Trypanocidal and leishmanicidal activity of six limonoids

Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1–4 displayed anti-leishmanial activity. The 50% growth inhibition (GI 50) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI 50 values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI 50 values of 100 μM and 31.5–46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI 50 value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis

HERA bound on X-ray luminosity weakens when accounting for Population III stars

Recent upper bounds from the Hydrogen Epoch of Reionization Array (HERA) on the cosmological 21-cm power spectrum at redshifts $z \approx 8, 10$, have been used to constrain $L_{\rm X<2 \, keV}/{\rm SFR}$, the soft-band X-ray luminosity measured per unit star formation rate (SFR), strongly disfavoring values lower than $\approx 10^{39.5} \, {\rm erg} \;{\rm s}^{-1} \;{\rm M}_{\odot}^{-1} \;{\rm yr}$ . In this work, we first reproduce the bounds on $L_{\rm X<2 \, keV}/{\rm SFR}$ and other parameters using a pipeline that combines machine learning emulators for the power spectra and the intergalactic medium characteristics, together with a standard Markov chain Monte Carlo parameter fit. We then use this approach when including molecular cooling galaxies that host PopIII stars in the cosmic dawn 21-cm signal, and show that lower values of $L_{\rm X<2 \, keV}/{\rm SFR}$ are hence no longer strongly disfavored. The revised HERA bound does not require high-redshift X-ray sources to be significantly more luminous than high-mass X-ray binaries observed at low redshift.Comment: 20 pages, 13 figures, 2 table

Addressing Corporate Ties to Slavery: Corporate Apologia in a Discourse of Reconciliation

Pressured by activists to take responsibility, American corporations recently found themselves in the spotlight for their past ties to slavery. Responding to the issue, they stepped into a complex discourse of reconciliation. Taking a rhetorical approach, this article analyzes the response of Aetna Inc. It explores how corporate rhetoric functions within present discourses about historical injustices and illustrates that Aetna\u27s response informed by common strategies of corporate apologia inhibited meaningful reconciliation. The article thus furthers criticisms of (corporate) apologia in the context of historical injustice and raises questions about the potentialities and limitations of corporate rhetoric for reconciliation

A new lightning scheme in the Canadian Atmospheric Model (CanAM5.1): implementation, evaluation, and projections of lightning and fire in future climates

Lightning is an important atmospheric process for generating reactive nitrogen, resulting in the production of tropospheric ozone, as well as igniting wildland fires, which result in potentially large emissions of many pollutants and short-lived climate forcers. Lightning is also expected to change in frequency and location with the changing climate. As such, lightning is an important component of Earth system models. Until now, the Canadian Earth System Model (CanESM) did not contain an interactive-lightning parameterization. The fire parameterization in CanESM5.1 was designed to use prescribed monthly climatological lightning. In this study, we have added a logistical regression lightning model that predicts lightning occurrence interactively based on three environmental variables and their interactions in CanESM5.1's atmospheric model, CanAM5.1 (Canadian Atmospheric Model), creating the capacity to interactively model lightning, allowing for future projections under different climate scenarios. The modelled lightning and resulting burned area were evaluated against satellite measurements over the historical period, and model biases were found to be acceptable. Modelled lightning had a small negative bias and excellent land–ocean ratio compared to satellite measurements. The modified version of CanESM5.1 was used to simulate two future climate scenarios (SSP2-4.5 and SSP5-8.5; Shared Socioeconomic Pathway) to assess how lightning and burned area change in the future. Under the higher-emissions scenario (SSP5-8.5), CanESM5.1 predicts almost no change to the global mean lightning flash rate by the end of the century (2081–2100 vs. 2015–2035 average). However, there are substantial regional changes to lightning – particularly over land – such as a mean increase of 6 % in the northern mid-latitudes and decrease of −8 % in the tropics. By the century's end, the change in global total burned area with prescribed climatological lightning was about 2 times greater than that with interactive lightning (42 % vs. 26 % increase, respectively). Conversely, in the northern mid-latitudes the use of interactive lightning resulted in 3 times more burned area compared to that with unchanging lightning (48 % vs. 16 % increase, respectively). These results show that the future changes to burned area are greatly dependent on a model's lightning scheme, both spatially and overall.</p

Organizational and Supervisory Apology Effectiveness: Apology Giving in Work Settings

We synthesize the interdisciplinary literature into a heuristic for crafting effective organizational and supervisory apologies (the OOPS four-component apology). In the first experiment, we demonstrate how an offense committed by an organization is perceived to be more egregious than an offense committed by a friend or supervisor. Furthermore, results did not support that OOPS apologies are unequally effective if issued by a friend, supervisor, or organization. In the second experiment, we test OOPS apology-training effectiveness. Results indicated that trained participants crafted more effective apologies. Our apology heuristic is an innovation for training business communicators how to apologize effectively.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Settler state apologies and the elusiveness of forgiveness : The purification ritual that does not purify

Peer reviewedPostprin

Life satisfaction and resilience in medical school – a six-year longitudinal, nationwide and comparative study

BACKGROUND: This study examined the relationship between life satisfaction among medical students and a basic model of personality, stress and coping. Previous studies have shown relatively high levels of distress, such as symptoms of depression and suicidal thoughts in medical undergraduates. However despite the increased focus on positive psychological health and well-being during the past decades, only a few studies have focused on life satisfaction and coping in medical students. This is the first longitudinal study which has identified predictors of sustained high levels of life satisfaction among medical students. METHODS: This longitudinal, nationwide questionnaire study examined the course of life satisfaction during medical school, compared the level of satisfaction of medical students with that of other university students, and identified resilience factors. T-tests were used to compare means of life satisfaction between and within the population groups. K-means cluster analyses were applied to identify subgroups among the medical students. Analysis of Variance (ANOVA) and logistic regression analyses were used to compare the subgroups. RESULTS: Life satisfaction decreased during medical school. Medical students were as satisfied as other students in the first year of study, but reported less satisfaction in their graduation year. Medical students who sustained high levels of life satisfaction perceived medical school as interfering less with their social and personal life, and were less likely to use emotion focused coping, such as wishful thinking, than their peers. CONCLUSION: Medical schools should encourage students to spend adequate time on their social and personal lives and emphasise the importance of health-promoting coping strategies

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for genetic disease diagnosis and acute management guidance. Diagnosis is achieved in 13.5 h by expedited whole genome sequencing, with superior analytic performance for structural and copy number variants. An expert panel adjudicated the indications, contraindications, efficacy, and evidence-of-efficacy of 9911 drug, device, dietary, and surgical interventions for 563 severe, childhood, genetic diseases. The 421 (75%) diseases and 1527 (15%) effective interventions retained are integrated with 13 genetic disease information resources and appended to diagnostic reports ( https://gtrx.radygenomiclab.com ). This system provided correct diagnoses in four retrospectively and two prospectively tested infants. The Genome-to-Treatment system facilitates optimal outcomes in children with rapidly progressive genetic diseases