ARS Accreditation Framework – School Organization

This session will guide you through the step by step accreditation standards for running the business side of Recovery High Schools. Learn from the best as you navigate selecting the model, identifying leadership, energizing a Board of Directors, building community partners and much more. 1. Business Planning: How do high schools operate with a revised strategic business plan that provides for a reasonable level of organizational autonomy and is created for longterm survivability and viability, 2. Board of Directors: How does the school have a functional and involved Board of Directors?, 3. School Leadership: How does the school have a recognized and fully trained leader or leaders who operate with a level of autonomy and flexibility within the larger organizational system?, 4. Community Partnerships: How does the school establish collaborative partnerships with local schools, treatment centers, and other community resources to create a coordinated system of support?, 5. Public Relations & Privacy Issues: How does the school have a plan to promote the school and its programs while respecting the privacy and safety of its students and families?, and 6. Program Evaluation: How does the school regularly evaluate the academic and therapeutic programs for continuous program improvement

POP-UP: University and Community Collaborations Towards Addressing Youth Substance Misuse

This presentation shares the process and findings of a funded interdisciplinary project involving researchers engaging in the difficult integrative dialogues to incorporate findings from diverse areas of research and practice. This interdisciplinary project, part of the Pop-Up Institute initiative at UT Austin, brought together researchers, community partners, peers, and students for one year to foster the kind of collaborative deconstruction of silos that is essential to the progression of the addiction recovery field. Results, lessons learned, and future directions gleaned from the Pop-Up Institute's year of activities will be discussed during this presentation

Maternal Parenting Stress In Autism, Autism Associated With Fragile X, and Fragile X Alone: An Examination of Associated Child and Maternal Factors In Three High-Risk Groups

The current study examined the association between specific child and maternal factors and parenting stress in three high-risk groups of mothers - mothers of boys diagnosed with idiopathic autism (IA), mothers of boys diagnosed with autism spectrum disorder (ASD) associated with fragile X syndrome (AFXS), and mothers of boys diagnosed with fragile X syndrome (FXS) alone. These three groups of mothers are thought to share some degree of genetic vulnerability to stress, as well as exposure to varying levels of challenging child behavioral characteristics. Theories of parenting stress incorporate multiple components, including parent, child, and parent-child interaction factors. The current study examined differences in maternal parenting stress across groups of high-risk mothers, as well as the relationship between child problem behaviors and the various dimensions of parenting stress. Additionally, the current study examined the relationship between maternal characteristics of the broader autism phenotype (BAP) and parenting stress in mothers of children with IA. The differential impact of maternal BAP across dimensions of parenting stress was explored. The primary sample of participants for the present study came from an extant dataset including 48 mothers of boys with IA, 20 mothers of boys with AFXS, and 56 mothers of boys with FXS alone. A secondary sample of 20 biological mothers of male children with IA was recruited to address secondary questions related to the maternal BAP - parenting stress relationship. Results indicated a significant difference in child- related parenting stress among groups of mothers from the primary sample. Regression analysis indicated significant main effects for general child behavior problems and maternal IQ, but not for ASD symptomatology for the primary sample. Results also indicated a significant interaction between maternal group and general child behavior problems. Exploratory secondary analyses indicated that scores from one subscale of a BAP measure significantly predicted both child- and parent-related stress scores. Surprisingly, general child behavior problems did not make a significant contribution to the prediction of parenting stress scores for mothers from this secondary sample. Limitations of the current study and potential implications for practice are discussed

Two-Dimensional Planetary Surface Landers

We proposed to develop a new landing approach that significantly reduces development time and obviates the most complicated, most expensive, and highest-risk phase of a landing mission. The concept is a blanket- or carpet-like two-dimensional (2D) lander (~1-m 1-m surface area and <1-cm thick) with a low mass/drag ratio, which allows the lander to efficiently shed its approach velocity and provide a more robust structure for landing integrity. The form factor of these landers allows dozens to be stacked on a single spacecraft for transport and distributed en masse to the surface. Lander surfaces will be populated on both sides by surface-mount, low-profile sensors and instruments, surface-mount telecom, solar cells, batteries, processors, and memory. Landers will also incorporate thin flexible electronics, made possible in part by printable electronics technology. The mass and size of these highly capable technologies further reduces the required stiffness and mass of the lander structures to the point that compliant, lightweight, robust landers capable of passive landings are possible. This capability avoids the costly, complex use of rockets, radar, and associated structure and control systems. This approach is expected to provide an unprecedented science payload mass to spacecraft mass ratio of approximately 80% (estimated based on current knowledge). This compared to ~1% for Pathfinder, ~17% for MER, and 22% for MSL rovers. Clearly, one difference is rovers vs. a lower capability lander. An outcome of the Phase I study is a clear roadmap for near-term demonstration and long-term technology development

HIV-1 Superinfection in Women Broadens and Strengthens the Neutralizing Antibody Response

