Development of the neutral gas diagnostic system for neutral pressure measurements and gas analysis on the SPARC tokamak.

A suite of plasma diagnostics will be installed on the SPARC tokamak to allow for real-time plasma control, an investigation of high-field tokamak physics, and to de-risk the design of ARC, a compact fusion power plant with the aim to supply electricity to the grid. Among these diagnostics is the neutral gas diagnostics system (NTGS), a set of pressure sensors and gas analyzers used to monitor neutral pressure and gas composition for plasma control, optimization of wall conditioning, and helium ash removal, among other measurement functions linked to operational and scientific research needs. While reliable measurements of neutral pressure and gas composition have been fielded on existing magnetic-confinement fusion devices, SPARC represents a step increase in challenge due to its larger power density, higher field, high vacuum vessel bake temperatures, and higher neutron flux environment, as well as a step decrease in the accessibility for maintenance of in-vessel sensors. Multiple sensor types will be employed to have defense-in-depth and mitigate common failure modes. The NTGS system is currently progressing through final design, working to close out decisions using prototyping and analysis, and then moving on to procuring sensors for assembly and installation on SPARC. This paper outlines the current status of the system design and the diagnostic requirements that motivate neutral gas measurements on SPARC, as well as highlights the planned prototyping activities.

Overview of the early campaign diagnostics for the SPARC tokamak (invited).

The SPARC tokamak is a high-field, Bt0 ∼12 T, medium-sized, R0 = 1.85 m, tokamak that is presently under construction in Devens, MA, led by Commonwealth Fusion Systems. It will be used to de-risk the high-field tokamak path to a fusion power plant and demonstrate the commercial viability of fusion energy. SPARC's first campaign plan is to achieve Qfus > 1 using an ICRF-heated, <10 MW, high current, Ip ∼ 8.5 MA, L-mode fueled by D-T gas injection, and its second campaign will investigate H-mode operations in D-D. To facilitate plasma control and scientific learning, a targeted set of ∼50 plasma diagnostics are being designed and built for operation during these campaigns. While nearly all diagnostics are based on established techniques, the pace of deployment, relative to the first plasma, and the harshness of the thermal, electromagnetic, and radiation environment are unprecedented for medium-sized tokamaks. An overview of the SPARC diagnostic set is given, providing context to further details communicated by the SPARC team in companion publications that are system-specific. The system engineering philosophy for SPARC diagnostics is outlined, and the design and engineering verification process for components inside and outside the primary vacuum boundary are described. Diagnostics are mounted directly to the vacuum vessel as well as housed within a series of eight midplane and 24 off-midplane replaceable port plugs. With limited exceptions, signal conditioning, digitization electronics and cameras as well as lasers and microwave sources are localized to a series of five Diagnostic Lab spaces, totaling ∼350 m2, located >15 m from the center of the tokamak, on the other side of a 2.4 m concrete shielding wall. A series of 31 large-scale penetrations have been included in the SPARC Tokamak Hall to facilitate integration of early campaign diagnostics and to provide upgradability.

Development of a thermal diagnostic system for the SPARC tokamak.

The SPARC tokamak will have scrape-off layer parallel heat fluxes on the order of GW/m2. Managing power exhaust of this magnitude will be mandatory for a reactor-scale device. To enable this mission, a thermal diagnostic suite will be deployed to measure the in-vessel structural temperatures to ensure they do not exceed their design limits and to determine the spatial distribution and magnitude of energy deposited onto the first wall. Thermocouples and fiber Bragg gratings have been selected for their environmental compatibility and proven useful on other fusion devices. High-density thermocouple arrays in the divertor will have two spring-loaded thermocouples per divertor target tile, which are being used as calorimeters, and will look to resolve the temperature distribution within the tile due to a swept or static strike point. All systems will need to survive the vacuum vessel bake, set at a minimum plasma facing surface temperature of 350 °C, which presents a particularly challenging environment for the fiber-based subsystem. Along with this temperature design requirement, all the materials in the primary vacuum need to be ultra-high vacuum compatible, able to handle the expected neutron and gamma radiation, as well as tritium exposure, all of which restrict material options. Finally, due to the expected activated environment in SPARC, there will be little chance to replace defective sensors, so system resilience is ensured through toroidal redundancy, probe material selection, and mitigating the impact of common-mode failures. Initial testing of sensors show that intershot structural measurements are sufficiently captured with the raw output, but intrashot measurements of the plasma facing material requires model-based interpretive tools.

