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Technical complexity associated with biodegradation testing, particularly for substances of unknown or variable composition, complex reaction products, or biological materials (UVCB), necessitates the advancement of non‐testing methods such as quantitative structure–property relationships (QSPRs). Models for describing the biodegradation of petroleum hydrocarbons (HCs) have been previously developed. A critical limitation of available models is their inability to capture the variability in biodegradation rates associated with variable test systems and environmental conditions. Recently, the Hydrocarbon Biodegradation System Integrated Model (HC‐BioSIM) was developed to characterize the biodegradation of HCs in aquatic systems with the inclusion of key test system variables. The present study further expands the HC‐BioSIM methodology to soil and sediment systems using a database of 2195 half‐life (i.e., degradation time [DT]50) entries for HCs in soil and sediment. Relevance and reliability criteria were defined based on similarity to standard testing guidelines for biodegradation testing and applied to all entries in the database. The HC‐BioSIM soil and sediment models significantly outperformed the existing biodegradation HC half‐life (BioHCWin) and virtual evaluation of chemical properties and toxicities (VEGA) quantitative Mario Negri Institute for Pharmacological Research (IRFMN) models in soil and sediment. Average errors in predicted DT50s were reduced by up to 6.3‐ and 8.7‐fold for soil and sediment, respectively. No significant bias as a function of HC class, carbon number, or test system parameters was observed. Model diagnostics demonstrated low variability in performance and high consistency of parameter usage/importance and rule structure, supporting the generalizability and stability of the models for application to external data sets. The HC‐BioSIM provides improved accuracy of Persistence categorization, with correct classification rates of 83.9%, and 90.6% for soil and sediment, respectively, demonstrating a significant improvement over the existing BioHCWin (70.7% and 58.6%) and VEGA (59.5% and 18.5%) models. Environ Toxicol Chem 2024;43:1352–1363. © 2024 Concawe. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was –0·57 letters (95% CI –2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and –1·44 letters (–3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. Regeneron Pharmaceuticals and Bayer. [ABSTRACT FROM AUTHOR]

Neuropathic pain affects a large percentage of the U.S. population and leads to tremendous morbidity. Numerous nonsurgical and surgical treatments have been utilized to try and manage neuropathic pain with varying degrees of success. Recent research investigating ways to improve prosthetic control have identified new mechanisms for preventing neuromas in both motor and sensory nerves with free muscle and dermal grafts, respectively. These procedures have been used to treat chronic neuropathic pain in nonamputees, as well, in order to reduce failure rates found with traditional neurectomy procedures. Herein, we focus our attention on Dermal Sensory-Regenerative Peripheral Nerve Interfaces (DS-RPNI, free dermal grafts) which can be used to physiologically "cap" sensory nerves following neurectomy and have been shown to significantly decrease neuropathic pain. [ABSTRACT FROM AUTHOR]

A method is given to reduce the problem of finding a nontrivial factorization of a positive integer α , greater than one, to the problem of finding a solution to a system of Boolean equations, that is, a system of equations such that each equation is of the form f = g where f and g are Boolean functions, meaning { 0 , 1 } -valued functions in zero or more Boolean ( { 0 , 1 } -valued) variables. Our system is obtained by applying a sequence of reductions to an initial system of equations of the form { f i (x → , y →) = α i ∣ i ∈ { 0 , ⋯ , 2 n } } where for each i f i (x → , y →) = f i (x 0 , ⋯ , x n , y 0 , ⋯ , y n) gives the coefficient of 2 i in the binary expansion of (x 0 + 2 x 1 + ⋯ + 2 n x n) (y 0 + 2 y 1 + ⋯ + 2 n y n) , α i gives the coefficient of 2 i in the binary expansion of α , and x i and y i are { 0 , 1 } -valued variables. That is, the initial system represents a binary multiplier whose output bits have been set equal to the bits of α . It is shown that each Boolean function in our reduced system, that is, each Boolean function (g - h) mod 2 = 0 ⟺ g = h 1 ⟺ g ≠ h such that g = h is an equation in the reduced system, can be represented by a type of graph called an ordered binary decision diagram (OBDD) with an upper bound on its number of vertices of O log 2 (α / log 2 (α)) ) 3 . Previous work has shown that the initial system has at least one Boolean function with an OBDD representation with number of vertices exponential in log 2 (α) . [ABSTRACT FROM AUTHOR]

