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The differences between nuclear fission and fusion have been discussed widely in the literature. However, little has been done to investigate the key differences in safety designs and regulatory requirements between the nuclear reactor types. In this study, an innovative methodology was successfully developed to map nuclear safety features to the fundamental safety principles set out by the nuclear regulators. Three safety cases were assessed in the mapping study, a research fusion reactor (Joint European Torus), a research fission reactor (Tsing Hua Open-pool Reactor) and a commercial fission reactor (Hinkley Point C). The graphical representation allowed a comparative analysis of the safety features and fundamental principles which revealed differences between the hazard profiles of fission and fusion reactors and provided important insights for the creation of a similar map for a future commercial fusion device.

The high levels of biodiversity supported by mountains suggest a possible link between geologic processes and biological evolution. Freshwater biodiversity is high not only in tectonically active settings but also in tectonically quiescent montane regions such as the Appalachian Mountains. We show that erosion through different rock types drove allopatric divergence between lineages of the Greenfin Darter ( Nothonotus chlorobranchius ), a fish species endemic to rivers draining metamorphic rocks in the Tennessee River basin in the United States. In the past, metamorphic rock preferred by N. chlorobranchius was more widespread, but as erosion exposed other rock types, lineages of this species were progressively isolated in tributaries farther upstream, where metamorphic rock remained. Our results suggest a geologic mechanism for initiating allopatric diversification in mountains long after tectonic activity ceases.

In 2021, the Evidence into Practice Special Interest Group was launched with online events. At the 11th European Conference for Social Work Research in Amsterdam in April 2022, the Evidence into Practice Special Interest Group had its inaugural in-person sessions. This short article in the ‘Research, policy and practice exchange’ section of this new journal, European Social Work Research (a collaborative venture involving European Social Work Research Association), has been written to bring the launch of the Evidence into Practice Special Interest Group to a wider audience and to encourage participation. The article gives something of the context for the Evidence into Practice Special Interest Group and a flavour of the presentations at the 2022 European Conference for Social Work Research.

We write as a collaborative mode of embodied writing that moves, tags, and re-sites us elsewhere, that mis/dis/aligns self-other, and permeates various stable body(boundaries). We write as a group of (un)bounded (virtual) bodies who aim to collectively create and tag arguments. We write as a collective body where materialities, ideas, discussions and writing become in the doing. Different relational collective practices shared here disturb, disperse, question, undo and undermine sole authorship and consider how tags work and what tags might produce when these objects/things shape our academic lives. While engaged in tagging we also considered how tags tug, how tags shape the ways we think, feel and experience our academic lives. How are we produced by tags? What do tags produce (in/on) us and in our embodied lives? ispartof: Culture And Organization status: Published online

Functionalization of C-H bonds is a key challenge in medicinal chemistry, particularly for fragment-based drug discovery (FBDD) where such transformations require execution in the presence of polar functionality necessary for protein binding. Recent work has shown the effectiveness of Bayesian optimization (BO) for the self-optimization of chemical reactions; however, in all previous cases these algorithmic procedures have started with no prior information about the reaction of interest. In this work, we explore the use of multitask Bayesian optimization (MTBO) in several in silico case studies by leveraging reaction data collected from historical optimization campaigns to accelerate the optimization of new reactions. This methodology was then translated to real-world, medicinal chemistry applications in the yield optimization of several pharmaceutical intermediates using an autonomous flow-based reactor platform. The use of the MTBO algorithm was shown to be successful in determining optimal conditions of unseen experimental C-H activation reactions with differing substrates, demonstrating an efficient optimization strategy with large potential cost reductions when compared to industry-standard process optimization techniques. Our findings highlight the effectiveness of the methodology as an enabling tool in medicinal chemistry workflows, representing a step-change in the utilization of data and machine learning with the goal of accelerated reaction optimization.

