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The cooperative guidance problem of multiple inferior missiles intercepting a hypersonic target with the specific impact angle constraint in the two-dimensional plane is addressed in this paper, taking into consideration variations in a missile’s speed. The guidance law is designed with two subsystems: the direction of line-of-sight (LOS) and the direction of normal to LOS. In the direction of LOS, by applying the algebraic graph theory and the consensus theory, the guidance command is designed to make the system convergent in a finite time to satisfy the goal of cooperative interception. In the direction of normal to LOS, the impact angle is constrained to transform into the LOS angle at the time of interception. In view of the difficulty of measuring unknown target acceleration information in real scenarios, the guidance command is designed by utilising a super-twisting algorithm based on a nonsingular fast-terminal sliding mode (NFTSM) surface. Numerical simulation results manifest that the proposed guidance law performs efficiently and the guidance commands are free of chattering. In addition, the overall performance of this guidance law is assessed with Monte Carlo runs in the presence of measurement errors. The simulation results demonstrate that the robustness can be guaranteed, and that overall efficiency and accuracy in intercepting the hypersonic target are achieved.
Background: Treatment decisions for patients with autoimmune encephalitis (AE) frequently need to be made before results from autoantibody testing are available, as early treatment is associated with better outcomes. Cerebrospinal fluids (CSF) white blood cell (WBC) count and protein concentration measured early on in the disease process is often used, in combination with other clinical factors, to evaluate the likelihood that a patient has AE. Methods: CSF characteristics (WBC count, protein concentration, and oligoclonal banding) measured in a first AE presentation, prior to results of autoantibodies being available, were retrospectively analyzed at two tertiary care centers. Results: Ninety-five patients were included in the study. CSF WBC counts and protein levels were within normal limits for 27% (CI95%: 19–37) of patients with AE. When results of oligoclonal banding were added, 14% (CI95%: 6–16) of patients had “normal” CSF. The median CSF white blood cell count was 8 cells/mm3 (range: 0–544) and the median CSF protein concentration was 0.42 g/L (range: 0.15–3.92). Conclusions: A substantial proportion of patients with early active AE had a CSF WBC count or protein concentration within the normal. Inclusion of CSF oligoclonal banding may help identify a higher proportion of patients with an inflammatory CSF profile early in the disease process.
Background: Phase 3 COMET trial (NCT02782741) compares avalglucosidase alfa (n=51) with alglucosidase alfa (n=49) in treatment-naïve LOPD. Methods: Primary objective: determine avalglucosidase alfa effect on respiratory muscle function. Secondary/other objectives include: avalglucosidase alfa effect on functional endurance, inspiratory/expiratory muscle strength, lower/upper extremity muscle strength, motor function, health-related quality of life, safety. Results: At Week 49, change (LSmean±SE) from baseline in upright forced vital capacity %predicted was greater with avalglucosidase alfa (2.89%±0.88%) versus alglucosidase alfa (0.46%±0.93%)(absolute difference+2.43%). The primary objective, achieving statistical non-inferiority (p=0.0074), was met. Superiority testing was borderline significant (p=0.0626). Week 49 change from baseline in 6-minute walk test was 30.01-meters greater for avalglucosidase alfa (32.21±9.93m) versus alglucosidase alfa (2.19±10.40m). Positive results for avalglucosidase alfa were seen for all secondary/other efficacy endpoints. Treatment-emergent adverse events (AEs) occurred in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, 4 for AEs, all on alglucosidase alfa. Serious AEs occurred in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both. High titers and neutralizing antibodies were more common for alglucosidase alfa. Conclusions: Results demonstrate improvements in clinically meaningful outcome measures and a more favorable safety profile with avalglucosidase alfa versus alglucosidase alfa. Funding: Sanofi Genzyme
The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to
$\sim\!5$
yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of
$\sim\!162$
h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of
$0.24\ \mathrm{mJy\ beam}^{-1}$
and angular resolution of
$12-20$
arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.
Apparent inconsistency between (i) experimental and direct numerical simulation (DNS) data that show the significant influence of differential diffusion on the turbulent burning rate and (ii) recent complex-chemistry DNS data that indicate mitigation of the influence of differential diffusion on conditioned profiles of various local flame characteristics at high Karlovitz numbers, is explored by analysing new DNS data obtained from lean hydrogen–air turbulent flames. Both aforementioned effects are observed by analysing the same DNS data provided that the conditioned profiles are sampled from the entire computational domain. On the contrary, the conditioned profiles sampled at the leading edge of the mean flame brush do not indicate the mitigation, but are significantly affected by differential diffusion phenomena, e.g. because reaction zones are highly curved at the leading edge. This observation is consistent with a significant increase in the computed turbulent burning velocity with decreasing Lewis number, with all the results considered jointly being consonant with the leading point concept of premixed turbulent combustion. The concept is further supported by comparing DNS data obtained by allowing for preferential diffusion solely for a single species, either atomic or molecular hydrogen.