This study examined potential bias with respect to perceived gender and race in pre-service teachers' professional noticing of children's mathematical thinking. The goal of the study was to explore emerging connections between professional noticing and equity concerns in mathematics education and discover the extent to which such noticing may be influenced by a student's race and gender. A sample of 151 preservice teachers participated, and our findings suggest that bias tends to emerge in the interpreting phase of professional noticing; however, such emergence was not statistically significant when compared across the perceived race and gender of the students. [ABSTRACT FROM AUTHOR]

Fluorinated polyimides incorporated with triptycene units have gained growing attention over the last decade since they present potentially interesting selectivities and a higher free volume with respect to their triptycene-free counterparts. This work examines the transport of single-gas and mixed-gas N2 and CH4 in the triptycene-based 6FDA-BAPT homopolyimide and in a block 15,000 g mol−1/15,000 g mol−1 6FDA-mPDA/BAPT copolyimide by using molecular dynamics (MD) simulations. The void-space analyses reveal that, while the free volume consists of small-to-medium holes in the 6FDA-BAPT homopolyimide, there are more medium-to-large holes in the 6FDA-mPDA/BAPT copolyimide. The single-gas sorption isotherms for N2 and CH4 over the 0–70 bar range at 338.5 K show that both gases are more soluble in the block copolyimide, with a higher affinity for methane. CH4 favours sites with the most favourable energetic interactions, while N2 probes more sites in the matrices. The volume swellings remain limited since neither N2 nor CH4 plasticise penetrants. The transport of a binary-gas 2:1 CH4/N2 mixture is also examined in both polyimides under operating conditions similar to those used in current natural gas processing, i.e., at 65.5 bar and 338.5 K. In the mixed-gas simulations, the solubility selectivities in favour of CH4 are enhanced similarly in both matrices. Although diffusion is higher in 6FDA-BAPT/6FDA-mPDA, the diffusion selectivities are also close. Both triptycene-based polyimides under study favour, to a similar extent, the transport of methane over that of nitrogen under the conditions studied. [ABSTRACT FROM AUTHOR]

This paper highlights how immersive educational experiences can help students understand the United Nations' Sustainable Development Goals (SDGs) and their relation to leadership. The paper provides an example of how a carefully designed faculty‐led program using original research can cultivate cross‐cultural competencies and build student knowledge and skills to support sustainability. Educators can use this paper as a guide to other immersive experiences to address the SDGs while developing student leadership capacity. [ABSTRACT FROM AUTHOR]

Manchester 'working men' approved an address in support of Abraham Lincoln's emancipation policy and the American Union at the Free Trade Hall on 31 December 1862. The US president described their gesture as 'sublime Christian heroism' when hopes of restoring the cotton supply and reopening the mills were better served by Confederate recognition. This transatlantic exchange became an integral part of the scholarly traditional interpretation that the British working class frustrated the pro-Confederate designs of the upper classes during the American Civil War. It formed the historiographical orthodoxy until revisionists countered that Lancashire workers advocated Confederate recognition. The Manchester meeting, revisionists claimed, was contrived to give the impression of working-class support for Lincoln which was, in fact, a myth. These two incompatible interpretations simplify and flatten the complexity of an event with local, national, and international ramifications. This article presents the first detailed examination of who organized the Free Trade Hall meeting and why. It moves scholarly understanding of the British public response to the American Civil War beyond its current stasis of 'traditional' versus 'revisionist' by placing the field in conversation with the recent history of radicalism and 'class' in the Victorian era. [ABSTRACT FROM AUTHOR]

Background Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies. Methods We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition. Results A CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69–0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67–0.69). This model uses traveller's diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors. Conclusions We demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic made it difficult for Native American populations to access health information. Through funding from the Network of The National Library of Medicine Region 4, a community library was able to enhance their native and nonnative health collections for distribution on the Wind River Reservation in Central Wyoming. The book mobile was originally funded by the Wyoming State Library through American Rescue Plan Act of 2021 funding to increase literacy efforts during the pandemic. Materials were distributed at multiple locations throughout the reservation and individuals indicated they appreciated the materials being provided. This program was successful in distributing health information to an underserved priority population within the United States. Hopefully, similar programs would be successful in enhancing health education programs with other priority populations in both the United States and the world. [ABSTRACT FROM AUTHOR]

