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Promoting excellence in autism intervention is arguably more urgent than ever for the field of applied behavior analysis. To fulfill this objective, autism agencies must operate from validated program systems and do so with fidelity. Program components include, but are not limited to, staff training and evaluation of clinical skills, functional personnel roles designed to promote positive outcomes for those served, and professional staff-communication-skill repertoires. Data on client outcomes must be tied to implementation of core program variables; and, contingencies between the data on client outcomes and staff performance must exist. Furthermore, these contingencies must be yoked across members of the organization to ensure a sustainable and effective program model. Finally, data on consumer satisfaction must be collected and used to evaluate program components and agency practices. Members of the Alliance for Scientific Autism Intervention have implemented key program-wide systems based upon the work of McClannahan and Krantz Journal of Applied Behavior Analysis, 26, 589-596 (1993) for decades and across various agency cultures. Data collected by six independent educational agencies on client outcomes, program implementation, and consumer feedback for a 10-year time span demonstrate the sustainability of the model and support the importance of key organizational systems and the relationship between implementation of the model and high-quality outcomes for individuals with autism.
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Lyme disease is a tick-borne infection caused by the spirochete Borrelia (Borreliella) burgdorferi. Borrelia species have highly fragmented genomes composed of a linear chromosome and a constellation of linear and circular plasmids some of which are required throughout the enzootic cycle. Included in this plasmid repertoire by almost all Lyme disease spirochetes are the 32-kb circular plasmid cp32 prophages that are capable of lytic replication to produce infectious virions called ÏBB-1. While the B. burgdorferi genome contains evidence of horizontal transfer, the mechanisms of gene transfer between strains remain unclear. While we know that ÏBB-1 transduces cp32 and shuttle vector DNA during in vitro cultivation, the extent of ÏBB-1 DNA transfer is not clear. Herein, we use proteomics and long-read sequencing to further characterize ÏBB-1 virions. Our studies identified the cp32 pac region and revealed that ÏBB-1 packages linear cp32s via a headful mechanism with preferential packaging of plasmids containing the cp32 pac region. Additionally, we find ÏBB-1 packages fragments of the linear chromosome and full-length plasmids including lp54, cp26, and others. Furthermore, sequencing of ÏBB-1 packaged DNA allowed us to resolve the covalently closed hairpin telomeres for the linear B. burgdorferi chromosome and most linear plasmids in strain CA-11.2A. Collectively, our results shed light on the biology of the ubiquitous ÏBB-1 phage and further implicates ÏBB-1 in the generalized transduction of diverse genes and the maintenance of genetic diversity in Lyme disease spirochetes.
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Bacteriófagos , Borrelia burgdorferi , Enfermedad de Lyme , Humanos , Borrelia burgdorferi/genética , Bacteriófagos/genética , Plásmidos/genética , Enfermedad de Lyme/genética , Genómica , ADNRESUMEN
Lyme disease is a tick-borne infection caused by the spirochete Borrelia (Borreliella) burgdorferi. Borrelia species have highly fragmented genomes composed of a linear chromosome and a constellation of linear and circular plasmids some of which are required throughout the enzootic cycle. Included in this plasmid repertoire by almost all Lyme disease spirochetes are the 32-kb circular plasmid cp32 prophages that are capable of lytic replication to produce infectious virions called ÏBB-1. While the B. burgdorferi genome contains evidence of horizontal transfer, the mechanisms of gene transfer between strains remain unclear. While we know that ÏBB-1 transduces cp32 and shuttle vector DNA during in vitro cultivation, the extent of ÏBB-1 DNA transfer is not clear. Herein, we use proteomics and long-read sequencing to further characterize ÏBB-1 virions. Our studies identified the cp32 pac region and revealed that ÏBB-1 packages linear cp32s via a headful mechanism with preferentially packaging of plasmids containing the cp32 pac region. Additionally, we find ÏBB-1 packages fragments of the linear chromosome and full-length plasmids including lp54, cp26, and others. Furthermore, sequencing of ÏBB-1 packaged DNA allowed us to resolve the covalently closed hairpin telomeres for the linear B. burgdorferi chromosome and most linear plasmids in strain CA-11.2A. Collectively, our results shed light on the biology of the ubiquitous ÏBB-1 phage and further implicates ÏBB-1 in the generalized transduction of diverse genes and the maintenance of genetic diversity in Lyme disease spirochetes.
