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This paper explores Erich Fromm's concept of humanism, arguing that it provides us with a unified theory for both clinical work as well as social criticism. Fromm's humanistic ideas are rooted in a structure of thought that sees our existence, our ontology as human beings, as constituted by our inherent capacities for both relatedness as well as positing ends and purposes in the world. By cultivating a self-awareness of these dual capacities, we can achieve a state of freedom, a self-consciousness of our capacity to shape our reality as opposed to conforming ourselves to it. In this way, Fromm's ideas constitute a critical humanism that can be realized in the world via self- and social transformation and not merely an abstract set of principles or concepts. [ABSTRACT FROM AUTHOR]

Crown rot (CR; Fusarium pseudograminearum) is a serious disease in winter cereals. Soil type, temperature, nutrients, water availability and stubble‐borne inoculum levels play major roles in determining disease severity. This paper reports the impact of two different watering regimes on the disease severity and gas exchange of F. pseudograminearum infected bread wheat for the first time. Fusarium pseudograminearum inoculated and noninoculated genotypes with different susceptibility to CR were watered to either field capacity or a reduced watering regime in three controlled environment experiments. Rate of photosynthesis, stomatal conductance, internal CO2 concentration and transpiration rate were measured using a portable photosynthesis system, together with disease severity of leaf sheaths at 28 days after planting. Significant differences in disease severity were reported between watering treatments with reduction in CR symptoms in the partially resistant genotypes in the reduced water treatment. Photosynthesis, stomatal conductance and transpiration rate were significantly decreased across most genotypes when inoculated with F. pseudograminearum. Differences in gas exchange between inoculum treatments were more evident in plants watered to field capacity. Water availability has been reported to be one of the crucial factors for initiating F. pseudograminearum infection and subsequent development of CR disease. This research demonstrates significant variation in genotype‐related responses to the complex interactions of F. pseudograminearum infection and water treatment, with a negative impact of both limited soil water availability and CR disease severity on plant gas exchange in bread wheat. [ABSTRACT FROM AUTHOR]

With continued smoking of tobacco products and expanded use of nicotine delivery devices worldwide, understanding the impact of smoking and vaping on respiratory health remains a major global unmet need. Although multiple studies have shown a strong association between smoking and asthma, there is a relative paucity of mechanistic understanding of how elements in cigarette smoke impact the airway. Recognizing that nicotine is a major component in both smoking and vaping products, it is critical to understand the mechanisms by which nicotine impacts airways and promotes lung diseases such as asthma. There is now increasing evidence that α7 nicotinic acetylcholine receptors (α7nAChRs) are critical players in nicotine effects on airways, but the mechanisms by which α7nAChR influences different airway cell types have not been widely explored. In this review, we highlight and integrate the current state of knowledge regarding nicotine and α7nAChR in the context of asthma and identify potential approaches to alleviate the impact of smoking and vaping on the lungs. [ABSTRACT FROM AUTHOR]

Exposure to cigarette smoke and e-cigarettes, with nicotine as the active constituent, contributes to increased health risks associated with asthma. Nicotine exerts its functional activity via nicotinic acetylcholine receptors (nAChRs), and the alpha7 subtype (α7nAChR) has recently been shown to adversely affect airway dynamics. The mechanisms of α7nAChR action in airways, particularly in the context of airway smooth muscle (ASM), a key cell type in asthma, are still under investigation. Mitochondria have garnered increasing interest for their role in regulating airway tone and adaptations to cellular stress. Here mitochondrial dynamics such as fusion versus fission, and mitochondrial Ca2+ ([Ca2+]m), play an important role in mitochondrial homeostasis. There is currently no information on effects and mechanisms by which nicotine regulates mitochondrial structure and function in ASM in the context of asthma. We hypothesized that nicotine disrupts mitochondrial morphology, fission-fusion balance, and [Ca2+]m regulation, with altered mitochondrial respiration and bioenergetics in the context of asthmatic ASM. Using human ASM (hASM) cells from nonasthmatics, asthmatics, and smokers, we examined the effects of nicotine on mitochondrial dynamics and [Ca2+]m. Fluorescence [Ca2+]m imaging of hASM cells with rhod-2 showed robust responses to 10 μM nicotine, particularly in asthmatics and smokers. In both asthmatics and smokers, nicotine increased the expression of fission proteins while decreasing fusion proteins. Seahorse analysis showed blunted oxidative phosphorylation parameters in response to nicotine in these groups. α7nAChR siRNA blunted nicotine effects, rescuing [Ca2+]m, changes in mitochondrial structural proteins, and mitochondrial dysfunction. These data highlight mitochondria as a target of nicotine effects on ASM, where mitochondrial disruption and impaired buffering could permit downstream effects of nicotine in the context of asthma. NEW & NOTEWORTHY Asthma is a major healthcare burden, which is further exacerbated by smoking. Recognizing the smoking risk of asthma, understanding the effects of nicotine on asthmatic airways becomes critical. Surprisingly, the mechanisms of nicotine action, even in normal and especially asthmatic airways, are understudied. Accordingly, the goal of this research is to investigate how nicotine influences asthmatic airways in terms of mitochondrial structure and function, via the a7nAChR. [ABSTRACT FROM AUTHOR]

This article discusses the significance of how Christians relate to issues of knowledge, expertise, and authority in the public sphere, particularly in the context of the events of 2020. The symposium explored the historical crises behind the present situation, examining themes such as racial justice, the authority of science, and decolonization in the US and Australian contexts. The symposium aimed to widen and build on previous work by including the Australian context and exploring the racialization of intellectual authority in Christianity. Keynotes and papers discussed the role of popular culture, creationism, and Indigenous religion in shaping intellectual authority. The symposium also considered the ongoing imperative to decolonize knowledge production. Two papers from the symposium, one on the history of missions and colonial theologies in Australia and one on the history of theological education, have been published in the Journal of Religious History. [Extracted from the article]

OBJECTIVES: To evaluate hospital performance and behaviors in the first 2 years of a statewide commercial insurance episode-based incentive pay-for-performance (P4P) program. STUDY DESIGN: Retrospective cohort study of price- and risk-standardized episode-of-care spending from the Michigan Value Collaborative claims data registry. METHODS: Changes in hospital-level episode spending between baseline and performance years were estimated during the program years (PYs) 2018 and 2019. The distribution and hospital characteristics associated with P4P points earned were described for both PYs. A difference-indifferences (DID) analysis compared changes in patient-level episode spending associated with program implementation. RESULTS: Hospital-level episode spending for all conditions declined significantly from the baseline year to the performance year in PY 2018 (-$671; 95% CI, -$1113 to -$230) but was not significantly different for PY 2019 ($177; 95% CI, -$412 to $767). Hospitals earned a mean (SD) total of 6.3 (3.1) of 10 points in PY 2018 and 4.5 (2.9) of 10 points in PY 2019, with few significant differences in P4P points across hospital characteristics. The highest-scoring hospitals were more likely to have changes in case mix index and decreases in spending across the entire episode of care compared with the lowest-scoring hospitals. DID analysis revealed no significant changes in patient-level episode spending associated with program implementation. CONCLUSIONS: There was little evidence for overall reductions in spending associated with the program, but the performance of the hospitals that achieved greatest savings and incentives provides insights into the ongoing design of hospital P4P metrics. [ABSTRACT FROM AUTHOR]

