We present the third data release from the Parkes Pulsar Timing Array (PPTA) project. The release contains observations of 32 pulsars obtained using the 64-m Parkes “Murriyang” radio telescope. The data span is up to 18 years with a typical cadence of 3 weeks. This data release is formed by combining an updated version of our second data release with ∼ 3 years of more recent data primarily obtained using an ultra-wide-bandwidth receiver system that operates between 704 and 4032 MHz. We provide calibrated pulse profiles, flux-density dynamic spectra, pulse times of arrival, and initial pulsar timing models. We describe methods for processing such wide-bandwidth observations, and compare this data release with our previous release.

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.

The effect of sheared E × B flow on the blob dynamics in the scrape-off layer (SOL) of HL-2A tokamak has been studied during the plasma current ramp-up in ohmically heated deuterium plasmas by the combination of poloidal and radial Langmuir probe arrays. The experimental results indicate that the SOL sheared E × B flow is substantially enhanced as the plasma current exceeds a certain value and the strong sheared E × B flow has the ability to slow the blob radial motion via stretching its poloidal correlation length. The locally accumulated blobs are suggested to be responsible for the increase of plasma density just outside the Last Closed Flux Surface (LCFS) observed in this experiment. The results presented here reveal the significant role played by the strong sheared E × B flow on the blob dynamics, which provides a potential method to control the SOL width by modifying the sheared E × B flow in future tokamak plasmas.

Steinernema populi n. sp. was recovered by baiting from beneath poplar trees in China. Morphological and molecular features provided evidence for placing the new species into the Kushidai clade. The new species is characterized by the following morphological features: third-stage infective juveniles (IJ) with a body length of 1095 (973–1172) μm, a distance from the anterior end to excretory pore of 77 (70–86) μm and a tail length of 64 (55–72) μm. The Body length/Tail length (c) ratio and Anterior end to Excretory pore/ Tail length × 100 (E%) of S. populi n. sp. are substantially greater than those of all other ‘Feltiae–Kushidai–Monticolum’ group members. The first-generation males can be recognized by a spicule length of 66 (57–77) μm and a gubernaculum length of 46 (38–60) μm. The new species is further characterized by sequences of the internal transcribed spacer and partial 28S regions of the ribosomal DNA. Phylogenetic analyses show that Steinernema akhursti and Steinernema kushidai are the closest relatives to S. populi n. sp.

Biomarkers may be useful endophenotypes for genetic studies if they share genetic sources of variation with the outcome, for example, with all-cause mortality. Australian adult study participants who had reported their parental survival information were included in the study: 14,169 participants had polygenic risk scores (PRS) from genotyping and up to 13,365 had biomarker results. We assessed associations between participants’ biomarker results and parental survival, and between biomarker results and eight parental survival PRS at varying p-value cut-offs. Survival in parents was associated with participants’ serum bilirubin, C-reactive protein, HDL cholesterol, triglycerides and uric acid, and with LDL cholesterol for participants’ fathers but not for their mothers. PRS for all-cause mortality were associated with liver function tests (alkaline phosphatase, butyrylcholinesterase, gamma-glutamyl transferase), metabolic tests (LDL and HDL cholesterol, triglycerides, uric acid), and acute-phase reactants (C-reactive protein, globulins). Association between offspring biomarker results and parental survival demonstrates the existence of familial effects common to both, while associations between biomarker results and PRS for mortality favor at least a partial genetic cause of this covariation. Identification of genetic loci affecting mortality-associated biomarkers offers a route to the identification of additional loci affecting mortality.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led the implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 6 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=150 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.

Novel concepts are essential for design innovation and can be generated with the aid of data stimuli and computers. However, current generative design algorithms focus on diagrammatic or spatial concepts that are either too abstract to understand or too detailed for early phase design exploration. This paper explores the uses of generative pre-trained transformers (GPT) for natural language design concept generation. Our experiments involve the use of GPT-2 and GPT-3 for different creative reasonings in design tasks. Both show reasonably good performance for verbal design concept generation.

