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Several polygynous mammals exhibit reproductive skew in which only a few males reproduce. Successful males need strength, stamina and fighting ability to exclude competitors. Consequently, during the mating season their androgens and glucocorticoids are expected to increase to support spermatogenesis and aggressive behavior. But, during the nonmating season these hormones should decline to minimize deleterious effects, such as reduced immune function. Bats that exhibit harem polygyny in which males aggressively defend large groups of females year-round are ideal for assessing hormonal and other consequences of extreme polygyny. Here we use DNA methylation to estimate age and gas chromatography, tandem mass spectrometry to profile steroid metabolites in urine of wild greater spear-nosed bats, Phyllostomus hastatus, across seasons. We find that condition, measured by relative weight, is lower during the mating season for both sexes, although it remains high in harem males during the mating season. Average age of females is greater than males, and females exhibit substantial seasonal differences in androgens, estrogens and glucocorticoids with higher levels of all hormones during the mating season. Males, however, show little seasonal differences but substantial age-associated increases in most steroid metabolites. Harem males have larger, persistently scrotal testes and are older than bachelor males. While cortisone generally declines with age, harem males maintain higher amounts of biologically active cortisol than bachelor males all year and cortisol levels increase more quickly in response to restraint in males than in females. Taken together, these results suggest that attaining reproductive dominance requires hormone levels that reduce lifespan.
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Quirópteros , Estaciones del Año , Conducta Sexual Animal , Animales , Masculino , Femenino , Quirópteros/orina , Quirópteros/fisiología , Conducta Sexual Animal/fisiología , Factores de Edad , Metilación de ADN/fisiología , Envejecimiento/orina , Envejecimiento/fisiología , Reproducción/fisiología , Glucocorticoides/orina , Glucocorticoides/metabolismo , Andrógenos/orinaRESUMEN
Community Mental Health Centers (CMHCs) and Federally Qualified Health Centers (FQHCs) are critical access points for families with adolescents needing mental health care, especially those enrolled in Medicaid. However, barriers exist which may reduce their accessibility. This study aims to describe the availability and accessibility of outpatient mental health services for children and adolescents at safety-net health centers in a large metropolitan county. Approximately one year after the COVID-19 pandemic began in the U.S., a comprehensive sample of 117 CMHCs and 117 FQHCs were called and administered a 5-minute survey. Approximately 10% of health centers were closed, and 20% (28.2% of FQHCs and 7.7% of CMHCs) reported not offering outpatient mental health services. Despite CMHCs having 5.4 more clinicians on staff on average, reported wait times were longer at CMHCs than FQHCs. These findings indicate that online directories intended to be a comprehensive and accessible resource, such as the SAMHSA Treatment Locator, are often inaccurate or out-of-date.
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COVID-19 , Servicios de Salud Mental , Niño , Estados Unidos/epidemiología , Humanos , Adolescente , Pandemias , Accesibilidad a los Servicios de Salud , COVID-19/epidemiología , MedicaidRESUMEN
Most people who seek mental health treatment cannot access it. Certain groups (e.g., Medicaid enrollees and the uninsured) face particularly severe treatment access barriers along the care continuum. We interviewed 31 clinicians across two studies about their perspectives working in New York City's public mental health system. Because every clinician across both studies reported gaps in the system, we deployed an emergent, "serendipitous finding" approach and qualitatively analyzed the interviews together. Clinicians described three public mental health system gaps. First, many treatment-seekers must wait long periods of time to receive care and some never receive it at all. Second, patients with more serious challenges cannot access longer-term, higher-intensity, or specialized treatment. Third, some patients receiving high-intensity services may benefit from lower-intensity mental health support that is better integrated with medical and social service support. Coordinated and sustained financial investments at every step of the mental healthcare continuum are needed.
