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How do galaxies transform from blue, star-forming spirals to red, quiescent early-type galaxies? To answer this question, we analyzed a set of 26 gas-rich, shocked post-starburst galaxies with Hubble Space Telescope (HST) imaging in B, I, and H bands and Sloan Digital Sky Survey (SDSS) i -band imaging of similar depth but lower resolution. We found that post-starbursts in our sample have intermediate morphologies between disk- and bulge-dominated (SĂ©rsic n = 1.7 âˆ' 0.0 + 0.3 ) and have red bulges, likely due to dust obscuration in the cores. A majority of galaxies in our sample are more morphologically disturbed than regular galaxies (88%, corresponding to >3 σ significance) when observed with HST, with asymmetry and SĂ©rsic residual flux fraction being the most successful measures of disturbance. Most disturbances are undetected at the lower resolution of SDSS imaging. Although ∼27% galaxies are clear merger remnants, we found that disturbances in another ∼30% of the sample are internal, caused by small-scale perturbations or dust substructures rather than tidal features, and require high-resolution imaging to detect. We found 2.8 σ evidence that asymmetry features fade on timescales ∼200 Myr, and may vanish entirely after ∼750 Myr, so we do not rule out a possible merger origin of all post-starbursts given that asymmetric features may have already faded. This work highlights the importance of small-scale disturbances, detected only in high-resolution imaging, in understanding structural evolution of transitioning galaxies. [ABSTRACT FROM AUTHOR]

We present Hubble Space Telescope imaging of a pre-explosion counterpart to SN 2019yvr obtained 2.6 yr before its explosion as a type Ib supernova (SN Ib). Aligning to a post-explosion Gemini-S/GSAOI image, we demonstrate that there is a single source consistent with being the SN 2019yvr progenitor system, the second SN Ib progenitor candidate after iPTF13bvn. We also analysed pre-explosion Spitzer /Infrared Array Camera (IRAC) imaging, but we do not detect any counterparts at the SN location. SN 2019yvr was highly reddened, and comparing its spectra and photometry to those of other, less extinguished SNe Ib we derive |$E(B-V)=0.51\substack{+0.27\\ -0.16}$|  mag for SN 2019yvr. Correcting photometry of the pre-explosion source for dust reddening, we determine that this source is consistent with a log (L /L⊙) = 5.3 ± 0.2 and |$T_{\mathrm{eff}} = 6800\substack{+400\\ -200}$|  K star. This relatively cool photospheric temperature implies a radius of 320 |$\substack{+30\\ -50}~\mathrm{ R}_{\odot}$|⁠ , much larger than expectations for SN Ib progenitor stars with trace amounts of hydrogen but in agreement with previously identified SN IIb progenitor systems. The photometry of the system is also consistent with binary star models that undergo common envelope evolution, leading to a primary star hydrogen envelope mass that is mostly depleted but still seemingly in conflict with the SN Ib classification of SN 2019yvr. SN 2019yvr had signatures of strong circumstellar interaction in late-time (>150 d) spectra and imaging, and so we consider eruptive mass-loss and common envelope evolution scenarios that explain the SN Ib spectroscopic class, pre-explosion counterpart, and dense circumstellar material. We also hypothesize that the apparent inflation could be caused by a quasi-photosphere formed in an extended, low-density envelope, or circumstellar matter around the primary star. [ABSTRACT FROM AUTHOR]

Recent claimed detections of tidal disruption events (TDEs) in multi-wavelength data have opened potential new windows into the evolution and properties of otherwise dormant supermassive black holes (SMBHs) in the centres of galaxies. At present, there are several dozen TDE candidates, which share some properties and differ in others. The range in properties is broad enough to overlap other transient types, such as active galactic nuclei (AGN) and supernovae (SNe), which can make TDE classification ambiguous. A further complication is that "TDE signatures" have not been uniformly observed to similar sensitivities or even targeted across all candidates. This chapter both reviews those events that are unusual relative to other TDEs, including the possibility of TDEs in pre-existing AGN, and summarises those characteristics thought to best distinguish TDEs from continuously accreting AGN, strongly flaring AGN, SNe, and Gamma-Ray Bursts (GRBs), as well as other potential impostors like stellar collisions, "micro-TDEs," and circumbinary accretion flows. We conclude that multiple observables should be used to classify any one event as a TDE. We also consider the TDE candidate population as a whole, which, for certain host galaxy or SMBH characteristics, is distinguishable statistically from non-TDEs, suggesting that at least some TDE candidates do in fact arise from SMBH-disrupted stars. [ABSTRACT FROM AUTHOR]

Time-domain science has undergone a revolution over the past decade, with tens of thousands of new supernovae (SNe) discovered each year. However, several observational domains, including SNe within days or hours of explosion and faint, red transients, are just beginning to be explored. Here we present the Young Supernova Experiment (YSE), a novel optical time-domain survey on the Pan-STARRS telescopes. Our survey is designed to obtain well-sampled griz light curves for thousands of transient events up to z ≈ 0.2. This large sample of transients with four-band light curves will lay the foundation for the Vera C. Rubin Observatory and the Nancy Grace Roman Space Telescope, providing a critical training set in similar filters and a well-calibrated low-redshift anchor of cosmologically useful SNe Ia to benefit dark energy science. As the name suggests, YSE complements and extends other ongoing time-domain surveys by discovering fast-rising SNe within a few hours to days of explosion. YSE is the only current four-band time-domain survey and is able to discover transients as faint as ∼21.5 mag in gri and ∼20.5 mag in z, depths that allow us to probe the earliest epochs of stellar explosions. YSE is currently observing approximately 750 deg2 of sky every 3 days, and we plan to increase the area to 1500 deg2 in the near future. When operating at full capacity, survey simulations show that YSE will find ∼5000 new SNe per year and at least two SNe within 3 days of explosion per month. To date, YSE has discovered or observed 8.3% of the transient candidates reported to the International Astronomical Union in 2020. We present an overview of YSE, including science goals, survey characteristics, and a summary of our transient discoveries to date. [ABSTRACT FROM AUTHOR]

