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The SARS-CoV-2 pandemic reasserted the importance of epidemic preparedness and surveillance systems for infectious diseases (1). Informed responses to public health challenges require that data be available to decision-makers in [...]

The long-standing assumption that aboveground plant litter inputs have a substantial influence on soil organic carbon storage (SOC) and dynamics has been challenged by a new paradigm for SOC formation and persistence. We tested the importance of plant litter chemistry on SOC storage, distribution, composition, and age by comparing two highly contrasting ecosystems: an old-growth coast redwood (Sequoia sempervirens) forest, with highly aromatic litter, and an adjacent coastal prairie, with more easily decomposed litter. We hypothesized that if plant litter chemistry was the primary driver, redwood would store more and older SOC that was less microbially processed than prairie. Total soil carbon stocks to 110 cm depth were higher in prairie (35 kg C m-2) than redwood (28 kg C m-2). Radiocarbon values indicated shorter SOC residence times in redwood than prairie throughout the profile. Higher amounts of pyrogenic carbon and a higher degree of microbial processing of SOC appear to be instrumental for soil carbon storage and persistence in prairie, while differences in fine-root carbon inputs likely contribute to younger SOC in redwood. We conclude that at these sites fire residues, root inputs, and soil properties influence soil carbon dynamics to a greater degree than the properties of aboveground litter.

Background: Trauma team leadership is a core skill for the practice of emergency medicine (EM). In this study our goal was to explore EM residents’ perception of their trauma leadership skill development through formal and informal processes and to understand factors that may impact the development and implementation of trauma leadership skills.Methods: Using qualitative semi-structured interviews, we explored the leadership experiences of 10 EM residents ranging from second to fourth postgraduate year. Interviews were conducted between July 26–October 31, 2019 and were audio-recorded, transcribed, and de-identified. We analyzed data using qualitative content analysis.Results: Residents discussed three main themes: 1) sources of leadership development; 2) challenges with simultaneously assuming a dual leader-learner role; and 3) contextual factors that impact their ability to assume the leadership role, including the professional hierarchy in the clinical environment, limitations in the physical environment, and gender bias.Conclusion: This study describes the complex factors and experiences that contribute to the development and implementation of trauma team leadership skills in EM residents. This includes three primary sources of leadership development, the dual role of leader and learner, and various contextual factors. Research is needed to understand how these factors and experiences can be leveraged or mitigated to improve resident leadership training outcomes.

Background: The Canadian fetal alcohol spectrum disorder (FASD) diagnostic guideline provides clinicians with the process and procedure to reach an accurate diagnosis. However, organisational structure, culture, and resource utilisation vary. The objectives of this study were to identify the key challenges and strengths of successful FASD diagnostic clinics. Method: Qualitative interviews were conducted with 12 key informants from 10 clinics representing different regions, populations served, and clinic structures. Data analysis was performed using iterative thematic inquiry. Results: Three themes related to challenges and four themes related to strengths were identified. Human resources were identified as both a challenge and strength. Additional challenges were diagnostic capacity and system level support. Additional strengths were clinic adaptability, relational connections, and culturally responsive approaches. Conclusions: FASD clinics are more alike than not in their approach to assessment and diagnosis. Some clinics are facing similar challenges that others have overcome, supporting the need for mentorship and consistent operating standards.

Abstract Tropical forests account for over 50% of the global terrestrial carbon sink, but climate change threatens to alter the carbon balance of these ecosystems. We show that warming and drying of tropical forest soils may increase soil carbon vulnerability, by increasing degradation of older carbon. In situ whole-profile heating by 4 °C and 50% throughfall exclusion each increased the average radiocarbon age of soil CO2 efflux by ~2–3 years, but the mechanisms underlying this shift differed. Warming accelerated decomposition of older carbon as increased CO2 emissions depleted newer carbon. Drying suppressed decomposition of newer carbon inputs and decreased soil CO2 emissions, thereby increasing contributions of older carbon to CO2 efflux. These findings imply that both warming and drying, by accelerating the loss of older soil carbon or reducing the incorporation of fresh carbon inputs, will exacerbate soil carbon losses and negatively impact carbon storage in tropical forests under climate change.

