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Acquired cardiomyopathies have been described in human patients with hypoadrenocorticism. Several mechanisms have been described to explain the cardiac effects of primary adrenal insufficiency, but, clinically, these manifestations may be underappreciated in dogs. In humans, there is an infrequently described, reversible dilated cardiomyopathy in patients with hypoadrenocorticism. Two dogs were presented to a single referral center for evaluation of weakness or collapse and were subsequently diagnosed with hypoadrenocorticism after a full diagnostic workup. Following the diagnosis of hypoadrenocorticism and administration of glucocorticoids and desoxycorticosterone pivalate, both dogs developed left-sided congestive heart failure and had systolic dysfunction diagnosed by echocardiogram. Both dogs were euthanized; one because of recurrent congestive heart failure and another because of a concern for poor long-term prognosis and decreased quality of life. The purpose of this case report is to document multiple cases of hypoadrenocorticism-associated systolic dysfunction and subsequent cardiogenic pulmonary edema in dogs.

Smoking remains the leading cause of preventable death in the United States, with 87% of smokers starting before the age of 18. Age of initiation is a major predictive factor for smoking frequency and successful smoking cessation. People who initiate smoking during adolescences are 2.33 times more likely to become heavy smokers and half as likely to quit compared with smokers who started during adulthood. Additionally, schizophrenia, a disease state linked to altered neurodevelopment during adolescence, is a major predictive factor for smoking status. Smoking rates among people suffering from schizophrenia are between 60% and 90%. Interestingly, the Neuregulin Signalling Pathway (NSP), which plays an important role in neurodevelopment, is implicated in both schizophrenia and nicotine use disorder. Specifically, SNPS in neuregulin 3 (Nrg3) and Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4) have been associated with smoking cessation outcomes and schizophrenia. Here, we examine the effects of chronic nicotine (18 mg/kg/day) and 24-h withdrawal on NSP gene expression in the hippocampus of adult (20-week-old) and adolescent (4-week-old) mice. We show that withdrawal from chronic nicotine decreased the expression of Erbb4 mRNA in the hippocampus of the adult mice but increased the expression of cytosolic Erbb4 protein in adolescent mice. Nrg3 mRNA and protein expression was not altered by chronic nicotine or withdrawal in the adult or adolescent cohorts, but Nrg3 mRNA and synaptosomal protein expression was lower in the adult withdrawal group when compared with their adolescent counterparts. These results highlight the age-specific effects of nicotine withdrawal on the NSP and may contribute to the lower quit rate and higher cigarette consumption of smokers who initiation during adolescences.

PurposeThis study centers the reflections of principals across the USA as they navigated the overwhelming stress of closing and reopening schools during a global pandemic. Specifically, the authors explored how school principals addressed self-care and their own well-being during the pandemic.Design/methodology/approachThis research study is part of a broader qualitative study conducted by 20 scholars from across the USA in Spring 2020 and organized by the Consortium for Policy Research in Education (CPRE). This national research team conducted 120 qualitative interviews with public school principals in 19 different states and 100 districts. As part of this team, the authors coded and analyzed all 120 transcripts in NVivo using a self-care framework.FindingsThe responses from the participants capture some of the complexity of self-care during the COVID-19 pandemic. The authors found evidence of both negative and positive sentiments towards self-care that will be described in five major themes. For the tensions with self-care, the authors developed two primary themes: leaders eat last and keep from falling off the cliff. For the demonstrations of self-care, the authors also developed three primary themes: release the endorphins, people need people and unplug from work.Originality/valueAlthough researchers have identified the stressors and reactions of principals during the early months of the COVID-19 pandemic, little is known on how principals engaged in self-care practices. This study aims to identify these self-care practices and offer recommendations for principals.

Background Intronic WT1 mutations are usually causative of Frasier syndrome with focal segmental glomerulosclerosis as the characteristic nephropathy. Membranoproliferative glomerulonephritis is not commonly associated with disorders of sex development but has been recently identified as a WT1-associated nephropathy, but usually in cases of exonic mutations in either isolated Wilms tumor or Denys-Drash syndrome. Methods The clinical and genetic data from 3 individuals are reported. Results This report describes the kidney manifestations in 3 individuals from 2 unrelated families with Frasier syndrome intronic WT1 mutations, noting that 2 of the 3 individuals have histologically confirmed membranoproliferative glomerulonephritis. Conclusions These case reports support expansion of the clinical spectrum of the kidney phenotypes associated with Frasier syndrome providing evidence of an association between WT1 mutation and an immune complex-related membranoproliferative glomerulonephritis. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Genomic medicine, an emerging medical discipline, applies the principles of evolution, developmental biology, functional genomics, and structural genomics within clinical care. Enabling widespread adoption and integration of genomic medicine into clinical practice is key to achieving precision medicine. We delineate a biological framework defining diagnostic utility of genomic testing and map the process of genomic medicine to inform integration into clinical practice. This process leverages collaboration and collective cognition of patients, principal care providers, clinical genomic specialists, laboratory geneticists, and payers. We detail considerations for referral, triage, patient intake, phenotyping, testing eligibility, variant analysis and interpretation, counseling, and management within the utilitarian limitations of health care systems. To reduce barriers for clinician engagement in genomic medicine, we provide several decision-making frameworks and tools and describe the implementation of the proposed workflow in a prototyped electronic platform that facilitates genomic care. Finally, we discuss a vision for the future of genomic medicine and comment on areas for continued efforts.