Summary: Weedy plants pose a major threat to food security, biodiversity, ecosystem services and consequently to human health and wellbeing. However, many currently used weed management approaches are increasingly unsustainable. To address this knowledge and practice gap, in June 2014, 35 weed and invasion ecologists, weed scientists, evolutionary biologists and social scientists convened a workshop to explore current and future perspectives and approaches in weed ecology and management. A horizon scanning exercise ranked a list of 124 pre‐submitted questions to identify a priority list of 30 questions. These questions are discussed under seven themed headings that represent areas for renewed and emerging focus for the disciplines of weed research and practice. The themed areas considered the need for transdisciplinarity, increased adoption of integrated weed management and agroecological approaches, better understanding of weed evolution, climate change, weed invasiveness and finally, disciplinary challenges for weed science. Almost all the challenges identified rested on the need for continued efforts to diversify and integrate agroecological, socio‐economic and technological approaches in weed management. These challenges are not newly conceived, though their continued prominence as research priorities highlights an ongoing intransigence that must be addressed through a more system‐oriented and transdisciplinary research agenda that seeks an embedded integration of public and private research approaches. This horizon scanning exercise thus set out the building blocks needed for future weed management research and practice; however, the challenge ahead is to identify effective ways in which sufficient research and implementation efforts can be directed towards these needs. [ABSTRACT FROM AUTHOR]

Seed-attacking microorganisms have an undefined potential for management of the weed seedbank, either directly through inundative inoculation of soils with effective pathogenic strains, or indirectly by managing soils in a manner that promotes native seed-decaying microorganisms. However, research in this area is still limited and not consistently successful because of technological limitations in identifying the pathogens involved and their efficacy. We suggest that these limitations can now be overcome through application of new molecular techniques to identify the microorganisms interacting with weed seeds and to decipher their functionality. However, an interdisciplinary weed management approach that includes weed scientists, microbiologists, soil ecologists and molecular biologists is required to provide new insights into physical and chemical interactions between different seed species and microorganisms. Such insight is a prerequisite to identify the best candidate organisms to consider for seedbank management and to find ways to increase weed seed suppressive soil communities. [ABSTRACT FROM AUTHOR]

Histopathology of the dermo-epidermal junction in the lamellar region of front claws was examined in 6 dairy heifers given an alimentary oligofructose overload and compared with sections from a control group of 6 heifers. Four of the 6 heifers administered oligofructose developed clinical signs of acute laminitis before they were euthanized. Postmortem samples from front claws were processed for histology. Eleven histopathologic characteristics were selected from the existing literature and used in a blinded evaluation of sections. In total, 104 front claw samples, including 8 samples from 2 cows having spontaneously occurring acute laminitis, were evaluated histologically using hematoxylin and eosin as well as periodic acid-Schiff staining. The major morphological features associated with oligofructose-induced acute clinical laminitis were stretching of lamellae, dermal edema, hemorrhage, changes in basal cell morphology, presence of white blood cells in dermis, and signs of basement membrane detachment. Changes at the lamellar junction of claw tissue affected by oligofructose-induced clinical laminitis resembled tissue from the 2 cows suffering from spontaneous acute clinical laminitis, and generally were consistent with existing descriptions of laminitis histopathology. Important exceptions to existing descriptions in the literature were stretching of lamellae and basement membrane changes. Not previously described, we considered these early signs of acute laminitis. In conclusion, this study documents that oligofructose-induced clinical laminitis is associated with histopathological changes at the lamellar interface. A weakened dermo-epidermal junction is a possible intermediate stage in the pathophysiology of bovine sole ulceration at the typical site. [ABSTRACT FROM AUTHOR]

Compares the blood pressures of Black and White American schoolchildren and Nigerian schoolchildren. Factors contributing to childhood pressures; Influence of the environment on the behavior of the arterial pressure of Black and White Americans; Measurement of blood pressure.

Minipigs are valid nonrodent species infrequently utilized for pharmaceutical research and development (R&D) compared with dogs or nonhuman primates (NHPs). A 2022 IQ DruSafe survey revealed a modest increase in minipig use by pharmaceutical companies compared with a prior 2014 survey, primarily in the development of oral small molecules and parenteral protein molecules. Some companies considered using minipigs more often due to NHP shortages and regional ethical concerns with using NHPs and dogs. However, for most pharmaceutical companies, minipigs still represent ≤5% of their nonrodent animal use. Key challenges noted by companies to wider adoption of minipigs were high test article requirement, limited historical control data, and lack of relevant reagents or assays. Additionally, some companies expressed uncertainties about contract research organization (CRO) capabilities and experience, a perception not shared by respondent CROs. These latest survey results indicate persistence of many concerns previously identified in 2014. Several case studies are included to illustrate areas of expanded minipig use as well as the challenges that hinder broader adoption. Ongoing, focused, and industry-wide initiatives to address the identified or perceived challenges may lead to more frequent or routine consideration of minipigs as a test species in pharmaceutical R&D., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This publication was developed with the support of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ, www.iqconsortium.org). IQ is a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators and the broader research and development community., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality. Adipocyte-PHD2-deficient mice maintain higher energy expenditure having greater BAT thermogenic capacity. In human and murine adipocytes, a PHD inhibitor increases Ucp1 levels. In murine brown adipocytes, antagonising the major PHD2 target, hypoxia-inducible factor-(HIF)-2a abolishes Ucp1 that cannot be rescued by PHD inhibition. Mechanistically, PHD2 deficiency leads to HIF2 stabilisation and binding of HIF2 to the Ucp1 promoter, thus enhancing its expression in brown adipocytes. Serum proteomics analysis of 5457 participants in the deeply phenotyped Age, Gene and Environment Study reveal that serum PHD2 associates with increased risk of metabolic disease. Here we show that adipose-PHD2-inhibition is a therapeutic strategy for metabolic disease and identify serum PHD2 as a disease biomarker., (© 2024. The Author(s).)

