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Audrey White,1 Elizabeth Buschur,2 Cara Harris,2 Michael L Pennell,3 Adam Soliman,2 Kathleen Wyne,2 Kathleen M Dungan2 1Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; 2Division of Endocrinology, Diabetes & Metabolism, The Ohio State University, Columbus, OH, 43220, USA; 3The Ohio State University College of Public Health, Division of Biostatistics, Columbus, OH, 43210, USACorrespondence: Kathleen M Dungan, The Ohio State University, Division of Endocrinology, Diabetes and Metabolism, 5th Floor McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210-1296, USA, Email kathleen.dungan@osumc.eduObjective: To evaluate the relationship between health literacy, social support, and self-efficacy as predictors of change in A1c and readmission among hospitalized patients with type 2 diabetes (T2D).Methods: This is a secondary analysis of patients with T2D (A1c > 8.5%) enrolled in a randomized trial in which health literacy (Newest Vital Sign), social support (Multidimensional Scale of Perceived Social Support), and empowerment (Diabetes Empowerment Scale-Short Form) was assessed at baseline. Multivariable models evaluated whether these concepts were associated with A1c reduction at 12 weeks (absolute change, % with > 1% reduction, % reaching individualized target) and readmission (14 and 30 days).Results: A1c (N=108) decreased > 1% in 60%, while individualized A1c target was achieved in 31%. After adjustment for baseline A1c and potential confounders, health literacy was associated with significant reduction in A1c (Estimate − 0.21, 95% CI − 0.40, − 0.01, p=0.041) and > 1% decrease in A1c (OR 1.37, 95% CI 1.08, 1.73, p=0.009). However, higher social support was associated with greater adjusted odds of reaching the individualized A1c target (OR 1.63, 95% CI 1.04, 2.55, p=0.32). Both higher empowerment (OR 0.23, 95% CI 0.08, 0.64, p=0.005) and social support (OR 0.57, 95% CI 0.36, 0.91, p=0.018) were associated with fewer readmissions by 14 days, but not 30 days.Conclusion: The study indicates that health literacy and social support may be important predictors of A1c reduction post-discharge among hospitalized patients with T2D. Social support and diabetes self-management skills should be addressed and early follow-up may be critical for avoiding readmissions.Clinical Trial: NCT03455985.Keywords: type 2 diabetes, hospital discharge, basal insulin, A1c, readmission, social support, self-efficacy, literacy

Supplementary Tables 1-2 from Automated, Quantitative Screening Assay for Antiangiogenic Compounds Using Transgenic Zebrafish

Pathologic angiogenesis has emerged as an important therapeutic target in several major diseases. Zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. We developed the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos. This assay uses transgenic zebrafish with fluorescent blood vessels to facilitate image analysis. We developed methods for automated drugging and imaging of zebrafish in 384-well plates and developed a custom algorithm to quantify the number of angiogenic blood vessels in zebrafish. The assay was used to screen the LOPAC1280 compound library for antiangiogenic compounds. Two known antiangiogenic compounds, SU4312 and AG1478, were identified as hits. Additionally, one compound with no previously known antiangiogenic activity, indirubin-3′-monoxime (IRO), was identified. We showed that each of the hit compounds had dose-dependent antiangiogenic activity in zebrafish. The IC50 of SU4312, AG1478, and IRO in the zebrafish angiogenesis assay was 1.8, 8.5, and 0.31 μmol/L, respectively. IRO had the highest potency of the hit compounds. Moreover, IRO inhibited human umbilical vein endothelial cell tube formation and proliferation (IC50 of 6.5 and 0.36 μmol/L, respectively). It is therefore the first antiangiogenic compound discovered initially in a zebrafish assay that also has demonstrable activity in human endothelial cell-based angiogenesis assays. [Cancer Res 2007;67(23):11386–92]

Aims Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. Methods and results In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4–76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3–2.9) m/s vs. lower tertiles 2.7 (2.4–3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05–1.41) vs. lower tertiles 1.17 (1.06–1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (−0.1–0.2) m/s/year vs. lower tertiles 0.1 (0.0–0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. Conclusion Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration.