La réalisation de ce rapport de recherche a été motivée par deux rapports de cas indépendants portant sur des personnes vivant en Alberta, au Canada, qui ont subi une perte de vision permanente en raison de normes de pratique inadéquates entourant les tests de la vue. Les tests de la vue sont habituellement effectués par des opticiens indépendamment des examens oculovisuels complets. Une description des deux rapports de cas et une discussion sur les risques associés aux tests de la vue fournissent des données probantes liées au danger danger pour la santé publique que présentent ces tests. Afin d’étudier les méthodes possibles de réduction ou d’élimination des risques liés aux tests de la vue en Alberta, nous avons effectué une recension des lois et des normes de pratique régissant les tests de la vue au Canada, aux États-Unis, en Nouvelle-Zélande et au Royaume-Uni. Notre recension indique que l’interdiction pure et simple d’effectuer des tests de la vue en Alberta serait le meilleur moyen de protéger l’intérêt public et de réduire les cas évitables de perte de vision. Comme on le constate dans d’autres provinces canadiennes, d’autres approches pour réduire les risques associés aux tests de la vue comprennent 1) l’élaboration et l’application de restrictions concernant l’exécution des tests de la vue et 2) l’élaboration de scénarios clairement définis dans lesquels les opticiens collaborent avec les prescripteurs autorisés pour effectuer des tests de la vue en toute sécurité.

Les examens de réfraction comptent parmi les nombreuses procédures diag-nostiques effectuées par les optométristes et les ophtalmologistes en vue de prescrire des lunettes. En Alberta, les optométristes et les ophtalmologistes sont autorisés à effectuer des examens de réfraction et à prescrire des lunettes en fonction des résultats. Les opticiens sont aussi autorisés à effectuer des examens de réfraction sans toutefois avoir le droit de prescrire de lunettes. Cette étude vise à déterminer si la population a besoin que les opticiens soi-ent autorisés à effectuer des examens de réfraction et à prescrire des lunettes en solo compte tenu de la répartition géographique actuelle des optomé-tristes et des ophtalmologistes en Alberta. Pour répondre à cette question, les ratios des optométristes et des ophtalmologistes par rapport à la population pour chacune des cinq régions sanitaires de l’Alberta ont été calculés et com-parés aux ratios internationaux. Nos résultats montrent que les cinq régions sanitaires de l’Alberta ont des ratios optométriste-population qui atteignent ou dépassent l’indice de référence international de 1 pour 10 000 personnes permettant de répondre aux besoins de la population et que trois des cinq régions sanitaires ont des ratios ophtalmologiste-population équivalents ou supérieurs à l’indice de référence international de 3 pour 100 000 personnes qui permet de répondre aux besoins de la population. Ces données indiquent que la répartition des optométristes est adéquate dans la province mais que celle des ophtalmologistes est inadéquate. Compte tenu de la disponibilité ac-tuelle des optométristes et des ophtalmologistes en Alberta, il n’est pas néces-saire que les opticiens soient autorisés à effectuer des examens de réfraction et à prescrire des lunettes en solo.

A refraction is one of several tests performed by optometrists and ophthalmologists to issue a patient’s prescription for glasses. In Alberta, optometrists and ophthalmologists are authorized to perform refractions and prescribe based on that refraction; however, opticians are only authorized to refract. This study investigates whether there is a public need for opticians to be licensed to perform refractions and prescribe based on that refraction based on the adequacy of the geographic distribution of eye care professionals in Alberta. To answer this question, the optometrist and ophthalmologist to population ratios for each of Alberta’s five health zones were calculated and compared to international benchmarks. Our results show that all five of Alberta’s health zones have optometrist to population ratios that either meet or exceed the 1:10,000 international benchmark, and three of the five health zones have ophthalmologist to population ratios that meet or exceed the 3:100,000 international benchmark. Based on this data, there is an adequate distribution of optometrists but an inadequate distribution of ophthalmologists in the province. However, in regard to refractions, there is no overwhelming public need for opticians to refract and prescribe based on the refraction.