Impact of Periconceptional and Gestational Vitamin D3 Restriction on Fetal Folliculogenesis and Anti-Mullerian Hormone Secretion Using Sheep as a Model.

Ovarian reserve is a reflection of the overall female reproductive potential. Vitamin D status has been suspected to influence fetal development and female fertility. As maternal diet during pregnancy can affect fetal development and future fertility, we hypothesised that periconceptional and gestational Vitamin D restriction could affect folliculogenesis and AMH secretion in the offspring. Nineteen sexually mature Welsh mountain ewes were randomly assigned to Vitamin D3 deficient (VDD, n = 10) and Vitamin D3 control (VDC, n = 9) diets from 17 days (d) before mating, up to 127-130 days of gestation, when fetal ovaries were collected (3 from VDC and 6 from VDD). Serum 25(OH)D3 concentrations were lower in VDD compared with VDC (p < 0.05). Relative to total follicle number, the percentage of primordial follicles was higher (p < 0.05), while the percentage of primary follicles was lower (p < 0.05) in VDD group compared with VDC group fetal ovaries. The integrated density value and percentage of affected area in TUNEL staining in VDD group did not vary from VDC group fetal ovaries (p > 0.05). Relative expression of AMH mRNA and AMH protein in VDD fetal ovaries were not statistically different compared with controls (p > 0.05). The relative expression of VDR mRNA were lower in VDD compared with VDC group fetal ovaries (p < 0.05). These data indicate that maternal Vitamin D dietary restriction is associated with ovarian tissue stemness and increased primordial follicle number but does not promote normal follicle recruitment or development in sheep fetal ovaries.

Males miss and females forgo: Auditory masking from vessel noise impairs foraging efficiency and success in killer whales.

Understanding how the environment mediates an organism's ability to meet basic survival requirements is a fundamental goal of ecology. Vessel noise is a global threat to marine ecosystems and is increasing in intensity and spatiotemporal extent due to growth in shipping coupled with physical changes to ocean soundscapes from ocean warming and acidification. Odontocetes rely on biosonar to forage, yet determining the consequences of vessel noise on foraging has been limited by the challenges of observing underwater foraging outcomes and measuring noise levels received by individuals. To address these challenges, we leveraged a unique acoustic and movement dataset from 25 animal-borne biologging tags temporarily attached to individuals from two populations of fish-eating killer whales (Orcinus orca) in highly transited coastal waters to (1) test for the effects of vessel noise on foraging behaviors-searching (slow-click echolocation), pursuit (buzzes), and capture and (2) investigate the mechanism of interference. For every 1 dB increase in maximum noise level, there was a 4% increase in the odds of searching for prey by both sexes, a 58% decrease in the odds of pursuit by females and a 12.5% decrease in the odds of prey capture by both sexes. Moreover, all but one deep (≥75 m) foraging attempt with noise ≥110 dB re 1 µPa (15-45 kHz band; n = 6 dives by n = 4 whales) resulted in failed prey capture. These responses are consistent with an auditory masking mechanism. Our findings demonstrate the effects of vessel noise across multiple phases of odontocete foraging, underscoring the importance of managing anthropogenic inputs into soundscapes to achieve conservation objectives for acoustically sensitive species. While the timescales for recovering depleted prey species may span decades, these findings suggest that complementary actions to reduce ocean noise in the short term offer a critical pathway for recovering odontocete foraging opportunities.

Spatial and seasonal foraging patterns drive diet differences among north Pacific resident killer whale populations.

Highly social top marine predators, including many cetaceans, exhibit culturally learned ecological behaviours such as diet preference and foraging strategy that can affect their resilience to competition or anthropogenic impacts. When these species are also endangered, conservation efforts require management strategies based on a comprehensive understanding of the variability in these behaviours. In the northeast Pacific Ocean, three partially sympatric populations of resident killer whales occupy coastal ecosystems from California to Alaska. One population (southern resident killer whales) is endangered, while another (southern Alaska resident killer whales) has exhibited positive abundance trends for the last several decades. Using 185 faecal samples collected from both populations between 2011 and 2021, we compare variability in diet preference to provide insight into differences in foraging patterns that may be linked with the relative success and decline of these populations. We find broad similarities in the diet of the two populations, with differences arising from spatiotemporal and social variability in resource use patterns, especially in the timing of shifts between target prey species. The results described here highlight the importance of comprehensive longitudinal monitoring of foraging ecology to inform management strategies for endangered, highly social top marine predators.