Identifying naturally-occurring neutralizing antibodies (NAb) that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb breadth has previously been shown to be positively associated with viral diversity. Therefore, we hypothesized that superinfected individuals develop a broad NAb response as a result of increased antigenic stimulation by two distinct viruses. To test this hypothesis, plasma samples from 12 superinfected women each assigned to three singly infected women were tested against a panel of eight viruses representing four different HIV-1 subtypes at matched time points post-superinfection (∼5 years post-initial infection). Here we show superinfected individuals develop significantly broader NAb responses post-superinfection when compared to singly infected individuals (RR = 1.68, CI: 1.23–2.30, p = 0.001). This was true even after controlling for NAb breadth developed prior to superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both unadjusted and adjusted analyses showed significantly greater potency in superinfected cases compared to controls. Notably, two superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1∶300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth was detected within a year of superinfection in both of these individuals, which was within 1.5 years of their initial infection. These data suggest that sequential infections lead to augmentation of the NAb response, a process that may provide insight into potential mechanisms that contribute to the development of antibody breadth. Therefore, a successful vaccination strategy that mimics superinfection may lead to the development of broad NAbs in immunized individuals

Systems Analysis of MVA-C Induced Immune Response Reveals Its Significance as a Vaccine Candidate against HIV/AIDS of Clade C

Based on the partial efficacy of the HIV/AIDS Thai trial (RV144) with a canarypox vector prime and protein boost, attenuated poxvirus recombinants expressing HIV-1 antigens are increasingly sought as vaccine candidates against HIV/AIDS. Here we describe using systems analysis the biological and immunological characteristics of the attenuated vaccinia virus Ankara strain expressing the HIV-1 antigens Env/Gag-Pol-Nef of HIV-1 of clade C (referred as MVA-C). MVA-C infection of human monocyte derived dendritic cells (moDCs) induced the expression of HIV-1 antigens at high levels from 2 to 8 hpi and triggered moDCs maturation as revealed by enhanced expression of HLA-DR, CD86, CD40, HLA-A2, and CD80 molecules. Infection ex vivo of purified mDC and pDC with MVA-C induced the expression of immunoregulatory pathways associated with antiviral responses, antigen presentation, T cell and B cell responses. Similarly, human whole blood or primary macrophages infected with MVA-C express high levels of proinflammatory cytokines and chemokines involved with T cell activation. The vector MVA-C has the ability to cross-present antigens to HIV-specific CD8 T cells in vitro and to increase CD8 T cell proliferation in a dose-dependent manner. The immunogenic profiling in mice after DNA-C prime/MVA-C boost combination revealed activation of HIV-1-specific CD4 and CD8 T cell memory responses that are polyfunctional and with effector memory phenotype. Env-specific IgG binding antibodies were also produced in animals receiving DNA-C prime/MVA-C boost. Our systems analysis of profiling immune response to MVA-C infection highlights the potential benefit of MVA-C as vaccine candidate against HIV/AIDS for clade C, the prevalent subtype virus in the most affected areas of the world

Impact of LS Mutation on Pharmacokinetics of Preventive HIV Broadly Neutralizing Monoclonal Antibodies: A Cross-Protocol Analysis of 16 Clinical Trials in People without HIV

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications

Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition

BACKGROUND : Whether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear. METHODS : We enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay. RESULTS : Adverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/ HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], −11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, −45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates. CONCLUSIONS : VRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective.Supported by Public Health Service Grants (UM1 AI068614, to the HIV Vaccine Trials Network [HVTN]; UM1 AI068635, to the HVTN Statistical Data and Management Center [SDMC], Fred Hutchinson Cancer Research Center [FHCRC]; UM1 AI068618, to HVTN Laboratory Center, FHCRC; UM1 AI068619, to the HPTN Leadership and Operations Center; UM1 AI068613, to the HIV Prevention Trials Network [HPTN] Laboratory Center; UM1 AI068617, to the HPTN SDMC; and P30 AI027757, to the Center for AIDS Research, University of Washington) from the National Institute of Allergy and Infectious Diseases (NIAID) and by the Intramural Research Program of the NIAID.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH

PHOBOS Exploration using Two Small Solar Electric Propulsion Spacecraft

Primitive bodies are exciting targets for exploration as they provide clues to the early Solar system conditions and dynamical evolution. The two moons of Mars are particularly interesting because of their proximity to an astrobiological target. However, after four decades of Mars exploration, their origin and nature remain enigmatic. In addition, when considering the long-term objectives of the flexible path for the potential human exploration to Mars, Phobos and Deimos present exciting intermediate opportunities without the complication and expense of landing and ascending from the surface. As interest in these targets for the next frontier of human exploration grows, characterization missions designed specifically to examine surface properties, landing environments, and surface mapping prior to human exploration are becoming increasingly important. A precursor mission concept of this sort has been developed using two identical spacecraft designed from low cost, flight proven and certified off-the-shelf component and utilizing Solar Electric Propulsion (SEP) to orbit both targets as secondary payloads launched aboard any NASA or GTO launch. This precursor mission has the potential to address both precursor measurements that are strategic knowledge gaps and decadal science, including soil physical properties at the global and local (human) scale and the search for in situ resources