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The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.
Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces IgG autoantibody levels through FcRn blockade. This study reports safety of efgartigimod across IgG-mediated disorders. Methods: The safety of intravenous efgartigimod was evaluated in 204 efgartigimod-treated subjects with generalized myasthenia gravis (phase 3 ADAPT and 3-year open-label extension ADAPT+ trials), primary immune thrombocytopenia (phase 3 ADVANCE trial), or pemphigus (open-label phase 2 trial). These studies examined different efgartigimod doses (10–25 mg/kg), including cyclical dosing in generalized myasthenia gravis and continuous weekly dosing in primary immune thrombocytopenia and pemphigus. Results: Across all indications and doses studied, efgartigimod demonstrated a consistent safety profile, with treatment-emergent adverse event (TEAE) rates comparable to placebo (ADAPT, 77.4% efgartigimod/84.3% placebo; ADVANCE, 93.0% efgartigimod/95.6% placebo; and 85% in the pemphigus study). Most TEAEs were mild to moderate in severity. Discontinuation rates due to adverse events were consistently low (ADAPT, 3.6% efgartigimod/3.6% placebo; ADVANCE, 3.5% efgartigimod/2.2% placebo; and 3% of pemphigus study participants). In ADAPT+, no increases in TEAEs or infections occurred with additional efgartigimod dosing (19 cycles). Conclusions: Efgartigimod was well tolerated across indications and doses studied. Most TEAEs, including infections, were mild or moderate in severity and did not increase in frequency with recurrent dosing.
The incidence of adolescent depressive disorder is globally skyrocketing in recent decades, albeit the causes and the decision deficits depression incurs has yet to be well-examined. With an instrumental learning task, the aim of the current study is to investigate the extent to which learning behavior deviates from that observed in healthy adolescent controls and track the underlying mechanistic channel for such a deviation.
Methods
We recruited a group of adolescents with major depression and age-matched healthy control subjects to carry out the learning task with either gain or loss outcome and applied a reinforcement learning model that dissociates valence (positive v. negative) of reward prediction error and selection (chosen v. unchosen).
Results
The results demonstrated that adolescent depressive patients performed significantly less well than the control group. Learning rates suggested that the optimistic bias that overall characterizes healthy adolescent subjects was absent for the depressive adolescent patients. Moreover, depressed adolescents exhibited an increased pessimistic bias for the counterfactual outcome. Lastly, individual difference analysis suggested that these observed biases, which significantly deviated from that observed in normal controls, were linked with the severity of depressive symoptoms as measured by HAMD scores.
Conclusions
By leveraging an incentivized instrumental learning task with computational modeling within a reinforcement learning framework, the current study reveals a mechanistic decision-making deficit in adolescent depressive disorder. These findings, which have implications for the identification of behavioral markers in depression, could support the clinical evaluation, including both diagnosis and prognosis of this disorder.
As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.
Acritarch biostratigraphic and δ13C chemostratigraphic data from the Krol A Formation in the Solan area (Lesser Himalaya, northern India) are integrated to aid inter-basinal correlation of early–middle Ediacaran strata. We identified a prominent negative δ13C excursion (likely equivalent to EN2 in the lower Doushantuo Formation in the Yangtze Gorges area of South China), over a dozen species of acanthomorphs (including two new species—Cavaspina tiwariae Xiao n. sp., Dictyotidium grazhdankinii Xiao n. sp.), and numerous other microfossils from an interval in the Krol A Formation. Most microfossil taxa from the Krol A and the underlying Infra-Krol formations are also present in the Doushantuo Formation. Infra-Krol acanthomorphs support a correlation with the earliest Doushantuo biozone: the Appendisphaera grandis-Weissiella grandistella-Tianzhushania spinosa Assemblage Zone. Krol A microfossils indicate a correlation with the second or (more likely, when δ13C data are considered) the third biozone in the lower Doushantuo Formation (i.e., the Tanarium tuberosum-Schizofusa zangwenlongii or Tanarium conoideum-Cavaspina basiconica Assemblage Zone). The association of acanthomorphs with EN2 in the Krol Formation fills a critical gap in South China where chert nodules, and thus acanthomorphs, are rare in the EN2 interval. Like many other Ediacaran acanthomorphs assemblages, Krol A and Doushantuo acanthomorphs are distributed in low paleolatitudes, and they may represent a distinct paleobiogeographic province in east Gondwana. The Indian data affirm the stratigraphic significance of acanthomorphs and δ13C, clarify key issues of lower Ediacaran bio- and chemostratigraphic correlation, and strengthen the basis for the study of Ediacaran eukaryote evolution and paleobiogeography.
