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The topic of cheating at the college level has received greater attention since the 2019 pandemic. This is in part because countless institutions of higher education switched many of their live/inperson classes to an online learning format. In comparing cheating in live classes to online classes during the 2020-2021 academic year, our survey study results showed a stronger prevalence of cheating in online classes, and more than half (53.2%) of the students reported knowing a classmate who cheated during the pandemic. The aspects of gender and class rank are also discussed related to cheating.

Abstract Adoptive T-cell immunotherapy holds great promise for the treatment of viral complications in immunocompromised patients resistant to standard anti-viral strategies. We present a retrospective analysis of 78 patients from 19 hospitals across Australia and New Zealand, treated over the last 15 years with “off-the-shelf” allogeneic T cells directed to a combination of Epstein–Barr virus (EBV), cytomegalovirus (CMV), BK polyomavirus (BKV), John Cunningham virus (JCV) and/or adenovirus (AdV) under the Australian Therapeutic Goods Administration’s Special Access Scheme. Most patients had severe post-transplant viral complications, including drug-resistant end-organ CMV disease, BKV-associated haemorrhagic cystitis and EBV-driven post-transplant lymphoproliferative disorder. Adoptive immunotherapy is well tolerated with few adverse effects. Importantly, 46/71 (65%) patients show definitive clinical improvement including reduction in viral load, clinical symptoms and complete resolution of end-organ disease. In addition, seven high-risk patients remain disease free. Based on this long-term encouraging clinical experience, we propose that a dedicated nationally funded centre for anti-viral cellular therapies should be considered to provide T cell therapies for critically ill patients for compassionate use.

Abstract Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with > = 30 s treatment time, with a corresponding maximum reduction in stiffness of −90.9 ± 7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288 s (−91.6 ± 6.0(s.d.)%), and low-PRF CH achieved a (−82.1 ± 5.1(s.d.)%) reduction in stiffness at dose > = 144 s. Receiver operating characteristic curve analysis showed that a > ~ 75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression.

Abstract Low muscle mass is associated with numerous adverse outcomes independent of other associated comorbid diseases. We aimed to predict and understand an individual’s risk for developing low muscle mass using proteomics and machine learning. We identified eight biomarkers associated with low pectoralis muscle area (PMA). We built three random forest classification models that used either clinical measures, feature selected biomarkers, or both to predict development of low PMA. The area under the receiver operating characteristic curve for each model was: clinical-only = 0.646, biomarker-only = 0.740, and combined = 0.744. We displayed the heterogenetic nature of an individual’s risk for developing low PMA and identified two distinct subtypes of participants who developed low PMA. While additional validation is required, our methods for identifying and understanding individual and group risk for low muscle mass could be used to enable developments in the personalized prevention of low muscle mass.

Abstract Increasing access to water quality tests in low-income communities is a crucial strategy toward achieving global water equality. Recent studies in the Water Sanitation and Hygiene (WASH) sector underscore the importance of addressing practical concerns in water testing, such as robustness and results communication. In response, we present the WaterScope testing kit; an open-source, validated platform for drinking water quality assessment. It modernises the testing process with the inclusion of a unique cartridge/slider mechanism, machine-learning-enhanced classification and full digitalisation of results. WaterScope’s equivalency to conventional methods for quantifying E. coli is established through extensive validation experiments in both laboratory and field environments. This versatile platform provides potential to expand its applications to test other bacteria, perform colorimetric assays, and analyse clinical samples such as blood/urine samples. We anticipate that the system’s ease-of-use, portability, affordability, robustness, and digital nature will accelerate progress toward global water equality.