Objectives To assess whether implementation of the Strengthen Opioid Misuse Prevention (STOP) Act was associated with an increase in the percentage of opioid prescriptions written for 7 days or fewer among patients with acute or postsurgical musculoskeletal conditions. Design An interrupted time-series study was conducted to determine the change in duration of opioid prescriptions associated with the STOP Act. Setting Data were extracted from the electronic health record of a large health care system in North Carolina. Subjects Patients presenting from 2016 to 2020 with an acute musculoskeletal injury and the clinicians treating them were included in an interrupted time-series study (n  = 12 839). Methods Trends were assessed over time, including the change in trend associated with implementation of the STOP Act, for the percentage of prescriptions written for ≤7 days. Results Among patients with acute musculoskeletal injury, less than 30% of prescriptions were written for ≤7 days in January of 2016; by December of 2020, almost 90% of prescriptions were written for ≤7 days. Prescriptions written for ≤7 days increased 17.7% after the STOP Act was implemented (P  < .001), after adjustment for the existing trend. Conclusions These results demonstrate significant potential for legislation to influence opioid prescribing behavior. [ABSTRACT FROM AUTHOR]

A fundamental question of the 21st century centers around the role and place of humans in their environment. Given the great acceleration of consumptive practices engaged in the 20th century, humans stand on the brink of a 6th extinction event. In order to determine our place and role in our global environment, we need to reflect on where we are and what the future will be—we need to focus on the habits of our "co-inhabitation" of the planet. Given the positive and negative impacts of international and global activities, intercultural dialogues are necessary for the care of the ecology of the planet, and one of the most prescient dialogues is between Eastern and Western world views. While much comparative research has been conducted regarding the connection between American Transcendentalism and Chinese ancient philosophy, relatively little philosophical work has been conducted to demonstrate the connectivity between Henry David Thoreau and Taoism. Yet there are, in fact, profound similarities between the American naturalist and Chinese philosophy, in particular Taoism. This paper aimed to discover and manifest the connection and similarities between the philosophy of Thoreau and the ancient worldview of Taoism. Through this comparative study and intercultural dialogue, we seek to trace historical precedents and intercultural dialogue between American Transcendentalism and ancient Chinese philosophy in order to explore the groundwork for a new vision of environmental awareness in order to promote a better future with a community of co-inhabitants and emphasis on the well-being of all. [ABSTRACT FROM AUTHOR]

I argue in this paper for a critical social ontology, or an approach to theorizing social reality and social institutions that is more than descriptive of social reality, but is also able to provide practical reasoning with an ontological dimension for judgment. At the heart of this idea is a different take on social metaphysics from most standard current accounts in that it begins with empirical, phylogenetic capacities of human beings for social practices (realizing abstract thought in the world) as well as relationality (the need for attachments to others). The combination of these two essential human capacities, what I call the practical‐relational nexus, is generative of more complex social reality. The ontogeny of any social reality is the result of the ways that this practical‐relational nexus has been organized and shaped by external social structures and systems, themselves the product of certain kinds of social power. I then explore the metaphysics of social power before considering the ways that this approach to social metaphysics can inform practical reasoning with the capacity for social and political criticism. [ABSTRACT FROM AUTHOR]

The broadband photoelectron source realized by detaching O2−·X (X = neutral unsaturated molecule) complexes offers a unique opportunity to probe temporary anion states of the unsaturated species. Detachment of the ion molecule complex typically accesses a dissociative portion of the neutral potential, creating a continuum electron source that can undergo scattering with X. We present the application of this new approach to electron-neutral scattering toward a study of the series of fluorinated benzenes via photoelectron spectroscopy of O2−·C6H6−xFx (x = 0–6) measured with several photon energies. We compare these spectra to the reference O2−·hexane spectrum and observe evidence of temporary anion states of C6H6−xFx for species with x = 0–5 in the form of enhanced signal intensity at electron kinetic energies coinciding with the energies of the temporary anions. Furthermore, we observe autodetachment features in the x = 3, 5 spectra. Results of calculations on the isolated symmetric isomer of C6H3F3 suggest that the molecule cannot support a weakly-bound non-valence state that could be associated with the observed autodetachment. However, C6HF5− is predicted to support a valence bound state, which, if produced by charge transfer from O2− with sufficient vibrational energy, may undergo autodetachment. Finally, the [O2·C6F6]− spectrum is unique insofar as the spectrum is substantially higher in binding energy and qualitatively different from the x = 0–5 spectra. This result suggests much stronger interactions and charge delocalization between O2− and C6F6. [ABSTRACT FROM AUTHOR]

Domain experts prefer interactive and targeted control-point tone mapping operations (TMOs) to enhance underwater image quality and feature visibility; though this comes at the expense of time and training. In this paper, we provide end-users with a simpler and faster interactive tone-mapping approach. This is built upon Weibull Tone Mapping (WTM) theory; introduced in previous work as a preferred tool to describe and improve domain expert TMOs. We allow end-users to easily shape brightness distributions according to the Weibull distribution, using two parameter sliders which modify the distribution peak and spread. Our experiments showed that 10 domain experts found the two-slider Weibull manipulation sufficed to make a desired adjustment in >80% of images in a large dataset. For the remaining ∼20%, observers opted for a control-point TMO which can, broadly, encompass many global tone mapping algorithms. Importantly, 91% of these control-point TMOs can actually be visually well-approximated by our Weibull slider manipulation, despite users not identifying slider parameters themselves. Our work stresses the benefit of the Weibull distribution and significance of image purpose in underwater image enhancement. [ABSTRACT FROM AUTHOR]

Herbicide resistance is an important weed management issue. Glyphosate is the most dominant herbicide, which controls a broad spectrum of weeds, including grasses such as Lolium rigidum. Lolium rigidum is a major weed of winter crops in Australia that is developing glyphosate resistance in increasing numbers of populations and has been observed growing throughout summer in recent years. Three L. rigidum populations, one summer-emerging glyphosate-resistant (GR), one winter-emerging glyphosate-susceptible (GS), and one winter-emerging population with unknown resistance status (CC04), were analyzed for target-site resistance to glyphosate after confirming their resistance or susceptibility to glyphosate in a dose–response experiment. Population GR was obtained from plants that emerged in summer and contained plants that survived all rates of glyphosate applied (0 to 4560 g a.e. ha−1). It was found to be 6.1 and 4.4 times more resistant than population GS across two experiments. Population CC04 was identified as susceptible. Plants from each population were analyzed for the presence of target-site mutations in the conserved region of the EPSPS gene; however, no mutations were identified that could cause resistance, suggesting non-target-site resistance in population GR. The effectiveness of alternative herbicides was also analyzed for each population. Paraquat was the most effective herbicide, with 0% survival across all populations. The ACCase-inhibiting herbicide clethodim was also highly effective (0 to 8% survival across populations). Other ACCase-inhibiting herbicides, propaquizafop, haloxyfop, and pinoxaden, were effective at controlling the two susceptible populations, CC04 and GS (0 to 36% and 0 to 20% survival, respectively), but were only moderately effective for controlling GR (28 to 51% survival). Paraquat and clethodim may be alternative options for controlling GR populations of L. rigidum and could be effective for use in management programs to slow the development of GR populations. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study is to explore the characteristics of the subset of patients with hematologic malignancies (HMs) who had little to no change in SARS-CoV-2 spike antibody index value levels after a third mRNA vaccine dose (3V) and to compare the cohort of patients who did and did not seroconvert post-3V to get a better understanding of the demographics and potential drivers of serostatus. Study design This retrospective cohort study analyzed SARS-CoV-2 spike IgG antibody index values pre and post the 3V data on 625 patients diagnosed with HM across a large Midwestern United States healthcare system between 31 October 2019 and 31 January 2022. Methods To assess the association between individual characteristics and seroconversion status, patients were placed into two groups based on IgG antibody status pre and post the 3V dose, (−/+) and (−/−). Odds ratios were used as measures of association for all categorical variables. Logistic regressions were used to measure the association between HM condition and seroconversion. Results HM diagnosis was significantly associated with seroconversion status (P = 0.0003) with patients non-Hodgkin lymphoma six times the odds of not seroconverting compared with multiple myeloma patients (P = 0.0010). Among the participants who were seronegative prior to 3V, 149 (55.6%) seroconverted after the 3V dose and 119 (44.4%) did not. Conclusion This study focuses on an important subset of patients with HM who are not seroconverting after the COVID mRNA 3V. This gain in scientific knowledge is needed for clinicians to target and counsel these vulnerable patients. [ABSTRACT FROM AUTHOR]