A new near-infrared direct acceleration mechanism driven by Laguerre–Gaussian laser is proposed to stably accelerate and concentrate electron slice both in longitudinal and transversal directions in vacuum. Three-dimensional simulations show that a 2-μm circularly polarized ${\mathrm{LG}}_p^l$ (p = 0, l = 1, σz = −1) laser can directly manipulate attosecond electron slices in additional dimensions (angular directions) and give them annular structures and angular momentums. These annular vortex attosecond electron slices are expected to have some novel applications such as in the collimation of antiprotons in conventional linear accelerators, edge-enhancement electron imaging, structured X-ray generation, and analysis and manipulation of nanomaterials.
Efficient photosynthesis requires a balance of ATP and NADPH production/consumption in chloroplasts, and the exportation of reducing equivalents from chloroplasts is important for balancing stromal ATP/NADPH ratio. Here, we showed that the overexpression of purple acid phosphatase 2 on the outer membranes of chloroplasts and mitochondria can streamline the production and consumption of reducing equivalents in these two organelles, respectively. A higher capacity of consumption of reducing equivalents in mitochondria can indirectly help chloroplasts to balance the ATP/NADPH ratio in stroma and recycle NADP+, the electron acceptors of the linear electron flow (LEF). A higher rate of ATP and NADPH production from the LEF, a higher capacity of carbon fixation by the Calvin–Benson–Bassham (CBB) cycle and a greater consumption of NADH in mitochondria enhance photosynthesis in the chloroplasts, ATP production in the mitochondria and sucrose synthesis in the cytosol and eventually boost plant growth and seed yields in the overexpression lines.
A study of low-speed streaks (LSSs) embedded in the near-wall region of a turbulent boundary layer is performed using selective visualization and analysis of time-resolved tomographic particle image velocimetry (tomo-PIV). First, a three-dimensional velocity field database is acquired using time-resolved tomo-PIV for an early turbulent boundary layer. Second, detailed time-line flow patterns are obtained from the low-order reconstructed database using ‘tomographic visualizations’ by Lagrangian tracking. These time-line patterns compare remarkably well with previously observed patterns using hydrogen bubble flow visualization, and allow local identification of LSSs within the database. Third, the flow behaviour in proximity to selected LSSs is examined at varying wall distances ($10 < y^+ < 100$) and assessed using time-line and material surface evolution, to reveal the flow structure and evolution of a streak, and the flow structure evolving from streak development. It is observed that three-dimensional wave behaviour of the detected LSSs appears to develop into associated near-wall vortex flow structures, in a process somewhat similar to transitional boundary layer behaviour. Fourth, the presence of Lagrangian coherent structures is assessed in proximity to the LSSs using a Lagrangian-averaged vorticity deviation process. It is observed that quasi-streamwise vortices, adjacent to the sides of the streak-associated three-dimensional wave, precipitate an interaction with the streak. Finally, a hypothesis based on the behaviour of soliton-like coherent structures is made which explains the process of LSS formation, bursting behaviour and the generation of hairpin vortices. Comparison with other models is also discussed.
