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The rapid development of AI has resulted in an unprecedented paradigm shift across various industries, with aerospace among the laureates of this transformation. This review paper attempts to explore and provide comprehensive overview of the aerospace research imperatives from the AI perspective, detailing the technical sides of the full lifecycle from vehicle design and operational optimisation to advanced air traffic management systems. By examining real-world engineering implementations, the review demonstrates how AI-driven solutions are directly addressing longstanding challenges in aerospace, such as optimising flight performance, reducing operational costs and improving system reliability. A significant emphasis is placed on the crucial roles of AI in health monitoring and predictive maintenance, areas that are pivotal for ensuring the safety and longevity of aerospace endeavors, and which are now increasingly adopted in industry for remaining useful life (RUL) forecasting and condition-based maintenance strategies. The paper also discusses AI embedded in quality control and inspection processes, where it boosts accuracy, efficiency and fault detection capability. The review provides insight into the state-of-the-art applications of AI in planetary exploration, particularly within the realms of autonomous scientific instrumentation and robotic prospecting, as well as surface operations on extraterrestrial bodies. An important case study is India’s Chandrayaan-3 mission, demonstrating the application of AI in both autonomous navigation and scientific exploration within the challenging environments of space. By furnishing an overview of the field, the paper frames the ever-important, increasing domains of AI as the forefront in the advancement of aerospace engineering and opens avenues for further discussion regarding the limitless possibilities at the juncture of intelligent systems and aerospace innovation.
Malacological surveys were conducted in 2021 in the Kimpese region of Central Kongo Province, west of the Democratic Republic of Congo (DRC). Snail specimens were collected following a standardised protocol, identified using morphological and molecular methods, and tested for schistosome infection using a diagnostic PCR assay. Positive snail samples were sequenced to characterise the infecting schistosome species. Partial mitochondrial cytochrome c oxidase subunit 1 (COX1) gene sequences were used in phylogenetic analyses to explore the evolutionary position of these snail species within the broader African context. At least four intermediate snail hosts were identified: Bulinus truncatus, Bulinus forskalii, Biomphalaria pfeifferi, and a Biomphalaria species belonging to the Nilotic species complex (tentatively named Biomphalaria cf sudanica), of which the species identity needs to be confirmed. A total of 37 out of 1,196 snails (3.1%) tested positive for schistosome infection, with an infection prevalence of 7.4% for B. truncatus with Schistosoma haematobium and 1.5% for Biomphalaria spp. with Schistosoma mansoni. The S. mansoni sequence retrieved from these samples formed a basal clade relative to Zambian isolates, whereas S. haematobium grouped with the most frequently characterised haplotype cluster previously identified across mainland Africa. It is important to note that no animal schistosome species were identified in this study. Both the sequences from the snail hosts and the parasites represent novel contributions from the DRC. Additionally, the findings update the current knowledge of schistosomiasis transmission in the Kimpese region by providing insight into the phylogenetic placement, species diversity, and infection status of local snail populations.
Background: While efgartigimod usage is expected to reduce immunoglobulin (IG) utilization, evidence in clinical practice is limited. Methods: In this retrospective cohort study, patients with gMG treated with efgartigimod for ≥1-year were identified from US medical/pharmacy claims data (April 2016-January 2024) and data from the My VYVGART Path patient support program (PSP). The number of IG courses during 1-year before and after efgartigimod initiation (index date) were evaluated. Patients with ≥6 annual IG courses were considered chronic IG users. Myasthenia Gravis Activities of Daily Living (MG-ADL) scores before and after index were obtained from the PSP where available. Descriptive statistics were used without adjustment for covariates. Results: 167 patients with ≥1 IG claim before index were included. Prior to efgartigimod initiation, the majority of patients (62%) received IG chronically. During the 1-year after index, the number of IG courses fell by 95% (pre: 1531, post: 75). 89% (n=149/167) of patients fully discontinued IG usage. Mean (SD) best-follow up MG-ADL scores were significantly reduced after index (8.0 [4.1] to 2.8 [2.1], P<0.05, n=73/167, 44%). Conclusions: Based on US claims, IG utilization was substantially reduced among patients who continued efgartigimod for ≥1-year, with patients demonstrating a favorable MG-ADL response.
Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.
Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.
Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.
Background: Late-onset Pompe disease (LOPD) is caused by a deficiency of acid α-glucosidase (GAA), leading to progressive muscle and respiratory decline. Cipaglucosidase alfa (cipa), a recombinant human GAA naturally enriched with bis-mannose-6-phosphate, exhibits improved muscle uptake but is limited by inactivation at near-neutral blood pH. Miglustat (mig), an enzyme stabiliser, binds competitively and reversibly to cipa, enhancing its stability and activity. Methods: In dose-finding studies, Gaa-/- mice were treated with cipa (20 mg/kg) +/- mig (10 mg/kg; equivalent human dose ~260 mg). Clinical study methodologies have been published (Schoser et al. Lancet Neurol 2021:20;1027–37; Schoser et al. J Neurol 2024:271;2810–23). Results: In Gaa-/- mice, cipa+mig improved muscle glycogen reduction more than cipa alone and grip strength to levels approaching wild-type mice. LOPD patients (n=11) treated with cipa alone showed dose-dependent decreases in hexose tetrasaccharide (Hex4) levels by ~15% from baseline, decreasing another ~10% with added mig (260 mg). In a head-to-head study, cipa+mig had a similar safety profile to alglucosidase alfa. Among 151 patients (three trials), mig-related adverse events occurred in 21 (13.9%), none serious. Conclusions: Mig stabilised cipa in circulation, improving cipa exposure, further reducing Hex4 levels and was well tolerated in clinical studies in patients with LOPD. Sponsored by Amicus Therapeutics, Inc.
