Effects of particle-size ratio on jamming of binary mixtures

We perform a systematic numerical study of the effects of the particle-size ratio $R \ge 1$ on the properties of jammed binary mixtures. We find that changing $R$ does not qualitatively affect the critical scaling of the pressure and coordination number with the compression near the jamming transition, but the critical volume fraction at the jamming transition varies with $R$. Moreover, the static structure factor (density correlation) $S(k)$ strongly depends on $R$ and shows distinct long wave-length behaviors between large and small particles. Thus the previously reported behavior of $S(k)\sim k$ in the long wave-length limit is only a special case in the $R\to 1$ limit, and cannot be simply generalized to jammed systems with $R>1$.Comment: 5 pages and 4 figures, submitted to Soft Matter, special issue on Granular and Jammed Material

Is it Too Optimistic to Assume Light Touch Interventions can Improve Educational Workers’ Wellbeing? Insights from a Field Randomized Control Trial in Canada

Educator wellbeing has broad implications for students and schools. Current approaches to address this problem are generally resource-intensive. This trial used novel nudges to increase wellbeing and decrease burnout among educators and other school-based faculty. We designed a light touch intervention where T1 received evidence-based wellbeing weekly text messages and T2 received weekly messages plus leadership endorsement emails. We evaluated this intervention in a large-scale three-arm RCT with participants (n=1,155) from K-12 schools in Manitoba, Alberta, and British Columbia. When compared to the control group, we saw no significant difference between the control group and T1 and T2 groups on burnout or wellbeing. The failure of these evidence-based text messages in increasing educators’ wellbeing and reducing their burnout highlights both the difficulty of addressing this problem and the importance of learning lessons from trials with null results to contribute to our knowledge base of improving educators’ wellbeing

Pharmacokinetic investigation of dose proportionality with a 24-hour controlled-release formulation of hydromorphone

BACKGROUND: The purpose of this study was investigate the dose proportionality of a novel, once-daily, controlled-release formulation of hydromorphone that utilizes the OROS(® )Push-Pull™ osmotic pump technology. METHODS: In an open-label, four-way, crossover study, 32 healthy volunteers were randomized to receive a single dose of OROS(® )hydromorphone 8, 16, 32, and 64 mg, with a 7-day washout period between treatments. Opioid antagonism was provided by three or four doses of naltrexone 50 mg, given at 12-hour intervals pre- and post-OROS(® )hydromorphone dosing. Plasma samples for pharmacokinetic analysis were collected pre-dose and at regular intervals up to 48 hours post-dose (72 hours for the 64-mg dose), and were assayed for hydromorphone concentration to determine peak plasma concentration (C(max)), time at which peak plasma concentration was observed (T(max)), terminal half-life (t(1/2)), and area under the concentration-time curve for zero to time t (AUC(0-t)) and zero to infinity (AUC(0–∞)). An analysis of variance (ANOVA) model on untransformed and dose-normalized data for AUC(0-t), AUC(0–∞), and C(max )was used to establish dose linearity and proportionality. RESULTS: The study was completed by 31 of 32 subjects. Median T(max )(12.0–16.0 hours) and mean t(1/2 )(10.6–11.0 hours) were found to be independent of dose. Regression analyses of C(max), AUC(0–48), and AUC(0–∞ )by dose indicated that the relationship was linear (slope, P ≤ 0.05) and that the intercept did not differ significantly from zero (P > 0.05). Similar analyses with dose-normalized parameters also indicated that the slope did not differ significantly from zero (P > 0.05). CONCLUSION: The pharmacokinetics of OROS(® )hydromorphone are linear and dose proportional for the 8, 16, 32, and 64 mg doses. TRIAL REGISTRATION: Clinical Trials.gov NCT0039895

Functional Characterization and Evolution of the Isotuberculosinol Operon in Mycobacterium Tuberculosis and Related Mycobacteria

Terpenoid metabolites are important to the cellular function, structural integrity, and pathogenesis of the human-specific pathogen Mycobacterium tuberculosis (Mtb). Genetic and biochemical investigations have indicated a role for the diterpenoid isotuberculosinol (isoTb) early in the infection process. There are only two genes (Rv3377c and Rv3378c) required for production of isoTb, yet these are found in what appears to be a five-gene terpenoid/isoprenoid biosynthetic operon. Of the three remaining genes (Rv3379c, Rv3382c, and Rv3383c), previous work has indicated that Rv3379c is an inactive pseudo-gene. Here we demonstrate that Rv3382c and Rv3383c encode biochemically redundant machinery for isoprenoid metabolism, encoding a functional 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB) for isoprenoid precursor production and a geranylgeranyl diphosphate (GGPP) synthase, respectively, for which the Mtb genome contains other functional isozymes (Rv1110 and Rv0562, respectively). These results complete the characterization of the isoTb biosynthetic operon, as well as further elucidating isoprenoid metabolism in Mtb. In addition, we have investigated the evolutionary origin of this operon, revealing Mtb-specific conservation of the diterpene synthase genes responsible for isoTb biosynthesis, which supports our previously advanced hypothesis that isoTb acts as a human-specific pathogenic metabolite and is consistent with the human host specificity of Mtb. Intriguingly, our results revealed that many mycobacteria contain orthologs for both Rv3383c and Rv0562, suggesting a potentially important role for these functionally redundant GGPP synthases in the evolution of terpenoid/isoprenoid metabolism in the mycobacteria

Segmental Tracheal Resection in Advanced Thyroid Cancer Patients

https://openworks.mdanderson.org/sumexp22/1134/thumbnail.jp

Stochastic Variational Inference for Hidden Markov Models

Variational inference algorithms have proven successful for Bayesian analysis in large data settings, with recent advances using stochastic variational inference (SVI). However, such methods have largely been studied in independent or exchangeable data settings. We develop an SVI algorithm to learn the parameters of hidden Markov models (HMMs) in a time-dependent data setting. The challenge in applying stochastic optimization in this setting arises from dependencies in the chain, which must be broken to consider minibatches of observations. We propose an algorithm that harnesses the memory decay of the chain to adaptively bound errors arising from edge effects. We demonstrate the effectiveness of our algorithm on synthetic experiments and a large genomics dataset where a batch algorithm is computationally infeasible.Comment: Appears in Advances in Neural Information Processing Systems (NIPS), 201

Takin\u27 Care of Small Business: The Rise of Stakeholder Influence

In this Exchange, we consider three crucial boundary conditions that Barnett, Henriques, and Husted (2020) overlooked in their model of diminished stakeholder influence. Although we agree that social media platforms have weakened stakeholder influence in certain conditions, such is not the case for all firms, all stakeholders, or all situations. Drawing from socio-cognitive and self-determination theories, we contend that (a) independent, owner-managed small firms present a context wherein information overload is rendered less of an issue because the information about the firm is more salient to locals; (b) stakeholders can be motivated to influence firms via social media platforms, which facilitate the collective engagement of local community members; and (c) uncertain economic circumstances (e.g., COVID-19) activate stakeholder information searches, which often occur through social media. Together, these three conditions enhance stakeholder power and influence. We also contemplate how, even under these conditions, stakeholder influence may change over time vis-à-vis the issue–attention cycle and societalization. We conclude our Exchange with a call for more research on stakeholder influence over independent, owner-manager small businesses