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Use of immunosuppressant calcineurin inhibitors (CNIs) is limited by irreversible kidney damage, hallmarked by renal fibrosis. CNIs directly damage many renal cell types. Given the diverse renal cell populations, additional targeted cell types and signaling mechanisms warrant further investigation. We hypothesized that fibroblasts contribute to CNI-induced renal fibrosis and propagate profibrotic effects via the transforming growth factor-ß (TGF-ß)/Smad signaling axis. To test this, kidney damage-resistant mice (C57BL/6) received tacrolimus (10 mg/kg) or vehicle for 21 days. Renal damage markers and signaling mediators were assessed. To investigate their role in renal damage, mouse renal fibroblasts were exposed to tacrolimus (1 nM) or vehicle for 24 h. Morphological and functional changes in addition to downstream signaling events were assessed. Tacrolimus-treated kidneys displayed evidence of renal fibrosis. Moreover, α-smooth muscle actin expression was significantly increased, suggesting the presence of fibroblast activation. TGF-ß receptor activation and downstream Smad2/3 signaling were also upregulated. Consistent with in vivo findings, tacrolimus-treated renal fibroblasts displayed a phenotypic switch known as fibroblast-to-myofibroblast transition (FMT), as α-smooth muscle actin, actin stress fibers, cell motility, and collagen type IV expression were significantly increased. These findings were accompanied by concomitant induction of TGF-ß signaling. Pharmacological inhibition of the downstream TGF-ß effector Smad3 attenuated tacrolimus-induced phenotypic changes. Collectively, these findings suggest that 1) tacrolimus inhibits the calcineurin/nuclear factor of activated T cells axis while inducing TGF-ß1 ligand secretion and receptor activation in renal fibroblasts; 2) aberrant TGF-ß receptor activation stimulates Smad-mediated production of myofibroblast markers, notable features of FMT; and 3) FMT contributes to extracellular matrix expansion in tacrolimus-induced renal fibrosis. These results incorporate renal fibroblasts into the growing list of CNI-targeted cell types and identify renal FMT as a process mediated via a TGF-ß-dependent mechanism.NEW & NOTEWORTHY Renal fibrosis, a detrimental feature of irreversible kidney damage, remains a sinister consequence of long-term calcineurin inhibitor (CNI) immunosuppressive therapy. Our study not only incorporates renal fibroblasts into the growing list of cell types negatively impacted by CNIs but also identifies renal fibroblast-to-myofibroblast transition as a process mediated via a TGF-ß-dependent mechanism. This insight will direct future studies investigating the feasibility of inhibiting TGF-ß signaling to maintain CNI-mediated immunosuppression while ultimately preserving kidney health.
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Miofibroblastos , Insuficiencia Renal , Tacrolimus , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Actinas/metabolismo , Inhibidores de la Calcineurina/farmacología , Fibroblastos/metabolismo , Fibrosis , Ratones Endogámicos C57BL , Miofibroblastos/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Tacrolimus/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Insuficiencia Renal/patologíaRESUMEN
BACKGROUND: Anorexia nervosa (AN) is a psychiatric disorder associated with marked morbidity. Whilst AN genetic studies could identify novel treatment targets, integration of functional genomics data, including transcriptomics and proteomics, would assist to disentangle correlated signals and reveal causally associated genes. METHODS: We used models of genetically imputed expression and splicing from 14 tissues, leveraging mRNA, protein, and mRNA alternative splicing weights to identify genes, proteins, and transcripts, respectively, associated with AN risk. This was accomplished through transcriptome, proteome, and spliceosome-wide association studies, followed by conditional analysis and finemapping to prioritise candidate causal genes. RESULTS: We uncovered 134 genes for which genetically predicted mRNA expression was associated with AN after multiple-testing correction, as well as four proteins and 16 alternatively spliced transcripts. Conditional analysis of these significantly associated genes on other proximal association signals resulted in 97 genes independently associated with AN. Moreover, probabilistic finemapping further refined these associations and prioritised putative causal genes. The gene WDR6, for which increased genetically predicted mRNA expression was correlated with AN, was strongly supported by both conditional analyses and finemapping. Pathway analysis of genes revealed by finemapping identified the pathway regulation of immune system process (overlapping genes = MST1, TREX1, PRKAR2A, PROS1) as statistically overrepresented. CONCLUSIONS: We leveraged multiomic datasets to genetically prioritise novel risk genes for AN. Multiple-lines of evidence support that WDR6 is associated with AN, whilst other prioritised genes were enriched within immune related pathways, further supporting the role of the immune system in AN.