BACKGROUND While electronic order sets have become standard practice for inpatient diabetes management, there is limited decision support at discharge. OBJECTIVE This study assessed whether an electronic discharge order set (DOS) plus nurse follow up calls improves discharge orders and post-discharge outcomes among hospitalized patients with type 2 diabetes (T2D). METHODS This is a randomized open label single center study comparing an electronic DOS and nurse phone calls to enhanced standard care (ESC) in hospitalized insulin-requiring patients with T2D. The primary outcome was change in HbA1c at 24 weeks post-discharge. Secondary outcomes included completeness and accuracy of discharge prescriptions related to diabetes. RESULTS The study was stopped early due to feasibility concerns related to long-term follow-up. However a total of 158 subjects were enrolled (DOS=82, ESC=76), 155 of whom had discharge data. The DOS group had a greater frequency of prescriptions for bolus insulin (81% vs 44%; P=0.01), needles/syringes (95% vs 63%; P=0.03), and glucometers (86% vs 36%; P=0.0002). Clarity of orders was similar. HbA1c was available in 27 subjects in each arm at 12 weeks, and 20/21 subjects in the DOS/ESC arms at 24 weeks. The adjusted difference in change in HbA1c (DOS-ESC) was -0.5 ± 0.4% at 12 weeks (P = 0.20) and -0.7 ± 0.4% at 24 weeks (P= 0.09). Achievement of individualized HbA1c target was greater in the DOS group at 12 weeks but not 24 weeks. CONCLUSIONS A DOS resulted in more complete discharge prescriptions. Assessment of post-discharge outcomes was limited due to loss of long-term follow-up but suggests possible benefit in glucose control. CLINICALTRIAL NCT03455985 Effectiveness of a Diabetes Focused Discharge Order Set Among Poorly Controlled Hospitalized Patients Transitioning to Glargine U300 Insulin

Background Although the use of electronic order sets has become standard practice for inpatient diabetes management, there is limited decision support at discharge. Objective In this study, we assessed whether an electronic discharge order set (DOS) plus nurse follow-up calls improve discharge orders and postdischarge outcomes among hospitalized patients with type 2 diabetes mellitus. Methods This was a randomized, open-label, single center study that compared an electronic DOS and nurse phone calls to enhanced standard care (ESC) in hospitalized insulin-requiring patients with type 2 diabetes mellitus. The primary outcome was change in glycated hemoglobin (HbA1c) level at 24 weeks after discharge. The secondary outcomes included the completeness and accuracy of discharge prescriptions related to diabetes. Results This study was stopped early because of feasibility concerns related to the long-term follow-up. However, 158 participants were enrolled (DOS: n=82; ESC: n=76), of whom 155 had discharge data. The DOS group had a greater frequency of prescriptions for bolus insulin (78% vs 44%; P=.01), needles or syringes (95% vs 63%; P=.03), and glucometers (86% vs 36%; P Conclusions An intervention that included a DOS plus a postdischarge nurse phone call resulted in more complete discharge prescriptions. The assessment of postdischarge outcomes was limited, owing to the loss of the long-term follow-up, but it suggested a possible benefit in glucose control. Trial Registration ClinicalTrials.gov NCT03455985; https://clinicaltrials.gov/ct2/show/NCT03455985

IntroductionSurvivors of acute pancreatitis (AP) have shorter overall survival and increased incidence of new-onset cardiovascular, respiratory, liver and renal disease, diabetes mellitus and cancer compared with the general population, but the mechanisms that explain this are yet to be elucidated. Our aim is to characterise the precise nature and extent of organ dysfunction following an episode of AP.Methods and analysisThis is an observational prospective cohort study in a single centre comprising a University hospital with an acute and emergency receiving unit and clinical research facility. Participants will be adult patient admitted with AP. Participants will undergo assessment at recruitment, 3 months and 3 years. At each time point, multiple biochemical and/or physiological assessments to measure cardiovascular, respiratory, liver, renal and cognitive function, diabetes mellitus and quality of life. Recruitment was from 30 November 2017 to 31 May 2020; last follow-up measurements is due on 31 May 2023. The primary outcome measure is the incidence of new-onset type 3c diabetes mellitus during follow-up. Secondary outcome measures include: quality of life analyses (SF-36, Gastrointestinal Quality of Life Index); montreal cognitive assessment; organ system physiological performance; multiomics predictors of AP severity, detection of premature cellular senescence. In a nested cohort within the main cohort, individuals may also consent to multiparameter MRI scan, echocardiography, pulmonary function testing, cardiopulmonary exercise testing and pulse-wave analysis.Ethics and disseminationThis study has received the following approvals: UK IRAS Number 178615; South-east Scotland Research Ethics Committee number 16/SS/0065. Results will be made available to AP survivors, caregivers, funders and other researchers. Publications will be open-access.Trial registration numbersClinicalTrials.gov Registry (NCT03342716) and ISRCTN50581876; Pre-results.

