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Background: Over the past decade, progress in the diagnosis and treatment of Non-Small Cell Lung Cancer (NSCLC) has led to the identification of many targeted mutations. This has enhanced PFS and OS in both advanced and early-stage NSCLC. The current standard of care for stage III NSCLC varies, and it may combine chemotherapy with either immunotherapy or radiotherapy. This study evaluated the role of induction targeted therapies in patients with driver mutations and inoperable NSCLC., Methods: This is a single-center, retrospective study assessing the efficacy of targeted therapy in resectable stage III NSCLC patients who are EGFR or ALK -positive, using patient records, PET-CT, brain MRI staging, and mediastinal lymph node evaluation., Results: Between January 2020 and February 2024, we identified four patients with either EML4-ALK fusions (2/4) or EGFR mutations (2/4) who underwent treatment with brigatinib or osimertinib before surgery. All patients experienced clinical benefits. Of the two patients with ALK fusion, one responded almost completely, while the other exhibited a notable partial response. Among the patients with EGFR mutations, one had a complete response and the other displayed a significant partial response. All four patients subsequently underwent lobectomy surgical resection., Conclusions: This case series highlights the potential of targeted therapies for resectable NSCLC in the neoadjuvant setting. Further research is required to confirm their benefits, assess their safety and efficacy, and determine optimal timing and sequencing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kian, Krayim, Giles, Elkiaan, Idris, Fink, Peled and Roisman.)

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10 -9 ) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10 -16 and CPA3; p = 2.39 × 10 -14 ) and wound healing (FN1; p = 7.63 × 10 -9 ). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora., (© 2024. The Author(s).)

Abstract: Giles, B, Peeling, P, and Reid, M. Quantifying change of direction movement demands in professional tennis matchplay: An analysis from the Australian Open Grand Slam. J Strength Cond Res 38(3): 517-525, 2024-Change of direction (COD) contributes significantly to the movement repertoire of professional tennis players, yet the time-motion and degree demands of these changes are poorly understood. This study examines the velocity, acceleration, and angular displacement profiles of COD movements in modern professional tennis. One hundred eighty-two singles matches of Hawk-Eye player tracking data collected from the Australian Open Grand Slam were used for analysis. A novel COD classification algorithm was used to identify >120,000 medium and high-intensity CODs for analysis. Descriptive characteristics of the COD performance were calculated using player coordinate and time variables. Sex comparisons were analyzed using 2 mixed-effects models assessed for differences via likelihood ratios. Players performed 1.6 CODs per point. Both sexes executed, on average, 1.3-1.4 shots and covered 4.8 m per COD, with men performing changes every 2.7 seconds and women every 3.1 seconds. Medium-intensity COD comprised 88-94% of all identified changes. Approximately 2 in 3 CODs involved a degree of change >105°, whereas cutting maneuvers (<45°) were most commonly high-intensity COD. This study is the first to quantify the COD characteristics of professional tennis matchplay. Both sexes performed the same average number of CODs per point, however, men executed high-intensity changes twice as frequently as women, at an average of 1 every 5 points. These novel findings will help to improve the specificity of training interventions in elite tennis conditioning., (Copyright © 2024 National Strength and Conditioning Association.)

Pediatric pulmonology fellowship training programs are required by the Accreditation Council for Graduate Medical Education to report Pediatric Subspecialty Milestones biannually to track fellow progress. However, several issues, such as lack of subspecialty-specific context and ambiguous language, have raised concerns about their validity and applicability to use for fellow assessment and curriculum development. In this Perspective, we briefly share the process of the Pediatric Pulmonology Milestones 2.0 Work Group in creating new specialty-specific Milestones and tailoring information on the Harmonized Milestones to pediatric pulmonologists, with the goal of improving the Milestones' utility for stakeholders, including pulmonology fellows, faculty, program directors, and accrediting bodies. In addition, we created a supplemental guide to better link the Milestones to pulmonary-specific scenarios to create a shared mental model between stakeholders and remove a potential detriment to validity. Through the process, a number of guiding principles were clarified, including: 1 ) every Milestone should be able to be assessed independently, without overlap with other Milestones; 2 ) there should be clear developmental progression from one Milestone to the next; 3 ) Milestones should be based on the unique skills expected of pediatric pulmonologists; and 4 ) health equity should be a core component to highlight as a top priority to all stakeholders. In this Perspective, we describe these principles that guided formulation of the Pediatric Pulmonary Milestones to help familiarize the pediatric pulmonary community with the new Milestones. In addition, we share lessons learned and challenges in our process to inform other specialties that may soon participate in this process., (Copyright © 2024 by the American Thoracic Society.)

