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Abstract Background In humanitarian settings, brief screening instruments for child psychological distress have potential to assist in assessing prevalence, monitoring outcomes, and identifying children and adolescents in most need of scarce resources, given few mental health professionals for diagnostic services. Yet, there are few validated screening tools available, particularly in Arabic. Methods We translated and adapted the Child Psychosocial Distress Screener (CPDS) and the Pediatric Symptom Checklist (PSC) and conducted a validation study with 85 adolescents (aged 10–15) in Lebanon. We assessed internal consistency; test-retest reliability; convergent validity between adolescent- and caregiver-report and between the two measures; ability to distinguish between clinical and non-clinical samples; and concurrent validity against psychiatrist interview using the Kiddie Schedule for Affective Disorders and Schizophrenia. Results The translated and adapted child-reported PSC-17 and PSC-35, and caregiver-reported PSC-35 all showed adequate internal consistency and test-retest reliability and high concurrent validity with psychiatrist interview and were able to distinguish between clinical and non-clinical samples. However, the caregiver-reported PSC-17 did not demonstrate adequate performance in this setting. Child-reported versions of the PSC outperformed caregiver-reported versions and the 35-item PSC scales showed stronger performance than 17-item scales. The CPDS showed adequate convergent validity with the PSC, ability to distinguish between clinical and non-clinical samples, and concurrent validity with psychiatrist interview. Internal consistency was low for the CPDS, likely due to the nature of the brief risk-screening tool. There were discrepancies between caregiver and child-reports, worthy of future investigation. For indication of any diagnosis requiring treatment, we recommend cut-offs of 5 for CPDS, 12 for child-reported PSC-17, 21 for child-reported PSC-35, and 26 for caregiver-reported PSC-35. Conclusions The Arabic PSC and CPDS are reliable and valid instruments for use as primary screening tools in Lebanon. Further research is needed to understand discrepancies between adolescent and caregiver reports, and optimal methods of using multiple informants.

Abstract The Paramyxoviridae family encompasses medically significant RNA viruses, including human respiroviruses 1 and 3 (RV1, RV3), and zoonotic pathogens like Nipah virus (NiV). RV3, previously known as parainfluenza type 3, for which no vaccines or antivirals have been approved, causes respiratory tract infections in vulnerable populations. The RV3 fusion (F) protein is inherently metastable and will likely require prefusion (preF) stabilization for vaccine effectiveness. Here we used structure-based design to stabilize regions involved in structural transformation to generate a preF protein vaccine antigen with high expression and stability, and which, by stabilizing the coiled-coil stem region, does not require a heterologous trimerization domain. The preF candidate induces strong neutralizing antibody responses in both female naïve and pre-exposed mice and provides protection in a cotton rat challenge model (female). Despite the evolutionary distance of paramyxovirus F proteins, their structural transformation and local regions of instability are conserved, which allows successful transfer of stabilizing substitutions to the distant preF proteins of RV1 and NiV. This work presents a successful vaccine antigen design for RV3 and provides a toolbox for future paramyxovirus vaccine design and pandemic preparedness.

Abstract Background This study involved a scoping review to explore factors influencing dental hygienist demand and supply in high-income countries. Methods A six-stage scoping review was conducted with separate search strategies tailored to four databases (MEDLINE, CINAHL, Google Scholar, and Google) plus a targeted scan of dental hygienist organization websites. This yielded 2,117 unique citations, leading to 148 articles included in the review. Results Nearly half of the articles (47%) focused on the United States, with 11% on Canada. Most articles (91%) were in English, alongside 13 in Korean and one in French. Journal articles comprised 62% of the publications, followed by reports/working papers (11%) and websites (11%). Other types included conference abstracts, policy briefs, and presentation slides. Content-wise, 47% were original research, with analysis articles (14%), commentaries (11%), and reviews (8%) also present. The articles were coded into three main categories: workforce characteristics/projections, factor-specific analyses, and workforce opportunities. The articles on workforce characteristics covered demographic, geographic, and employment aspects of dental hygienists, along with projections for supply and demand using simulation modelling and geospatial analyses. Factor-specific articles investigated the (1) working environment, (2) policy/regulatory/training environment, (3) job/career satisfaction and related human resource issues, and (4) scope of practice. The third key category of articles highlighted opportunities for expanding the workforce through alternative models in different sectors/settings (e.g., public health, primary care, long-term care, hospitals, mobile outreach, and non-clinical roles including research, education and leadership) and for a range of vulnerable or underserved populations (e.g., geriatric and pediatric populations, persons with disabilities, those living in rural/remote areas, Indigenous peoples, and incarcerated people). Conclusions This review provides a comprehensive documentation of the current state of the dental hygienist workforce, compiling factors affecting demand and supply, and highlighting opportunities for the dental hygienist workforce in Canada and other high-income countries. The findings offer a foundation for future research, highlighting the need for more focused and rigorous reviews and underscoring the necessity of high-quality studies to verify the effectiveness of various interventions and policies. This is crucial to address dental hygienist workforce challenges and ensure the sustainability and effectiveness of oral health care delivery.

Ischemia-reperfusion injury (IRI) during liver transplantation has been implicated in the recurrence of hepatocellular carcinoma (HCC). This systematic review aimed to evaluate interventions to reduce IRI during liver transplantation for HCC and their impact on oncologic outcomes. A comprehensive literature search retrieved four retrospective studies involving 938 HCC patients, utilising interventions such as post-operative prostaglandin administration, hypothermic machine perfusion, and normothermic machine perfusion. Overall, treated patients exhibited reduced post-operative hepatocellular injury and inflammation and significantly enhanced recurrence-free survival. Despite these promising results, the impact of these interventions on overall survival remains unclear. This underscores the imperative for further prospective research to comprehensively understand the efficacy of these interventions in HCC patients undergoing transplantation. The findings highlight the potential benefits of these strategies while emphasising the need for continued investigation into their overall impact.

Objectives: The purpose of this study is to identify if construct length affects the rate of surgical complications and instrumentation revision following surgical fixation of subaxial and thoracolumbar Type B and C fractures. This study evaluates the effect of ankylosing spondylitis/diffuse idiopathic skeletal hyperostosis (AS/DISH) within this population on outcomes. Methods: Retrospective review of 91 cervical and 89 thoracolumbar Type B and C fractures. Groups were divided by construct length for analysis: short-segment (constructs spanning two or less segments adjacent to the fracture) and long-segment (constructs spanning more than two segments adjacent to the vertebral fracture). Results: For cervical fractures, construct length did not impact surgical complications (P = 0.641), surgical hardware revision (P = 0.167), or kyphotic change (P = 0.994). For thoracolumbar fractures, construct length did not impact surgical complications (P = 0.508), surgical hardware revision (P = 0.224), and kyphotic change (P = 0.278). Cervical Type B fractures were nonsignificantly more likely to have worsened kyphosis (P = 0.058) than Type C fractures. Assessing all regions of the spine, a diagnosis of AS/DISH was associated with an increase in kyphosis (P = 0.030) and a diagnosis of osteoporosis was associated with surgical hardware failure (P = 0.006). Conclusion: Patients with short-segment instrumentation have similar surgical outcomes and changes in kyphosis compared to those with long-segment instrumentation. A diagnosis of AS/DISH or osteoporosis was associated with worse surgical outcomes.

