy) elements. Before the Juno mission, the lack of high-precision gravity harmonics precluded the use of statistical analyses in a robust determination of the heavy-elements distribution in Jupiter's envelope. In this paper, we assemble the most comprehensive and diverse collection of Jupiter interior models to date and use it to study the distribution of heavy elements in the planet's envelope. We apply a Bayesian statistical approach to our interior model calculations, reproducing the Juno gravitational and atmospheric measurements and constraints from the deep zonal flows. Our results show that the gravity constraints lead to a deep entropy of Jupiter corresponding to a 1 bar temperature 5-15 K higher than traditionally assumed. We also find that uncertainties in the equation of state are crucial when determining the amount of heavy elements in Jupiter's interior. Our models put an upper limit to the inner compact core of Jupiter of 7 Earth masses, independently on the structure model (with or without dilute core) and the equation of state considered. Furthermore, we robustly demonstrate that Jupiter's envelope is inhomogenous, with a heavy-element enrichment in the interior relative to the outer envelope. This implies that heavy element enrichment continued through the gas accretion phase, with important implications for the formation of giant planets in our solar system and beyond., Accepted for publication in A&A

Background External evidence is commonly used to inform survival modeling for health technology assessment (HTA). While there are a range of methodological approaches that have been proposed, it is unclear which methods could be used and how they compare. Purpose This review aims to identify, describe, and categorize established methods to incorporate external evidence into survival extrapolation for HTA. Data Sources Embase, MEDLINE, EconLit, and Web of Science databases were searched to identify published methodological studies, supplemented by hand searching and citation tracking. Study Selection Eligible studies were required to present a novel extrapolation approach incorporating external evidence (i.e., data or information) within survival model estimation. Data Extraction Studies were classified according to how the external evidence was integrated as a part of model fitting. Information was extracted concerning the model-fitting process, key requirements, assumptions, software, application contexts, and presentation of comparisons with, or validation against, other methods. Data Synthesis Across 18 methods identified from 22 studies, themes included use of informative prior(s) ( n = 5), piecewise ( n = 7), and general population adjustment ( n = 9), plus a variety of “other” ( n = 8) approaches. Most methods were applied in cancer populations ( n = 13). No studies compared or validated their method against another method that also incorporated external evidence. Limitations As only studies with a specific methodological objective were included, methods proposed as part of another study type (e.g., an economic evaluation) were excluded from this review. Conclusions Several methods were identified in this review, with common themes based on typical data sources and analytical approaches. Of note, no evidence was found comparing the identified methods to one another, and so an assessment of different methods would be a useful area for further research. Highlights This review aims to identify methods that have been used to incorporate external evidence into survival extrapolations, focusing on those that may be used to inform health technology assessment. We found a range of different approaches, including piecewise methods, Bayesian methods using informative priors, and general population adjustment methods, as well as a variety of “other” approaches. No studies attempted to compare the performance of alternative methods for incorporating external evidence with respect to the accuracy of survival predictions. Further research investigating this would be valuable.

We perform deformation constraint symmetry-unrestricted three-dimensional time-dependent density functional theory (TDDFT) calculations for the isoscalar monopole (ISM) mode in 100Mo. Monopole moments are obtained as a function of time using time propagating states based on different deformations. A Fourier transform is then performed on the obtained response functions. The resulting ISM strength functions are compared with experimental data. For the static potential-energy-surface (PES) calculations, the results using the SkM* and UNEDF1 energy-density functionals (EDFs) show spherical ground states and considerable softness in the triaxial deformation. The PES obtained with the SLy4 EDF shows static triaxial deformation. The TDDFT results based on different deformations show that a quadrupole deformation (characterized by ) value of 0.25–0.30 gives a two-peak structure of the strength functions. Increasing triaxial deformation (characterized by γ) from 0 to 30 results in the occurrence of an additional peak between the two, making the general shape of the strength functions closer to that of the data. Our microscopic TDDFT analyses suggest that 100Mo is triaxially deformed in the ground state. The calculated isoscalar and strength functions show peaks at lower energies. The coupling of these two modes with the ISM mode is the reason for the three-peak/plateau structure in the strengths of 100Mo.