LAY SUMMARY Military personnel frequently report actions taken by themselves or others that violate deeply held moral beliefs, which can be experienced as a kind of moral injury. Some have questioned whether existing treatments for posttraumatic stress disorder (PTSD), such as cognitive processing therapy, are effective for those who have been exposed to a morally injurious traumatic event. These analyses demonstrate that active duty service members and Veterans seeking treatment for PTSD who reported potentially morally injurious trauma had PTSD and depression outcomes that were as good as those whose traumas were not primarily seen as morally injurious, suggesting that cognitive processing therapy is an efficacious treatment for PTSD in the context of morally injurious trauma.

Context Class III acyl-CoA-binding proteins such as those from dicots (Arabidopsis and grapevine) play a role in defence against biotrophic pathogens. The overexpression of the monocot Oryza sativa (rice) OsACBP5 in Arabidopsis and rice has been demonstrated to enhance broad-spectrum disease resistance against selected phytopathogens in OsACBP5-overexpressing (OsACBP5-OE) lines. Aims We aimed to develop transgenic rapid-cycling Brassica napus (B. napus-RC) and canola cv. Westar OsACBP5-OEs using tissue culture-based Agrobacterium-mediated transformation and to evaluate transgenic plants for resistance against Alternaria blight, blackleg and Sclerotinia rot diseases. Methods Transgenic B. napus-RC and cv. Westar OsACBP5-OEs were generated through Agrobacterium-mediated transformation using Agrobacterium strain LBA4404 harbouring a plasmid with the rice complementary DNA encoding OsACBP5 driven by the cauliflower mosaic virus 35S promoter. Alternaria blight and blackleg pathogen assays were based on infecting young cotyledons, while detached leaf assay was used to test the tolerance of B. napus plants toward Sclerotinia sclerotiorum. Key results Average transformation efficiencies of 24.2% and 29.1% were obtained for B. napus-RC and B. napus cv. Westar cotyledons respectively. OsACBP5-OE plants exhibited resistance 5 days after inoculation with Alternaria brassicae, 12 days after inoculation with Leptosphaeria maculans, and 24 h after inoculation with S. sclerotiorum. Conclusions Transformation of B. napus-RC was shown herein to be an effective trait testing platform for canola. This study also provides an insight into the usefulness of OsACBP5 in enhancing resistance to necrotrophic phytopathogens. Implications OsACBP5 can be overexpressed in other crops to generate pathogen-resistant varieties.

Development of scalable processes for C­(sp3)–H oxidative carbonylation of alkylamines is reported to provide convenient access to the β-lactam scaffol d. A study of the kinetics of the process revealed that the reaction is CO-limited even at elevated pressures and that there is an optimal CO concentration for the most effective outcomethis understanding led to an increase in the turnover number from 7 to 420 in the optimized process. Two scalable processes were then developed: a batch process, characterized by a very low catalyst loading, and a continuous process for an oxidative C–H carbonylation reaction that uses a copper-tube-flow reactor as a heterogeneous source of Cu2+ oxidant. The continuous process was tested on oxidative carbonylation of several alkylamines, yielding very good results with virtually no optimization required. This study thereby builds upon the utility of flow chemistry applications to oxidative carbonylations and scalable metal-catalyzed processes more generally.

Wearing a face mask is a primary public health method to reduce SARS-CoV-2 transmission.We performed a nested case-control analysis within the North Carolina COVID-19 Community Research Partnership (NC-CCRP) of adults who completed daily surveillance surveys, April 2020 - February 2022. We assessed the association between self-reported mask wearing behavior during nonhousehold interactions and COVID-19 infection during 3 pandemic periods using conditional logistic regression models of risk of infection that were adjusted for demographics, vaccination status, and recent known exposure to COVID-19.Among 3,901 cases and 27,813 date-matched controls, there was a significant interaction between mask use and time period (P.001). Prior to July 2021, the odds of a reported infection were 66% higher (aOR = 1.66, 95% CI = 1.43-1.91) among participants reporting ≥1 day not wearing a mask compared to those who reported no days (1,592 cases, 11,717 controls). During the Delta-predominant period, the results were similar (aOR = 1.53, 95% CI = 1.23-1.89; 659 cases, 4,649 controls). This association was attenuated during the Omicron-predominant period, where odds of an infection was 16% higher (aOR = 1.16, 95% CI = 1.03-1.32; 1,563 cases, 10,960 controls).While the effect of not wearing a mask remains significant, during the Omicron-predominant period we observed a decrease in the association between self-reported mask wearing and risk of SARS-CoV-2 infection.