Tsing Hong Wang,1 Tin Aung,2– 4 Da-Wen Lu,5 Ronnie George,6 Sirisha Senthil,7 Fenghe Lu,8 Noriko Odani-Kawabata,9 Ki Ho Park10 1Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; 2Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; 3Duke-NUS Medical School, Singapore; 4Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 5Department of Ophthalmology, Tri-Service General Hospital, Taipei, Taiwan; 6Sankara Nethralaya, Chennai, India; 7VST Centre for Glaucoma Care, Kallam Anji Reddy Campus, Hyderabad, India; 8Santen Pharmaceuticals, Inc, Emeryville, CA, USA; 9Santen Pharmaceuticals, Ltd, Osaka, Japan; 10Department of Ophthalmology, Seoul National University, Seoul, Republic of KoreaCorrespondence: Tsing Hong Wang, Department of Ophthalmology National Taiwan University Hospital, Taipei, Taiwan, Email thwangglaucoma@ntu.edu.twPurpose: To compare the efficacy and safety of omidenepag isopropyl (OMDI) 0.002% with latanoprost 0.005% once daily in Asian subjects with open-angle glaucoma (OAG)/ocular hypertension (OHT).Methods: In this Phase III randomized, observer-masked, active-controlled, multinational trial (NCT02981446), subjects aged ≥ 18 years with OAG/OHT in both eyes and baseline intraocular pressure (IOP) ≥ 22 mmHg and ≤ 34 mmHg were randomized 1:1 to OMDI or latanoprost. IOP was measured at 9AM, 1PM, and 5PM at baseline, 1 week, 6 weeks, and 3 months. Adverse events (AEs) were recorded. Non-inferiority of OMDI to latanoprost was tested for primary and key secondary endpoints.Results: Each group included 185 subjects. Mean diurnal IOP from baseline to month 3 was reduced 7.1 mmHg (28.8%) with OMDI and 7.8 mmHg (31.3%) with latanoprost, with the least-squares mean difference (OMDI minus latanoprost) being 0.6 mmHg (95% CI: 0.0, 1.2 mmHg; p = 0.0366), indicating non-inferiority. Mean IOP reductions at the nine timepoints were − 5.8 to − 7.3 mmHg (23.5– 29.5%) for OMDI and − 6.1 to − 7.9 mmHg (24.3– 31.7%) for latanoprost. Non-inferiority per FDA criteria was also met. Rates of all AEs, ocular AEs, and ocular AEs associated with treatment were 40.0%, 36.8%, and 23.2%, respectively, for OMDI and 29.7%, 21.1%, and 11.9%, respectively, for latanoprost. Conjunctival hyperemia rates were higher with OMDI than latanoprost (11.9% vs 5.4%). Most AEs were mild, with no serious ocular AEs.Conclusion: OMDI safely and effectively reduces IOP in Asian subjects with OAG/OHT, with mean diurnal IOP at Month 3 and per-timepoint IOP reductions non-inferior to those of latanoprost.Plain Language Summary: PEONY Study: Testing How Well and How Safely Omidenepag Isopropyl Eye Drops Treat People with Glaucoma or Ocular Hypertension Compared with Latanoprost.Who took part in the study?Three hundred and seventy participants average age of 57 years, from 34 centers across four Asian countries who had glaucoma or high pressure in both eyes were randomly divided into two groups. One group (185 people; 50%) was given OMDI, and the other group (185 people; 50%) latanoprost for 3 months. The intraocular pressure of both eyes was measured in all participants at three time points (9 AM, 1 PM, and 5 PM) after 1 week, 6 weeks, and 3 months of treatment. The primary endpoint was the average of the daily eye pressure after 3 months of treatment. The safety of OMDI was also assessed.Study results.After 3 months of treatment, OMDI decreased the eye pressure by 29%. This was similar to latanoprost, which decreased the eye pressure by 31% over the same time period. OMDI was safe and well tolerated by those participants who received it. The most common side-effect in people receiving OMDI or latanoprost was conjunctival hyperemia (red eye) (experienced by 22 people receiving OMDI, and 10 people receiving latanoprost).ConclusionsAfter 3 months of use, OMDI was found to safely reduce high eye pressure to a similar level as latanoprost in Asian people with glaucoma or high eye pressure.Keywords: omidenepag isopropyl, latanoprost, intraocular pressure, glaucoma, ocular hypertension

