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The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E7.5 through E13.5. We demonstrate the utility of the TCreERT2 line for determining rate of posterior axis extension and somite formation, thus providing the first in vivo tool for such measurements. To test the usefulness of TCreERT2 for genetic manipulation, we demonstrate that an early deletion of ß-Catenin via TCreERT2 induction phenocopies the TCre-mediated deletion of ß-Catenin defect, whereas a later induction bypasses this early phenotype and produces a similar defect in more caudal tissues. TCreERT2 provides a useful and novel tool for the control of gene expression of emerging embryonic lineages throughout development.

The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E7.5 through E13.5. We demonstrate the utility of the TCreERT2 line for determining rate of posterior axis extension and somite formation, thus providing the first in vivo tool for such measurements. To test the usefulness of TCreERT2 for genetic manipulation, we demonstrate that an early deletion of s-Catenin via TCreERT2 induction phenocopies the TCre-mediated deletion of s-Catenin defect, whereas a later induction bypasses this early phenotype and produces a similar defect in more caudal tissues. TCreERT2 provides a useful and novel tool for the control of gene expression of emerging embryonic lineages throughout development.

We draw upon literature examining cross-modal sensory interactions and congruence to explore the impact of smell on touch. In line with our predictions, two experiments show that smell can impact touch in meaningful ways. Specifically, we show that multisensory semantic congruence between smell and touch properties of a stimulus enhances haptic perception and product evaluation. We explore this relationship in the context of two properties of touch, namely texture and temperature, and demonstrate that both smell and touch can have semantic associations, which can affect haptic perception and product evaluation depending on whether they match or not. In study 1, we focus on the semantic association of smell and touch (texture) with gender and in study 2 with temperature. Our results extend prior work on smell and touch within consumer behavior, and further contribute to emerging literature on multisensory interactions.

Ventricular septal myomectomy (VSM) is the primary modality for left ventricular outflow tract gradient reduction in patients with obstructive hypertrophic cardiomyopathy with refractory symptoms. Comprehensive postprocedural data for VSM from a large multicenter registry are sparse. The primary objective of this study was to evaluate postprocedural mortality, complications, length of stay (LOS), and cost of hospitalization after VSM and to further appraise the multivariate predictors of these outcomes. The Healthcare Cost and Utilization Project's Nationwide Inpatient Sample was queried from 1998 through 2010 using International Classification of Diseases, Ninth Revision, procedure codes 37.33 for VSM and 425.1 for hypertrophic cardiomyopathy. The severity of co-morbidities was defined using the Charlson co-morbidity index. Hierarchical mixed-effects models were generated to identify independent multivariate predictors of in-hospital mortality, procedural complications, LOS, and cost of hospitalization. The overall mortality was 5.9%. Almost 9% (8.7%) of patients had postprocedural complete heart block requiring pacemakers. Increasing Charlson co-morbidity index was associated with a higher rate of complications and mortality (odds ratio 2.41, 95% confidence interval 1.17 to 4.98, p = 0.02). The mean cost of hospitalization was $41,715 ± $1,611, while the average LOS was 8.89 ± 0.35 days. Occurrence of any postoperative complication was associated with increased cost of hospitalization (+$33,870, p <0.001) and LOS (+6.08 days, p <0.001). In conclusion, the postoperative mortality rate for VSM was 5.9%; cardiac complications were most common, specifically complete heart block. Age and increasing severity of co-morbidities were predictive of poorer outcomes, while a higher burden of postoperative complications was associated with a higher cost of hospitalization and LOS. •Higher postoperative mortality was found after VSM than reported in recent studies.•Age was predictive of higher postoperative mortality and complications.•Higher burden of co-morbidities predicted higher postoperative mortality and complications.•More postoperative complications were associated with longer LOS.

Background The current standard of care for patients with a large brain metastasis and limited intracranial disease burden is surgical resection and post-operative single fraction stereotactic radiosurgery (SRS). However, post-operative SRS can still lead to substantial rates of local failure (LF), radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated treatments may improve local control by allowing delivery of higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) can minimize rates of LF, RN, and MD. Methods A retrospective, multi-institutional analysis was conducted and included patients who had pre-operative FSRT for a large or symptomatic brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. A primary measurement was the rate of a composite endpoint of (1) LF, (2) MD, and/or (3) Grade 2 or higher (symptomatic) RN. Results 53 patients with 55 lesions were eligible for analysis. FSRT was prescribed to a dose of 24–25 Gy in 3–5 fractions. There were 0 LFs, 3 Grade 2–3 RN events, and 1 MD occurrence, which corresponded to an 8% per-patient composite endpoint event rate. Conclusions In this study, the composite endpoint of 8% for pre-operative FSRT was improved compared to previously reported rates with post-operative SRS of 49–60% (N107C, Mahajan etal. JCOG0504) and pre-operative SRS endpoints of 20.6% (PROPS-BM). Pre-operative FSRT appears to be safe, effective, and may decrease the incidence of adverse outcomes. Prospective validation is needed.