Soybean meal is rich in soybean isoflavones, which exhibit antioxidant, anti-inflammatory, antiviral and anticancer functions in humans and animals. This study was conducted to investigate the effects of soybean isoflavones on the growth performance, intestinal morphology and antioxidative properties in pigs. A total of 72 weaned piglets (7.45 ± 0.13 kg; 36 males and 36 females) were allocated into three treatments and fed corn-soybean meal (C-SBM), corn-soy protein concentrate (C-SPC) or C-SPC supplemented with equal levels of the isoflavones found in the C-SBM diet (C-SPC + ISF) for a 72-day trial. Each treatment had six replicates and four piglets per replicate, half male and half female. On day 42, one male pig from each replicate was selected and euthanized to collect intestinal samples. The results showed that compared to pigs fed the C-SPC diet, pigs fed the C-SBM and C-SPC + ISF diets had higher BW on day 72 (P < 0.05); pigs fed the C-SBM diet had significantly higher average daily gain (ADG) during days 14 to 28 (P < 0.05), with C-SPC + ISF being intermediate; pigs fed the C-SBM diet tended to have higher ADG during days 42 to 72 (P = 0.063), while pigs fed the C-SPC + ISF diet had significantly higher ADG during days 42 to 72 (P < 0.05). Moreover, compared to pigs fed the C-SPC diet, pigs fed the C-SBM diet tended to have greater villus height (P = 0.092), while pigs fed the C-SPC + ISF diet had significantly greater villus height (P < 0.05); pigs fed the C-SBM and C-SPC + ISF diets had significantly increased villus height-to-crypt depth ratio (P < 0.05). Compared with the C-SPC diet, dietary C-SPC + ISF tended to increase plasma superoxide dismutase activity on days 28 (P = 0.085) and 42 (P = 0.075) and reduce plasma malondialdehyde (MDA) content on day 42 (P = 0.089), as well as significantly decreased jejunal mucosa MDA content on day 42 (P < 0.05). However, no significant difference in the expression of tight junction genes among the three groups was found (P > 0.05). In conclusion, our results suggest that a long-term exposure to soybean isoflavones enhances the growth performance, protects the intestinal morphology and improves the antioxidative properties in pigs.
At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case–control and one nested case–cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
There seems to be geographical differences in decisions about breast conserving surgery (BCS) in breast cancer patients. This study was to evaluate patients’ attitude to BCS and to assess the factors affecting cancer practice in West China.
Methods:
A structured questionnaire was distributed to 184 patients, eliciting information about the patients’ characteristics, occupation, education, family life, recognition of illness, knowledge about BCS, the main means of gaining surgery information, selecting surgery approaches, preferences to breast reservation.
Results:
In all, 163 patients completed the questionnaire. The results indicated that only 7.4% of patients received BCS and 23% of the remaining patients desired to have BCS and the affecting factors were significantly associated with their family life, recognition of illness and the main means of gaining surgery information (P < 0.05). No associations were between BCS selecting and the other variables studied. The most frequent reasons for selecting BCS were keeping the female shape and improving quality of life (71%), the second most were postoperative recovery, minimal influence of physical function (47%) and patients’ knowledge about BCS (42%). The most frequent reasons for not selecting BCS were uncertainty about BCS results and worry about recurrence (81%), the second most was the elderly age unnecessary for BCS (40%).
Conclusions:
The findings indicate that breast cancer patients in West China do not take BCS as the first choice as the best treatment method. It is warranted that further study of more patients, attitude of patients’ partners and physicians to BCS.
To evaluate functioning, well being, and pain outcomes with desvenlafaxine succinate (DVS) treatment in depressed men and women of different age groups.
Methods:
Data from the Sheehan Disability Scale (SDS), 5-item World Health Organization Well-Being Index (WHO-5), and Visual Analog Scale–Pain Intensity (VAS-PI) were pooled from 6 double-blind, placebo-controlled, 8-week DVS trials conducted in outpatients with major depressive disorder (MDD). Patients were divided into 3 age groups. The 18-39 and >55 years of age groups were chosen as proxies for pre- and postmenopausal status; the age group of 40-55 years, which was likely to include perimenopausal women, was also evaluated. Male patients were similarly grouped to differentiate effects of menopausal status from age on treatment response.
Results:
Patients were randomized to receive DVS 100-400mg (N=1048; 18-39 years [n=451]; 40-55 years [n=457]; >55 [n=140]) or placebo (N=718; 18-39 years [n=306]; 40-55 years [n=310]; >55 [n=102]). The final SDS, WHO-5, and VAS-PI overall pain change from baseline for the total population were significantly greater in the DVS vs the placebo group (P<0.001). Mean differences (adjusted ANCOVA) from placebo in women were: SDS: 18-39: –2.1, 40-55: –2.1, >55: –3.2; WHO-5: 18-39: +1.1, 40-55: +1.8, >55: +3.3; VAS-PI 18-39: –1.4, 40-55: –5.2, >55: –9.1. In men, results were consistent across age groups studied (SDS: 18-39: –2.9, 40-55: –3.4, >55: +2.6; WHO-5: 18-39: +1.5, 40-55: +2.4, >55: –0.3; VAS-PI 18-39: –3.0, 40-55: –7.7, >55: +2.0).
Conclusions:
DVS improves functional outcomes and pain symptoms in depressed men and women across the age groups studied.