Abstract Background Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine. Methods A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), sleep-related impairments (SRI), and insomnia. Each model was controlled for age, sex, headache frequency, anxiety, and depression. Results A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p

Abstract Background The reporting of surgical instrument errors historically relies on cumbersome, non-automated, human-dependent, data entry into a computer database that is not integrated into the electronic medical record. The limitations of these reporting systems make it difficult to accurately estimate the negative impact of surgical instrument errors on operating room efficiencies. We set out to determine the impact of surgical instrument errors on a two-hospital healthcare campus using independent observers trained in the identification of Surgical Instrument Errors. Methods This study was conducted in the 7 pediatric ORs at an academic healthcare campus. Direct observations were conducted over the summer of 2021 in the 7 pediatric ORs by 24 trained student observers during elective OR days. Surgical service line, error type, case type (inpatient or outpatient), and associated length of delay were recorded. Results There were 236 observed errors affecting 147 individual surgical cases. The three most common errors were Missing+ (n = 160), Broken/poorly functioning instruments (n = 44), and Tray+ (n = 13). Errors arising from failures in visualization (i.e. inspection, identification, function) accounted for 88.6% of all errors (Missing+/Broken/Bioburden). Significantly more inpatient cases (42.73%) had errors than outpatient cases (22.32%) (p = 0.0129). For cases in which data was collected on whether an error caused a delay (103), over 50% of both IP and OP cases experienced a delay. The average length of delays per case was 10.16 min. The annual lost charges in dollars for surgical instrument associated delays in chargeable minutes was estimated to be between $6,751,058.06 and $9,421,590.11. Conclusions These data indicate that elimination of surgical instrument errors should be a major target of waste reduction. Most observed errors (88.6%) have to do with failures in the visualization required to identify, determine functionality, detect the presence of bioburden, and assemble instruments into the correct trays. To reduce these errors and associated waste, technological advances in instrument identification, inspection, and assembly will need to be made and applied to the process of sterile processing.

Abstract Intensification of northern hemisphere glaciation (iNHG), ~2.7 million years ago (Ma), led to establishment of the Pleistocene to present-day bipolar icehouse state. Here we document evolution of orbital- and millennial-scale Asian winter monsoon (AWM) variability across the iNHG using a palaeomagnetically dated centennial-resolution grain size record between 3.6 and 1.9 Ma from a previously undescribed loess-palaeosol/red clay section on the central Chinese Loess Plateau. We find that the late Pliocene–early Pleistocene AWM was characterized by combined 41-kyr and ~100-kyr cycles, in response to ice volume and atmospheric CO2 forcing. Northern hemisphere ice sheet expansion, which was accompanied by an atmospheric CO2 concentration decline, substantially increased glacial AWM intensity and its orbitally oscillating amplitudes across the iNHG. Superposed on orbital variability, we find that millennial AWM intensity fluctuations persisted during both the warmer (higher-CO2) late Pliocene and colder (lower-CO2) early Pleistocene, in response to both external astronomical forcing and internal climate dynamics.

Abstract Background Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD). Methods/design The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child–Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival. Discussion The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care. Ethics and dissemination The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation. Trial registration EUDRACT reference number: 2018–002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.

Rationale: F18-FDG PET/CT may be helpful in baseline staging of patients with high-risk LARC presenting with vascular tumor deposits (TDs), in addition to standard pelvic MRI and CT staging. Methods: All patients with locally advanced rectal cancer that had TDs on their baseline MRI of the pelvis and had a baseline F18-FDG PET/CT between May 2016 and December 2020 were included in this retrospective study. TDs as well as lymph nodes identified on pelvic MRI were correlated to the corresponding nodular structures on a standard F18-FDG PET/CT, including measurements of nodular SUVmax and SUVmean. In addition, the effects of partial volume and spill-in on SUV measurements were studied. Results: A total number of 62 patients were included, in which 198 TDs were identified as well as 106 lymph nodes (both normal and metastatic). After ruling out partial volume effects and spill-in, 23 nodular structures remained that allowed for reliable measurement of SUVmax: 19 TDs and 4 LNs. The median SUVmax between TDs and LNs was not significantly different (p = 0.096): 4.6 (range 0.8 to 11.3) versus 2.8 (range 1.9 to 3.9). For the median SUVmean, there was a trend towards a significant difference (p = 0.08): 3.9 (range 0.7 to 7.8) versus 2.3 (range 1.5 to 3.4). Most nodular structures showing either an SUVmax or SUVmean ≥ 4 were characterized as TDs on MRI, while only two were characterized as LNs. Conclusions: SUV measurements may help in separating TDs from lymph node metastases or normal lymph nodes in patients with high-risk LARC.

Abstract Schizophrenia ranks as the third-most common cause of disability among mental disorders globally. This study presents findings on the prevalence, incidence and years lived with disability (YLDs) as a result of schizophrenia in the Middle East and North Africa (MENA), stratified by age, sex and sociodemographic index (SDI). We collected publicly accessible data from the Global Burden of Disease (GBD) study 2019. This study reports the burden of schizophrenia, from 1990 to 2019, for the 21 countries that comprise MENA. In 2019, MENA exhibited an age-standardised point prevalence of 248.2, an incidence rate of 14.7 and an YLD rate of 158.7 per 100,000, which have not changed substantially between 1990 and 2019. In 2019, the age-standardised YLD rate was highest in Qatar and lowest in Afghanistan. No MENA countries demonstrated noteworthy changes in the burden of schizophrenia from 1990 to 2019. Furthermore, in 2019, the highest number of prevalent cases and the point prevalence were observed among those aged 35–39, with a higher prevalence among males in almost all age categories. Additionally, in 2019, the age-standardised YLD rates in MENA were below the worldwide average. Finally, there was a positive correlation between the burden of schizophrenia and the SDI from 1990 to 2019. The disease burden of schizophrenia has remained relatively stable over the past thirty years. Nevertheless, as the regional life-expectancy continues to increase, the burden of schizophrenia is also expected to rise. Therefore, early planning for the increase in the burden of the disease is urgently needed in the region.

Abstract Palaeocurrent analysis is vital for basin analysis and helps in the interpretation of depositional environments (along‐slope or downslope). For that, it is crucial to have multiple measuring methods at hand to apply palaeocurrent analysis with a wide range of different datasets (outcrops, cores and photographs). Here, two relatively underexploited palaeocurrent measurement techniques are assessed when applied to trough cross‐stratification observed in the Arenazzolo Formation at Eraclea Minoa (Sicily). The first technique is a novel design of a qualitative approach to infer palaeocurrent directions from photographs of two‐dimensional sedimentary structures. The second technique involves measurements of the anisotropy of magnetic susceptibility from drilled samples. A broad agreement, with overlapping uncertainty boundaries, is observed between results from both techniques. This agreement validates the use of trough cross‐strata to infer palaeocurrent directions. Moreover, the addition of photographs improves reproducibility and prevents a bias towards the best‐exposed troughs. The application of both techniques to outcrops and sedimentary cores provides new opportunities for palaeocurrent analysis in any type of sedimentary environment.