Background: Inflammatory skin diseases, such as psoriasis, atopic eczema, and contact dermatitis pose diagnostic challenges due to their diverse clinical presentations and the need for rapid and precise diagnostic assessment., Objective: While recent studies described non-invasive imaging devices such as Optical coherence tomography and Line-field confocal OCT (LC-OCT) as possible techniques to enable real-time visualization of pathological features, a standardized analysis and validation has not yet been performed., Methods: One hundred forty lesions from patients diagnosed with atopic eczema (57), psoriasis (50), and contact dermatitis (33) were imaged using OCT and LC-OCT. Statistical analysis was employed to assess the significance of their characteristic morphologic features. Additionally, a decision tree algorithm based on Gini's coefficient calculations was developed to identify key attributes and criteria for accurately classifying the disease groups., Results: Descriptive statistics revealed distinct morphologic features in eczema, psoriasis, and contact dermatitis lesions. Multivariate logistic regression demonstrated the significance of these features, providing a robust differentiation between the three inflammatory conditions. The decision tree algorithm further enhanced classification accuracy by identifying optimal attributes for disease discrimination, highlighting specific morphologic criteria as crucial for rapid diagnosis in the clinical setting., Conclusion: The combined approach of descriptive statistics, multivariate logistic regression, and a decision tree algorithm provides a thorough understanding of the unique aspects associated with each inflammatory skin disease. This research offers a practical framework for lesion classification, enhancing the interpretability of imaging results for clinicians., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Purpose: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics., Methods: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were compared using Mann-Whitney U tests., Results: Individual patient encounter data for 1,328 consults before the intervention and 1,234 afterward across all sections were included. The median overall cycle time was reduced by 21% in GI (19 minutes), 18% in GU (16 minutes), and 12% at the community sites (9 minutes). The median financial savings per consult were $52 in US dollars (USD) for the GI, $33 USD for GU, $30 USD for thoracic, and $42 USD for the community sites. Patient satisfaction surveys (from 127 of 228 patients) showed that 99% of patients reported that their providers spent adequate time with them and 91% reported being seen by a care provider in a timely manner., Conclusion: TDABC can effectively identify opportunities to improve clinical efficiency. Implementing workflow changes on the basis of our findings led to substantial reductions in overall encounter cycle times across several departments, as well as high patient satisfaction and significant financial savings.

Background: Propofol is often used for sedation during colonoscopy. We assessed the impact of propofol sedation on colonoscopy related quality metrics and cost in a population-based cohort study., Methods: All colonoscopies performed at 21 hospitals in the province of Ontario, Canada, during an 18-month period, from April 1, 2017 to October 31, 2018, using either propofol or conscious sedation were evaluated. The primary outcome was adenoma detection rate (ADR) and secondary outcomes were sessile serrated polyp detection rate (ssPDR), polyp detection rate (PDR), cecal intubation rate (CIR), and perforation rate. Binary outcomes were assessed using a modified Poisson regression model adjusted for clustering and potential confounders based on patient, procedure, and physician characteristics., Findings: A total of 46,634 colonoscopies were performed, of which 16,408 (35.2%) received propofol and 30,226 (64.8%) received conscious sedation. Compared to conscious sedation, the use of propofol was associated with a lower ADR (24.6% vs. 27.0%, p < 0.0001) but not ssPDR (5.0% vs. 4.7%, p = 0.26), PDR (40.5% vs 40.4%, p = 0.79), CIR (97.1% vs. 96.8%, p = 0.15) or perforation rate (0.04% vs. 0.06%, p = 0.45). On multi-variable analysis, propofol sedation was not associated with any differences in ADR (RR = 0.90, 95% CI 0.74-1.10, p = 0.30), ssPDR (RR = 1.20, 95% CI 0.90-1.60, p = 0.22), PDR (RR = 1.00, 95% CI 0.90-1.11, p = 0.99), or CIR (RR = 1.00, 95% CI 0.80-1.26, p = 0.99). The additional cost associated with propofol sedation was $12,730,496 for every 100,000 cases., Interpretation: The use of propofol sedation was not associated with improved colonoscopy related quality metrics but increased costs. The routine use of propofol for colonoscopy should be reevaluated., Funding: None., Competing Interests: AW receives consulting fees from Fresnius Kabi and speaker fees from Takeda and Pfizer. MS is the Regional Endoscopy Lead for Ontario Health, a government agency tasked with quality assurance and quality improvement in the region's endoscopy units and receives a stipend for this work., (© 2024 The Authors.)