Using a sample of US adults aged 65 years and older, we examined the role of dietary quality in cystatin C change over 4 years and whether this association varied by race/ethnicity. The Health and Retirement Study provided observations with biomarkers collected in 2012 and 2016, participant attributes measured in 2012, and dietary intake assessed in 2013. The sample was restricted to respondents who were non-Hispanic/Latino White (n 789), non-Hispanic/Latino Black (n 108) or Hispanic/Latino (n 61). Serum cystatin C was constructed to be equivalent to the 1999–2002 National Health and Nutrition Examination Survey (NHANES) scale. Dietary intake was assessed by a semi-quantitative FFQ with diet quality measured using an energy-adjusted form of the Alternative Healthy Eating Index-2010 (AHEI-2010). Statistical analyses were conducted using autoregressive linear modelling adjusting for covariates and complex sampling design. Cystatin C slightly increased from 1·2 mg/l to 1·3 mg/l over the observational period. Greater energy-adjusted AHEI-2010 scores were associated with slower increase in cystatin C from 2012 to 2016. Among respondents reporting moderately low to low dietary quality, Hispanic/Latinos had significantly slower increases in cystatin C than their non-Hispanic/Latino White counterparts. Our results speak to the importance of considering racial/ethnic determinants of dietary intake and subsequent changes in health in ageing populations. Further work is needed to address measurement issues including further validation of dietary intake questionnaires in diverse samples of older adults.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

Background: The coronavirus disease 2019 (COVID-19) pandemic has led an implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 9 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=144 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during the pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.

The early identification and prediction of hand-foot-and-mouth disease (HFMD) play an important role in the disease prevention and control. However, suitable models are different in regions due to the differences in geography, social economy factors. We collected data associated with daily reported HFMD cases and weather factors of Zibo city in 2010~2019 and used the generalised additive model (GAM) to evaluate the effects of weather factors on HFMD cases. Then, GAM, support vectors regression (SVR) and random forest regression (RFR) models are used to compare predictive results. The annual average incidence was 129.72/100 000 from 2010 to 2019. Its distribution showed a unimodal trend, with incidence increasing from March, peaking from May to September. Our study revealed the nonlinear relationship between temperature, rainfall and relative humidity and HFMD cases and based on the predictive result, the performances of three models constructed ranked in descending order are: SVR > GAM> RFR, and SVR has the smallest prediction errors. These findings provide quantitative evidence for the prediction of HFMD for special high-risk regions and can help public health agencies implement prevention and control measures in advance.

Vertical chutes and pipes are a common component of many industrial apparatus used in the transport and processing of powders and grains. Here, a typical arrangement is considered first in which a hopper at the top feeds the chute and a converging outlet at the bottom controls the mass flux. Discrete element method (DEM) simulations reveal that steady uniform flow is only observed for intermediate flow rates, with jamming and unsteady waves dominating slow flows and non-uniform wall detachment in fast flow. Focusing on the steady uniform regimes, a progressive idealisation is carried out by matching with equivalent DEM simulations in periodic cells. These investigations justify a one-dimensional continuum modelling of the problem and provide key test data. Novel exact solutions are derived here for vertical flow using a linear version of the ‘$\mu(I),\varPhi(I)$-rheology’, for which the bulk friction $\mu$ and steady solid volume fraction $\varPhi$ depend on the inertial number I. Despite not capturing the full nonlinear complexities, the solutions match important aspects of the DEM flow fields and reveal simple scaling laws linking many quantities of interest. In particular, this study clearly demonstrates a linear relation between the chute width and the size of the shear zones at the walls. This finding contrasts with previous works on purely quasi-static flow, which instead predict a roughly constant shear zone width, a difference which implies that finite-size effects are minimal for the inertial flows studied here.

Later Cambrian and earliest Ordovician trilobites and brachiopods spanning eight horizons from five localities within the Sông Mã, Hàm Rồng and Đông Sơn formations of the Thanh Hóa province of Việt Nam, constrain the age and faunal affinities of rocks within the Sông Đà terrane, one of several suture/fault-bounded units situated between South China to the north and Indochina to the south. ‘Ghost-like’ preservation in dolomite coupled with tectonic deformation leaves many of the fossils poorly preserved, and poor exposure precludes collecting within continuously exposed stratigraphic successions. Cambrian carbonate facies pass conformably into Lower Ordovician carbonate-rich strata that also include minor siliciclastic facies, and the recovered fauna spans several uppermost Cambrian and Lower Ordovician biozones. The fauna is of equatorial Gondwanan affinity, and comparable to that from South China, North China, Sibumasu and Australia. A new species of Miaolingian ‘ptychopariid’ trilobite, Kaotaia xuanensis, is described. Detrital zircon samples from Cambrian–Ordovician rocks of the North Việt Nam and Sông Đà terranes, and from Palaeozoic samples from the Trường Sơn sector of Indochina immediately to the south, contain a predominance of ages spanning the Neoproterozoic period and have a typical equatorial Gondwanan signature. We associate the Cambrian and Tremadocian of the Sông Đà terrane with areas immediately to the north of it, including the North Việt Nam terrane and the southern parts of Yunnan and Guangxi provinces of China.