L’Alberta est l’une des trois provinces canadiennes qui autorisent les opticiens à effectuer des examens de la réfraction. Récemment, l’Alberta College and Asso-ciation of Opticians (ACAO) a demandé que le champ d’exercice des opticiens soit élargi pour inclure la capacité de prescrire des appareils optiques, qui est actuellement réservée aux optométristes et aux ophtalmologistes. Tout au long du présent document, le terme « prescrire » devrait être interprété comme la prescription d’un appareil optique, et non comme celle d’un agent pharmaceu-tique thérapeutique. Dans le présent document, nous cherchons à déterminer si les opticiens qui effectuent des examens de la réfraction désignés en Alberta ont une formation et des connaissances adéquates pour exécuter un examen et pre-scrire un appareil optique de façon autonome en toute sécurité. Pour répondre à cette question de recherche, nous avons dressé une liste de 27 compétences qui selon nous sont requises pour prescrire et faire des examens de la réfrac-tion de façon autonome en toute sécurité. Nous avons ensuite évalué les pro-grammes d’optique du Northern Alberta Institute of Technology (NAIT) et les examens d’entrée dans la profession administrés par l’Association nationale des autorités de réglementation des opticiens du Canada (NACOR) de même que le Bureau des examinateurs en optométrie du Canada (BEOC) pour déterminer s’ils couvrent ces 27 compétences. Nos constatations montrent que les pro-grammes de sciences optiques du NAIT ne couvrent pas ou n’évaluent pas dans la pratique plus de la moitié (59 %) des compétences requises pour prescrire et exécuter des examens de la réfraction de façon autonome en toute sécurité, et que l’examen de la NACOR ne couvre pas 77 % de ces compétences. Selon cette information, les opticiens qui effectuent des examens de la réfraction désignés en Alberta ne possèdent pas la formation et les connaissances nécessaires pour exécuter cet examen et prescrire un appareil optique de façon autonome en toute sécurité. Le fait d’accorder aux opticiens le pouvoir légal de prescrire et d’exécuter des examens de façon autonome peut donner lieu à un problème de santé publique, car il pourrait y avoir une augmentation du nombre de maladies oculaires et systémiques non diagnostiquées ou non détectées.

Alberta is one of three Canadian provinces that permits optician-performed refractions. Recently, the Alberta College and Association of Opticians (ACAO) has requested an expansion of opticians’ scope of practice to include the ability to prescribe optical appliances, an activity currently restricted to optometrists and ophthalmologists. For the remainder of this paper, the term “prescribe” should be interpreted as the prescription of an optical appliance, not a therapeutic pharmaceutical agent. In this paper, we investigate whether designated refracting opticians in Alberta have adequate training and knowledge to safely and independently perform a refraction and prescribe an optical appliance. To answer this research question, we composed a list of 27 skills we deem necessary to safely and independently refract and prescribe. We then evaluated the Northern Alberta Institute of Technology’s (NAIT) opticianry programs and the entry to practice examinations administered by the National Association of Canadian Optician Regulators (NACOR) and the Optometry Examining Board of Canada (OEBC) in terms of their coverage of these 27 skills. Our findings show that NAIT’s optical science programs either do not cover or do not practically assess students on over half (59 percent) of the skills required to safely and independently refract and prescribe, and the NACOR examination fails to cover 77 percent of the skills required to safely refract and prescribe. Based on this information, refracting opticians in Alberta do not possess adequate training and knowledge to safely and independently perform a refraction and prescribe an optical appliance. Granting opticians the legislative authority to independently refract and prescribe may result in a public health issue, as there may be an increase in the number of un-diagnosed or un-detected eye and systemic diseases.

PurposeThe authors demonstrate the usage of data visualization for conveying educational administration research, with a specific focus on differential principal turnover. They model when and how principals move, over time, between six categories of turnover.Design/methodology/approachThe authors construct several easy-to-interpret alluvial diagrams that reveal the patterns of differential turnover among 1,113 first-time Texas principals. Furthermore, the authors investigate how these patterns differ across educator characteristics (i.e. race and sex) and school contexts (i.e. school level and campus urbanicity).FindingsHalf of all first-time principals turn over within two years. Most principals who stay in leadership roles leave the district where they were first entered the principalship. Men are promoted more and women turn over less. In a connected finding, the authors conclude that elementary principals turn over less, and middle and high school principals are promoted more often. Principals of color are demoted more often than White principals. Urban school principals exit the system at a greater rate than rural principals.Originality/valueThe significance of this study lies in its direct response to two problems facing the administrator turnover knowledge base – a lack of methodological accessibility and the underutilization of data visualization. The authors’ is the first study to contain visualization of differential turnover outcomes over time. Second, the authors’ study provides a blueprint for data visualization that not only creates new knowledge but also speaks to a wider variety of education stakeholders by presenting complex data in a visual format.