Background: Acute coronary syndrome (ACS) hospital admissions decreased during the start of the COVID-19 outbreak. Information is limited on how Google searches were related to patients' behaviour during this time. Methods: We examined de-identified data from 2019 through 2020 regarding the following monthly items: (i) admissions for ACS from the Veterans Affairs Healthcare System; (ii) out-of-hospital cardiac arrest (OHCA) from the National Emergency Medical Services Information System (NEMSIS) public dataset; and (iii) Google searches for “chest pain,” “coronavirus,” “chest pressure,” and “hospital safe” from Google Trends. We analyzed the trends for ACS admissions, OHCA, and Google searches. Results: During the early months of the first COVID-19 outbreak, the following occurred: (i) Veterans Affairs data showed a significant reduction in ACS admissions at a national and regional (Florida) level; (ii) the NEMSIS database showed a marked increase in OHCA at a national level; and (iii) Google Trends showed a significant increase in the before-mentioned Google searches at a national and regional level. Conclusions: ACS hospital admissions decreased during the beginning of the pandemic, likely owing to delayed healthcare utilization secondary to patients fear of acquiring a COVID-19 infection. Concordantly, the volume of Google searches for hospital safety and ACS symptoms increased, along with OHCA events, during the same time. Our results suggest that Google Trends may be a useful tool to predict patients’ behaviour and increase preparedness for future events, but statistical strategies to establish association are needed. Résumé: Contexte: Les admissions à l’hôpital pour un syndrome coronarien aigu (SCA) ont diminué au début de la pandémie de COVID-19. Or, il existe peu de données sur les recherches effectuées par les patients dans Google pendant cette période. Méthodologie: Nous avons examiné des données mensuelles dépersonnalisées de 2019 à 2020 sur les éléments suivants : i) admissions pour un SCA dans le système de santé de Veterans Affairs aux États-Unis; ii) arrêts cardiaques extrahospitaliers (ACEH) de l’ensemble de données publiques du National Emergency Medical Services Information System (NEMSIS); et iii) les recherches dans Google selon Google Trends pour « chest pain » (douleur thoracique), « coronavirus », « chest pressure » (oppression thoracique) et « hospital safe » (sécurité dans les hôpitaux). Nous avons également analysé les tendances relatives aux admissions pour un SCA, aux ACEH et aux recherches dans Google. Résultats: Pour les premiers mois de la première vague de COVID-19, les observations sont les suivantes : i) les données de Veterans Affairs ont montré une réduction significative des admissions pour un SCA à l’échelle nationale et régionale (Floride); ii) la base de données du NEMSIS a montré une augmentation marquée des ACEH à l’échelle nationale; et iii) les tendances observées au moyen de Google Trends indiquent une augmentation significative à l’échelle nationale et régionale des recherches dans Google à l’aide des termes mentionnés précédemment. Conclusions: Les admissions à l’hôpital pour un SCA ont diminué au début de la pandémie, probablement en raison de la crainte des patients de contracter la COVID-19, qui les a amenés à repousser le recours à des soins de santé. Pendant la même période, le volume des recherches dans Google à propos de la sécurité dans les hôpitaux et les symptômes de SCA a augmenté, tout comme le nombre d’ACEH. Nos résultats semblent indiquer que Google Trends pourrait être un outil pratique pour prédire les comportements des patients et mieux se préparer aux événements futurs, mais il convient d’élaborer des stratégies statistiques permettant de mieux caractériser ces liens.

In the long history of higher education, there have been many endowment gifts that have strengthened institutions and brought about profound public benefits, but there are sometimes disappointment and controversy. Savvy donors need to think carefully before entering into endowment agreements which are difficult to change before death and virtually impossible after death. Investing in higher education is a worthy goal, but it should be done with both eyes open.