The regeneration potential of the mammalian heart is incredibly limited, as cardiomyocyte proliferation ceases shortly after birth. β-adrenergic receptor (β-AR) blockade has been shown to improve heart functions in response to injury; however, the underlying mechanisms remain poorly understood. Here, we inhibited β-AR signaling in the heart using metoprolol, a cardio-selective β blocker for β1-adrenergic receptor (β1-AR) to examine its role in heart maturation and regeneration in postnatal mice. We found that metoprolol enhanced cardiomyocyte proliferation and promoted cardiac regeneration post myocardial infarction, resulting in reduced scar formation and improved cardiac function. Moreover, the increased cardiomyocyte proliferation was also induced by the genetic deletion of Gnas, the gene encoding G protein alpha subunit (Gαs), a downstream effector of β-AR. Genome wide transcriptome analysis revealed that the Hippo-effector YAP, which is associated with immature cardiomyocyte proliferation, was upregulated in the cardiomyocytes of β-blocker treated and Gnas cKO hearts. Moreover, the increased YAP activity is modulated by RhoA signaling. Our pharmacological and genetic studies reveal that β1-AR-Gαs-YAP signaling axis is involved in regulating postnatal cardiomyocyte proliferation. These results suggest that inhibiting β-AR-Gαs signaling promotes the regenerative capacity and extends the cardiac regenerative window in juvenile mice by activating YAP-mediated transcriptional programs. [ABSTRACT FROM AUTHOR]

Predictions for wheat grown under future climate conditions indicate a decline in grain protein concentration accompanied with an increase in yield due to increasing carbon dioxide concentrations. Currently, there is a lack of understanding as to the complete mechanism that governs the response of grain protein concentration (GPC) to elevated carbon dioxide (e[CO 2 ]). We investigated the GPC of 18 wheat genotypes from a doubled haploid wheat population and the two parental genotypes, Kukri and RAC0875. In addition, other nitrogen and biomass related traits were analysed to further elucidate which traits are connected with the decline in GPC. Wheat was grown under ambient and elevated [CO 2 ] in an environmentally controlled glasshouse. Plant nitrogen and biomass accumulation were measured at anthesis and maturity. We found that GPC declined under e[CO 2 ] and that the response of GPC to e[CO 2 ] was negatively correlated with nitrogen utilisation efficiency and harvest index. The extent that total biomass (anthesis), harvest index, photosynthesis, nitrogen utilisation and remobilisation efficiency, total nitrogen remobilisation and post-anthesis nitrogen uptake impacted GPC in response to e[CO 2 ] varied across genotype, suggesting that multiple mechanisms are responsible for GPC decline at e[CO 2 ] and that these mechanisms are effected differentially across genotypes. • GPC declines in some wheat genotypes under e[CO 2 ], but not all. • GPC response correlated negatively with both NUtE and HI response. • Nitrogen remobilisation contributes to maintaining GPC. • No single trait was involved in preventing GPC decline under e[CO 2 ]. [ABSTRACT FROM AUTHOR]

Mice exposed in gestation to maternal high-fat/high-sucrose (HF/HS) diet develop altered bile acid (BA) homeostasis. We hypothesized that these reflect an altered microbiome and asked if microbiota transplanted from HF/HS offspring change hepatic BA and lipid metabolism to determine the directionality of effect. Female mice were fed HF/HS or chow (CON) for 6 wk and bred with lean males. 16S sequencing was performed to compare taxa in offspring. Cecal microbiome transplantation (CMT) was performed from HF/HS or CON offspring into antibiotic-treated mice fed chow or high fructose. BA, lipid metabolic, and gene expression analyses were performed in recipient mice. Gut microbiomes from HF/HS offspring segregated from CON offspring, with increased Firmicutes to Bacteriodetes ratios and Verrucomicrobial abundance. After CMT was performed, HF/HS-recipient mice had larger BA pools, increased intrahepatic muricholic acid, and decreased deoxycholic acid species. HF/HS-recipient mice exhibited downregulated hepatic Mrp2, increased hepatic Oatp1b2, and decreased ileal Asbt mRNA expression. HF/HS-recipient mice exhibited decreased cecal butyrate and increased hepatic expression of Il6. HF/HS-recipient mice had larger livers and increased intrahepatic triglyceride versus CON-recipient mice after fructose feeding, with increased hepatic mRNA expression of lipogenic genes including Srebf1, Fabp1, Mogat1, and Mogat2. CMT from HF/HS offspring increased BA pool and shifted the composition of the intrahepatic BA pool. CMT from HF/HS donor offspring increased fructose-induced liver triglyceride accumulation. These findings support a causal role for vertical transfer of an altered microbiome in hepatic BA and lipid metabolism in HF/HS offspring. [ABSTRACT FROM AUTHOR]

Analytical chemists in the food sector are well acquainted with the empirically observed Horwitz function. It relates reproducibility (interlaboratory) standard deviations estimated by collaborative trial with the mass fraction of the analyte. No compelling theory accounts for the power-law form of the function or its parameters. The equation of Zitter and God, ostensibly covering the same ground, is less well known but, in spite of its secure foundation in theory and practice, seems at first sight to be incompatible with the Horwitz function. In this paper, we see that because of the limited range of mass fractions in which a single collaborative trial is usually conducted, collections of statistics from collaborative trials exhibit the Horwitz function over the mass fraction range from about 10−7 (100 ppb) to about 10−1 (10%). [ABSTRACT FROM AUTHOR]

The relationship between reproducibility standard deviation and mass fraction in food analysis has been studied in compilations of statistics from collaborative trials and from proficiency tests. There was a broad tendency for both categories of statistics to follow the Horwitz function although systematic deviations from it were easily detected at both extremes of the mass fraction range (below 10−7 and above 10−2). The two compilations were found to have very similar properties over the whole range of mass fractions, that is from about 10−10 (0.1 ppb) upwards. This similarity has implications for the determination of detection limit. [ABSTRACT FROM AUTHOR]