Background: Plasma pTau217 is a robust biomarker for the diagnosis of Alzheimer’s disease (AD). However, most pTau217 assays are not widely available for clinical testing. We assessed the performance of two commercially available plasma pTau217 immunoassays in a clinical diagnostic laboratory for AD diagnosis. Methods: 219 plasma samples from healthy controls with negative amyloid PET, 115 plasma samples from pathology-confirmed and 263 samples with confirmed amyloid PET were selected. Plasma pTau217 levels were measured using the ALZpath pTau217 assay on the Quanterix HD-X Simoa platform and the Lumipulse pTau217 assay on the Lumipulse G1200 platform at and BC Neuroimmunology Lab and Neurocode USA. Results: For the ALZpath assay, the coefficients were 10.4%, 10.4%, and 9.9%, and for the Fujirebio assay, were 12.1%, 12.2%, and 5.3%, respectively. Sample stability and interference were similar between the two assays, although moderate heterophilic antibody interference and reduced frozen sample stability at -20˚C were observed for the Fujirebio assay. Both assays demonstrated similar clinical performance and differentiated individuals with AD (ALZpath AUC = 0.94; Fujirebio AUC = 0.90). Conclusions: The performance of the two pTau 217 assays was comparable. The clinical separation between the healthy controls and those with Amyloid pathology was nearly complete for both assays.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
Determining the factors that impact the risk for infection with SARS-CoV-2 is a priority as the virus continues to infect people worldwide. The objective was to determine the effectiveness of vaccines and other factors associated with infection among Canadian healthcare workers (HCWs) followed from 15 June 2020 to 1 December 2023. We also investigate the association between antibodies to SARS-CoV-2 and subsequent infections with SARS-CoV-2. Of the 2474 eligible participants, 2133 (86%) were female, 33% were nurses, the median age was 41 years, and 99.3% had received at least two doses of COVID-19 vaccine by 31 December 2021. The incidence of SARS-CoV-2 was 0.91 per 1000 person-days. Prior to the circulation of the Omicron variants, vaccine effectiveness (VE) was estimated at 85% (95% CI 1, 98) for participants who received the primary series of vaccine. During the Omicron period, relative adjusted VE was 43% (95% CI 29, 54), 56% (95% CI 42, 67), and 46% (95% CI 24, 62) for 3, 4, and ≥ 5 doses compared with those who received primary series after adjusting for previous infection and other covariates. Exposure to infected household members, coworkers, or friends in the previous 14 days were risk factor for infection, while contact with an infected patient was not statistically significant. Participants with higher levels of immunoglobulin G (IgG) anti-receptor binding domain (RBD) antibodies had lower rates of infection than those with the lowest levels. COVID-19 vaccines remained effective throughout the follow-up of this cohort of highly vaccinated HCWs. IgG anti-RBD antibody levels may be useful as correlates of protection for issues such as vaccine development and testing. There remains a need to increase the awareness among HCWs about the risk of contracting SARS-CoV-2 from contacts at a variety of venues.
Distinguishing early domesticates from their wild progenitors presents a significant obstacle for understanding human-mediated effects in the past. The origin of dogs is particularly controversial because potential early dog remains often lack corroborating evidence that can provide secure links between proposed dog remains and human activity. The Tumat Puppies, two permafrost-preserved Late Pleistocene canids, have been hypothesized to have been littermates and early domesticates due to a physical association with putatively butchered mammoth bones. Through a combination of osteometry, stable isotope analysis, plant macrofossil analysis, and genomic and metagenomic analyses, this study exploits the unique properties of the naturally mummified Tumat Puppies to examine their familial relationship and to determine whether dietary information links them to human activities. The multifaceted analysis reveals that the 14,965–14,046 cal yr BP Tumat Puppies were littermates who inhabited a dry and relatively mild environment with heterogeneous vegetation and consumed a diverse diet, including woolly rhinoceros in their final days. However, because there is no evidence of mammoth consumption, these data do not establish a link between the canids and ancient humans.
Cortical excitability has been proposed as a novel neurophysiological marker of neurodegeneration in Alzheimer’s dementia (AD). However, the link between cortical excitability and structural changes in AD is not well understood.
Objective:
To assess the relationship between cortical excitability and motor cortex thickness in AD.