The systematic review examined the phenomenon of trust during public health emergency events. The literature reviewed was field studies done with people directly affected or likely to be affected by such events and included quantitative, qualitative, mixed-method, and case study primary studies in English (N = 38) as well as Arabic, Chinese, French, Russian, and Spanish (all non-English N = 30). Studies were mostly from high- and middle-income countries, and the event most covered was infectious disease. Findings from individual studies were first synthesized within methods and evaluated for certainty/confidence, and then synthesized across methods. The final set of 11 findings synthesized across methods identified a set of activities for enhancing trust and showed that it is a multi-faceted and dynamic concept.
An acute gastroenteritis (AGE) outbreak caused by a norovirus occurred at a hospital in Shanghai, China, was studied for molecular epidemiology, host susceptibility and serological roles. Rectal and environmental swabs, paired serum samples and saliva specimens were collected. Pathogens were detected by real-time polymerase chain reaction and DNA sequencing. Histo-blood group antigens (HBGA) phenotypes of saliva samples and their binding to norovirus protruding proteins were determined by enzyme-linked immunosorbent assay. The HBGA-binding interfaces and the surrounding region were analysed by the MegAlign program of DNAstar 7.1. Twenty-seven individuals in two care units were attacked with AGE at attack rates of 9.02 and 11.68%. Eighteen (78.2%) symptomatic and five (38.4%) asymptomatic individuals were GII.6/b norovirus positive. Saliva-based HBGA phenotyping showed that all symptomatic and asymptomatic cases belonged to A, B, AB or O secretors. Only four (16.7%) out of the 24 tested serum samples showed low blockade activity against HBGA-norovirus binding at the acute phase, whereas 11 (45.8%) samples at the convalescence stage showed seroconversion of such blockade. Specific blockade antibody in the population played an essential role in this norovirus epidemic. A wide HBGA-binding spectrum of GII.6 supports a need for continuous health attention and surveillance in different settings.
Metabolic syndrome - a significant risk factor for cardiovascular morbidity and mortality - is twice as prevalent among psychiatric patients (21-63%) as general populations (20-24%). Although there is an inherent illness-associated metabolic risk, medications do contribute. Atypicals vary in metabolic risk from high (clozapine, olanzapine), moderate (risperidone, quetiapine) to low (aripiprazole, ziprasidone) (ADA, 2004). Few studies have comprehensively measured cardiovascular risk or directly compared antipsychotics. Limited controlled data show that antipsychotic-induced metabolic abnormalities may be reversible, rationalizing the switch to a lower-risk agent (DeNayer, 2004). Non-HDL-cholesterol encompasses all atherogenic cholesterols and provides a marker of CV risk: an increase of 29ng/dL in diabetics is associated with 50% increased risk (Jiang, 2004). Non-HDL-cholesterol is independently associated with increased risk of non-fatal myocardial infarction and angina.
Aim:
This study will provide cross-European data from 13 countries on MS rates in schizophrenia and will assess antipsychotic metabolic profiles and benefits of antipsychotic switching.
Methods:
In this ongoing, 16-week, open-label, European multicentre study, 258 schizophrenia patients treated for ≥3 months with olanzapine, risperidone or quetiapine and who have MS will be randomized to switch to aripiprazole (Week 1: 5mg/day; Week 2: 10mg/day; flexible 10-30mg/day after Week 2) or continue with previous antipsychotic. the primary objective is to demonstrate superiority of aripiprazole versus atypicals on mean percentage change of fasting non-HDL-cholesterol from baseline to Week 16.
Conclusion:
This study will provide the first direct and comprehensive comparison of metabolic risk with various atypicals in Europe and should impact the future management of schizophrenia.
Stress is a key feature of many aetiological models of psychosis and there is considerable empirical evidence implicating stress in the development of psychosis. This paper investigates the role of psychosocial stress in the onset of psychosis by examining the relationship between current and lifetime exposure to traumatic experiences and psychosocial stressors, HPA axis function, and psychopathology in people at high risk of developing psychosis.
Methods
Sixty ‘high risk’ (HR) participants were compared with 50 healthy control (HC) participants on measures of exposure to psychosocial stressors. Subgroups of HR and HC participants which provided saliva samples were compared regarding measures of HPA axis function.