Background:. Advances in surgical planning and 3-dimensional (3D) printing have benefitted the field of craniomaxillofacial surgery by allowing visualization of patient anatomy in settings of otherwise restricted surgical fields. Long 3D print times limit the usability of surgical planning workflows in acute trauma reconstruction. We sought to identify variables affecting print time and produce rapid-printed models with sufficient quality for prebending osteosynthesis plates. Methods:. Three-dimensional printing variables, including resolution, print orientation, and region of interest cropping, were optimized on a single mandibular and midface fracture model to maximize print time efficiency. Five mandibular and 5 midface fractures were printed both in the high-resolution and time-efficient protocol. Fixation plates were contoured to fit the optimized models and computed tomography scan. Distances and volumes between the fracture surface and plate were computed. Results:. High-resolution mandible models were printed in 7.47 hours and maxillae in 7.53 hours. Optimized models were printed in 0.93 and 1.07 hours, respectively. Cropping to regions of interest, rotating the model, and decreasing print resolution significantly reduced print time. The difference (optimized versus high resolution) in distance between the plate and model averaged 0.22 and 0.34 mm for mandibles and maxillae; the air space volume differed by 1.39 and 0.90 mm3, respectively. Conclusions:. Adjusting size, resolution, and position on the printing platform allows rapid fabrication of 3D models for surgical reconstruction without sacrificing surface quality. These edits reduce printing time, enabling the implementation of 3D-printing workflows for surgical planning in acute craniomaxillofacial trauma settings.

Background Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.Methods Tumor molecular profiles were obtained from patients with stage I–IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF was defined as any progression of primary lung cancer after neoadjuvant ICI therapy in patients without surgery, radiographic and/or biopsy-proven primary lung cancer recurrence after surgery, or death from possibly treatment-related complications or from primary lung cancer since randomization. Tumors with AGAs (n=12) were compared with tumors without AGAs and non-profiled squamous cell carcinomas (non-AGAs+NP SCC, n=20).Results With a median follow-up of 60.2 months, the overall TF rate was 34.1% (15/44). Tumor molecular profiling was retrospectively obtained in 47.7% (21/44) of patients and select AGAs were identified in 12 patients: 5 epidermal growth factor receptor (EGFR), 2 KRAS, 1 ERBB2, and 1 BRAF mutations, 2 anaplastic lymphoma kinase (ALK) and 1 RET fusions. The median time to TF in patients with AGAs was 24.7 months (95% CI: 12.6 to 40.4), compared with not reached (95% CI: not evaluable (NE)–NE) in the non-AGAs+NP SCC group. The TF risk was higher in AGAs (HR: 5.51, 95% CI: 1.68 to 18.1), and lower in former/current smokers (HR: 0.24, 95% CI: 0.08 to 0.75). The odds of major pathological response were 4.71 (95% CI: 0.49 to 45.2) times higher in the non-AGAs+NP SCC group, and the median percentage of residual viable tumor was 72.5% in AGAs compared with 33.0% in non-AGS+NP SCC tumors.Conclusions Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.

Ocean observing systems in coastal, shelf and marginal seas collect diverse oceanographic information supporting a wide range of socioeconomic needs, but observations are necessarily sparse in space and/or time due to practical limitations. Ocean analysis and forecast systems capitalize on such observations, producing data-constrained, four-dimensional oceanographic fields. Here we review efforts to quantify the impact of ocean observations, observing platforms, and networks of platforms on model products of the physical ocean state in coastal regions. Quantitative assessment must consider a variety of issues including observation operators that sample models, error of representativeness, and correlated uncertainty in observations. Observing System Experiments, Observing System Simulation Experiments, representer functions and array modes, observation impacts, and algorithms based on artificial intelligence all offer methods to evaluate data-based model performance improvements according to metrics that characterize oceanographic features of local interest. Applications from globally distributed coastal ocean modeling systems document broad adoption of quantitative methods, generally meaningful reductions in model-data discrepancies from observation assimilation, and support for assimilation of complementary data sets, including subsurface in situ observation platforms, across diverse coastal environments.

