Waterloo Better Beginnings as a Transformative Prevention Project: Impacts on Children, Parents, and the Community.

Better Beginnings Waterloo (BBW) is an ecological, community-driven, prevention program for children aged 4-8 and their families. BBW was implemented in two low-income communities with high percentages of visible minorities. Data on Grade 1-2 children and their parents (the baseline comparison group) were gathered through parent interviews (n = 34) and teacher reports (n = 68) in 2015, prior to BBW programs, and in the period 2018-2019, the same data were collected through parent interviews (n = 47) and teacher reports (n = 46) for children and parents participating in programs (the BBW group). As well, qualitative, open-ended individual interviews with parents (n = 47) and two focus groups were conducted in the period 2018-2019. Children in the BBW cohort were rated by their teachers as having a significantly lower level of emotional and behavioural problems than those in the baseline sample; parents in the BBW cohort had significantly higher levels of social support than parents in the baseline cohort; BBW parents rated their communities significantly more positively than parents at baseline. The qualitative data confirmed these findings. The quantitative and qualitative short-term findings from the BBW research showed similar positive impacts to previous research on program effectiveness, thus demonstrating that the Better Beginnings model can be successfully transferred to new communities.

Examining peer networking as a capacity-building strategy for Housing First implementation.

AIMS: This study examines peer networking as a capacity-building strategy for the implementation of Housing First (HF), a complex community intervention targeting chronic homelessness. METHODS: A qualitative, multiple case study was conducted to examine the capacity-building activities of two, multicommunity peer networks established by community leaders in the Canadian Homelessness sector. Data collection activities included document analysis, key informant interviews (n = 10), and a follow-up focus group with interview participants in each network. Thematic analyses were conducted for each network, followed by a cross-case analysis. RESULTS: Engaging in a multicommunity peer network enhances leaders' capacity to advance HF by creating opportunities to foster trust and communication, inform continuous improvement, and navigate ambiguity. A number of contextual factors influence connections between peer networking and capacity building. CONCLUSION: Peer networks are a valuable source of support and timely, contextually relevant knowledge for community leaders advancing local adaptation and implementation of HF.

Knowledge translation and implementation of housing first in Canada: A qualitative assessment of capacity building needs for an evidence-based program.

We examined communities' expressed needs for capacity building in the implementation of Housing First (HF) for persons experiencing homelessness. The findings are based on thematic analyses of qualitative data obtained from participants (n = 77) in 11 focus groups conducted in seven Canadian cities. We identified capacity building needs in the areas of training (e.g., HF principles, clinical services, landlord engagement) and technical assistance (e.g., intake coordination, client prioritization, fidelity assessment). These findings were used to tailor training and technical assessment (TTA) to the stages of HF implementation in these cities. Limitations and implications for future theory, research, and practice are discussed.

Systems change in the context of an initiative to scale up Housing First in Canada.

In this study, we examine changes in the homeless-serving system in the context of a training and technical assistance initiative to scale up Housing First (HF) in 6 Canadian communities. Based on qualitative data from focus groups and individual interviews with key stakeholders (k = 7, n = 35) and field notes gathered over a 3-year period (n = 146), we found 2 main system changes: (a) changes in the capacity of the service delivery system at multiple levels of analysis (from individual to policy) to implement HF, and (b) changes in the coordination of parts of the service delivery system and collaboration among local stakeholders to enhance HF implementation. These changes were facilitated or constrained by the larger context of evidence, climate, policy, and funding. The findings were discussed in terms of systems change theory and implications for transformative systems change in the mental health and homelessness sectors.

Navigating Complex Implementation Contexts: Overcoming Barriers and Achieving Outcomes in a National Initiative to Scale Out Housing First in Canada.