Abstract Despite expanded antiretroviral therapy (ART) in South Africa, HIV-1 transmission persists. Integrase strand transfer inhibitors (INSTI) and long-acting injectables offer potential for superior viral suppression, but pre-existing drug resistance could threaten their effectiveness. In a community-based study in rural KwaZulu-Natal, prior to widespread INSTI usage, we enroled 18,025 individuals to characterise HIV-1 drug resistance and transmission networks to inform public health strategies. HIV testing and reflex viral load quantification were performed, with deep sequencing (20% variant threshold) used to detect resistance mutations. Phylogenetic and geospatial analyses characterised transmission clusters. One-third of participants were HIV-positive, with 21.7% having detectable viral loads; 62.1% of those with detectable viral loads were ART-naïve. Resistance to older reverse transcriptase (RT)-targeting drugs was found, but INSTI resistance remained low (

Personal care products (PCPs) are intended for regular application by consumers and therefore assuring the safety of these products is very important. Recently, benzene contamination has been highlighted in certain PCPs. The present study applies selected ion flow tube mass spectrometry (SIFT-MS) to a simultaneous headspace analysis of benzene, 1,4-dioxane, and formaldehyde—all known or suspected carcinogens—in nine haircare products with supporting qualitative analysis by gas chromatography–mass spectrometry (GC-MS). Headspace-SIFT-MS method development is compatible with the method of standard additions, which is necessary for the quantitation of volatile impurities in these complex emulsions. Benzene was quantified above the low-ng g−1 limit of quantitation (LOQ) in three products, dioxane above the sub-μg g−1 LOQ in all products, and formaldehyde above the low-μg g−1 LOQ in two products, providing a quantitative analysis at concentrations relevant to consumer safety. This study facilitated the development of generic workflows for SIFT-MS method development and application in routine analysis of PCPs. The assessment of workflows for SIFT-MS compared to a conventional GC-MS analysis suggests that 8- to 30-fold throughput enhancements may be possible for quantitative and screening analysis using SIFT-MS.

Grape phylloxera, Daktulosphaira vitifoliae (Fitch), is an economically significant pest of grapevines. Identification of phylloxera genotypes is an important aspect of management as genotypes differ in virulence and susceptibility to control using resistant rootstocks. Microsatellite markers developed on polyacrylamide gel systems have been the most widely used molecular method for phylloxera genotype identification, but this approach has been superseded by fluorescent capillary-based genotyping. The current study presents new laboratory methods for amplifying a standard set of eight phylloxera microsatellite markers using PCR-incorporated fluorescently labelled primers, genotyped on an ABI capillary platform. Comparison of allele size data scored on (i) polyacrylamide, (ii) capillary, and (iii) high-throughput sequencing (HTS) platforms revealed that the capillary genotyping most closely matched the HTS allele sizes, while alleles of loci originally scored on a polyacrylamide platform differ in size by up to three base pairs, mostly due to the presence of previously uncharacterised DNA sequence indels. Seven common clonal lineages of phylloxera known from Australia are proposed as reference samples for use in calibrating genotyping systems between platforms and laboratories to ensure universal scoring of allele sizes, providing a critical link for accurately matching previous phylloxera genotype studies with current research.

This article explores Ephesians, asking how the theme of the new creation is developed in Ephesians. Rather than specifying matters like authorship, date, and recipients, it takes a broad view of the situation of the letter so that the focus can be on exploring the theme. It argues that the new creation idea is developed in three main ways. First, while Ephesians has a decidedly realized eschatology, there are hints throughout the letter of the consummation when the whole Earth is freed from corruption and reconciled under one head, Jesus Christ. Second, particularly in chapters 1–3, the writer of Ephesians focuses on realized aspects of eschatology to strengthen the readers’ understanding of their identity in Christ and their status as people of the new creation. The writer does this to strengthen the readers to assume the posture of the new creation while living in a fallen world beset with sin and under spiritual powers. In Ephesians 4–6, the writer describes this new creation virtues the readers are to embody as they contend for God in the world. Finally, the article explores the missional appeal of the letter. The writer challenges the readers to embody the new creation ethic and join God’s mission that calls all humankind to believe in the gospel and become people of the new creation.

Support to improve teacher wellbeing is scarce in almost all contexts, but especially so in low- and middle-income settings in which teachers face both professional and personal challenges (Kirk and Winthrop 2007; Mendenhall, Gomez, and Varni 2018). In this field note, we discuss War Child's development of Coaching-Observing-Reflecting-Engaging (CORE) for Teachers, an intervention that focuses on improving teachers' wellbeing. CORE is grounded in acceptance and commitment therapy and in the social-emotional framework of the Collaborative for Academic, Social, and Emotional Learning. It also draws from current research, including Jennings and Greenberg's (2009) prosocial classroom model. CORE aims to have a positive influence on classroom climate by providing teachers with the skills and knowledge they need to create an enabling, impactful, and safe learning environment for their students. In this field note, we outline the background on the development of the CORE intervention, including a literature review, the development of a theory of change, and field testing conducted in Chocó, Colombia. Having been field tested and adapted, CORE now is ready for further studies to determine feasibility and effectiveness.

This study evaluates the performance of continuous flow and drop-based microfluidic devices for the synthesis of silver nanoparticles (AgNPs) under identical hydrodynamic and chemical conditions. Flows at low values of Dean number (De < 1) were investigated, where the contribution of the vortices forming inside the drop to the additional mixing inside the reactor should be most noticeable. In the drop-based microfluidic device, discrete aqueous drops serving as reactors were generated by flow focusing using silicone oil as the continuous phase. Aqueous solutions of reagents were supplied through two different channels merging just before the drops were formed. In the continuous flow device, the reagents merged at a Tee junction, and the reaction was carried out in the outlet tube. Although continuous flow systems may face challenges such as particle concentration reduction due to deposition on the channel wall or fouling, they are often more practical for research due to their operational simplicity, primarily through the elimination of the need to separate the aqueous nanoparticle dispersion from the oil phase. The results demonstrate that both microfluidic approaches produced AgNPs of similar sizes when the hydrodynamic conditions defined by the values of De and the residence time within the reactor were similar.

Adequate water supplies are crucial for missions to the Moon, since water is essential for astronauts’ health. Ionic liquids (ILs) have been investigated for processing metal oxides, the main components of lunar regolith, to separate oxygen and metals. The IL must be diluted in the process. Recycling this diluted IL post-processing is important to reduce the materials required in resupply missions. In addition, water will be needed in lunar greenhouses for growing food and aiding in sustaining a habitable environment. Direct contact membrane distillation (DCMD) is a new technology for water purification that was examined in this study for its feasibility to concentrate IL. Hydrophobic membranes composed of polytetrafluoroethylene (PTFE) and polyvinylidene (PVDF) were found to hold promise in separating solutes from water to concentrate a diluted IL solution and to recover water. A bench-scale DCMD system was employed to test this method at temperatures of 50 °C, 65 °C, and 80 °C. Hence, the benefits and limitations of DCMD with PTFE and PVDF membranes were explored for the aqueous IL 1-ethyl-3 methylimidazolium hydrogen sulfate for DCMD performed at different temperatures.

