Search

What is the central question of this study? Exposure to chronic intermittent hypoxia (CIH) evokes redox changes, culminating in impaired upper airway muscle function: what is the specific source of CIH-induced reactive oxygen species? What is the main finding and its importance? Profound sternohyoid muscle dysfunction following exposure to CIH was entirely prevented by apocynin co-treatment or NADPH oxidase 2 (NOX2) deletion. The results have implications for human obstructive sleep apnoea syndrome and point to antioxidant intervention, potentially targeting NOX2 blockade, as a therapeutic strategy.Exposure to chronic intermittent hypoxia (CIH) evokes redox changes, culminating in impaired upper airway muscle function. We sought to determine if NADPH oxidase 2 (NOX2)-derived reactive oxygen species underpin CIH-induced maladaptive changes in upper airway (sternohyoid) muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); CIH-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) given in the drinking water throughout exposure to CIH. In addition, we studied sham and CIH-exposed NOX2-null mice (B6.129S-CybbTM

A mild and inexpensive method for direct hydrodecarboxylation of aliphatic carboxylic acids has been developed. The reaction does not require metals, light, or catalysts, rendering the protocol operationally simple, easy to scale, and more sustainable. Crucially, no additional H atom source is required in most cases, while a broad substrate scope and functional group tolerance are observed.

In humans, the ability to discriminate object features and location decreases around the onset of saccades, a phenomenon usually referred to as ‘saccadic suppression’. The underlying mechanism of suppression remains elusive, however recent evidence suggests a retinal origin of this phenomenon, following strong disruption in visual flow even in the absence of eye-movements. Here we asked whether the explicit temporal control over a visual shift onset would modulate individual performance. Participants were asked to discriminate shapes presented around the onset of saccades, self-induced (active) visual shifts, and spontaneous (passive) visual shifts. As predicted from previous reports, we observed a decrease in discrimination accuracy around the onset of both saccades and passive shifts. We report stronger suppression during saccades compared to shifts, as well as no significant difference between self-induced and spontaneous shifts. We discuss our findings in relation to current literature, suggesting further studies aimed contributions to suppression of peri-saccadic motion as well as retinal contributions to suppression.

Demands for energy storage and delivery continue to rise worldwide, making it imperative that reliable performance is achievable in diverse climates. Lithium-sulfur (Li-S) batteries offer a promising alternative to lithium-ion batteries owing to their substantially higher specific capacity and energy density. However, improvements to Li-S systems are still needed in low-temperature environments where polysulfide clustering and solubility limitations prohibit complete charge/discharge cycles. We address these issues by introducing thiophosphate-functionalized metal-organic frameworks (MOFs), capable of tethering polysulfides, into the cathode architecture. Compared to cells with the parent MOFs, cells containing the functionalized MOFs exhibit greater capacity delivery and decreased polarization for a range of temperatures down to -10 °C. We conduct thorough electrochemical analyses to ascertain the origins of performance differences and report an altered Li-S redox mechanism enabled by the thiophosphate moiety. This investigation is the first low-temperature Li-S study using MOF additives and represents a promising direction in enabling energy storage in extreme environments.

Lithium–sulfur (Li–S) batteries have great potential as next generation energy storage devices. However, the redox chemistry mechanism involves the generation of solubilized lithium polysulfides, which can lead to leaching of the active material and, consequently, passivated electrodes and diminished capacities. Chemical tethering of lithium polysulfides to materials in the sulfur cathode is a promising approach for resolving this issue in Li–S batteries. Borrowing from the field of synthetic chemistry, we utilize maleimide functional groups in a Zr-based metal–organic framework to chemically interact with polysulfides through the Michael Addition reaction. A combination of molecular and solid-state spectroscopies confirms covalent attachment of Li2Sx to the maleimide functionality. When integrated into Li–S cathodes, the maleimide-functionalized framework exhibits notable performance enhancements over that of the unfunctionalized material, revealing the promise of polysulfide anchors for Li–S battery cycling.

Knowledge for clinical social work practice is ever evolving and consists of underlying explanatory concepts, practice models, and intervention skills. Conceptualization and identification of competencies for practice provides a bridge from knowledge and understanding to actual skills needed in clinical sessions. Articulating competencies also guides education of students and provides grounded skills and behaviors needed for clinical research. Analysis of simulation-based practice provides a useful methodology to identify generic practice competencies as well as competencies in specialized fields of practice. This paper presents a simulation education model and illustrates how the use of simulation enabled clinical scholars to articulate core competencies in specialized areas of social work practice. Case examples and related competencies for practice with adolescents, victims of elder abuse, and in mental health practice will demonstrate this process. Examples are drawn from reflections on practice wisdom, analysis of experienced social work practitioners, and relevant literature. Resulting competencies contribute to scholarship for clinical practice.

