Child and Family Therapy Process: Concordance of Therapist and Observational Perspectives

The objective of this study is to examine the characteristics of outpatient mental health services delivered in community-based outpatient clinics, comparing information obtained from two different sources, therapists serving children and families, and observational coders viewing tapes of the same treatment sessions. Videotaped therapy sessions were rated by therapists and independent coders regarding goals and strategies pursued during each session. Sixty-three sessions were taped of outpatient care provided to 18 children and their caregivers by 11 therapists. Children were 4–13 years old and families were receiving services at least in part due to reported child behavior problems, confirmed by ratings from the Child Behavior Checklist and Conners Parent Rating Scale—Revised. Analyses assessed the frequency, type, and intensity of goals and strategies pursued in therapy sessions from both therapist and observational coders’ perspectives. Reliability of observer ratings and correspondence between therapist and observer reports were also examined. The reliability of observational coding of goals and strategies was moderate to good, with 76% of 39 codes having ICCs of .5 or greater. Therapists reported pursuing 2.5 times more goals and strategies per session, on average, than identified by observational coders. Correspondence between therapists and coders about the occurrence of specific goals and strategies in treatment sessions was low, with 20.5% of codes having a Kappa of .4 or higher. Substantial differences exist in what therapists and independent coders report as occurring in outpatient treatment sessions. Both perspectives suggest major differences between the content of services provided in community-based outpatient clinics and the structure of evidence-based programs, which emphasize intense pursuit of a small number of goals and strategies in each treatment session. Implications of the findings for quality improvement efforts in community-based mental health care settings are discussed

Paired-Homeodomain Transcription Factor PAX4 Acts as a Transcriptional Repressor in Early Pancreatic Development

The paired-homeodomain transcription factor PAX4 is expressed in the developing pancreas and along with PAX6 is required for normal development of the endocrine cells. In the absence of PAX4, the numbers of insulin-producing β cells and somatostatin-producing δ cells are drastically reduced, while the numbers of glucagon-producing α cells are increased. To gain insight into PAX4 function, we cloned a full-length Pax4 cDNA from a β-cell cDNA library and identified a bipartite consensus DNA binding sequence consisting of a homeodomain binding site separated from a paired domain binding site by 15 nucleotides. The paired half of this consensus sequence has similarities to the PAX6 paired domain consensus binding site, and the two proteins bind to common sequences in several islet genes, although with different relative affinities. When expressed in an α-cell line, PAX4 represses transcription through the glucagon or insulin promoters or through an isolated PAX4 binding site. This repression is not simply due to competition with the PAX6 transcriptional activator for the same binding site, since PAX4 fused to the unrelated yeast GAL4 DNA binding domain also represses transcription through the GAL4 binding site in the α-cell line and to a lesser degree in β-cell lines and NIH 3T3 cells. Repressor activity maps to more than one domain within the molecule, although the homeodomain and carboxyl terminus give the strongest repression. PAX4 transcriptional regulation apparently plays a role only early in islet development, since Pax4 mRNA as determined by reverse transcriptase PCR peaks at embryonic day 13.5 in the fetal mouse pancreas and is undetectable in adult islets. In summary, PAX4 can function as a transcriptional repressor and is expressed early in pancreatic development, which may allow it to suppress α-cell differentiation and permit β-cell differentiation

Abstract P4-04-05: Differential mRNA expression patterns in breast tumors with high vs. low quantity of stromal tumor–Infiltrating lymphocytes