The haptic fidelity of biomimetic materials used in the design of procedural task trainers is of growing interest to the medical community. Shore hardness has been proposed as a method for assessing tissue biomechanics and replicating the results as a way to increase the fidelity of biomimetics to tissues. However, there is limited research on the reliability of human tissue measurements using Shore scales. Using human tissues (internal carotid artery [ICA], internal jugular vein [IJV], vagus nerve [VN], sternocleidomastoid muscle [SCM], and overlying skin [skin]), this study evaluates (1) the inter-rater reliability of Shore hardness measurements, (2) examines the relationship between tissue thickness and hardness, and (3) investigates the impact of a measurement method (freehand vs. durometer stand). Preserved tissues, specifically a liver and components of the anterior triangle of the neck, were extracted from cadavers and measured by three independent raters using digital Shore durometers. Testing revealed that although Shore A demonstrated better inter-rater reliability compared to Shore OO, both scales exhibited poor-to-moderate reliability. ICC values for Shore A ranged from 0.21 to 0.80 and were statistically significant (p < 0.05) for all tissue types except the SCM. In contrast, Shore OO demonstrated poorer reliability, with ICC values ranging from 0.00 to 0.41. The ICC values were only significant for the ICA, IJV, and VN (p < 0.05). An inverse correlation between tissue thickness and hardness on the Shore A scale was found for all tissues and was significant (p < 0.05) for ICA, VN, and skin. There were mixed results for the correlation between tissue thickness and hardness on the Shore OO scale (−0.06–0.92), and only IJV had a statistically significant correlation (p < 0.05). Finally, the median hardness values on the Shore OO scale were significantly greater when measured using a durometer stand vs. freehand (Z = 4.78, p < 0.05). In summary, when using appropriate standards and addressing the challenges of tissue thickness and variability in freehand measures, Shore hardness has the potential to be used by clinicians in the clinical setting and in the selection of biomimetic materials in the design of task trainers.

We examine images of the protoplanetary disk 114–426 with JWST/NIRCam in 12 bands. This large disk is oriented edge on with a dark midplane flanked by lobes of scattered light. The outer edges of the midplane are seen in silhouette against the Orion Nebula, providing a unique opportunity to study planet-forming material in absorption. We discover a dip in the scattered light of the disk at 3 μ m—compelling evidence for the presence of water ice. The 3 μ m dip is also seen in the silhouette of the disk, where we quantify the ice abundance with models of pure absorption and avoid the complications of disk scattering effects. We find grain ice-to-refractory mass ratios of up to ~0.2, maximum grain sizes of 0.25–5 μ m, and a total dust plus ice mass of 0.46 M _⊕ in the silhouette region. We also discover excess absorption in the NIRCam bands that include the Pa α line, suggesting there may be excited atomic hydrogen in the disk. Examining the morphology of the scattered light lobes reveals that they are laterally offset from each other and exhibit a brightness asymmetry that flips with wavelength—both evidence for a tilted inner disk in this system.

The Simons Observatory will map the temperature and polarization over half of the sky at millimeter wavelengths in six spectral bands from the Atacama Desert in Chile. These data will provide new insights into the genesis, content, and history of our Universe, the astrophysics of galaxies and galaxy clusters, objects in our solar system, and time-varying astrophysical phenomena. This ambitious new instrument suite, initially comprising three 0.5 m diameter small aperture telescopes and one 6 m diameter large aperture telescope, is designed using a common combination of new technologies and new implementations to realize an observatory significantly more sensitive than the previous generation. In this paper, we present the predeployment performance of the first mid-frequency “optics tube,” which will be fielded on the large aperture telescope with sensitivity to the 90 and 150 GHz spectral bands. This optics tube contains lenses, filters, detectors, and readout components, all of which operate at cryogenic temperatures. It is one of seven that form the core of the large aperture telescope receiver in its initial deployment. We describe this optics tube, including details of comprehensive testing methods, new techniques for beam and passband characterization, and its measured performance. The performance metrics include beams, optical efficiency, passbands, and forecasts for the on-sky performance of the system. We forecast a sensitivity that exceeds the requirements of the large aperture telescope with greater than 30% margin in each spectral band and predict that the instrument will realize diffraction-limited performance and the expected detector passbands.

Summary: Sensing is a critical function of artificial cells; however, this is challenging to realize using bottom-up approaches. Here, we present a protocol for building protocell membranes that sense cues important for redox biochemistry and signaling by combining synthetic phospholipids and natural lipids. We detail procedures for building giant unilamellar vesicles as protocell models that fluoresce in response to the biologically significant redox agents peroxynitrite, hydrogen peroxide, and hydrogen sulfide.For complete details on the use and execution of this protocol, please refer to (i) Gutierrez and Aggarwal et al.1 as well as (ii) Erguven and Wang et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Despite the availability of a wide range of antihypertensive agents, a significant proportion of individuals with resistant hypertension (RHTN) struggle to achieve blood pressure (BP) control. Obesity ranks among the most significant modifiable risk factors for RHTN, with 56–91% of patients with RHTN classified as overweight or obese. Glucagon-like peptide-1 receptor agonist (GLP-1 RAs) are a class of anti-obesity medications that have recently demonstrated efficacy in reducing BP and improving cardiovascular (CV) outcomes in individuals with overweight or obesity. Among the available GLP-1-based therapies, liraglutide, semaglutide, and tirzepatide have been approved for chronic weight management in this population. Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, has the greatest effect on weight loss and BP reduction compared to GLP-1 RAs alone. To our knowledge, no trials have directly evaluated the effect of GLP-1 RAs or dual GLP-1/GIP receptor agonists on RHTN management. In this review article, we propose that targeting weight loss through GLP-1-based therapies should be explored as a treatment option for individuals with RHTN who are overweight or obese.

Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2-/-γc-/- mice. We conclude that in addition to NSG and NXG mice, RAG2-/-γc-/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.

BackgroundWhile smoking cessation has been linked to substantial weight gain, the potential influence of e-cigarettes on weight changes among individuals who use these devices to quit smoking is not fully understood. ObjectiveThis study aims to reanalyze data from the Evaluating the Efficacy of e-Cigarette Use for Smoking Cessation (E3) trial to assess the causal effects of e-cigarette use on change in body weight. MethodsThis is a secondary analysis of the E3 trial in which participants were randomized into 3 groups: nicotine e-cigarettes plus counseling, nonnicotine e-cigarettes plus counseling, and counseling alone. With adjustment for baseline variables and the follow-up smoking abstinence status, weight changes were compared between the groups from baseline to 12 weeks’ follow-up. Intention-to-treat and as-treated analyses were conducted using doubly robust estimation. Further causal analysis used 2 different propensity scoring methods to estimate causal regression curves for 4 smoking-related continuous variables. We evaluated 5 different subsets of data for each method. Selection bias was addressed, and missing data were imputed by the machine learning method extreme gradient boosting (XGBoost). ResultsA total of 257 individuals with measured weight at week 12 (mean age: 52, SD 12 y; women: n=122, 47.5%) were included. Across the 3 treatment groups, of the 257 participants, 204 (79.4%) who continued to smoke had, on average, largely unchanged weight at 12 weeks, with comparable mean weight gain ranging from –0.24 kg to 0.33 kg, while 53 (20.6%) smoking-abstinent participants gained weight, with a mean weight gain ranging from 2.05 kg to 2.70 kg. After adjustment, our analyses showed that the 2 e-cigarette arms exhibited a mean gain of 0.56 kg versus the counseling alone arm. The causal regression curves analysis also showed no strong evidence supporting a causal relationship between weight gain and the 3 e-cigarette–related variables. e-Cigarettes have small and variable causal effects on weight gain associated with smoking cessation. ConclusionsIn the E3 trial, e-cigarettes seemed to have minimal effects on mitigating the weight gain observed in individuals who smoke and subsequently quit at 3 months. However, given the modest sample size and the potential underuse of e-cigarettes among those randomized to the e-cigarette treatment arms, these results need to be replicated in large, adequately powered trials. Trial RegistrationClinicalTrials.gov NCT02417467; https://www.clinicaltrials.gov/study/NCT02417467