Development of a bolometry diagnostic for SPARC.

To control and optimize the power of the SPARC tokamak, we require information on the total radiated power of the plasma and its 2D and 3D spatial distribution. The SPARC bolometry diagnostic is being designed and built to measure the radiated power for controlling power balance, investigating the dissipation capabilities of various divertor concepts, and measuring the efficacy of the disruption thermal load mitigation. Proven resistive bolometer sensor technology will be used, with 248 lines of sight integrated into pinhole cameras in 20 different locations. This diversity of views will allow the bolometers to view the core, divertor, and particularly X-points of the plasma with high resolution. 14 of these camera locations are dedicated to 2D equilibrium radiated power, while the remaining six locations are designed to measure 3D radiated energy during disruptions. The bolometer sensor holders, pinhole camera boxes, and cabling have been designed to survive the high neutron flux (but low fluence) and up to 400 °C temperatures seen during operation and vacuum bake. The resistive bolometer sensors use Au absorbers with an Al heat conduction layer and C anti-reflective layer. These sensor chips are wire-bonded to an AlN circuit board, both of which are held inside a custom AlN and stainless steel bolometer holder. Design and optimization of the pinhole camera lines of sight are performed using Cherab. This work details the current state of the design of the SPARC bolometry diagnostic and its interfaces, as well as ongoing work to validate the design.

A phase 2, randomized, blinded, dose-finding, controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults 65 years and older.

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

Impaired memory in Sprague-Dawley rats exposed to complex groundwater mixtures of contaminants is associated with reduced cranial blood flow and hippocampal neurotoxicity.

Exposure to industrial contaminants has been implicated in neurobehavioral toxicity in humans. To explore this potential risk, we investigated the neurotoxic effects of oral exposure to a complex groundwater mixture containing petroleum hydrocarbons, pesticides, heavy metals, and unknown parent and breakdown products using male and female Sprague Dawley rats. Rats were randomly divided into six groups and orally exposed daily via drinking water to: (i) tap water, (ii) 10 % v/v low impact groundwater, and (iii) 0.01 %, 0.1 %, 1 %, and 10 % high-impact groundwater for 60 days. Medium- and long-term memory (measured using the novel object recognition task) were impaired. However, no gross motor or coordination deficits were observed by the end of the study period (rotarod test). Doppler ultrasound of the middle cerebral and common carotid arteries was performed to examine the hemodynamic changes. The common carotid blood flow decreased in the groundwater-exposed rats compared to that in the control. However, no significant differences in cerebral blood velocity were observed between the exposed and control groups. A significant reduction in hippocampal serotonin levels was observed in groundwater-exposed rats relative to that in the control group. Collectively, these results indicate that impaired recognition memory in rats exposed to groundwater is accompanied by reduced cranial blood flow and hippocampal neurotoxicity, characterized by altered serotonergic signalling. The levels of detected contaminants known to cause neural or vascular damage were of magnitudes lower than the concentrations of contaminants found in the groundwater mixture, meaning the culprit chemical identity remains unknown. This study emphasizes the need to use whole mixture in exposures when dealing with complex contaminated sites rather than the use of individual compounds.

Supporting and Retaining Nurses in Trying Times.

The nursing profession has witnessed its share of challenging and trying times including toxic or unhealthy work environments, unsustainable workloads, an aging workforce, inadequate staffing, nurse burnout, staff retention, inadequately trained staff, an increase in workplace violence, and several pandemics. Both individually and collectively, these thorny issues have placed a heavy burden on nurses. Unfortunately, many capable and competent nurses have left the profession altogether, which further compounds an already problematic situation. This article highlights several important strategies for recruiting, retaining, and supporting a high functioning nursing workforce in challenging and trying times.

Estimated Investment Need to Increase England's Capacity to Diagnose Eligibility for an Alzheimer's Treatment to G7 Average Capacity Levels.