Background Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. Methods We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Findings Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Interpretation Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. Funding British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

OBJECTIVES. Humans receiving tissue-engineered tracheal grafts have experienced poor outcomes ultimately resulting in death or the need for graft explantation. We assessed the performance of the synthetic scaffolds used in humans with an ovine model of orthotopic tracheal replacement, applying standard postsurgical surveillance and interventions to define the factors that contributed to the complications seen at the bedside. STUDY DESIGN. Large animal model. SETTING. Pediatric academic research institute. SUBJECTS AND METHODS. Human scaffolds were manufactured with an electrospun blend of polyethylene terephthalate and polyurethane reinforced with polycarbonate rings. They were seeded with autologous bone marrow–derived mononuclear cells and implanted in sheep. Animals were evaluated with routine bronchoscopy and fluoroscopy. Endoscopic dilation and stenting were performed to manage graft stenosis for up to a 4-month time point. Grafts and adjacent native airway were sectioned and evaluated with histology and immunohistochemistry. RESULTS. All animals had signs of graft stenosis. Three of 5 animals (60%) designated for long-term surveillance survived until the 4-month time point. Graft dilation and stent placement resolved respiratory symptoms and prolonged survival. Necropsy demonstrated evidence of infection and graft encapsulation. Granulation tissue with signs of neovascularization was seen at the anastomoses, but epithelialization was never observed. Acute and chronic inflammation of the native airway epithelium was observed at all time points. Architectural changes of the scaffold included posterior wall infolding and scaffold delamination. CONCLUSIONS. In our ovine model, clinically applied synthetic tissue-engineered tracheas demonstrated infectious, inflammatory, and mechanical failures with a lack of epithelialization and neovascularization.

Treatment options for congenital or secondary long segment tracheal defects have historically been limited due to an inability to replace functional tissue. Tissue engineering holds great promise as a potential solution with its ability to integrate cells and signaling molecules into a 3-dimensional scaffold. Recent work with tissue engineered tracheal grafts (TETGs) has seen some success but their translation has been limited by graft stenosis, graft collapse, and delayed epithelialization. In order to investigate the mechanisms driving these issues, we have developed a mouse model for tissue engineered tracheal graft implantation. TETGs were constructed using electrospun polymers polyethylene terephthalate (PET) and polyurethane (PU) in a mixture of PET and PU (20:80 percent weight). Scaffolds were then seeded using bone marrow mononuclear cells isolated from 6-8 week-old C57BL/6 mice by gradient centrifugation. Ten million cells per graft were seeded onto the lumen of the scaffold and allowed to incubate overnight before implantation between the third and seventh tracheal rings. These grafts were able to recapitulate the findings of stenosis and delayed epithelialization as demonstrated by histological analysis and lack of Keratin 5 and Keratin 14 basal epithelial cells on immunofluorescence. This model will serve as a tool for investigating cellular and molecular mechanisms involved in host remodeling.

The ideal construct for tracheal replacement remains elusive in the management of long segment airway defects. Tissue engineered tracheal grafts (TETG) have been limited by the development of graft stenosis or collapse, infection, or lack of an epithelial lining. We applied a mouse model of orthotopic airway surgery to assess the impact of three critical barriers encountered in clinical applications: the scaffold, the extent of intervention, and the impact of cell seeding and characterized their impact on graft performance. First, synthetic tracheal scaffolds electrospun from polyethylene terephthalate / polyurethane (PET/PU) were orthotopically implanted in anterior tracheal defects of C57BL/6 mice. Scaffolds demonstrated complete coverage with ciliated respiratory epithelium by 2 weeks. Epithelial migration was accompanied by macrophage infiltration which persisted at long term (>6 weeks) time points. We then assessed the impact of segmental tracheal implantation using syngeneic trachea as a surrogate for the ideal tracheal replacement. Graft recovery involved local upregulation of epithelial progenitor populations and there was no evidence of graft stenosis or necrosis. Implantation of electrospun synthetic tracheal scaffold for segmental replacement resulted in respiratory distress and required euthanasia at an early time point. There was limited epithelial coverage of the scaffold with and without seeded bone marrow-derived mononuclear cells (BM-MNCs). We conclude that synthetic scaffolds support re-epithelialization in orthotopic patch implantation, syngeneic graft integration occurs with focal repair mechanisms, however epithelialization in segmental synthetic scaffolds is limited and is not influenced by cell seeding. STATEMENT OF SIGNIFICANCE: The life-threatening nature of long-segment tracheal defects has led to clinical use of tissue engineered tracheal grafts in the last decade for cases of compassionate use. However, the ideal tracheal reconstruction using tissue-engineered tracheal grafts (TETG) has not been clarified. We addressed the core challenges in tissue engineered tracheal replacement (re-epithelialization and graft patency) by defining the role of cell seeding with autologous bone marrow-derived mononuclear cells, the mechanism of respiratory epithelialization and proliferation, and the role of the inflammatory immune response in regeneration. This research will facilitate comprehensive understanding of cellular regeneration and neotissue formation on TETG, which will permit targeted therapies for accelerating re-epithelialization and attenuating stenosis in tissue engineered airway replacement.