Objective: Patients hospitalised with decompensated cirrhosis have high rates of early unplanned readmission. Many readmissions are avoidable with secondary preventative strategies, but patients are often readmitted prior to outpatient review. To address this, we established a novel, nurse-led early postdischarge (EPD) clinic delivering goal-directed care for cirrhosis complications and evaluated the impact., Methods: Retrospective cohort study comparing outcomes in 78 patients seen in the EPD clinic with 91 phenotypically matched controls receiving standard, consultant hepatologist care. Follow-up for 12 months from index admission with endpoints including survival, time to readmission, number of readmissions and healthcare burden., Results: Median time to readmission was 51 days in controls and 98 days in the intervention group (p<0.01). The intervention cohort had significantly fewer readmissions at 30 days (12% vs 30%, p<0.01) and 90 days (27% vs 49%, p<0.01) but not significantly at 12 months (58% vs 68%, p=0.16) with an overall reduction in bed day usage of 29%. Mortality for the control group was 4% at 30 days with no deaths in the intervention group. There were significantly fewer deaths in the intervention group at 90 days (5% vs 15%, p<0.05) and 12 months (22% vs 41%, p<0.01)., Conclusions: Following an index hospitalisation with decompensated cirrhosis, goal-directed postdischarge care can be effectively delivered by specialist nurses, prior to outpatient review by hepatologists. This model was associated with significantly fewer readmissions, lower bed day usage and a reduced mortality. Our data suggest such models of care deserve wider implementation and further evaluation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The key challenges to treating glioblastoma multiforme (GBM) are the heterogeneous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood-brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components, including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM. Specifically, we explore the potential of aptamer-targeted delivery as a successful approach to treating brain cancers. Aptamers have emerged as promising therapeutic drug delivery vehicles with the potential to cross the BBB and deliver payloads to GBM and brain metastases. By targeting specific ligands within the TME, aptamers could potentially improve treatment outcomes and overcome the challenges associated with larger therapies such as antibodies.

Asthma is one of the most common chronic diseases affecting the pediatric population. The diagnosis and management of asthma is constantly evolving, and recently the National Heart, Lung, and Blood Institute published an updated guideline regarding various aspects of pediatric asthma. In this report, we review and summarize these guidelines and compare them with the Global Initiative for Asthma guidelines. [ Pediatr Ann . 2023;52(4):e153-e158.] .

Arsenic exposure is correlated with atherosclerosis in epidemiological studies and in animal models. We have previously shown that arsenic exposure enhanced the atherosclerotic plaque size, increased the plaque lipid content, and decreased the plaque smooth muscle cell and collagen contents in the apolipoprotein E knockout (apoE-/-) mice. However, the percentage of plaque-resident macrophages, the primary drivers of atherosclerosis remained unchanged. Therefore, we hypothesized that although arsenic does not change the quantity of macrophages, it alters the macrophage transcriptome towards a proatherogenic state. To test this hypothesis, we used bone marrow-derived macrophages, polarized them to either interferon-γ (IFN-ɣ) stimulated, proinflammatory or interleukin-4 (IL-4) stimulated, alternatively activated macrophages in the presence or absence of 0.67 µM (50 ppb) arsenic and performed RNA sequencing. Arsenic exposure altered the gene expression of the macrophages in a subtype-specific manner. Most differentially expressed genes (88%) were altered specifically in either IFN-ɣ- or IL-4-stimulated macrophages, whereas in the remaining 12% of genes that changed in both cell types, did so in opposite directions. In IL-4-stimulated macrophages, arsenic significantly downregulated the genes involved in cholesterol biosynthesis and the chemokines CCL17/CCL22, whereas in IFN-ɣ-stimulated macrophages, the genes associated with the liver X receptor (LXR) pathway were downregulated by arsenic. Using a bone marrow transplant experiment, we validated that the deletion of LXRα from the hematopoietic compartment rescued arsenic-enhanced atherosclerosis in the apoE-/- mouse model. Together, these data suggest that arsenic modulates subtype-specific transcriptomic changes in macrophages and further emphasize the need to define macrophage heterogeneity in atherosclerotic plaques in order to evaluate the proatherogenic role of arsenic., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lung cancer is the most common cancer-related cause of death worldwide, most of which are non-small cell lung cancers (NSCLC). Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. Treatment plans for NSCLC, specifically adenocarcinomas, rely heavily on the presence or absence of specific actionable driver mutations. Liquid biopsy can guide the treatment protocol to detect the presence of various mechanisms of resistance to treatment. We report three NSCLC EGFR mutated cases, each treated with Osimertinib in a combination therapy regimen to combat resistance mechanisms. The first patient presented with EGFR L858R/L833V compound mutation with MET amplification alongside CEP85L-ROS1 fusion gene, the second with EGFR exon 19del and MKRN1-BRAF fusion, and the last EGFR L858R/V834L compound mutation with MET amplification. Each regimen utilized a tyrosine kinase inhibitor or monoclonal antibody in addition to osimertinib and allowed for a prompt and relatively durable treatment response., Competing Interests: NP declares Advisor & Honorarium from & Research with AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merk, MSD, Novartis, NovellusDx, Pfizer, Roche, Takeda. WK declares lecture fees from Bristol-Myers Squibb and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kian, Krayim, Alsana, Giles, Purim, Alguayn, Alguayn, Peled and Roisman.)

