Current and ideal living arrangements and supports for Canadian adults with fetal alcohol spectrum disorder: Part II-Perspectives from caregivers.

BACKGROUND: Caregivers supporting adults with fetal alcohol spectrum disorder (FASD) report concerns regarding living arrangements and services for their adult children with FASD. Best practices for living support for adults with FASD are under-researched, and few studies have explored the experiences of caregivers whose children are adults. This study examined the perspectives of caregivers who support adults (18+) with FASD regarding: (1) current ways adults with FASD are supported with daily life activities; and (2) ideal future living arrangements and supports. METHODS: This article presents findings from the perspective of caregivers who support adults with FASD, as part of a broader project involving both adults with FASD and caregivers. Semi-structured interviews were conducted with 11 Canadian caregivers who live at home with an adult with FASD (aged 18+). Responses were examined using framework analysis, a structured approach to analyzing qualitative data. RESULTS: Caregivers described their experiences and perspectives regarding: (1) current ways adults with FASD are supported in their daily activities; (2) strategies for successful support; (3) ideal future living arrangements and supports; and (4) concerns for the future. Notably, almost every participant raised pressing concerns regarding the future living arrangements for the person they support once they are no longer able to provide care. CONCLUSIONS: This study explores caregivers' perspectives regarding living support needed by adults with FASD, which can inform support programs and housing services. Findings demonstrate an urgent need for policy change directed toward developing available, affordable, and appropriate housing for adults with FASD.

Liquid Structure of Ionic Liquids with [NTf2]- Anions, Derived from Neutron Scattering.

The liquid structure of three common ionic liquids (ILs) was investigated by neutron scattering for the first time. The ILs were based on the bis(trifluoromethanesulfonyl)imide anion, abbreviated in the literature as [NTf2]- or [TFSI]-, and on the following cations: 1-ethyl-3-methylimidazolium, [C2mim]+; 1-decyl-3-methylimidazolium, [C10mim]+; and trihexyl(tetradecyl)phosphonium, [P666,14]+. Comparative analysis of the three ILs confirmed increased size of nonpolar nanodomains with increasing bulk of alkyl chains. It also sheds light on the cation-anion interactions, providing experimental insight into strength, directionality, and angle of hydrogen bonds between protons on the imidazolium ring, as well as H-C-P protons in [P666,14]+, to oxygen and nitrogen atoms in the [NTf2]-. The new Dissolve data analysis package enabled, for the first time, the analysis of neutron scattering data of ILs with long alkyl chains, in particular, of [P666,14][NTf2]. Results generated with Dissolve were validated by comparing outputs from three different models, starting from three different sets of cation charges, for each of the three ILs, which gave convergent outcomes. Finally, a modified method for the synthesis of perdeuterated [P666,14][NTf2] has been reported, with the aim of reporting a complete set of synthetic and data processing approaches, laying robust foundations that enable the study of the phosphonium ILs family by neutron scattering.

Comparing clinical acne vulgaris severity to adolescent and parent perceptions of acne severity and impact on quality of life.

BACKGROUND/OBJECTIVES: Little research has compared clinician acne severity assessment with either adolescent- or parent-rated scales of acne severity or impact on quality of life (QOL). We sought to assess how adolescents and their parents perceive the severity and impact of acne on the adolescent's QOL and correlate this with clinical severity. METHODS: Each adolescent and a parent completed a validated QOL survey regarding the adolescent's acne and rated the adolescent's acne severity and QOL impact using a Likert scale. Clinicians assessed the adolescent's acne using a standardized acne severity scale. Statistical analysis compared adolescent scores with respective parent scores or with clinician assessment using a paired t test or Spearman rank-order correlation test. RESULTS: The Likert impact score more accurately reflected acne impact on QOL for adolescents than for parents when considering the validated QOL survey as the gold standard (r2  = .56 vs r2  = .36). Likert scores for adolescents and parents were weakly correlated for acne severity but not for acne QOL impact (r2  = .36 vs r2  = .18). Correlations of acne severity scores between clinician and either adolescent or parent were weak. CONCLUSIONS: Parents and adolescents are in relative agreement regarding acne severity and QOL impact. However, parent and adolescent perceptions are disparate from clinician acne assessment. It is important that physicians identify and consider adolescent and parent perceptions in addition to clinical assessment to better inform the approach to acne management.

Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8+ effector recruitment to mucosal tissues.

CD8+ T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protective CD8+ T cells to mucosal tissues. Here we dissect the underlying mechanism. We show that adenovirus serotype 5 (Ad5) bio-distributes at very low level to non-lymphoid tissues after skin immunisation. This drives the expansion and activation of CD3- NK1.1+ group 1 innate lymphoid cells (ILC1) within the FRT, essential for recruitment of CD8+ T-cell effectors. Interferon gamma produced by activated ILC1 is critical to licence CD11b+Ly6C+ monocyte production of CXCL9, a chemokine required to recruit skin primed CXCR3+ CD8+T-cells to the FRT. Our findings reveal a novel role for ILC1 to recruit effector CD8+ T-cells to prevent virus spread and establish immune surveillance at barrier tissues.

Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays.

The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8+ T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8+ T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8+ T cell expression of CXCR3+, CD103+, CD49a+, CD69+, CD127+ homing, retention and survival markers. Furthermore, memory CD8+ T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8+ T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces.

Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions.

Osteosarcoma is the most common bone cancer in children and adolescents. Although 70% of patients with localized disease are cured with chemotherapy and surgical resection, patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T lymphocytes (CTLs) limit the development of metastatic osteosarcoma. We have investigated the role of PD-1, an inhibitory TNFR family protein expressed on CTLs, in limiting the efficacy of immune-mediated control of metastatic osteosarcoma. We show that human metastatic, but not primary, osteosarcoma tumors express a ligand for PD-1 (PD-L1) and that tumor-infiltrating CTLs express PD-1, suggesting this pathway may limit CTLs control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor-infiltrating CTLs during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTLs in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. Our results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy.

Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats.

RATIONALE: Vulnerability to alcoholism is determined by many factors, including the balance of pleasurable vs. aversive alcohol-induced sensations: pleasurable sensations increase intake, while aversive sensations decrease it. Female sex and adolescent age are associated with lower sensitivity to intake-reducing effects and more rapid development of alcohol abuse. OBJECTIVES: This study assessed voluntary drinking and the aversive effects of alcohol to determine whether these measures are inversely related across the sexes and development. METHODS: Voluntary drinking of 20 % ethanol in an every-other-day (EOD) availability pattern and the dose-response relationship of ethanol conditioned taste aversion (CTA) were assessed in male and female adolescent and adult rats. RESULTS: CTA was sex specific in adult but not adolescent rats, with adult females exhibiting less aversion. Voluntary ethanol consumption varied according to age and individual differences but was not sex specific. Adolescents initially drank more than adults, exhibited greater day-to-day variation in consumption, were more susceptible to the alcohol deprivation effect, and took longer to establish individual differences in consumption patterns. CONCLUSIONS: These results show that the emergence of intake patterns differs between adolescents and adults. Adolescents as a group initiate drinking at high levels but decrease intake as they mature. A subset of adolescents maintained high drinking levels into adulthood. In contrast, most adults consumed at steady, low levels, but a small subset quickly established and maintained high-consumption patterns. Adolescents also showed marked deprivation-induced increases. Sex differences were not observed in EOD drinking during either adolescence or adulthood.