Background: SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier. Methods: SUNFISH is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2/3 SMA. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2/3 SMA. Part 2 assessed the efficacy and safety of the selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. Results: Change from baseline in MFM32 total score (Part 2- primary endpoint) in patients treated with risdiplam versus placebo was met at month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment. Here we present 4-year efficacy and safety data from SUNFISH. Conclusions: SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of individuals with SMA.

In Paper I, we presented an overview of the Southern-sky MWA Rapid Two-metre (SMART) survey, including the survey design and search pipeline. While the combination of MWA’s large field-of-view and the voltage capture system brings a survey speed of ${\sim} 450\, {\textrm{deg}}^{2}\,\textrm{h}^{-1}$, the progression of the survey relies on the availability of compact configuration of the Phase II array. Over the past few years, by taking advantage of multiple windows of opportunity when the compact configuration was available, we have advanced the survey to 75% of the planned sky coverage. To date, about 10% of the data collected thus far have been processed for a first-pass search, where 10 min of observation is processed for dispersion measures out to 250 ${\textrm{pc cm}}^{-3}$, to realise a shallow survey that is largely sensitive to long-period pulsars. The ongoing analysis has led to two new pulsar discoveries, as well as an independent discovery and a rediscovery of a previously incorrectly characterised pulsar, all from ${\sim} 3\% $ of the data for which candidate scrutiny is completed. In this sequel to Paper I, we describe the strategies for further detailed follow-up including improved sky localisation and convergence to timing solution, and illustrate them using example pulsar discoveries. The processing has also led to re-detection of 120 pulsars in the SMART observing band, bringing the total number of pulsars detected to date with the MWA to 180, and these are used to assess the search sensitivity of current processing pipelines. The planned second-pass (deep survey) processing is expected to yield a three-fold increase in sensitivity for long-period pulsars, and a substantial improvement to millisecond pulsars by adopting optimal de-dispersion plans. The SMART survey will complement the highly successful Parkes High Time Resolution Universe survey at 1.2–1.5 GHz, and inform future large survey efforts such as those planned with the low-frequency Square Kilometre Array (SKA-Low).

We present an overview of the Southern-sky MWA Rapid Two-metre (SMART) pulsar survey that exploits the Murchison Widefield Array’s large field of view and voltage-capture system to survey the sky south of 30$^{\circ}$ in declination for pulsars and fast transients in the 140–170 MHz band. The survey is enabled by the advent of the Phase II MWA’s compact configuration, which offers an enormous efficiency in beam-forming and processing costs, thereby making an all-sky survey of this magnitude tractable with the MWA. Even with the long dwell times employed for the survey (4800 s), data collection can be completed in $<$100 h of telescope time, while still retaining the ability to reach a limiting sensitivity of $\sim$2–3 mJy (at 150 MHz, near zenith), which is effectively 3–5 times deeper than the previous-generation low-frequency southern-sky pulsar survey, completed in the 1990s. Each observation is processed to generate $\sim$5000–8000 tied-array beams that tessellate the full $\sim 610\, {\textrm{deg}^{2}}$ field of view (at 155 MHz), which are then processed to search for pulsars. The voltage-capture recording of the survey also allows a multitude of post hoc processing options including the reprocessing of data for higher time resolution and even exploring image-based techniques for pulsar candidate identification. Due to the substantial computational cost in pulsar searches at low frequencies, the survey data processing is undertaken in multiple passes: in the first pass, a shallow survey is performed, where 10 min of each observation is processed, reaching about one-third of the full-search sensitivity. Here we present the system overview including details of ongoing processing and initial results. Further details including first pulsar discoveries and a census of low-frequency detections are presented in a companion paper. Future plans include deeper searches to reach the full sensitivity and acceleration searches to target binary and millisecond pulsars. Our simulation analysis forecasts $\sim$300 new pulsars upon the completion of full processing. The SMART survey will also generate a complete digital record of the low-frequency sky, which will serve as a valuable reference for future pulsar searches planned with the low-frequency Square Kilometre Array.

Within growing marketisation of publicly funded services, the internet has provided new opportunities for marketing, delivery, and coordination of those services. Using web scraping and hyperlink network analysis techniques, this paper examines the ways in which organisations operating in Australia’s evolving National Disability Insurance Scheme (NDIS) system inter-connect online. Social media plays the most important role in the online network. Government agencies also play a central role, with many disability service organisations linking their web users to them. Government agency websites do not hyperlink to disability service providers, suggesting that governments do not see their role as assisting access to such services. Advocacy and peak disability organisations are important in online connections between the websites of government and service organisations. Innovative uses of the internet for online brokerage of disability services are evident. The implications of these findings for service delivery are discussed.

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.

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.

We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band ( ${\sim}60\%$ ), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.