PurposePrincipal preparation program pedagogy and course delivery are critical to principal candidates' preparedness to lead. Research around online program delivery, however, is relatively sparse. This study examined the extent to which university-based educational leadership programs offered fully online (FOL) pathways to the principalship, as well as program geographic locations and institutional characteristics most associated with FOL offerings.Design/methodology/approachData were collected through website reviews and coding checks, and then merged with national postsecondary data. Data were analyzed using descriptive statistics, classification tree analysis, and geographic information system (GIS) mapping.FindingsRoughly 43 percent of all reviewed programs offered an FOL pathway to licensure, which suggests substantial growth in FOL offerings over the last 10 years. While a number of factors were deemed important, geographic characteristics were most associated with FOL status. GIS mapping further illustrated findings with a visual landscape of program FOL offerings.Research limitations/implicationsThis study considered only programs for which degrees or certificates could be earned without ever visiting campus in-person for classes. Hybrid programs were excluded from the analysis.Practical implicationsFindings make a clear call for more research into online principal preparation program design and course delivery.Originality/valueThis study provides the first overview of fully online university-based principal preparation programs in the United States while also offering a previously unavailable landscape of all programs specifically leading to licensure. It is also the only higher education study to map or investigate factors associated with FOL offerings and raises questions about prior FOL higher education research.

This research report is motivated by two independent case reports featuring individuals living in Alberta, Canada who experienced permanent vision loss as a result of inadequate standards of practice surrounding sight tests. Sight tests are usually performed by opticians and are conducted independently of a comprehensive eye exam. A description of the two case reports in addition to a discussion of the potential dangers of sight tests provide evidence of the public health risks associated with sight tests. To investigate potential approaches to reduce or eliminate the risks of sight tests in Alberta, we conducted a jurisdictional review examining the laws and standards of practice governing sight tests in Canada, the United States, New Zealand, and the United Kingdom. Based on the jurisdictional review, the outright prohibition of sight tests in Alberta may be the best approach to protect the public interest and reduce cases of avoidable vision loss. As seen in other Canadian provinces, alternative approaches to reduce the risk of sight tests may involve 1) developing and enforcing restrictions around the performance of sight tests or 2) developing clearly defined scenarios in which opticians can collaborate with authorized prescribers to deliver safe sight tests.

Significant reduction in quality of life among patients with autoimmune hepatitis (AIH) patients has been observed in several studies. While acute symptoms associated with AIH have been well described, little is known about the overall impact of living with AIH on patients' quality of life. The aim of this qualitative descriptive study was to describe the impact of AIH and associated symptoms on quality of life from the perspectives of patients living with AIH.Patients from Autoimmune Hepatitis Association support groups were recruited to participate in one of five online focus groups conducted between August and September 2020. After enrollment, patients were asked to complete a brief demographic and disease history questionnaire. A single moderator conducted interviews with each group guided by seven questions focused on the impact of AIH on the participants' quality of life. Each session was recorded, transcribed, and verified. Content analysis was used to summarize the participants' responses.The participants' discussed three overarching topics: (a) symptoms of AIH and medication side effects, (b) the impact the disease and symptoms/side effects on five domains of quality of life (work life, relationships with friends and family, social life, leisure activities, and diet and exercise) and (c) interactions with healthcare providers and recommendations for future research.Living with AIH can have profound effects on patients' quality of life in several domains. Healthcare providers and the AIH research community should focus on developing further strategies that can improve the quality of life in persons suffering from AIH.

The authors piloted a weight stigma psychotherapy group at an eating disorder partial hospitalization (PHP) and intensive outpatient program (IOP). This was an optional, transdiagnostic eating disorder group for patients with past/present weight stigma experiences related to being in large bodies. A total of 36 individuals participated in the weekly group from June 2018 to June 2019 during their PHP/IOP episode of care. We present the group's overarching framework of destigmatizing language and intersectional discussions of weight stigma. We also discuss clinical processes that unfolded during this group including simulated dialog from the group. Finally, we present relevant client quotes that provide preliminary support for future exploration in this area, as client subjective experiences of the group were positive. Our preliminary pilot experience suggests that delivering a group of this nature in a PHP/IOP eating disorder treatment setting is feasible and that further work is needed to build upon this antiweight stigma framework as a critical piece of eating disorder treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Research indicates that preparation programs featuring partnerships between universities and districts have a greater impact on career advancement of graduates than more conventional university-bas...

As the collection and dissemination of “big data” become easier, we are exposed to increasing numbers of visuals, or infographics, that convey this data. Students are likely to interact wit...

Children’s understanding of rewards for task completion was examined in the context of gender, and gender-based stereotypes. Eighty-eight children (43 girls, Moverall = 58.39 months) completed a measure assessing gender-based occupational stereotypes. This measure, along with gender, was used to predict children’s self-reward for undergoing the testing, as well as their reward for a fictional other child having undergone the same procedure. The methodology provided a novel approach for studying reward allocation in children, as it did not require children to divide resources between themselves and another child for completing the same task. An occupation-based stereotype measure was found to predict the self-reward, as well as the reward allocated to the other child. In addition, the participant’s gender predicted self-reward, and an interaction between participant gender and gender of the experimenter contributed to predicting the other child reward. Overall, these findings suggest that gender an...