BackgroundIntrapulmonary placements of feeding tubes inserted with use of an electromagnetic placement device (EMPD) continue to occur.ObjectiveTo describe circumstances and outcomes associated with intrapulmonary feeding tube placements during use of an EMPD.MethodsA retrospective review of reports to the US Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database of intrapulmonary feeding tube placements during use of an EMPD from 2019 through 2021. Complications, outcomes, operator training, interference from anatomical variations and medical devices, and the use and accuracy of radiographs in identifying pulmonary placements were recorded.ResultsSixty-two cases of intrapulmonary tube placement were identified; 10 were associated with a fatal outcome. Pneumothorax occurred in 35 cases and feedings were delivered into the lung in 11 cases. User error was cited in 6 cases and was implicit in most others. Little information was provided about operator training. Four intrapulmonary placements were associated with anatomical variations and 1 with a left ventricular assist device. Radiographic follow-up was described in 28 cases and correctly identified 23 of the intrapulmonary placements.ConclusionsUser error was a significant factor, which highlights the need for empirical data to clarify the amount of training needed to safely credential EMPD operators. Clearer information is needed about anatomical variations that may contraindicate use of an EMPD, as well as medical devices that may interfere with an EMPD. Use of follow-up radiographs, interpreted by qualified personnel, is supported to increase the probability of identifying intrapulmonary tube placements.

Background: Women with HR+ breast cancer experience a persistent risk of distant recurrence (DR) even after completion of 5 years of adjuvant endocrine therapy, with more than 50% of DR occurring after 5 years (late DR). The prognostic genomic signatures currently being used in the clinic were not developed or optimized specifically for late DR. We have previously shown that the Breast Cancer Index (BCI) and BCIN+ prognostic models were significantly prognostic for risk of overall (0-10y) and late (5-10y) distant recurrence (DR) in N0 and N1 HR+ patients in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial. Here, the prognostic performance of the BCI and BCIN+ models with alternative cut-points optimized for late DR were evaluated in patients from the TEAM trial, who were free from DR for at least 5 years. Methods: BCI testing was performed blinded to clinical outcome. The pre-specified alternative cut-points 4.4 and 1.8 for BCI and BCIN+ models were determined previously from Trans-aTTom and IDEAL studies, respectively (ESMO 2021). Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic significance of BCI/BCIN+ risk groups based on DR. Univariate and multivariate Cox models were used to estimate hazard ratios (HRs) and the associated 95% confidence intervals (CIs). Results: 1285 HR+ N0 (median age 69.2, 54.2% T1, 92.5% G2-3, 21.3% chemotherapy) and 1762 N1 (median age 68.5, 49.7% T1, 80.8% G2-3, 42.6% chemotherapy) patients who remained free from DR at 5 years post randomization were included in the current analysis. For N0 patients, BCI identified 439 (34%) and 846 (66%) patients as low and high-risk with late 10-year DR rates of 3.8% (95% CI: 1.5-6.0%) and 9.1% (95% CI: 6.8-11.4%), respectively (HR: 2.6, 95% CI: 1.4-5.0; p=0.0025). For N1 patients, BCIN+ identified 287 (16%) and 1475 (84%) patients as low and high-risk with late 10-year DR rates of 3.4% (95% CI: 1.2-5.5%) and 12.3% (95% CI: 10.4-14.2%), respectively (HR: 3.5, 95% CI: 1.8-6.9; p< 0.0001). Similar results were observed in the HER2- patients. Notably, BCI/BCIN+ remained a statistically significant prognostic factor in the multivariate analysis after controlling for age, tumor size, grade, treatment. (Table). Conclusions: Compared to the original BCI/BCIN+ models, the optimized BCI and BCIN+ models showed improved prognostic performance for identifying low-risk patients with a very low risk of late DR (< 4%), for both N0 and N1 patients. These results provide further validation of BCI clinical utility as an aid in the decision-making for extended endocrine therapies for HR+ breast cancer, particularly in patients with N1 disease that may be spared extended endocrine treatment. Table Citation Format: John MS Bartlett, Keying Xu, Jenna Wong, Gregory R. Pond, Yi Zhang, Melanie Spears, Ranelle Salunga, Elizabeth Mallon, Karen J. Taylor, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, Cornelis J.H. van de Velde, Daniel Rea, Catherine A. Schnabel, Kai Treuner, Jane Bayani. Validation of the Breast Cancer Index (BCI) prognostic models optimized for late distant recurrence in postmenopausal women with early-stage HR+ breast cancer in the TEAM trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-10.