The scaling out of Housing First (HF) programs was examined in six Canadian communities, in which a multi-component HF training and technical assistance (TTA) was provided. Three research questions were addressed: (a) What were the outcomes of the TTA in terms of the development of new, sustained, or enhanced programs, and fidelity to the HF model? (b) How did the TTA contribute to implementation and fidelity? and (c) What contextual factors facilitated or challenged implementation and fidelity? A total of 14 new HF programs were created, and nine HF programs were sustained or enhanced. Fidelity assessments for 10 HF programs revealed an average score of 3.3/4, which compares favorably with other HF programs during early implementation. The TTA influenced fidelity by addressing misconceptions about the model, encouraging team-based practice, and facilitating case-based dialogue on site specific implementation challenges. The findings were discussed in terms of the importance of TTA for enhancing the capacities of the HF service delivery system-practitioners, teams, and communities-while respecting complex community contexts, including differences in policy climate across sites. Policy climate surrounding accessibility of housing subsidies, and use of Assertive Community Treatment teams (vs. Intensive Case Management) were two key implementation issues.

Understanding Systems Change in Early Implementation of Housing First in Canadian Communities: An Examination of Facilitators/Barriers, Training/Technical Assistance, and Points of Leverage.

We present interim findings of a cross-site case study of an initiative to expand Housing First (HF) in Canada through training and technical assistance (TTA). HF is an evidence-based practice designed to end chronic homelessness for consumers of mental health services. We draw upon concepts from implementation science and systems change theory to examine how early implementation occurs within a system. Case studies examining HF early implementation were conducted in six Canadian communities receiving HF TTA. The primary data are field notes gathered over 1.5 years and evaluations from site-specific training events (k = 5, n = 302) and regional network training events (k = 4, n = 276). We report findings related to: (a) the facilitators of and barriers to early implementation, (b) the influence of TTA on early implementation, and (c) the "levers" used to facilitate broader systems change. Systems change theory enabled us to understand how various "levers" created opportunities for change within the communities, including establishing system boundaries, understanding how systems components can function as causes of or solutions to a problem, and assessing and changing systems interactions. We conclude by arguing that systems theory adds value to existing implementation science frameworks and can be helpful in future research on the implementation of evidence-based practices such as HF which is a complex community intervention. Implications for community psychology are discussed.

IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2014 there were six themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of animal models, xenobiotics, pathological biomarkers, genetics and epigenetics, and stillbirth and fetal growth restriction.

IFPA Gábor Than Award Lecture: Recognition of placental failure is key to saving babies' lives.

In high-income countries, placental failure is implicated in up to 65% of cases of stillbirth. Placental failure describes the situation where the placenta cannot meet the fetus' needs and may be the end-result of a variety of underlying pathological processes evident in the placental disc, membranes and umbilical cord. These include lesions with genetic, environmental, infectious, inflammatory, mechanical, metabolic, traumatic or vascular origin. Investigation of placental tissue from stillbirths and from pregnancies at an increased risk of stillbirth has demonstrated changes in macroscopic and microscopic structure which are themselves related to abnormal placental function. A better understanding and identification of placental failure may improve the management of pregnancy complications and of pregnancies after stillbirth (which have a 5-fold increased risk of stillbirth). The majority of current antenatal tests focus on the fetus and its response to the intrauterine environment; few of these investigations reduce stillbirths in low-risk pregnancies. However, some currently used investigations reflect placental development, structure and vascular function, while other investigations employed in clinical research settings such as the evaluation of placental structure and shape have a good predictive value for adverse fetal outcome. In addition, recent studies suggest that biomarkers of placental inflammation and deteriorating placental function can be detected in maternal blood suggesting that holistic evaluation of placental structure and function is possible. We anticipate that development of reliable tests of placental structure and function, coupled to assessment of fetal wellbeing offer a new opportunity to identify pregnancies at risk of stillbirth and to direct novel therapeutic strategies to prevent it.

