Exploring the Use of Trauma Informed Practices in Campus as Lab Programs: Learnings from a Workshop Series

With the intersectional challenges of the climate crisis, the COVID-19 pandemic, and mental health challenges in various forms, empowerment can hold a significant key to mitigating and preventing traumatic experiences at post-secondary institutions. Campus as Lab (CaL) is a growing trend in higher education whereby students, faculty, and staff use experiential learning and applied research projects to advance sustainability on their campuses. It is a unique, empowering learning methodology that can synergistically benefit academic and operational sustainability efforts at post-secondary institutions. In July 2021, a group of professionals who support or lead CaL initiatives gathered to participate in four Summer Series webinars to explore the use of trauma informed practices in CaL programs. This paper provides a high-level overview of the Summer Series webinar structure and explores how participants identified opportunities to use a trauma informed framework for future CaL initiatives. Because of the Summer Series webinars, we believe there is a need for greater familiarity of trauma informed practices on campuses and amongst sustainability staff. Future research could explore the broader application of trauma informed approaches in the various fields of sustainability within post-secondary institutions

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Standardising the elusive diagnosis of NEC in the premature infant - A practical score

Objective The perceived risk of necrotising enterocolitis (NEC) can result in overtreatment of the otherwise adapting preterm neonate. We aim to develop an assessment tool to aid the decision making in the management of preterm neonates at risk of NEC. Method An evidence-based assessment tool was designed bringing together clinical, laboratory and radiological signs commonly associated with NEC. A numerical score was awarded for each sign, with those more specific to NEC being graded higher. A multi-centre validation was conducted of the proposed assessment tool over three tertiary neonatal units. Results A total of 125 patients were included, 53 (42.4 %) with a final diagnosis of NEC and 72 (57.6 %) with an alternative diagnosis. The NEC group had a significantly higher total score compared to the non-NEC group; 15(2–28) vs. 4(1–9) (p ≤ 0.0001). In ROC analysis, using a cut-off of eight, the assessment tool gave a sensitivity of 92.3 % and a specificity of 90.4 % for identifying NEC compared to an alternative diagnosis. Conclusion This comprehensive scoring system encourages a full assessment of the infant before deciding on withholding feeds, starting antibiotics, and transferring to a surgical centre. It is a safe objective measure to support a diagnosis of NEC in the presence of certain clinical signs

A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential.

The synthesis and SAR of 5-heterocycle-substituted aminothiazole adenosine receptor antagonists is described. Several compounds show high affinity and selectivity for the A2B and A3 receptors. One compound (5f) shows good ADME properties in the rat and as such may be an important new compound in testing the current hypotheses proposing a therapeutic role for a dual A2B/A3 antagonist in allergic diseases

The Discovery And Optimisation of 4-(8-(3-Fluorophenyl)-1,7-naphthyridin-6-yl)cyclohexanecarboxylic acid, An Improved PDE4 Inhibitor For The Treatment of COPD.

Herein we describe the optimisation of a series of PDE4 inhibitors, with special focus on solubility and pharamcokinetics, to clinical compound 2, 4-(8-(3-fluorophenyl)-1,7-naphthyridin-6-yl)cyclohexanecarboxylic acid. Compound 2 was found to have exemplary pharmacokinetics in humans, which enabled a novel dosing regime and the achievement of high plasma drug levels without associated nausea or emesis

Solubility-Driven Optimisation of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate

The solubility-driven optimisation of a series of 1,7-napthyridine phosphodiesterase 4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties, with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesised. Compound 2d was taken forward as a clinical candidate for the treatment of COPD

The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1- hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project. © 2014 Elsevier Ltd. All rights reserved

The Identification of Indacaterol as an Ultra-Long-Acting Inhaled Beta-2-Adrenoceptor Agonist

Following a lipophilicity-based hypothesis, a series of 2-aminoindan and 8-hydroxyquinolinone derived 2-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultra-long-acting bronchodilators. Determination of their activities at the human 2-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference 2-adrenoceptor agonists. Further assessment with an in vitro super-fused electrically-stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses which could be rationalised by considering the lipophilicity, potency and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung which led to the compound being selected as a development candidate