Liquid phase analysis dominates the field of blood diagnostics and requires drawing blood volumes of several ml for each test. To achieve acceptable accuracy, each single liquid blood test requires ∼7 mL per blood sample, and repeated blood tests are often needed. Frequent testing ca result in Hospital Acquired Anemia for infants, chronically ill, and critically ill patients. Blood testing methods that can be utilized with small amounts of blood are a critical need to save lives. Theranos claimed to have developed novel methods requiring only a few nL of blood. However, Theranos’ techniques led to errors that exceeded beyond the medically acceptable threshold of 10%. This work investigates solid state blood analysis using low volumes of several µL. The most common blood tests used as first line for diagnostics and monitoring patients’ status, always include blood electrolytes, iron, and in some cases, heavy metals.

The present work investigates the formation of rapidly solidified Homogeneous Thin Solid Films (HTSFs) formed from blood drops, in order to make them suitable for solid state analysis in vacuo and in air. The solidification of ∼5 micro-liter (µL)-sized blood droplets into HTSFs is studied with two goals: achieve reproducible HTSFs optimized for producing accurate analysis, and successfully measure the potential accuracy of measurements made on HTSFs for blood electrolytes Na, K, Mg, Ca, and Cl and heavy metals such as Fe.

The blood volumes selected for this work are in the µL range, one thousandth volumes drawn for current liquid phase analysis. Balanced Saline Solution (BSS) is used as an initial liquid for testing solidification uniformity and a potential calibration material. Next, canine and human blood are studied on two types of HemaDropTM coatings for solidification: super-hydrophilic and hyper-hydrophilic. HTSF formation from BSS and blood drops are compared on both coated and uncoated surfaces.

Three solid state analytical methods are investigated in parallel to probe composition at different depths and test each for reproducibility and accuracy: Ion Beam Analysis (IBA), X-ray Fluorescence (XRF), and X-ray Photoelectron Spectroscopy (XPS). The results show that using solid films of blood yields composition, which can be reproducibly measured by IBA, XPS and XRF to varying degrees. XPS’s depth of analysis, limited to ∼5 nm, probes a small fraction of the HTSF, but provides insights into the range of thickness for homogeneous compositions in HTSFs. Statistical and error analysis help establish whether measurements taken in sets of three typically used in lab fall below the medically accepted error threshold (<10%) for each technique and element detected. Measurements are repeated and taken at various locations and on different HTSFs to establish reproducibility. XRF is of particular interest, because it is fast, accurate, portable and can be conducted in air, making it ideal for areas with limited resources.

In vivo and in vitro trials were conducted to assess the effects of tributyrin (TB) supplementation on short-chain fatty acid (SFCA) concentrations, fibrolytic enzyme activity, nutrient digestibility and methanogenesis in adult sheep. Nine 12-month-old ruminally cannulated Small Tail ewes (initial body weight 55 ± 5.0 kg) without pregnancy were used for the in vitro trial. In vitro substrate made to offer TB at 0, 2, 4, 6 and 8 g/kg on a dry matter (DM) basis was incubated by ruminal microbes for 72 h at 39°C. Forty-five adult Small Tail ewes used for the in vivo trial were randomly assigned to five treatments with nine animals each for an 18-d period according to body weight (55 ± 5.0 kg). Total mixed ration fed to ewes was also used to offer TB at 0, 2, 4, 6 and 8 g/kg on a DM basis. The in vitro trial showed that TB supplementation linearly increased apparent digestibility of DM, crude protein, neutral detergent fibre and acid detergent fibre, and enhanced gas production and methane emissions. The in vivo trial showed that TB supplementation decreased DM intake, but enhanced ruminal fermentation efficiency. Both in vitro and in vivo trials showed that TB supplementation enhanced total SFCA concentrations and carboxymethyl cellulase activity. The results indicate that TB supplementation might exert advantage effects on rumen microbial metabolism, despite having an enhancing effect on methanogenesis.

Cucumber powdery mildew is a destructive foliar disease caused by Podosphaera xanthii (formerly known as Sphaerotheca fuliginea) that substantially damages the yield and quality of crops. The control of this disease primarily involves the use of chemical pesticides that cause serious environmental problems. Currently, numerous studies have indicated that some plant extracts or products potentially have the ability to act as natural pesticides to control plant diseases. It has been reported that turmeric (Curcuma longa L.) and its extract can be used in agriculture due to their insecticidal and fungicidal properties. However, the most effective fungicidal component of this plant is still unknown. In the current study, the crude extract of C. longa L. was found to have a fungicidal effect against P. xanthii. Afterwards, eight fractions (Fr.1–Fr.8) were gradually separated from the crude extract by column chromatography. Fraction 1 had the highest fungicidal effect against this pathogen among the eight fractions. The active compound, (+)-(S)-ar-turmerone, was separated from Fr 1 by semi-preparative high-performance liquid chromatography and identified based on its 1H nuclear magnetic resonance (NMR) and 13C NMR spectrum data. The EC50 value of (+)-(S)-ar-turmerone was found to be 28.7 µg/ml. The compound also proved to have a curative effect. This is the first study to report that the compound (+)-(S)-ar-turmerone has an effect on controlling this disease. These results provide a basis for developing a new phytochemical fungicide from C. longa L. extract.

Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

The effects of crystal orientation and doping on the surface energy, γT, of native oxides of Si(100) and Si(111) are measured via Three Liquid Contact Angle Analysis (3LCAA) to extract γT, while Ion Beam Analysis (IBA) is used to detect Oxygen. During 3LCAA, contact angles for three liquids are measured with photographs via the “Drop and Reflection Operative Program (DROP™). DROP™ removes subjectivity in image analysis, and yields reproducible contact angles within < ±1°. Unlike to the Sessile Drop Method, DROP can yield relative errors < 3% on sets of 20-30 drops. Native oxides on 5 x 1013 B/cm3 p- doped Si(100) wafers, as received in sealed, 25 wafer teflon boats continuously stored in Class 100/ISO 5 conditions at 24.5°C in 25% controlled humidity, are found to be hydrophilic. Their γT, 52.5 ± 1.5 mJ/m2, is reproducible between four boats from three sources, and 9% greater than γT of native oxides on n- doped Si(111), which averages 48.1 ± 1.6 mJ/m2 on four 4” Si(111) wafers. IBA combining 16O nuclear resonance with channeling detects 30% more oxygen on native oxides of Si(111) than Si(100). While γT should increase on thinner, more defective oxides, Lifshitz-Van der Waals interactions γLW on native oxides of Si(100) remain at 36 ± 0.4 mJ/m2, equal to γLW on Si(111), 36 ± 0.6 mJ/m2, since γLW arises from the same SiO2 molecules. Native oxides on 4.5 x 1018 B/cm3 p+ doped Si(100) yield a γT of 39 ± 1 mJ/m2, as they are thicker per IBA. In summary, 3LCAA and IBA can detect reproducibly and accurately, within a few %, changes in the surface energy of native oxides due to thickness and surface composition arising from doping or crystal structure, if conducted in well controlled clean room conditions for measurements and storage.

Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is a new outbreak pest in China. Consequently, it is unclear whether the emergence and spread of the outbreak of this pest are triggered by rapid in situ population size increases in each outbreak area, or by immigrants from a potential source area in China. In order to explore the outbreak process of this pest through a population genetics approach, we developed ten novel polymorphic expressed sequence tags (EST)-derived microsatellites. These new microsatellites had moderately high levels of polymorphism in the tested population. The number of alleles per locus ranged from 3 to 19, with an average of 8.6, and the expected heterozygosity ranged from 0.269 to 0.783. A preliminary population genetic analysis using these new microsatellites revealed a lack of population genetic structure in natural populations of A. lepigone. The estimates of recent migration rate revealed strong gene flow among populations. In conclusion, our study developed the first set of EST-microsatellite markers and shed a new light on the population genetic structure of this pest in China.

By introducing the concept of forming springback anti-coupled systems and considering the influence of the self damping effect, meanwhile establishing higher-order geometrical nonlinear equation of a high strength and low alloy (HSLA) steel plate, then a set of nonlinear dynamic springback governing equations of the plate are obtained. The finite difference method, Newmark method and iterative method are applied to solve the whole problem. Numerical results denote that the boundary conditions, thickness-length ratio of the plate and initial impact velocity of the impactor have great influence on the springback amount of the rectangular HSLA steel plate, besides the natural frequency is affected a lot by the boundary conditions and thickness-length ratio. The effect of higher-order geometrical nonlinearity on the springback amount of the plate can be ignored, considering the first-order geometrical nonlinearity is enough accurate for such similar nonlinear dynamic problems.

Spray and granular forms of isopropyl N-(3-chlorophenyl)-carbamate (CIPC, ethyl N,N-dipropylthiocarbamate (EPTC), a,a,a-trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine (trifluralin) and 2,4-bis(isopropylamino) -6-methylmercapto-s-triazine (prometryne) were incorporated preemergence to barnyardgrass Echinochloa crusgalli (1.) Beauv.) and broadleaf weeds with a rotary tiller, wheel hoe, rotary spike, or row wheel into pre-irrigated or dry soil at three locations. The locations varied in type of soil, climatic conditions, and the species of broadleaf weeds. Rotary tiller incorporation generally resulted in best weed control with both spray and granular forms under all conditions. Herbicides usually performed best in pre-irrigated soil. Sprays and granules were equal in performance at coastal and intermediate locations; granules were more effective in the desert location. Herbicidal effectiveness was influenced by method of incorporation, form of treatment, soil moisture, environmental location, and weed type.