The beginning of laminar–turbulent transition is usually associated with a wave-like disturbance, but its evolution and role in precipitating the development of other flow structures are not well understood from a structure-based view. Nonlinear parabolized stability equations (NPSE) were solved numerically to simulate the transition of K-regime, N-regime and O-regime. However, only the K-regime transition was examined experimentally using both hydrogen bubble visualization and time-resolved tomographic particle image velocimetry (tomo-PIV). Based on the ‘NPSE visualization’ and ‘tomographic visualization’, at least four common characteristics of the generic transition process were identified: (i) inflectional regions representing high-shear layers (HSL) that develop in vertical velocity profiles, accompanied by ejection–sweep behaviours; (ii) low-speed streak (LSS) patterns, manifested in horizontal timelines, that seem to consist of several three-dimensional (3-D) waves; (iii) a warped wave front (WWF) pattern, displaying multiple folding processes, which develops adjacent to the LSS in the near-wall region, prior to the appearance of 𝛬-vortices; (iv) a coherent 3-D wave front, similar to a soliton, in the upper boundary layer, accompanied by regions of depression along the flanks of the wave. It was determined that the amplification and lift-up of a 3-D wave causes the development of the HSL, WWF and multiple folding behaviour of material surfaces, that all contribute to the development of a 𝛬-vortex. The amplified 3-D wave is hypothesized as a soliton-like coherent structure. Based on our results, a path to transition is proposed, which hypothesizes the function of the WWF in boundary-layer transition.
This paper proposes a fault-tolerant control (FTC) method based on fast fault observer (FFO) to solve the problem of actuator gain loss fault and stuck fault for hypersonic vehicles. Firstly, an input-output feedback linearisation model is presented that considers parametric uncertainties, control input saturation, disturbances and actuator faults. Secondly, the above factors are defined as an integrated fault item, and an improved fast fault observer is designed to estimate the integrated fault in real time. Finally, the fault-tolerant controller is constructed based on the sliding mode and fault estimation. In case of unknown faults, the effects of gain loss fault or stuck fault happen on elevators and the engine can be quickly processed, Also, the asymptotically stable tracking of the flight output reference command is completed to achieve fault-tolerant control. The final simulation experiment verifies the effectiveness of the proposed method.
To determine feasibility and efficacy of an Emergency Department Violence Intervention Program (EDVIP) to reduce violence related injuries in youth.
Methods
One hundred and thirty youth aged 14–24 presenting to an emergency with violence related injury were randomized in parallel to receive EDVIP for 1 year (n = 65) or a waitlist control (n = 65). The primary outcome was to determine feasibility. Secondary outcomes are incidence, number/severity of repeat violence related injury, justice and education systems interactions, substance misuse and mental health presentations, and ED length of stay (LOS).
Results
This study established feasibility in recruitment, outcomes collection and safety. Fidelity and adherence measures required optimization during the study. Efficacy analysis of EDVIP vs. the control group demonstrates an absolute decrease of 10.4% in repeat violence related injury (13.7% vs. 24.1%) (p = 0.15), reduction in new interactions in the justice system (OR = 0.36 (0.07–1.77)), improved engagement in education (11.8% EDVIP vs. 7.6% control, p = 0.42) and no change in repeat visits for substance or mental health. LOS decreased by 59.5 min (p = 0.21).
Conclusions
This program is feasible for ED implementation and for completion of a future RCT to measure effectiveness.
The effect of hot streaks from a gas turbine combustor on the thermodynamic load of internally air-cooled nozzle guide vanes (NGVs) and shrouds has been numerically investigated under flight conditions. The study follows two steps: one for the high-fidelity 60° combustor sector with simplified ten NGVs and three thermocouples attached; and the other for the NGV sectors where each sector consists of one high-fidelity NGV (probe NGV) and nine dummy NGVs. The first step identifies which NGV has the highest thermal load and provides the inlet flow boundary conditions for the second step. In the second step, the flow fields and thermal loads of the probe NGVs are resolved in detail.
With the systematically validated physical models, the two-phase flowfield of the combustor-NGVs sector has been successfully simulated. The predicted mean and maximum temperature at the combustor sector exit are in excellent agreement with the experimental data, which provides a solid basis for the hot-streak effect investigation. The results indicate that the second NGV, looking upstream from left, has the highest thermal load. Its maximum surface temperature is 8.4% higher than that for the same NGV but with the mean inlet boundary conditions, and 14.1% higher than the ninth NGV. The finding is consistent with the field-observed NGV damage pattern. To extend the service life of these vulnerable NGVs, some protection methods should be considered.