The viability of philosophy of education as a distinct and valued field of inquiry in educational research is under significant threat. While the debate over the proper role and value of philosophy of education continues, courses and faculty positions in philosophy of education become increasingly rare. I advance the view that this situation requires philosophers of education find new ways to bring their work to practicing educators. I propose a particular kind of normative analysis, within the context of moral education, as one way to bring valuable philosophic work to the daily practice of teaching. It is argued that the use of normative criteria, comprised of certain key characteristics for moral education, can serve not only as valuable analytic tools but may also draw practicing educators into conversations that generally take place between philosophers of education in the academy.

In his 1993 book, Hare asks “What Makes a Good Teacher?” In this paper we ask, “What makes a good education researcher?” We begin our discussion with Richard Rudner's classic 1953 essay, The Scientist Qua Scientist Makes Value Judgments, which confronted science with the internal subjectivity it had long ignored. Rudner's bold claim that scientists do make value judgments as scientists called attention to the very foundations of scientific conduct. In an era of institutional research ethics, like the Tri-Council’s ethics policy, Rudner's call for an approach to these value judgments is even more relevant. The contemporary education researcher primarily engages with ethics procedurally, which provides a certain level of consistency and objectivity. This approach has its roots in principle-based theories of ethics that have long been dominant in Western universities. We argue that calls, like Rudner's, for an objective science of ethics, are at the root of this dominant institutional approach. This paper critiques the suitability of such principle-based ethics for solving Rudner's concerns, and posits that educational research ethics is better understood as a matter of character and virtue. We argue that, much like the ethical teacher, the ethical education researcher is a certain kind of person.

As a subject for philosophizing about education, there are few topics as rich and significant as the role of public schools in fostering respect for sexual and religious diversity. The liberal state, it is said, has a clear mission to teach students to respect the rights of others to lead fundamentally different ways of life, and to provide students with the tools needed to make similarly fundamental choices about their own lives. The liberal state must do this, however, without undue or excessive infringement on the rights of children and parents who believe that some common ways of life are, writ large, morally objectionable. This symposium paper features three arguments, each formulated by a different student in education or a related field. The first argues that LGBTQ role models must be provided in schools (through school resources or in person). The second argues that teachers are being placed in a very difficult position when such provision causes controversy with the surrounding community. The third argues that parents must not be given unchecked power over their children’s exposure to LGBTQ role modeling.

Gold-catalyzed hydroarylation of unactivated alkynes with indoles have previously been reported to proceed with double indole addition to produce symmetrical bis(indolyl)methanes (BIMs). We demonstrate for the first time that the selectivity of the gold-catalyzed reaction can be fully switched to allow for isolation of the vinylindole products instead. Furthermore, this selective reaction can be utilized to synthesize the more difficult to access unsymmetrical BIMs from readily available starting materials.

In an age of rapid acceleration toward next-generation energy storage technologies, lithium-sulfur (Li-S) batteries offer the desirable combination of low weight and high specific energy. Metal-organic frameworks (MOFs) have been recently studied as functionalizable platforms to improve Li-S battery performance. However, many MOF-enabled Li-S technologies are hindered by low capacity retention and poor long-term performance due to low electronic conductivity. In this work, we combine the advantages of a Zr-based MOF-808 loaded with sulfur as the active material with a graphene/ethyl cellulose additive, leading to a high-density nanocomposite electrode requiring minimal carbon. Our electrochemical results indicate that the nanocomposites deliver enhanced specific capacity over conventionally used carbon/binder mixtures, and postsynthetic modification of the MOF with lithium thiophosphate results in further improvement. Furthermore, the dense form factor of the sulfur-loaded MOF-graphene nanocomposite electrodes provides high volumetric capacity compared to other works with significantly more carbon additives. Overall, we have demonstrated a proof-of-concept paradigm where graphene nanosheets facilitate improved charge transport because of enhanced interfacial contact with the active material. This materials engineering approach can likely be extended to other MOF systems, contributing to an emerging class of two-dimensional nanomaterial-enabled Li-S batteries.

