Sorbus

The generation of JAM-B-CreER and W3 mice has been described previously (Kim et al., 2008 (link)); Y. Z, I. J. K, J. R. S. and M. M., in preparation). Briefly, the JAM-B-CreER transgene was generated from a bacterial artificial chromosome (BAC) by insertion of a CreER cDNA at the initiation codon of the JAM-B coding sequence. The recombineering method of Lee et al. (2001) (link) was used to remove the loxP site from the BAC, and to insert a frt-neo-frt cassette, Cre-ER and a polyadenylation signal. Following generation of transgenic mice by standard methods, mice were mated to mice that expressed flp recombinase ubiquitously (Farley et al., 2000 (link)) to excise the frt-neo-frt cassette. FSTL4-CreER mice were generated by the same strategy, except that the BAC contained approximately 128kB from the FSTL4 gene, including ~100kB upstream and ~28kB downstream of the initiation codon (Children’s Hospital Research Institute; Oakland, CA). JAM-B-CreER and FSTL4-CreER mice were crossed to mice that express the Yellow Fluorescent Protein (YFP) following Cre-mediated excision of sequences that block terminate transcription and translation (Thy1-STOP-YFP mice line 15, called TSY here; Fig. 1a; Buffelli et al., 2003 (link)). Tamoxifen (100 µg, Sigma) was injected intraperitoneally into double transgenics at postnatal day (P) 0–1 to activate CreER and thereby initiate expression of YFP.
W3 and W7 mice were generated from a vector in which Thy1 regulatory elements drive expression of YFP, wheat germ agglutinin (WGA) and E. Coli β-galactosidase (LacZ; Thy1-lox-YFP-STOP-lox-WGA-LacZ; Fig. 1a; called TYW3 and TYW7, respectively). The transgene was intended to express WGA plus LacZ following excision of YFP by Cre, but neither WGA nor LacZ were expressed at detectable levels. YFP was expressed in distinct and non-overlapping subsets of RGCs in the W3 and W7 lines, presumably due to effects of sequences near the site of transgene integration in the genome (see Feng et al., 2000 (link) for discussion). To decrease the number of YFP-positive RGCs in these lines, an adeno-associated virus (AAV, serotype 2) that expressed Cre under the control of a CMV-promoter (Harvard Gene Therapy Core, Children’s Hospital, Boston) was injected into the retina as described below.
Mice in which the regulatory elements of the Ch×10 gene drive expression of Cre (Rowan and Cepko, 2004 (link)) were provided by Constance Cepko (Harvard). Ch×10-Cre mice were crossed to TSY mice to label a large subset of RGCs.

Eight of the largest residential prison-based treatment programs operating in two states located in the central and southwest regions of the U.S. were selected for this study. They represented the first wave of large treatment programs to begin implementing selected elements of the TCU Short Forms while working collaboratively with the IBR staff on longitudinal research projects starting in 2008. All programs were classified as minimum security and operated as stand-alone treatment facilities, following modified therapeutic community principles delivered in three phases (orientation, treatment, and re-entry). Five programs were for males, including three representing regular treatment units (bed space ranging from 504 to 650) and two for special medical and mental health needs (with beds for 212 and 323). In addition, three female programs were included, two of which were regular treatment units (with beds for 240 and 612) and another operated to address special medical and mental health needs (288 beds). Planned length of stay varied for these eight programs. For the regular male programs, two were programmed for stays of 6 months and one for 12-to-24 months. The two male special needs programs had planned tenures of 6-to-12 months. The female programs operated within this time spectrum as well. Planned durations for special needs programs was 6-to-12 months, the one regular program was 6-to-9 months, and the third program had three different tenure tracks that depended on client severity (90 days, 6 months, and 12-to-24 months).
The total sample for the study consisted of 5,022 inmates participating in these eight prison-based treatment programs, including 3,025 males (60%) and 1,997 females (40%). Whites comprised 48%, Blacks (31%), and Hispanics (21%). Average age overall was 36 years, and weekly drug use before prison included alcohol (34%), marijuana (28%), crack cocaine (15%), cocaine alone (11%), illegal methadone (19%), heroin alone (9%), and other opiates (9%). The sample was diversified within and between the programs and therefore appropriate for studying properties of assessment instruments (see Rowan-Szal, Joe, Bartholomew, Pankow, & Simpson, in this volume , for further analysis of females and additional assessment forms).
The TCU Short Forms reported below were collected from inmates at four time points – Time 1 (intake), Time 2 (end of orientation), Time 3 (end of treatment), and Time 4 (re-entry, prior to release) – and 55% of the 5,022 treatment participants completed at least one administration of all six forms (and with another 28% completing five of the six). However, there was no mandated or standard assessment schedule across treatment sites, and there also were variations in the particular forms these programs chose to use. Program specialization and planned duration were determining factors in their administering of forms. Exceptions were that TCUDS II was completed only once (at intake, Time 1), and ENGForm for measuring during-treatment engagement was completed at subsequent time points, but not at intake. Furthermore, all eight prison treatments began data collection for this study at different dates, starting in November 2008 and ending in May 2010, so that not all inmates entering treatment had sufficient time in their programs to complete later administrations for some assessments (e.g., at Times 3 or 4). All available records for each form were used for analyses, resulting in sample sizes ranging from 5,022 for TCUDS II (from its one-time administration at intake) to 15,818 for TCU PSYForm (combined from multiple administrations over four possible time points).

The Cardiotoxicity of Cancer Therapy (CCT) study is an ongoing, prospective, longitudinal cohort study of breast cancer participants at the Rena Rowan Breast Cancer Center at the University of Pennsylvania (Philadelphia, PA). This study was approved by the Institutional Review Board of the University of Pennsylvania and all participants provided informed consent.
The study protocol has been previously described.^{19 (link)} Briefly, participants were eligible to be included if they were at least 18 years of age, diagnosed with breast cancer, and treated with doxorubicin and/or trastuzumab therapy. The only exclusion criterion was pregnancy; participants with an abnormal baseline LVEF were not excluded. Treatment regimens were determined by the treating oncologist and classified into 3 primary categories: 1) doxorubicin (240 mg/m²) with concurrent cyclophosphamide, followed by paclitaxel (Dox); 2) trastuzumab with docetaxel and either cyclophosphamide or carboplatin (Tras); and 3) doxorubicin (240 mg/m²) with concurrent cyclophosphamide, followed by trastuzumab and paclitaxel (Dox+Tras).
Detailed clinical data, verified via physician medical records, and the MD Anderson Symptom Inventory – Heart Failure (MDASI-HF) survey assessing HF symptoms on a scale of 0–10, were obtained at baseline and followup.^{20 (link)} Echocardiograms were also performed at standardized time intervals according to the prescribed treatment regimen.^{19 (link)} In the Dox group, echocardiography was performed at baseline, at completion of paclitaxel (approximately 4 months after initiation of chemotherapy), and annually. In the Tras group, echocardiography was performed at baseline, every 3 months during trastuzumab, and annually. In the Dox+Tras group, echocardiography was performed at baseline, after doxorubicin (approximately 2 months after initiation of chemotherapy), every 3 months during trastuzumab, and annually.
The current analyses were limited to those participants enrolled between August 2010 and August 2015 who had a baseline assessment of cardiac function and at least 1 followup echocardiogram, and include echocardiography data up to 3.2 years after initiation of therapy.