Search

The potential for multiyear prediction of impactful Earth system change remains relatively underexplored compared to shorter (subseasonal to seasonal) and longer (decadal) timescales. In this study, we introduce a new initialized prediction system using the Community Earth System Model version 2 (CESM2) that is specifically designed to probe potential and actual prediction skill at lead times ranging from 1 month out to 2 years. The Seasonal-to-Multiyear Large Ensemble (SMYLE) consists of a collection of 2-year-long hindcast simulations, with four initializations per year from 1970 to 2019 and an ensemble size of 20. A full suite of output is available for exploring near-term predictability of all Earth system components represented in CESM2. We show that SMYLE skill for El Niño–Southern Oscillation is competitive with other prominent seasonal prediction systems, with correlations exceeding 0.5 beyond a lead time of 12 months. A broad overview of prediction skill reveals varying degrees of potential for useful multiyear predictions of seasonal anomalies in the atmosphere, ocean, land, and sea ice. The SMYLE dataset, experimental design, model, initial conditions, and associated analysis tools are all publicly available, providing a foundation for research on multiyear prediction of environmental change by the wider community.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children, involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up, or would equally recover by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, school absences and NHS costs. Objectives: To establish whether treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (“offer of bandage”), provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (“rigid immobilisation”). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: 23 UK Emergency Departments. Participants: 965 children (4-15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online encrypted randomisation service. Exclusion criteria included presentation >36 hours after injury, multiple injuries and inability to complete follow-up. Interventions: Offer of bandage (n= 489) of whom the bandage was applied in 458, versus rigid immobilisation (n= 476). Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: Pain at 3-days post-randomisation measured using the WongBaker FACES Pain Rating Scale. Secondary outcomes were the PROMIS Upper Extremity score for children, health related quality of life (QoL), complications, school absence, analgesia use and resource use collected up to 6 weeks post-randomisation. Results: 94% of participants provided primary outcome data. Pain was equivalent at the 3 day primary outcome for both groups. With reference to the pre-specified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was -0.10; 95% CI -0.37 to 0.17 and the per-protocol population was -0.06; 95% CI -0.34 to 0.21. There was equivalence in pain for both age subgroups (4-7 and 8–15 years). There was no difference in the rate of complications, with five (1.0%) in the offer of bandage group and three (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, QoL or school absence at any point during follow-up. Analgesia use was marginally higher at Day 1 in the offer of bandage group (83% vs 78% participants), though was no different at other times. The offer of bandage significantly reduced the cost of treatment, and had a high probability of cost-effectiveness. Limitations: Families had a strong pre-existing preference for rigid immobilisation. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of bandage in children with a distal radius torus fracture.

The ability to anticipate marine habitat responses to climate variability has high socioeconomic value. Here we quantify interannual-to-decadal predictability of habitat shifts by combining trait-based aerobic habitat constraints with a suite of initialized retrospective Earth System Model forecasts, for diverse marine species in the North American Large Marine Ecosystems. We find that aerobic habitat viability, defined by joint constraints of temperature and oxygen on organismal energy balance, is potentially predictable in the upper-600 m of the ocean, showing a substantial improvement over a simple persistence forecast. The skillful multiyear predictability is dominated in most regions by the oxygen component, yielding habitat predictions with longer lead time than previously estimated based on temperature alone. Notable predictability differences exist among species differing in temperature sensitivity of hypoxia vulnerability, especially along the northeast coast. This tool will be critical in predicting marine habitat shifts in face of a changing climate.

