Intimate partner violence exposure during infancy and social functioning in middle childhood: An Australian mother and child cohort study.

Social functioning of children with experiences of intimate partner violence (IPV) between caregivers in early childhood has received less attention than emotional-behavioral outcomes. Drawing on data from 1507 ten-year-old Australian-born children and their mothers participating in a community-based longitudinal study, this study examined the associations between IPV exposure during infancy and social development during middle childhood. IPV during the first 12 months of life was associated with lower social skills, higher peer problems, and peer victimization at age 10 years, while accounting for concurrent IPV. This study provides evidence for the long-term impacts of early-life IPV exposure on children's social functioning, and the importance of prevention and early intervention programs focused on social development following experiences of IPV.

A randomised controlled trial of long NY-ESO-1 peptide-pulsed autologous dendritic cells with or without alpha-galactosylceramide in high-risk melanoma.

AIM: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells. OBJECTIVE: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV). DESIGN, SETTING AND PARTICIPANTS: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II-IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board. INTERVENTIONS: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 106 cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer. OUTCOME MEASURES: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over. RESULTS: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4+ T cells, but the difference between the treatment arms was not statistically significant (difference - 6.85, 95% confidence interval, - 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms. CONCLUSIONS: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design. CLINICAL TRIAL REGISTRATION: ACTRN12612001101875. Funded by the Health Research Council of New Zealand.

"We're in the background": Facilitators and barriers to fathers' engagement and participation in a health intervention during the early parenting period.

ISSUES ADDRESSED: Little is known about the barriers and facilitators associated with engaging fathers in interventions targeting their physical and mental health. The current research therefore aimed to explore fathers' perceived barriers and facilitators to engagement and participation in a health intervention delivered during the early parenting period. METHODS: Eleven fathers of young children (0-4 years) were interviewed about their perceptions and experiences of facilitators and barriers to engaging and participating in an intervention (Working Out Dads) to target their mental and physical health. Interviews were recorded and transcribed. Transcripts were analysed using thematic analysis. RESULTS: Fathers identified a number of program-related and father-related facilitators and barriers which impacted their engagement and participation. Program-related facilitators included: accessibility of the program; father advocacy of the program; group fitness/exercise component; and having a father-specific program. Facilitating factors related to fathers included: making social connections; learning how to be a better dad/partner; and partner support and encouragement to attend. Program-related barriers included: travel; lack of awareness; and gender roles. While father-related barriers included: being time poor; sacrifices to family; and apprehension. CONCLUSIONS: The current findings identified many areas that facilitate, encourage and motivate men to participate in interventions which support their mental and physical health during the early parenting period. RELEVANCE: Generating evidence on barriers and facilitators to health interventions is important to improving the current intervention along with informing the development of engaging and targeted health interventions for fathers in early parenthood.

A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients.

Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). In this phase I dose escalation study, we treated eight patients with high-risk surgically resected stage II-IV melanoma with intravenous autologous monocyte-derived DCs loaded with the NKT cell agonist α-GalCer and peptides derived from the cancer testis antigen NY-ESO-1. Two synthetic long peptides spanning defined immunogenic regions of the NY-ESO-1 sequence were used. This therapy proved to be safe and immunologically effective, inducing increases in circulating NY-ESO-1-specific T cells that could be detected directly ex vivo in seven out of eight patients. These responses were achieved using as few as 5 × 105 peptide-loaded cells per dose. Analysis after in vitro restimulation showed increases in polyfunctional CD4+ and CD8+ T cells that were capable of manufacturing two or more cytokines simultaneously. Evidence of NKT cell proliferation and/or NKT cell-associated cytokine secretion was seen in most patients. In light of these strong responses, the concept of including NKT cell agonists in vaccine design requires further investigation.

Dendritic cell vaccination combined with temozolomide retreatment: results of a phase I trial in patients with recurrent glioblastoma multiforme.

There is no standard treatment for recurrent glioblastoma multiforme (GBM). Retreatment with temozolomide (TMZ) is one treatment option. We reasoned this could be more effective if combined with a vaccine that preferentially targeted TMZ-resistant cells. To test the feasibility and safety of such an approach, a phase 1 trial was conducted in which patients with GBM tumors relapsing after standard chemoradiotherapy were retreated with TMZ in combination with a vaccine consisting of monocyte-derived dendritic cells (DC) pulsed with autologous tumor cells that had previously been exposed to TMZ in vivo in the course of primary treatment. Of 14 participants, nine patients completed the initial phase of priming vaccinations and two cycles of TMZ, one proved to have radionecrosis, one rapidly progressed, and in three the yield of DC vaccine was insufficient to proceed with treatment. Other than expected toxicities related to TMZ, there were no adverse events attributable to the combined treatment. Two patients had objective radiological responses. Six month progression-free survival was 22 %, similar to retreatment with TMZ alone. Anti-tumor immune responses were assessed in peripheral blood mononuclear cells using interferon-γ ELISpot, with two patients meeting criteria for a vaccine-induced immune response, one of whom remained disease-free for nearly three years. Another patient with an anti-tumor immune response at baseline that was sustained post-vaccination experienced a 12-month period of progression-free survival. In summary, the combined treatment was safe and well-tolerated but feasibility in the recurrent setting was marginal. Evidence of immune responses in a few patients broadly correlated with better clinical outcome.