This work determines the phase stabilities and point defect energetics of TiSi2 and TiGe2 allotropes using density functional theory. The primary focus is on the C49 and C54 allotropes, which compete during TiSi2 phase formation. It is found that the ground state structure for TiGe2 is the C54 allotrope, desirable for its low sheet resistance, while the less desirable, higher resistance C49 allotrope forms the ground state structure of TiSi2. A first attempt to understand the Ge atom's role in lowering the enthalpy of formation for the C54 structure is made from the perspective of the extended Born model. Charge density differences, the density of states, and Bader charge analysis show that these systems are predominantly ionically bonded, with the Ge atoms introducing additional covalent bond stability for the C54 allotrope. It is known that higher temperatures favor C54 formation in TiSi2. Helmholtz free energy calculations for TiSi2 suggest that the vibrational free energy does not drive the system to the C54 phase. The formation energies of certain point defects within the C49 structure of TiSi2 are less than 1 eV, which is consistent with experiments that show high defect concentrations. Thus, the driving force for C54 formation at higher temperatures may be related to the high defect concentration in the C49 allotrope. [ABSTRACT FROM AUTHOR]

This paper examines democracy's impact on the labor share of income: the share of Gross Domestic Product (GDP) dedicated to wages, salaries, and benefits. I hypothesize democratic regimes afford labor the opportunity to increase its share of national income. While previous empirical work finds cross-sectional evidence for the hypothesis, this paper employs a time-series cross-sectional analysis using data for 119 countries between 1950 and 2017, indicating the labor share of income is higher in democratic countries. The estimates are robust to different specifications of the statistical model. This paper also examines a potential causal mechanism that links democracy to a higher labor share through the supply of labor (the average number of hours worked in the economy). The relationship between democracy and the supply of labor lends additional evidence to my hypothesis. In a world characterized by diverging democracy, the results imply the path countries choose between democracy and dictatorship matters. [ABSTRACT FROM AUTHOR]

Suppliers and large buyers of electricity often sign load-following forward contracts (LFFCs). A LFFC obligates an electricity supplier to deliver at a pre-specified unit price a fraction of the buyer’s ultimate demand for electricity. We show that relative to more standard (“swap”) forward contracts, LFFCs can reduce the variation in the wholesale price of electricity. However, LFFCs also can increase the expected wholesale price and thereby reduce expected consumer surplus and total surplus. [ABSTRACT FROM AUTHOR]

Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population. [ABSTRACT FROM AUTHOR]

The Department of Defense (DoD) is increasingly dependent on highly technological weapon systems, but the human is still at the heart of our war-fighting efforts. In order to maintain an effective fighting force, we must optimize and sustain human performance, which is defined as the successful completion of a specified task within an available performance capacity that meets or exceeds the mission demands. When health and performance are optimized and sustained, the costs of warfighter care and disability compensation are reduced and the quality of life is enhanced. Therefore, we propose that the Military Health System (MHS) reshape its focus on disease and injury treatment and prevention to embrace health enhancement for optimal human performance in a technology-rich battle space. This commentary develops a high-level strategy and policy framework to enable the MHS to optimize health and human performance for all DoD warfighters. We conducted a review of human performance literature, assessed existing health programs across the services, and conducted interviews with MHS and Line representatives. We found that the MHS has thus far met warfighter needs in a haphazard fashion. We propose an orchestrated approach to warfighter health and performance across the DoD and a more substantial partnership between Total Force Fitness and the MHS. We provide a notional concept for how the parts of this system could interact and a strategic framework for the delivery of health and performance to the warfighter. [ABSTRACT FROM AUTHOR]