Abstract Background Asthma is a leading cause of children’s hospitalizations, emergency department visits, and missed school days. Our school-based asthma intervention has reduced asthma exacerbations for children experiencing health disparities in the Denver Metropolitan Area, due partly to addressing care coordination for asthma and social determinants of health (SDOH), such as access to healthcare and medications. Limited dissemination of school-based asthma programs has occurred in other metropolitan and rural areas of Colorado. We formed and engaged community advisory boards in socioeconomically diverse regions of Colorado to develop two implementation strategy packages for delivering our school-based asthma intervention — now termed “Better Asthma Control for Kids (BACK)" — with tailoring to regional priorities, needs and resources. Methods In this proposed type 2 hybrid implementation-effectiveness trial, where the primary goal is equitable reach to families to reduce asthma disparities, we will compare two different packages of implementation strategies to deliver BACK across four Colorado regions. The two implementation packages to be compared are: 1) standard set of implementation strategies including Tailor and Adapt to context, Facilitation and Training termed, BACK-Standard (BACK-S); 2) BACK-S plus an enhanced implementation strategy, that incorporates network weaving with community partners and consumer engagement with school families, termed BACK-Enhanced (BACK-E). Our evaluation will be guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, including its Pragmatic Robust Implementation Sustainability Model (PRISM) determinants of implementation outcomes. Our central hypothesis is that our BACK-E implementation strategy will have significantly greater reach to eligible children/families than BACK-S (primary outcome) and that both BACK-E and BACK-S groups will have significantly reduced asthma exacerbation rates (“attacks”) and improved asthma control as compared to usual care. Discussion We expect both the BACK-S and BACK-E strategy packages will accelerate dissemination of our BACK program across the state – the comparative impact of BACK-S vs. BACK-E on reach and other RE-AIM outcomes may inform strategy selection for scaling BACK and other effective school-based programs to address chronic illness disparities. Trial registration Clinicaltrials.gov identifier: NCT06003569, registered on August 22, 2023, https://classic.clinicaltrials.gov/ct2/show/NCT06003569 .

Wastewater surveillance is an effective way to track the prevalence of infectious agents within a community and, potentially, the spread of pathogens between jurisdictions. We conducted a retrospective wastewater surveillance study of the 2022–23 influenza season in 2 communities, Detroit, Michigan, USA, and Windsor-Essex, Ontario, Canada, that form North America’s largest cross-border conurbation. We observed a positive relationship between influenza-related hospitalizations and the influenza A virus (IAV) wastewater signal in Windsor-Essex (ρ = 0.785; p

Abstract Objective Insertion and deletion (indel) analysis of CRISPR-Cas guide RNAs (gRNAs) is crucial in gene editing to assess gRNA efficiency and indel frequency. This study evaluates the utility of CRISPResso2 with Oxford Nanopore sequencing data (nCRISPResso2) for gRNA indel screening, compared to two common Sanger sequencing-based methods, TIDE and ICE. To achieve this, sheep and horse fibroblasts were transfected with Cas9 and a gRNA targeting the myostatin (MSTN) gene. DNA was subsequently extracted, and PCR products exceeding 600 bp were sequenced using both Sanger and Nanopore sequencing. Indel profiling was then conducted using TIDE, ICE, and nCRISPResso2. Results Comparison revealed close correspondence in indel formation among methods. For the sheep MSTN gRNA, indel percentages were 52%, 58%, and 64% for TIDE, ICE, and nCRISPResso2, respectively. Horse MSTN gRNA showed 81%, 87%, and 86% edited amplicons for TIDE, ICE, and nCRISPResso2. The frequency of each type of indel was also comparable among the three methods, with nCRISPResso2 and ICE aligning the closest. nCRISPResso2 offers a viable alternative for CRISPR-Cas gRNA indel screening, especially with large amplicons unsuitable for Illumina sequencing. CRISPResso2’s compatibility with Nanopore data enables cost-effective and efficient indel profiling, yielding results comparable to common Sanger sequencing-based methods.

