Influence of the biomechanical variables of the gait cycle in running economy. [Influencia de variables biomecánicas del ciclo de paso en la economía de carrera].

<p algn="justify">The aim of this study was to investigate the relationships between biomechanical variables and running economy (RE). Eleven recreational (RR) and 14 well-trained runners (WT) completed 4 min stages on a treadmill at different speeds. During the test, biomechanical variables such as ground contact time (tc), swing time (tsw), stride length, frequency and angle and the length of the different subphases of ground contact were calculated using an optical measurement system. VO2 was measured in order to calculate RE. The WT runners were more economical than the RR at all speeds and presented lower tc, higher tsw, longer strides, lower stride frequencies and higher stride angles (P<0.05). Similarly, the WT runners experienced a later propulsion subphase than the RR runners (P<0.05). RE was positively related to tc, stride frequency and 10-km race pace, whereas it was negatively related to tsw, stride length, stride angle and the propulsive subphase. Our results suggest that running patterns characterized by longer stride lengths and higher stride angles, lower stride frequencies and tc, higher tsw and later propulsion suphases may enable an efficient energy use per stride. </p> Resumen <p align="justify">El objetivo de este estudio fue el investigar las relaciones entre diferentes variables biomecánicas y la economía de carrera (RE). Once atletas populares (RR) y 14 atletas altamente entrenados (WT) completaron estadios de 4 min en tapiz rodante a diferentes velocidades. Durante el test, el tiempo de contacto (tc) y de vuelo (tsw), la longitud, frecuencia y ángulo de zancada y la duración de las diferentes sub-fases del tiempo de contacto se calcularon usando un sistema óptico. Se midió el VO2 para calcular la RE. Los atletas WT fueron más económicos que los RR y presentaron menores tc, mayores tsw, zancadas más largas, frecuencias más bajas y ángulos mayores (P<0.05). Además, los atletas WT experimentaron la sub-fase propulsiva más tarde que los RR (P<0.05). La RE estuvo positivamente relacionada con el tc, la frecuencia de zancada y el ritmo de 10 km, mientras que estuvo negativamente relacionada con el tsw, longitud y ángulo de zancada y la sub-fase propulsiva. Estos resultados sugieren que una biomecánica caracterizada por zancadas más largas, ángulos de zancada y tsw mayores, menores frecuencias y tc, y sub-fases propulsivas más tardías pueden favorecer un uso energético más eficiente.</p

A social-ecological approach to conservation planning: embedding social considerations

Many conservation plans remain unimplemented, in part because of insufficient consideration of the social processes that influence conservation decisions. Complementing social considerations with an integrated understanding of the ecology of a region can result in a more complete conservation approach. We suggest that linking conservation planning to a social-ecological systems (SES) framework can lead to a more thorough understanding of human-environment interactions and more effective integration of social considerations. By characterizing SES as a set of subsystems, and their interactions with each other and with external factors, the SES framework can improve our understanding of the linkages between social and ecological influences on the environment. Using this framework can help to identify socially and ecologically focused conservation actions that will benefit ecosystems and human communities, and assist in the development of more consistent evidence for evaluating conservation actions by comparing conservation case studies

High-K dielectric sulfur-selenium alloys.

Upcoming advancements in flexible technology require mechanically compliant dielectric materials. Current dielectrics have either high dielectric constant, K (e.g., metal oxides) or good flexibility (e.g., polymers). Here, we achieve a golden mean of these properties and obtain a lightweight, viscoelastic, high-K dielectric material by combining two nonpolar, brittle constituents, namely, sulfur (S) and selenium (Se). This S-Se alloy retains polymer-like mechanical flexibility along with a dielectric strength (40 kV/mm) and a high dielectric constant (K = 74 at 1 MHz) similar to those of established metal oxides. Our theoretical model suggests that the principal reason is the strong dipole moment generated due to the unique structural orientation between S and Se atoms. The S-Se alloys can bridge the chasm between mechanically soft and high-K dielectric materials toward several flexible device applications

Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells

The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs.National Cancer Institute (U.S.) (Grant P01-CA080111)National Institutes of Health (U.S.) (Grant R01-CA078461