Purpose: Recent explorations of tennis-specific movements have developed contemporary methods for identifying and classifying changes of direction (COD) during match-play. The aim of this research was to employ these new analysis techniques to objectively explore individual nuance and style factors in the execution of COD movements in professional tennis., Methods: Player tracking data from 62 male and 77 female players at the Australian Open Grand Slam were analysed for COD movements using a model algorithm, with a sample of 150,000 direction changes identified. Hierarchical clustering methods were employed on the time-motion and degree characteristics of these direction changes to identify groups of different COD performers., Results: Five unique clusters, labelled "Cutters", "Gear Changers", "Lateral Changers", "Balanced Changers" and "Passive Changers" were identified in accordance with their varying speed, acceleration, degree and directionality of change features., Conclusions: Player COD clustering challenge previously held assumptions regarding on-court movement style, highlighting the complexity and variation in the sport's locomotion demands. In practice, the speed, acceleration, directionality and degree of change characteristics of each COD style can facilitate athlete profiling and the specificity of training interventions.HighlightsWe used machine learning techniques and cluster analysis methodology to explore the time motion characteristics of direction change skill in professional tennis.We present five unique types of change of direction style in professional tennis players. These include "Cutters", "Gear Changers", "Lateral Changers", "Balanced Changers" & "Passive Changers". These style classifications were established in accordance with their varying speed, acceleration, degree and directionality of change features.We show that the application of machine learning techniques to player tracking data can facilitate a more intricate understanding the sport's physical demands, which can be used to inform training programme design.

Electromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA's Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations., (© 2022. The Author(s).)

A key challenge in developing an anticancer aptamer is to efficiently determine the selectivity and specificity of the developed aptamer to the target protein. Due to its several advantages over monoclonal antibodies, aptamer development has gained enormous popularity among cancer researchers. Systematic evolution of ligands by exponential enrichment (SELEX) is the most common method of developing aptamers specific for proteins of interest. Following SELEX, a quick and efficient binding assay accelerates the process of identification, confirming the selectivity and specificity of the aptamer. This paper explains a step-by-step flow cytometric-based binding assay of an aptamer specific for epithelial cellular adhesion molecule (EpCAM). The transmembrane glycoprotein EpCAM is overexpressed in most carcinomas and plays roles in cancer initiation, progression, and metastasis. Therefore, it is a valuable candidate for targeted drug delivery to tumors. To evaluate the selectivity and specificity of the aptamer to the membrane-bound EpCAM, EpCAM-positive and -negative cells are required. Additionally, a non-binding EpCAM aptamer with a similar length and 2-dimensional (2D) structure to the EpCAM-binding aptamer is required. The binding assay includes different buffers (blocking buffer, wash buffer, incubation buffer, and FACS buffer) and incubation steps. The aptamer is incubated with the cell lines. Following the incubation and washing steps, the cells will be evaluated using a sensitive flow cytometry assay. Analysis of the results shows the binding of the EpCAM-specific aptamer to EpCAM-positive cells and not the EpCAM-negative cells. In EpCAM-positive cells, this is depicted as a band shift in the binding of the EpCAM aptamer to the right compared to the non-binding aptamer control. In EpCAM-negative cells, the corresponding bands of EpCAM-binding and -non-binding aptamers overlap. This demonstrates the selectivity and specificity of the EpCAM aptamer. While this protocol is focused on the EpCAM aptamer, the protocol is applicable to other published aptamers.

We present observations in Earth's magnetotail by the Magnetospheric Multiscale spacecraft that are consistent with magnetic field annihilation, rather than magnetic topology change, causing fast magnetic-to-electron energy conversion in an electron-scale current sheet. Multi-spacecraft analysis for the magnetic field reconstruction shows that an electron-scale magnetic island was embedded in the observed electron diffusion region (EDR), suggesting an elongated shape of the EDR. Evidence for the annihilation was revealed in the form of the island growing at a rate much lower than expected for the standard X-type geometry of the EDR, which indicates that magnetic flux injected into the EDR was not ejected from the X-point or accumulated in the island, but was dissipated in the EDR. This energy conversion process is in contrast to that in the standard EDR of a reconnecting current sheet where the energy of antiparallel magnetic fields is mostly converted to electron bulk-flow energy. Fully kinetic simulation also demonstrates that an elongated EDR is subject to the formation of electron-scale magnetic islands in which fast but transient annihilation can occur. Consistent with the observations and simulation, theoretical analysis shows that fast magnetic diffusion can occur in an elongated EDR in the presence of nongyrotropic electron effects. We suggest that the annihilation in elongated EDRs may contribute to the dissipation of magnetic energy in a turbulent collisionless plasma., (© 2022. The Authors.)