A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.

Phosphoinositide 3-kinase alpha (PI3Kα) H1047R mutations are activating oncogenic events that occur in ~15% of advanced breast cancers. While there is one PI3Kα inhibitor FDA-approved for patients with PI3Kα-mutated breast cancer, and many others in clinical development, all of these agents inhibit wild-type PI3Kα and its mutated form with approximate equal potency. As a result, their efficacy is limited by toxicities associated with on target wild-type PI3Kα inhibition, notably hyperglycemia as well as cutaneous and GI toxicity. LOX-22783 is a highly potent, mutant-selective and brain-penetrant allosteric PI3Kα H1047R inhibitor. Here, we describe the preclinical profile of LOX-22783. H1047R selectivity was measured using biochemical kinase activity and cell-titer Glo and signal transduction assays. Tumor growth inhibition, pharmacokinetic and pharmacodynamic effects were assessed in in vivo studies using xenograft and patient-derived xenograft (PDX)-models. LOX-22783 inhibited growth and signaling responses in multiple H1047R-driven breast cancer cell lines and demonstrated high selectivity for H1047R mutated PI3Kα (EC50 values 250 nM) as well as the other wild-type PI3K isoforms (beta, gamma, and delta, all EC50 >250nM). In enzyme and cell-based assays, LOX-22783 dissociated from PI3Kα H1047R at a slower rate (3-6 hrs) compared to alpelisib (≤10 mins), potentially allowing for extended inhibition of PI3Kα H1047R by LOX-22783. LOX-22783 also normalized the EGF-stimulated membrane-localization of PI3Kα H1047R while alpelisib did not. LOX-22783 was highly kinome-selective when assayed at 3 µM, with no inhibitory activity on 17 lipid kinases or 374 protein kinases. In preclinical species, LOX-22783 demonstrated high oral bioavailability, including exposure in the CNS, a common site of metastases for patients with breast cancer. In vivo, LOX-22783 demonstrated dose-dependent tumor regression in H1047R breast cancer models without inducing hyperglycemia or other toxicities. Tumor pharmacodynamic analyses confirmed successful pathway inhibition. At doses resulting in 90% pathway inhibition, tumor regressions of ≥60% were observed. This wide therapeutic index is predicted to allow for maximizing dose intensity and efficacy in patients, without wild-type PI3Kα inhibition limiting target coverage for the H1047R mutant form. These data demonstrate that LOX-22783 potently and selectively inhibits mutant H1047R, but not wild-type PI3Kα, or other PI3K isoforms. LOX-22783 binds to an allosteric pocket distinct from the ATP binding site used by the approved and investigational PI3Kα inhibitors. We hypothesize that this profile will lead to differentiated efficacy and tolerability for patients with PI3Kα H1047R-mutated cancers, with the additional potential to address brain metastases. An IND submission is planned for 2022. Citation Format: Anke Klippel, Rui Wang, Loredana Puca, Andrew Lee Faber, Weihua Shen, Shripad V. Bhagwat, Kannan Karukurichi, Feiyu Fred Zhang, Carmen Perez, Ramon Rama, Ana Ramos, Yi Zheng, Zahid Bonday, James Thomas, Harold B. Brooks, Lisa J. Kindler, Sarah M. Bogner, Parisa Zolfaghari, Mark Hicks II, Sophie Callies, Brian Mattioni, Laurie LeBrun, Jim Durbin, Erin Anderson, Chris Mayne, Edward Kesicki, Gabrielle Kolakowski, Steven W. Andrews, Barbara J. Brandhuber. Preclinical characterization of LOX-22783, a highly potent, mutant-selective and brain-penetrant allosteric PI3Kα H1047R inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P142.

Antibiotics are used for fighting pathogens, but also target our commensal bacteria as a side effect, disturbing the gut microbiota composition and causing dysbiosis and disease1-3. Despite this well-known collateral damage, the activity spectrum of the different antibiotic classes on gut bacteria remains poorly characterized. Having monitored the activities of >1,000 marketed drugs on 38 representative species of the healthy human gut microbiome4, we here characterize further the 144 antibiotics therein, representing all major classes. We determined >800 Minimal Inhibitory Concentrations (MICs) and extended the antibiotic profiling to 10 additional species to validate these results and link to available data on antibiotic breakpoints for gut microbes. Antibiotic classes exhibited distinct inhibition spectra, including generation-dependent effects by quinolones and phylogeny-independence by β-lactams. Macrolides and tetracyclines, two prototypic classes of bacteriostatic protein synthesis inhibitors, inhibited almost all commensals tested. We established that both kill different subsets of prevalent commensal bacteria, and cause cell lysis in specific cases. This species-specific activity challenges the long-standing divide of antibiotics into bactericidal and bacteriostatic, and provides a possible explanation for the strong impact of macrolides on the gut microbiota composition in animals5-8 and humans9-11. To mitigate the collateral damage of macrolides and tetracyclines on gut commensals, we exploited the fact that drug combinations have species-specific outcomes in bacteria12 and sought marketed drugs, which could antagonize the activity of these antibiotics in abundant gut commensal species. By screening >1,000 drugs, we identified several such antidotes capable of protecting gut species from these antibiotics without compromising their activity against relevant pathogens. Altogether, this study broadens our understanding of antibiotic action on gut commensals, uncovers a previously unappreciated and broad bactericidal effect of prototypical bacteriostatic antibiotics on gut bacteria, and opens avenues for preventing the collateral damage caused by antibiotics on human gut commensals.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3–5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota. This study systematically profiles the activity of several classes of antibiotics on gut commensal bacteria and identifies drugs that mitigate their collateral damage on commensal bacteria without compromising their efficacy against pathogens.

