Understanding how time averaging changes during burial is essential for using Holocene and Anthropocene cores to analyze ecosystem change, given the many ways in which time averaging affects biodiversity measures. Here, we use transition-rate matrices to explore how the extent of time averaging changes downcore as shells transit through a taphonomically complex mixed layer into permanently buried historical layers: this is a null model, without any temporal changes in rates of sedimentation or bioturbation, to contrast with downcore patterns that might be produced by human activity. Assuming stochastic burial and exhumation movements of shells between increments within the mixed layer and stochastic disintegration within increments, we find that almost all combinations of net sedimentation, mixing, and disintegration produce a downcore increase in time averaging (interquartile range [IQR] of shell ages), this trend is typically associated with a decrease in kurtosis and skewness and by a shift from right-skewed to symmetrical age distributions. A downcore increase in time averaging is thus the null expectation wherever bioturbation generates an internally structured mixed layer (i.e., a surface, well-mixed layer is underlain by an incompletely mixed layer): under these conditions, shells are mixed throughout the entire mixed layer at a slower rate than they are buried below it by sedimentation. This downcore trend created by mixing is further amplified by the downcore decline in disintegration rate. We find that transition-rate matrices accurately reproduce the downcore changes in IQR, skewness, and kurtosis observed in bivalve assemblages from the southern California shelf. The right-skewed shell age-frequency distributions typical of surface death assemblages—the focus of most actualistic research—might be fossilized under exceptional conditions of episodic anoxia or sudden burial. However, such right-skewed assemblages will typically not survive transit through the surface mixed layer into subsurface historical layers: they are geologically transient. The deep-time fossil record will be dominated instead by the more time-averaged assemblages with weakly skewed age distributions that form in the lower parts of the mixed layer.

The EU-funded Animal Welfare Indicators (AWIN) research project (2011-2015) aimed to improve animal welfare through the development of practical on-farm animal welfare assessment protocols. The present study describes the application of the AWIN approach to the development of a welfare assessment protocol for horses (Equus caballus). Its development required the following steps: (i) selection of potential welfare indicators; (ii) bridging gaps in knowledge; (iii) consulting stakeholders; and (iv) testing a prototype protocol on-farm. Compared to existing welfare assessment protocols for other species, the AWIN welfare assessment protocol for horses introduces a number of innovative aspects, such as implementation of a two-level strategy focused on improving on-farm feasibility and the use of electronic tools to achieve standardised data collection and so promote rapid outcomes. Further refinement to the AWIN welfare assessment protocol for horses is needed in order to firstly gather data from a larger reference population and, secondly, enhance the welfare assessment protocol with reference to different horse housing and husbandry conditions.

The adaptability of horses and donkeys to different types of activity has seen the European equine industry become an important economic sector, giving rise to increasing concern regarding equine welfare. As part of the AWIN (Animal Welfare Indicators) project, this review focuses on scientific literature to find potential animal-based welfare indicators — the initial step in developing a valid, reliable and feasible on-farm welfare assessment protocol for equines. Forty-nine indicators were considered and classified in accordance with the four Principles and twelve Criteria developed by Welfare Quality®. Only practical indicators specifically for on-farm use were included, those requiring the use of specific instruments or laboratory analysis were excluded. Academic scientists, partners and collaborators of the AWIN project, discussed and agreed on validity, reliability, on-farm feasibility and acceptance by farmers for each indicator. Some aspects of equine welfare have been thoroughly investigated and appear to have indicators ready for on-farm use (eg ‘absence of prolonged hunger’, ‘absence of injuries and diseases’). On the other hand, a lack of animal-based measures were identified for other Criteria such as ‘absence of pain’ and ‘positive emotional state’. Ongoing research within the AWIN project has begun exploring some of the aforementioned Criteria — these preliminary results of promising indicators have been included (eg Horse Grimace Scale and Qualitative Behaviour Assessment). Further research should address the validity and reliability of indicators, such as human-animal relationship tests and signs of cold stress. As well as for working equines, the development and application of a welfare assessment protocol could be the first step for enhancing on-farm equine welfare.

As TeV gamma-ray astronomy progresses into the era of the Cherenkov Telescope Array (CTA), there is a desire for the capacity to instantaneously follow up on transient phenomena and continuously monitor gamma-ray flux at energies above $10^{12}\,\mathrm{eV}$ . To this end, a worldwide network of Imaging Air Cherenkov Telescopes (IACTs) is required to provide triggers for CTA observations and complementary continuous monitoring. An IACT array sited in Australia would contribute significant coverage of the Southern Hemisphere sky. Here, we investigate the suitability of a small IACT array and how different design factors influence its performance. Monte Carlo simulations were produced based on the Small-Sized Telescope (SST) and Medium-Sized Telescope (MST) designs from CTA. Angular resolution improved with larger baseline distances up to 277 m between telescopes, and energy thresholds were lower at 1 000 m altitude than at 0 m. The ${\sim} 300\,\mathrm{GeV}$ energy threshold of MSTs proved more suitable for observing transients than the ${\sim}1.2\,\mathrm{TeV}$ threshold of SSTs. An array of four MSTs at 1 000 m was estimated to give a 5.7 $\sigma$ detection of an RS Ophiuchi-like nova eruption from a 4-h observation. We conclude that an array of four MST-class IACTs at an Australian site would ideally complement the capabilities of CTA.