Recent years have seen major advances in our understanding of primary biliary cholangitis, with the condition now renamed to reflect the majority of patients who do not have cirrhosis. Data from large multicentre studies have greatly increased our knowledge of the natural history of primary biliary cholangitis, making the identification of higher risk patients clearer and facilitating the development of new medications. Recent guidelines have emphasised the importance of risk stratification, targeted treatment of symptoms and early prioritisation for second line therapies. The review summarises recent major developments in our understanding of primary biliary cholangitis and its management.

Background: Vascular endothelial growth factor (VEGF)-D was identified as a potential predictive biomarker for ramucirumab efficacy in second-line metastatic colorectal cancer using a research use only (RUO) assay. We describe results with a new assay for detecting VEGF-D in human plasma., Methods: In RAISE (Clinical Trial Registration: NCT01183780), 1072 patients were randomized 1:1 to ramucirumab or placebo plus FOLFIRI. All patients were then randomized 1:2 to marker exploratory (ME) and marker confirmatory (MC) groups, and those with plasma samples were analyzed accordingly. A new assay validated for investigational use only (IUO) was used to measure VEGF-D levels in plasma, which were analyzed for correlation with overall and progression-free survival (OS/PFS). IUO assay data were compared with historical RUO assay data., Results: ME subset analyses determined the optimal cutpoint of 5.4 ng/mL for defining high/low VEGF-D subgroups. In the combined ME/MC placebo arms, OS/PFS were numerically greater for patients with low vs high VEGF-D (OS: 12.8 vs 11.1 months; PFS: 5.6 vs 4.2 months). In patients with high VEGF-D, ramucirumab vs placebo demonstrated a numerically greater improvement in OS and PFS. Differential efficacy by VEGF-D level was statistically significant for PFS, but not OS., Conclusion: In patients with high VEGF-D, ramucirumab demonstrated a greater improvement in OS and PFS vs placebo; however, baseline VEGF-D level was not predictive of ramucirumab OS benefit using VEGF-D assay for IUO. The RAISE intent-to-treat results remain valid.

The shift of discussions on wastewater management to realize a circular water economy requires rethinking of how the existing systems are managed. The collection system, a physical infrastructure that collects and transports wastewater, is often overlooked in innovation studies in wastewater management. Hence, a review of the collection system is required to realize overlooked innovation points, especially those of its functions and configurations. In this paper, we highlight the possibility of the collection system to contribute to wastewater management, not only to collect and transport wastewater, but to treat wastewater through enhancing sewer self-purification. To realize this, a systems analysis of the forms and functions of the collection system was first conducted to see how the collection system supports different wastewater management systems. It was found that emphasis on the collection system's function to treat wastewater is beneficial because of the transition of wastewater management towards a circular water economy. Second, a scenario analysis of applying enhanced sewer self-purification technologies was conducted to determine communities which would most benefit from using the collection system to treat wastewater. The findings highlight that communities with as much as 100 cap ha-1, typical of urban peripheries, could have their pollutant load reduced to about half if the pipe length per capita is 5 m. It was seen in this study that while the collection system supports wastewater management by functioning to collect and transport wastewater, it can further be elevated into a treatment technology within appropriate localities and thus, contribute to a circular water economy., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Electromagnetic ion cyclotron (EMIC) waves play important roles in particle loss processes in the magnetosphere. Determining the evolution of EMIC waves as they propagate and how this evolution affects wave-particle interactions requires accurate knowledge of the wave vector, k . We present a technique using the curl of the wave magnetic field to determine k observationally, enabled by the unique configuration and instrumentation of the Magnetospheric MultiScale (MMS) spacecraft. The wave curl analysis is demonstrated for synthetic arbitrary electromagnetic waves with varying properties typical of observed EMIC waves. The method is also applied to an EMIC wave interval observed by MMS on October 28, 2015. The derived wave properties and k from the wave curl analysis for the observed EMIC wave are compared with the Waves in Homogenous, Anisotropic, Multi-component Plasma (WHAMP) wave dispersion solution and with results from other single- and multi-spacecraft techniques. We find good agreement between k from the wave curl analysis, k determined from other observational techniques, and k determined from WHAMP. Additionally, the variation of k due to the time and frequency intervals used in the wave curl analysis is explored. This exploration demonstrates that the method is robust when applied to a wave containing at least 3-4 wave periods and over a rather wide frequency range encompassing the peak wave emission. These results provide confidence that we are able to directly determine the wave vector properties using this multi-spacecraft method implementation, enabling systematic studies of EMIC wave k properties with MMS., (© 2021. The Authors.)