Hadrosaurids are a diverse and widely distributed group of ornithischian dinosaurs that are particularly well represented in the upper Campanian Dinosaur Park Formation of the Belly River Group of Alberta. However, the origin of this hadrosaurid diversity in Alberta is poorly understood, as the lower Campanian terrestrial deposits of the underlying Oldman and Foremost formations of the group have produced comparatively few body fossils. Here we provide the first description of a partially articulated hadrosaurid and hadrosaurid material from a bonebed from the Foremost Formation and refer it to the brachylophosaurin Probrachylophosaurus sp. indet. The material represents the oldest occurrence of Brachylophosaurini in Alberta and the oldest known hadrosaurid diagnostic to the genus level from Canada. In Alberta, Hadrosaurinae display a distinct pattern of replacement with the tribes Brachylophosaurini and Kritosaurini being confined to the lower to middle Campanian strata (below the marine Bearpaw Formation) and replaced above the Bearpaw Formation by members of Saurolophini (Prosaurolophus, Saurolophus) and Edmontosaurini (Edmontosaurus), with the latter clade persisting to the end of the Maastrichtian. Although the worldwide stratigraphic distribution of the Hadrosaurinae is complex, this pattern generally holds true for northern Laramidian hadrosaurine tribes, suggesting that their pattern of evolution and replacement may be driven by some common underlying factor such as an environmental response to fluctuations in the margins of the Western Interior Seaway due to sea level change. [ABSTRACT FROM AUTHOR]

This work forms a background to the recent discussion about normal and log-normal distributions in the results of proficiency tests for GMO analysis. In order to clear up some common confusions, the paper first covers some basic principles, viz., a comparison of normally and log-normally distributed samples of results at various precisions, and a background to the determination of assigned values and scoring in proficiency tests. Then follows brief discussions on the identification of outliers and the use of 'tests for normality'. In conclusion, there is a broad outline of the steps that may assist a proficiency testing scheme in deciding on a suitable model of dispersion. [ABSTRACT FROM AUTHOR]

We report infrared photodissociation spectra of nitrous oxide cluster anions of the form (N2O)nO- (n = 1-12) and (N2O)n- (n = 7-15) in the region 800-1600 cm-1. The charge carriers in these ions are NNO2- and O- for (N2O)nO- clusters with a solvation induced core ion switch, and N2O- for (N2O)n - clusters. The N-N and N-O stretching vibrations of N2O- (solvated by N2O) are reported for the first time, and they are found at (1595 ± 3) cm-1 and (894 ± 5) cm-1, respectively. We interpret our infrared spectra by comparison with the existing photoelectron spectroscopy data and with computational data in the framework of density functional theory. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). Methods: We included 222 participants (mean age 62 years, 52% female) from the two‐year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time‐varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Results: Over a mean follow‐up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2–14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9–53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5–1.8) and the study knee (HR 1.4, 95%CI 0.5–2.2). Conclusion: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN. [ABSTRACT FROM AUTHOR]

Background Bisulfite sequencing is commonly used to measure DNA methylation. Processing bisulfite sequencing data is often challenging owing to the computational demands of mapping a low-complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis-ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt), a fast and scalable bisulfite sequencing analysis platform. BSBolt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries. Findings We evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. Conclusion BSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a Python package and command line utility for flexibility when building informatics pipelines. BSBolt is available at https://github.com/NuttyLogic/BSBolt under an MIT license. [ABSTRACT FROM AUTHOR]

We report infrared spectra of nitromethane anion, CH3NO2-, in the region 700-2150 cm-1, obtained by Ar predissociation spectroscopy and electron detachment spectroscopy. The data are interpreted in the framework of second-order vibrational perturbation theory based on coupled-cluster electronic structure calculations. The modes in the spectroscopic region studied here are mainly based on vibrations involving the heavier atoms; this work complements earlier studies on nitromethane anion that focused on the CH stretching region of the spectrum. Electron detachment begins at photon energies far below the adiabatic electron affinity due to thermal population of excited vibrational states. [ABSTRACT FROM AUTHOR]

Background: Early involvement of palliative care and advance care planning improves quality‐of‐life outcomes and survival for patients with advanced lung cancer; however, there are barriers to implementation. Aims: A single‐centre prospective audit reviewing 'Goals of Care' (GOC) form completion and palliative care referrals in an oncology clinic was undertaken with the aim of increasing GOC completion and palliative care referrals for patients with advanced lung cancer. Methods: Involved physicians attended a communication skills course and then received a communication‐priming intervention. Clinicopathological factors associated with GOC completion and palliative care referral were explored. Results: A total of 84 patients receiving palliative treatment for advanced lung cancer was enrolled. Clinicopathological factors, such as poorer performance status, were associated with higher likelihood of GOC completion (P = 0.018) prior to the intervention. Male sex (P = 0.023), absence of sensitising epidermal growth factor receptor mutation or anaplastic lymphoma kinase rearrangement (P = 0.017), type of systemic therapy (P = 0.031) and poorer performance status (P < 0.001) were associated with higher likelihood of palliative care referral. The intervention improved GOC completion (relative risk (RR) 1.29, P = 0.004); however, this was not sustained in a follow‐up audit (RR 0.98, P = 0.92) and there was no change in palliative care referral rate (RR 2.5, P = 0.16). Predictors of palliative referral following clinical review included age (RR 1.16, P = 0.001), male sex (RR 14.2, P = 0.02) and poorer performance status (RR 1.76, P < 0.001). Conclusions: Communication‐priming interventions can improve GOC completion for patients with advanced lung cancer. Further investigation is needed to pursue sustainable options for managing this complex patient group and improve guideline‐adherence and patient care. [ABSTRACT FROM AUTHOR]

This article discusses Rousseau's theory of the genesis and development of a "post-liberal self" and its political implications. In his Emile, or Education, Rousseau explores the distinctive features of the post-liberal self through Emile's growing capacity to think in terms of his social interdependence with others and yet to maintain his critical autonomy. For Rousseau it is only such individuals with a highly developed moral and civic consciousness who are capable of articulating the general will and of properly participating in a modern republic. I argue that the general will for Rousseau is therefore not a property of the community but of the post-liberal self, for whom the common good is a larger dimension of the individual good. I then discuss the political implications of this theory by relating it to The Social Contract where Rousseau urges us to examine the legitimacy of existing social norms, laws and practices. Rousseau, I conclude, is one of the great radical thinkers of self-transformation as the prerequisite for overcoming the pathologies and limitations of liberal society. [ABSTRACT FROM AUTHOR]