Uvite, CaMg3(Al5Mg)(Si6O18)(BO3)3(OH)3(OH), is a new mineral of the tourmaline supergroup. It occurs in the Facciatoia quarry, San Piero in Campo, Elba Island, Italy (42°45′04.55″N, 10°12′50.89″E) at the centre of a narrow (2–3 cm wide) vein composed of aggregates of dark brown to black tourmaline, penetrating (magnesite + dolomite)-rich hydrothermally altered metaserpentinite. Crystals are euhedral and up to 1 cm in size, brown with a vitreous lustre, conchoidal fracture and grey streak. Uvite has a Mohs hardness of ~7½, a calculated density of 3.115 g/cm3 and is uniaxial (–). Uvite has trigonal symmetry, space group R3m, a = 15.9519(10) Å, c = 7.2222(5) Å, V = 1597.3(1) Å3 and Z = 3. The crystal structure was refined to R1 = 1.77% using 1666 unique reflections collected with MoKα X-rays. Crystal-chemical analysis resulted in the empirical crystal-chemical formula $^X ({\rm Ca}_{0.61}{\rm Na}_{{0.35}} \square_{{0.04}})_{\Sigma 1.00}{}^{Y} \left( {{\rm Mg}_{1.50}{\rm Fe}^{2 + }_{0.47} {\rm Al}_{0.71}{\rm Fe}^{3 + }_{0.14} {\rm Ti}_{0.18}} \right)_{\Sigma 3.00}$${}^{Z} \left( {{\rm Al}_{4.54}{\rm Fe}^{3 + }_{0.18} {\rm V}^{3 + }_{0.02} {\rm Mg}_{1.27}} \right)_{\Sigma 6.00}{}^{T}\left[ {{\left( {{\rm Si}_{5.90}{\rm Al}_{0.10}} \right)}_{\Sigma 6.00}{\rm O}_{18}} \right]{\rm } \left( {\rm BO_3} \right)_3^{} {^{\rm O(3)}}\left( {\rm OH} \right)_3{}^{{\rm O}\left( 1 \right)} [\left( {\rm OH} \right)_{0.55}{\rm F}_{0.05}{\rm O}_{0.40}]_{\Sigma 1.00}$

which recast in its ordered form for classification purposes is:

$$\eqalign{& ^{\rm X} ({\rm Ca}_{0.61}{\rm Na}_{0.35}\squ _{0.04})_{\Sigma 1.00}{}^{\rm Y} \left( {{\rm Mg}_{2.35}{\rm Fe}^{2 + }_{0.47} {\rm Ti}_{0.18}} \right)_{\Sigma 3.00} \cr & {}^{\rm Z} \left( {{\rm Al}_{5.25}{\rm Fe}^{3 + }_{0.32} {\rm V}^{3 + }_{0.02} {\rm Mg}_{0.42}} \right)_{\Sigma 6.00}{}^{\rm T} \left[ {{\left( {{\rm Si}_{5.90}{\rm Al}_{0.10}} \right)}_{\Sigma 6.00}{\rm O}_{18}} \right]{\rm }\left( {\rm BO_3} \right)_3{}^{\rm V} \left( {\rm OH} \right)_3{}^{\rm W} [\left( {\rm OH} \right)_{0.55}{\rm F}_{0.05}{\rm O}_{0.40}]_{\Sigma 1.00}}$$

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

Background: Assays capable of detecting prions in CSF (e.g., RT-QuIC) have greatly improved the antemortem diagnosis of Creutzfeldt-Jakob disease (CJD) yet take time to conduct and are not widely accessible. There is a need to identify clinical features and common tests that identify mimics at presentation. Methods: Mimics were identified within longitudinal studies of rapidly progressive dementia at study sites. Mimics met clinical criteria for probable CJD but did not have CJD. Clinical features were compared between mimics and patients with CJD assessed at Mayo Clinic Enterprise (n=79) and Washington University in St. Louis (n=10; Jan-2014 to Oct-2020). Results: Mimics (10/155; 6.5%) were diagnosed with autoimmune encephalitis (n=7), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, and unknown dementia. Age-at-symptom onset, gender, presenting symptoms, and EEG and MRI findings were similar between mimics and CJD patients. Focal motor abnormalities (49/93, 10/10), elevations in CSF leukocytosis (4/92, 5/10) and protein (39/92, 9/10) were more common in mimics (p<0.01). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (4/9) and CSF (5/10) of mimics, but not CJD cases. Conclusions: Autoimmune encephalitis, neurosarcoidosis and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies.