This document analysis provides a summary of the research from high-impact journals published between 2008 and 2013 with the explicit purpose of determining the extent to which the current empirical evidence supports the individual 2011 Educational Leadership Constituent Council Program Standards and their elements. We found that the standards are unevenly represented and supported in the research. In general, the research was stronger for Standards 2 and 3 and building-level leadership standards. Without a more substantial research foundation for leadership preparation, program faculty are limited in their ability to design evidence-supported learning content and experiences for the next generation of educational leaders.

Policies for principal preparation and licensure are important levers for improving school leadership. By developing a rubric of research-based practices, this University Council of Educational Administration study aims to provide a formative tool for policy makers. Using a policy analysis frame by Roach et al., this study explores the state code, rules and regulations, and accompanying state board/department of education documents to describe state policies for principal preparation program approval and candidate licensure. There is variation in the extent to which states have adopted policies in these areas. Proportionately, more states have adopted policies for licensure despite greater empirical evidence for preparation program approval.

Although dance/movement therapy (DMT) is often used in conjunction with traditional therapies for treating children with psychiatric disorders, the evidence base for this therapy is currently small. The goal of this retrospective research is to examine whether DMT, embedded within larger psychiatric therapeutic programs, affects changes in mood states of adolescents suffering from a variety of psychiatric illnesses. Participants include 402 predominately white, non-Hispanic patients (14–21 years old, with a mean age of 14.56 ± 1.70 years) who completed 671 mood measures between August 2010 and December 2011. Participants completed the Fast Assessment of Children's Emotions before and after a group DMT session. When controlling for pre-mood scores, there was a significant change in all mood states and a significant odds of a change in total mood score, per unit increase in pre-total mood score, after one DMT session (odds ratio = 1.84; p ≤ .01). There was no significant association between patient characteristics and changes in individual or total mood scores, indicating that DMT may be useful for a wide range of patients. The results from this formative study will help researchers develop prospective studies focusing on therapeutic effects of DMT for a wide range of patients.

There is emerging evidence for the important role of metacognitions in the presentation of eating disorders (EDs); however it is unclear to what extent these metacogntions are transdiagnostic. This study used a mixed methods convergent design to explore this question by triangulating both qualitative and quantitative data from 27 women, aged 18-55 years, with diagnoses of anorexia nervosa, bulimia nervosa, or eating disorders not otherwise specified. The results indicated that metacognitions in EDs may be transdiagnostic and may in part explain temporal migration between diagnoses and the degree of comorbidity associated with EDs.

The extension of an elastic body almost always leads to mechanical tension in the stretching direction. Here, we report an unusual phenomenon of global mechanical compression in the stretching direction of an elastic body containing sinusoidal wavy interfaces. When the elastic body with a wavy interface is subjected to tensile loading, the local stress state along the interface is mixed-mode. Finite element simulations show that the resistance of the interface to shear-slip locks the interface together, and generates a moment couple which rotates the interface. Once the local adhesive shear strength of the interface is reached, the interface slips and separates. Then, the rotated interface triggers a restoring moment couple which releases the stored elastic energy. The structure subsequently undergoes global compression in the stretching direction until the interface completely separates. This moment-couple-induced internal energy storage and release mechanism leads to a material structure that exhibits high initial strength and toughness, followed by post-peak compliant softening with negative stiffness. This structural negative stiffness behavior is closely-tied with the ability of the interface to store and release energy by rotation, and is also exhibited by polycrystalline structures where grain rotation is possible.

While self-archiving gains more traction as a means for scholars to make their research freely available, a perception persists that certain disciplines in the humanities lag behind the sciences in this regard. This article investigates the rate of self-archiving by scholars contributing to the top journals in the field of music, a discipline that traditionally falls within the humanities, although research in the field is highly interdisciplinary and draws heavily on multiple scientific fields. The contributors to these journals come from a range of background and interests, and represent colleges and universities from six continents.