Study Design: Retrospective review of deaths in Ontario where there was Coroner's investigation and a postmortem examination between 2018 and 2021 to compare year by year changes before and during the COVID-19 pandemic., Objective: To establish the changes in patterns of toxicological deaths over the pandemic., Methods: Using the database of the Office of the Chief Coroner for Ontario to determine the numbers of postmortem examinations for the province of Ontario as well as the primary cause and manner of death. Those with a toxicological primary cause of death were isolated from 2003 to the first half of 2022 and divided by year. For those between the years 2018 and 2021 deaths were divided by manner of death. Further all deaths with either a toxicological primary cause of death or unfinalized investigations which were highly suspicious for a toxicological cause based on circumstance with a positive toxicology were isolated. From these the data on demographics and substances detected were compiled by year for comparison., Results: Comparing two years prior to the COVID-19 pandemic to the following two years there was an increase in total case load of 22%. Comparing the year before the pandemic to the first year of the pandemic deaths from natural causes fell from 52% to 47% of total cases, while drug-related cases increased from 24% to 36%. Fentanyl remained as the most prevalent detected substance in toxicological deaths. Combined opioid toxicity with stimulants increased, as well as the detection of nonpharmaceutical benzodiazepines. Deaths in men increased to comprise 3 in 4 drug-related deaths with the 30 to 39 years age-group remaining the most impacted., Conclusions: There was an increase in numbers and relative proportions of cases attributed to drug-related deaths which remained high over the two years of the pandemic., Competing Interests: The authors, reviewers, editors, and publication staff do not report any relevant conflicts of interest., (© The Author(s) 2024.)

Background: We present the conceptual framework, design, and study measures of Nurturing Healthy Teachers, a quasi-experimental study to examine the short- and long-term effectiveness of the Nurturing Healthy Teachers (NHT) nutrition intervention on food insecurity, dietary behaviors, mental health and cardiometabolic health among preschool and elementary school teachers., Methods: A convenience sample of 28 elementary schools with pre-kindergarten and elementary classrooms were recruited in Houston, Texas. Nurturing Healthy Teacher intervention includes Brighter Bites, an evidence-based coordinated school health program that combines access to fresh produce and nutrition education, and Create Healthy Futures, a web-based nutrition education program that targets nutrition knowledge, self-efficacy, mindfulness, and social support to create healthy habits among teachers. The primary outcome is food insecurity. Secondary outcomes include diet quality, mental health, and cardiometabolic health. Metabolic markers and skin carotenoid levels were assessed using in-person assessments, while all other measures were obtained via questionnaire., Results: At baseline, most of the participants were female, 63 % identified as Hispanic, were highly educated, and had a mean age of 42.6 years. Overall, 50 % of teachers were classified as being obese and 20 % had high cholesterol. At baseline teachers had a mean HbA1c (%) of 5.6 %. Moderate to severe depression was experienced by 18 % of teachers and 23 % of teachers experienced moderate to severe anxiety., Conclusions: The results of this study will inform next steps towards future implementation and evaluation of teacher-focused interventions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Shreela Sharma serves on the board of directors of Brighter Bites 501c3 non-profit organization. This is an unpaid board position. No other authors report any conflicts of interest.., (© 2024 The Authors.)

Transplant-associated thrombotic microangiopathy (TA-TMA) is a common, severe complication of allogeneic hematopoietic cellular therapy (HCT). Even when treated in many studies, morbidity and mortality rates are high. This prospective single-institution cohort study serially enrolled all allogeneic HCT recipients from August 2019-August 2022. Patients were universally screened for TA-TMA and intermediate and high-risk patients were immediately treated with eculizumab. Sub-distribution cox-proportional hazards models were used to identify sub-distribution hazard ratios (sHR)  for multi-organ dysfunction (MOD) and non-relapse-related mortality (NRM). Of 136 patients, 36 (26%) were diagnosed with TA-TMA and 21/36 (58%) developed MOD, significantly more than those without TA-TMA, (p < .0001). Of those with TA-TMA, 18 (50%) had high-risk TA-TMA (HR-TA-TMA), 11 (31%) had intermediate-risk TA-TMA (IR-TA-TMA), and 8 (22%) had standard risk (SR-TA-TMA). Twenty-six were treated with eculizumab (1/8 SR, 7/11 IR, and 18/18 HR). Elevated D-dimer predicted the development of MOD (sHR 7.6, 95% confidence interval [CI] 1.8-32.3). Children with concurrent sinusoidal obstructive syndrome (SOS) and TA-TMA had an excess risk of MOD of 34% and data supported a biologic interaction. The adjusted NRM risk was significantly higher in the TA-TMA patients (sHR 10.54, 95% CI 3.8-29.2, p < .0001), despite prompt treatment with eculizumab. Significant RF for NRM in TA-TMA patients included SOS (HR 2.89, 95% 1.07-7.80) and elevated D-dimer (HR 3.82, 95% CI 1.14-12.84). An unrelated donor source and random urine protein to creatine ratio ≥2 mg/mg were significantly associated with no response to eculizumab (odds ratio 15, 95% CI 2.0-113.6 and OR 6.5, 95% CI 1.1-38.6 respectively). TA-TMA was independently associated with NRM despite early diagnosis and treatment with eculizumab in this large pediatric transplant cohort. Prognostic implications of D-dimer in TA-TMA merit further investigation as this is a readily accessible biomarker. Concurrent SOS is an exclusion criterion of many ongoing clinical trials, but these data highlight these patients could benefit from novel therapeutic approaches. Multi-institutional clinical trials are needed to understand the impact of TA-TMA-targeted therapies., (© 2024 Wiley Periodicals LLC.)