Limited contrast, along with speckle and acoustic noise, can reduce the diagnostic value of echocardiographic images. This study introduces dynamic histogram-based intensity mapping (DHBIM), a novel approach employing temporal variations in the cumulative histograms of cardiac ultrasound images to contrast enhance the imaged structures. DHBIM is then combined with spatial compounding to compensate for noise and speckle. The proposed techniques are quantitatively assessed (32 clinical data sets) employing (i) standard image quality measures and (ii) the repeatability of routine clinical measurements, such as chamber diameter and wall thickness. DHBIM introduces a mean increase of 120.9% in tissue/chamber detectability, improving the overall repeatability of clinical measurements by 17%. The integrated approach of DHBIM followed by spatial compounding provides the best overall enhancement of image quality and diagnostic value, consistently outperforming the individual approaches and achieving a 401.4% average increase in tissue/chamber detectability with an associated 24.3% improvement in the overall repeatability of clinical measurements.

Congenital cytomegalovirus (CMV) affects ~1 of 150 births and is a leading cause of hearing loss and intellectual disability. It has been suggested that transmission may occur via contaminated surfaces. CMV AD169 in filtered human saliva, applied to environmental surfaces, was recovered at various time points. Samples were evaluated by culture and real-time polymerase chain reaction. CMV was found viable on metal and wood to 1 hour, glass and plastic to 3 hours, and rubber, cloth, and cracker to 6 hours. CMV was cultured from 83 of 90 wet and 5 of 40 dry surfaces. CMV was more likely to be isolated from wet, highly absorbent surfaces at earlier time points.

PurposeThe purpose of this article is to detail the importance of providing structured learning solutions and to give an overview of the Alcatel‐Lucent University.Design/methodology/approachThe article looks into the Alcatel‐Lucent University itself, its approach, the benefits to employees and customers and its future.FindingsThis article shows that a structured, comprehensive approach to learning, such as a corporate university, can bring company‐wide benefits.Originality/valueThe corporate university solution of the Alcatel‐Lucent University has brought a number of benefits to both employees and customers and proved the best solution to Alcatel‐Lucent's learning needs.

Pathologic angiogenesis has emerged as an important therapeutic target in several major diseases. Zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. We developed the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos. This assay uses transgenic zebrafish with fluorescent blood vessels to facilitate image analysis. We developed methods for automated drugging and imaging of zebrafish in 384-well plates and developed a custom algorithm to quantify the number of angiogenic blood vessels in zebrafish. The assay was used to screen the LOPAC1280 compound library for antiangiogenic compounds. Two known antiangiogenic compounds, SU4312 and AG1478, were identified as hits. Additionally, one compound with no previously known antiangiogenic activity, indirubin-3′-monoxime (IRO), was identified. We showed that each of the hit compounds had dose-dependent antiangiogenic activity in zebrafish. The IC50 of SU4312, AG1478, and IRO in the zebrafish angiogenesis assay was 1.8, 8.5, and 0.31 μmol/L, respectively. IRO had the highest potency of the hit compounds. Moreover, IRO inhibited human umbilical vein endothelial cell tube formation and proliferation (IC50 of 6.5 and 0.36 μmol/L, respectively). It is therefore the first antiangiogenic compound discovered initially in a zebrafish assay that also has demonstrable activity in human endothelial cell-based angiogenesis assays. [Cancer Res 2007;67(23):11386–92]