A Parabolised Stability Equation based Broadband Shock-Associated Noise Model

International audienceWavepacket models have been used extensively to predict the noise produced from turbulent subsonic and supersonic jets. Such wavepackets, which represent the organised structures of the flow, are solutions to the linearised Navier-Stokes equations. Using a kinematic two-point model, Wong et al. [1] have indicated the importance of incorporating coherence decay in modelling broadband shock-associated noise (BBSAN) in supersonic jets. In this work, we aim to improve the model by using solutions from linear parabolised stability equations (PSE) to model the wavepacket part of the BBSAN source. The two-point coherence of the wavepackets is obtained from large-eddy simulation (LES) data of a M j = 1.5 fully-expanded isothermal supersonic jet [2]. The aim is to build a dynamic sound-source model for BBSAN that would improve on the simplified line-source model proposed by Wong et al. [3]. We find that a frequency dependent coherence decay length scale is important in order to suppress the higher-order harmonic peaks [4] and to obtain the correct BBSAN peak shape. Moderate agreement up to St = 1 was found between the current noise predictions and those from experimental data. I. Nomenclature ω = wavepacket frequency θ = azimuthal coordinate c s n = amplitude coefficient of the shock cells G = Green's function k s = shock-cell wavenumber k h = hydrodynamic wavenumber L = longitudinal extent of wavepacket L c = coherence length of wavepacket m = azimuthal mode number M j = ideally-expanded Mach number r = radial coordinate u s = shock cell velocity fluctuation u t = wavepacket fluctuationŝ u * ω = velocity fluctuations at a frequency ω x = axial coordinat

Nivolumab With or Without Ipilimumab in Pediatric Patients With High-Grade CNS Malignancies: Safety, Efficacy, Biomarker, and Pharmacokinetics: CheckMate 908

BACKGROUND: Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO+ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies. METHODS: Patients (N=166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg+IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts). Secondary endpoints included other efficacy metrics and safety. Exploratory endpoints included pharmacokinetics and biomarker analyses. RESULTS: As of January 13, 2021, median OS (80% CI) was 11.7 (10.3-16.5) and 10.8 (9.1-15.8) months with NIVO and NIVO+IPI, respectively, in newly diagnosed DIPG. Median PFS (80% CI) with NIVO and NIVO+IPI was 1.7 (1.4-2.7) and 1.3 (1.2-1.5) months, respectively, in recurrent/progressive high-grade glioma; 1.4 (1.2-1.4) and 2.8 (1.5-4.5) months in relapsed/resistant medulloblastoma; and 1.4 (1.4-2.6) and 4.6 (1.4-5.4) months in relapsed/resistant ependymoma. In patients with other recurrent/progressive CNS tumors, median PFS (95% CI) was 1.2 (1.1-1.3) and 1.6 (1.3-3.5) months, respectively. Grade 3/4 treatment-related adverse-event rates were 14.1% (NIVO) and 27.2% (NIVO+IPI). NIVO and IPI first-dose trough concentrations were lower in youngest and lowest-weight patients. Baseline tumor programmed death ligand 1 expression was not associated with survival. CONCLUSIONS: NIVO±IPI did not demonstrate clinical benefit relative to historical data. The overall safety profiles were manageable with no new safety signals

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1–2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.National Institute of Allergy and Infectious Diseases (U.S.) (Awards UM1AI100663)National Institute of Allergy and Infectious Diseases (U.S.) (Awards AI110657

Cohort Profile: The Flu Watch Study

Influenza is a common, highly contagious respiratory virus which infects all age groups, causing a range of outcomes from asymptomatic infection and mild respiratory disease to severe respiratory disease and death.1 If infected, the adaptive immune system produces a humoral (antibody) and cell-mediated (T cell) immune response to fight the infection.2 Influenza viruses continually evolve through antigenic drift, resulting in slightly different ‘seasonal’ influenza strains circulating each year. Population-level antibody immunity to these seasonal viruses builds up over time, so in any given season only a proportion of the population is susceptible to the circulating strains. Occasionally, influenza A viruses evolve rapidly through antigenic shift by swapping genes with influenza viruses usually circulating in animals. This process creates an immunologically distinct virus to which the population may have little to no antibody immunity. The virus can result in a pandemic if a large portion of the population is susceptible and the virus is easily spread

Rapid literature mapping on the recent use of machine learning for wildlife imagery

Machine (especially deep) learning algorithms are changing the way wildlife imagery is processed. They dramatically speed up the time to detect, count, and classify animals and their behaviours. Yet, we currently have very few systematic literature surveys on its use in wildlife imagery. Through a literature survey (a ‘rapid’ review) and bibliometric mapping, we explored its use across: 1) species (vertebrates), 2) image types (e.g., camera traps, or drones), 3) study locations, 4) alternative machine learning algorithms, 5) outcomes (e.g., recognition, classification, or tracking), 6) reporting quality and openness, 7) author affiliation, and 8) publication journal types. We found that an increasing number of studies used convolutional neural networks (i.e., deep learning). Typically, studies have focused on large charismatic or iconic mammalian species. An increasing number of studies have been published in ecology-specific journals indicating the uptake of deep learning to transform the detection, classification and tracking of wildlife. Sharing of code was limited, with only 20% of studies providing links to analysis code. Much of the published research and focus on animals came from India, China, Australia, or the USA. There were relatively few collaborations across countries. Given the power of machine learning, we recommend increasing collaboration and sharing approaches to utilise increasing amounts of wildlife imagery more rapidly and transform and improve understanding of wildlife behaviour and conservation. Our survey, augmented with bibliometric analyses, provides valuable signposts for future studies to resolve and address shortcomings, gaps, and biases