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma gangrenosum (PG)-like skin ulcers (PGLUs) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1., Objective: Our aim was to report the case of a 10-year-old boy presenting with PGLUs as the first manifestation of LAD-1 treated with ustekinumab., Methods: We obtained in situ cytokine profiles., Results: PGLUs were triggered by cutaneous ringworm infection ( Trichophyton tonsurans ). Skin biopsy samples showed increased intralesional expression of IL-17A, Il-23, and IL-1β as compared with their expression in healthy controls. After an unsuccessful attempt at treatment with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile., Conclusions: PGLUs, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for patients with LAD-1 and PGLUs while bridging the time until stem cell transplantation., (© 2024 The Author(s).)

Integrating Polyvagal Theory and Reinforcement Sensitivity Theory (RST), we examined pre-ejection period (PEP) reward reactivity, which was suggested to index trait impulsivity, as a moderator between respiratory sinus arrhythmia (RSA) reactivity and antisocial behavior (ASB), and substance use in an urban male, adult sample. To understand the inconsistent findings between RSA reactivity and externalizing problems, we proposed to study both negatively and positively valenced tasks for RSA reactivity and to include PEP reward reactivity as a moderator for the RSA-behavior link. Data were collected from an urban sample of 131 male adults (active offenders, demographic controls, and college students). ICG (impedance cardiography) and ECG (electrocardiogram) were recorded, computing PEP (sympathetic nervous system activity marker) and RSA (parasympathetic nervous system activity marker), while participants completed the modified Trier Social Stress Test and a simple reward task. Reactivity was calculated by subtracting the baseline from the task activity. Consistent with prior studies, more RSA withdrawal to stress and less PEP shortening to reward predicted the most ASB and substance use. Less RSA withdrawal to reward and more PEP shortening to reward predicted the most ASB and substance use. We incorporated autonomic space, RST, and Polyvagal Theory to discuss our findings, and specifically highlight how clarifying what each reactivity captures based on the task demand (e.g., presence of social threat, need for vagal-mediated social affiliative behavior) can illuminate our understanding of the result patterns., (© 2023 Society for Psychophysiological Research.)

Aims: We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM)., Methods and Results: We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF) < 40%, development of heart failure within the last month of pregnancy or 5 months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4 ± 6.8 years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP ≥ 30 mmHg. After a median follow-up of 3.4 years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P = 0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP ≥ 30 mmHg had a lower probability of survival free from adverse events (log-rank P = 0.04)., Conclusions: African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Although highly efficacious, immune checkpoint inhibitors induce a multitude of immune-related adverse events including lichenoid skin reactions (irLP) that are often therapy-resistant., Objectives: To compare the clinical, histological, and transcriptional features of irLP with spontaneous lichen planus (LP)., Methods: Clinical and histological presentations of irLP and LP, as well as the gene expression profiles of irLP and LP lesional and healthy skin were assessed., Results: irLP differed considerably from LP with regard to the distribution pattern of skin lesions with irLP appearing mostly in an exanthematous form, whereas lesions were more localized in the LP group. Histologically, dermal lymphocyte infiltration was significantly lower in irLP compared with LP, whereas lymphocyte exocytosis and apoptotic keratinocytes were significantly higher in irLP. Gene expression analysis revealed irLP to have a more inflammatory profile with elevated IFNG levels and a possible role of phagosome signaling compared with LP., Limitations: The study is descriptive and necessitates further investigation with larger cohorts and broader analyses., Conclusion: irLP differs from spontaneous LP on the clinical, histopathological, and gene expression level. The inflammatory gene signature in irLP suggests that topical JAK inhibitors could be an effective treatment, targeting local skin inflammation without systemic immunosuppression., Competing Interests: None disclosed., (© 2024 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Approximately 25% of accidents in the United States are caused by texting while driving, prompting the creation of several media campaigns to reduce such risky behavior. The current research examined whether death-related advertisements increase cell phone use while driving. Studies 1-3 found that individuals engaged in greater distracted driving in the presence of a mortality-themed texting advertisement. Study 2 demonstrated that participants were more likely to text on their cell phone using a driving simulator, leading to more swerving and collisions after viewing a death-related (vs. neutral) poster. Finally, using eye-tracking, Study 3 showed that participants who viewed a death advertisement looked away from the road and texted more as compared to persons in the control condition. Implications and future directions are discussed.

Background: In the United States (US), many obstetrics & gynecology (OB-GYN) trainees feel unprepared to care for lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) individuals, but interest in this topic is rising. Residency program websites are one way that directors can advertise whether this training is offered within their program. We aimed to describe the extent to which LGBTQI content is currently featured on OB-GYN residency websites across the country., Methods: We identified all OB-GYN residency programs in the United States using a publicly available database. We systematically searched for select LGBTQI keywords on program websites. We collected data on mentions of LGBTQI didactics and rotations. We also searched whether LGTBQI keywords were included in diversity, equity, and inclusion (DEI) statements. We used multivariable logistic regression to compare the characteristics of programs that do and do not include this content. We used STATA SE Version 16.0 for all analyses and set the level of significance at 5%., Results: We included 287/295 US OB-GYN residency programs in our analysis (97.3%) and excluded 8 that did not have websites. We identified any LGBTQI content on 50 program websites (17.4%), and specific mention of didactics or rotations on 8 websites (2.8%). On multivariable analysis, programs in the West were more likely to include any LGBTQI content compared to programs in the South (OR 2.81, 95%CI 1.04-7.63), as were programs with 1 or 2 fellowships (OR 3.41, 95%CI 1.43-8.14) or 3 or more fellowships (OR 4.85, 95%CI 2.03-11.57) compared to those without fellowships. Programs in departments led by female chairs were also more likely to include LBTQI content (OR 3.18, 95%CI 1.55-6.51)., Conclusions: Academic programs, West Coast programs, and those with departments led by female chairs are more likely to mention LGBTQI keywords on their websites. Given the increasing interest in LGBTQI education for OB-GYN trainees, program directors should consider providing training opportunities and including this content on their websites., (© 2023. The Author(s).)