Purpose: Movement and stroke production are coupled when playing tennis but generally decoupled in training and research. This study explored the lower limb, trunk and racquet mechanics of tennis players performing running forehands at varying movement speeds. Methods : Eleven female and seven male professional tennis players hit forehand groundstrokes while travelling at different movement speeds (Low: 1.4-2.0 m s - 1 , Medium: 2.70-2.90 m s - 1 , High: 4.0-4.3 m s - 1 ). Kinematics were captured using a VICON camera system. Speed and sex effects were analysed using linear mixed-effects models. Results : Prior to impact, females increased drive leg loading kinematics, and reduced preparatory trunk rotation (-9°), while both sexes lengthened their final stride and backswing during high-speed trials. At impact, racquet-head speed was unchanged for male players but dropped 14% when females travelled at high entry speed (p < 0.001). Conclusions : Reduced trunk rotation and lower limb drive contributed to female players being unable to maintain racquet-head speed when moving at high speed. Conversely, male players generated similar racquet-head speed despite the different entry speeds necessitating lower limb joint adjustments. These findings highlight the different deceleration strategies employed by male and female tennis professionals and challenge the widely accepted training theory in tennis that emphasises hitting and moving actions being rehearsed separately.

Magnetic reconnection is of fundamental importance to plasmas because of its role in releasing and repartitioning stored magnetic energy. Previous results suggest that this energy is predominantly released as ion enthalpy flux along the reconnection outflow. Using Magnetospheric Multiscale data we find the existence of very significant electron energy flux densities in the vicinity of the magnetopause electron dissipation region, orthogonal to the ion energy outflow. These may significantly impact models of electron transport, wave generation, and particle acceleration.

Human health and wellbeing and the health of the biosphere are inextricably linked. The state of Earth's life-support systems, including freshwater, oceans, land, biodiversity, atmosphere, and climate, affect human health. At the same time, human activities are adversely affecting natural systems. This review paper is the outcome of an interdisciplinary workshop under the auspices of the Future Earth Health Knowledge Action Network (Health KAN). It outlines a research agenda to address cross-cutting knowledge gaps to further understanding and management of the health risks of these global environmental changes through an expert consultation and review process. The research agenda has four main themes: (1) risk identification and management (including related to water, hygiene, sanitation, and waste management); food production and consumption; oceans; and extreme weather events and climate change. (2) Strengthening climate-resilient health systems; (3) Monitoring, surveillance, and evaluation; and (4) risk communication. Research approaches need to be transdisciplinary, multi-scalar, inclusive, equitable, and broadly communicated. Promoting resilient and sustainable development are critical for achieving human and planetary health.

Magnetotail reconnection plays a crucial role in explosive energy conversion in geospace. Because of the lack of in-situ spacecraft observations, the onset mechanism of magnetotail reconnection, however, has been controversial for decades. The key question is whether magnetotail reconnection is externally driven to occur first on electron scales or spontaneously arising from an unstable configuration on ion scales. Here, we show, using spacecraft observations and particle-in-cell (PIC) simulations, that magnetotail reconnection starts from electron reconnection in the presence of a strong external driver. Our PIC simulations show that this electron reconnection then develops into ion reconnection. These results provide direct evidence for magnetotail reconnection onset caused by electron kinetics with a strong external driver.

We report measurements of lower-hybrid drift waves driving electron heating and vortical flows in an electron-scale reconnection layer under a guide field. Electrons accelerated by the electrostatic potential of the waves exhibit perpendicular and nongyrotropic heating. The vortical flows generate magnetic field perturbations comparable to the guide field magnitude. The measurements reveal a new regime of electron-wave interaction and how this interaction modifies the electron dynamics in the reconnection layer.

In this study, the ion composition of flux transfer events (FTEs) observed within the magnetosheath proper is examined. These FTEs were observed just upstream of the Earth's postnoon magnetopause by the National Aeronautics and Space Administration (NASA) Magnetospheric Multiscale (MMS) spacecraft constellation. The minor ion characteristics are described using energy spectrograms, flux distributions, and ion moments as the constellation encountered each FTE. In conjunction with electron data and magnetic field observations, such observations provide important contextual information on the formation, topologies, and evolution of FTEs. In particular, minor ions, when combined with the field-aligned streaming of electrons, are reliable indicators of FTE topology. The observations are also placed (i) in context of the solar wind magnetic field configuration, (ii) the connection of the sampled flux tube to the ionosphere, and (iii) the location relative to the modeled reconnection line at the magnetopause. While protons and alpha particles were often depleted within the FTEs relative to the surrounding magnetosheath plasma, the He + and O + populations showed clear enhancements either near the center or near the edges of the FTE, and the bulk plasma flow directions are consistent with magnetic reconnection northward of the spacecraft and convection from the dayside toward the flank magnetopause., (©2020. The Authors.)