ABSTRACT Identifying improved treatments for severe and refractory coccidioidomycosis (Valley fever) is needed. This endemic fungal disease is common in North and South America, and cases have increased substantially over the last 30 years. The current standard of care, oral daily fluconazole, often fails to completely eradicate Coccidioides infection; however, the high cost of identifying new compounds effective in treating Valley fever is a barrier to improving treatment. Therefore, repurposing existing pharmaceutical agents in combination with fluconazole therapy is an attractive option. We screened the Library of Pharmacologically Active Compounds (LOPAC) small molecule library for compounds that inhibited fungal growth in vitro and determined IC50 values for a subset of compounds. Based on these findings, we tested a small subset of these agents to validate the screen, as well as to test the performance of fluconazole in a combination therapy approach, as compared with fluconazole alone, in a murine model. We observed that combination therapy of tamoxifen:fluconazole and sertraline:fluconazole significantly reduced the burden of live fungus in the lung compared with fluconazole alone, and we observed reduced or nonexistent dissemination. These results suggest that tamoxifen and sertraline may be repurposed as adjunctive agents in the treatment of this important fungal disease.IMPORTANCEDeveloping new drugs, especially for regional orphan diseases, such as Valley Fever, is a slow and costly endeavor. However, there is a wealth of FDA-approved drugs available for repurposing, offering a more economical and expedited approach to improve treatment. Those existing compounds with antifungal properties can become novel therapies with relative ease: a considerable advantage for patients in need of alternative treatment. Despite the scope of remaining tasks, our comprehensive screening of potential candidates has revealed promising combinations for further exploration. This effort outlines a practical pipeline for Valley fever drug screening and identifies viable drug combinations that could impact patients more rapidly than single drug development pathways.

Abstract Background Obesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis. Methods We conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS). Results 22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52–6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06–4.51) and non-obese (HR = 2.11, 95% CI = 1.05–4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS. Conclusions Results suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.

Abstract Humans increasingly dominate Earth’s natural freshwater ecosystems, but biomass production of modified ecosystems is rarely studied. We estimate potential fish total standing stock in USA reservoirs is 3.4 billion (B) kg, and approximate annual secondary production is 4.5 B kg y−1. We also observe varied and non-linear trends in reservoir fish biomass over time, thus previous assertions that reservoir fisheries decline over time are not universal. Reservoirs are globally relevant pools of freshwater fisheries, in part due to their immense limnetic footprint and spatial extent. This study further shows that reservoir ecosystems play major roles in food security and fisheries conservation. We encourage additional effort be expended to effectively manage reservoir environments for the good of humanity, biodiversity, and fish conservation.

Abstract Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978–2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.

Summary: Background: In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions. Methods: In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906. Findings: Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], −5.3 [5.2] versus −6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): −2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], −19.5 [26.9] versus −32.2 [38.5]; least squares mean difference, 11.5 [96% CI: −4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group. Interpretation: In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group. Funding: Funded by Sanifit, a CSL Vifor company.

In advanced photonics, there is a growing interest in piezochromic luminescent materials that exhibit multicolor switching, driven by their potential applications in optical recording, memory, and sensors. Here, the piezochromic behavior of 2,4,6‐triphenylpyrylium tetrachloroferrate (Py‐FeCl4) under high pressures from 0 to 9 GPa is reported. The observed multicolor changing properties of Py‐FeCl4 (yellow–orange–red–maroon–black) are found to be fully reversible upon decompression to ambient conditions. The mechanism of Py‐FeCl4 piezochromism is investigated via Raman, infrared, and UV–vis spectroscopy combined with powder X‐ray Diffraction. The absence of structural phase transitions as well as the abrupt shifts of bandgap values together with characteristic Raman and IR peaks within 0‐9 GPa suggests that the Py‐FeCl4 multicoloring switching behavior is driven by an electron transfer between the inorganic FeCl4− anion and the organic pyrylium cation. The obtained results demonstrate that Py‐FeCl4 dye is a good candidate for developing high‐pressure sensing technologies designed to function in extreme environments. Moreover, due to the inherent role of molecular‐structure relationships in the pyrylium salt's photophysical properties, findings suggest the potential discovery of piezochromic behavior in other pyrylium compounds.

