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Preclinical studies of viral vector–based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys.

Beginning parenting programs in the prenatal and early postnatal periods have a large potential for impact on later child and maternal outcomes. Home-based parenting programs, such as the Nurse Family Partnership (NFP), have been established to help address this need. Program reach and impact is dependent on successful engagement of expecting mothers with significant risks; however, NFP attrition rates remain high. The current study qualitatively examined engagement and attrition from the perspectives of NFP nurses and mothers in order to identify mechanisms that enhance service engagement. Semi-structured interviews were conducted in focus groups composed of either engaged (27 total mothers) or unengaged (15 total mothers) mothers from the NFP program. NFP nurses (25 total nurses) were recruited for individual semi-structured interviews. Results suggest that understanding engagement in the NFP program requires addressing both initial and sustained engagement. Themes associated with enhanced initial engagement include nurse characteristics (e.g., flexible, supportive, caring) and establishment of a solid nurse-family relationship founded on these characteristics. Factors impacting sustained engagement include nurse characteristics, provision of educational materials on child development, individualized services for families, and available family support. Identified barriers to completing services include competing demands and lack of support. Findings of this study have direct relevance for workforce planning, including hiring and training through integrating results regarding effective nurse characteristics. Additional program supports to enhance parent engagement may be implemented across home-based parenting programs in light of the current study’s findings.

An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs). To test whether rLCMV vectors constitute an effective vaccine platform in NHPs, we developed rLCMV vectors expressing SIVmac239 Env and Gag antigens and assessed their immunogenicity in mice and cynomolgus macaques. Immunization with rLCMV vaccine vectors expressing SIV Env and Gag was effective at generating SIV-specific T cell and antibody responses in both mice and NHPs. Epitope mapping using SIV Env in C57BL/6 mice demonstrated that rLCMV vectors induced sustained poly-functional responses to both dominant and subdominant epitopes. Our results suggest the potential of rLCMV vectors as vaccine candidates. Future SIV challenge experiments in rhesus macaques will be needed to assess immune protection by these vaccine vectors.

Objective Blunt cerebrovascular injury (BCVI) is a collective term describing blunt-force trauma involving the carotid and/or vertebral arteries. As awareness, screening protocols, and diagnostic modalities have advanced over recent decades, reported incidence has risen accordingly. This bibliometric review examines the most highly cited literature on BCVI, spotlighting key academic trends, influential authors, and journals that have shaped our current understanding. Methods The Scopus database was queried for BCVI-related articles published through June 2024 with titles, abstracts, and/or keywords containing the terms \"BCVI\" OR \"blunt cerebrovascular injury\" OR \" blunt carotid artery injury\" OR “blunt carotid artery trauma” OR “traumatic carotid artery dissection” OR \"blunt vertebral artery injury\" OR “blunt vertebral artery trauma” OR “traumatic vertebral artery dissection.” Results were organized by descending citation count and followed by citations per year. The top 50 most-cited articles were selected for analysis. Additional data collected included document titles, publication year, authors, specialty of the first author, affiliations, country of origin, and publishing journal. Results This study retrieved 426 BCVI-related articles published since 1974. The top 50, published between 1974 and 2018, garnered 6,760 citations, with an average of 135.2 citations per article, and a mean self-citation rate of 8.83%. Conclusions This bibliometric analysis maps the academic landscape of BCVI, presenting valuable insights into its evolution and the pivotal studies that have informed our knowledge and clinical practice thus far. It serves as a foundation for future research directions and clinical advancements, aimed at enhancing patient outcomes in the face of blunt cerebrovascular trauma. Clinical Trial Number Not applicable.

Estimates for the UK suggest that alcohol consumption during pregnancy and prevalence of fetal alcohol spectrum disorder (FASD)—the most common neurodevelopmental condition—are high. Considering the significant health and social impacts of FASD, there is a public health imperative to prioritise prevention, interventions and support. In this article, we outline the current state of play regarding FASD knowledge and research in the UK, which is characterised by a lack of evidence, a lack of dedicated funding and services, and consequently little policy formulation and strategic direction. We highlight progress made to date, as well as current knowledge and service gaps to propose a way forward for UK research.

Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains. This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365. All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine. No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited. NCT02218125.