Trajectories of psychological distress for Australian fathers parenting a child on the autism spectrum: Evidence from early childhood to adolescence.

LAY ABSTRACT: This study explores the mental health journey of fathers with children on the autism spectrum. Little is known about mental health over time for these fathers. This research spans six-timepoints from when children were aged 4 to 14 years, to track fathers' mental health. This study had three aims: (1) report estimates of fathers' psychological distress across 10 years of child development; (2) identify separate courses of psychological distress over time; and (3) identify early risk factors associated with these courses. This study used data from 281 fathers of children on the autism spectrum who took part in the Longitudinal Study of Australian Children. Using a statistical method to group fathers based on their psychological distress scores over 10 years of child development, the results showed that two groups best explained the data; this included a group of fathers who experienced low levels of psychological distress over the 10 years of child development (84%), and another group of fathers who experienced heightened psychological distress across this time (16%). Further analysis showed that fathers who had an ongoing medical condition and higher levels of interparental conflict with their partners were more likely to be in the heightened psychological distress group. These findings show that almost one in six fathers deal with persistent psychological distress throughout their child's early childhood and into early adolescence. This study advocates for interventions focusing on improving fathers' physical health and the couple relationship as ways to positively impact fathers' mental health in the long run.

Mothers' experiences of emotional abuse from an intimate partner and its associations with children's developmental outcomes at 5 years.

BACKGROUND: Intimate partner violence (IPV) is associated with an increased risk of poorer child development. Existing research has focused on physical abuse with less known about the associations with emotional IPV. OBJECTIVE: To describe the period prevalence of mother's experiences of emotional IPV during children's preschool years and associations with child mental, physical, social, and cognitive development. METHODS: Secondary analysis of control group data (n = 194) from an Australian randomised trial (right@home), which recruited pregnant women experiencing social adversity from antenatal clinics in 2013-14. Women reported emotional abuse (Composite Abuse Scale) at child ages 3-5 years. Measures of child development at 5 years included: Strengths and Difficulties Questionnaire, Social Skills Improvement System, Pediatric Quality of Life Inventory, Clinical Evaluation of Language Fundamentals, School Entry Alphabetic and Phonological Awareness Readiness Test, NIH executive function subtests, sleep and health. The prevalence of emotional IPV from 3 to 5 years was estimated. Regression models compared developmental outcomes according to emotional IPV exposure, adjusted for child age, child gender, and maternal education. Missing data were accounted for using multiple imputation. RESULTS: From 3-5 years, emotional IPV was experienced by 57% of women. Emotional IPV exposure was consistently associated with poorer child developmental outcomes. Differences were most apparent for SDQ internalising (mean difference 1.2, 95% CI 0.2 to 2.1) and externalising difficulties (1.2, 95% CI -0.1 to 2.4). CONCLUSIONS: Emotional IPV was highly prevalent amongst families experiencing social adversity. Developing acceptable and effective identification processes and interventions that prioritise families experiencing co-occurring social adversities should be a public health priority.

A longitudinal study of the relationships between sleep problems in autistic children and maternal mental health.

LAY ABSTRACT: Autistic children experience increased the rates of sleep problems. These sleep problems have been associated with mother's mental health symptoms. However, the direction of these relationships is not well understood. This study investigated the relationships between autistic children's sleep problems and mothers' mental health over a 12-year period using data collected as part of the Longitudinal Study of Australian Children. Data from 397 autistic children and their mothers were included in this study. Mothers completed a questionnaire about their own mental health and common childhood sleep problems at four time points from 4-5 years to 14-15 years. The results showed important relationships between mothers' mental health symptoms and child sleep problems at two time points. Specifically, (1) mothers' mental health symptoms when the child was aged 4 to 5 years predicted child sleep problems at age 6 to 7 years; and (2) child sleep problems at age 12-13 years predicted mothers' mental health symptoms when the child was aged 14 to 15 years. Interestingly, these significant relationships also coincide with key developmental transition time points, when the child is transitioning in and out of primary school. These findings highlight the need for increased support for both the child and mother at these times to optimise outcomes for both.

Melanocytic neoplasms in a black rhinoceros (Diceros bicornis) and an Indian rhinoceros (Rhinoceros unicornis).