Background Glenoid implant positioning is an important and challenging step in total shoulder arthroplasty. Accurate glenoid positioning is considered essential to prosthesis longevity and functional outcomes. This paper presents Bullseye, a novel system to ensure accurate glenoid guide pin placement using a hand-held structured light scanner and computer vision algorithms. Methods Preclinical evaluation of the intra-operative structured light-based Bullseye system was conducted for 10 sawbone and 18 cadaveric procedures. Each scapula was instrumented with a 3.2 mm glenoid guide pin. The Bullseye system was used to determine the position of the guide pin within the scapulae. The accuracy of Bullseye for assessing guide pin start-point and trajectory was validated using CT as a gold standard. Results All procedures were carried out successfully, requiring less than 1 min of intra-operative imaging time. Guide pin start-point was measured to within 0.37±0.28 mm and 0.38±0.32 mm and trajectory to within 0.92±0.40° and 1.27±0.80°, respectively for the sawbone and cadaveric procedures. There was no significant difference in accuracy between the sawbone and cadaveric procedures. No relationships were found between system accuracy and glenoid version or arthritic grade. Conclusion Intra-operative structured light imaging can be used to efficiently and accurately evaluate the 3D position of the glenoid guide pin for total shoulder arthroplasty in-vitro and ex-vivo. Clinical validation is required to determine if use of the Bullseye system improves component positioning outcomes and patient clinical outcomes in the context of a randomized controlled trial. Level of evidence Level IV; Case Series

Summary Background Long-acting injectable cabotegravir is a novel integrase inhibitor currently in advanced clinical development for HIV prevention and treatment. We aimed to assess the terminal phase pharmacokinetics and safety of long-acting injectable cabotegravir in participants included in the HPTN 077 trial. Methods HPTN 077 was a multicentre, double-blind, randomised, placebo-controlled phase 2a trial done at eight sites in Brazil, Malawi, South Africa, and the USA. Participants (aged 18–65 years), who were HIV-uninfected and at low-risk for HIV, were randomly assigned (3:1) to long-acting injectable cabotegravir (800 mg given three times at 12 week intervals or 600 mg given five times, administered at one 4 week interval, and every 8 weeks thereafter) or placebo. Participants were followed up to 76 weeks after final injection. In a prespecified analysis of secondary and exploratory outcomes, we assessed the safety, measured by the proportion of participants with grade 2 or worse adverse events, and pharmacokinetics, measured by apparent terminal phase half-life (t1/2app) and estimated time to lower limit of quantification (LLOQ) of long-acting injectable cabotegravir during the injection phase (defined as the time between first injection and 12 weeks or 8 weeks after the last injection in cohort 1 or cohort 2 respectively) and tail phase (defined as the time between final injection and 52–76 weeks post-final injection). Safety was analysed in all participants who received at least one injection. Pharmacokinetic analyses included all participants who had received at least one injection and had at least three cabotegravir measurements higher than the LLOQ after the final injection. Pharmacokinetic outcomes were estimated using non-compartmental methods. The trial is completed, and was registered with ClinicalTrials.gov , NCT02178800 . Findings Between Feb 9, 2015, and May 27, 2016, 177 participants (134 participants in the cabotegravir group [74 participants in cohort 1; 60 participants in cohort 2] and 43 participants in the placebo group [25 participants in cohort 1; 18 participants in cohort 2) were enrolled and received at least one injection and thus were included in the safety analysis. The incidence of grade 2 or worse adverse events was significantly lower during the tail phase than the injection phase (p Interpretation The clinical significance of the long pharmacokinetic tail of cabotegravir observed in female participants compared with male participants, and those with higher BMI compared with a lower BMI, need to be addressed in future trials. Funding National Institute of Allergy and Infectious Diseases.

Though students can learn a great deal about ethics as they play sport, the authors of this article ask what, exactly, they learn from playing dodgeball. As they look beyond the usual arguments offered for and against the teaching of the game, they view it through three ethical lenses: the ethic of care, the ethic of anti-oppressive education, and the ethics of virtue. They conclude that in terms of modelling, confirming, and practising caring behaviours, or offering opportunities to discuss and process what might be considered fair, dodgeball can be considered miseducative. They further argue that the hidden curriculum of dodgeball reinforces the five faces of oppression defined by the feminist theorist Iris Young as marginalization, powerlessness, and the helplessness of those perceived as weaker individuals through the exercise of violence and dominance by those who are considered more powerful. They conclude that the playing of dodgeball habituates the practice of aggression and fails to contribute positively to an ethical education.