Search

Part C Early Intervention (EI) systems are an entry point to services for autistic toddlers and can be leveraged to facilitate access to autism evidence-based practices (EBPs). However, EI systems are complex and limited research has examined how an EI system's infrastructure (i.e. system-level factors) impacts the adoption and implementation of EBPs. To address this gap, 36 EI providers and 9 EI administrators completed a semi-structured interview or focus group about factors impacting the implementation of autism EBPs. Qualitative analysis included a combination of grounded theory and causative coding. Analyses were refined by input from providers, administrators, and family stakeholders in the form of round tables and presentations at the state's interagency coordinating council. Primary themes centered on: (1) the costs associated with independent contracting structures; (2) operational demands; (3) workforce stability; (4) communication consistency; and (5) implementation supports for EBP implementation. Causative coding helped to demonstrate the perceived relationships between these factors and underscored the important role of incentivization structures, collaboration opportunities, and championing in supporting the use of EBPs within a system that primarily uses independent contracting structures. The current study extends previous research by demonstrating how several system-level factors are perceived to play a role in the adoption and implementation of EBPs by independently contracted EI providers. These findings underscore the need for implementation strategies, such as incentivization strategies and social network building, to increase providers' implementation of autism EBPs within EI systems.

Naturalistic developmental behavioral interventions are an empirically supported intervention approach for young autistic children. Despite the prevalence of disruptive behaviors among autistic children, most manualized caregiver-mediated naturalistic developmental behavioral interventions include limited formal guidance on when and how to manage disruptive behavior. The present study sought to characterize how clinicians address disruptive behaviors within the caregiver-mediated naturalistic developmental behavioral intervention, Project ImPACT, the effect of disruptive behavior on Project ImPACT delivery, and the extent to which disruptive behavior impacts social communication outcomes. Data collection was embedded within outpatient early intervention services and included clinicians' report of adaptations to address behavior within the electronic medical record, child social communication outcomes from 124 children and their caregivers, and interviews with certified Project ImPACT coaches and trainers. Results indicate that close to one-third of Project ImPACT sessions included adaptations made to address behavior and regulation. Furthermore, adaptations made to address disruptive behavior were associated with more adaptations to Project ImPACT overall, although behavior adaptations were not associated with child social communication outcomes. Qualitatively, clinicians described using a flexible approach to integrate content and coaching related to behavior and regulation. The present study indicates several future directions for supporting clinicians in addressing behavior and regulation within the naturalistic developmental behavioral intervention framework.

Naturalistic, Developmental, and Behavioral Interventions (NDBIs) are an empirically supported intervention approach for young autistic children and their families. Spanish-speaking (SS) Latinx families have been underrepresented in autism intervention research, limiting our understanding of whether NDBIs are aligned with Latinx family values and belief systems. This study piloted a parent-mediated NDBI, Project ImPACT, within outpatient services for SS Latinx families. We aimed to examine the preliminary impact of Project ImPACT on family and child outcomes while using the Ecological Validity Model to evaluate program adaptations made by bilingual clinicians. Results from 15 families indicated good treatment completion and high satisfaction, alongside significant increases in child social communication skills and parent self-efficacy in supporting their child's development. Mixed-methods data examining program adaptations indicated the need to provide additional information related to autism, bilingual language development, and service navigation, as well as adaptations to language and metaphors used in the program.

Culturally responsive adaptations of commonly used interventions are key to supporting the diverse needs of all students. For check-in/check-out (CICO), a particular focus on adult--student mentoring relationships can improve effectiveness. Research suggests that CICO can be modified to support students from a variety of cultural backgrounds. Adaptations to CICO can help increase the success of the intervention. Specifically, matching students with a mentor who has a shared racial or cultural identity as well as incorporating cultural considerations into mentorship may help make CICO more culturally responsive and beneficial to students from diverse backgrounds.

Parent-mediated interventions (PMIs) are considered an evidence-based practice for fostering social communication skills in young autistic children and for promoting parent responsivity and empowerment, yet barriers to caregiver engagement are evident when PMIs are implemented within historically underserved community settings. Issues of caregiver engagement can reflect a lack of fit between PMIs and the needs of diverse families. We used a mixed methods approach to examine barriers to participating in an evidence-based PMI, Project ImPACT (Ingersoll & Dvortcsak, 2019), within an outpatient setting, as well as strategies that clinicians reported using to deliver and adapt Project ImPACT for minoritized families. Participants included 134 caregivers of a child 13 to 48 months with autism or other social communication differences and six clinicians delivering Project ImPACT. Findings suggest that caregivers experience barriers to participating in Project ImPACT and that these barriers are associated with caregivers' ability to complete the program. Although quantitative findings indicate that adaptation to Project ImPACT did not differ by caregiver and child background, qualitative findings highlighted that clinicians attempt to deliver Project ImPACT to respond to the needs of families from minoritized backgrounds by actively considering the family's culture, psychosocial experiences, goals, and specific barriers. Further, both qualitative and quantitative findings suggest that culturally responsive care and adaptations may support caregiver engagement, including rapport, trust, buy-in, and attendance. Approaches to center cultural alongside contextual/psychosocial considerations within family-centered care in the implementation of PMIs are also highlighted.