Background: Frontline providers mostly outside specific emergency areas deliver emergency care around the world, yet often they do not receive dedicated training in managing emergency conditions. When designed for low-resource settings, emergency care training has been shown to improve provider skills, facilitate efficient use of available resources, and reduce death and disability by ensuring timely access to life-saving care. Methods: The WHO/ICRC Basic Emergency Care (BEC) Course with follow up longitudinal mentorship for 6 months was implemented in rural Neno District Malawi from September 2019-April 2020. We completed a mixed-methods analysis of the course and mentorship included mentor and participant surveys and feedback, mentorship quantification, and participant examination results. Simple descriptive statistics and boxplot visuals were used to describe participant demographics and mentorship quantification with a Wilcoxon signed-rank test to evaluate pre- and post-test scores. Qualitative feedback from participants and mentors were inductively analyzed using Dedoose. Results: The median difference of BEC course examination percentage score between participants before the BEC course and immediately following the course was 18.0 (95% CI 14.0–22.0; p<0.001). Examination scores from the one-year post-test was lower but sustained above the pre-course test score with a median difference of 11.9 (95% CI 4.0–16.0; p<0.009). There were 174 mentorship activities with results suggesting that a higher number of mentorship touches and hours of mentor-mentee interactions may assist in sustained knowledge test scores. Reported strengths included course delivery approach leading to improved knowledge with mentorship enhancing skills, learning and improved confidence. Suggestions for improvement included more contextualized training and increased mentorship. Conclusion: The BEC course and subsequent longitudinal mentorship were feasible and acceptable to participants and mentors in the Malawian low resource context. Follow-up longitudinal mentorship was feasible and acceptable and is likely important to cementing the course concepts for long-term retention of knowledge and skills. [ABSTRACT FROM AUTHOR]

Purpose: To collect data on efficacy and safety of brolucizumab 6 mg drug product intended for commercialization in patients with neovascular age-related macular degeneration to support comparability to brolucizumab product used in the Phase III HAWK and HARRIER studies. Methods: The HAWK extension study was a 24-week, double-masked, multicenter study of patients with neovascular age-related macular degeneration who completed the 96-week HAWK core study. All patients were planned to receive three intravitreal injections of either brolucizumab 6 mg or aflibercept 2 mg. Key endpoint measures included change in best-corrected visual acuity and central subfield thickness from baseline, and incidence and characteristics of treatment emergent adverse events. Results: Best-corrected visual acuity gain and central subfield thickness reduction observed at the end of the core study were maintained to Week 24 of the extension study. There was no indication of difference in the safety profile of the brolucizumab 6 mg drug product intended for commercialization and the brolucizumab 3 mg or 6 mg drug product used in the Phase III clinical trials. Conclusions: Efficacy and safety with the intended commercial formulation of brolucizumab 6 mg in neovascular age-related macular degeneration patients was consistent with that observed in the Phase III studies. [ABSTRACT FROM AUTHOR]

Kentucky’s breeding Haliaeetus leucocephalus (Bald Eagle) population began recovering in 1986, with a single nest, and has since expanded from the state’s western portion to the central and eastern regions. We used aerial survey data to describe the spatiotemporal distribution of Bald Eagle nests in Kentucky, to examine changes in nest-site selection relative to natural and anthropogenic features, and to create a nesting-habitat suitability model. Our results highlight increased nesting near developed areas in recent years. Although nests in these areas productively contribute to populations, we note some considerations of increased risks associated with nesting in developed areas. We also provide predictions of available nesting areas and data to direct the future monitoring and management of Bald Eagles in Kentucky. [ABSTRACT FROM AUTHOR]

This article addresses the role of nationalism and identity in relation to the experience of Italians in Australia, and more specifically, North Queensland, during World War One. Through a comparative study with the experience of Italians in the United States during World War One it is possible to comprehend further how the events of World War One impacted the Italian communities of Australia. World War One was a seminal event for the Italian communities in Australia as, unlike World War Two, the fact Italy and Australia were fighting on the same side gave Italians a sense of place in their new country they had not experienced before. However, when the Italian government attempted to forcibly conscript overseas Italians to fight on the Italian front, a policy they were helped with by the Australian government, it brought about challenging questions concerning citizenship, identity and the rights of immigrants residing in Australia. [ABSTRACT FROM AUTHOR]

St. George Jackson Mivart is mostly remembered as a cautionary tale. If Mivart is mentioned at all in modern debates, it is to offer an example of how not to do biology and theology. However, in this paper I argue that, ongoing developments in evolutionary biology have produced genuine alternatives to strict neo-Darwinism that not only seek to downplay the role of natural selection, but do so in ways that are strikingly reminiscent of Mivart's unpopular theory. Similarly, modern Thomists are also taking an approach to science and religion that mirrors Mivarts own approach. [ABSTRACT FROM AUTHOR]