Supplementary figures and tables

Limited clinical data are available regarding the utility of multikinase inhibition in neuroblastoma. Repotrectinib (TPX-0005) is a multikinase inhibitor that targets ALK, TRK, JAK2/STAT, and Src/FAK, which have all been implicated in the pathogenesis of neuroblastoma. We evaluated the preclinical activity of repotrectinib monotherapy and in combination with chemotherapy as a potential therapeutic approach for relapsed/refractory neuroblastoma. In vitro sensitivity to repotrectinib, ensartinib, and cytotoxic chemotherapy was evaluated in neuroblastoma cell lines. In vivo antitumor effect of repotrectinib monotherapy, and in combination with chemotherapy, was evaluated using a genotypically diverse cohort of patient-derived xenograft (PDX) models of neuroblastoma. Repotrectinib had comparable cytotoxic activity across cell lines irrespective of ALK mutational status. Combination with chemotherapy demonstrated increased antiproliferative activity across several cell lines. Repotrectinib monotherapy had notable antitumor activity and prolonged event-free survival compared with vehicle and ensartinib in PDX models (P < 0.05). Repotrectinib plus chemotherapy was superior to chemotherapy alone in ALK-mutant and ALK wild-type PDX models. These results demonstrate that repotrectinib has antitumor activity in genotypically diverse neuroblastoma models, and that combination of a multikinase inhibitor with chemotherapy may be a promising treatment paradigm for translation to the clinic.

Background: The benefits of guideline-directed medical therapy (GDMT) in heart failure (HF) are well established, but the optimization of GDMT prior to and following transcatheter edge-to-edge repair (TEER) remains understudied. The purpose of this study was to evaluate GDMT use pre-and post-TEER. Methods: We performed a retrospective analysis of the electronic health records from 2019 to 2021 at the University of Illinois at Chicago of patients that underwent TEER. Patients were included if they had follow-up records within 6 months and a baseline ejection fraction (EF) < 50%. Demographic information, vitals, labs, and pertinent echocardiogram information were obtained at baseline and 6 months. GDMT doses were collected at baseline, discharge, 30 days, 3, and 6 months. Results: In total, 20 patients were included: 15 were male (75%) and 19 were non-white (95%). The average age was 66.8 years old (range 32.8-86.5). Past medical history was significant for 19 with hypertension (95%) and 15 with hyperlipidemia, coronary artery disease, and smoking history, respectively (75%). Pre-procedure mean blood pressure and heart rate were 123/74 mmHg and 81 bpm. Average creatinine was 1.66 ± 0.94 mg/dL and 1.10 ± 0.97 mg/dL at baseline and 6 months, respectively. A total of 9 patients (45%) had functional mitral regurgitation, 11 (65%) had primary or degenerative mitral regurgitation. A total of 6 patients (30%) had 11 readmissions for acute decompensated HF, 2 patients died, and 1 patient’s EF improved to > 50% by 6 months. GDMT is described in Table 1. No patients were prescribed SGLT2 inhibitors. Conclusion: GDMT for patients pre-and post-TEER procedure is neither prescribed nor titrated effectively. Further investigation will focus on confounding factors affecting prescribing patterns and titrations. Our findings demonstrate a continued opportunity for quality improvement in GDMT optimization during TEER hospital admission and follow-up visits.

International climate goals require over 5 gigatons/year (Gt/year) of CO2 to be removed from the atmosphere by midcentury. Macroalgae mariculture has been proposed as a strategy for such carbon dioxide removal (CDR). However, the global potential for seaweed cultivation has not been assessed in detail. Here, we develop and use a dynamic seaweed growth model, the Global MacroAlgae Cultivation MODeling System (G-MACMODS), to estimate potential yields of four different types of seaweed worldwide, and test the sensitivity of these estimates to uncertain biophysical parameters under two nutrient scenarios (one in which the surface ocean nutrient budget is unaltered by the presence of seaweed farms, and another in which seaweed harvest is limited by nutrients that are resupplied by vertical transport). We find that 1 Gt of seaweed carbon could be harvested in 0.8% of global exclusive economic zones (EEZs; equivalent to ~1 million km2) if farms were located in the most productive areas, but potential harvest estimates are highly uncertain due to ill-constrained seaweed mortality and nitrogen exudation rates. Our results suggest that seaweed farming could produce climate-relevant quantities of biomass carbon and highlight key uncertainties to be resolved by future research.

Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. In vitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. In vivo anti-tumor activity was assessed in patient-derived xenograft (PDX) models of MRTs and WTs.metaVIPER analysis identified markedly aberrant activation of XPO1 in MRTs and WTs compared with other tumor types. All MRT and most WT cell lines demonstrated baseline, aberrant XPO1 activity with in vitro sensitivity to selinexor via cell-cycle arrest and induction of apoptosis. In vivo, XPO1 inhibitors significantly abrogated tumor growth in PDX models, inducing effective disease control with sustained treatment. Corroborating human relevance, we present a case report of a child with multiply relapsed WTs with prolonged disease control on selinexor.We report on a novel systems-biology-based comparative framework to identify non-genetically encoded vulnerabilities in genomically quiescent pediatric cancers. These results have provided preclinical rationale for investigation of XPO1 inhibitors in an upcoming investigator-initiated clinical trial of selinexor in children with MRTs and WTs and offer opportunities for exploration of inferred XPO1 activity as a potential predictive biomarker for response.This work was funded by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO Foundation, Cycle for Survival, Paulie Strong Foundation, and the Grayson Fund.

Author(s): Tan, Zaldy S; Soh, Michael; Knott, Alexis; Ramirez, Karina; Ercoli, Linda; Caceres, Nenette; Yuan, Stanley; Long, Matthew; Jennings, Lee A

The growth of global energy consumption and the depletion of the non-renewable recourses had caused many environment issues. These environmental issues and the demand of global energy had driven up the implementation of solar energy. The optimization of PV power output can be achieved using solar tracking and MPPT algorithm. Comparison of power output had been made with a system that does not have solar tracking to show the improvements made using a single axis solar tracking system. Power of 100 W solar tracker and two 50 W stationary panels connected in parallel. The values of the resistors of 4 and 8 Ω have been chosen based on the solar panels R characteristics. The system consists of three (3) important parts, software hardware, and electronic circuits. DC motor is used to rotate the solar PV panel (100 W) and Two (2) light dependent resistors (LDR) were used as light detectors. Solar tracker and stationary panels facing the East-West direction at University of Wollongon Malaysia KDU, Glenmarie Campus at the coordinates (3.092008, 101.559373). Two prototypes are built for data collection based on Arduino Mega 2560. An increase of 35–40% in power output compared to fixed rooftop installation.

International audience

Crowdsourcing enables human workers to perform designated tasks unbounded by time and location. As mobile devices and embedded cameras have become widely available, we deployed an image capture task globally for more geographically diverse images. Via our micro-crowdsourcing mobile application, users capture images of surrounding subjects, tag with keywords, and can choose to open source their work. We open-sourced 478,000 images collected from worldwide users as a dataset "Open Images Extended" that aims to add global diversity to imagery training data. We describe our approach and workers' feedback through survey responses from 171 global contributors to this task.

Abstract. Background: Police officers are frequently the first responders to individuals in crisis, but generally receive little training for this role. We developed and evaluated training in suicide awareness and prevention for frontline rail police in the UK. Aims: To investigate the impact of training on officers’ suicide prevention attitudes, confidence, and knowledge. Method: Fifty-three participants completed a brief questionnaire before and after undertaking training. In addition, two focus groups were conducted with 10 officers to explore in greater depth their views and experiences of the training program and the perceived impact on practice. Results: Baseline levels of suicide prevention attitudes, confidence, and knowledge were mixed but mostly positive and improved significantly after training. Such improvements were seemingly maintained over time, but there was insufficient power to test this statistically. Feedback on the course was generally excellent, notwithstanding some criticisms and suggestions for improvement. Conclusion: Training in suicide prevention appears to have been well received and to have had a beneficial impact on officers’ attitudes, confidence, and knowledge. Further research is needed to assess its longer-term effects on police attitudes, skills, and interactions with suicidal individuals, and to establish its relative effectiveness in the context of multilevel interventions.

There is significant interest in using battery energy storage systems (BESS) to reduce peak demand charges, and therefore the life cycle cost of electricity, in commercial buildings. This paper explores the drivers of economic viability of BESS in commercial buildings through statistical analysis. A sample population of buildings was generated, a techno-economic optimization model was used to size and dispatch the BESS, and the resulting optimal BESS sizes were analyzed for relevant predictor variables. Explanatory regression analyses were used to demonstrate that, of the variables considered, peak demand charges are the most significant predictor of an economically viable battery, and that the shape of the load profile is the most significant predictor of the size of the battery.