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BACKGROUND: Transgender and gender diverse (TGD) populations require personalized care. Lived experiences and needs TGD populations express, compounded by limited care access, negatively shape health care involvement. Manifestations from these barriers may present as health care avoidance, identity concealment, or preventive care hinderance. Community pharmacies remain engagement points for TGD patients, but gender diverse services remain limited. What remains unknown is how TGD pharmacy perceptions and behaviors are influenced with gender-affirming care (GAC) accessibility. OBJECTIVES: The primary objective is to assess how TGD patient perceptions and behaviors toward community pharmacy experiences are affected through a lesbian, gay, bisexual, transgender, queer/questioning, and others (LGBTQ+) community-based health system. METHODS: A cross-sectional, multisite, reflective survey was conducted at 4 LGBTQ+ community pharmacies in central and southwest Ohio. Nine 5-point Likert-item questions and one ordinal question were used to analyze perception and behavior. Participants responded for LGBTQ+ and external pharmacy experiences respectively. Data were analyzed through descriptive methods, paired Student's t test, and Fisher's exact test or c2 test where appropriate. RESULTS: In total, 267 surveys were completed with 96 TGD submissions qualifying for analysis. Perceptions toward pharmacy experience saw statistically significant differences among all evaluations of perception. Behavioral assessment demonstrated statistically significant improvements in pharmacy outreach except for seeking medications from outside sources. Respondents indicated more involvement with the LGBTQ+ pharmacies versus external pharmacies in discussing medications (96.9% vs. 60.4%), care plans (64.6% vs. 41.6%), disclosure of pronouns or gender (97.9% vs. 43.8%), and feeling needs were understood (96.8% vs. 51%). CONCLUSION: Inclusive community pharmacies may positively affect pharmacy perceptions and behaviors of TGD patients. These findings call attention to barriers in the provision of care for TGD patients while highlighting the change community pharmacies can have when providing these services. Community pharmacies should be encouraged to incorporate inclusive environments to improve TGD patient care involvement and access.
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Farmacias , Minorías Sexuales y de Género , Personas Transgénero , Femenino , Humanos , Estudios Transversales , Atención de Afirmación de Género , Participación del PacienteRESUMEN
Long-lived T-dependent B cell responses fail to develop during persistent infection of mice with Borrelia burgdorferi, the causative agent of Lyme disease, raising questions about the induction and/or functionality of anti-B. burgdorferi adaptive immune responses. Yet, a lack of reagents has limited investigations into B. burgdorferi-specific T and B cells. We attempted two approaches to track B. burgdorferi-induced CD4 T cells. First, a B. burgdorferi mutant was generated with an influenza hemagglutinin (HA) peptide, HA111-119, inserted into the B. burgdorferi arthritis-related protein (Arp) locus. Although this B. burgdorferi arp::HA strain remained infectious, peptide-specific TCR transgenic CD4 T cells in vitro, or adoptively transferred into B. burgdorferi arp::HA-infected BALB/c mice, did not clonally expand above those of recipients infected with the parental B. burgdorferi strain or a B. burgdorferi mutant containing an irrelevant peptide. Some expansion, however, occurred in B. burgdorferi arp::HA-infected BALB/c SCID mice. Second, a (to our knowledge) newly identified I-Ab-restricted CD4 T cell epitope, Arp152-166, was used to generate Arp MHC class II tetramers. Flow cytometry showed small numbers of Arp-specific CD4 T cells emerging in mice infected with B. burgdorferi but not with Arp-deficient Borrelia afzelii. Although up to 30% of Arp-specific CD4 T cells were ICOS+PD-1+CXCR5+BCL6+ T follicular helper cells, their numbers declined after day 12, before germinal centers (GCs) are prominent. Although some Arp-specific B cells, identified using fluorochrome-labeled rArp proteins, had the phenotype of GC B cells, their frequencies did not correlate with anti-Arp serum IgG. The data suggest a failure not in the induction, but in the maintenance of GC T follicular helper and/or B cells to B. burgdorferi.
