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Parents of children with ASD (N = 86; mean age 44.8 months; 67 boys) were randomized to either WHO Caregiver Skills Training (CST) delivered in public health settings in Italy or enhanced treatment-as-usual. Primary blinded outcomes were 3-months post-intervention change scores of autism severity and engagement during caregiver-child interaction. CST was highly acceptable to caregivers and feasibly delivered by trained local clinicians. Intention-to-treat analysis showed a large and significant effect on parent skills supporting joint engagement and a smaller significant effect on flow of interaction. Expected changes in child autism severity and joint engagement did not meet statistical significance. Analysis of secondary outcomes showed a significant effect on parenting stress, self-efficacy, and child gestures. Strategies to improve the effectiveness of CST are discussed.

Interindividual immune variability is driven predominantly by environmental factors, including exposure to chronic infectious agents such as cytomegalovirus (CMV). We investigated the effects of rhesus CMV (RhCMV) on composition and function of the immune system in young macaques. Within months of infection, RhCMV was associated with impressive changes in antigen presenting cells, T cells, and NK cells-and marked expansion of innate-memory CD8(+) T cells. These cells express high levels of NKG2A/C and the IL-2 and IL-15 receptor beta chain, CD122. IL-15 was sufficient to drive differentiation of the cells in vitro and in vivo. Expanded NKG2A/C(+)CD122(+)CD8(+) T cells in RhCMV-infected macaques, but not their NKG2-negative counterparts, were endowed with cytotoxicity against class I-deficient K562 targets and prompt IFN-gamma production in response to stimulation with IL-12 and IL-18. Because RhCMV clone 68-1 forms the viral backbone of RhCMV-vectored SIV vaccines, we also investigated immune changes following administration of RhCMV 68-1-vectored SIV vaccines. These vaccines led to impressive expansion of NKG2A/C(+)CD8(+) T cells with capacity to inhibit SIV replication ex vivo. Thus, CMV infection and CMV-vectored vaccination drive expansion of functional innate-like CD8 cells via host IL-15 production, suggesting that innatememory expansion could be achieved by other vaccine platforms expressing IL-15.

A closed-form analytical solution is developed for the first time that fully addresses the problem of choosing feedback gains that minimize the control effort required for partial pole placement in multi-input, multi-output systems. The norm of the feedback gain matrix is shown to take the form of an inverse Rayleigh quotient, such that the optimal closed-loop system eigenvectors are given as a function of the dominant (highest)eigenvectors of the matrix in the quotient. The feedback gains that deliver the required pole placement with minimum effort may then be determined using standard procedures. The original formulation by the receptance method proposed an arbitrary choice of the closed loop eigenvectors that assigned the poles exactly but was generally wasteful of control effort that might otherwise be conserved or put to good use in satisfying additional control objectives. The analytical solution is validated against a set of numerical examples.

Sparse data exist on the penetration of antiretrovirals into brain tissue. In this work, we present a framework to use efavirenz (EFV) pharmacokinetic (PK) data in plasma, cerebrospinal fluid (CSF), and brain tissue of eight rhesus macaques to predict brain tissue concentrations in HIV-infected individuals. We then perform exposure-response analysis with the model-predicted EFV area under the concentration-time curve (AUC) and neurocognitive scores collected from a group of 24 HIV-infected participants. Adult rhesus macaques were dosed daily with 200 mg EFV (as part of a four-drug regimen) for 10 days. Plasma was collected at 8 time points over 10 days and at necropsy, whereas CSF and brain tissue were collected at necropsy. In the clinical study, data were obtained from one paired plasma and CSF sample of participants prescribed EFV, and neuropsychological test evaluations were administered across 15 domains. PK modeling was performed using ADAPT version 5.0 Biomedical Simulation Resource, Los Angeles, CA) with the iterative two-stage estimation method. An eight-compartment model best described EFV distribution across the plasma, CSF, and brain tissue of rhesus macaques and humans. Model-predicted median brain tissue concentrations in humans were 31 and 8,000 ng/mL, respectively. Model-predicted brain tissue AUC was highly correlated with plasma AUC (γ = 0.99, P < 0.001) but not CSF AUC (γ = 0.34, P = 0.1) and did not show any relationship with neurocognitive scores (γ < 0.05, P > 0.05). This analysis provides an approach to estimate PK the brain tissue in order to perform PK/pharmacodynamic analyses at the target site. © 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

Early spontaneous gesture specifically deictic gesture predicts subsequent vocabulary development in typically developing (TD) children. Here we ask whether deictic gesture plays a similar role in predicting later vocabulary size in children with Down Syndrome (DS) who have been shown to have difficulties in speech production but strengths in spontaneous gesture and baby sign use. We compared the gestures and baby signs produced by twenty three children with DS (Mage = ?;?) and twenty three TD children (Mage = ?;?) in relation to their expressive spoken vocabulary size one year later. Children with DS showed significant deficits in gesture production particularly for deictic gestures but strengths in baby sign production compared to their typically developing peers. More importantly it was the baby signs produced by children with DS but not deictic gestures that predicted their spoken vocabulary size one year later. Our results further highlight the important role baby signs can play in language development in children with developmental disorders.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of ;omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution. (C) 2013 Published by IFPA and Elsevier Ltd.

Short interview with Stephen Wolfram (1/2 page).