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BACKGROUND: Clear evidence of overprescribing of psychotropic medicines to manage behaviours that challenges in people with intellectual disabilities has led to national programmes within the U.K. such as NHS England's STOMP to address this. The focus of the intervention in our review was deprescribing of psychotropic medicines in children and adults with intellectual disabilities. Mental health symptomatology and quality of life were main outcomes. METHODS: We reviewed the evidence using databases Medline, Embase, PsycINFO, Web of Science, CINAHL and Open Grey with an initial cut-off date of 22nd August 2020 and an update on 14th March 2022. The first reviewer (DA) extracted data using a bespoke form and appraised study quality using CASP and Murad tools. The second reviewer (CS) independently assessed a random 20% of papers. RESULTS: Database searching identified 8675 records with 54 studies included in the final analysis. The narrative synthesis suggests that psychotropic medicines can sometimes be deprescribed. Positive and negative consequences were reported. Positive effects on behaviour, mental and physical health were associated with an interdisciplinary model. CONCLUSIONS: This is the first systematic review of the effects of deprescribing psychotropic medicines in people with intellectual disabilities which is not limited to antipsychotics. Main risks of bias were underpowered studies, poor recruitment processes, not accounting for other concurrent interventions and short follow up periods. Further research is needed to understand how to address the negative effects of deprescribing interventions. TRIAL REGISTRATION: The protocol was registered with PROSPERO (registration number CRD42019158079).
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Deprescripciones , Discapacidad Intelectual , Niño , Adulto , Humanos , Discapacidad Intelectual/tratamiento farmacológico , Discapacidad Intelectual/psicología , Calidad de Vida , Salud Mental , Psicotrópicos/uso terapéuticoRESUMEN
Transition-age youth with mental health conditions from low socio-economic backgrounds often drop out of mental health services and, as such, do not receive therapeutic doses of treatment. Cornerstone is an innovative team-based, multi-component intervention designed to address the clinical needs of this understudied population through coordination and extensive provision of services in vivo (in the community). The present study used a convergent parallel mixed-methods design. Researchers collected quantitative and qualitative data during a small developmental trial, analyzing the two data types independently and then exploring them side-by-side to evaluate feasibility, acceptability, and preliminary implementation. Semi-structured interviews and quantitative surveys were conducted with transition-age youth, clinic staff, and policy makers. Qualitative interview guides were developed using the Consolidated Framework for Implementation Research to build understanding on implementation determinants alongside feasibility and acceptability. A two-group preliminary randomized trial was conducted to assess feasibility outcomes, such as recruitment, randomization, measurement performance, and trends in pre- to post- outcomes. Using grounded theory coding techniques, transcripts were coded by multiple coders, and themes were identified on acceptability and implementation. The team recruited fifty-six transition-age youth. Randomization was used in the study and the intervention was provided without incident. Results suggest individual components with both the social worker and mentor were more acceptable to participants than group-based approaches. Thematic analyses revealed themes associated with the inner, outer, and policy contexts describing a range of critical implementation determinants. Findings suggest that Cornerstone is feasible, acceptable, and promising for transition-age youth. It represents an innovative multi-component intervention worth exploring for transition-age youth with mental health conditions in a larger efficacy trial.Trial registration: The trial was registered at ClinicalTrials.gov (NCT02696109) on 22 April 16, Protocol Record R34-MH102525-01A1, New York University, Cornerstone program for transition-age youth with serious mental illness: study protocol for a randomized controlled trial.