Physical and Name Identity letter-matching tasks were used to explore differences in interhemispheric collaboration in younger and older adults. To determine whether other factors might also be related to across/within-hemisphere processing or visual field asymmetries, neuropsychological tests measuring frontal/executive functioning were administered, and comparisons were made for participants split into low and high efficiency groups based on performance on the letter-matching tasks. A Task by Across/Within interaction was found for both groups, but with a stronger within-hemisphere advantage for the Physical Task and a weaker across-hemisphere advantage for the Name Task for older participants. More efficient groups and better performers on several neuropsychological tasks showed a reduced across-hemisphere advantage for the Name Identity task. Findings suggest that computational complexity, specific task demands, and perhaps trade-offs between age-related changes in gray and white matter all contribute to whether processing loads are distributed across or within hemispheres as we age.

This paper adopts a configuration theory perspective to investigate how inconsistencies among the perceived elements of a sales force control system influence salesperson performance. Analysis based on a sample of 1,290 salespeople suggests that these inconsistencies hurt salesperson performance. Furthermore, this relationship is moderated by professional maturity, a combined index of age, selling experience, and organizational tenure. Implications for management and future research are offered.

Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachusetts are exposed to cumulative, chronic built-environment stressors, and have limited capacity to respond, magnifying their vulnerability to adverse health outcomes. “Neighborhood STRENGTH”, our community-based participatory research (CBPR) project, comprised four partners: a youth center; an environmental non-profit; a community-based health center; and a university. Unlike most CBPR projects that are single topic-focused, our ‘holistic’, systems-based project targeted five priorities. The three research-focused/action-oriented components were: (1) participatory monitoring of indoor and outdoor pollution; (2) learning about health needs and concerns of residents through community-based listening sessions; (3) engaging in collaborative survey work, including a household vulnerability survey and an asthma prevalence survey for schoolchildren. The two action-focused/research-informed components were: (4) tackling persistent street trash and illegal dumping strategically; and (5) educating and empowering youth to promote environmental justice. We used a coupled CBPR-capacity building approach to design, vulnerability theory to frame, and mixed methods: quantitative environmental testing and qualitative surveys. Process and outcomes yielded important lessons: vulnerability theory helps frame issues holistically; having several topic-based projects yielded useful information, but was hard to manage and articulate to the public; access to, and engagement with, the target population was very difficult and would have benefited greatly from having representative residents who were paid at the partners’ table. Engagement with residents and conflict burden varied highly across components. Notwithstanding, we built enabling capacity, strengthened our understanding of vulnerability, and are able to share valuable experiential knowledge.

We look at a channel compensation strategy frequently adopted by business-to-business manufacturers that use their own channels and independent entities simultaneously to sell their products in a given territory: compensating both channels (double compensation) for a sale when both channels interacted with the customer in that sale (independently of who gets the order). Using original data from prominent manufacturers operating in competitive markets worldwide, we present an exploratory investigation into the determinants of usage of double compensation. We show that manufacturers sacrifice short-term profits (by double compensation) when the expected costs associated with failing to compensate a channel that has responsibility for a sale increase. We identify such circumstances.

This descriptive study explores the reasons for integration of the personal selling function, i.e., the use of employee (“direct”) salespeople rather than manufacturers' representatives (“reps”). A hypothesized model is developed based on both transaction cost analysis and the sales force management literature. Data from 13 electronic component manufacturers covering 159 U.S. sales districts are used to estimate a logistic model of the probability of “going direct” in a given district. Results are shown to be stable across specification and estimation methods and to fit the data well. The transaction cost model is generally supported. The principal finding is that the greater the difficulty of evaluating a salesperson's performance, the more likely the firm to substitute surveillance for commission as a control mechanism, i.e., to use a direct sales force. Among other findings, direct sales forces are also associated with complex, hard-to-learn product lines and with districts that demand considerable nonselling activities. Several factors prove unrelated, including company size, the amount of travel a district requires, and the importance of key accounts. This article was originally published in Marketing Science, Volume 4, Issue 3, Pages 234–254, in 1985.

The authors dedicate this paper in honor of the memory of their deceased co-author, Erin Anderson. In dyadic business relationships, parties can be incorrect in reading their counterparts' relational closeness. For example, they can overestimate or underestimate the counterpart's commitment to their relationship. In the business-to-business (B2B) literature, the consequences of such inaccurate perceptions have not been empirically investigated. We advance and test the proposition that the impact of misreading the other party's relational closeness depends on the direction of the error. We propose that overestimating the counterpart's relational closeness (CRC) is beneficial, while underestimating the counterpart's relational closeness is detrimental for the relationship's functioning. Using original dyadic data in the service sector, we show that most companies underestimate their CRC, in which case becoming perceptually more accurate would improve their relationships. But the opposite holds for parties that overestimate their CRC, in which case becoming perceptually more accurate would actually make the relationship deteriorate. Furthermore, we show that even in long-standing relationships, companies do not know how accurate their perceptions are, even when they believe that they correctly perceive their CRC. We discuss managerial implications of our findings and encourage future research to determine why most decision makers underestimate their CRC, which can lead to impaired functioning of B2B relationships.

