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BackgroundImplementation research infrequently addresses economic factors, despite the importance of understanding the costs of implementing evidence-based practices (EBPs). Though partnerships with health economists have the potential to increase attention to economic factors within implementation science, barriers to forming these collaborations have been noted. This study investigated the experiences of health economists and implementation researchers who have partnered across disciplines to inform strategies to increase such collaborations.MethodsA purposeful sampling approach was used to identify eight health economists and eight implementation researchers with experience participating in cross-disciplinary research. We used semi-structured interviews to gather information about participants' experiences with collaborative research. Thematic analysis was conducted to identify core themes related to facilitators and barriers to collaborations.ResultsHealth economists and implementation researchers voiced different perspectives on collaborative research, highlighting the importance of increasing cross-disciplinary understanding. Implementation researchers described a need to measure costs in implementation studies, whereas many health economists described that they seek to collaborate on projects that extend beyond conducting cost analyses. Researchers in both disciplines articulated motivations for collaborative research and identified strategies that promote successful collaboration, with varying degrees of convergence across these themes. Shared motivations included improving methodological rigor of research and making a real-world impact. Strategies to improve collaboration included starting partnerships early in the study design period, having a shared interest, and including health economists in the larger scope of the research.ConclusionsHealth economists and implementation researchers both conduct research with significant policy implications and have the potential to inform one another's work in ways that might more rapidly advance the uptake of EBPs. Collaborative research between health economists and implementation science has the potential to advance the field; however, researchers will need to work to bridge disciplinary differences. By beginning to develop strong working relationships; increasing their understanding of one another's disciplinary culture, methodology, and language; and increasing the role economists have within research design and execution, both implementation researchers and health economists can support successful collaborations and robust and informative research.

Although engaging fathers effectively can bolster and sustain treatment outcomes, fathers participate in their children's treatment at lower rates than mothers and have been left out of the literature on caregiver engagement. Because provider attitudes and behaviors shape the course of treatment, therapist perspectives on father attendance and engagement should be investigated. A mixed-method study design examined rates and predictors of father attendance in treatment and therapist perspectives on father engagement in Parent-Child Interaction Therapy (PCIT). Quantitative data were gathered through a survey distributed to PCIT therapists (n = 267) to identify the effects of: 1) therapist and caseload characteristics, 2) therapist confidence working with fathers, 3) therapist use of father engagement strategies, and 4) organizational practices for engaging fathers, on father attendance rates. Qualitative interviews with 23 therapists were thematically analyzed to expand upon therapist experiences engaging fathers. Therapists reported that on average, 60.97% of cases with a father available had regular session attendance by the father. Only frequency of therapist use of father engagement strategies predicted father attendance rate. Qualitative interviews expanded on the many barriers therapists face to engaging fathers and the variety of strategies they employ to engage fathers. Rates of father attendance in PCIT are higher than what has been previously reported in the literature but still show room for improvement. Despite barriers, therapists remain dedicated to developing solutions to elicit father engagement. Future research should evaluate whether therapist-reported engagement strategies effectively increase father participation and can be more widely disseminated. [ABSTRACT FROM AUTHOR]

Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasimesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identify two markers--HNF1A and KRT81--that enable stratification of tumors into different subtypes by using immunohistochemistry. Individuals with tumors of these subtypes showed substantial differences in overall survival, and their tumors differed in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. Cytochrome P450 3A5 (CYP3A5) metabolizes these compounds in tumors of the exocrine-like subtype, and pharmacological or short hairpin RNA (shRNA)-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Whereas hepatocyte nuclear factor 4, alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC, and it is highly expressed in several additional malignancies. These findings designate CYP3A5 as a predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance., PDAC is a very aggressive disease with poor prognosis (1). In both Europe and the USA, pancreatic cancer is the fourth leading cause of cancer deaths (2,3). Treatment with gemcitabine [...]

Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system. Stress-linked HSC DNA damage The accumulation of DNA damage as haematopoietic stem cells (HSCs) age is thought to contribute to age-related degeneration, an idea that is supported by the fact that accelerated ageing syndrome caused by defects in DNA repair, such as Fanconi anaemia syndrome, is associated with bone marrow failure. Michael Milsom and colleagues show here that DNA damage is a direct outcome of forcing HSCs to exit quiescence in response to a wide range of stimuli that mimic conditions of stress. In mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system. These findings highlight the possible role of stress-induced HSC DNA damage in diseases that that have a pro-inflammatory component, as well as in normal ageing. Haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation.sup.1. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia.sup.2,3. However, the physiological source of DNA damage in HSCs from both normal and diseased individuals remains unclear. Here we show in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss. Repeated activation of HSCs out of their dormant state provoked the attrition of normal HSCs and, in the case of mice with a non-functional Fanconi anaemia DNA repair pathway, led to a complete collapse of the haematopoietic system, which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia patients. Our findings establish a novel link between physiological stress and DNA damage in normal HSCs and provide a mechanistic explanation for the universal accumulation of DNA damage in HSCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients., Author(s): Dagmar Walter [sup.1] , Amelie Lier [sup.1] , Anja Geiselhart [sup.2] , Frederic B. Thalheimer [sup.3] , Sina Huntscha [sup.1] , Mirko C. Sobotta [sup.4] , Bettina Moehrle [sup.5] [...]

Parent-Child Interaction Therapy (PCIT) is an evidence-based practice (EBP) for young children with challenging behaviors. PCIT has been adapted to treat varying presentations and culturally diverse families. Although efforts have been made to disseminate PCIT into community settings, which often serve clinically complex, socio-culturally diverse, and marginalized communities, barriers to disseminating adapted models remain. An alternative strategy to understanding how to increase access to appropriately adapted PCIT is to learn from community clinicians' practice-based adaptations to meet their clients' diverse needs related to clinical presentation, culture, and language. This mixed-method study investigated community clinician adaptations of PCIT. Clinicians (N = 314) were recruited via PCIT listservs to complete a survey collecting background information, and adaptations to PCIT. Most clinicians had a master's degree (72.1%), were licensed (74.2%), and were PCIT-certified (70.7%). Qualitative interviews were conducted with a purposeful sample of 23 community clinicians, who were 39% Spanish-speaking, were 30% Latinx, and 30% reported serving a ≥50% Latinx clientele. Clinicians reported engaging in adaptations aimed at augmenting PCIT more extensively than adaptations involving removing core components. Themes from qualitative interviews converged with quantitative findings, with clinicians most frequently describing augmenting adaptations, and highlighted reasons for adapting PCIT. Clinicians primarily augmented treatment to address clients' clinical presentations. Clinicians rarely adapted treatment specifically for culture, but when mentioned, clinicians discussed tailoring idioms and phrases to match clients' culture for Spanish-speaking clients. Implications for training PCIT clinicians in intervention adaptations will be discussed. [ABSTRACT FROM AUTHOR]

Engaging caregivers in their children's mental health treatment is critical for delivering high quality, evidence-based care, particularly for young children with externalizing behaviors. Lay health workers (LHWs), including peer providers and promotoras de salud, have been identified as important workforces in addressing structural and stigma-related barriers to engagement in mental health services. Importantly, research has suggested that LHWs may be integral in efforts to address engagement disparities in evidence-based behavioral parent training programs (BPTs) for Latinx caregivers. The purpose of the study was to understand how different LHW workforces engage caregivers within their usual services, in order to inform strategies that improve access to and engagement in BPTs. Qualitative interviews were conducted with two different LHW workforces: volunteer LHWs (i.e., promotoras de salud) (n = 14), who were part of a community-embedded network, and paid LHWs (i.e., parent support partners, home visitors) (n = 9) embedded within children's mental health agencies. Participants were predominately Latinx (79%) and female (96%). Qualitative analyses revealed three primary themes related to engagement strategies used by LHWs to address barriers to care: 1.) Building Trust, 2.) Empowerment, 3.) Increasing Access. Although the majority of themes and sub-themes were consistent across the two LHW workforces, agency-embedded LHWs often discussed having the means to provide resources through their organizations, whereas community-embedded LHWs discussed acting as a bridge to services by providing information and conducting outreach. Findings have implications for partnering with different workforces of LHWs to increase equity in access to BPTs. [ABSTRACT FROM AUTHOR]