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 recent increase in well-localised fast radio bursts (FRBs) has facilitated in-depth studies of global FRB host properties, the source circumburst medium, and the potential impacts of these environments on the burst properties. The Australian Square Kilometre Array Pathfinder (ASKAP) has localised 11 FRBs with sub-arcsecond to arcsecond precision, leading to sub-galaxy localisation regions in some cases and those covering much of the host galaxy in others. The method used to astrometrically register the FRB image frame for ASKAP, in order to align it with images taken at other wavelengths, is currently limited by the brightness of continuum sources detected in the short-duration (‘snapshot’) voltage data captured by the Commensal Real-Time ASKAP Fast Transients (CRAFT) software correlator, which are used to correct for any frame offsets due to imperfect calibration solutions and estimate the accuracy of any required correction. In this paper, we use dedicated observations of bright, compact radio sources in the low- and mid-frequency bands observable by ASKAP to investigate the typical astrometric accuracy of the positions obtained using this so-called ‘snapshot’ technique. Having captured these data with both the CRAFT software and ASKAP hardware correlators, we also compare the offset distributions obtained from both data products to estimate a typical offset between the image frames resulting from the differing processing paths, laying the groundwork for future use of the longer duration, higher signal-to-noise ratio (S/N) data recorded by the hardware correlator. We find typical offsets between the two frames of ${\sim}0.6$ and ${\sim}0.3$ arcsec in the low- and mid-band data, respectively, for both RA and Dec. We also find reasonable agreement between our offset distributions and those of the published FRBs. We detect only a weak dependence in positional offset on the relative separation in time and elevation between target and calibrator scans, with the trends being more pronounced in the low-band data and in Dec. Conversely, the offsets show a clear dependence on frequency in the low band, which we compare to the frequency-dependent Dec. offsets found in FRB 200430. In addition, we present a refined methodology for estimating the overall astrometric accuracy of CRAFT FRBs.

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.

This comparison study of two groups within an inception cohort aimed to compare the frequency of motor impairment between preschool children with univentricular and biventricular critical congenital heart disease (CHD) not diagnosed with cerebral palsy/acquired brain injury, describe and compare their motor profiles and explore predictors of motor impairment in each group.

Children with an intellectual quotient <70 or cerebral palsy/acquired brain injury were excluded. Motor skills were assessed with the Movement Assessment Battery for Children-2. Total scores <5th percentile indicated motor impairment. Statistical analysis included χ2 test and multiple logistic regression analysis.

At a mean age of 55.4 (standard deviation 3.77) months, motor impairment was present in 11.8% of those with biventricular critical CHD, and 32.4% (p < 0.001) of those with univentricular critical CHD. The greatest difference between children with biventricular and univentricular CHD was seen in total test scores 8.73(2.9) versus 6.44(2.8) (p < 0.01) and in balance skills, 8.84 (2.8) versus 6.97 (2.5) (p = 0.001). Manual dexterity mean scores of children with univentricular CHD were significantly below the general population mean (>than one standard deviation). Independent odds ratio for motor impairment in children with biventricular critical CHD was presence of chromosomal abnormality, odds ratio 10.9 (CI 2.13–55.8) (p = 0.004); and in children with univentricular critical CHD odds ratio were: postoperative day 1–5 highest lactate (mmol/L), OR: 1.65 (C1.04–2.62) (p = 0.034), and dialysis requirement any time before the 4.5-year-old assessment, OR: 7.8 (CI 1.08–56.5) (p = 0.042).

Early assessment of motor skills, particularly balance and manual dexterity, allows for intervention and supports that can address challenges during the school years.

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.

Over the past seventy-five years, the UN has evolved significantly, often in response to geopolitical dynamics and new waves of thinking. In some respects, the UN has registered remarkable achievements, stimulating a wide range of multilateral treaties, promoting significant growth of human rights, and at times playing a central role in containing and preventing large-scale armed conflict. As part of the special issue on “The United Nations at Seventy-Five: Looking Back to Look Forward,” this essay argues that the organization has been the most impactful in three areas: producing, shaping, and driving key ideas, particularly on development and rights; generating such effective operational agencies as UNICEF and the World Food Program; and, especially in the immediate post–Cold War period, addressing major conflict risks through the Security Council. Since then, however, the UN has struggled to meet emerging challenges on many fronts and been increasingly hampered by internal ossification and institutional sprawl as well as internecine dysfunction. The twenty-first century has confronted the UN with further challenges relating most notably to climate change; to risks arising from new technologies; and to the increasingly fraught relationships between China, Russia, and the United States. If the past seventy-five years can offer one lesson, it is that new thinking and new ideas will need to drive the organization to evolve still further and faster, or else risk irrelevance.