Today’s undergraduate students seldom question women’s presence or roles in the workplace. Because they have come to see women’s employment as common place, they are often less aware of the persistent gender inequalities in the workplace or the historical roots of these patterns. Throughout my course on Work and Gender I challenge students to think critically about what constitutes “work” and the disparity in the social and economic value of paid and unpaid labor, how race, ethnicity, and social class have influenced gender roles and rewards over time, and how social policy, gendered organizations, and family roles impact the opportunities, experiences, and compensation workers can expect as a result of their gender. These objectives are accomplished through the reading and discussion of empirical research, personal reflections, guest speakers, and documentary film. My goals in teaching this course are for students to come away with a greater awareness of the intersection of race, class, and gender in work and family roles as well as perspective to draw on in their own personal and professional paths.

This research examines the evolution of cooperative interorganizational relationships and provides an empirical test of four propositions from the DSO (Dwyer et al. 1987) life-cycle theory, and one proposition from the RV (Ring and Van de Ven 1994) theory of relationship development. Using primary data from over 1,500 resellers in a channel of distribution, we find that the mature phase is not the pinnacle of the relationship lifecycle; relationship properties (e.g., relationship harmony, overall dependence, and the reseller’s trust in the manufacturer) in this stage are no different than in the build-up phase. However, relationship properties that support relationship expansion (e.g., goal congruence and information exchange norms) reach their zenith in the build-up phase and afterwards fade into the background. All of the various relationship properties hit their nadir in the decline phase. We also examine the development of relationships over a five-year period and consider whether movement across the stages in accordance with DSO’s theory has the same association to overall performance evaluations as movement through regressive patterns. We find that a negative history extracts a price: Movement through regressive patterns is negatively related to performance, and these relationships do not enjoy a fresh start. Instead, these movements can last for an extended period of time and are negatively related to performance outcomes during the decline phase. Thus, the development path taken appears to be related to the results achieved. Finally, we also find evidence of the critical role that individual sales representatives play in creating successful interorganizational relationships.

The creation of welfare-to-work programs across the country has led to a number of questions about the effectiveness of this reform effort and the experiences of welfare recipients. This study of seventeen welfare recipients in the state of Oregon reports on what the welfare-to-work experience is like for women in two types of communities, one rural and one urban. Our findings suggest that women in both communities share similar frustrations, but overall assess the welfare-to-work program ideology positively. Women in the rural community do report more personal challenges in finding and keeping a job based on the lack of public transportation, limited job prospects in the rural area, and dissatisfaction with the education and job skill training available to them.

The authors study business-to-business manufacturers' simultaneous usage of vertically integrated (direct) and third-party (indirect) channels of distribution to serve one geographical market (possibly comprising several market segments) with the same product line. Most theoretical approaches to vertical integration of the distribution function pose the classic question of whether to forward integrate or use independent entities. Having concurrent channels means doing both. This phenomenon is poorly understood, even though it has been growing rapidly. The authors argue that under certain circumstances, it is impossible for manufacturers to prevent channel types from competing with each other, either because both channel types contact the same customer or because the customer sets them in competition against each other. The authors argue that when these situations are frequent or more consequential for the parties involved, firms reduce their usage of concurrent channels to prevent severe channel conflict. The authors posit five such circumstances. Using original data from prominent manufacturers operating in competitive markets worldwide, they model usage of both types of channels to cover one geography with the same products. They find substantial support for their model. Furthermore, in a subset of firms that use both channel types in the same market, they model the degree to which direct and indirect channels compete destructively against each other when contacting the same customers. The authors find that suppliers reduce such behavior by incurring costs to differentiate each channel's offerings, setting out ”rules of engagement,” and compensating both channel types when either one makes a sale.

Opportunism is a central construct in exchange theory. Economists contend that despite the firm's best efforts to erect governance structures that reduce opportunism and preserve outcomes, some opportunism always remains once the transaction is in place. Despite this fact, few studies systematically investigate the safeguarding efficacy of relationship attributes in the presence of such ex post opportunism. In this research, we develop a theoretical framework and provide a longitudinal test of the ability of various relationship safeguards to preserve performance outcomes and future expectations given varying levels of ex post opportunism in the relationship. Our survey results from over 300 buyers and suppliers indicate that in relationships with extremely low levels of ex post opportunism, bilateral idiosyncratic investments and interpersonal trust enhance performance outcomes and future expectations, while goal congruence produces no discernable effect. However, at higher levels of ex post opportunism, goal congruence gains efficacy, becoming a more powerful safeguard, while interpersonal trust loses efficacy, becoming a less effective safeguard. Bilateral idiosyncratic investments continue to preserve performance outcomes and future expectations, and with the same efficacy, at higher and lower levels of opportunism. Implications for the long-term management of interorganizational alliances are discussed.