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Borrelia burgdorferi , Enfermedad de Lyme , Ratones , Animales , Linfocitos T CD4-Positivos , Ratones SCID , Linfocitos BRESUMEN
PlzA is a c-di-GMP-binding protein crucial for adaptation of the Lyme disease spirochete Borrelia (Borreliella) burgdorferi during its enzootic life cycle. Unliganded apo-PlzA is important for vertebrate infection, while liganded holo-PlzA is important for survival in the tick; however, the biological function of PlzA has remained enigmatic. Here, we report that PlzA has RNA chaperone activity that is inhibited by c-di-GMP binding. Holo- and apo-PlzA bind RNA and accelerate RNA annealing, while only apo-PlzA can strand displace and unwind double-stranded RNA. Guided by the crystal structure of PlzA, we identified several key aromatic amino acids protruding from the N- and C-terminal domains that are required for RNA-binding and unwinding activity. Our findings illuminate c-di-GMP as a switch controlling the RNA chaperone activity of PlzA, and we propose that complex RNA-mediated modulatory mechanisms allow PlzA to regulate gene expression during both the vector and host phases of the B. burgdorferi life cycle.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Ixodes , Enfermedad de Lyme , Proteínas Bacterianas/metabolismo , Borrelia burgdorferi/metabolismo , Grupo Borrelia Burgdorferi/genética , Enfermedad de Lyme/genética , ARN/metabolismoRESUMEN
BACKGROUND: The transgender population has disparities and predictors of smoking unique from the general population. Although culturally tailored smoking cessation programs have been created for minority populations with increased burden of tobacco use, there are no such pharmacist-led smoking cessation interventions for transgender patients. OBJECTIVES: The objective is to describe the development and implementation of a culturally tailored smoking cessation program for transgender and gender diverse patients and highlight an opportunity for pharmacist involvement in the interdisciplinary health care team for trans patients. METHODS: The BreatheOut program was devised as a pharmacist-led smoking cessation program for transgender and gender diverse patients. The program was designed based on the PEN-3 model for centering cultural identity in behavior change and was administered in an ambulatory care setting at a community health center with integrated clinical pharmacists. Patients are offered pharmacotherapy for treatment of smoking cessation in accordance with guideline-directed therapy. RESULTS: Preliminary evaluation of this program was conducted through a prospective, observational study. To assess long-term feasibility of the program, time spent at each visit was tracked to calculate cost using a pharmacy resident versus a clinical pharmacist to provide the service. The program was financially feasible when the cost of personnel time was compared with medical billing and pharmacy revenue. CONCLUSION: This culturally tailored smoking cessation program for a population with a high burden of smoking was found to be feasible when administered by a pharmacy resident or clinical pharmacist. Preliminary data support expansion of this program and the use of a culturally tailored approach to smoking cessation in this population.
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Cese del Hábito de Fumar , Personas Transgénero , Humanos , Farmacéuticos , Estudios Prospectivos , FumarRESUMEN
Many Health Sciences Librarians (HSLs) affiliated with academic health centers in the US have faculty status. Faculty status enables HSLs to collaborate with their health sciences faculty colleagues as peers. Translating HSL faculty responsibilities into terms their faculty counterparts can understand represents an ongoing challenge for HSLs. This translation process becomes crucial when HSLs with faculty status seek a promotion or wish to secure tenure. The authors used job analysis to clarify faculty roles for HSLs to create a "Crosswalk" that enables the reader to identify an HSL role and find an equivalent health sciences faculty role.
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Bibliotecólogos , Medicina , Humanos , Docentes MédicosRESUMEN
Although parents of children with autism who are also experts in a related profession have been instrumental in shaping current practices, there is little known about parent-researchers and the benefits and obstacles to including individuals with these intersectional identities on autism focused research teams. The following study used collaborative autoethnographies from three parent-researchers hired for a large scale, federally funded project. The parent-researchers, and co-authors, collaborated on all phases of the reported study. Common themes generated from the shared perspectives included: prioritizing children and professional sacrifices; professional training as an asset for parents; potential bias toward parents in professional contexts; assets as parent-professionals; and obstacles for maintaining intersectional roles of parent-professionals. Recommendations for autism researchers and considerations for employing and supporting parent-researchers are discussed.
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Individuals with autism experience challenges in social communication that directly impacts in-school and post-school performance. A growing number of these students are taught in general education settings in public high schools, where creating opportunities for practice of social communication skills is frequently a challenge. This exploratory, mixed methods pilot investigation explores existing and potential opportunities for high school students with autism to practice 21st century skills, including communication, in extracurricular club environments. Findings indicate that extracurricular club settings are rich environments in which all participating students, including those with autism, have opportunities to practice critical 21st century skills in a context related to their interests.
