We provide an assessment of the Infinity Two Fusion Pilot Plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio A = 10, quasi-isodynamic stellarator with improved confinement appealing to a max-J approach, elevated plasma density and high magnetic fields (⟨B⟩ = 9 T). At the envisioned operating point [800 MW deuterium-tritium (DT) fusion], the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current (|Ibootstrap| ∼ 2 kA). Calculations of collisional alpha particle confinement in a DT FPP scenario show small energy losses to the first wall (< 1.5%) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the Pfus = 800 MW operating point is attainable with high fusion gain (Q = 40) at volume-averaged electron densities ne ≈ 2×1020 m−3, below the Sudo density limit. Additional transport calculations show that an ignited (Q = ∞) solution is available at slightly higher density (2.2×1020 m−3) with Pfus = 1.5 GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed Helium Cooled Pebble Bed is TBR ∼ 1.3. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.

The selection, design, and optimization of a suitable blanket configuration for an advanced high-field stellarator concept is seen as a key feasibility issue and has been incorporated as a vital and necessary part of the Infinity Two Fusion Pilot Plant (FPP) physics basis. The focus of this work was to identify a baseline blanket which can be rapidly deployed for Infinity Two while also maintaining flexibility and opportunities for higher performing concepts later in development. Results from this analysis indicate that gas-cooled solid breeder designs such as the Helium Cooled Pebble Bed (HCPB) are the most promising concepts, primarily motivated by the neutronics performance at applicable blanket build depths, and the relatively mature technology basis. The lithium lead (PbLi) family of concepts, particularly the Dual Cooled Lithium Lead (DCLL), offer a compelling alternative to solid blanket concepts as they have synergistic developmental pathways while simultaneously mitigating much of the technical risk of those designs. Homogenized 3-dimensional neutronics analysis of the Infinity Two configuration indicates that the HCPB achieves an adequate tritium breeding ratio (TBR) (1.30 which enables sufficient margin at low engineering fidelity), and near appropriate shielding of the magnets (average fast fluence of 1.3 x 1018 n/cm2 per fullpower year). The thermal analysis indicates that reasonably high thermal efficiencies (greater than 30%) are readily achievable with the HCPB paired with a simple Rankine cycle using reheat. Finally, the tritium fuel cycle analysis for Infinity Two shows viability, with anticipated operational inventories of less than one kilogram (approximately 675 grams) and a required TBR (TBRreq) of less than 1.05 to maintain fuel self-sufficiency (approximately 1.023 for a driver blanket with no inventory doubling). Although further optimization and engineering design is still required, at the physics basis stage all initial targets have been met for the Infinity Two configuration.

Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\alpha$. We find an approximately linear dependence of $L_\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\langle L_\alpha \rangle = ( ( 1154 \pm 121) - ( 0.81 \pm 0.14) \, ( \nu /{\rm MHz}) ) \,{\rm m}$ for frequencies ν ∈ [145 − 350] MHz.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

We present the most sensitive and detailed view of the neutral hydrogen ( ${\rm H\small I}$ ) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ( $1.6\,\mathrm{mJy\ beam}^{-1}$ ) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ ( ${\sim}10\,\mathrm{pc}$ ). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

Research indicates that sexual harassment and assault commonly occur during archaeological field research, and students, trainees, and early career professionals are more frequently subjected to harassing behaviors compared to mid-career and senior scientists. Specific to archaeological education, the undergraduate educational requirement of a field school puts students and trainees in situations where harassment historically has been unchecked. We present the results of a systematic content analysis of 24 sets of field school documents. We analyzed these documents with attention to how field school policies, procedures, and language may impact students’ perceptions of their expected behaviors, logistics and means of reporting, and stated policies surrounding sexual harassment and assault. Coding was conducted using an a priori coding scheme to identify practices that should lead to a safe and supportive field learning environment. Our coding scheme resulted in 11 primary codes that we summarized as three primary themes: (1) field school organization and expected student behavior, (2) logistics of the course, and (3) stated policies surrounding sexual harassment and assault. Based on these themes, we provide recommendations to modify field school documents and practices to create a field school that provides safe opportunities for students to learn.

The rapid development of high-intensity laser-generated particle and photon secondary sources has attracted widespread interest during the last 20 years not only due to fundamental science research but also because of the important applications of this developing technology. For instance, the generation of relativistic particle beams, betatron-type coherent X-ray radiation and high harmonic generation have attracted interest from various fields of science and technology owing to their diverse applications in biomedical, material science, energy, space, and security applications. In the field of biomedical applications in particular, laser-driven particle beams as well as laser-driven X-ray sources are a promising field of study. This article looks at the research being performed at the Institute of Plasma Physics and Lasers (IPPL) of the Hellenic Mediterranean University Research Centre. The recent installation of the ZEUS 45 TW laser system developed at IPPL offers unique opportunities for research in laser-driven particle and X-ray sources. This article provides information about the facility and describes initial experiments performed for establishing the baseline platforms for secondary plasma sources.

Various host and parasite factors interact to determine the outcome of infection. We investigated the effects of two factors on the within-host dynamics of malaria in mice: initial infectious dose and co-infection with a helminth that limits the availability of red blood cells (RBCs). Using a statistical, time-series approach to model the within-host ‘epidemiology’ of malaria, we found that increasing initial dose reduced the time to peak cell-to-cell parasite propagation, but also reduced its magnitude, while helminth co-infection delayed peak cell-to-cell propagation, except at the highest malaria doses. Using a mechanistic model of within-host infection dynamics, we identified dose-dependence in parameters describing host responses to malaria infection and uncovered a plausible explanation of the observed differences in single vs co-infections. Specifically, in co-infections, our model predicted a higher background death rate of RBCs. However, at the highest dose, when intraspecific competition between malaria parasites would be highest, these effects of co-infection were not observed. Such interactions between initial dose and co-infection, although difficult to predict a priori, are key to understanding variation in the severity of disease experienced by hosts and could inform studies of malaria transmission dynamics in nature, where co-infection and low doses are the norm.

Spot urinary polyphenols have potential as a biomarker of polyphenol-rich food intakes. The aim of this study is to explore the relationship between spot urinary polyphenols and polyphenol intakes from polyphenol-rich food sources. Young adults (18–24 years old) were recruited into a sub-study of an online intervention aimed at improving diet quality. Participants’ intake of polyphenols and polyphenol-rich foods was assessed at baseline and 3 months using repeated 24-h recalls. A spot urine sample was collected at each session, with samples analysed for polyphenol metabolites using LC-MS. To assess the strength of the relationship between urinary polyphenols and dietary polyphenols, Spearman correlations were used. Linear mixed models further evaluated the relationship between polyphenol intakes and urinary excretion. Total urinary polyphenols and hippuric acid (HA) demonstrated moderate correlation with total polyphenol intakes (rs = 0·29–0·47). HA and caffeic acid were moderately correlated with polyphenols from tea/coffee (rs = 0·26–0·46). Using linear mixed models, increases in intakes of total polyphenols or polyphenols from tea/coffee or oil resulted in a greater excretion of HA, whereas a negative relationship was observed between soya polyphenols and HA, suggesting that participants with higher intakes of soya polyphenols had a lower excretion of HA. Findings suggest that total urinary polyphenols may be a promising biomarker of total polyphenol intakes foods and drinks and that HA may be a biomarker of total polyphenol intakes and polyphenols from tea/coffee. Caffeic acid warrants further investigation as a potential biomarker of polyphenols from tea/coffee.