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Trastornos Mentales , Servicios de Salud Mental , Adolescente , Humanos , Estudios de Factibilidad , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Salud Mental , Encuestas y CuestionariosRESUMEN
Comparative analyses of bats indicate that hibernation is associated with increased longevity among species. However, it is not yet known if hibernation affects biological ageing of individuals. Here, we use DNA methylation (DNAm) as an epigenetic biomarker of ageing to determine the effect of hibernation on the big brown bat, Eptesicus fuscus. First, we compare epigenetic age, as predicted by a multi-species epigenetic clock, between hibernating and non-hibernating animals and find that hibernation is associated with epigenetic age. Second, we identify genomic sites that exhibit hibernation-associated change in DNAm, independent of age, by comparing samples taken from the same individual in hibernating and active seasons. This paired comparison identified over 3000 differentially methylated positions (DMPs) in the genome. Genome-wide association comparisons to tissue-specific functional elements reveals that DMPs with elevated DNAm during winter occur at sites enriched for quiescent chromatin states, whereas DMPs with reduced DNAm during winter occur at sites enriched for transcription enhancers. Furthermore, genes nearest DMPs are involved in regulation of metabolic processes and innate immunity. Finally, significant overlap exists between genes nearest hibernation DMPs and genes nearest previously identified longevity DMPs. Taken together, these results are consistent with hibernation influencing ageing and longevity in bats.
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Envejecimiento , Quirópteros , Hibernación , Envejecimiento/genética , Animales , Quirópteros/genética , Epigénesis Genética , Estudio de Asociación del Genoma CompletoRESUMEN
While randomized controlled trials of trauma-focused cognitive behavioral therapy (TF-CBT) have demonstrated efficacy for youth with posttraumatic stress disorder, TF-CBT effectiveness trials typically show attenuated outcomes. This decrease in effectiveness may be due to the differences in sociodemographic characteristics of youth in these trials; youth in efficacy trials are more often white and middle-income, whereas youth in effectiveness trials are more often racial/ethnic minorities, of low socioeconomic status (SES) and live in high crime neighborhoods. In this study-drawn from an effectiveness trial of TF-CBT in community mental health clinics across Philadelphia-we describe the sociodemographic characteristics of enrolled youth. We measured neighborhood SES by matching participants' addresses to American Community Survey data from their Census tracts, housing stability using the National Outcomes Measurement System, and neighborhood violence using police department crime statistics. Our results suggest that the majority of youth presenting for TF-CBT in mental health clinics in the City of Philadelphia live in poor and high-crime neighborhoods, experience substantial housing instability, and are predominantly ethnic and racial minorities. Thus, youth presenting for treatment experience significant racial and socioeconomic adversity. We also explored the association between these characteristics and youth symptom severity upon presenting for treatment. These factors were not associated with youth symptom severity or overall mental health functioning in our sample (with small effect sizes and p > .05 for all). Implications for future research, such as the need for efficacy and effectiveness trials to more fully characterize their samples and the need for pragmatic trials are discussed.
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Terapia Cognitivo-Conductual/métodos , Servicios Comunitarios de Salud Mental/organización & administración , Trastornos por Estrés Postraumático/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Philadelphia , Características de la Residencia , Índice de Severidad de la Enfermedad , Factores Socioeconómicos , Trastornos por Estrés Postraumático/etnología , Trastornos por Estrés Postraumático/psicología , Adulto JovenRESUMEN
Quality or performance management capabilities allow agencies to identify effective practices in routine care, implement new practices, and learn to adapt practices as contexts change. Within child-serving human service systems there is not a dominant model of quality management capabilities and how they are deployed. Quality management capabilities and their development were explored at nine different child serving agencies. Agency respondents described four emergent core quality management capabilities: generating shared goals, managing information, routinizing problem-solving, and propagating a culture of quality. None of the nine agencies we studied excelled at all four. Each capability is described and implications for research, policy and practice are discussed.