BACKGROUND: As disease-modifying Alzheimer's (AD) treatments are becoming available, concerns have been raised that even high-income countries lack the diagnostic capacity to accurately identify eligible patients in a timely manner. OBJECTIVES: We analyze how much NHS England would have to invest in capacity for AD specialists, biomarker testing with PET scans or CSF testing and MRI scans to reach G7 average levels and estimate the effect on wait times in the diagnostic process. DESIGN: Desk research and expert interviews for cost and capacity data. Markov model to estimate wait times. SETTING: NHS England. MEASUREMENTS: AD specialists, and PET and MRI scanners per capita in G7 countries and wait times in England under different investment scenarios. RESULTS: England has the lowest number of PET and MRI scanners and the second-lowest of AD specialists per capita among the G7 countries. An investment of GBP 14 billion over ten years would be needed to reach G7 average levels, of which 31%, 22%, 10%, 37% would be devoted to capacity for memory assessment services, PET scanning, CSF analysis, and MRI scanning, respectively. This investment would reduce estimated average wait times by around 87% between 2023 and 2032. CONCLUSIONS: The NHS England has large gaps in diagnostic capacity for AD. Without substantial investments, AD patients in England would experience substantial wait times and avoidable disease progression.

Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment.

The protection of Earth's stratospheric ozone (O3) is an ongoing process under the auspices of the universally ratified Montreal Protocol and its Amendments and adjustments. A critical part of this process is the assessment of the environmental issues related to changes in O3. The United Nations Environment Programme's Environmental Effects Assessment Panel provides annual scientific evaluations of some of the key issues arising in the recent collective knowledge base. This current update includes a comprehensive assessment of the incidence rates of skin cancer, cataract and other skin and eye diseases observed worldwide; the effects of UV radiation on tropospheric oxidants, and air and water quality; trends in breakdown products of fluorinated chemicals and recent information of their toxicity; and recent technological innovations of building materials for greater resistance to UV radiation. These issues span a wide range of topics, including both harmful and beneficial effects of exposure to UV radiation, and complex interactions with climate change. While the Montreal Protocol has succeeded in preventing large reductions in stratospheric O3, future changes may occur due to a number of natural and anthropogenic factors. Thus, frequent assessments of potential environmental impacts are essential to ensure that policies remain based on the best available scientific knowledge.

Health Economic Considerations in the Deployment of an Alzheimer's Prevention Therapy.

INTRODUCTION: As treatments for secondary prevention of Alzheimer's disease (AD) are being studied, concerns about their value for money have appeared. We estimate cost-effectiveness of a hypothetical screening and prevention program. METHODS: We use a Markov model to project cost-effectiveness of a treatment that reduces progression to symptomatic AD by 50% with either chronic treatment until progression to mild cognitive impairment or treatment for one year followed by monitoring with AD blood tests and retreatment with one dose in case of amyloid re-accumulation. Diagnoses would be made with an AD blood test with sensitivity and specificity of 80%, and inconclusive results in 20%. Individuals testing negative would be re-tested in five years and those with inconclusive results in one. RESULTS: The program would generate per-person value of $53,721 from a payer (reduction of direct cost and patient QALY gains) and $69,861 from a societal perspective (adding valuation of reduced caregiver burden). With chronic treatment, it would be cost-effective up to annual drug prices of $7,000 and $10,300, respectively. Time-limited treatment would be cost-effective at annual drug prices of $54,257 and $78,458 from a payer and societal perspective, respectively. Higher specificity of the blood test would decrease cost per person with similar value generation DISCUSSION: A hypothetical prevention treatment for AD could be economically viable from a payer and societal perspective.

Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila.

Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, we reveal the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments.

Epidemiology of skin changes in endangered Southern Resident killer whales (Orcinus orca).

Photographic identification catalogs of individual killer whales (Orcinus orca) over time provide a tool for remote health assessment. We retrospectively examined digital photographs of Southern Resident killer whales in the Salish Sea to characterize skin changes and to determine if they could be an indicator of individual, pod, or population health. Using photographs collected from 2004 through 2016 from 18,697 individual whale sightings, we identified six lesions (cephalopod, erosions, gray patches, gray targets, orange on gray, and pinpoint black discoloration). Of 141 whales that were alive at some point during the study, 99% had photographic evidence of skin lesions. Using a multivariate model including age, sex, pod, and matriline across time, the point prevalence of the two most prevalent lesions, gray patches and gray targets, varied between pods and between years and showed small differences between stage classes. Despite minor differences, we document a strong increase in point prevalence of both lesion types in all three pods from 2004 through 2016. The health significance of this is not clear, but the possible relationship between these lesions and decreasing body condition and immunocompetence in an endangered, non-recovering population is a concern. Understanding the etiology and pathogenesis of these lesions is important to better understand the health significance of these skin changes that are increasing in prevalence.