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Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective strategy to prevent serious coronavirus disease 2019 (COVID-19) and is important for oncology patients. mRNA-based COVID-19 vaccines are contraindicated in those with a history of severe or immediate allergy to any vaccine component, including polyethylene glycol (PEG)2000. Patients with acute lymphoblastic leukemia/lymphoma receive asparaginase conjugated to PEG5000 (PEG-ASNase) and those with PEG-ASNase-associated hypersensitivity may be unnecessarily excluded from receiving mRNA COVID-19 vaccines. We, therefore, surveyed oncologists on COVID-19 vaccine counseling practice and vaccination outcomes in COVID-19 vaccination-eligible patients and show safe receipt of mRNA vaccines despite PEG-ASNase hypersensitivity.
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Asparaginasa , Vacunas contra la COVID-19 , COVID-19 , Hipersensibilidad a las Drogas , Polietilenglicoles , Asparaginasa/efectos adversos , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Consejo , Hipersensibilidad a las Drogas/etiología , Humanos , Oncólogos , Polietilenglicoles/efectos adversos , ARN Mensajero , SARS-CoV-2 , Vacunación/efectos adversosRESUMEN
We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is essential for murine infection and crucial for persistence of the spirochete in the tick. B. burgdorferi has a limited biosynthetic and metabolic capacity; the linchpin connecting central carbohydrate and lipid metabolism is at the interconversion of glycerol-3-phosphate and dihydroxyacetone phosphate, catalyzed by GpsA and another glycerol-3-phosphate dehydrogenase, GlpD. Using a broad metabolomics approach, we found that GpsA serves as a dominant regulator of NADH and glycerol-3-phosphate levels in vitro, metabolic intermediates that reflect the cellular redox potential and serve as a precursor for lipid and lipoprotein biosynthesis, respectively. Additionally, GpsA was required for survival under nutrient stress, regulated overall reductase activity and controlled B. burgdorferi morphology in vitro. Furthermore, during in vitro nutrient stress, both glycerol and N-acetylglucosamine were bactericidal to B. burgdorferi in a GlpD-dependent manner. This study is also the first to identify a suppressor mutation in B. burgdorferi: a glpD deletion restored the wild-type phenotype to the pleiotropic gpsA mutant, including murine infectivity by needle inoculation at high doses, survival under nutrient stress, morphological changes and the metabolic imbalance of NADH and glycerol-3-phosphate. These results illustrate how basic metabolic functions that are dispensable for in vitro growth can be essential for in vivo infectivity of B. burgdorferi and may serve as attractive therapeutic targets.
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Grupo Borrelia Burgdorferi , Borrelia burgdorferi , Enfermedad de Lyme , Garrapatas , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Glicerol/metabolismo , Glicerolfosfato Deshidrogenasa/genética , Glicerolfosfato Deshidrogenasa/metabolismo , Ratones , NAD/metabolismo , Oxidación-Reducción , Fosfatos/metabolismoAsunto(s)
COVID-19 , Hipersensibilidad Inmediata , Asparaginasa , Vacunas contra la COVID-19 , Humanos , Polietilenglicoles , ARN Mensajero , SARS-CoV-2RESUMEN
BACKGROUND: Seasonal influenza vaccine (SIV) uptake in the United States remains suboptimal, requiring new and innovative strategies. OBJECTIVE: To evaluate the impact of a behavioral peer comparison (PC) intervention on SIV uptake in community pharmacies across the United States. METHODS: A cluster randomized study was conducted across a national network of Walmart community pharmacies (> 4500 sites) during the 2019-2020 influenza season. The clusters consisted of 416 markets, each containing an average of 11 pharmacies. All pharmacies in a market were randomly assigned to either no intervention or the PC intervention, a software-delivered communication informing on-site staff, including pharmacists and pharmacy technicians, of their pharmacy's weekly performance, measured as SIV doses administered, compared with that of peer pharmacies within their market. The outcome was the pharmacy-level cumulative SIV doses administered during the intervention period (September 1, 2019,-February 29, 2020). Linear regression models were used to estimate the PC impact, with multiway cluster-robust SEs estimated by market and state. RESULTS: A total of 4589 pharmacies were enrolled in the study, with 2297 (50.1%) randomized to the control group and 2292 (49.9%) randomized to the PC intervention group. Overall, compared with the control pharmacies, the PC pharmacies administered 3.7% (95% CI -0.3% to 7.9%) additional SIV doses. Among large-format pharmacies, the PC pharmacies administered 4.1% (95% CI 0.1%-8.3%) additional SIV doses compared with the controls. Historically low-performing large-format PC pharmacies administered 6.1% (95% CI 0.5%-11.9%) additional SIV doses compared with the controls. No statistically significant treatment effects were observed among small-format pharmacies. CONCLUSION: Our findings demonstrate that PCs can improve SIV uptake among large-format community pharmacies, with historically low-performing pharmacies potentially exhibiting the greatest relative impact. Wide-scale implementation of PCs in community pharmacies may help to further improve SIV uptake in these settings.