In response to the coronavirus (COVID-19) pandemic, there has been an increased need for personal and environmental decontamination to aid in curbing transmission of the SARS-CoV-2 virus. Products used for this purpose include sanitizers for hands and disinfectants for surfaces. The active chemical ingredients used in these products, termed antimicrobials, can enter waste streams after application and may be emerging as more prominent environmental contaminants. Even prior to COVID-19, there was recognized need to examine their implications for aquatic biota, which is now made more pressing due to their exaggerated use in response to the pandemic. Our objectives were to identify current antimicrobial active ingredients, quantify their increased use, and determine which may be candidates for further consideration as possible aquatic contaminants. By consulting multiple sources of publicly available information in Canada, we identified current-use antimicrobials from the lists of sanitizers and surface disinfectants approved for use against SARS-CoV-2 by Health Canada and the drug registration database. To estimate the use of sanitizers and disinfectants, we evaluated import quantities and grocery store retail sales of related compounds and products (Statistics Canada) and both lines of evidence supported increased use trends. The list of identified antimicrobials was refined to include only candidates with potential to reach aquatic ecosystems, and information on their environmental concentrations and toxicity to aquatic biota was reviewed. Candidate antimicrobials ( n = 32) fell into four main categories: quaternary ammonium compounds (QACs), phenols, acids, and salts. Benzalkonium chloride, a QAC, was the most prominent active ingredient used in both nonalcohol-based hand sanitizers and surface disinfectants. Four QACs followed in prevalence and the next most used antimicrobial was triclosan (hand sanitizers only), an established and regulated environmental contaminant. Little information was found on environmental concentrations of other candidates, suggesting that the majority would fall into the category of emerging contaminants if they enter aquatic systems. Several were classified as acutely or chronically toxic to aquatic biota (Globally Harmonized System), and thus we recommend empirical research begin focusing on environmental monitoring of all candidate antimicrobials as a critical next step, with detection method development first where needed.

The study of antigen-specific lymphocytes has been a key advancement in immunology the past few decades. The development of multimerized probes containing antigens, peptide:MHC complexes, or other ligands was one innovation allowing the direct study antigen-specific lymphocytes by flow cytometry. While these types of studies are now common and performed by thousands of laboratories, quality control and assessment of probe quality is often minimal. In fact, many of these types of probes are made in-house and protocols vary between labs. While peptide:MHC multimers can often be obtained from commercial sources or core facilities, few such services exist for antigen multimers. To ensure high quality and consistency with ligand probes, we have developed an easy and robust multiplexed approach using commercially available beads able to bind antibodies specific for the ligand of interest. Using this assay, we have sensitively assessed the performance of peptide:MHC and antigen tetramers and find considerable batch-to-batch variability in performance and stability over time. This assay can also reveal common production errors such as miscalculation of antigen concentration. Unexpectedly, probes including the fluorochrome allophycocyanin exhibited more rapid performance decline compared to probes including the fluorochrome R-phycoerythrin when both were stored at 4°C. This performance decline was reduced for most, but not all, batches when antigen tetramers were instead stored at −20°C in 50% glycerol. This work could set the stage for the development of standardized assays for all commonly used ligand probes to limit lab-to-lab technical variation, and experimental failure due to probe underperformance.

