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The purpose of this study was to evaluate the effect of a multicomponent mathematics intervention (modified schema-based instruction, video anchors, and goal setting with self-graphing) on mathematical problem-solving skills of secondary students with intellectual and developmental disabilities. Three participants were taught to solve percent of change word problems, which involved calculating the discounted price of an item or activity after using a coupon and then determining whether they had enough money to make the purchase. Results of the multiple probe across participant design indicate a functional relation between the intervention and problem solving, and all participants were able to generalize skills from word problems to real-world stimuli (i.e., coupons, receipts, menus). Implications for practice and future research are discussed.

In the current study, we taught three middle school peers without disabilities to implement a commercially available literacy program with students with extensive support needs (ESN). Our teaching package included behavior skills training, ongoing feedback, and visual supports. We employed a multiple probe across participants design to evaluate the efficacy of the training package. Data indicated it was effective in improving the peers’ performance. Further, the majority of participants reported favorable perceptions of the peer implemented package.

There is very limited research on inclusive mathematics instruction for students with extensive support needs (i.e., moderate to severe intellectual disability, autism, multiple disabilities) and this is a critical area of need. The purpose of this article is to propose a framework for mathematics instruction for students with extensive support needs in inclusive settings using practices that have been found effective in more restrictive settings, combined with the limited findings on effective inclusive practices for students with extensive support needs. A conceptual model for mathematics instruction for students with extensive support needs is illustrated and described. The proposed model provides guidance for collaborative teams and key stakeholders when planning for mathematics instruction in inclusive settings. Barriers to including students with extensive support needs in general education mathematics settings are discussed and recommendations for overcoming these barriers are described.

Although solving word problems involves both literacy and mathematics skills, research to date has only targeted mathematical learning. This study sought to increase teaching efficiency by embedding literacy instruction within mathematical word problem solving instruction for three elementary students with intellectual and developmental disabilities. A multiple probe across participants design showed a functional relation between modified schema-based instruction (MSBI) and mathematical word problem solving. All participants increased knowledge of nontargeted literacy skills using instructive feedback, and two participants demonstrated a further increase following the use of constant-time delay (CTD). The results highlight several implications for practice regarding the feasibility of MSBI with instructive feedback to simultaneously address multiple academic domains or skills. Limitations and suggestions for future research are discussed.

The Common Core State Standards (CCSS) in mathematics were created to help all students become prepared for the demands of future careers and life in an age of technology. Similarly, students with moderate and severe disability will need these skills to meet these changing expectations. Although mathematics instruction could focus on a few of the earliest mathematics skills throughout the students school career, research presented in this article shows students with moderate and severe disability can learn skills that align with the grade level of their chronological age while also practicing early numeracy skills. This article provides teachers with a 6-step approach to providing instruction to students with moderate and severe disability aligned to the new CCSS. (Contains 2 tables and 2 figures.)

Mrs. Lewis's high school English language arts class has 12 students with a wide range of ability levels: two students use wheelchairs and have limited mobility in their arms, one student has low vision, five students are nonverbal, four have autism spectrum disorder, three students use English as their second language, and all have moderate or severe intellectual disability. Each of the ELA anchor standard strands contain subgroups: * Reading and informational text: key ideas and details, craft and structure, integration of knowledge and ideas, and range of reading and level of text complexity. * Writing: text types and purposes, production and distribution of writing, research to build and present knowledge, and range of writing. * Speaking and listening: comprehension and collaboration and presentation of knowledge and ideas. * Language: conventions of standard English, knowledge of language, and vocabulary acquisition and use.\\n Technology also can be used to increase independence during a story-based lesson.

Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusions of bnAbs. In this study, we administered a recombinant bicistronic adeno-associated virus (AAV8) vector coding for both the light and heavy chains of the potent broadly neutralizing HIV-1 antibody VRC07 (AAV8-VRC07) to eight adults living with HIV. All participants remained on effective anti-retroviral therapy (viral load (VL) <50 copies per milliliter) throughout this phase 1, dose-escalation clinical trial ( NCT03374202 ). AAV8-VRC07 was given at doses of 5 × 10 10 , 5 × 10 11 and 2.5 × 10 12 vector genomes per kilogram by intramuscular (IM) injection. Primary endpoints of this study were to assess the safety and tolerability of AAV8-VRC07; to determine the pharmacokinetics and immunogenicity of in vivo VRC07 production; and to describe the immune response directed against AAV8-VRC07 vector and its products. Secondary endpoints were to assess the clinical effects of AAV8-VRC07 on CD4 T cell count and VL and to assess the persistence of VRC07 produced in participants. In this cohort, IM injection of AAV8-VRC07 was safe and well tolerated. No clinically significant change in CD4 T cell count or VL occurred during the 1–3 years of follow-up reported here. In participants who received AAV8-VRC07, concentrations of VRC07 were increased 6 weeks ( P  = 0.008) and 52 weeks ( P  = 0.016) after IM injection of the product. All eight individuals produced measurable amounts of serum VRC07, with maximal VRC07 concentrations >1 µg ml −1 in three individuals. In four individuals, VRC07 serum concentrations remained stable near maximal concentration for up to 3 years of follow-up. In exploratory analyses, neutralizing activity of in vivo produced VRC07 was similar to that of in vitro produced VRC07. Three of eight participants showed a non-idiotypic anti-drug antibody (ADA) response directed against the Fab portion of VRC07. This ADA response appeared to decrease the production of serum VRC07 in two of these three participants. These data represent a proof of concept that adeno-associated viral vectors can durably produce biologically active, difficult-to-induce bnAbs in vivo, which could add valuable new tools to the fight against infectious diseases. Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

Despite the success of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at‐risk patient populations, including the immunocompromised. While many neutralizing antibodies have been identified, and several approved, to treat COVID‐19, systemic delivery, large doses, and high costs have the potential to limit their widespread use, especially in low‐ and middle‐income countries. To use these antibodies more efficiently, an inhalable formulation is developed that allows for the expression of mRNA‐encoded, membrane‐anchored neutralizing antibodies in the lung to mitigate SARS‐CoV‐2 infections. First, the ability of mRNA‐encoded, membrane‐anchored, anti‐SARS‐CoV‐2 antibodies to prevent infections in vitro is demonstrated. Next, it is demonstrated that nebulizer‐based delivery of these mRNA‐expressed neutralizing antibodies potently abrogates disease in the hamster model. Overall, these results support the use of nebulizer‐based mRNA expression of neutralizing antibodies as a new paradigm for mitigating respiratory virus infections. Despite the success of vaccination, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) remains an ongoing threat worldwide. Monoclonal antibody therapies have proven useful but are expensive and require high systemic doses. This study reports mRNA‐expressed membrane‐anchored antibodies along with an inhalable polymeric nanoparticle formulation that prevent SARS‐CoV‐2 infection in the stringent hamster model.

Purpose To determine whether hydrocortisone improves mortality in severe community-acquired pneumonia (CAP). Methods In an international adaptive randomized controlled platform trial testing multiple interventions, adults admitted to the intensive care unit (ICU) with severe CAP were randomized to a 7-day course of intravenous hydrocortisone (50 mg every 6 h) or control (no corticosteroid). The primary end point was 90-day all-cause mortality, analyzed iteratively by a Bayesian hierarchical model estimating distinct treatment effects for patients presenting with influenza (Y/N) and shock (Y/N). Results Fixed 7-day course hydrocortisone enrollment was stopped for futility (< 5% probability of > 20% relative improvement). Of 658 patients enrolled, 536 were randomized to hydrocortisone and 122 to control. Vital status at day 90 was missing for 15 patients. Day 90 mortality was 15% (78/521) and 9.8% (12/122) for the hydrocortisone and control groups. The adjusted odds ratio ranged from 1.52 to 1.63 (with all 95% CrI crossing 1), while the probability of > 20% relative reduction of day 90 mortality ranged from 7.1 to 3.3% across influenza and shock strata. Results were consistent in sensitivity and pre-specified secondary outcomes. In exploratory analyses, the duration of shock appeared lower in the hydrocortisone group compared with control (median (IQR) of 2 (2–5) days compared to control 3 (2–6.75) days, p value = 0.05). Conclusions Among patients with severe CAP, treatment with a 7-day course of hydrocortisone, compared with no hydrocortisone, appears unlikely to yield a large reduction in mortality. Smaller benefits and possible harm are not excluded. Trial registration Clinicaltrials.gov identifier: NCT02735707 (registration date: November 4th, 2016).