A critical step in the immunogenicity cascade is attributed to human leukocyte antigen (HLA) II presentation triggering T cell immune responses. The liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based major histocompatibility complex (MHC) II-associated peptide proteomics (MAPPs) assay is implemented during preclinical risk assessments to identify biotherapeutic-derived T cell epitopes. Although studies indicate that HLA-DP and HLA-DQ alleles are linked to immunogenicity, most MAPPs studies are restricted to using HLA-DR as the dominant HLA II genotype due to the lack of well-characterized immunoprecipitating antibodies. Here, we address this issue by testing various commercially available clones of MHC-II pan (CR3/43, WR18, and Tü39), HLA-DP (B7/21), and HLA-DQ (SPV-L3 and 1a3) antibodies in the MAPPs assay, and characterizing identified peptides according to binding specificity. Our results reveal that HLA II receptor-precipitating reagents with similar reported specificities differ based on clonality and that MHC-II pan antibodies do not entirely exhibit pan-specific tendencies. Since no individual antibody clone is able to recover the complete HLA II peptide repertoire, we recommend a mixed strategy of clones L243, WR18, and SPV-L3 in a single immunoprecipitation step for more robust compound-specific peptide detection. Ultimately, our optimized MAPPs strategy improves the predictability and additional identification of T cell epitopes in immunogenicity risk assessments.

The aim of this study is to evaluate the effect of over-the-counter (OTC) at-home whitening products with LED light on partially- and fully-crystalized CAD/CAM lithium disilicate ceramics. Two partially-crystalized CAD/CAM lithium disilicate ceramics, Amber Mill and IPS e.max CAD, and one fully-crystalized CAD/CAM lithium disilicate ceramic, n!ce Straumann, were used. The specimens were divided based on treatment with OTC whitening products: no treatment provided, Colgate Optic, Crest 3D and Walgreens Deluxe. The surface roughness of the specimens was evaluated with an optical profilometer and scanning electron microscopy. The three LED whitening products significantly increased the surface roughness and changed surface morphology of Amber Mill and IPS e.max CAD but no differences for n!ce Straumann. OTC at-home whitening products with LED light can significantly increase the surface roughness of restorations fabricated with these partially-crystalized CAD/CAM lithium disilicate ceramic restorations. However, these products do not increase the surface roughness of restorations fabricated with this fully-crystalized lithium disilicate ceramic.

Aphantasia is the experience of having little to no visual imagery. We assessed the prevalence rate of aphantasia in 5,010 people from the general population of adults in the United States through self-report and responses to two visual imagery scales. The self-reported prevalence rate of aphantasia was 8.9% in this sample. However, not all participants who reported themselves as aphantasic showed low-imagery profiles on the questionnaire scales, and scale prevalence was much lower (1.5%). Self-reported aphantasic individuals reported lower dream frequencies and self-talk and showed poorer memory performance compared to individuals who reported average and high mental imagery. Self-reported aphantasic individuals showed a greater preference for written instruction compared to video instruction for learning a hypothetical new task although there were differences for men and women in this regard. Categorizing aphantasia using a scale measure and relying on self-identification may provide a more consistent picture of who lacks visual imagery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: International consensus advises patient safety education (PSE) for dental undergraduates. A previous systematic review found no articles describing PSE in dentistry. This article aimed to review the evidence base for, and the current practice of, PSE in UK dental schools., Methods: Literature search and surveys were sent via email to all 16 UK dental schools., Results: Six articles describing PSE interventions were found: 2 small-scale studies for dental students and 4 interprofessional studies. Patient safety education is effective for undergraduate dental students with significant improvement in knowledge and interest. Interprofessional studies reported improved teamwork skills and more positive attitudes toward interprofessional working.The 2018 and 2021 surveys had response rates of 56% and 100%, respectively. An increase in integrated formal PSE and assessment in UK dental schools is demonstrated. No barriers to implementation were reported. Forty-six percent of schools deliver interprofessional PSE, 38% deliver human factors, 81% teach communication, 94% teach professionalism, and 31% of schools have a patient safety (PS) champion., Conclusions: Limited published literature on PSE in dentistry is available. However, the lack of published articles does not mean that PS is not being taught, as many UK dental schools were found to have formal PSE integrated and assessed within their curriculum. Further development is needed in terms of appointing PS champions for leadership and human factors training. Patient safety must form a part of an undergraduate student's core values., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Mobile applications (apps) are increasingly being used to access health-related information, but it may be challenging for consumers to identify accurate and reliable platforms. We conducted a systematic review of applications that provide information about abortion. We searched the iTunes and Google Play stores and queried professional networks to identify relevant apps. To evaluate the apps, we used the validated Mobile App Rating Scale (MARS) and added relevant abortion-specific elements. Two reviewers independently rated each app, and we report mean scores on a 5-point scale across the domains of engagement, functionality, esthetics, and information. We also rated app characteristics (including target population and reach), and number of desirable abortion-specific features. We defined recommended apps as those that achieved a score of 4.0 or above for the question: "would you recommend this app to people who may benefit from it?" Our search initially yielded 282 apps and we identified two additional apps through professional mailing lists. Most were irrelevant or not abortion-specific. We excluded 37 apps that sought to discourage users from seeking abortion. Only 10 apps met inclusion criteria for this review. The Euki app had the highest overall score (4.0). Half of the apps achieved a score of 3.0 or greater. Most of the apps had few desirable design features. Some apps provided significant information but had poor functionality. Only four apps met criteria for being recommended: Euki, Safe Abortion by Hesperian, Ipas Mexico, and Marie Stopes Mexico. In conclusion, we found few apps that provide unbiased information about abortion, and their quality varied greatly. App developers and abortion experts should consider designing additional apps that are clinically accurate, unbiased and well-functioning. We registered this review in the PROSPERO database (Registration # CRD42020195802)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Stifani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Seed fungal endophytes play a crucial role in assisting the overall health and success of their host plant; however, little is known about the factors that influence the diversity and composition of these endophytes, particularly with respect to how they change over time and within urban environments. Using culturing techniques, morphological analyses, and Sanger sequencing, we identified the culturable seed fungal endophytes of Banksia ericifolia at two urban and two natural sites in Sydney, New South Wales, Australia. A total of 27 Operational Taxonomic Units were obtained from 1200 seeds. Older cones were found to contain, on average, more colonised endophytes than younger cones. Species richness was also significantly influenced by cone age, with older cones being more speciose. Between urban and natural sites, the overall community composition did not change, although species richness and diversity were greatest at urban sites. Understanding how these endophytes vary in time and space may help provide an insight into the transmission pathways used and the potential role they play within the development and survival of the seed. This knowledge may also be crucial for restoration purposes, especially regarding the need to consider endophyte viability in ex situ seed collection and storage in seed-banking practices., Competing Interests: The authors declare no conflicts of interest.