The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed. This study employed H295R adrenocortical cells and enzyme activity assays to assess the potential risk of oteseconazole and two other tetrazoles, VT-1598 and quilseconazole, to inhibit adrenal steroidogenesis or 11β-HSD2. Steroidomic footprint analyses of H295R cell supernatants using untargeted liquid-chromatography-high-resolution mass-spectrometry (LC-HRMS) indicated overall patterns common to oteseconazole, quilseconazole and itraconazole, as well as similarities between VT-1598 and isavuconazole. Additionally, more specific features of the steroid signatures were observed. Targeted quantification of nine adrenal steroids in supernatants from treated H295R cells revealed an overall inhibition of adrenal steroidogenesis by the three tetrazoles, itraconazole and isavuconazole, providing an explanation for their similar steroidomic pattern. Applying recombinant enzymes indicated that this effect is not due to direct inhibition of steroidogenic enzymes because no or only weak inhibition could be observed. Moreover, oteseconazole and the two other tetrazoles did not inhibit 11β-HSD2, suggesting that they do not pose a risk of pseudohyperaldosteronism. Furthermore, oteseconazole did not alter steroid concentrations in a recent clinical study. Nevertheless, follow-up studies should assess the mechanism underlying the observed overall steroidogenesis inhibition by tetrazoles, itraconazole and isavuconazole, and whether concentrations achievable in a subgroup of susceptible patients might cause adrenal insufficiency and hyperplasia.

Adaptive management, a process of planning, implementing, and evaluating management strategies, is often recommended for monitoring ecological systems. However, few examples of successful implementation and retrospective case studies exist. We provide a case study of adaptively managing hatchery-assisted protection and recovery for Chinook salmon (Oncorhynchus tshawytscha) and winter steelhead trout (O. mykiss) during and after the removal of two large mainstem dams in the Elwha River, WA. We summarize key aspects of the monitoring and adaptive management plan over the last decade and highlight successes, challenges, and complications during the plan’s implementation. The Elwha Monitoring and Adaptive Management Guidelines included a trigger-based system for moving through four phases of recovery that included preservation, recolonization, local adaptation, and viable natural population, each with differing levels of hatchery production as the management actions. The monitoring component of the plan has been very successful, providing critical data to guide management actions that otherwise may not have occurred and, opportunistically, provided data for other native species in the Elwha River. Implementing adaptive management provided mixed results and was at times hindered by divergent management goals among project partners, the inflexibility of the Endangered Species Act regulatory requirements as implemented for this project, and conflicting information among guidance documents. We learned that some metrics and triggers in the plan were ill-defined or too difficult to measure in the field. In some cases, the performance indicators and/or triggers were successfully modified to incorporate what was learned; however, in other cases, we were unable to revise the values due to differing opinions among partners. The ability to reach consensus on revised triggers appeared to be influenced by the recovery trajectory of the species involved. The implemented adaptive management strategy resulted in substantial collaboration and learning, which resulted in revised management strategies, but was imperfect. Sufficient long-term funding is necessary to implement a well-designed monitoring program and could benefit from including a defined leadership position to shepherd and facilitate a multi-stakeholder adaptive management program. Additionally, incorporating adaptive management into legally binding conditions under the Endangered Species Act is feasible, but requires substantial pre-planning in close coordination with regulatory agencies.