Abscission, known as shattering in crop species, is a highly regulated process by which plants shed parts. Although shattering has been studied extensively in cereals and a number of regulatory genes have been identified, much diversity in the process remains to be discovered. Teff (Eragrostis tef) is a crop native to Ethiopia that is potentially highly valuable worldwide for its nutritious grain and drought tolerance. Previous work has suggested that grain shattering in Eragrostis might have little in common with other cereals. In this study, we characterize the anatomy, cellular structure, and gene regulatory control of the abscission zone (AZ) in E. tef. We show that the AZ of E. tef is a narrow stalk below the caryopsis, which is common in Eragrostis species. X-ray microscopy, scanning electron microscopy, transmission electron microscopy, and immunolocalization of cell wall components showed that the AZ cells are thin walled and break open along with programmed cell death (PCD) at seed maturity, rather than separating between cells as in other studied species. Knockout of YABBY2/SHATTERING1, documented to control abscission in several cereals, had no effect on abscission or AZ structure in E. tef. RNA sequencing analysis showed that genes related to PCD and cell wall modification are enriched in the AZ at the early seed maturity stage. These data show that E. tef drops its seeds using a unique mechanism. Our results provide the groundwork for understanding grain shattering in Eragrostis and further improvement of shattering in E. tef.

Optometrists are well-placed to provide helpful advice and guidance to patients with visual impairment but may not know how best to do this. The availability of a reliable and comprehensive conversational agent to which patients could be directed would be a valuable supplement to clinical intervention. The Artificial Intelligence in Visual Impairment (AIVI) Study is a proof-of-concept study to investigate whether ongoing information support for people with visual impairment (VI) can be provided by a dialogue-based digital assistant. The phase of the AIVI Study reported here explored the different dimensions of the information-seeking behaviour of individuals with VI: in particular, their need for information, the methods for obtaining it at present, and their views on the use of a digital assistant. Qualitative data were collected from 120 UK-resident adults who responded to an online survey who were either visually impaired (86.7%), a carer or family member of someone with VI (5.8%), or a professional involved in the support of those with VI (7.5%). In addition, 10 in-depth 1:1 semi-structured interviews explored opinions in more detail. Thematic analysis was used to analyse the findings. Analysis of information needs identified 7 major themes: ocular condition; equipment, technology and adaptations; daily activities; registration; finance/employment; emotional support; and support for the carer. Participants used a wide variety of methods to access information from many sources and explained the barriers to access. Participants accepted the merit of a dialogue system aiding in a goal-directed search for specific information, but expressed reservations about its abilities in other areas, such as providing emotional support. Participants highlighted potential benefits, limitations, and requirements in using a digital assistant to access information about VI. These findings will inform the design of dialogue systems for populations with VI.

Aims Ischaemic heart disease results from insufficient coronary blood flow. Direct measurement of absolute flow (mL/min) is feasible, but has not entered routine clinical practice in most catheterization laboratories. Interventional cardiologists, therefore, rely on surrogate markers of flow. Recently, we described a computational fluid dynamics (CFD) method for predicting flow that differentiates inlet, side branch, and outlet flows during angiography. In the current study, we evaluate a new method that regionalizes flow along the length of the artery. Methods and results Three-dimensional coronary anatomy was reconstructed from angiograms from 20 patients with chronic coronary syndrome. All flows were computed using CFD by applying the pressure gradient to the reconstructed geometry. Side branch flow was modelled as a porous wall boundary. Side branch flow magnitude was based on morphometric scaling laws with two models: a homogeneous model with flow loss along the entire arterial length; and a regionalized model with flow proportional to local taper. Flow results were validated against invasive measurements of flow by continuous infusion thermodilution (Coroventis™, Abbott). Both methods quantified flow relative to the invasive measures: homogeneous (r 0.47, P 0.006; zero bias; 95% CI −168 to +168 mL/min); regionalized method (r 0.43, P 0.013; zero bias; 95% CI −175 to +175 mL/min). Conclusion During angiography and pressure wire assessment, coronary flow can now be regionalized and differentiated at the inlet, outlet, and side branches. The effect of epicardial disease on agreement suggests the model may be best targeted at cases with a stenosis close to side branches.