Methods:
In 62 participants with AD (38 females, mean ± SD age = 74.6 ± 8.0) and 47 healthy control (HC) individuals (26 females, mean ± SD age = 71.0 ± 7.9), transcranial magnetic stimulation resting motor threshold (rMT) was determined, and T1-weighted MRI scans were obtained. Skull-to-cortex distance was obtained manually for each participant using MNI coordinates of the motor cortex (x = −40, y = −20, z = 52).
Results:
The mean skull-to-cortex distances did not differ significantly between participants with AD (22.9 ± 4.3 mm) and HC (21.7 ± 4.3 mm). Participants with AD had lower motor cortex thickness than healthy individuals (t(92) = −4.4, p = <0.001) and lower rMT (i.e., higher excitability) than HC (t(107) = −2.0, p = 0.045). In the combined sample, rMT was correlated positively with motor cortex thickness (r = 0.2, df = 92, p = 0.036); however, this association did not remain significant after controlling for age, sex and diagnosis.
Conclusions:
Patients with AD have decreased cortical thickness in the motor cortex and higher motor cortex excitability. This suggests that cortical excitability may be a marker of neurodegeneration in AD.
The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.
Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.
Methods
We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).
Results
Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.
Conclusions
Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.
Objectives/Goals: Early childhood obesity is a major concern for Latin American children in the U.S., with gut barrier dysfunction as a key risk factor. Diet plays a role in gut development, but few studies have focused on Latin American infants. Our objective is to identify culturally relevant introductory foods that promote in vitro gut barrier development and function. Methods/Study Population: Pooled human milk (2.5 mL) from 6-month postpartum Hispanic mothers was combined with fruit and vegetable baby food products (2.5 g) and subjected to a 3-phase in vitro digestion system that simulates oral, gastric, and intestinal digestion. Digesta products were then anaerobically fermented for 24-hours using human stool inoculum, centrifuged, and filter sterilized. Intestinal epithelial cells (Caco-2, ATCC) were grown to confluence on 0.4 μm polystyrene transwell inserts using a DMEM + 10% FBS medium and allowed to differentiate for 21-days. Highly differentiated monolayers were treated with a 1:4 dilution of fermenta with medium in triplicate. The cell experiment was conducted twice. Cell layer integrity was measured using transepithelial electrical resistance (TEER) 24- and 48-hours after treatment. Results/Anticipated Results: Dietary intake data from the What We Eat in America database indicated that the top 3 fruit and vegetable exposures for infants with Mexican or Hispanic ethnicity were banana, apple, and carrot. Commercial baby food purees of these fruits and vegetables, in addition to baby foods with blueberry and spinach (Natural for Baby, Gerber Products Company) were acquired for digestion and fermentation experiments. Caco-2 cell experiments with these foods are ongoing. We expect Caco-2 monolayer incubated with fermenta from human milk and fruit or vegetables will have greater TEER values due to increased integrity of the cell layer as compared to those with breast milk alone. We also expect that exposure to fruit and vegetable fermenta will increase gene expression of tight junctions compared to exposure to media and human milk. Discussion/Significance of Impact: Using an in vitro digestion and fermentation system coupled with cell culture studies, we are identifying cellular mechanisms that link individual fruits and vegetables to gut barrier function. This will support translational work focused on mitigating obesity development in vulnerable populations.
Bobtail squids of the family Sepiolidae, which includes the genus Euprymna, are closely related to, but distinct from the true squids (Teuthoidea). Despite their ecological importance, there have been few studies on the age and growth of bobtail squids using hard parts. This study is the first to use statolith increments to estimate the age of Euprymna hyllebergi collected from the southeastern Arabian Sea. Statoliths were extracted from 80 individuals (24 males, 56 females) of dorsal mantle length (DML) 8–50 mm and total weight 0.45–37 g and assessed for their age. Statolith size ranged from 328 to 836 μm. Assuming a daily deposition of increments, growth was rapid and adult sizes were attained in around 2 months. The age of the individuals varied between 25 days (DML = 8 mm) and 91 days (DML = 37 mm) for males; 33 days (DML = 10 mm) and 92 days (DML = 44 mm) for females. The daily growth rate ranged from 0.20 to 0.49 mm DML day−1 for males and 0.23–0.59 mm DML day−1 for females. The lifespan of E. hyllebergi is short, based on the statolith increment analysis.
We report a set of radiocarbon dating of prehistoric settlements located on the paleolake Baruun Khuree shores in the Gobi-Altai area, southern Mongolia. The obtained series of 11 AMS 14C measurements on charcoal and other charred plant macro-remains can be associated with one of the earliest episodes of the Holocene highly mobile desert-adapted hunter-gatherers activities from the Gobi desert (ca. 11,250–10,500 cal BP). Exploiting a wide range of environments, including dune fields, they are characterized by pottery usage and microblade core technology with wedge-shaped cores as well as osteological materials. These preliminary results are part of a project analyzing the nature of long-lasting prehistoric occupation around Tsakhiurtyn Hundi (Eng. Flint Valley)—one of the most extensive early prehistoric sites of Central Asia owing its name to the presence of abundant flint outcrops, lithic workshops and their innumerable flint artifacts.
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 ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. 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 ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) 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 DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ 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 $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.