Our Texas schools are becoming more diverse in terms of language, race, and culture, but our curriculum often does not reflect this same diversity. Despite the availability of texts featuring Latinx youth identities, English curriculum still centers on canonical texts that often bolster the privilege of dominant groups over the marginalization of others. The authors assert that the English curriculum must shift to provide the large population of Latinx students in Texas, and beyond, with a curriculum that reflects their cultural identities, experiences, and languages. We make this case by discussing the necessity of incorporating culturally relevant texts and pedagogies, beginning with the engagement of Latinx culture in the curriculum, to affirm youth and empower them as bold readers, writers, and critical thinkers. We then provide practical suggestions for teachers, including a list of culturally relevant books to use with Latinx adolescent students, lesson plans, discussion questions, teaching ideas, and writing prompts for use with Elizabeth Acevedo's "The Poet X."

The learning process through forecasting patent information based on technology can provide the direction in which technology is needed, especially supporting developments into the future. Technology mapping through patent information in the market becomes leverage development of products. Foresight technology in a patent is a tool to predict advanced technology that brings a competitive product to the market needs. This paper discusses patent information that becomes useful for developing technology through emerging market segmentation through a portfolio, innovation, and emerging market based on the WIPO database. This paper used a qualitative method with descriptive analysis and study literature using Innography software to see related information utilization of bioethanol from sorghum plants. This paper aims to obtain information technology from the patent analysis in bioethanol from sorghum plants to develop foresight products. The results show 310 patents registered in WIPO fields from 2006-2021 with dominant IP Class dominate from sectors C and A, also economic value range held by the Republic of Korea. Foresight technology through patent analysis provides information for industry and stakeholders who need the impact of the implementation of the latest technology and the appropriate level of competition in the commercialization of bioethanol products from sorghum plants.

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its Minimal Information for Studies of Extracellular Vesicles, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Advanced melanoma is considered the most aggressive and deadly form of skin cancer whose incidence has been rising over the past three decades. In the absence of treatment, the median overall survival for advanced-stage metastatic disease is less than 6 months. Although most melanomas detected at an early stage can be cured with surgery, a subset of these eventually metastasize. Therefore, a critical need exists to identify unique molecular features that would be predictive of long-term outcome and response to specific therapies. Recent promising therapeutic regimens have included the use of immune checkpoint inhibitors, such as anti-PD1 antibodies. However, the ability to identify responders and non-responders to this therapy remains elusive. To address this challenge at the molecular level, previously our laboratory identified the emergence of a stem cell phenotype associated with advanced melanoma and other aggressive forms of cancer. Underlying this phenotype is the aberrant re-expression of the embryonic morphogen Nodal. Particularly noteworthy, we have observed Nodal to remain in advanced tumors of non-responders to standard-of-care therapies (i.e., BRAFi). This pilot study is the first proof-of-principle attempt to predict treatment response survival outcome in a small cohort of melanoma patients receiving anti-PD1 immune checkpoint inhibitor therapy - based on their Nodal expression profile. Using advanced multiplex immunohistochemistry-based digital pathology, the major finding of this preliminary study indicates that higher Nodal expression is often associated with poorer overall survival after anti-PD1 therapy, reaching nearly statistical relevance.

Involving communities in research prioritization is an important component of developing relevant research, policy, and healthcare questions. The coronavirus disease 2019 (COVID-19) pandemic has led to an increased need for research prioritization methods which align with public health protections. The Research Prioritization by Affected Communities (RPAC) protocol is a participatory method which directly involves historically excluded communities in developing and prioritizing research questions. We adapted the RPAC protocol for the virtual environment (RPAC-ve) to understand the research, healthcare delivery, and policy priorities of greatest importance to communities affected by the COVID-19 pandemic in relation to pregnancy in the United States. RPAC-ve included the use of a web-based platform, sharable documents for listing and ranking research questions, and a scribe to capture a visual representation of RPAC-ve sessions. RPAC-ve is a flexible and effective priority setting method which can be used to engage high risk populations.