On 5 May 2017, MMS observed a crater-type flux rope on the dawnside tailward magnetopause with fluctuations. The boundary-normal analysis shows that the fluctuations can be attributed to nonlinear Kelvin-Helmholtz (KH) waves. Reconnection signatures such as flow reversals and Joule dissipation were identified at the leading and trailing edges of the flux rope. In particular, strong northward electron jets observed at the trailing edge indicated midlatitude reconnection associated with the 3-D structure of the KH vortex. The scale size of the flux rope, together with reconnection signatures, strongly supports the interpretation that the flux rope was generated locally by KH vortex-induced reconnection. The center of the flux rope also displayed signatures of guide-field reconnection (out-of-plane electron jets, parallel electron heating, and Joule dissipation). These signatures indicate that an interface between two interlinked flux tubes was undergoing interaction, causing a local magnetic depression, resulting in an M-shaped crater flux rope, as supported by reconstruction., (©2020. The Authors.)

During the September 2015 to March 2016 duration (sometimes referred to as Phase 1A) of the Magnetospheric Multiscale Mission, the Dual Electron Spectrometers (DES) were configured to generously utilize lossy compression. While this maximized the number of velocity distribution functions downlinked, it came at the expense of lost information content for a fraction of the frames. Following this period of lossy compression, the DES was reconfigured in a way that allowed for 95% of the frames to arrive to the ground without loss. Using this high-quality set of frames from on-orbit observations, we compressed and decompressed the frames on the ground to create a side-by-side record of the compression effect. This record was used to drive an optimization method that (a) derived basis functions capable of approximating the lossless sample space and with nonnegative coefficients and (b) fitted a function which maps the lossy frames to basis weights that recreate the frame without compression artifacts. This method is introduced and evaluated in this paper. Data users should expect a higher level of confidence in the absolute scale of density/temperature measurements and notice less sinusoidal bias in the velocity X and Y components (GSE)., (©2020. The Authors.)

Electrostatic solitary wave (ESW)-a Debye-scale structure in space plasmas-was believed to accelerate electrons. However, such a belief is still unverified in spacecraft observations, because the ESW usually moves fast in spacecraft frame and its interior has never been directly explored. Here, we report the first measurements of an ESW's interior, by the Magnetospheric Multiscale mission located in a magnetotail reconnection jet. We find that this ESW has a parallel scale of 5λ&#95;{De} (Debye length), a superslow speed (99  km/s) in spacecraft frame, a longtime duration (250 ms), and a potential drop eφ&#95;{0}/kT&#95;{e}∼5%. Inside the ESW, surprisingly, there is no electron acceleration, no clear change of electron distribution functions, but there exist strong electrostatic electron cyclotron waves. Our observations challenge the conventional belief that ESWs are efficient at particle acceleration.

The first-order Fermi acceleration of electrons requires an injection of electrons into a mildly relativistic energy range. However, the mechanism of injection has remained a puzzle both in theory and observation. We present direct evidence for a novel stochastic shock drift acceleration theory for the injection obtained with Magnetospheric Multiscale observations at the Earth's bow shock. The theoretical model can explain electron acceleration to mildly relativistic energies at high-speed astrophysical shocks, which may provide a solution to the long-standing issue of electron injection.

The Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth's magnetopause. The EDR is characterized by agyrotropic electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.

The purpose of this study was to develop an automated method for identifying and classifying change of direction (COD) movements in professional tennis using tracking data. Three sport science and strength and conditioning experts coded match-play footage of nineteen professional tennis players (9 male and 10 female) from the Australian Open Grand Slam for COD of medium and high intensity. A total of 1,494 changes were identified and aligned with 2D player position sampled at 25 Hz based on camera tracking data. Several machine learning classifiers were trained and tested on a set of 1,128 time-motion features. A random forest algorithm was found to have the best out-of-sample performance, classifying medium and high intensity changes with an F1-score of 0.729. This research offers a novel and applicable way for utilising player tracking data and machine learning techniques to automatically identify and classify COD movements in professional tennis.

While vorticity defined as the curl of the velocity has been broadly used in fluid and plasma physics, this quantity has been underutilized in space physics due to low time resolution observations. We report Magnetospheric Multiscale (MMS) observations of enhanced electron vorticity in the vicinity of the electron diffusion region of magnetic reconnection. On 11 July 2017 MMS traversed the magnetotail current sheet, observing tailward-to-earthward outflow reversal, current-carrying electron jets in the direction along the electron meandering motion or out-of-plane direction, agyrotropic electron distribution functions, and dissipative signatures. At the edge of the electron jets, the electron vorticity increased with magnitudes greater than the electron gyrofrequency. The out-of-plane velocity shear along distance from the current sheet leads to the enhanced vorticity. This, in turn, contributes to the magnetic field perturbations observed by MMS. These observations indicate that electron vorticity can act as a proxy for delineating the electron diffusion region of magnetic reconnection., (©2019. The Authors.)