Results
HR participants were exposed to greater levels of psychosocial stress than HC participants. Specifically, HR participants were more likely to have been separated from their parents (p = .003), report severe parental antipathy (p = .011), and have been bullied while growing up (p = .024). HR participants experienced greater levels of perceived stress than HC participants (p = .001) and were more likely to have had a negative life event in the previous 6 months (p < .001). Positive correlations were found between current stress and number of life events and attenuated psychotic symptoms (r = .585, p < .001, and r = .384, p = < .001, respectively) in the HR participants.
Discussion
This study shows that people at high risk of developing psychosis experience greater levels of psychosocial stress than matched healthy control participants throughout the lifetime, from early childhood to the present day, and that current stress is strongly associated with psychotic symptomatology.
We followed up a cohort (n = 35) of clients with an “At Risk Mental State” (ARMS) for almost 2 years (mean 21.3 months). At baseline, these clients had taken part in research looking at the relationship between reasoning biases, memory, personality styles and delusional ideation. During the follow-up period, clients underwent a package of intervention from a specialist early detection team. Eighty percent (n = 28) of these clients were successfully re-interviewed. There was improvement across the cohort as a whole, however five participants (17.9%) had made the transition to psychosis at follow-up. Those who had become psychotic had lower levels of manic symptomatology at baseline than those who did not enter the first episode. Further, across the cohort, impaired working memory and delusional ideation at baseline combined to predict 45% of the delusional ideation at follow-up. These preliminary findings suggest that working memory impairments may be linked to the persistence of delusional ideation and that manic symptoms in someone with an ARMS may suggest that such an individual is less likely to develop a frank psychotic episode.
We define a measure for the accuracy of tomographic reconstruction in atom probe tomography, named here the spatial error index. We demonstrate that this index can be used to compare rigorously the spatial accuracy of various different approaches to the calculation of tomographic reconstruction. This is useful, for example, to evaluate the performance of alternate tomographic reconstruction approaches, and ensures that the comparisons are independent of individual data quality or other instrumental parameters. We then introduce a new “adaptive reconstruction” formalism that uses a progression of reconstruction parameters based on a per-atom correction from the cube root of the inverse of the voltage, along with linear correction factors linked to the evaporation sequence. We apply the measure for spatial accuracy to this new reconstruction protocol.
Amorphous Mg-Fe silicates are produced from microwave-dried sol-gels and their thermal crystallisation is studied via in situ synchrotron X-ray powder diffraction. Mg-pyroxene crystallised to forsterite, enstatite and cristobalite. The inclusion of 10% Fe formed only forsterite at much higher temperature, while pure Mg-olivine crystallised at a lower temperature than Mg-pyroxene. Cristobalite is observed as a high-temperature crystallite in the pure-Mg compositions. Crystallisation activation energies are derived and discussed in relation to protoplanetary disks.
Current approaches to reconstruction in atom probe tomography produce results that exhibit substantial distortions throughout the analysis depth. This is largely because of the need to apply a multitude of assumptions when estimating the evolution of the tip shape, and other pseudo-empirical reconstruction factors, which vary both across the face of the tip and throughout the analysis depth. We introduce a new crystallography-mediated reconstruction to improve the spatial accuracy and dramatically reduce these in-depth variations. To achieve this, we developed a barycentric transform to directly relate atomic positions in detector space to real space. This is mediated by novel crystallographic analysis techniques, including: (1) calculating the orientation of a crystal directly from the field evaporation map, (2) tracking pole locations throughout the evaporation sequence, and (3) accounting for the evolving tip radius in a manner that removes the dependence on the geometric field factor. By improving the in-depth spatial accuracy of the atom probe reconstruction, a greater accuracy of the atomic neighborhood relationships is available. This is critical in modern materials science and engineering, where an understanding of the solid solution architecture, precipitate dispersions, and descriptions of the interfaces between phases or grains are key inputs to microstructure–property relationships.
Coastal ecosystems are particularly vulnerable to alien invasions. Regular, standardized, targeted monitoring of coastal areas helps to detect the arrival of non-native species early, identify sites most vulnerable to invasion, and assess potential for further spread. This study quantified the spread and changes in distribution of non-native oyster, Crassostrea gigas, populations around the coast of Ireland. In total 37 sites were surveyed, in areas which either currently or previously harboured cultivated C. gigas, for the presence and abundance of ‘wild’ C. gigas. Wild populations were identified at 20 sites and at four additional sites C. gigas was observed as recently discarded from aquaculture activity. Five of the invaded sites were identified as being highly suitable for a population expansion based on their current population status. Importantly, we also identified individuals of C. gigas and native European oysters, Ostrea edulis, co-occurring within the same shore at five sites. This is the first record to our knowledge of such co-occurrence within Europe. This evidence of co-existing oyster species raises concerns regarding the potential impact of C. gigas on recovering O. edulis populations. In Ireland, however, C. gigas does not typically spread extensively from introduction points, and although self-containing populations exist, they are currently sustained at a much lower density than those observed in other regions such as the Wadden Sea or French Atlantic coasts. We suggest, therefore, that to protect native oyster populations, C. gigas should be eradicated where co-occurring with O. edulis and recommend continuous monitoring of invaded sites.