Background: Patients with mutations of succinate dehydrogenase B (SDHB) and succinate dehydrogenase D (SDHD) are at high risk of paraganglioma necessitating surveillance. Chromogranin A has been proposed as a biochemical marker of paraganglioma. We sought to determine the diagnostic utility of chromogranin A in a population-based SDHx sample.Methods: Tasmania is an island state with one tertiary referral centre for endocrine neoplasia. We performed a cross-sectional analysis of all adult SDHB ( n = 52) and SDHD ( n = 10) patients undergoing paraganglioma surveillance between 2011 and 2017. Chromogranin A was referenced against the outcome of paraganglioma surveillance with a minimum of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and plasma metanephrines (metanephrine and normetanephrine).Results: Chromogranin A correctly predicted the result of paraganglioma surveillance more often in patients with SDHB compared with those with SDHD (77% vs. 22%, P = 0.003). In the SDHB group, chromogranin A demonstrated a sensitivity of 67% and specificity of 79% compared with 22% and 0% in the SDHD group. Chromogranin A identified one of three PET/CT-visualized SDHB-related paragangliomas with normal plasma metanephrines at the expense of nine false-positive results. A normal chromogranin A demonstrated a negative predictive value of 92% for SDHB-related paraganglioma. In patients with SDHB, plasma normetanephrine and metanephrine offered superior specificity (100%, P = 0.01 and 100%, P < 0.01, respectively) with comparable sensitivity (67%, P = 1.0 and 11%, P = 0.06, respectively) to chromogranin A.Conclusion: Chromogranin A does not provide additive benefit to standard surveillance for predicting the presence of SDHB- or SDHD-related paraganglioma, but has a useful negative predictive value when normal in patients with SDHB mutation. [ABSTRACT FROM AUTHOR]

Context: Multiple endocrine neoplasia type 1 (MEN 1) is characterized by multisystem neoplasia including primary hyperparathyroidism and pituitary adenoma. Despite the adolescent onset of endocrinopathies, information regarding the impact of maternal MEN 1 on pregnancy is limited to case reports. Objective: To explore pregnancy outcomes in MEN 1 positive women. Methods: Retrospective case series of maternofoetal outcomes MEN 1 positive mothers managed at the Royal Hobart Hospital between 1967 and 2018. Data were retrieved from medical records and Australian averages calculated based on the Australian Institute of Health and Welfare data. Results: Twenty‐six women with MEN 1 were identified accounting for 96 pregnancies and 76 live born infants. Hyperparathyroidism was evident in 16 pregnancies. A significant increase in serum calcium in the second trimester (β = 0.14, P <.001) occurred that was not mediated by parathyroid hormone. Hypercalcaemia was mild‐moderate with parathyroidectomy or medical management required in one and four pregnancies, respectively. Compared to the Australian average, women with MEN 1 were more likely to develop gestational diabetes (56% vs 8.9%, P =.001), hypertensive disorders (25.9% vs 7.6, P =.018), have shorter gestations (38.1 vs 38.7 weeks, P =.015) and have low birthweight infants (30.1% vs 6.5%, P =.001). However, emergency caesarean deliveries (63.2% vs 52.3%) and miscarriage rate (20.8% vs 20%) were not significantly different. Conclusion: Maternal MEN 1 is associated with an increased risk of gestational diabetes, hypertensive disorders and low neonatal birthweight, but not with an increased miscarriage rate. Whilst hypercalcaemia worsens during the second trimester, most pregnancies progressed without overt complications or requirement for intervention. [ABSTRACT FROM AUTHOR]

Naturally occurring proteins vary the precise geometries of structural elements to create distinct shapes optimal for function. We present a computational design method, loop-helix-loop unit combinatorial sampling (LUCS), that mimics nature’s ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization showed that 17 (38%) of 45 tested LUCS designs encompassing two different structural topologies were well folded, including 16 with designed non-native geometries. Four experimentally solved structures closely matched the designs. LUCS greatly expands the designable structure space and offers a new paradigm for designing proteins with tunable geometries that may be customizable for novel functions. [ABSTRACT FROM AUTHOR]

Australian lizards are a diverse group distributed across the continent and inhabiting a wide range of environments. Together, they exhibit a remarkable diversity of reproductive morphologies, physiologies, and behaviours that is broadly representative of vertebrates in general. Many reproductive traits exhibited by Australian lizards have evolved independently in multiple lizard lineages, including sociality, complex signalling and mating systems, viviparity, and temperature-dependent sex determination. Australian lizards are thus outstanding model organisms for testing hypotheses about how reproductive traits function and evolve, and they provide an important basis of comparison with other animals that exhibit similar traits. We review how research on Australian lizard reproduction has contributed to answering broader evolutionary and ecological questions that apply to animals in general. We focus on reproductive traits, processes, and strategies that are important areas of current research, including behaviours and signalling involved in courtship; mechanisms involved in mating, egg production, and sperm competition; nesting and gestation; sex determination; and finally, birth in viviparous species. We use our review to identify important questions that emerge from an understanding of this body of research when considered holistically. Finally, we identify additional research questions within each topic that Australian lizards are well suited for reproductive biologists to address. Australian lizards exhibit a diversity of reproductive traits and provide excellent opportunities to study how those traits function and evolve. We review the contributions that Australian lizard research has made to understanding animal reproductive biology. We then highlight major emergent and outstanding research questions, and urge readers to consider Australian lizards as ideal model organisms for addressing these questions. Photo by C. Friesen. [ABSTRACT FROM AUTHOR]

Broad geographical distributions that include marked climatic variation may expose populations to distinct selective pressures. Local adaptation to differences in developmental conditions may lead to divergence in embryonic and hatchling traits for populations of oviparous reptiles. Among‐population differences in hatchling size and the duration of development are often observed in lizards with wide and climatically diverse distributions. Variation in hatchling phenotypes can arise from variation in maternal allocation, developmental plasticity or selection acting on embryonic traits. We studied variation in hatchlings of the Australian water dragon (Intellagama lesueurii), comparing traits related to growth and patterns of developmental plasticity. We recorded marked differences in hatchling sizes among populations from different climate types, which did not result from differences in maternal investment or from a plastic response to incubation temperatures. Embryos from southern, temperate populations exhibited shorter incubation times when incubated at cold temperatures but utilized less yolk during development and hatched smaller, with more residual yolk, regardless of incubation treatment. We suggest that these findings represent the first example of among‐population variation in patterns of embryonic resource allocation and a novel mechanism mediating offspring size in reptiles. We further suggest that variation in embryonic resource allocation in I. lesueurii, together with evolutionary changes in reaction norms for developmental rate, evolved as adaptations to seasonal length and conditions associated with a tropical‐temperate gradient. [ABSTRACT FROM AUTHOR]

Our understanding of the evolution of complex biological traits is greatly advanced by examining taxa with intermediate phenotypes. The transition from oviparity (egg‐laying) to viviparity (live‐bearing) has occurred independently in many animal lineages, but there are few phenotypic intermediates. The lizard Saiphos equalis exhibits bimodal reproduction, with some viviparous populations, and other oviparous populations with long egg‐retention, a rare trait where most of embryonic development occurs inside the mother prior to late ovipositioning. We posit that oviparous S. equalis represent an intermediate form between "true" oviparity and viviparity. We used transcriptomics to compare uterine gene expression in these two phenotypes, and provide a molecular model for the genetic control and evolution of reproductive mode. Many genes are differentially expressed throughout the reproductive cycle of both phenotypes, which have clearly different gene expression profiles overall. The differentially expressed genes within oviparous and viviparous individuals have broadly similar biological functions putatively important for sustaining embryos, including uterine remodelling, respiratory gas and water exchange, and immune regulation. These functional similarities indicate either that long egg‐retention is an exaptation for viviparity, or might reflect parallel evolution of similar gravidity‐related changes in gene expression in long egg‐retention oviparity. In contrast, gene expression changes across the reproductive cycle of long egg‐retaining oviparous S. equalis are dramatically different from those of "true" oviparous skinks (such as Lampropholis guichenoti), supporting our assertion that oviparous S. equalis exhibit an intermediate phenotype between "true" oviparity and viviparity. [ABSTRACT FROM AUTHOR]