Heatwaves are increasingly occurring out-of-season, which may affect plants not primed for the event. Further, heat stress often coincides with water and/or nutrient stress, impairing short-term physiological function and potentially causing downstream effects on reproductive fitness. We investigated the response of water-stressed arid-zone Solanum oligacanthum and Solanum orbiculatum to spring vs summer heat stress under differing nutrient conditions. Heat stress events were imposed in open-topped chambers under in situ desert conditions. To assess short-term impacts, we measured leaf photosystem responses (F v /F m ) and membrane stability; long-term effects were compared via biomass allocation, visible damage, flowering and fruiting. Plants generally fared more poorly following summer than spring heat stress, with the exception of F v /F m . Summer heat stress caused greater membrane damage, reduced growth and survival compared with spring. Nutrient availability had a strong influence on downstream effects of heat stress, including species-specific outcomes for reproductive fitness. Overall, high temperatures during spring posed a lower threat to fitness than in severe arid summer conditions of high temperature and low water availability, which were more detrimental to plants in both the short and longer term. Our study highlights the importance of considering ecologically relevant, multiple-stressor events to understand different species responses to extreme heat.

The neuroimmune system of the brain, which is comprised primarily of astrocytes and microglia, regulates a variety of homeostatic mechanisms that underlie normal brain function. Numerous conditions, including alcohol consumption, can disrupt this regulatory process by altering brain levels of neuroimmune factors. Alcohol and neuroimmune factors, such as proinflammatory cytokines IL-6 and TNF-alpha, act at similar targets in the brain, including excitatory and inhibitory synaptic transmission. Thus, alcohol-induced production of IL-6 and/or TNF-alpha could be important contributing factors to the effects of alcohol on the brain. Recent studies indicate that IL-6 plays a role in alcohol drinking and the effects of alcohol on the brain activity following the cessation of alcohol consumption (post-alcohol period), however information on these topics is limited. Here we used homozygous and heterozygous female and male transgenic mice with increased astrocyte expression of IL-6 to examined further the interactions between alcohol and IL-6 with respect to voluntary alcohol drinking, brain activity during the post-alcohol period, IL-6 signal transduction, and expression of synaptic proteins. Wildtype littermates (WT) served as controls. The transgenic mice model brain neuroimmune status with respect to IL-6 in subjects with a history of persistent alcohol use. Results showed a genotype dependent reduction in voluntary alcohol consumption in the Drinking in the Dark protocol and in frequency-dependent relationships between brain activity in EEG recordings during the post-alcohol period and alcohol consumption. IL-6, TNF-alpha, IL-6 signal transduction partners pSTAT3 and c/EBP beta, and synaptic proteins were shown to play a role in these genotypic effects., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The relationship between sublethal pesticide exposure and oxidative stress in an ecologically relevant field setting is relatively unknown for reptiles. Oxidative stress is a multi-faceted concept that dictates key survival and fitness parameters in any organism. Fipronil and fenitrothion are two pesticides widely used globally for agricultural pest management. Using a field-based, BACI designed experiment we investigated the impact of sublethal pesticide exposure on oxidative stress biomarkers protein carbonyl and DNA damage (8-OHdG), in an arid-zone lizard species, Pogona vitticeps. A single ecologically relevant dose of pesticide was applied via oral gavage to treatment animals. Lizard condition, activity measures, and blood biomarkers were measured at relevant sampling intervals. Cholinesterase (ChE) and acetylcholinesterase (AChE) enzymatic biomarkers were measured in response to fenitrothion, and fipronil blood residues were measured for fipronil-treated lizards. Results suggested no significant treatment effect of either pesticide on parameters measured, however, 8-OHdG levels decreased by ≥ 45% for both pesticide treatment groups and not controls. Protein carbonyl levels showed a high degree of individual variation that proved more influential than pesticide exposure. Building our understanding of the macromolecular impacts of sublethal pesticide exposure on wild lizard populations is an integral step in addressing the current gap in literature and management practices. Our study has also highlighted the complex nature of studying oxidative stress in the field and the sheer necessity of future study., (© 2023. The Author(s).)