Inbreeding depression is a key factor regulating the evolution of self-fertilization in plants. Despite predictions that inbreeding depression should evolve with selfing rates as deleterious alleles are increasingly exposed and removed by selection, evidence of purging the genetic load in wild populations is equivocal at best. This discordance could be explained, in part, if the load underlying inbreeding depression is subject to soft selection, i.e., the fitness of selfed individuals depends on the frequency and density of selfed vs. outcrossed individuals in the population. Somewhat counterintuitively, this means that populations with contrasting mutation load can have similar fitness. Soft selection against selfed individuals may be expected when there is inbreeding depression for competitive ability in density-regulated populations. We tested population-level predictions of inbreeding depression in competitive ability by creating a density series of potted plants consisting of either purely outcrossed, purely selfed, or mixed (50% outcrossed, 50% selfed) seed of the mixed-mating biennial Sabatia angularis (Gentianaceae) representing ecological neighborhoods. Focusing on the growth and survival of juveniles, we show that mean plant size is independent of neighborhood composition when resources are limiting, but greatest in outcrossed neighborhoods at low densities. Across a range of densities, this manifests as stronger density-dependence in outcrossed populations compared to selfed or mixed ones. We also found significantly greater size inequalities among individuals in mixed neighborhoods, even at high densities where mean juvenile size converged, a key signature of asymmetric competition between outcrossed and selfed individuals. Our work illustrates how soft selection could shelter the genetic load underlying inbreeding depression and its demographic consequences.

Few studies have considered household interventions for reducing endocrine disrupting chemical (EDC) exposures. We conducted a secondary analysis of a randomized controlled trial, originally designed to reduce lead exposure, to evaluate if the intervention lowered EDC exposures in young children. Study participants were children from the Cincinnati, Ohio area (n = 250, HOME Study). Prenatally, families received a housing intervention that included paint stabilization and dust mitigation, or as a control, injury prevention measures. At 24-months, we measured organophosphate esters (OPEs) and phthalates or their metabolites in dust and urine. We measured perfluoroalkyl substances (PFAS) in dust and serum at 24- and 36-months, respectively. We assessed associations between dust and biomarker EDCs using Spearman correlations, characterized EDC mixtures via principal components analysis, and investigated treatment effects using linear regression. To mitigate selection bias, we fit statistical models using inverse probability of retention weights. Correlations between dust EDCs and analogous biomarkers were weak-to-moderate (ρ’s ≤ 0.3). The intervention was associated with 23 % (95 % CI: −38, −3) lower urinary DEHP metabolites and, in a per-protocol analysis, 34 % lower (95 % CI: −55, −2) urinary MBZP. Additionally, among Black or African American children, the intervention was associated with lower serum concentrations of several PFAS (e.g., −42 %; 95 % CI: −63, −8 for PFNA). Household interventions that include paint stabilization and dust mitigation may reduce childhood exposures to some phthalates and PFAS in Blacks/African Americans. These findings highlight the need for larger studies with tailored and sustained housing interventions.

Biological invasions of freshwater habitats are of increasing biological and economical concern, and both, salinity and parasites are considered to be key contributors to invasion success. Salinity, for example, influences the distribution of invasive mosquitofish (Gambusia holbrooki) and native killifish (Aphanius fasciatus) in Europe, with the latter now predominantly confined to high-salinity habitats. Here, we examined how salinity might affect female activity and preference for large and non-parasitized males in multiple populations of mosquitofish and killifish in Sardinia, Italy. We predicted that (1) females of both species would associate preferentially with larger and uninfected males, and that (2) female behavior in both species would be significantly influenced by salinity. We used dichotomous choice tests, in which we presented focal females with video animations of photos of the same male but differing in body size and presence/absence of an ectoparasite (Lernaea cyprinacea). We calculated female preference based on association time and quantified female inactivity as time spent in the central neutral zone during trials. Contrary to prediction 1, females did not prefer the large or uninfected male stimuli over their counterparts in any of the populations. However, while salinity did not significantly affect female preferences, it did significantly affect their activity, with mosquitofish becoming more inactive at higher salinities and killifish exhibiting the opposite pattern, matching prediction 2. These results suggest that salinity limits mosquitofish invasiveness by reducing their activity and thus provides a refuge for the Mediterranean killifish.

Abstract The Cuo E (CE) core contains the entire Quaternary stratigraphy of the CE Lake (31°24′–31°.32′ N, 91°28′–91°33′E, Tibetan Plateau, China). Here, we study the magnetic properties of 1,748 samples from the CE core, combined with scanning electron microscopy and X‐ray energy dispersive spectrometer analysis on selected samples. The main magnetic minerals appear to be magnetite and greigite. To further quantify the presence of greigite in CE core, 84 samples were analyzed using rock magnetism in more detail including: susceptibility (χ) versus temperature, coercivity component analysis of acquisition curves of the isothermal remanent magnetization (IRM), and principal component analysis of the first‐order reversal curve (FORC) diagrams. The greigite content and saturation IRM over susceptibility (SIRM/χ) appear to be exponentially related. SIRM/χ can be used as greigite concentration indicator. We also propose a rapid way to identify greigite in the CE core: When SIRM/χ increases and anhysteretic remanent susceptibility (χARM) increases only slowly, the sample contains greigite. Samples with SIRM/χ

Abstract Background Research on genetic and environmental influences on speech and/or language difficulties (SaLD) is sparse, with inconsistent heritability estimates. We aimed to estimate the prevalence of parental reported SaLD and the relative contributions of genetic and environmental factors for the phenotype using a Swedish population‐based twin sample. We hypothesized that there would be a stronger genetic than environmental effect on SaLD. Methods Data were collected from The Child and Adolescent Twin Study in Sweden. The study sample included 16,774 twin pairs (16,946 males, 16,602 females), of which 5141 were monozygotic, 5861 dizygotic (DZ), and 5772 opposite‐sex DZ pairs. The language items in the Autism–Tics, Attention‐Deficit Hyperactivity Disorder, and other Comorbidities inventory were used to categorize individuals as having parental‐reported SaLD. A classical twin design was used to estimate the relative contribution of genetic and environmental factors to the liability of SaLD. Results The prevalence of SaLD was 7.85% (95% confidence interval (CI) [7.57%–8.15%]) and 7.27% (95% CI [6.99%–7.55%]) when excluding individuals with autism and intellectual disability (ID). We also found that SaLD were significantly more prevalent in males than females with a ratio of 2:1. The heritability was estimated to be 75% (95% CI [67%–83%]) for SaLD. Shared environment played a significant role with an estimated contribution of 22% (95% CI [14%–30%]). The heritability estimate was reduced to 70% but with overlapping CI when excluding individuals with autism and ID. Conclusions We provide evidence that SaLD is common in the population and under strong genetic influence. Future studies should focus on mapping the genetic architecture of SaLD and related disorders.