Poorly water-soluble compounds are being found with increasing frequency among pharmacologically active new chemical entities, which is a major concern to the pharmaceutical industry. Some particle engineering technologies have been shown to enhance the dissolution of many promising new compounds that perform poorly in formulation and clinical studies (Rogers et. al., Drug Dev Ind Pharm 27:1003-1015). One novel technology, controlled precipitation, shows significant potential for enhancing the dissolution of poorly soluble compounds. In this study, controlled precipitation is introduced; and process variables, such as mixing zone temperature, are investigated. Finally, scale-up of controlled precipitation from milligram or gram to kilogram quantities is demonstrated. Dissolution enhancement capabilities were established using two poorly water-soluble model drugs, danazol and naproxen. Stabilized drug particles from controlled precipitation were compared to milled, physical blend, and bulk drug controls using particle size analysis (Coulter), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), dissolution testing (USP Apparatus 2), and residual solvent analysis. Stabilized nano- and microparticles were produced from controlled precipitation. XRD and SEM analyses confirmed that the drug particles were crystalline. Furthermore, the stabilized particles from controlled precipitation exhibited significantly enhanced dissolution properties. Residual solvent levels were below FDA limits. Controlled precipitation is a viable and scalable technology that can be used to enhance the dissolution of poorly water-soluble pharmaceutical compounds.

The increase in the number of carotid artery stenting (CAS) procedures over the last decade has necessitated critical appraisal of procedural outcomes and patterns of utilization including cost analysis. The main objectives of our study were to evaluate the postprocedural mortality and complications after CAS and the patterns of resource utilization in terms of length of stay (LOS) and cost of hospitalization. We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample from 2006 to 2010 using the International Classification of Diseases, Ninth Revision, procedure code of 00.63 for CAS. Hierarchical mixed-effects models were generated to identify the independent multivariate predictors of in-hospital mortality, procedural complications, LOS, and cost of hospitalization. A total of 13,564 CAS procedures (weighted n = 67,344) were analyzed. The overall postprocedural mortality was low at 0.5%, whereas the complication rate was 8%, both of which remained relatively steady over the time frame of the study. Greater postoperative mortality and complications were noted in symptomatic patients, women, and those with greater burden of baseline co-morbidities. A greater operator volume was associated with a lower rate of postoperative mortality and complications, as well as shorter LOS and lesser hospitalization costs. In conclusion, the postprocedural mortality after CAS has remained low over the recent years. Operator volume is an important predictor of postprocedural outcomes and resource utilization.

Contemporary large-scale data, regarding in-hospital outcomes depending on the types of stent used for percutaneous coronary intervention (PCI) is lacking. We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample from 2006 to 2011 using the International Classification of Diseases, Ninth Revision, Clinical Modification procedure code 36.06 (bare-metal coronary artery stent, BMS) or 36.07 (drug-eluting coronary artery stent, DES) for PCI. All analyses were performed using the designated weighting specified to the Nationwide Inpatient Sample database to minimize bias. Primary outcome was in-hospital mortality. Wald's chi-square test was used for categorical variables. We built a hierarchical 2 level model adjusted for multiple confounding factors, with hospital identification incorporated as random effects in the model and propensity match analyses were used to adjust confounding variables. A total of 665,804 procedures were analyzed, which were representative of 3,277,884 procedures in the United States. Use of bare-metal stents (BMS) was associated with greater occurrence of in-hospital mortality compared with that of drug-eluting stents (DES; 1.4% vs 0.5%, p <0.001). The association stayed significant after adjustment of various possible confounding factors (odds ratio for DES versus BMS 0.59 [0.54 to 0.64, p <0.001]) and also in propensity matched cohorts (1.2% vs 0.7%, p <0.001). The results continued to be similar in the following high-risk subgroups: diabetes (0.57 [0.50 to 0.64, <0.001]), acute myocardial infarction and/or shock (0.53 [0.49 to 0.57, <0.001]), age >80 (0.66 [0.58 to 0.74, <0.001]), and multivessel PCI (0.55 [0.46 to 0.66, <0.001]). In conclusion, DES use was associated with lesser in-hospital mortality compared with BMS. This outcome benefit was seen across subgroups in various subgroups including elderly, diabetics, and acute myocardial infarction as well as multivessel interventions.