Location‐specific information is required to support decision making in crop variety management, especially under increasingly challenging climate conditions. Data synthesis can aggregate data from individual trials to produce information that supports decision making in plant breeding programs, extension services, and of farmers. Data from on‐farm trials using the novel approach of triadic comparison of technologies (tricot) are increasingly available, from which more insights could be gained using a data synthesis approach. The objective of our study was to present the applicability of a rank‐based data synthesis approach to several datasets from tricot trials to generate location‐specific information supporting decision making in crop variety management. Our study focuses on tricot data from 14 trials of common bean (Phaseolus vulgaris L.) performed between 2015 and 2018 across four countries in Central America (Costa Rica, El Salvador, Honduras, and Nicaragua). The combined data of 17 common bean genotypes were rank aggregated and analyzed with the Plackett–Luce model. Model‐based recursive partitioning was used to assess the influence of spatially explicit environmental covariates on the performance of common bean genotypes. Location‐specific performance was predicted for the three main growing seasons in Central America. We demonstrate how the rank‐based data synthesis methodology allows integrating tricot trial data from heterogenous sources to provide location‐specific information to support decision making in crop variety management. Maps of genotype performance can support decision making in crop variety evaluation such as variety recommendations to farmers and variety release processes. Core Ideas: We aggregate data from trials established by different organizations across different seasons and locations.We generate location‐specific insights on genotype performance and environmental interaction.We characterize uncertainty of model predictions using Shannon's entropy and area of applicability assessment. [ABSTRACT FROM AUTHOR]

To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid. Multicenter, randomized, double-masked phase 3a study. Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti–vascular endothelial growth factor treatment). Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100. The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety. At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, –0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], –2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9–29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively. Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination. [ABSTRACT FROM AUTHOR]

As the counseling profession has increased focus on spiritual integration into counseling sessions, such integration brings necessary attention to professional ethics. While ethical guidelines mandate that counselors not impose values on clients, this has oftentimes been confused with the false idea that counselors who are Christian may not or cannot practice ethically due to potential conflicts between ethical practice and religious beliefs. This study helps explore professional counselors' understanding of the integration of Christianity into professional counseling. Such an understanding may help correct biases regarding ethical use of Christianity in professional mental health counseling. [ABSTRACT FROM AUTHOR]

The objective of this paper is to update and summarize the arguments behind the Integrated Heritage Rehabilitation (IHR) for Wooden Cities methodology. Building in the Coastal Temperate Rainforest ecoregion relied on native species, and is still characteristic of the towns in southern Chile, including the city of Valdivia. However, the historic town's urban fabric is vulnerable to natural disasters and neoliberal market practices. Regulations and instruments for architectural restoration hinder IHR since their primary focus lies in social sciences, excluding the fundamental architectonic technical aspects, as well as a broader understanding of the context. Through an analysis of a set of historic buildings restored with public funds, the relationship between social sciences, engineering, architecture, and the theories of public use and landscape is patent. It is evident that there is a need to establish effective practices to extend the service life of buildings through cultural heritage management. Eight key points were identified, that connect history with the material conditions, which today are lacking in the Chilean Public Service. For the restoration processes to be integrated, evaluations must include new dimensions, such as the economic relationship and the material or tangible management, as well as the integration with the surrounding original architectural identity and the ease with which it can be culturally associated. From the harmonization of these eight points within the heritage regulatory framework, an improvement of the integrated rehabilitation of heritage buildings in the southern Chilean towns is expected, with priority given to timber conservation and public contribution. [ABSTRACT FROM AUTHOR]

Recently, formative feedback in writing instruction has been supported by technologies generally referred to as Automated Writing Evaluation tools. However, such tools are limited in their capacity to explore specific disciplinary genres, and they have shown mixed results in student writing improvement. We explore how technology-enhanced writing interventions can positively affect student attitudes toward and beliefs about writing, both reinforcing content knowledge and increasing student motivation. Using a student-facing text-visualization tool called Write & Audit , we hosted revision workshops for students (n = 30) in an introductory-level statistics course at a large North American University. The tool is designed to be flexible: instructors of various courses can create expectations and predefine topics that are genre-specific. In this way, students are offered non-evaluative formative feedback which redirects them to field-specific strategies. To gauge the usefulness of Write & Audit, we used a previously validated survey instrument designed to measure the construct model of student motivation (Ling et al. 2021). Our results show significant increases in student self-efficacy and beliefs about the importance of content in successful writing. We contextualize these findings with data from three student think-aloud interviews, which demonstrate metacognitive awareness while using the tool. Ultimately, this exploratory study is non-experimental, but it contributes a novel approach to automated formative feedback and confirms the promising potential of Write & Audit. • A new student-facing writing technology, Write & Audit, is introduced. • The tool offers formative feedback for specialized, disciplinary genres. • Our initial implementation of the tool in a statistics workshop shows promising results. • Student participants showed improvements in motivation. • Think-aloud data display the tool's encouragement of metacognitive reflection. [ABSTRACT FROM AUTHOR]