Background: Transcatheter aortic valve replacement (TAVR) is an important treatment option for patients with severe symptomatic aortic stenosis. It is important to identify predictors of excellent outcomes (good clinical outcomes, more time spent at home) after TAVR that are potentially amenable to improvement. Objectives: The purpose of the study was to use machine learning to identify potentially modifiable predictors of clinically relevant patient-centered outcomes after TAVR. Methods: We used data from 8,332 TAVR cases (January 2016-December 2021) from 21 hospitals to train random forest models with 57 patient characteristics (demographics, comorbidities, surgical risk score, lab values, health status scores) and care process parameters to predict the end point, a composite of parameters that designated an excellent outcome and included no major complications (in-hospital or at 30 days), post-TAVR length of stay of 1 day or less, discharge to home, no readmission, and alive at 30 days. We used recursive feature elimination with cross-validation and Shapley Additive Explanation feature importance to identify parameters with the highest predictive values. Results: The final random forest model retained 29 predictors (15 patient characteristics and 14 care process components); the area under the curve, sensitivity, and specificity were 0.77, 0.67, and 0.73, respectively. Four potentially modifiable predictors with relatively high Shapley Additive Explanation values were identified: type of anesthesia, direct movement to stepdown unit post-TAVR, time between catheterization and TAVR, and preprocedural length of stay. Conclusions: This study identified four potentially modifiable predictors of excellent outcome after TAVR, suggesting that machine learning combined with hospital-level data can inform modifiable components of care, which could support better delivery of care for patients undergoing TAVR.

BackgroundPrevious work reported increased rates of cardiovascular hospitalizations associated with increased source-specific PM2.5 concentrations in New York State, despite decreased PM2.5 concentrations. We also found increased rates of ST elevation myocardial infarction (STEMI) associated with short-term increases in concentrations of ultrafine particles and other traffic-related pollutants in the 2014–2016 period, but not during 2017–2019 in Rochester. Changes in PM2.5 composition and sources resulting from air quality policies (e.g., Tier 3 light-duty vehicles) may explain the differences. Thus, this study aimed to estimate whether rates of STEMI were associated with organic carbon and source-specific PM2.5 concentrations.MethodsUsing STEMI patients treated at the University of Rochester Medical Center, compositional and source-apportioned PM2.5 concentrations measured in Rochester, a time-stratified case-crossover design, and conditional logistic regression models, we estimated the rate of STEMI associated with increases in mean primary organic carbon (POC), secondary organic carbon (SOC), and source-specific PM2.5 concentrations on lag days 0, 0–3, and 0–6 during 2014–2019.ResultsThe associations of an increased rate of STEMI with interquartile range (IQR) increases in spark-ignition emissions (GAS) and diesel (DIE) concentrations in the previous few days were not found from 2014 to 2019. However, IQR increases in GAS concentrations were associated with an increased rate of STEMI on the same day in the 2014–2016 period (Rate ratio [RR] = 1.69; 95% CI = 0.98, 2.94; 1.73 μg/m3). In addition, each IQR increase in mean SOC concentration in the previous 6 days was associated with an increased rate of STEMI, despite imprecision (RR = 1.14; 95% CI = 0.89, 1.45; 0.42 μg/m3).ConclusionIncreased SOC concentrations may be associated with increased rates of STEMI, while there seems to be a declining trend in adverse effects of GAS on triggering of STEMI. These changes could be attributed to changes in PM2.5 composition and sources following the Tier 3 vehicle introduction.

Introduction Promoting mental health, preventing and treating mental disorders are critically important in public health, and many randomised controlled trials (RCTs) evaluate intervention strategies for these objectives. However, distinguishing promotion from prevention and from treatment RCTs is challenging. A tool to place studies along the promotion-to-treatment continuum in mental health research does not exist, leaving it to researchers and policymakers to decide on how to classify individual RCTs, which hinders evidence synthesis.Methods and analysis We present a protocol for the development of a new tool to assist researchers in distinguishing RCTs along the promotion-to-treatment continuum. We will establish a Tool Development Group, and use the Population, Intervention, Comparison and Outcome framework to define constructs. We will generate, define, categorise and reduce the items in the tool using qualitative methods, including cognitive interviews and a Delphi exercise. Psychometric evaluation—including unidimensionality, local independence, monotonicity and item homogeneity—will include data collection, scoring, internal consistency checks and factor analysis of the tool’s indicators for available RCTs. We will use standard Cohen’s kappa statistics to assess the reliability of the tool.Ethics and dissemination This study involves data collection from the already published literature. However, this protocol has been approved by the ethics committee of the Università della Svizzera Italiana (CE 2024 04). The results of the present project will be disseminated in peer-reviewed journals and at international and national scientific meetings. Training materials for the application of the tool will also be developed and disseminated to the scientific community. The tool and all related implementation materials will be published on a website and will be freely accessible to the public.

Background: Escalating street violence and criminal homicides have an adverse impact on psychological well-being. However, these consequences have been difficult to evaluate. Using a recently validated scale, we aimed to assess the impact of fear of crime on the psychological status of middle-aged and older adults living in a rural setting afflicted by endemic violence. Methods: Participants were selected from Atahualpa residents included in previous studies targeting psychological distress in the population. A validated scale was used to objectively quantify fear of crime in participants. Differences in symptoms of depression and anxiety between baseline and follow-up were used as distinct dependent variables and the continuous score of the fear of crime scale was used as the independent variable. Linear regression models were fitted to assess the association between the exposure and the outcomes, after adjusting for relevant confounders. Results: A total of 653 participants (mean age = 53.2 ± 11.5 years; 57% women) completed the requested tests. We found a 13% increase in symptoms of depression and anxiety during the peak of violence in the village compared with previous years. Linear regression models showed a significant association between the total score on the fear of crime questionnaire and worsening symptoms of depression (β = .24; 95% CI = 0.14-0.35) and anxiety (β = .31; 95% CI = 0.24-0.37), after adjustment for relevant confounders. Conclusions: This study shows a significant aggravating effect of fear of crime on pre-existing symptoms of depression and anxiety and a deleterious effect of these conditions on overall well-being.