BackgroundInjectable cabotegravir was superior to daily oral tenofovir disoproxil fumarate plus emtricitabine for HIV prevention in two clinical trials. Both trials had the primary aim of establishing the HIV prevention efficacy of long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) compared with tenofovir disoproxil fumarate plus emtricitabine daily oral PrEP. Long-acting PrEP was associated with diagnostic delays and integrase strand-transfer inhibitor (INSTI) resistance. This report presents findings from the first unblinded year of the HIV Prevention Trials Network (HPTN) 083 study.MethodsThe HPTN 083 randomised controlled trial enrolled HIV-uninfected cisgender men and transgender women at elevated HIV risk who have sex with men, from 43 clinical research sites in Africa, Asia, Latin America, and the USA. Inclusion criteria included: a negative HIV serological test at the screening and study entry, undetectable HIV RNA levels within 14 days of study entry, age 18 years or older, overall good health as determined by clinical and laboratory evaluations, and a creatinine clearance of 60 mL/min or higher. Participants were randomly allocated to receive long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP. After study unblinding, participants remained on their original regimen awaiting an extension study. HIV infections were characterised retrospectively at a central laboratory. Here we report the secondary analysis of efficacy and safety for the first unblinded year. The primary outcome was incident HIV infection. Efficacy analyses were done on the modified intention-to-treat population using a Cox regression model. Adverse events were compared across treatment groups and time periods (blinded vs unblinded). This trial is registered with ClinicalTrials.gov, NCT02720094.FindingsOf the 4488 participants who contributed person-time to the blinded analysis, 3290 contributed person-time to the first unblinded year analysis between May 15, 2020, and May 14, 2021. Updated HIV incidence in the blinded phase was 0·41 per 100 person-years for long-acting injectable cabotegravir PrEP and 1·29 per 100 person-years for daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP (hazard ratio [HR] 0·31 [95% CI 0·17-0·58], p=0·0003). HIV incidence in the first unblinded year was 0·82 per 100 person-years for long-acting PrEP and 2·27 per 100 person-years for daily oral PrEP (HR 0·35 [0·18-0·69], p=0·002). Adherence to both study products decreased after study unblinding. Additional infections in the long-acting PrEP group included two with on-time injections; three with one or more delayed injections; two detected with long-acting PrEP reinitiation; and 11 more than 6 months after their last injection. Infection within 6 months of cabotegravir exposure was associated with diagnostic delays and INSTI resistance. Adverse events were generally consistent with previous reports; incident hypertension in the long-acting PrEP group requires further investigation.InterpretationLong-acting injectable cabotegravir PrEP retained high efficacy for HIV prevention in men and transgender women who have sex with men during the first year of open-label follow-up, with a near-identical HR for HIV risk reduction between long-acting injectable cabotegravir and daily oral tenofovir disoproxil fumarate plus emtricitabine PrEP during the first year after unblinding compared with the blinded period. Extended follow-up further defined the risk period for diagnostic delays and emergence of INSTI resistance.FundingDivision of AIDS at the National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and Gilead Sciences.

Abstract HIV prevention with pre‐exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long‐acting (LA‐)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA‐PrEP, but dose‐dependent reductions in CD4+ T cell and lymphocyte counts were observed at high doses. We developed a mathematical model to predict ISL pro‐drug levels in plasma and active intracellular ISL‐triphosphate concentrations after oral vs. subcutaneous implant dosing. Using phase II trial data, we simulated antiviral effects and estimated HIV risk reduction for multiple dosages and dosing frequencies. We then established exposure thresholds where no adverse effects on immune cells were observed. Our findings suggest that implants with 56–62 mg ISL offer effective HIV risk reduction without reducing lymphocyte counts. Oral 0.1 mg daily, 3–5 mg weekly, and 10 mg biweekly ISL provide comparable efficacy, but weekly and biweekly doses may affect lymphocyte counts, while daily dosing regimen offered no advantage over existing oral PrEP. Oral 0.5–1 mg on demand provided >90% protection, while not being suitable for post‐exposure prophylaxis. These findings suggest ISL could be considered for further development as a promising and safe agent for implantable PrEP.

Abstract Type IV pili (T4P) are thin, flexible filaments exposed on the cell surface of gram-negative bacteria and are involved in pathogenesis-related processes, including cell adsorption, biofilm formation, and twitching motility. Bacteriophages often use these filaments as receptors to infect host cells. Here, we describe the identification of a protein that inhibits T4P assembly in Pseudomonas aeruginosa, discovered during a screen for host factors influencing phage infection. We show that expression of PA2560 (renamed PlzR) in P. aeruginosa inhibits adsorption of T4P-dependent phages. PlzR does this by directly binding the T4P chaperone PilZ, which in turn regulates the ATPase PilB and results in disturbed T4P assembly. As the plzR promoter is induced by cyclic di-GMP, PlzR might play a role in coupling T4P function to levels of this second messenger.

Abstract There is a compelling demand for approved plague vaccines due to the endemicity of Yersinia pestis and its potential for pandemic spread. Whilst substantial progress has been made, we recommend that the global funding and health security systems should work urgently to translate some of the efficacious vaccines reviewed herein to expedite clinical development and to prevent future disastrous plague outbreaks, particularly caused by antimicrobial resistant Y. pestis strains. Content includes material subject to Crown Copyright © 2024.This is an open access article under the Open Government License ( http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/ ).

STEM (Science, Technology, Engineering, and Mathematics) education is becoming an integral part of modern agricultural education. If the integration of STEM into agricultural education is to succeed, it is vital that educators feel confident in their ability to teach such material. This study examines Mississippi and Tennessee agricultural educators' personal teaching efficacy towards STEM subjects. Analysis indicated that educators felt most confident in their ability to teach science, followed by technology, mathematics, and then engineering. Recommendations for future research and practice include exploring agricultural educators' perceptions of and methods for teaching engineering, understanding the experience of minorities in STEM, and developing new courses for STEM-enhanced postsecondary agricultural educator preparation programs.