Melanocytic neoplasms were diagnosed in a captive black rhinoceros (Diceros bicornis) and a captive Indian rhinoceros (Rhinoceros unicornis) from different facilities. The first case was a 10-yr-old, captive-born male black rhinoceros that presented with a small firm cutaneous mass on the dorsal midline. Aspirate cytology results were suggestive of a melanocytic neoplasm, and histologic examination of the excised mass confirmed a well-differentiated neoplasm with much pigment production, minimal anaplasia, and no mitotic figures. Several months after mass removal, a similar mass with identical histologic features was excised from the right medial thigh. The second case was a 28-yr-old, wild-born female Indian rhinoceros that presented with a draining wound at the coronary band of a rear digit. Histologic examination of a biopsy from this lesion revealed a melanocytic neoplasm with moderate cellular anaplasia, frequent mitoses, and scant pigment production. At necropsy, the tumor was found to ablate P3 and most deep tissues of the toe. No evidence of vascular invasion or metastasis was found. These two cases represent the only melanocytic neoplasms in Rhinoceridae reported in detail in the literature.

Bio-ecological factors associated with the psychological distress of fathers of children with autism spectrum disorder: A population-based study of Australian families.

Using a bio-ecological framework, the aim of this study was to examine factors associated with psychological distress experienced by fathers of children with autism spectrum disorder from a nationally representative sample of Australian children and their families. Individual (e.g. age and self-efficacy), interpersonal (e.g. partner distress, couple relationship, child behaviour and social support) and social environmental factors (e.g. job quality and financial hardship) were explored as potential predictors of fathers' distress. Data were drawn from the Longitudinal Study of Australian Children, where 159 fathers of children with autism spectrum disorder were identified. As comparison, 6578 fathers of children without developmental disabilities were identified. Multiple regression analyses showed that experiencing depression within the past year, job quality (e.g. autonomy and access to parental leave) and social support were significant predictors for fathers of children with autism spectrum disorder. The importance of supporting the well-being of fathers of children with autism spectrum disorder is discussed.

The psychological and physical health of fathers of children with Autism Spectrum Disorder compared to fathers of children with long-term disabilities and fathers of children without disabilities.

BACKGROUND: The psychological and physical health of fathers of children with Autism Spectrum Disorder (ASD) is under-researched. Due to the unique parenting demands, fathers of children with ASD may be at increased risk of experiencing psychological and physical health difficulties compared to fathers of children without disabilities (W/OD) and fathers of children with other long-term disabilities (LTD). What little research there is on fathers of children with ASD is often conducted on small clinical samples, or embeds the experiences of fathers within other groups. AIM: The current study aimed to explore the extent to which fathers of children with ASD experience psychological distress and physical health issues (e.g., general health, smoking, chronic pain) compared to fathers of children W/OD and fathers of children with a LTD. METHOD: From a large, nationally representative sample of children, 159 fathers of children with ASD were identified, along with 45 fathers of children with a LTD and 6578 fathers of children W/OD. RESULTS: The majority of fathers were experiencing good psychological and physical health. Approximately 1 in 6 fathers of children with ASD were experiencing elevated levels of psychological distress and poor global health, and were at significantly greater risk than fathers of children W/OD; although these differences were not found compared to fathers of children with a LTD. CONCLUSIONS: Some fathers of children with ASD may require additional support which not only focuses on their psychological wellbeing but also fathers' physical health. The current findings encourage health services to check-in with, or reach-out to fathers as they too may require additional support.

Expression of CD1a and Type-1 Polarization Are Dissociated in Human Monocyte-Derived Dendritic Cells.

Ex vivo generated monocyte-derived dendritic cell (moDC)-vaccines have long been touted as promising immunotherapeutic agents for cancer treatment, although the response rate generally remains low. The reasons for this are still unclear and confounded by the diversity in manufacturing protocols that may affect moDC function. Preclinical studies have shown that the stimulatory function of dendritic cells can be improved by engaging invariant NKT cells in vivo through the presentation of the glycolipid alpha-galactosylceramide via CD1d. However, expression of CD1d on moDC has been shown to be negatively correlated with expression of CD1a, which in turn has been suggested to be a surrogate marker for IL-12 secreting type-1 polarized moDC, the preferred functional characteristics for cancer vaccines. Here we challenge this notion by showing that plasma-derived lipids drive functional levels of CD1d expression, while CD1a expression can vary considerably in these cells without being correlated with a loss of polarization or immunogenicity.

Fatigue, wellbeing and parental self-efficacy in mothers of children with an autism spectrum disorder.

Raising a child with an Autism Spectrum Disorder (ASD) presents significant challenges for parents that potentially have a impact on their health and wellbeing. The current study examined the extent to which parents experience fatigue and its relationship to other aspects of wellbeing and parenting. Fifty mothers of children with an ASD aged 2-5 years participated in the study. Compared with mothers of typically developing children, mothers of children with an ASD reported significantly higher fatigue, with overall scores in the moderate range. Factors associated with high levels of fatigue were poor maternal sleep quality, a high need for social support and poor quality of physical activity. Fatigue was also significantly related to other aspects of wellbeing, including stress, anxiety and depression, and lower parenting efficacy and satisfaction. The need for interventions to specifically target parental fatigue and its impact on families affected by ASDs both in the short and long term is clearly indicated.