Invasive species often possess a great capacity to adapt to novel environments in the form of spatial trait variation, as a result of varying selection regimes, genetic drift, or plasticity. We explored the geographic differentiation in several phenotypic traits related to plant growth, reproduction, and defense in the highly invasive Centaurea solstitialis by measuring neutral genetic differentiation ( F ST ), and comparing it with phenotypic differentiation ( P ST ), in a common garden experiment in individuals originating from regions representing the species distribution across five continents. Native plants were more fecund than non-native plants, but the latter displayed considerably larger seed mass. We found indication of divergent selection for these two reproductive traits but little overall genetic differentiation between native and non-native ranges. The native versus invasive P ST - F ST comparisons demonstrated that, in several invasive regions, seed mass had increased proportionally more than the genetic differentiation. Traits displayed different associations with climate variables in different regions. Both capitula numbers and seed mass were associated with winter temperature and precipitation and summer aridity in some regions. Overall, our study suggests that rapid evolution has accompanied invasive success of C .  solstitialis and provides new insights into traits and their genetic bases that can contribute to fitness advantages in non-native populations., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Background: Interventional pulmonology (IP) is a growing field that has not yet been recognized by the American Board of Medical Specialties or incorporated into national benchmark organizations. As a result, there is a lack of data on IP practice patterns, physicians' compensation and productivity targets., Methods: We sent an anonymous survey to 647 current or past physician members of the AABIP. Domains included demographics, training background, academic rank, practice settings, work relative value unit (wRVU) targets, salary, and career satisfaction., Results: The response rate to the survey was 28.3%; 17.8% were female. The median salary for IP faculty in academic institutions was $320,000 for assistant professors, $338,000 for associate professors, and $350,000 for full professors. Salaries were lower for women than for men in academic practice, even after adjusting for the number of years in practice (mean salary difference after adjustment $57,175, 95% CI: $19,585-$94,764, P =0.003). The median salary for private practice was higher at $428,000. Among respondents that used wRVU targets, the median targets for academic and private practice were 5500 and 6300, respectively. The majority of IP physicians are satisfied with their career choice., Conclusions: Productivity targets in IP are used less than half the time, and when they are used, they are set in line with the lower wRVU of IP procedures. IP compensation is higher than that of general pulmonary medicine, as reported by national benchmark associations. In academic practices, gender differences in salaries were found., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Antibody-based T cell-activating biologics are promising therapeutic medicines being developed for a number of indications, mainly in the oncology field. Among those, T cell bispecific antibodies are designed to bind one tumor-specific antigen and the T cell receptor at the same time, leading to a robust T cell response against the tumor. Although their unique format and the versatility of the CrossMab technology allows for the generation of safer molecules in an efficient manner, product-related variants cannot be completely avoided. Therefore, it is of extreme importance that both a manufacturing process that limits or depletes product-related impurities, as well as a thorough analytical characterization are in place, starting from the development of the manufacturing cell line until the assessment of potential toxicities. Here, we describe such an end-to-end approach to minimize, quantify and control impurities and -upon their functional characterization- derive specifications that allow for the release of clinical material., Competing Interests: Valeria Runza reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks. Laurent Lariviere reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks. Julia Krüger reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks. Tilman Schlothauer reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks. Martin Bader reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks. Katharine Bray-French reports a relationship with F. Hoffmann-La Roche AG that includes: employment and equity or stocks. Thomas von Hirschheydt reports a relationship with Roche Diagnostics GmbH that includes: employment and equity or stocks., (© 2023 The Authors.)

Background: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24-48 h after the intake of the culprit drug., Summary: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value., Key Messages: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug., (© 2023 S. Karger AG, Basel.)

Immunogenicity, defined as the ability to provoke an immune response, can be either wanted (i.e., vaccines) or unwanted. The latter refers to an immune response to protein or peptide therapeutics, characterized by the production of anti-drug antibodies, which may affect the efficacy and/or the safety profiles of these drugs. Consequently, evaluation of the risk of immunogenicity early in the development of biotherapeutics is of critical importance for defining their efficacy and safety profiles. Here, we describe and validate a fit-for-purpose FluoroSpot-based in vitro assay for the evaluation of drug-specific T cell responses. A panel of 24 biotherapeutics with a wide range of clinical anti-drug antibody response rates were tested in this assay. We demonstrated that using suitable cutoffs and donor cohort sizes, this assay could identify most of the compounds with high clinical immunogenicity rates (71% and 78% for sensitivity and specificity, respectively) while we characterized the main sources of assay variability. Overall, these data indicate that the dendritic cell and CD4+ T cell restimulation assay published herein could be a valuable tool to assess the risk of drug-specific T cell responses and contribute to the selection of clinical candidates in early development.