A cadmium germanium arsenide compound, Cd3Ge2As4, was synthesized using a double-containment fused quartz ampoule method within a rocking furnace and a melt-quench technique. The crystal structure was determined from single-crystal X-ray diffraction (SC-XRD), scanning and transmission electron microscopies (i.e. SEM, STEM, and TEM), and selected area diffraction (SAD) and confirmed with electron backscatter diffraction (EBSD). The chemistry was verified with electron energy loss spectroscopy (EELS). [ABSTRACT FROM AUTHOR]

In this article, I set out to describe my 7-year apprenticeship with R. D. Laing in London, between 1973 and 1980, 4 of those year which comprised my living in one of Laing's post-Kingsley Hall houses, Portland Road. My goal is to use the metaphor of friendship to explain how living in a house with no ostensible treatment or therapy can engender a healing experience for the people living in that house, many of whom would be diagnosed as schizophrenic if admitted to mental hospital. Though this particular example of this concept is located in a residential living situation, I believe that it holds much broader application, including individual psychotherapy. [ABSTRACT FROM AUTHOR]

As of March 23, 2012, the Internal Revenue Service (IRS) requires tax-exempt hospitals to conduct a Community Health Needs Assessment (CHNA) every 3 years. This study assessed whether the IRS CHNA mandate incentivized North Carolina's tax-exempt hospitals to increase investments in community health programs. The authors gathered the 2012–2016 community benefit reports of 53 North Carolina private, nonprofit hospitals from the North Carolina Hospital Association. Community benefit spending data from the year of the first CHNA were compared to that 2 years later using paired t tests among matched subjects. No significant increases were found in hospitals' community health programs spending (P = 0.6920) or in providing patient care financial assistance (charity or discounted care) (P = 0.0934). In fact, aggregate community health programs spending effectively decreased by 4%, from $393.3 million to $377.5 million. Among all community benefit items, only the unreimbursed cost for treating Medicare patients increased significantly (P = 0.0297). The proportion of spending on community health programs relative to patient care financial assistance decreased significantly (P = 0.0338). Performing CHNAs did not incentivize North Carolina's tax-exempt hospitals to progressively invest in community health programs. The hospitals continue to spend heavily on patient care financial assistance and little on disease prevention and community health improvement activities. These findings suggest that tax-exempt hospitals continue to function as a safety net for the poor and the uninsured rather than as active partners in population health management initiatives. At present, performing CHNAs may be more a demonstration of compliance than a tool to improve population health. [ABSTRACT FROM AUTHOR]

Poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] thin films have been extensively studied for their ferroelectric properties and are a promising material for sensing and memory applications. Imprint, the time-dependent resistance to polarization reversal, is a key material property that limits applications and is poorly understood. We have used a fast ramp rate thermally stimulated current (FR-TSC) technique to investigate the proposed link between imprint time and filling of charge trap states, and to characterize these traps in an appropriate time-frame. Thin films of P(VDF-TrFE) on oxidized Si substrates were characterized following controlled initialization, fatigue, polarization, and imprint. Traps were allowed to fill during room temperature imprint for times from 1 to 104 s. Remaining unfilled traps were subsequently filled and quantified by FR-TSC temperature cycling from 20 to 100 °C at 1 K/s. Results confirm that charge trap filling occurs both with time, under isothermal conditions, as well as with increasing temperature. The rate of charge accumulation induced by FR-TSC exhibits the same logarithmic dependence with time as the experimentally measured imprint voltage; this strongly suggests a direct link between these trapped charges and the imprint field. Furthermore, measurements of the switching speed in post FR-TSC films were found to be independent of the imprint time, confirming that thermal cycling brought all samples to a common final state. These results provide further understanding of the polarization dynamics and materials interactions affecting the ferroelectric properties of P(VDF-TrFE). [ABSTRACT FROM AUTHOR]

Poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ferroelectric thin films are promising materials for sensors, nonvolatile memory applications, and energy harvesting. Imprint, the time-dependent resistance to polarization reversal, is a key material property that limits electronic applications and is poorly understood. In this work, we investigated the link between imprint and charge trap states within the film. A fast ramp rate thermally stimulated current (FR-TSC) measurement was developed to quantify and characterize trapped charge dynamics in imprinted P(VDF-TrFE) thin films in an appropriate time frame. Thin films of P(VDF-TrFE) on oxidized Si substrates were characterized following controlled initialization, polarization, and imprint. Trap states were thermally filled/emptied by temperature cycling between 20 °C and 100 °C using heating and cooling rates of 1 K/s. Dynamics of this fast-ramp TSC indicate the presence of not only trap states but also reversible and irreversible charge accumulation. Results also show an asymmetry with respect to poling orientation, indicating that traps are influenced by processing conditions and contact materials. The development of this FR-TSC technique provides understanding of polarization dynamics and material interactions affecting ferroelectric properties of P(VDF-TrFE). [ABSTRACT FROM AUTHOR]

Submerged nearshore structure designs are commonly tested and optimised in scale model wave basins prior to construction in the field. Depending on the purpose of the structure, different measurement methods are used. In this paper, a camera-based measurement method called Wave Peel Tracking (WPT) was adapted and evaluated for quantifying wave breaking over submerged structures purposed for surf amenity. The WPT algorithm was successfully applied to the wave basin through controlled artificial lighting at night, precise image rectification, and modification to a classifier model. The WPT results were verified using overhead footage and had similar accuracy to the WPT algorithm previously applied in the field (Thompson et al., 2021a). Results from wave basin testing of two rock reef structures and three sand mound structures are presented for both regular and irregular waves and were analysed to show the effectiveness of the WPT algorithm in quantifying surf amenity for informing design optimisation. The algorithm applied to the wave basin is open-source, enabling further use and adoption by other laboratories. • Open-source software tracks surfable rides in a wave basin. • 2 rock reef and 3 sand mound physical models were assessed for surf amenity. • WPT results revealed how surf amenity was created in different ways. [ABSTRACT FROM AUTHOR]

Submerged nearshore structure designs are commonly tested and optimised in scale model wave basins prior to construction in the field. Depending on the purpose of the structure, different measurement methods are used. In this paper, a camera-based measurement method called Wave Peel Tracking (WPT) was adapted and evaluated for quantifying wave breaking over submerged structures purposed for surf amenity. The WPT algorithm was successfully applied to the wave basin through controlled artificial lighting at night, precise image rectification, and modification to a classifier model. The WPT results were verified using overhead footage and had similar accuracy to the WPT algorithm previously applied in the field (Thompson et al., 2021a). Results from wave basin testing of two rock reef structures and three sand mound structures are presented for both regular and irregular waves and were analysed to show the effectiveness of the WPT algorithm in quantifying surf amenity for informing design optimisation. The algorithm applied to the wave basin is open-source, enabling further use and adoption by other laboratories. • Open-source software tracks surfable rides in a wave basin. • 2 rock reef and 3 sand mound physical models were assessed for surf amenity. • WPT results revealed how surf amenity was created in different ways. [ABSTRACT FROM AUTHOR]