Respiratory distress occurs in 5% to 7% of live births at term gestation. Most cases are mild and transient and can be attributed to transient tachypnea of the newborn or "wet lung." Severe respiratory distress is often due to nonpulmonary causes such as sepsis or congenital heart disease. Occasionally, term neonatal respiratory distress is associated with an inherited primary lung disease such as primary ciliary dyskinesia or surfactant metabolism defects. These lung diseases have characteristic presentations in the neonatal period and are important to recognize, as they necessitate different management approaches and have lifelong implications. Suspicion for these diseases should prompt referral to a pediatric pulmonologist. [Pediatr Ann. 2019;48(4):e175-e181.]., (Copyright 2019, SLACK Incorporated.)

The electron diffusion region (EDR) is the region where magnetic reconnection is initiated and electrons are energized. Because of experimental difficulties, the structure of the EDR is still poorly understood. A key question is whether the EDR has a homogeneous or patchy structure. Here we report Magnetospheric Multiscale (MMS) spacecraft observations providing evidence of inhomogeneous current densities and energy conversion over a few electron inertial lengths within an EDR at the terrestrial magnetopause, suggesting that the EDR can be rather structured. These inhomogenenities are revealed through multipoint measurements because the spacecraft separation is comparable to a few electron inertial lengths, allowing the entire MMS tetrahedron to be within the EDR most of the time. These observations are consistent with recent high-resolution and low-noise kinetic simulations.

The purpose of this study was to explore the processes associated with successful on-court movement in professional tennis. To date, research has only provided generalised insight into the physical demands of tennis movement and the requisite physical skills. Data were collected through semi-structured interviews with 15 international tennis and/or strength and conditioning coaches involved in the development of tennis-specific movement in professional men's and women's tennis. A descriptive, qualitative approach was adopted, with interviews transcribed verbatim and analysed using an inductive to deductive thematic analysis. The highlighted ideas and concepts enabled the dynamic construction of higher-order themes representative of "good" tennis movers, alongside the conceptual development of a common movement "goal" or "outcome". The established higher-order themes portrayed three "styles" of "good" movers in modern professional tennis: those who were "fast" around the court, those who "read the play" well, and those who were "efficient" in their movement. The established themes provide a framework for interpreting and categorising the movement of professional tennis players as well as its underpinning skill.

The description of the local turbulent energy transfer and the high-resolution ion distributions measured by the Magnetospheric Multiscale mission together provide a formidable tool to explore the cross-scale connection between the fluid-scale energy cascade and plasma processes at subion scales. When the small-scale energy transfer is dominated by Alfvénic, correlated velocity, and magnetic field fluctuations, beams of accelerated particles are more likely observed. Here, for the first time, we report observations suggesting the nonlinear wave-particle interaction as one possible mechanism for the energy dissipation in space plasmas.

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans., Electronic Supplementary Material: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

We study spectral features of ion velocity and magnetic field correlations in the magnetosheath and in the solar wind using data from the Magnetospheric Multiscale (MMS) spacecraft. High-resolution MMS observations enable the study of the transition of these correlations between their magnetofluid character at larger scales into the subproton kinetic range, previously unstudied in spacecraft data. Cross-helicity, angular alignment, and energy partitioning is examined over a suitable range of scales, employing measurements based on the Taylor frozen-in approximation as well as direct two-spacecraft correlation measurements. The results demonstrate signatures of alignment at large scales. As kinetic scales are approached, the alignment between v and b is destroyed by demagnetization of protons.

Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Magnetic reconnection is a fundamental process in magnetized plasma where magnetic energy is converted to plasma energy. Despite huge differences in the physical size of the reconnection layer, remarkably similar characteristics are observed in both laboratory and magnetosphere plasmas. Here we present the comparative study of the dynamics and physical mechanisms governing the energy conversion in the laboratory and space plasma in the context of two-fluid physics, aided by numerical simulations. In strongly asymmetric reconnection layers with negligible guide field, the energy deposition to electrons is found to primarily occur in the electron diffusion region where electrons are demagnetized and diffuse. A large potential well is observed within the reconnection plane and ions are accelerated by the electric field toward the exhaust region. The present comparative study identifies the robust two-fluid mechanism operating in systems over six orders of magnitude in spatial scales and over a wide range of collisionality.