The average number of hours we spend at work varies dramatically by country. Previous research focuses on tax policy, social security, and labor market regulation to explain the differences. This paper builds on previous work by focusing on politics. Specifically, it examines the relationship between democracy and the average number of hours worked per person employed. Using data on the supply of labor from the Penn World Tables 9.1, I find there is an important difference between democracies and dictatorships: as GDP/capita increases, individuals in democracies spend fewer hours at work than their counterparts in dictatorships. The results are robust to various specifications of the model that account for selection bias and data that are missing not at random (MNAR). These findings imply that the elections, civil rights, and the political liberties associated with democracy influence the amount of time people spend at work. [ABSTRACT FROM AUTHOR]

Chemical treatments are used to protect Tsuga canadensis (Eastern Hemlock) from Adelges tsugae (Hemlock Woolly Adelgid), yet little is known about how avian communities respond. We tested the efficacy of imidacloprid soil drenches on hemlocks and its impact on avian indicator species in the Appalachian Mountains of Kentucky at 65 sites (37 treated) in 2009 and 2018. Percent dead hemlock increased 11%, regardless of chemical treatment. Hemlock had higher vigor in treated sites, but a hemlock-decline index did not differ by treatment. None of 6 indicator bird species showed a significant population response to chemical treatments. Setophaga virens (Black-throated Green Warbler) declined between years across treated and untreated sites, whereas Contopus virens (Eastern Wood-Pewee) increased between years. Treatments positively affected individual hemlocks, but this did not carry over to influence avian species. Hemlock health may need to decline below some threshold before avian species respond. [ABSTRACT FROM AUTHOR]

A literary criticism of the play "Macbeth," by William Shakespeare is presented. It examines the racialized sounds of whiteness, the importance of Shakespeare's depiction of whiteness in the play for interpreting blackness, the contextualization of the play's soundscape by the social production of whiteness, and the disorder of the geographical outskirts evoked by Shakespeare via animal sounds heard by the characters.

An introduction is presented in which the editor discusses articles within the issue, including essays examining playwright William Shakespeare's drama and whiteness.

Background and objective. Multiple mastopexy techniques have been described, however, reports of long-term results in different techniques are scarce. The inverted-T and periaerolar techniques continue to be the most used, reason why we describe our experience with the long-term comparison of the two techniques. Methods. A longitudinal, comparative, observational, retrospective study comparing aesthetic satisfaction, speed of recovery and the probability of long-term associated complications was carried out in 97 mastopexy cases: 48 operated with the inverted-T technique and 49 with the periareolar technique. The homogenization of the data was analyzed with the x² and Fisher tests and the odds ratio (OR, 95% CI) was used as a measure of association between the surgical technique used and the probability of presenting complications. Results. At 5 years, of 48 patients who declared satisfaction of 100-80% all were operated with the inverted-T technique (p <0.001). For both the inverted T technique and the periareolar technique, the p-value according to the Friedman test for related samples was <0.000. Conclusions. In our experience, the periareolar mastopexy pattern has less satisfaction and more long-term complications than the inverted-T technique, from which we conclude that the periareolar mastopexy pattern is recommended in patients with grade I mammary ptosis and/or with small volume breast implants; mastopexy with the inverted-T technique has more satisfaction and fewer long-term complications like widening of the nipple-areola complex and breast asymmetry. [ABSTRACT FROM AUTHOR]

The American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions have recently released their joint guideline on coronary artery revascularization [[1]]. Considering that only 26% of patients in the revascularization arm underwent CABG, one can hardly consider this trial as an adequate comparison of CABG plus OMT versus OMT alone. The largest trial to date is the ISCHEMIA trial, which randomized patients with SIHD to revascularization or OMT in patients with moderate to severe ischaemia. [Extracted from the article]

