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.

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.

With further climate change still expected, it is predicted to increase the frequency with plants will be water stressed, which subsequently influences phytophagous insects, particularly Lepidoptera with limited mobility of larvae. Previous studies have indicated that oviposition preference and offspring performance of Lepidoptera insects are sensitive to drought separately. However, the integration of their two properties is not always seen. Here, we evaluated changes in oviposition selection and offspring fitness of a Lepidoptera insect under three water-stressed treatments using a model agroecosystem consisting of maize Zea mays, and Asian corn borer Ostrinia furnacalis. Results found that female O. furnacalis preferred to laying their eggs on well-watered maize, and then their offspring tended to survive better, attained bigger larvae mass, and developed more pupae and adults on the preferred maize. Oviposition selection of O. furnacalis positively correlated with height and leaf traits of maize, and offspring fitness positively related with water content and phytochemical traits of hosts. Overall, these results suggest that oviposition choice performed by O. furnacalis reflects the maximization of offspring fitness, supporting preference–performance hypothesis. This finding further highlights that the importance of simultaneous evaluation of performance and performance for water driving forces should be involved, in order to accurately predict population size of O. furnacalis under altered precipitation pattern.

Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May–June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2–10.5) and black race (OR, 8.4; 95% CI, 2.7–27.4) were associated with SARS-CoV-2 seropositivity.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

The butterfly plastic zone theory based on Mohr Coulomb criterion has been widely used in coal mine production. In order to verify the universality of the theory, it is necessary to compare the distribution of plastic zone under different strength criteria. Based on the elastic-plastic mechanics, the principal stress distribution function around the circular tunnel is deduced in the paper, and the boundary and radius of the plastic zone under different strength criteria are calculated. The results show that the change laws of the plastic zone around the circular tunnel under different strength criteria has the following commonness: firstly, with the increase of the lateral pressure coefficient, the shape of the plastic zone presents the change laws of “circle ellipse butterfly”; Secondly, with the increase of the lateral pressure coefficient, the radius of the plastic zone is exponential distribution, while the characteristic value is different when the radius of the plastic zone is infinite. At same time, it shows that the butterfly plastic zone has a low sensitivity dependence on the strength criterion, no matter which strength criterion is adopted, and the butterfly plastic zone will inevitably appear in the surrounding rock mass of circular tunnel in the high deviator stress environment; The plastic zone with butterfly shape is highly sensitive to the stress change, and the small stress change may promote the expansion of the plastic zone. This result is significant for us to understand and prevent rock engineering disasters and accidents.

A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.

The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.

A theoretical model based on linear potential flow theory and an eigenfunction matching method is developed to analyse the hydroelastic interaction between water waves and multiple circular floating porous elastic plates. The water domain is divided into the interior and exterior regions, representing the domain beneath each plate and the rest, which extends towards infinity horizontally, respectively. Spatial potentials in these two regions can be expressed as a series expansion of eigenfunctions. Three different types of edge conditions are considered. The unknown coefficients in the potential expressions can be determined by satisfying the continuity conditions for pressure and velocity at the interface of the two regions, together with the requirements for the motion/force at the edge of the plates. Apart from the straightforward method to evaluate the exact power dissipated by the array of porous elastic plates, an indirect method based on Green's theorem is determined. The indirect method expresses the wave-power dissipation in terms of Kochin functions. It is found that wave-power dissipation of an array of circular porous elastic plates can be enhanced by the constructive hydrodynamic interaction between the plates, and there is a profound potential of porous elastic plates for wave-power extraction. The results can be applied to a range of floating structures but have special application in modelling energy loss in flexible ice floes and wave-power extraction by flexible plate wave-energy converters.

We propose two linearly implicit energy-preserving schemes for the complex modified Korteweg–de Vries equation, based on the invariant energy quadratization method. First, a new variable is introduced and a new Hamiltonian system is constructed for this equation. Then the Fourier pseudospectral method is used for the space discretization and the Crank–Nicolson leap-frog schemes for the time discretization. The proposed schemes are linearly implicit, which is only needed to solve a linear system at each time step. The fully discrete schemes can be shown to conserve both mass and energy in the discrete setting. Some numerical examples are also presented to validate the effectiveness of the proposed schemes.

In this paper, the generation of relativistic electron mirrors (REM) and the reflection of an ultra-short laser off the mirrors are discussed, applying two-dimension particle-in-cell simulations. REMs with ultra-high acceleration and expanding velocity can be produced from a solid nanofoil illuminated normally by an ultra-intense femtosecond laser pulse with a sharp rising edge. Chirped attosecond pulse can be produced through the reflection of a counter-propagating probe laser off the accelerating REM. In the electron moving frame, the plasma frequency of the REM keeps decreasing due to its rapid expansion. The laser frequency, on the contrary, keeps increasing due to the acceleration of REM and the relativistic Doppler shift from the lab frame to the electron moving frame. Within an ultra-short time interval, the two frequencies will be equal in the electron moving frame, which leads to the resonance between laser and REM. The reflected radiation near this interval and corresponding spectra will be amplified due to the resonance. Through adjusting the arriving time of the probe laser, a certain part of the reflected field could be selectively amplified or depressed, leading to the selective adjustment of the corresponding spectra.

Flexibility is one of the important mechanical performance parameters of stent. The flexibility of tapered stents, especially self-expanding tapered stents, remains unknown. In this study, we developed a new selfexpanding tapered stent for tapered arteries and performed a numerical investigation of stent flexibility by using finite element method. The effect of stent design parameters, including taper and link space width, on stent flexibility was studied. The flexibility of the proposed stent was also compared with that of traditional cylindrical stents. Results show that the tapered stent is more flexible than the traditional cylindrical stent. Furthermore, the flexibility of the tapered stent increases with increasing stent taper and stent link space width. The increase in the stent link space width can contribute to the reduction in the peak stress. Therefore, tapered stents with high link space width will improve the stent flexibility. This work provides useful information for improvement of stent design and clinical selection.