We investigate the accuracy with which the reconnection electric field E M can be determined from in situ plasma data. We study the magnetotail electron diffusion region observed by National Aeronautics and Space Administration's Magnetospheric Multiscale (MMS) on 11 July 2017 at 22:34 UT and focus on the very large errors in E M that result from errors in an L M N boundary normal coordinate system. We determine several L M N coordinates for this MMS event using several different methods. We use these M axes to estimate E M . We find some consensus that the reconnection rate was roughly E M  = 3.2 ± 0.6 mV/m, which corresponds to a normalized reconnection rate of 0.18 ± 0.035. Minimum variance analysis of the electron velocity (MVA-v e ), MVA of E, minimization of Faraday residue, and an adjusted version of the maximum directional derivative of the magnetic field (MDD-B) technique all produce reasonably similar coordinate axes. We use virtual MMS data from a particle-in-cell simulation of this event to estimate the errors in the coordinate axes and reconnection rate associated with MVA-v e and MDD-B. The L and M directions are most reliably determined by MVA-v e when the spacecraft observes a clear electron jet reversal. When the magnetic field data have errors as small as 0.5% of the background field strength, the M direction obtained by MDD-B technique may be off by as much as 35°. The normal direction is most accurately obtained by MDD-B. Overall, we find that these techniques were able to identify E M from the virtual data within error bars ≥20%.

Despite the importance of millisecond duration spatial structures [chorus wave nonlinearity or time domain structures (TDS)] to plasma dynamics, there have been no direct observations of the generation and interaction of these waves and TDS with electrons at the millisecond timescale required for their understanding. Through superposition of 0.195 ms Magnetospheric Multiscale Satellite electron measurements inside 37 superposed, millisecond duration electron holes, the first observations of electron spectra and pitch angle distributions on a submillisecond timescale have been obtained. They show that keV electrons inside the superposed electron hole are accelerated by several hundred volts and that the spectrum of electrons inside the electron hole contain several maxima and minima that are explained by a model of electron energy changes on entering the holes. We report the first observation of trapped electrons inside the TDS, in accordance with the theoretical requirement that such electrons must be present in order to form the phase space holes. Mechanisms of electron acceleration by electron holes (through perpendicular energy gain as the TDS moves into a converging magnetic field) and scattering (due to the perpendicular electric field) are discussed.

Particle acceleration by plasma waves and spontaneous wave generation are fundamental energy and momentum exchange processes in collisionless plasmas. Such wave-particle interactions occur ubiquitously in space. We present ultrafast measurements in Earth's magnetosphere by the Magnetospheric Multiscale spacecraft that enabled quantitative evaluation of energy transfer in interactions associated with electromagnetic ion cyclotron waves. The observed ion distributions are not symmetric around the magnetic field direction but are in phase with the plasma wave fields. The wave-ion phase relations demonstrate that a cyclotron resonance transferred energy from hot protons to waves, which in turn nonresonantly accelerated cold He + to energies up to ~2 kilo-electron volts. These observations provide direct quantitative evidence for collisionless energy transfer in plasmas between distinct particle populations via wave-particle interactions., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism 1,2 , which results in the formation of a region called the ion foreshock 3 . In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies' 4-9 , which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges 5,10 , and potentially contribute to particle acceleration 11-13 , but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration 14,15 . The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.

Objectives: The purpose of this study was to conduct a conceptual replication of the proposition that mental toughness is associated positively with behavioural perseverance., Design: Repeated-measures design., Methods: In total, 38 male Australian rules footballers took part in this study (age, 21±3 y; mass, 82.7±11.0kg; height, 1.84±.07m; football experience, 13±4 y). Participants self-reported mental toughness approximately one week prior to their first testing session where we assessed their aerobic capacity via the measurement of peak oxygen consumption (V˙O 2peak ). Approximately one week later, participants completed a 20m shuttle run test (MST). The final testing session took place approximately one week later, where participants completed a simulated team game circuit (STGC; 60min) to simulate game-relevant level of fatigue, which was followed immediately by a 20m MST., Results: Mental toughness was a salient determinant of the variation in behavioural perseverance under typical circumstances, when prior knowledge from past research was incorporated directly into the estimation process. However, the positive association between mental toughness and behavioural perseverance did not generalise to a performance context in which participants were fatigued., Conclusions: The results of the current study suggest that mental toughness represents a salient psychological correlate of behavioural perseverance in a discrete physical task that taxes the aerobic energy system in some but not all situations. When fatigued, the effect of mental toughness is outweighed by greater underlying fitness., (Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Magnetospheric Multiscale observations are used to probe the structure and temperature profile of a guide field reconnection exhaust ~100 ion inertial lengths downstream from the X-line in the Earth's magnetosheath. Asymmetric Hall electric and magnetic field signatures were detected, together with a density cavity confined near 1 edge of the exhaust and containing electron flow toward the X-line. Electron holes were also detected both on the cavity edge and at the Hall magnetic field reversal. Predominantly parallel ion and electron heating was observed in the main exhaust, but within the cavity, electron cooling and enhanced parallel ion heating were found. This is explained in terms of the parallel electric field, which inhibits electron mixing within the cavity on newly reconnected field lines but accelerates ions. Consequently, guide field reconnection causes inhomogeneous changes in ion and electron temperature across the exhaust.

Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, this process occurs in a minuscule electron-scale diffusion region 1,2 . On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed 3-5 . Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region 6 . In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales 7-11 . However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.