Frequent anti-vascular endothelial growth factor A (VEGF-A) injections reduce the risk of rapid and severe vision loss in patients with neovascular age-related macular degeneration (nAMD); however, due to undertreatment, many patients lose vision over time. New treatments that provide sustained suppression of VEGF-A are needed. RGX-314 (currently known as ABBV-RGX-314) is an adeno-associated virus serotype 8 vector that expresses an anti-VEGF-A antigen-binding fragment, which provides potential for continuous VEGF-A suppression after a single subretinal injection. We report results on the safety and efficacy of subretinal injection of RGX-314 in patients with nAMD. For this open-label, multiple-cohort, multicentre, phase 1/2a, dose-escalation study conducted at eight sites in the USA, we enrolled participants with nAMD aged 50–89 years who had previously been treated with anti-VEGF injections into five cohorts (with five different doses of RGX-314). To be eligible, participants had to have macular neovascularisation secondary to nAMD with subretinal or intraretinal fluid in the centre subfield, be pseudophakic (after cataract removal), and have a best-corrected visual acuity (BCVA) in the study eye between 20/63 and 20/400 for the first participant in each cohort and between 20/40 and 20/400 for others. Subretinal injection of RGX-314 was done without a pre-bleb by a wet-laboratory-trained vitreoretinal surgeon. Cohort 1 received 3 × 109 genome copies per eye, cohort 2 received 1 × 1010, and cohort 3 received 6 × 1010. Two additional dose cohorts (cohort 4: 1·6 × 1011; cohort 5: 2·5 × 1011) were added. Participants were seen 1 day and 1 week after administration of RGX-314, and then monthly for 2 years (up to week 106). The primary outcome was safety of RGX-314 delivered by subretinal injection up to week 26. This analysis includes all 42 patients enrolled in the study. This study is registered with ClinicalTrials.gov , NCT03066258. Between May 12, 2017, and May 21, 2019, we screened 110 patients for eligibility and enrolled 68. 42 participants demonstrated the required anatomic response to intravitreal ranibizumab and then received a single RGX-314 injection (dose range 3 × 109 to 2·5 × 1011 genome copies per eye) and were followed up for 2 years. There were 20 serious adverse events in 13 participants, of which one was possibly related to RGX-314: pigmentary changes in the macula with severe vision reduction 12 months after injection of RGX-314 at a dose of 2·5 × 1011 genome copies per eye. Asymptomatic pigmentary changes were seen in the inferior retinal periphery several months after subretinal injection of RGX-314 most commonly at doses of 6 × 1010 genome copies per eye or higher. There were no clinically determined immune responses or inflammation beyond that expected following routine vitrectomy. Doses of 6 × 1010 genome copies or higher resulted in sustained concentrations of RGX-314 protein in aqueous humour and stable or improved BCVA and central retinal thickness with few or no supplemental anti-VEGF-A injections in most participants. Subretinal delivery of RGX-314 was generally well tolerated with no clinically recognised immune responses. RGX-314 gene therapy provides a novel approach for sustained VEGF-A suppression in patients with nAMD that has potential to control exudation, maintain vision, and reduce treatment burden after a single administration. Results from this study informed the pivotal programme to evaluate RGX-314 in patients with nAMD. RegenxBio. [ABSTRACT FROM AUTHOR]

This paper uses simple electricity market models to demonstrate the workings of, and problems with, Ontario's zonal price/two-schedule electricity market design. The roles played by zonal prices, Shadow LMP prices, and out-of-market congestion payments are explained. This market design is compared and contrasted to the much better-known single-schedule designs with LMP pricing used in neighboring U.S. markets. The ways in which congestion payments can, and have been, gamed is highlighted and shown to be special cases of counter-trading "inc-dec games". The bizarre outcomes for interjurisdictional trading arising from Ontario's use of congestion pricing on its interties combined with uniform pricing on the internal grid are demonstrated. Some gaming problems identified in other markets are reviewed compared to Ontario's situation. Finally, the paper recaps the system operator's efforts to remedy the various problems with the market while preparing a fundamental redesign. [ABSTRACT FROM AUTHOR]