During 2016 February, CSIRO Astronomy and Space Science and the Max-Planck-Institute for Radio Astronomy installed, commissioned, and carried out science observations with a phased array feed receiver system on the 64-m diameter Parkes radio telescope. Here, we demonstrate that the phased array feed can be used for pulsar observations and we highlight some unique capabilities. We demonstrate that the pulse profiles obtained using the phased array feed can be calibrated and that multiple pulsars can be simultaneously observed. Significantly, we find that an intrinsic polarisation leakage of −31 dB can be achieved with a phased array feed beam offset from the centre of the field of view. We discuss the possibilities for using a phased array feed for future pulsar observations and for searching for fast radio bursts with the Parkes and Effelsberg telescopes.
Correlative microscopy approaches offer synergistic solutions to many research problems. One such combination, that has been studied in limited detail, is the use of atom probe tomography (APT) and transmission Kikuchi diffraction (TKD) on the same tip specimen. By combining these two powerful microscopy techniques, the microstructure of important engineering alloys can be studied in greater detail. For the first time, the accuracy of crystallographic measurements made using APT will be independently verified using TKD. Experimental data from two atom probe tips, one a nanocrystalline Al–0.5Ag alloy specimen collected on a straight flight-path atom probe and the other a high purity Mo specimen collected on a reflectron-fitted instrument, will be compared. We find that the average minimum misorientation angle, calculated from calibrated atom probe reconstructions with two different pole combinations, deviate 0.7° and 1.4°, respectively, from the TKD results. The type of atom probe and experimental conditions appear to have some impact on this accuracy and the reconstruction and measurement procedures are likely to contribute further to degradation in angular resolution. The challenges and implications of this correlative approach will also be discussed.
A truthful snapshot of horse welfare conditions is a prerequisite for predicting the impact of any actions intended to improve the quality of life of horses. This can be achieved when welfare information, gathered by different assessors in diverse geographical areas, is valid, comparable and collected in a harmonized way. This paper aims to present the first outcomes of the Animal Welfare Indicators (AWIN) approach: the results of on-farm assessment and a reliable and harmonized data collection system. A total of 355 sport and leisure horses, stabled in 40 facilities in Italy and in Germany, were evaluated by three trained assessors using the AWIN welfare assessment protocol for horses. The AWINHorse app was used to collect, store and send data to a common server. Identified welfare issues were obesity, unsatisfactory box dimensions, long periods of confinement and lack of social interaction. The digitalized data collection was feasible in an on-farm environment, and our results suggest that this approach could prove useful in identifying the most relevant welfare issues of horses in Europe or worldwide.
Background: Ataluren is the first drug to treat the underlying cause of nmDMD. Methods: Phase 2 and 3 studies of ataluren in nmDMD were reviewed, with efficacy and safety/tolerability findings summarized. Results: Ataluren nmDMD trials include: a Phase 2a proof-of-concept study (N=38); a Phase 2b randomized controlled trial (RCT) (N=174); an ongoing US-based open-label safety extension study (N=108); an ongoing non-US-based open-label safety/efficacy extension study (N=94); and a Phase 3 RCT, ACT DMD (N=228), whose primary endpoint was change in six-minute walk distance (6MWD) over 48 weeks. The proof-of-concept study demonstrated increased dystrophin production in post-treatment muscle biopsies from ataluren-treated patients with nmDMD. The Phase 2b results demonstrated an ataluren treatment effect in 6MWD, timed function tests, and other measures of physical functioning, The Phase 3 ACT DMD results demonstrated an ataluren treatment effect in patients with nmDMD in both primary and secondary endpoints, particularly in those with a baseline 6MWD of 300-400m. Ataluren was consistently well-tolerated in all three trials, as well as in the ongoing extension studies. Trial findings will be presented in detail. Conclusions: The totality of the results demonstrates that ataluren enables nonsense mutation readthrough in the dystrophin mRNA, producing functional dystrophin and slowing disease progression.