Large dam removal is being used to restore river systems, but questions remain regarding their outcomes. We examine how the removal of two large dams in the Elwha River, coupled with hatchery production and fishing closures, affected population attributes of Chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss). Initial responses by returning adult Chinook salmon and steelhead was an increase in the number and spatial extent of natural and hatchery origin fish. Although few naturally produced juvenile Chinook salmon and steelhead outmigrants were observed prior to and during dam removal, abundances increased three years after adult fish passage was restored, suggesting that impacts due to downstream sedimentation after dam removal were reduced. The Chinook salmon population demographics remain dominated by hatchery production, while increases in winter steelhead abundance included both hatchery and natural-origin spawners. The spatial expansion of winter steelhead upstream of former dam sites was predominantly by natural-origin spawners. We also observed a natural “reawakening” of summer steelhead that were in part derived from an up-river resident population that returned to the Upper Elwha. Our results showed that a combination of habitat, hatchery, and harvest actions can result in positive responses for salmonid populations.

The problem is the widespread practice by many campuses in defining community membership in ways that deny their students the civil liberties and civil rights all other Americans are guaranteed. Thus, when forty-year old veterans enroll for even one part-time course, they may find that First and Fourteenth Amendment rights existing off campus no longer apply to them as students. They may seem to have joined a different nation with various sets of ambiguous rules. Some campuses place those sanctions not only on campus-based actions, but on social media comments made in the distant past as well. The reality is that there are more than 3,000 campuses in the United States. The efforts by Alliance Defending Freedom (ADF), Foundation for Individual Rights in Education (FIRE), Speech First, and other organizations have been essential in establishing legal precedents and at least providing temporary relief to victims of speech suppression on various campuses. But the new judicial openness to holding campus authorities accountable through the imposition of personal damages offers an alternative to the "whack a mole" approach now used. In this article, George La Noue argues to create damage precedents, litigation will have to be more time consuming and expensive requiring attorney fees to be sought when cases are won. Extensive discovery and depositions with the creators of speech suppression policies will be necessary. Who drafted the policy and which administrators and board members reviewed it? What role did campus activists or outside groups play in policy design? Was legal counsel involved and what was their advice? Given that sort of record, a court can determine whether damages should be assessed, how much they should be, and who should pay them? When those sorts of precedents are established, more responsible speech policies consistent with constitutional rights in higher education nationwide will start to be seen.

Abstract The cavity inside fullerene C60 provides a highly symmetric and inert environment for housing atoms and small molecules. Here we report the encapsulation of formaldehyde inside C60 by molecular surgery, yielding the supermolecular complex CH2O@C60, despite the 4.4 Å van der Waals length of CH2O exceeding the 3.7 Å internal diameter of C60. The presence of CH2O significantly reduces the cage HOMO-LUMO gap. Nuclear spin-spin couplings are observed between the fullerene host and the formaldehyde guest. The rapid spin-lattice relaxation of the formaldehyde 13C nuclei is attributed to a dominant spin-rotation mechanism. Despite being squeezed so tightly, the encapsulated formaldehyde molecules rotate freely about their long axes even at cryogenic temperatures, allowing observation of the ortho-to-para spin isomer conversion by infrared spectroscopy. The particle in a box nature of the system is demonstrated by the observation of two quantised translational modes in the cryogenic THz spectra.

Abstract Viable magnetic fusion devices necessitate combining good confinement with effective power flux handling. A major concern for ITER, and devices beyond, is the divertor heat load width, which sets peak boundary heat loads on the plasma-facing materials. Current estimates of the heat flux width are narrow for future reactors. Here, we demonstrate how pedestal turbulence can expand into, or entrain, the stable scrape-off-layer and so broaden the heat flux width beyond these neoclassical predictions. Employing combined theoretical, computational, and experimental approaches, we focus on quiescent high confinement discharges on the DIII-D tokamak, but the results are of broader significance. Our findings uncover common trends in the edge turbulence intensity flux, the pressure perturbation skewness, and the turbulence mixing length, which together determine the heat flux width. This research demonstrates the physics of scrape-off-layer broadening by turbulence and highlights the promise of a turbulent pedestal for successful core-edge integration in ITER and future fusion devices.

Abstract Background Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates. Results The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p