Ground, as the foundation for both architectural constructs and Cubist collages, is subtle and non-hierarchical: design potential exists at these moments of disconnect and overlap, where the relationship between figure and field is ambiguous and in flux. A topical architectural design studio explores these relationships, including fragmentation, aggregation, and synthesis, through the collage-making process. Collage is explored as a methodology for design, understanding collage as a vehicle for analysis, a vehicle for design and representation, and finally architecture itself as collage. With this in mind, the collage-making process serves as a venue for analysis of the industrial landscape, offering a greater understanding of the experiential phenomena extant in a site that can be heightened/subverted/manipulated to reveal the rich layers of physical and cultural memory imbedded in the industrial landscape. Engaging an abandoned industrial artifact in Charlottesville, Virginia’s Woolen Mills neighborhood, we have implemented a design methodology of collage, beginning with an analysis of the existing conditions of ground, including physical, perceptual, historical, and cultural phenomena as a means of understanding the site, and ultimately informing a design intervention.

A growing number of evidence-based services are available for fetal alcohol spectrum disorder (FASD), but few focus on caregiver psychoeducation. Despite new guidance in the UK requiring FASD services, the evidence base for effective interventions is currently lacking. An FASD caregiver training program would be a novel and valuable addition to service provision. SPECIFiC (Salford parents and carers education course for improvements in FASD outcomes in children) was developed using an evidence-based logic model with input from clinicians, families, and the charity sector. The course was delivered online to a small number ( n  = 9) of families in a mixed-methods, exploratory pre-feasibility study. Families were represented by either one or two caregivers, all of whom were adoptive parents or special guardians of a child with FASD. Parent perceptions were assessed using semi-structured interviews. The performance of proposed outcome measures (stress, psychological functioning, parenting self-efficacy, knowledge of FASD, and child behavioral difficulties) was evaluated. Pre- and post-measures were acceptable and showed promise as outcome measures for a future trial. Participants spoke positively about the course, welcomed the opportunity to discuss their own situations with other FASD caregivers, found the advice to be immediately useful, and described the course as therapeutic. Suggestions for improvements tended to focus on timing and technical issues. Based on a small sample, SPECIFiC was shown to be an acceptable and feasible psychoeducation program. Further evidence from a randomized controlled trial is needed to evaluate whether SPECIFiC can lead to reduced stress in parents, improved parenting self-efficacy, and ultimately a reduction in children’s behavioral difficulties. Highlights New psychoeducation program for caregivers of children with FASD Dual delivery by professional trainer and experienced caregiver Small pre-feasibility study ( n  = 9) suggests the program is acceptable and feasible Participants responded positively to the program

Reservoirs of virus infection represent the most important reason why HIV-1 cannot be cured with current antiretroviral drugs; now the refractory viral reservoir is shown to be seeded as early as 3 days after infection in a monkey model, even before the virus is detected in the blood. Early HIV-1 reservoir formation Reservoirs of virus infection, impervious to antiviral drugs, are a serious obstacle to attempts to eradicate human immunodeficiency virus type 1 (HIV-1). Dan Barouch and colleagues explore the timing of the formation of these reservoirs in a monkey model. They find that antiviral treatment as early as three days after infection of macaques with simian immunodeficiency virus — prior to the onset of viraemia — fails to prevent the seeding of viral reservoirs, and the virus eventually rebounds when drug treatment is discontinued. The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies 1 , 2 , 3 , 4 , 5 . However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIV MAC251 infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the ‘eclipse’ phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.

Pablo Picasso’s first act of collage-making in May of 1912, in its conceptual, material, and technical originality, has profoundly influenced numerous artists and architects throughout the twentieth century and into the twenty-first. Collage inherently emphasizes process over product, offering the potential for a multiplicity of readings while re-conceptualizing three-dimensional space. This ambiguity creates opportunities for multivalence in the architectural design process and the resultant work of architecture, responding to the richness and complexities extant in sites and cities. Collage can be considered in the following ways in its relevance to the field of architecture: collage as autonomous work of art, collage as analytical and/or design tool, and architecture as collage. The richness and potentiality of collage as a tool for analysis and design lies in the diversity of media and techniques. This paper will address the efficacy of collage as a representational medium integrated into the design process in the work of Le Corbusier and Eduardo Chillida, whose work proves a lineage of the Cubist conception of space through the translation from collage to built form. Considering collage as an instrument for analysis and design, drawing on decades of relevance in art and architecture, offers a diverse set of material, technical, and conceptual precedent for designers.