The exchange of a tracer material, e.g., a radioactive isotope, between two samples forming a diffusion couple depends on the rate of the diffusion of the tracer in each of the two samples and also on the rate of the transfer of the tracer across the interface between these samples which may or may not contain a barrier layer with a different chemical composition and/or structure. Diffusion couples with three different initial tracer distributions are considered. In order to extract from experimental data values for tracer diffusion coefficients and for the rate constant for the tracer transport across the interface, a detailed analysis of the required mathematics is given. This analysis is of interest as well for obtaining true values for bulk diffusivities and also to characterize quantitatively the resistance of interfaces (=barriers) to the exchange of certain species. Some examples of experimental results are presented and briefly discussed. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Women diagnosed with late-stage ovarian cancer suffer a very high rate of mortality. Accordingly, it is imperative to detect and diagnose the disease as early as possible in its development. Achievement of this aim implies relatively large scale screening of women at an age of clinically significance through assay of biomarkers for disease present in blood or serum. Biosensor detection offers an attractive technology for the automated detection of such species. Among several biomarkers that have been identified that are present in patients with ovarian cancer, the only one that is commonly tested for in clinical use is cancer antigen 125, which is considered to be poor biomarker for the disease. Here, we describe alternative biomarkers which overcome many of the problems associated with cancer antigen 125 such as increased sensitivity and specificity especially in the early stages of the disease and which could be employed successfully in a biosensor format. In particular, we discuss the chemistry of probes for the biomarkers, heat shock protein 10 and lysophosphatidic acid. The challenges presented by the fabrication of biosensor devices for the detection of the cancer, and the limited number of biosensors that have been developed for this purpose are discussed. • Ovarian cancer has the highest fatality-to-case ratio of all gynecological cancers. • CA125 acts as a poor biomarker for screening and diagnosis. • Lysophosphatidic acid and HSP10 are promising biomarkers for the cancer. • There have been few advances in biosensing related to ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Thirty-day readmission penalties implemented with the Hospital Readmission Reduction Program (HRRP) place a larger burden on safety-net hospitals which treat a disproportionate share of racial minorities, leading to concerns that already large racial disparities in readmissions could widen.Objective: To examine whether there were changes in Black-White disparities in 30-day readmissions for acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia following the passage and implementation of HRRP, and to compare disparities across safety-net and non-safety-net hospitals.Design: Repeated cross-sectional analysis, stratified by safety-net status.Subjects: 1,745,686 Medicare patients over 65 discharged alive from hospitals in 5 US states: NY, FL, NE, WA, and AR.Main Measures: Odds ratios comparing 30-day readmission rates following an index admission for AMI, CHF, or pneumonia for Black and White patients between 2007 and 2014.Key Results: Prior to the passage of HRRP in 2010, Black and White readmission rates and disparities in readmissions were decreasing. These reductions were largest at safety-net hospitals. In 2007, Blacks had 13% higher odds of readmission if treated in safety-net hospitals, compared with 5% higher odds in 2010 (P < 0.05). These trends continued following the passage of HRRP.Conclusions: Prior to HRRP, there were large reductions in Black-White disparities in readmissions at safety-net hospitals. Although HRRP tends to assess higher penalties for safety-net hospitals, improvements in readmissions have not reversed following the implementation of HRRP. In contrast, disparities continue to persist at non-safety-net hospitals which face much lower penalties. [ABSTRACT FROM AUTHOR]

Early posttrauma hyperglycemia (EPTH) is correlated with later adverse outcomes, including acute kidney injury (AKI). Controlling EPTH in the prehospital setting is difficult because of the variability in the ideal insulin dosage and the potential risk of hypoglycemia, especially in those with confounding medical comorbidities of obesity and insulin resistance. Glucagon-like peptide-1 (GLP-1) controls glucose levels in a glucose-dependent manner and is a current target in antidiabetic therapy. We have shown that after orthopedic trauma, obese Zucker rats exhibit EPTH and a later development of AKI (within 24 h). We hypothesized that GLP-1 treatment after trauma decreases EPTH and protects renal function in obese Zucker rats. Obese Zucker rats (~12 wk old) were fasted for 4 h before trauma. Soft tissue injury, fibula fracture, and homogenized bone component injection were then performed in both hind limbs to induce severe extremity trauma. Plasma glucose levels were measured before and 15, 30, 60, 120, 180, 240, and 300 min after trauma. GLP-1 (3 µg⋅kg-1h-1, 1.5 ml/kg total) or saline was continuously infused from 30 min to 5 h after trauma. Afterwards, rats were placed in metabolic cages overnight for urine collection. The following day, plasma interleukin (IL)-6 levels, renal blood flow (RBF), glomerular filtration rate (GFR), and renal oxygen delivery (Do2) and consumption (...o2) were measured. EPTH was evident within 15 min after trauma but was significantly ameliorated during the 5 h of GLP-1 infusion. One day after trauma, plasma IL-6 was markedly increased in the trauma group and decreased in GLP-1-treated animals. RBF, GFR, and Do2 all significantly decreased with trauma, but renal ...o2 was unchanged. GLP-1 treatment normalized RBF, GFR, and Do2 without affecting ...o2. These results suggest that GLP-1 decreases EPTH and protects against a later development of AKI. Early treatment with GLP-1 (or its analogs) to rapidly, effectively, and safely control EPTH may be beneficial in the prehospital care of obese patients after trauma. [ABSTRACT FROM AUTHOR]

Why is postnatal parental provisioning so rare in ectothermic vertebrates while prolonged parental care is almost ubiquitous in endotherms? We argue that the scarcity of postnatal parental care is a result of ectothermy itself. While almost all endothermic young require prolonged postnatal care due to thermal constraints, ectothermic physiology does not pose the same constraint. Most ectothermic young are thus independent from birth. Ectothermic mothers are better off investing in future reprod [ABSTRACT FROM AUTHOR]

Atmospheric carbon dioxide conditions predicted for future climates cause increases in wheat biomass, but also decreases wheat grain protein concentration. We investigated the response of grain protein concentration of wheat to elevated carbon dioxide in nineteen wheat genotypes, including five tetraploid, eleven hexaploid and three synthetic hexaploid genotypes to test whether decreased grain protein is genotype dependent and whether it is caused by biomass dilution. These were grown in ambient and elevated carbon dioxide conditions simultaneously. Shoot biomass and grain samples were taken at maturity. The grain protein concentration, grain biomass, shoot biomass and harvest index were analysed for each genotype. Despite most genotypes increasing in total grain protein (g), the majority of genotypes decreased in grain protein concentration (%) under elevated carbon dioxide. Elevated carbon dioxide caused an increase in grain biomass for all genotypes and total shoot biomass for most genotypes, with harvest index increasing for all genotypes except the two synthetic hexaploids CPI133814 and CPI133811. Most of the differences between wheat types were not statistically significant, suggesting that the individual genotype of wheat plants determines the response to elevated carbon dioxide rather than the wheat type. • Genotype is a greater determining factor for grain protein concentration decline under elevated CO 2 than wheat type. • Most genotypes declined in grain protein concentration under elevated CO 2 , while increasing in total grain protein. • Elevated CO 2 leads to a different response of harvest index between tetraploid and synthetic hexaploid genotypes. • Biomass dilution is not the sole cause of grain protein concentration decline under elevated CO 2 in wheat. [ABSTRACT FROM AUTHOR]