Background: Paramedics undertake visually demanding tasks, which may be adversely affected by low lighting conditions. Aims: The study aimed to: identify difficulties paramedics experience carrying out tasks in low light; and establish occupational health standards and adjustments that may improve working practices. Methods: A scoping review was undertaken informed by a professional panel of paramedics recruited through social media. A meta-analysis was conducted assessing visual acuity under different light levels. Findings: Difficulty in driving and in assessing/treating patients under low light conditions were reported. Sixty relevant studies were identified for review. Visual acuity reduces with decreasing luminance, causing increasing difficulties in performing critical tasks. Conclusion: Visual function testing can assess paramedics' visual health and ability to undertake critical tasks. Adjustments may help to improve conditions. Regular occupational health assessments could identify paramedics who need support. Further research should explore levels of visual function and practical adjustments needed for safe clinical practice.

Small molecule interaction hotpots were identified by screening small, low complexity fragments using X-ray crystallography. These hot spots include cryptic pockets and provide pharmacophore mapping that may be used in structure-based drug design.

The braiding of Indigenous knowledge systems and Western-based sciences offers insights into ecology and has emerged as a way to help address complex environmental issues. We reviewed the publicly available ecological research involving the braiding of Indigenous knowledge systems and Western-based sciences to support collaborative work in the Alberta oil sands region of Canada. We conducted a systematic review, coding for 78 questions in six categories: (1) literature search and bibliographic information; (2) research themes; (3) study setting and design; (4) knowledge systems; (5) power relationships, colonization, and ethical considerations in research; and (6) benefits and challenges of braiding. We identified six articles that braided knowledge, with those articles focusing on environmental management and monitoring for impacts of industrial activity in northern Alberta. Researchers used a broad range of approaches to gather Indigenous knowledge and scientific data and identified multiple challenges (e.g., asymmetries of power, resource availability, and funding) to research. Our findings show that more support is needed to foster, promote, and disseminate interdisciplinary collaborative work involving braiding. Additional support is also required to address Indigenous community research needs related to the assessment of environmental impact and reclamation, as well as the understanding of ecological threats across the region.

Background Gross motor intervention designs for children with diplegic cerebral palsy (DCP) require an improved understanding of the children’s potential for neuroplasticity. Objective To identify relations between functional neuroplasticity and motor skill changes following gross motor interventions for children with DCP. Methods There were 17 participants with DCP (ages 8-16 years; 6 females; Gross Motor Function Classification System Level I [n = 9] and II [n = 8]). Each completed a 6-week gross motor intervention program that was directed toward achievement of individualized motor/physical activity goals. Outcomes were assessed pre/post and 4 to 6 months post-intervention (follow-up). An active ankle dorsiflexion task was completed during functional magnetic resonance imaging. The ratio of motor cortical activation volume in each hemisphere was calculated using a laterality index. The Challenge was the primary gross motor skill measure. Change over time and relations among outcomes were evaluated. Results Challenge scores improved post-intervention (4.57% points [SD 4.45], P = .004) and were maintained at follow-up (0.75% [SD 6.57], P = 1.000). The laterality index for dominant ankle dorsiflexion increased ( P = .033), while non-dominant change was variable ( P = .534). Contralateral activation (laterality index ≥+0.75) was most common for both ankles. Challenge improvements correlated with increased ipsilateral activity (negative laterality index) during non-dominant dorsiflexion ( r = −.56, P = .045). Smaller activation volume during non-dominant dorsiflexion predicted continued gross motor gains at follow-up ( R2 = .30, P = .040). Conclusions Motor cortical activation during non-dominant ankle dorsiflexion is a modest indicator of the potential for gross motor skill change. Further investigation of patterns of neuroplastic change will improve our understanding of effects. ClinicalTrials.gov Registry: NCT02584491 and NCT02754128