BackgroundPostacute sequelae of COVID-19 (PASC), also known as long COVID, is a broad grouping of a range of long-term symptoms following acute COVID-19. These symptoms can occur across a range of biological systems, leading to challenges in determining risk factors for PASC and the causal etiology of this disorder. An understanding of characteristics that are predictive of future PASC is valuable, as this can inform the identification of high-risk individuals and future preventative efforts. However, current knowledge regarding PASC risk factors is limited. ObjectiveUsing a sample of 55,257 patients (at a ratio of 1 patient with PASC to 4 matched controls) from the National COVID Cohort Collaborative, as part of the National Institutes of Health Long COVID Computational Challenge, we sought to predict individual risk of PASC diagnosis from a curated set of clinically informed covariates. The National COVID Cohort Collaborative includes electronic health records for more than 22 million patients from 84 sites across the United States. MethodsWe predicted individual PASC status, given covariate information, using Super Learner (an ensemble machine learning algorithm also known as stacking) to learn the optimal combination of gradient boosting and random forest algorithms to maximize the area under the receiver operator curve. We evaluated variable importance (Shapley values) based on 3 levels: individual features, temporal windows, and clinical domains. We externally validated these findings using a holdout set of randomly selected study sites. ResultsWe were able to predict individual PASC diagnoses accurately (area under the curve 0.874). The individual features of the length of observation period, number of health care interactions during acute COVID-19, and viral lower respiratory infection were the most predictive of subsequent PASC diagnosis. Temporally, we found that baseline characteristics were the most predictive of future PASC diagnosis, compared with characteristics immediately before, during, or after acute COVID-19. We found that the clinical domains of health care use, demographics or anthropometry, and respiratory factors were the most predictive of PASC diagnosis. ConclusionsThe methods outlined here provide an open-source, applied example of using Super Learner to predict PASC status using electronic health record data, which can be replicated across a variety of settings. Across individual predictors and clinical domains, we consistently found that factors related to health care use were the strongest predictors of PASC diagnosis. This indicates that any observational studies using PASC diagnosis as a primary outcome must rigorously account for heterogeneous health care use. Our temporal findings support the hypothesis that clinicians may be able to accurately assess the risk of PASC in patients before acute COVID-19 diagnosis, which could improve early interventions and preventive care. Our findings also highlight the importance of respiratory characteristics in PASC risk assessment. International Registered Report Identifier (IRRID)RR2-10.1101/2023.07.27.23293272

Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.

The increase of antibiotic-resistant bacteria has become a global health emergency and the need to explore alternative therapeutic options arises. Phage therapy uses bacteriophages to target specific bacterial strains. Phages are highly specific and can target resistant bacteria. Currently, research in this regard is focused on ensuring reliability and safety to bring this tool into clinical practice. The first step is to conduct comprehensive preclinical research. In this work, we present two novel bacteriophages vB_Kpn_F13 and vB_Kpn_F14 isolated against clinical carbapenem-resistant Klebsiella pneumoniae strains obtained from hospital sewage. Multiple studies in vitro were conducted, such as sequencing, electron microscopy, stability, host range infectivity, planktonic effect and biofilm inhibition in order to discover their ability to be used against carbapenem-resistant K. pneumoniae pathogens causing difficult-to-treat infections.

Background: Patella baja is a known complication of total knee arthroplasty (TKA). There is a limited understanding of the association between patellar resurfacing and the incidence of patella baja. We aimed to compare rates of patella baja between unresurfaced and resurfaced patellas in patients undergoing TKA. Methods: A retrospective review of patients who underwent TKA between October 2009 and January 2020 was performed. Patients were included if they had at least one preoperative radiograph and a 1-year follow-up radiograph. Blackburne-Peel index (BPI) and Insall-Salvati ratios (ISRs) were measured on preoperative and 1-year postoperative radiographs and were used to define patella baja vs pseudopatella baja. Statistical analysis was performed using a linear model analysis of variance and the Fisher’s exact test. Results: Three hundred eighteen TKAs were included, with 176 being resurfaced and 142 unresurfaced patellas. Of the resurfaced group, 4% (7/176) had true patella baja, compared to 5.6% (8/142) of the unresurfaced patellas. Of the resurfaced patellas, 8% (14/176) had pseudopatella baja, compared to 7% (10/142) in the unresurfaced group. Patellar resurfacing was not associated with a higher incidence of patella baja (P = .60) or pseudopatella baja (P = .83). Lower preoperative ISRs (P = .04) and BPIs (0.03) were highly predictive of a higher incidence of patella baja post-TKA. Conclusions: Patellar resurfacing in TKA is not associated with a higher incidence of patella baja in TKA when compared to unresurfaced patellas. Lower preoperative ISRs and BPIs are highly predictive of a higher incidence of postoperative patella baja.

Background: The primary purpose of this study was to evaluate how utilization, physician reimbursement, and patient populations have changed for primary total knee arthroplasty (TKA) from 2013 to 2021 at both a regional and national level within the Medicare population. Methods: The Medicare Physician and Other Practitioners database was queried for all episodes of primary TKA between years 2013 and 2021. TKA utilization per 10,000 beneficiaries, inflation-adjusted physician reimbursement per TKA, and patient demographics of each TKA surgeon were extracted each year. Data were stratified geographically, and Kruskal-Wallis tests were utilized. Results: Between 2013 and 2021, TKA utilization per 10,000 beneficiaries increased at the greatest rate in the Northeast (+15.1%). In 2021, TKA utilization was highest in the Midwest (97.6/10,000; P < .001). The Midwest had the greatest decline in average physician reimbursement per TKA between 2013 and 2021 (−26.3%) and the lowest average reimbursement ($988.70, P < .001) in 2021. Alternatively, the Northeast had the smallest decline in average TKA reimbursement (−22.6%). Nationally, the average number of beneficiaries per TKA surgeon declined (−6.8%), while the average number of TKAs per surgeon (+5.7%) and average services per beneficiary (+24.3%) both increased. The average number of patient comorbidities and proportion of patients with dual Medicare-Medicaid eligibility decreased over time across all regions. Conclusions: This study demonstrates that TKA utilization is increasing and average physician reimbursement per TKA is declining at varying rates across the country, with the Northeast and Midwest most affected. These findings should be addressed in policy discussions to ensure equitable arthroplasty care.

Mark J. R. Smeets and Suzanne C. Cannegieter discuss the use of real world data to complement data generated by clinical trials of systemic anticoagulants.

Background Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin‐converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin‐converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. Methods and Results We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow‐up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus

Background: Women are at greater risk for heart failure with preserved ejection fraction (HFpEF). Objectives: The aim of the study was to compare sex differences in the pathophysiology of exertional breathlessness in patients with high vs low HFpEF likelihood. Methods: This cohort study evaluated consecutive patients (n = 1,936) with unexplained dyspnea using cardiopulmonary exercise testing and simultaneous echocardiography and quantified peak oxygen uptake (peak VO2) and its determinants. HFpEF was considered likely when the H2FPEF or HFA-PEFF score was ≥6 or ≥5, respectively. Sex differences were evaluated with the Student’s t-test or Mann-Whitney U test and determinants of exercise capacity with a multivariable linear regression. Results: The cohort included 1,963 patients (49% women and 28% [n = 555] with a high HFpEF likelihood). HFpEF likelihood did not impact the magnitude of sex differences in peak VO2 and its determinants. Overall, women had lower peak VO2 (mean difference −4.4 mL/kg/min [95% CI: −3.7 to −5.1 mL/kg/min]) secondary to a reduced O2 delivery (−0.5 L/min [95% CI: −0.4 to −0.6 L/min]) and less oxygen extraction (−2.9 mL/dL [95% CI: −2.5 to −3.2 mL/dL]). Reduced O2 delivery was due to lower hemoglobin (−1.2 g/dL [95% CI: −0.9 to −1.5 g/dL]) and smaller stroke volume (−15 mL [95% CI: −14 to −17 mL]). Women demonstrated increased mean pulmonary artery pressure/cardiac output slope (+0.5 mm Hg/L/min [95% CI: 0.3-0.7 mm Hg/L/min]) and left ventricular ejection fraction (+1% [95% CI: 1%-2%]), while they had smaller left ventricular end-diastolic volumes (−9 mL/m2 [95% CI: −8 to −11 mL/m2]) and mass (−12 g/m2 [95% CI: −9 to −14 g/m2]) and more often iron deficiency (55% vs 33%; P < 0.001). Conclusions: Women with unexplained dyspnea had significantly lower peak VO2, regardless of HFpEF likelihood, attributed to both lower peak exercise O2 delivery and extraction. This suggests that physiologic sex differences, and not HFpEF likelihood, are an important factor contributing to functional limitations in females with exertional breathlessness.