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Servicios de Salud del Niño/organización & administración , Hospitales Psiquiátricos/organización & administración , Organizaciones sin Fines de Lucro/organización & administración , Adolescente , Niño , Servicios de Salud del Niño/normas , Preescolar , Hospitales Psiquiátricos/normas , Humanos , Lactante , Estudios de Casos Organizacionales , Cultura Organizacional , Objetivos Organizacionales , Organizaciones sin Fines de Lucro/normas , Solución de ProblemasRESUMEN
Bats live longer than similar-sized mammals, but the number of lineages that have independently evolved extreme longevity has not previously been determined. Here we reconstruct the evolution of size-corrected longevity on a recent molecular phylogeny and find that at least four lineages of bats have lifespans more than fourfold those of similar-sized placental mammals, with the ancestral bat projected to live 2.6 times as long. We then evaluate a series of phylogenetic generalized least-squares models containing up to nine variables hypothesized to influence extrinsic mortality. These analyses reveal that body mass and hibernation predict longevity. Among hibernators, longevity is predicted by the absolute value of the median latitude of the species range and cave use, while cave use and lack of sexual dimorphism predict longevity among non-hibernators. The importance of torpor in extending lifespan is further supported by the one lineage with extreme longevity that does not hibernate but exhibits flexible thermoregulation, the common vampire bat. We propose several potential mechanisms that may enable bats to live so long, and suggest that the ability to tolerate a wide range of body temperatures could be important for surviving viral or other pathogen infections.
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Quirópteros , Hibernación , Animales , Femenino , Longevidad , Mamíferos , Filogenia , EmbarazoRESUMEN
It is critical for urban youth with post-traumatic stress disorder (PTSD) living in poverty to have access to evidence-based interventions for their traumatic stress. However, there is limited research on the effectiveness of these interventions when provided in urban, community settings. The objectives of the current study are to (a) evaluate the effectiveness of trauma-focused cognitive behavioral therapy delivered from 2013 to 2016 in 15 behavioral health agencies on youth (N = 114) PTSD as well as general mental health symptoms and functioning, and (b) benchmark these clinical outcomes against other published efficacy and effectiveness trials. Effectiveness data are from the Philadelphia County Community Behavioral Health System, a system that has invested significantly in the training and ongoing support of clinicians providing high-quality trauma services to youth since 2012. From baseline to last assessment, youth PTSD symptom severity (d = 0.34), PTSD functional impairment (d = 0.38), and overall mental health problem severity (d = 0.29) improved. The effect sizes of improvements were smaller than effect sizes observed in efficacy and effectiveness studies. This study is the first benchmarking study of TF-CBT and provides preliminary findings with regard to the effectiveness, and transportability, of TF-CBT to urban community settings that serve youth in poverty.
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Benchmarking , Terapia Cognitivo-Conductual/normas , Servicios de Salud Comunitaria , Trastornos por Estrés Postraumático/psicología , Trastornos por Estrés Postraumático/terapia , Adolescente , Niño , Femenino , Humanos , Masculino , Philadelphia , Resultado del TratamientoRESUMEN
BACKGROUND: People with intellectual disabilities are more likely to experience poor health than the general population and are frequently prescribed multiple medications. Therefore, it is important that people with intellectual disabilities understand their medication and potential adverse effects. METHOD: A scoping review explored people with intellectual disabilities' knowledge of prescription medications, their risks and how medication understanding can be improved. RESULTS: Ten journal articles were included. People with intellectual disabilities often lacked understanding of their medication, including its name, purpose and when and how to take it. Participants were often confused or unaware of adverse effects associated with their medication. Information was sometimes explained to carers rather than people with intellectual disabilities. Some interventions and accessible information helped to improve knowledge in people with intellectual disabilities. CONCLUSION: There is a need for accessible and tailored information about medication to be discussed with people with intellectual disabilities in order to meet legal and best practice standards.
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Discapacidad Intelectual , Conocimiento de la Medicación por el Paciente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Competencia Mental , Educación del Paciente como AsuntoRESUMEN
Therapist turnover is a major problem in community mental health. Financial strain, which is composed of cognitive, emotional, and behavioral responses to the experience of economic hardship, is an understudied antecedent of therapist turnover given the tumultuous financial environment in community mental health. We prospectively examined the relationship between therapist financial strain and turnover in 247 therapists in 28 community mental health agencies. We expected greater therapist financial strain to predict higher turnover and participation in a system-funded evidence-based practice (EBP) training initiative to alleviate this effect. Controlling for covariates, financial strain predicted therapist turnover (OR 1.12, p = .045), but not for therapists who participated in an EBP training initiative. Reducing financial strain and/or promoting EBP implementation may be levers to reduce turnover.