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Servicios Comunitarios de Farmacia , Vacunas contra la Influenza , Farmacias , Humanos , Farmacéuticos , Técnicos de Farmacia , Estaciones del Año , Estados UnidosRESUMEN
Commemorating the 40 th anniversary of the Diagnostic and Statistical Manual (DSM) III, the purpose of this commentary is to describe school-based and school-relevant interventions and instructional approaches for children and youth with autism that have been developed and employed during that time period. The commentary begins with a brief description of foundational research that provides an historical context. Research themes shaped by science, ethics, social policy, and the changes in the DSM provide an organization for describing the evolution of intervention and instructional practices over the four previous decades. The commentary concludes with a discussion of school-contextual variables that influence implementation and the promise of the "iSciences" for closing the research to practice gap in the future.
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Trastorno del Espectro Autista , Trastorno Autístico , Adolescente , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/terapia , Trastorno Autístico/terapia , Niño , Humanos , Instituciones AcadémicasRESUMEN
BACKGROUND: Seasonal influenza vaccine (SIV) uptake among US adults aged 65 years or older remains suboptimal and stagnant. Further, there is growing concern around racial and ethnic disparities in uptake. We aimed to assess racial and ethnic disparities in overall SIV and in high-dose vaccine (HDV) uptake among Medicare beneficiaries during the 2015-16 influenza season and sought to identify possible mediators for observed disparities. METHODS: We did a historical record-linkage cohort study using Medicare (a US national health insurance programme) databases, which included all older adults (≥65 years) enrolled in Medicare during the study period (July 1, 2015, to June 30, 2016). We excluded beneficiaries of Medicare Part C (managed care offered by private companies), and residents of long-term care facilities. The primary outcome was SIV receipt during the study period, classified into receipt of HDV and standard-dose vaccines (SDVs, representing all other SIVs). SIV uptake probabilities were estimated using competing-risk survival analysis methods. Mediation analyses were done to investigate potential mediators of the association between race and ethnicity and uptake. FINDINGS: During the study period, of 26·5 million beneficiaries in the study cohort, 47·4% received a SIV, 52·7% of whom received HDV. Compared with white beneficiaries (49·4%), Hispanic (29·1%), Black (32·6%), and Asian (47·6%) beneficiaries were less likely to be vaccinated and, when vaccinated, were less likely to receive HDV (37·8% for Hispanic people, 41·1% for Black people, and 40·3% for Asian people, compared with 53·8% of white people who received HDV). Among those vaccinated, after accounting for region, income, chronic conditions, and health-care use, minority groups were 26-32% less likely to receive HDV, relative to white people (odds ratio [OR] 0·68 [95% CI 0·68-0·69] for Black people; OR 0·71 [0·71-0·72] for Asian people; and OR 0·74 [0·73-0·74] for Hispanic people). INTERPRETATION: Substantial racial and ethnic disparities in SIV uptake among Medicare beneficiaries aged 65 years or older are evident. New legislative, fiscal, and educational strategies are urgently needed to address these inequities. FUNDING: Sanofi Pasteur.
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OBJECTIVE: Ambulatory care safety is of emerging concern, especially in light of recent studies related to diagnostic errors and health information technology-related safety. Safety reporting systems in outpatient care must address the top safety concerns and be practical and simple to use. A registry that can identify common near misses in ambulatory care can be useful to facilitate safety improvements. We reviewed the literature on medical errors in the ambulatory setting to inform the design of a registry for collecting near miss incidents. METHODS: This narrative review included articles from PubMed that were: 1) original research; 2) discussed near misses or adverse events in the ambulatory setting; 3) relevant to US health care; and 4) published between 2002 and 2013. After full text review, 38 studies were searched for information on near misses and associated factors. Additionally, we used expert opinion and current inpatient near miss registries to inform registry development. RESULTS: Studies included a variety of safety issues including diagnostic errors, treatment or management-related errors, communication errors, environmental/structural hazards, and health information technology (health IT)-related concerns. The registry, based on the results of the review, updates previous work by including specific sections for errors associated with diagnosis, communication, and environment structure and incorporates specific questions about the role of health information technology. CONCLUSIONS: Through use of this registry or future registries that incorporate newly identified categories, near misses in the ambulatory setting can be accurately captured, and that information can be used to improve patient safety.