Divergent foraging strategies between populations of sympatric matrilineal killer whales.

In cooperative species, human-induced rapid environmental change may threaten cost-benefit tradeoffs of group behavioral strategies that evolved in past environments. Capacity for behavioral flexibility can increase population viability in novel environments. Whether the partitioning of individual responsibilities within social groups is fixed or flexible across populations is poorly understood, despite its relevance for predicting responses to global change at the population and species levels and designing successful conservation programs. We leveraged bio-logging data from two populations of fish-eating killer whales (Orcinus orca) to quantify patterns of fine-scale foraging movements and their relationships with demography. We reveal striking interpopulation differences in patterns of individual foraging behavior. Females from the endangered Southern Resident (SRKW) population captured less prey and spent less time pursuing prey than SRKW males or Northern Resident (NRKW) females, whereas NRKW females captured more prey than NRKW males. The presence of a calf (≤3 years) reduced the number of prey captured by adult females from both populations, but disproportionately so for SRKW. SRKW adult males with a living mother captured more prey than those whose mother had died, whereas the opposite was true for NRKW adult males. Across populations, males foraged in deeper areas than females, and SRKW captured prey deeper than NRKW. These population-level differences in patterns of individual foraging behavior challenge the existing paradigm that females are the disproportionate foragers in gregarious resident killer whales, and demonstrate considerable variation in the foraging strategies across populations of an apex marine predator experiencing different environmental stressors.

DNA methylation-based biomarkers for ageing long-lived cetaceans.

Epigenetic approaches for estimating the age of living organisms are revolutionizing studies of long-lived species. Molecular biomarkers that allow age estimates from small tissue biopsies promise to enhance studies of long-lived whales, addressing a fundamental and challenging parameter in wildlife management. DNA methylation (DNAm) can affect gene expression, and strong correlations between DNAm patterns and age have been documented in humans and nonhuman vertebrates and used to construct "epigenetic clocks". We present several epigenetic clocks for skin samples from two of the longest-lived cetaceans, killer whales and bowhead whales. Applying the mammalian methylation array to genomic DNA from skin samples we validate four different clocks with median errors of 2.3-3.7 years. These epigenetic clocks demonstrate the validity of using cytosine methylation data to estimate the age of long-lived cetaceans and have broad applications supporting the conservation and management of long-lived cetaceans using genomic DNA from remote tissue biopsies.

Inbreeding depression explains killer whale population dynamics.

Understanding the factors that cause endangered populations to either grow or decline is crucial for preserving biodiversity. Conservation efforts often address extrinsic threats, such as environmental degradation and overexploitation, that can limit the recovery of endangered populations. Genetic factors such as inbreeding depression can also affect population dynamics but these effects are rarely measured in the wild and thus often neglected in conservation efforts. Here we show that inbreeding depression strongly influences the population dynamics of an endangered killer whale population, despite genomic signatures of purging of deleterious alleles via natural selection. We find that the 'Southern Residents', which are currently endangered despite nearly 50 years of conservation efforts, exhibit strong inbreeding depression for survival. Our population models suggest that this inbreeding depression limits population growth and predict further decline if the population remains genetically isolated and typical environmental conditions continue. The Southern Residents also had more inferred homozygous deleterious alleles than three other, growing, populations, further suggesting that inbreeding depression affects population fitness. These results demonstrate that inbreeding depression can substantially limit the recovery of endangered populations. Conservation actions focused only on extrinsic threats may therefore fail to account for key intrinsic genetic factors that also limit population growth.

The Challenges of Characterizing the Zooplankton Community Response Following Simulated Spills of Diluted Bitumen into Boreal Lake Limnocorrals.

We attempted to characterize zooplankton community response following spills of the unconventional crude oil, diluted bitumen (dilbit), into 10-m diameter, ~ 100 m3, ~ 1.5-m deep boreal lake limnocorrals, including two controls and seven dilbit treatments ranging from 1.5 to 180 L (1:100,000 to 1:1,000 v/v, dilbit:water). Community composition and abundances were monitored weekly to bi-weekly over three months. Total zooplankton biomass and abundance seemingly collapsed in all limnocorrals, regardless of treatment, though some rotifer species persisted. As a result, it was not possible to determine the impacts of dilbit. We theorize several potential non-oil-related reasons for the sudden community collapse - including elevated zinc levels, fish grazing pressures, and sampling biases - and provide guidance for future work using in-lake enclosures.