Healthcare workers (HCWs) are at risk of acquiring and transmitting respiratory viruses while working in healthcare settings.
Objectives:
To investigate the incidence of and factors associated with HCWs working during an acute respiratory illness (ARI).
Methods:
HCWs from 9 Canadian hospitals were prospectively enrolled in active surveillance for ARI during the 2010–2011 to 2013–2014 influenza seasons. Daily illness diaries during ARI episodes collected information on symptoms and work attendance.
Results:
At least 1 ARI episode was reported by 50.4% of participants each study season. Overall, 94.6% of ill individuals reported working at least 1 day while symptomatic, resulting in an estimated 1.9 days of working while symptomatic and 0.5 days of absence during an ARI per participant season. In multivariable analysis, the adjusted relative risk of working while symptomatic was higher for physicians and lower for nurses relative to other HCWs. Participants were more likely to work if symptoms were less severe and on the illness onset date compared to subsequent days. The most cited reason for working while symptomatic was that symptoms were mild and the HCW felt well enough to work (67%). Participants were more likely to state that they could not afford to stay home if they did not have paid sick leave and were younger.
Conclusions:
HCWs worked during most episodes of ARI, most often because their symptoms were mild. Further data are needed to understand how best to balance the costs and risks of absenteeism versus those associated with working while ill.
The release of buoyant harmful gases within enclosed spaces, such as tunnels and corridors, may engender specific health, industrial and transportation risks. For safety, a simple ventilation strategy for these spaces is to impose a flow along the tunnel, whose velocity is defined as ‘critical’, that confines the front of harmful buoyant gases immediately downstream of the source of emission. Determining the critical velocity as a function of the geometrical and dynamical conditions at the source is a fundamental fluid mechanics problem which has yet to be elucidated; this problem concerns the dynamics of non-Boussinesq releases relating to large differences between the densities of the buoyant and the ambient fluids. We have investigated this problem theoretically, by means of a simplified model of a top-hat plume in a cross-flow, and in complementary experiments by means of tests in a reduced-scale ventilated tunnel, examining releases from circular sources. Experimental results reveal: (i) the existence of two flow regimes depending on the plume Richardson number at the source $\unicode[STIX]{x1D6E4}_{i}$, one for momentum-dominated releases, $\unicode[STIX]{x1D6E4}_{i}\ll 1$, and a second for buoyancy-dominated releases, $\unicode[STIX]{x1D6E4}_{i}\gg 1$, with a smooth transition between the two; and (ii) the presence of relevant non-Boussinesq effects only for momentum-dominated releases. All these features can be conveniently predicted by the plume-based model, whose validity is, strictly speaking, limited to releases issuing from ‘small’ sources in ‘weak’ ventilation flows. Analytical solutions of the model are generally in good agreement with the experimental data, even for values of the governing parameters that are beyond the range of validity for the model. The solutions aid to clarify the effect of the source radius, and reveal interesting behaviours in the limits $\unicode[STIX]{x1D6E4}_{i}\rightarrow 0$ and $\unicode[STIX]{x1D6E4}_{i}\rightarrow \infty$. These findings support the adoption of simplified models to simulate light gas releases in confined ventilated spaces.
High-rate lithium ion batteries with long cycling lives can provide electricity grid stabilization services in the presence of large fractions of intermittent generators, such as photovoltaics. Engineering for high rate and long cycle life requires an appropriate selection of materials for both electrode and electrolyte and an understanding of how these materials degrade with use. High-rate lithium ion batteries can also facilitate faster charging of electric vehicles and provide higher energy density alternatives to supercapacitors in mass transport applications.
High-rate lithium ion batteries can play a critical role in decarbonizing our energy systems both through their underpinning of the transition to use renewable energy resources, such as photovoltaics, and electrification of transport. Their ability to be rapidly and frequently charged and discharged can enable this energy storage technology to play a key role in stabilizing future low-carbon electricity networks which integrate large fractions of intermittent renewable energy generators. This decarbonizing transition will require lithium ion technology to provide increased power and longer cycle lives at reduced cost. Rate performance and cycle life are ultimately limited by the materials used and the kinetics associated with the charge transfer reactions and ionic and electronic conduction. We review material strategies for electrode materials and electrolytes that can facilitate high rates and long cycle lives and discuss the important issues of cost, resource availability and recycling.