Better Beginnings, Better Futures: Theory, research, and knowledge transfer of a community-based initiative for children and families / Better Beginnings, Better Futures [a mejor comienzo, mejor futuro]: teoría, investigación y transferencia de conocimientos de una iniciativa comunitaria con niños y familias

Better Beginnings, Better Futures is an early childhood initiative focused on promoting healthy development of children and families in economically disadvantaged communities. The Better Beginnings approach is ecological and holistic, community-driven, integrated with existing community services and supports, and universally available to children aged 4-8 within communities in which it is offered. The Better Beginnings initiative effectively illustrates the concept of wellness as fairness through its efforts to create more just social conditions and its connection to both procedural and distributive justice, the two principles of fairness outlined by Prilleltensky (2012). Through the development of programs that support children, parents, families, and the community as a whole, Better Beginnings initiatives are able to promote children’s development by building community capacity to create healthy and positive environments for children. This paper provides an overview of the Better Beginnings, Better Futures initiative from its outset in 1990 to the present, with a view towards examining the ways in which knowledge generated from such initiatives can be transferred to other communities

Better Beginnings, Better Futures [a mejor comienzo, mejor futuro] es una iniciativa dirigida a la primera infancia para fomentar el desarrollo de la salud de niños y familias en comunidades económicamente des favorecidas. El enfoque Better Beginnings es ecológico, holístico, impulsado por la comunidad, integrado en los servicios y el apoyo existentes en la comunidad y de acceso universal para niños de entre 4 y 8 años en aquellas comunidades a las que se ofrece. Esta iniciativa ilustra meridianamente el concepto de bienestar como justicia a través de su esfuerzo por crear unas condiciones sociales más justas y su relación tanto con la justicia procedimental como con la distributiva, los dos principios descritos por Prilleltensky (2012). Mediante la puesta en marcha de programas de apoyo a niños, padres, familias y comunidad como un todo, estas iniciativas pueden impulsar el desarrollo de los niños al crear la capacidad comunitaria para potenciar entornos saludables y positivos para los niños. Este trabajo presenta una descripción de la iniciativa Better Beginnings, Better Futures desde su arranque en 1990 hasta la actualidad, con la vista puesta en el análisis de las distintas maneras de traspasar los conocimientos surgidos de estas iniciativas a otras comunidades

Review: The effects of oxygen on normal and pre-eclamptic placental tissue--insights from metabolomics.

Placental dysfunction is central to many complications of human pregnancy including pre-eclampsia (PE), intra-uterine growth restriction (IUGR) and stillbirth. The precise molecular pathophysiology of placental dysfunction in these conditions is not known, although oxidative and nitrative stresses have been implicated. Metabolites are low molecular weight chemicals which play an important role in biological function, primarily through metabolism and regulation of biological processes. The holistic study of metabolites, defined as metabolomics or metabolic profiling, has the objective to detect and identify all, or a large complement of all metabolites. Metabolomics is applied to discover new knowledge regarding biological processes and systems. We hypothesised that a metabolomic strategy could (1) provide a reproducible technique to investigate the intracellular metabolism of placental tissue and also metabolites consumed from or secreted in to the extracellular 'metabolic footprint' of in vitro culture systems (2) identify metabolic related differences in placental tissue culture systems subjected to perturbations in oxygen tension and from pregnancies complicated by PE. We review our early studies which demonstrate that a reproducible experimental protocol is required, including the preparation of culture medium and the site of the placenta applied for sampling tissue. We have detected changes in the intracellular metabolome and metabolic footprint of placental tissue in response to altered oxygen tension and PE. We have demonstrated that placental tissue from uncomplicated pregnancies cultured in 1% oxygen (hypoxia) had metabolic similarities to explants from PE pregnancies cultured at 6% oxygen (normoxia). Metabolites requiring further study include lipids, glutamate and glutamine and metabolites related to tryptophan, leukotriene and prostaglandin metabolism. Metabolomics has the potential to identify changes in clinical conditions, such as PE, that are associated with placental molecular pathophysiology.

Translation of flecainide- and mexiletine-induced cardiac sodium channel inhibition and ventricular conduction slowing from nonclinical models to clinical.