Abstract Background: Tumor-infiltrating lymphocytes (TIL) have prognostic and potentially predictive significance in the (neo)adjuvant treatment of high-risk breast cancer. However, quantitative TIL measurement is not routinely performed. It is unclear why some tumors attract large quantities of TIL while others do not. We sought to confirm the association between TIL and pathologic complete response rate (pCR) and to further use next generation sequencing (NGS) to identify genes and gene pathways associated with the presence/absence of TIL. Methods: We studied 140 women with high risk stage I-III breast cancer, enrolled in the Breast Cancer Genome Guided Therapy Study (BEAUTY), obtaining serial biopsies for DNA/RNA sequencing and MRI imaging to assess response to neoadjuvant chemotherapy (NAC) with taxane (+/- trastuzumab+/-pertuzumab for HER2+ disease) followed by AC or (F)EC. Diagnostic pre-NAC core needle biopsies and surgical resection specimens post-NAC were available from 110 patients. Stromal TIL were semi-quantitated on a scale of 1-4 (with 1: ≤10/hpf, 2: subtle infiltrate &amp;gt;10/hpf, 3: moderate infiltrate readily visible at low power magnification, 4: dense infiltrate with innumerable lymphocytes). For this analysis, low TIL was defined as scores of 1-2 vs. high defined as 3-4. Using pre-NAC biopsies, RNAseq was performed using the Illumina HiSeq2000 and the Mayo Analysis Pipeline for RNAseq (MAP-Rseq) for quality control, sequence alignment, and gene counts. The quantity of TIL was associated with transcripts across the transcriptome after conditional quantile normalization. Differentially expressed genes were obtained using EdgeR analysis, using a false discovery rate of 0.05, and pathways were evaluated using GAGE methods. Results: The pCR and residual cancer burden (RCB)-0/I rates by stromal TIL status within each molecular subtype are presented in the table. A diverse spectrum of 1344 genes with differential expression between tumors with high vs. low stromal TIL was identified. The genes with &amp;gt;2.0-fold change (FC) and p&amp;lt;1e-09 included S100A7 (4.49 FC), LCN2 (2.48 FC), and ART3 (2.82 FC) (genes known to be involved in immune regulation), as well as TDRD1 (2.71 FC) (a gene related to ERG [ETS-related gene] expression). In addition, the "regulation of actin cytoskeleton" pathway was upregulated in tumors with high TIL, while the "Hedgehog signaling" and "Wnt signaling" pathways were downregulated. Molecular SubtypeStromal TILspCR rate n (%)RCB-0/I rateLuminal AHigh------Luminal ALow0/9 (0%)0/9 (0%)Luminal BHigh1/9 (11.1%)1/8 (12.5%)Luminal BLow3/24 (12.5%)6/23 (26.1%)ER+/HER2+High3/9 (33.3%)4/9 (44.4%)ER+/HER2+Low1/6 (16.7%)1/6 (16.7%)ER-/HER2+High8/9 (88.9%)7/7 (100%)ER-/HER2+Low4/8 (50.0%)6/8 (75.0%)Triple NegativeHigh10/19 (52.6%)13/19 (68.4%)Triple NegativeLow7/14 (50.0%)9/13 (69.2%) Conclusions: We identified genes and gene pathways associated with high TIL expression in breast tumors prior to NAC that provide insight into the interactions between TIL and tumors. TIL can be easily semi-quantitated on H&amp;E and along with these novel biomarkers, may contribute to the personalization of breast cancer therapy. Citation Format: Moyer AM, Boughey JC, Kalari KR, Suman VJ, McLaughlin SA, Moreno-Aspitia A, Northfelt DW, Gray RJ, Sinnwell JP, Carlson EE, Dockter TJ, Jones KN, Felten SJ, Conners AL, Wieben ED, Ingle JN, Wang L, Weinshilboum RM, Visscher DW, Goetz MP. Differential mRNA expression patterns in breast tumors with high vs. low quantity of stromal tumor–Infiltrating lymphocytes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-05.</jats:p

Central Implementation Strategies Outperform Local Ones in Improving HIV Testing in Veterans Healthcare Administration Facilities

BACKGROUND: Pilot data suggest that a multifaceted approach may increase HIV testing rates, but the scalability of this approach and the level of support needed for successful implementation remain unknown. OBJECTIVE: To evaluate the effectiveness of a scaled-up multi-component intervention in increasing the rate of risk-based and routine HIV diagnostic testing in primary care clinics and the impact of differing levels of program support. DESIGN: Three arm, quasi-experimental implementation research study. SETTING: Veterans Health Administration (VHA) facilities. PATIENTS: Persons receiving primary care between June 2009 and September 2011 INTERVENTION: A multimodal program, including a real-time electronic clinical reminder to facilitate HIV testing, provider feedback reports and provider education, was implemented in Central and Local Arm Sites; sites in the Central Arm also received ongoing programmatic support. Control Arm sites had no intervention MAIN MEASURES: Frequency of performing HIV testing during the 6 months before and after implementation of a risk-based clinical reminder (phase I) or routine clinical reminder (phase II). KEY RESULTS: The adjusted rate of risk-based testing increased by 0.4 %, 5.6 % and 10.1 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). During phase II, the adjusted rate of routine testing increased by 1.1 %, 6.3 % and 9.2 % in the Control, Local and Central Arms, respectively (all comparisons, p < 0.01). At study end, 70–80 % of patients had been offered an HIV test. CONCLUSIONS: Use of clinical reminders, provider feedback, education and social marketing significantly increased the frequency at which HIV testing is offered and performed in VHA facilities. These findings support a multimodal approach toward achieving the goal of having every American know their HIV status as a matter of routine clinical practice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-013-2420-6) contains supplementary material, which is available to authorized users