Background The open field assay is used to study anxiety-related traits and anxiolytic drugs in rodents. This assay entails measuring locomotor activity and time spent in the center of a chamber that is maintained at ambient room temperature. However, the ambient temperature in most laboratories varies daily and seasonally and can differ between buildings. We sought to evaluate how varying ambient temperature and core body temperature (CBT) affected open field locomotor activity and center time of male wild-type (WT, C57BL/6) and Transient Receptor Potential Subfamily M Member 8 (Trpm8) knock-out (Trpm8-/- ) mice. TRPM8 is an ion channel that detects cool temperatures and is activated by icilin. Methods Mice were placed in the open field at 4°C and 23°C for 1 hour. Distance traveled and time spent in the center were measured. Mice were injected with icilin, M8-B, diazepam, or saline, and changes in activity level were recorded. Results The cooling agent icilin increased CBT and profoundly reduced distance traveled and center time of WT mice relative to controls. Likewise, cooling the ambient temperature to 4°C reduced distance traveled and center time of WT mice relative to Trpm8-/- mice. Conversely, the TRPM8 antagonist (M8-B) reduced CBT and increased distance traveled and center time of WT mice when tested at 4°C. The TRPM8 antagonist (M8-B) had no effect on CBT or open field behavior of Trpm8-/- mice. The anxiolytic diazepam reduced CBT in WT and Trpm8-/- mice. When tested at 4°C, diazepam increased distance traveled and center time in WT mice but did not alter open field behavior of Trpm8-/- mice. Conclusions Environmental temperature and drugs that affect CBT can influence locomotor behavior and center time in the open field assay, highlighting temperature (ambient and core) as sources of environmental and physiologic variability in this commonly used behavioral assay.

Abstract The interacting threats of invasive predators and altered fire regimes are key conservation issues for many native species globally. Artificial refuges have been proposed as a potential conservation tool to provide prey species with protection from invasive predators after fire, but we do not yet know whether they improve animal survival. To address this knowledge gap, we experimentally tested how small mammal abundance and species richness were influenced by the provision of artificial refuges after prescribed burns. We surveyed small mammals across five unburnt sites, seven burnt sites with artificial refuges, and eight burnt control sites following two prescribed fires in southeastern Australia. There were negative and neutral responses of small mammals to the burns, and relative abundance was positively correlated with structurally complex vegetation. Artificial refuges had no impact on abundance or species richness, irrespective of burn coverage. These findings suggest that this artificial refuge design may not be an effective tool for improving small mammal population persistence postfire, and as such we should not yet scale up their application. However, given the inherent context‐dependency of field experiments involving fire, which include difficult‐to‐control variables such as fire severity, predator activity, and population dynamics, we encourage researchers to undertake further experiments with artificial refuges in fire‐affected areas, including after severe wildfires when less vegetation cover remains. Such studies will help to build our understanding of their utility as a conservation tool across different ecosystems and fire types.

Volcanic debris flows (lahars) are highly destructive volcanic phenomena and present significant challenges in numerical simulation. This manuscript tackles the three fundamental requirements for modelling gravitational flows: determining plausible source configurations; selecting suitable topographic data; and employing appropriate mathematical models to assess the current hazard posed by long-distance lahars at Cotopaxi volcano. After incorporating these elements, we successfully simulated the characteristics of a future 1877-type lahar under current conditions, accounting for glacier size and topography. For the source conditions, or “scenario”, we identified 27 equidistant source locations along the lower edge of the current glacier’s extent. Each source was assigned a hydrograph based on the weighted volume of water available on Cotopaxi’s current glacier. Additionally, we introduced a methodology for quantifying channel width when high-resolution digital elevation models (DEMs) are available. This method enabled us to determine the minimum pixel size required for accurate representation of ravine shapes. While higher resolution DEMs demand robust computational resources and extended computational timeframes, we upscaled Cotopaxi’s DEM from 3 m to 15 m to balance accuracy and efficiency, as a 15-m DEM capture over 90% of the topography and reduces computing time significantly. Optimizing DEM selection is crucial, especially when contemplating future ensemble approaches. After employing the dynamic-based model Kestrel, parameterised for large lahars, we obtained predictions closely aligned with field observations, historical flow conditions inferred for the 1877 lahar-event, and results from previous simulation studies. Notably, we observed higher depths and speeds in canyons compared to plains, consistent with historical reports and previous studies. Minor discrepancies in the inundation area, when compared with existing hazard maps, emphasize the importance of understanding flow dynamics and lahar trajectories for effective hazard assessment and mitigation strategies. Furthermore, our results contribute valuable information to current hazard maps and can aid in damage quantification and cost/benefit analyses, particularly when planning the construction of mitigation infrastructure.

The Health Impacts of Artificial Reef Advancement (HIARA; in the Malagasy language, “together”) study cohort was set up in December 2022 to assess the economic and nutritional importance of seafood for the coastal Malagasy population living along the Bay of Ranobe in southwestern Madagascar. Over the course of the research, which will continue until at least 2026, the primary question we seek to answer is whether the creation of artificial coral reefs can rehabilitate fish biomass, increase fish catch, and positively influence fisher livelihoods, community nutrition, and mental health. Through prospective, longitudinal monitoring of the ecological and social systems of Bay of Ranobe, we aim to understand the influence of seasonal and long-term shifts in marine ecological resources and their benefits to human livelihoods and health. Fourteen communities (12 coastal and two inland) were enrolled into the study including 450 households across both the coastal (n = 360 households) and inland (n = 90 households) ecosystems. In the ecological component, we quantify the extent and health of coral reef ecosystems and collect data on the diversity and abundance of fisheries resources. In the social component, we collect data on the diets, resource acquisition strategies, fisheries and agricultural practices, and other social, demographic and economic indicators, repeated every 3 months. At these visits, clinical measures are collected including anthropometric measures, blood pressure, and mental health diagnostic screening. By analyzing changes in fish catch and consumption arising from varying distances to artificial reef construction and associated impacts on fish biomass, our cohort study could provide valuable insights into the public health impacts of artificial coral reef construction on local populations. Specifically, we aim to assess the impact of changes in fish catch (caused by artificial reefs) on various health outcomes, such as stunting, underweight, wasting, nutrient intake, hypertension, anxiety, and depression.