INTRODUCTION: Nonclinical in vivo models used for cardiovascular safety testing have not previously been studied for their sensitivity for detection of conduction slowing resulting from cardiac sodium channel block. The goal of this study was to examine the sensitivity of in vivo models to cardiac sodium channel block, and translation of the effect from in vitro to in vivo models using sodium channel inhibitors flecainide and mexiletine; flecainide, but not mexiletine is commonly associated with QRS complex prolongation in humans. METHODS: Inhibition of cloned cardiac sodium channels (hNav1.5) was studied using the IonWorks platform. Conduction slowing was measured in vitro in the rabbit isolated ventricular wedge (RVW) and in vivo in the conscious telemetered rat and dog, and anaesthetised dog. RESULTS: Flecainide and mexiletine inhibited hNav1.5 channels with IC50 values of 10.7 and 67.2 µM respectively. In the RVW, QRS was increased by flecainide at 60 bpm, and at 120bpm, there was an increased effect of both drugs. In conscious rats, flecainide significantly increased QRS complex duration; mexiletine had no significant effect, but there was an increase at the highest dose in 4/6 animals. QRS complex was increased by flecainide and mexiletine in anaesthetised dogs but this was not statistically significant; in conscious dog, only flecainide produced a significant increase in QRS complex. DISCUSSION: When compared to clinical data, effects of flecainide and mexiletine in RVW and conscious dog compared well with effects in patients and healthy volunteers in terms of sensitivity. The anaesthetised dog was least sensitive for detection of changes in QRS. All assays showed some differentiation between the expected conduction slowing activity of flecainide and mexiletine. Based on these data, RVW and conscious dog were most predictive for effects of compounds on QRS complex and cardiac conduction.

Changes in the metabolic footprint of placental explant-conditioned culture medium identifies metabolic disturbances related to hypoxia and pre-eclampsia.

Pre-eclampsia (PE) is a multi-system disorder thought to be mediated by circulating factors released from damaged placental villous trophoblast. There is extensive evidence of changes in the villous tissue in PE, some of which may be replicated by culturing villous tissue in hypoxic conditions. Metabolic footprinting offers a hypothesis-generating strategy to investigate factors released from this tissue in vitro. This study investigated differences in the factors released from villous trophoblast from uncomplicated pregnancies (n=6) and those with PE (n=6). In both cases, explanted placental villous fragments were cultured for 96 h in 1% O(2) (hypoxia) or 6% O(2) (placental normoxia). Metabolites consumed from and released into serum-conditioned culture medium were analysed by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS). The relative concentration of 154 features of the metabolic footprint were observed to change in culture medium from uncomplicated pregnancies cultured in normoxic and hypoxic conditions (p<0.00005). 21 and 80 features were also different in culture medium from PE versus uncomplicated pregnancies cultured in hypoxic and normoxic conditions, respectively (p<0.00005). When comparing all 4 groups, 47 metabolic features showed a similar relative concentration in PE-derived media cultured in normoxic conditions to conditioned media from normal villous tissue cultured in hypoxic conditions. These data suggest that hypoxia may have a role in the placental pathogenesis of PE. Three areas of metabolism were highlighted for systems biology investigation; glutamate and glutamine, tryptophan metabolism and leukotriene or prostaglandin metabolism.

Analysis of the metabolic footprint and tissue metabolome of placental villous explants cultured at different oxygen tensions reveals novel redox biomarkers.