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Difusión de Innovaciones , Práctica Clínica Basada en la Evidencia , Reorganización del Personal/economía , Medicina de la Conducta , Servicios Comunitarios de Salud Mental , Femenino , Humanos , Masculino , Innovación OrganizacionalRESUMEN
Chemical signals are ubiquitous, but often overlooked as potentially important for conveying information relevant for sexual selection. The male greater spear-nosed bat, Phyllostomus hastatus, possesses a sexually dimorphic gland on the chest that produces an odoriferous secretion. Here, we investigate the potential for this glandular secretion to act as a sexually selected olfactory signal by examining gland activity in and out of the mating season and determining if variation in its chemical composition reflects variation in male mating status or attributes of the individual. Based on gas chromatography-mass spectrometry (GC-MS) measurements of samples collected from wild bats roosting in caves in Trinidad, West Indies, we find that males that defend and roost with groups of females (harem holders) have significantly different chemical profiles from males found roosting in all male groups (bachelors). Additionally, profiles differed significantly among individuals. Taken together, these results suggest that this chemical signal has the potential to communicate both mating status and individual identity and thus could be used to mediate interactions among individuals within this harem-based social mating system.
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Quirópteros/fisiología , Glándulas Odoríferas/química , Conducta Sexual Animal/fisiología , Envejecimiento , Animales , Análisis Discriminante , Femenino , Cromatografía de Gases y Espectrometría de Masas , Masculino , Análisis de Componente Principal , Glándulas Odoríferas/metabolismo , Atractivos Sexuales/análisisRESUMEN
Community-academic partnerships(CAPs) are a critical component of implementing and sustaining evidence-based practices (EBPs) in community settings; however, the approaches used and mechanisms of change within CAPs have not been rigorously studied. The first step to advancing the science of CAP is to operationally define and contextualize the approaches used in CAP as part of the implementation process. Our research group has gleaned valuable lessons about the best ways to develop, support, and nurture community partnerships within the context of implementation. In this article, we share these lessons learned and relate them to implementation strategies that are most relevant to community-partnered implementation endeavors. The implementation strategies most relevant to CAPs are as follows: (a) building a coalition, (b) conducting local consensus discussions, (c) identifying barriers and facilitators to implementation, (d) facilitating interactive problem solving, (e) using an advisory board or workgroup, (f) tailoring strategies, (g) promoting adaptability, and (h) auditing and providing feedback. We offer suggestions for future research to systematically evaluate these strategies, with an eye toward advancing the science of CAP and implementation science and the goal of guiding future research and improving the implementation of EBPs in community settings.
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Investigación Participativa Basada en la Comunidad , Relaciones Comunidad-Institución , Práctica Clínica Basada en la Evidencia , HumanosRESUMEN
Organizational culture and climate are important determinants of behavioral health service delivery for youth. The Organizational Social Context measure is a well validated assessment of organizational culture and climate that has been developed and extensively used in public sector behavioral health service settings. The degree of concordance between administrators and clinicians in their reports of organizational culture and climate may have implications for research design, inferences, and organizational intervention. However, the extent to which administrators' and clinicians' reports demonstrate concordance is just beginning to garner attention in public behavioral health settings in the United States. We investigated the concordance between 73 administrators (i.e., supervisors, clinical directors, and executive directors) and 247 clinicians in 28 child-serving programs in a public behavioral health system. Findings suggest that administrators, compared to clinicians, reported more positive cultures and climates. Organizational size moderated this relationship such that administrators in small programs (<466 youth clients served annually) provided more congruent reports of culture and climate in contrast to administrators in large programs (≥466 youth clients served annually) who reported more positive cultures and climates than clinicians. We propose a research agenda that examines the effect of concordance between administrators and clinicians on organizational outcomes in public behavioral health service settings.