Invasive non-native species (INNS) are key drivers of global biodiversity loss. This is particularly evident in freshwater ecosystems, where the rates of both vertebrate biodiversity loss and biological invasion exceed those of marine and terrestrial systems. Aotearoa New Zealand (henceforth Aotearoa) like many other island nations, has a troubled history with NNS. However, it is also unique, as the main islands were the last major landmasses on Earth to remain uninhabited by humans. The endemic fauna had evolved in isolation from any anthropogenic influence or introduced NNS, until the mid-thirteenth century with the arrival of Māori, the first people to inhabit Aotearoa. Centuries later, following European colonisation, many non-native freshwater fish were deliberately introduced by acclimatisation societies. Currently, most of the native freshwater fish species of Aotearoa are at risk of extinction, despite almost 90% of these being found nowhere else on earth. Many of these species are highly valued by the indigenous people of Aotearoa, who have repeatedly highlighted biases towards NNS in freshwater fish management. With the rate of biological invasions increasing, it is timely to address interconnected issues concerning the history, impacts, management and current / future policy directions, including those involving biosecurity, for non-native freshwater fish in Aotearoa. We do this by applying a social-ecological systems (SES) lens, with a focus on causal-loop relationships and feedbacks to improve understanding of the dynamics of drivers, mechanisms and impacts of such invasions. We highlight the tensions that have resulted from managing some NNS as ‘pests’ threatening native biodiversity, while simultaneously promoting a tourism and recreational fishery resource for specific NNS. This has generated extremely polarized views on the ‘status’ of non-native freshwater fish species and given rise to contradictory and divergent goals for their management. We show how a disjointed and often incoherent policy landscape has contributed to legal ‘anomalies’ for NNS, including policy misalignments and gaps, hampering effective use of resources, while also entrenching contradictory management programmes for different stakeholders. Our study shows how these interconnected issues have been manifested in social-ecological feedback loops on core aspects of NNS policy and management, past and present. Consequently, there is a need for increased comprehension of the diverse array of potential impacts of NNS for different environments, stakeholders and Māori while developing coherent and practical management methods to reduce such impacts and improve social-ecological resilience. We conclude that adopting a SES approach will aid this endeavour.

ObjectiveMarijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV.DesignWe undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women.MethodsWe quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors.ResultsMarijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively.ConclusionAmong a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.

This study is a semantic analysis that examines the meanings of two contemporary Japanese labels, hikikomori and soushokukei-danshi. This duo has often been linked to the late marriage age, declining marriage rate, shoushika (low birth rate), and koureika (the aging society). The goal of this thesis is to define these individuals according to the perceptions of native Japanese speakers and to convey the definitions by using the reductive paraphrase methodology. Accordingly, cultural values reflected in the labels will be revealed. The Natural Semantic Metalanguage (NSM) approach and corpus analysis are the chosen methodology. NSM is a universal mini metalanguage, while corpus analysis is a tool that can analyse data from online sources. Combined, these methods support the goal of delivering explications that reflect the labels from a Japanese perspective. Results from the study show that the values of Japanese society and the duos are at odds with one another, subsequently, fuelling the negative stigma directed towards both cohorts: Hikikomori are individuals who are emotionally withdrawn and bound to the house for the most part. Furthermore, their condition is something they feel they cannot change so easily; and Soushokukei-danshi are young men who are uninterested in romance or attaining stereotypical male positions in the workforce. Moreover, they would rather invest time in their hobbies. Through this study, a better comprehension of what these words mean is acquired.

Abstract Henry’s law constant, which describes the proportionality of dissolved gas to partial pressure of free gas in liquid–gas equilibrium systems, can also be applied to mass transport applications. In this work, we investigated an approach for determining the solubility of noble gases in a molten salt liquid utilizing the equilibrium concept of Henry’s gas constant. Henry’s gas constant is described as a mathematical function dependent on the van der Waals radius of the noble gas and the temperature of the molten salt. The alteration in Gibbs free energy encompasses contributions from both surface and volume energies. Enthalpy and entropy are deduced from these surface and volume energies in the Gibbs free energy formulation. A comparative analysis was conducted between the conventional method and our proposed model. Moreover, useful chemical properties can be determined from examination of surface and volume energies. Our findings provide an accurate and general theory of Gibbs free energy that can be validated experimentally based on the model proposed herein. This work unifies the prediction of Henry gas constant and subsequently the entropy and enthalpy calculation for noble gases in a molten salt solution to a single functional form using van der Waals radius of the gas and temperature of the system. This functional form is then used to perform a multiple regression method to find two parameters corresponding to the surface energy and volume energy. These two parameters are consistent between all combinations of noble gas and molten salt.