Pre-eclampsia (PE) is a multi-system disorder of pregnancy hypothesised to arise from circulating factors derived from an unhealthy placenta. Some changes in placental phenotype seen in PE can be reproduced by culture in altered oxygen (O2) tension. Currently, these circulating factors are unidentified, partly due to the complexity of maternal plasma. Investigation of factors released from placental tissue provides a potential method to identify bioactive compounds. Experimental strategies to study compounds present in a biological system have expanded greatly in recent years. Metabolomics can detect and identify endogenous and secreted metabolites. We aimed to determine whether metabolites could be identified in placental cultures with acceptable experimental variability and to determine whether altered O2 tension affects the composition of the placental metabolome. In this study we used gas-chromatography-mass spectroscopy to determine the presence of metabolites in conditioned culture medium (CCM) and tissue lysates of placental villous explants cultured in 1, 6 and 20% atmospheric O2 for 96h. This experimental strategy had an intra-assay variation of 6.1-11.6%. Intra and inter-placental variability were 15.7-35.8% and 44.8-46.2% respectively. Metabolic differences were identified between samples cultured in 1, 6 and 20% O2 in both CCM and tissue lysate. Differentially expressed metabolites included: 2-deoxyribose, threitol or erythritol and hexadecanoic acid. We conclude that metabolomic strategies offer a novel approach to investigate placental function. When conducted under carefully controlled conditions, with appropriate statistical analysis, metabolic differences can be identified in placental explants in response to altered O2 tension. Metabolomics could be used to identify changes in conditions associated with placental pathology.

Development of tolerance in mice to the sedative effects of the neuroactive steroid minaxolone following chronic exposure.

Minaxolone is a potent ligand for the neurosteroid binding site of the GABAA, receptor. In radioligand binding studies to rat brain membranes, minaxolone caused a 69% increase in [3H]muscimol binding and a 25% increase in [3H]flunitrazepam binding and inhibited the binding of [3H]TBOB with an IC50 of 1 microM. In mice, minaxolone (100 mg/kg, orally) had marked sedative effects as indicated by a reduction in locomotor activity. Chronic dosing with minaxolone (100 mg/kg, orally, once daily for 7 days) resulted in a loss of sedative response to an acute dose of the drug, indicating development of tolerance. Chronic dosing with temazepam (10 mg/kg, orally, once daily for 7 days) resulted in the development of tolerance to an acute dose of temazepam; however, the two drugs did not appear to be cross-tolerant, indicating that they may have a different mechanism of action at the level of the GABAA receptor.

Sensory nerve-mediated relaxation of guinea-pig isolated pulmonary artery: prejunctional modulation by alpha 2-adrenoceptor agonists but not sumatriptan.

1. Effects of the alpha 2-adrenoceptor agonists, UK14304 and clonidine, the 5-HT1 receptor agonist, sumatriptan and the kappa-opioid receptor agonist, GR103545, on sensory neurotransmission in histamine-contracted guinea-pig isolated pulmonary artery (GPPA) have been studied. 2. Electrical field stimulation (EFS) induced frequency-dependent relaxations of histamine-contracted GPPA, which were attenuated by tetrodotoxin and capsaicin pretreatment but not by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). 3. Substance P (0.3 microM) induced relaxations which were subject to rapid tachyphylaxis. Neither the NK1 receptor antagonist, (+/-)-CP 96,345, nor desensitization to substance P had any effect of EFS-induced relaxations of histamine-contracted GPPA. 4. Calcitonin gene-related peptide (CGRP; 3 and 30 nM) induced concentration-dependent relaxations of histamine-contracted GPPA. The putative CGRP receptor antagonist, CGRP8-37 (1 microM), markedly attenuated EFS-induced relaxations as well as relaxations induced by a low concentration of CGRP. 5. Sumatriptan (0.1 and 1 microM) and the selective kappa-opioid receptor agonist, GR103545 (10 and 100 nM) had no effect on EFS-induced relaxations of histamine-contracted GPPA. In contrast, the alpha 2-adrenoceptor agonists UK14304 (1-100 nM) and clonidine (300 nM) attenuated responses to EFS, the attenuation of UK14304 (100 nM) being reversed by yohimbine (300 nM). 6. It is concluded that in GPPA, where a presynaptic inhibition of sensory neurotransmission by alpha 2-adrenoceptor activation could be shown, there was no evidence for such modulation by either sumatriptan-sensitive 5-HT1 receptors or kappa-opioid receptors.