Police officers are frequently the first responders to individuals in crisis, but generally receive little training for this role. We developed and evaluated training in suicide awareness and prevention for frontline rail police in the UK.To investigate the impact of training on officers' suicide prevention attitudes, confidence, and knowledge.Fifty-three participants completed a brief questionnaire before and after undertaking training. In addition, two focus groups were conducted with 10 officers to explore in greater depth their views and experiences of the training program and the perceived impact on practice.Baseline levels of suicide prevention attitudes, confidence, and knowledge were mixed but mostly positive and improved significantly after training. Such improvements were seemingly maintained over time, but there was insufficient power to test this statistically. Feedback on the course was generally excellent, notwithstanding some criticisms and suggestions for improvement.Training in suicide prevention appears to have been well received and to have had a beneficial impact on officers' attitudes, confidence, and knowledge. Further research is needed to assess its longer-term effects on police attitudes, skills, and interactions with suicidal individuals, and to establish its relative effectiveness in the context of multilevel interventions.

Community has historically provided an essential psycho-spiritual framework for nursing. Changes in communication technology pose challenges for nurses internationally who create communities across borders. This article discusses The Bamboo Bridge online community, a project responding to the global call for nursing education about the complementarity of nursing and healing traditions. The project explores how technologies such as Centra and Ning promote community building and encourage belonging in members from 5 continents and 10 countries. This article includes detailed accounts of the project design, examples of cultural diplomacy as the emerging theoretical framework, and an African member's perspective of online community.

We investigate variability in the surface ocean carbonate ion concentration ([CO32−]) on the basis of a long control simulation with a fully-coupled Earth System Model. The simulation is run with a prescribed, pre-industrial atmospheric CO2 concentration for 1000 years, permitting investigation of natural [CO32−] variability on interannual to multi-decadal timescales. We find high interannual variability in surface [CO32−] in the tropical Pacific and at the boundaries between the subtropical and subpolar gyres in the Northern Hemisphere, and relatively low interannual variability in the centers of the subtropical gyres and in the Southern Ocean. Statistical analysis of modeled [CO32−] variance and autocorrelation suggests that significant anthropogenic trends in the saturation state of aragonite (Ωaragonite) are already or nearly detectable at the sustained, open-ocean timeseries sites, whereas several decades of observations are required to detect anthropogenic trends in Ωaragonite in the tropical Pacific, North Pacific, and North Atlantic. The detection timescale for anthropogenic trends in pH is shorter than that for Ωaragonite, due to smaller noise-to-signal ratios and lower autocorrelation in pH. In the tropical Pacific, the leading mode of surface [CO32−] variability is primarily driven by variations in the vertical advection of dissolved inorganic carbon (DIC) in association with El Niño–Southern Oscillation. In the North Pacific, surface [CO32−] variability is caused by circulation-driven variations in surface DIC and strongly correlated with the Pacific Decadal Oscillation, with peak spectral power at 20–30 year periods. North Atlantic [CO32−] variability is also driven by variations in surface DIC, and exhibits weak correlations with both the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation. As the scientific community seeks to detect the anthropogenic influence on ocean carbonate chemistry, these results will aid the interpretation of trends calculated from spatially- and temporally-sparse observations.

Androgens exert a significant effect on neutral and polar lipids in human meibomian gland secretions, and these hormonal effects may be mediated through androgen receptors causing tear film instability and evaporative dry eye (EDE).1–3 Consequently, the androgen deficiency that occurs during menopause, ageing, and even Sjogren's syndrome4 may contribute to meibomian gland dysfunction and EDE often observed in these conditions.5 Having frequently identified low serum testosterone in patients with EDE, in 2010, with specialist gynaecological consultation, we began recommending the use of a transdermal androgen patch (Intrinsa, Procter and Gamble, UK) therapy for patients attending an eye clinic with persistent and symptomatic EDE found to have low serum testosterone. We report the outcomes of our audit. A retrospective …