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Personal Administrativo , Actitud del Personal de Salud , Servicios Comunitarios de Salud Mental/organización & administración , Personal de Salud , Cultura Organizacional , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , PhiladelphiaRESUMEN
BACKGROUND: The detection of somatic mutations in primary tumors is critical for the understanding of cancer evolution and targeting therapy. Multiple technologies have been developed to enable the detection of such mutations. Next generation sequencing (NGS) is a new platform that is gradually becoming the technology of choice for genotyping cancer samples, owing to its ability to simultaneously interrogate many genomic loci at massively high efficiency and increasingly lower cost. However, multiple barriers still exist for its broader adoption in clinical research practice, such as fragmented workflow and complex bioinformatics analysis and interpretation. METHODS: We performed validation of the QIAGEN GeneReader NGS System using the QIAact Actionable Insights Tumor Panel, focusing on clinically meaningful mutations by using DNA extracted from formalin-fixed paraffin-embedded (FFPE) colorectal tissue with known KRAS mutations. The performance of the GeneReader was evaluated and compared to data generated from alternative technologies (PCR and pyrosequencing) as well as an alternative NGS platform. The results were further confirmed with Sanger sequencing. RESULTS: The data generated from the GeneReader achieved 100% concordance with reference technologies. Furthermore, the GeneReader workflow provides a truly integrated workflow, eliminating artifacts resulting from routine sample preparation; and providing up-to-date interpretation of test results. CONCLUSION: The GeneReader NGS system offers an effective and efficient method to identify somatic (KRAS) cancer mutations.
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Análisis Mutacional de ADN , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Colorrectales/genética , Fijadores/química , Formaldehído/química , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Adhesión en Parafina , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: This randomized trial will compare three methods of assessing fidelity to cognitive-behavioral therapy (CBT) for youth to identify the most accurate and cost-effective method. The three methods include self-report (i.e., therapist completes a self-report measure on the CBT interventions used in session while circumventing some of the typical barriers to self-report), chart-stimulated recall (i.e., therapist reports on the CBT interventions used in session via an interview with a trained rater, and with the chart to assist him/her) and behavioral rehearsal (i.e., therapist demonstrates the CBT interventions used in session via a role-play with a trained rater). Direct observation will be used as the gold-standard comparison for each of the three methods. METHODS/DESIGN: This trial will recruit 135 therapists in approximately 12 community agencies in the City of Philadelphia. Therapists will be randomized to one of the three conditions. Each therapist will provide data from three unique sessions, for a total of 405 sessions. All sessions will be audio-recorded and coded using the Therapy Process Observational Coding System for Child Psychotherapy-Revised Strategies scale. This will enable comparison of each measurement approach to direct observation of therapist session behavior to determine which most accurately assesses fidelity. Cost data associated with each method will be gathered. To gather stakeholder perspectives of each measurement method, we will use purposive sampling to recruit 12 therapists from each condition (total of 36 therapists) and 12 supervisors to participate in semi-structured qualitative interviews. DISCUSSION: Results will provide needed information on how to accurately and cost-effectively measure therapist fidelity to CBT for youth, as well as important information about stakeholder perspectives with regard to each measurement method. Findings will inform fidelity measurement practices in future implementation studies as well as in clinical practice. TRIAL REGISTRATION: NCT02820623 , June 3rd, 2016.
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Terapia Cognitivo-Conductual/economía , Terapia Cognitivo-Conductual/estadística & datos numéricos , Análisis Costo-Beneficio/economía , Análisis Costo-Beneficio/estadística & datos numéricos , Trastornos Mentales/terapia , Proyectos de Investigación , Adolescente , Adulto , Niño , Terapia Cognitivo-Conductual/métodos , Análisis Costo-Beneficio/métodos , Femenino , Humanos , Masculino , Philadelphia , Reproducibilidad de los Resultados , Autoinforme , Adulto JovenRESUMEN
Staff turnover rates in publicly-funded mental health settings are high. We investigated staff and organizational predictors of turnover in a sample of individuals working in an urban public mental health system that has engaged in a system-level effort to implement evidence-based practices. Additionally, we interviewed staff to understand reasons for turnover. Greater staff burnout predicted increased turnover, more openness toward new practices predicted retention, and more professional recognition predicted increased turnover. Staff reported leaving their organizations because of personal, organizational, and financial reasons; just over half of staff that left their organization stayed in the public mental health sector. Implications include an imperative to focus on turnover, with a particular emphasis on ameliorating staff burnout.