We previously reported that growth promoter-induced skeletal muscle hypertrophy co-ordinately upregulated expression of genes associated with an integrated stress response (ISR), as well as potential ISR regulators. We therefore used Adeno-Associated Virus (AAV)-mediated overexpression of these genes, individually or in combination, in mouse skeletal muscle to test whether they induced muscle hypertrophy. AAV of each target gene was injected into mouse Tibialis anterior (TA) and effects on skeletal muscle growth determined 28 days later. Individually, AAV constructs for Arginase-2 (Arg2) and Activating transcription factor-5 (Atf5) reduced hindlimb muscle weights and upregulated expression of genes associated with an ISR. AAV-Atf5 also decreased Myosin heavy chain (MyHC)-IIB mRNA, but increased MyHC-IIA and isocitrate dehydrogenase-2 (Idh2) mRNA, suggesting ATF5 is a novel transcriptional regulator of Idh2. AAV-Atf5 reduced the size of both TA oxidative and glycolytic fibres, without affecting fibre-type proportions, whereas Atf5 combined with Cebpg (CCAAT enhancer binding protein-gamma) only reduced the size of glycolytic fibres and tended to increase the proportion of oxidative fibres. It is likely that persistent Atf5 overexpression maintains activation of the ISR, thereby reducing protein synthesis and/or increasing protein degradation and possibly apoptosis, resulting in inhibition of muscle growth, with overexpression of Arg2 having a similar effect. [ABSTRACT FROM AUTHOR]

In this paper we use a case study, the co-production of a prostate cancer app with, and for, Black British African-Caribbean communities, to discuss benefits and tensions of inclusive practice and allyship. We view our collaborators as joint partners, and joint allies, for the Black British African-Caribbean community. Here, we document the research process and highlight successful aspects of our collaboration such as mentoring, recruitment, ideas on the format and presentation of the app, supportive data collection practices, useful community feedback and promotion of the app. We also highlight points in the research process that in hindsight needed more discussion and careful negotiation. We end with some recommendations based on our experience. [ABSTRACT FROM AUTHOR]

This paper provides a critical analysis of the Chartered Institute for Management of Sport and Physical Activity's (CIMSPA) transformative aspirations for UK Higher Education (HE) based Sport and Physical Activity Vocational Education and Training (SPAVET) provision. In doing so, we apply selected elements of Giddens' Structuration theory to offer an analysis of CIMSPA's structural properties (as rules and resources) and dimensions (signification, domination and legitimation). Illustration of CIMSPA's structural properties and dimensions was developed through adopting an institutional analysis strategy alongside a document analysis method. Publicly available strategic documents and web-based resources (N = 18) were selected and analysed using open-coding techniques. Our analysis shows how continued state-sanctioned decentralisation of the UK HE sector has led to CIMSPA becoming an increasingly influential transformative structure; attempting to use its structural dimensions and resources as a medium to gain and exercise power, to promote (signification) – market-orientated discourses, practices and pedagogies in HEI provision, (domination) – in an attempt to significantly influence regulatory control over UK SPAVET provision and (Legitimation) – create partnerships which normalise its position and message within selected UK HEIs. We conclude that whilst the transformative aspirations of CIMSPA offer a number of possibilities for the HE SPAVET sector, they also raise critical questions. The central issue requiring debate is how these aspirations shift dialectical control towards vocationally focused, market-orientated principles and away from the liberal educational, research-led principles of some current UK HE SPAVET provision. [ABSTRACT FROM AUTHOR]

Previous studies have investigated the character and distribution of intense precipitation events across the United States. Increasing trends in intense, daily precipitation events at heavy (90–< 95th percentile), very heavy (95–< 99th percentile), and extreme (≥ 99th percentile) thresholds have all been reported. However, no previous studies have investigated the potential application of stochastic weather generators in determining future, site-specific distributions of such intense precipitation occurrences. In this study, two scenarios of future changes in intense precipitation for Weatherford, Oklahoma were examined through the use of a specific weather generator, SYNTOR, and by examination of heavy, very heavy, and extreme precipitation categories. All precipitation events across the three categories were increased multiple times by eight different percentages ranging from 5% to 75%, while precipitation events within the three categories were simultaneously increased by 14%, 20%, and 30%, respectively. Projected changes in the occurrence and categorical thresholds of intense precipitation events, as well as total monthly and annual precipitation and wet-dry transition probabilities, were assessed. The findings of this study show that projected increases in intense precipitation ranging from 5% to 40% are plausible and within the margin of error, based on the application of the two intensification scenarios to the synthetically generated weather data. Overall, the precipitation intensification scenarios markedly impacted estimates of intense precipitation, as well as average annual and monthly precipitation totals, but did not markedly impact the temporal distribution of precipitation annually or across seasons, nor the transition probabilities of projected precipitation between wet and dry days. Precipitation intensification scenarios can ultimately benefit in simulating erosion, runoff, and crop productivity responses to future precipitation distributions in agricultural watersheds of the Southern Great Plains as well as other locations. [ABSTRACT FROM AUTHOR]