Abstract Background Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment. Tolinapant, developed by Astex Pharmaceuticals, is an IAP antagonist with an additional mechanism of action via down-regulation of NF-kB, an important regulator in cervical cancer. Preclinical studies performed using tolinapant in combination with cisplatin and radiotherapy showed inhibition of tumour growth and enhanced survival. There is therefore a strong rationale to combine tolinapant with chemoradiotherapy (CRT). Methods CRAIN is a phase Ib open-label, dose escalation study to characterise the safety, tolerability and initial evidence for clinical activity of tolinapant when administered in combination with cisplatin based CRT. Up to 42 patients with newly diagnosed cervix cancer will be recruited from six UK secondary care sites. The number of participants and the duration of the trial will depend on toxicities observed and dose escalation decisions, utilising a TiTE-CRM statistical design. Treatment will constist of standard of care CRT with 45 Gy external beam radiotherapy given in 25 daily fractions over 5 weeks with weekly cisplatin 40mg/m2. This is followed by brachytherapy for which common schedules will be 28 Gy in 4 fractions high-dose-rate or 34 Gy in 2 fractions pulsed-dose-rate. Tolinapant will be administered in fixed dose capsules taken orally daily for seven consecutive days as an outpatient on alternate weeks (weeks 1, 3, 5) during chemoradiation. Dose levels for tolinapant which will be assessed are: 60 mg; 90 mg (starting level); 120 mg; 150 mg; 180 mg. Escalation will be guided by emerging safety data and decisions by the Safety Review Committee. Discussion If this trial determines a recommended phase II dose and shows tolinapant to be safe and effective in combination with CRT, it would warrant future phase trials. Ultimately, we hope to provide a synergistic treatment option for these patients to improve outcome. Trial registrations EudraCT Number: 2021-006555-34 (issued 30th November 2021); ISRCTN18574865 (registered 30th August 2022).

Abstract Background Equal, diverse, and inclusive teams lead to higher productivity, creativity, and greater problem-solving ability resulting in more impactful research. However, there is a gap between equality, diversity, and inclusion (EDI) research and practices to create an inclusive research culture. Research networks are vital to the research ecosystem, creating valuable opportunities for researchers to develop their partnerships with both academics and industrialists, progress their careers, and enable new areas of scientific discovery. A feature of a network is the provision of funding to support feasibility studies – an opportunity to develop new concepts or ideas, as well as to ‘fail fast’ in a supportive environment. The work of networks can address inequalities through equitable allocation of funding and proactive consideration of inclusion in all of their activities. Methods This study proposes a strategy to embed EDI within research network activities and funding review processes. This paper evaluates 21 planned mitigations introduced to address known inequalities within research events and how funding is awarded. EDI data were collected from researchers engaging in a digital manufacturing network activities and funding calls to measure the impact of the proposed method. Results Quantitative analysis indicates that the network’s approach was successful in creating a more ethnically diverse network, engaging with early career researchers, and supporting researchers with care responsibilities. However, more work is required to create a gender balance across the network activities and ensure the representation of academics who declare a disability. Preliminary findings suggest the network’s anonymous funding review process has helped address inequalities in funding award rates for women and those with care responsibilities, more data are required to validate these observations and understand the impact of different interventions individually and in combination. Conclusions In summary, this study offers compelling evidence regarding the efficacy of a research network's approach in advancing EDI within research and funding. The network hopes that these findings will inform broader efforts to promote EDI in research and funding and that researchers, funders, and other stakeholders will be encouraged to adopt evidence-based strategies for advancing this important goal.

Abstract Spin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking – a directional relationship between an electron’s spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions. Here, we use spin- and angle-resolved photoemission spectroscopy to evidence Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. We find that the electron spin of the Fermi arc surface states is orthogonal to their Fermi surface contour for momenta close to the projection of the bulk multifold fermion at the Γ point, which is consistent with Weyl spin-momentum locking of the latter. The direct measurement of the bulk spin texture of the multifold fermion at the R point also displays Weyl spin-momentum locking. The discovery of Weyl spin-momentum locking may lead to energy-efficient memory devices and Josephson diodes based on chiral topological semimetals.