Studies show maternal obesity is a risk factor for metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in offspring. Here we evaluated potential mechanisms underlying these phenotypes. Female C57Bl6 mice were fed chow or an obesogenic high-fat/high-sucrose (HF/HS) diet with subsequent mating of F1 and F2 female offspring to lean males to develop F2 and F3 generations, respectively. Offspring were fed chow or fibrogenic (high transfat, cholesterol, fructose) diets, and histopathological, metabolic changes, and bile acid (BA) homeostasis was evaluated. Chow-fed F1 offspring from maternal HF/HS lineages (HF/HS) developed periportal fibrosis and inflammation with aging, without differences in hepatic steatosis but increased BA pool size and shifts in BA composition. F1, but not F2 or F3, offspring from HF/HS showed increased steatosis on a fibrogenic diet, yet inflammation and fibrosis were paradoxically decreased in F1 offspring, a trend continued in F2 and F3 offspring. HF/HS feeding leads to increased periportal fibrosis and inflammation in chow-fed offspring without increased hepatic steatosis. By contrast, fibrogenic diet-fed F1 offspring from HF/HS dams exhibited worse hepatic steatosis but decreased inflammation and fibrosis. These findings highlight complex adaptations in NAFLD phenotypes with maternal diet. [ABSTRACT FROM AUTHOR]

Summary: Objective: Literature concerning the impact of multiple endocrine neoplasia type 1 (MEN 1) on fertility is limited to case reports despite the early onset of endocrinopathies, such as primary hyperparathyroidism and prolactinoma, that may impact fertility. This study describes the impact of unrecognized and untreated MEN 1 on fertility and pregnancy outcomes in a multigenerational cohort of the Tasman 1 MEN 1 kindred. Methods: All MEN 1 positive (MEN 1+, n = 63) and MEN 1 negative (MEN 1−, n = 75) descendants born between 1825 and 1951 of a common founder. Review of birth, death, marriage and medical records provided data on date of birth and death, gender, MEN 1 status and the number of pregnancies and children per parent. Results: Compared to MEN 1− parents, MEN 1+ parents had more children (RR 1.30, 1.02‐1.66) and live births (RR 1.31, 1.02‐1.67) with no excess of stillbirths (RR 1.24, 0.24‐6.36). Compared to the era‐matched Tasmanian fertility rate, MEN 1+ parents had more children (4.87 ± 4.11 vs 3.40 ± 0.61, P = 0.048), whereas MEN 1− parents had similar numbers of children (3.67 ± 3.27 vs 3.36 ± 0.62, P = 0.55). MEN 1+ parents had a similar number of MEN 1+ and MEN 1− offspring (2.1 ± 1.9 vs 2.5 ± 2.3, P = 0.31). Indirectly assessed miscarriage rate was similar between MEN 1+ and MEN 1− mothers (P = 0.77). Clinically overt pituitary disease reduced MEN 1+ kindred member likelihood of parenthood (33% vs 97%). Conclusions: There was no adverse impact of MEN 1 on patient fertility overall; however, MEN 1‐related pathology may have impaired the reproductive potential of a subset of individuals with pituitary disease. [ABSTRACT FROM AUTHOR]

This article argues that the dynamics behind the generation of social pathologies in modern society also undermine the social-relational framework for recognition. It therefore claims that the theory of recognition is impotent in face of the kinds of normative power exerted by social hierarchies. The article begins by discussing the particular forms of social pathology and their relation to hierarchical forms of social structure that are based on domination, control and subordination and then shows how the internalization of the norms that shape and hold together hierarchical social formations causes pathologies within the self. As a result of these processes, the recognitive aspects of social action that the theory of recognition posits are unable to overcome and in fact reproduce and in many instances reinforce the pathologies themselves. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated an effect of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), on airway contractility [via increased airway smooth muscle (ASM) intracellular calcium [Ca2+]i] and remodeling (ASM proliferation and extracellular matrix formation) in the context of airway disease. In the present study, we examined the role of BDNF in allergen-induced airway inflammation using 2 transgenic models: 1) tropomyosin-related kinase B (TrkB) conditional knockin (TrkBKI) mice allowing for inducible, reversible disruption of BDNF receptor kinase activity by administration of 1NMPP1, a PP1 derivative, and 2) smooth muscle-specific BDNF knockout (BDNFfl/fl/SMMHC11Cre/0) mice. Adult mice were intranasally challenged with PBS or mixed allergen (Alternaria alternata, Aspergillus fumigatus, house dust mite, and ovalbumin) for 4 wk. Our data show that administration of 1NMPP1 in TrkBKI mice during the 4-wk allergen challenge blunted airway hyperresponsiveness (AHR) and reduced fibronectin mRNA expression in ASM layers but did not reduce inflammation per se. Smooth muscle-specific deletion of BDNF reduced AHR and blunted airway fibrosis but did not significantly alter airway inflammation. Together, our novel data indicate that TrkB signaling is a key modulator of AHR and that smooth muscle-derived BDNF mediates these effects during allergic airway inflammation. [ABSTRACT FROM AUTHOR]

Corticosteroids (CSs) are commonly used to manage wheezing and asthma in pediatric populations. Although corticosteroids are effective in alleviating airway diseases, some children with more moderate-severe asthma phenotypes show CS resistance and exhibit significant airflow obstruction, persistent inflammation, and more frequent exacerbations. Previous studies have demonstrated that Th1 cytokines, such as TNF-γ and IFN-γ, promote CS resistance in adult human airway smooth muscle (ASM). In the present study, using a human fetal ASM cell model, we tested the hypothesis that TNF-γ/IFN-γ induces CS resistance. In contrast to TNF-β or IFN-γ alone, the combination of TNF-β/IFN-γ blunted the ability of fluticasone propionate (FP) to reduce expression of the chemokines CCL5 and CXCL10 despite expression of key anti-inflammatory glucocorticoid receptor target genes being largely unaffected by TNF-β/IFN-γ. Expression of the NF-B subunit p65 and phosphorylation of Stat1 were elevated in cells treated with TNF-β/IFN-γ, an effect that remained in the presence of FP. siRNA knockdown studies demonstrated the effects of TNF-β/IFN-γ on increased p65 are mediated by Stat1, a transcription factor activated by IFN-γ. Expression of TNFAIP3, a negative regulator of NF-B activity, was not altered by TNF-β/IFN-γ. However, the effects of TNF-β/IFN-γ were partially reduced by overexpression of TNFAIP3 but did not influence p65 expression. Together, these data suggest that IFN-γ augments the effects of TNF-β on chemokines by enhancing expression of key inflammatory pathways in the presence of CS. Interactions between TNF-β- and IFN-γ-mediated pathways may promote inflammation in asthmatic children resistant to CSs. [ABSTRACT FROM AUTHOR]