Temporal compounding can be used to suppress acoustic noise in transthoracic cardiac ultrasound by spatially averaging partially decorrelated images acquired over consecutive cardiac cycles. However, the reliable spatial and temporal alignment of the corresponding frames in consecutive cardiac cycles is vital for effective implementation of temporal compounding. This study introduces a novel, efficient, accurate and robust technique for the spatiotemporal alignment of consecutive cardiac cycles with variable temporal characteristics. Furthermore, optimal acquisition parameters, such as the number of consecutive cardiac cycles used, are derived. The effect of the proposed implementation of temporal compounding on cardiac ultrasound images is quantitatively assessed (32 clinical data sets providing a representative range of image qualities and diagnostic values) using measures such as tissue signal-to-noise ratio, chamber signal-to-noise ratio, tissue/chamber contrast and detectability index, as well as a range of clinical measurements, such as chamber diameter and wall thickness, performed during routine echocardiographic examinations. Temporal compounding (as implemented) consistently improved the image quality and diagnostic value of the processed images, when compared with the original data by: (i) increasing tissue and cavity signal-to-noise ratios as well as tissue/cavity detectability index, (ii) improving the corresponding clinical measurement repeatability and inter-operator measurement agreement, while (iii) reducing the number of omitted measurements caused by data corruption.

With combined positron emission tomography and computed tomography (CT), we investigated coronary arterial uptake of 18F-sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) as markers of active plaque calcification and inflammation, respectively.The noninvasive assessment of coronary artery plaque biology would be a major advance particularly in the identification of vulnerable plaques, which are associated with specific pathological characteristics, including micro-calcification and inflammation.We prospectively recruited 119 volunteers (72 ± 8 years of age, 68% men) with and without aortic valve disease and measured their coronary calcium score and 18F-NaF and 18F-FDG uptake. Patients with a calcium score of 0 were used as control subjects and compared with those with calcific atherosclerosis (calcium score0).Inter-observer repeatability of coronary 18F-NaF uptake measurements (maximum tissue/background ratio) was excellent (intra-class coefficient 0.99). Activity was higher in patients with coronary atherosclerosis (n = 106) versus control subjects (1.64 ± 0.49 vs. 1.23 ± 0.24; p = 0.003) and correlated with the calcium score (r = 0.652, p0.001), although 40% of those with scores1,000 displayed normal uptake. Patients with increased coronary 18F-NaF activity (n = 40) had higher rates of prior cardiovascular events (p = 0.016) and angina (p = 0.023) and higher Framingham risk scores (p = 0.011). Quantification of coronary 18F-FDG uptake was hampered by myocardial activity and was not increased in patients with atherosclerosis versus control subjects (p = 0.498).18F-NaF is a promising new approach for the assessment of coronary artery plaque biology. Prospective studies with clinical outcomes are now needed to assess whether coronary 18F-NaF uptake represents a novel marker of plaque vulnerability, recent plaque rupture, and future cardiovascular risk. (An Observational PET/CT Study Examining the Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis; NCT01358513).

Observer variability may limit assessment of aortic stenosis by Doppler echocardiography. This study aimed to assess whether echocardiographic contrast agent improves reproducibility of aortic valve area (AVA) measurements for patients with aortic stenosis. In all, 20 patients with aortic stenosis (67 +/- 10 years old) underwent noncontrast and contrast Doppler echocardiography on 2 occasions, 3 weeks apart. Intraobserver and interobserver coefficients of reproducibility were 0.36 and 0.20 cm for left ventricular outflow tract (LVOT) diameter, and 0.38 and 0.24 cm(2) for AVA, respectively. Although intraobserver reproducibility was unaffected, contrast improved interobserver reproducibility for LVOT diameter (mean of differences -0.02 +/- 0.07 cm vs 0.01 +/- 0.10 cm, P.05) and AVA (mean of differences 0.02 +/- 0.10 cm(2) vs 0.07 +/- 0.12 cm(2), P.05). Prevalve and postvalve velocities were increased with contrast compared with noncontrast imaging (prevalve, 1.07 +/- 0.20 vs 0.94 +/- 0.19 m/s, P.01; postvalve, 3.76 +/- 0.87 vs 3.47 +/- 0.78 m/s, P.01). We conclude that contrast significantly increases Doppler velocities and produces modest improvements in reproducibility of LVOT diameter and AVA. We suggest that, when assessing patients with aortic stenosis, contrast agents should be considered in patients who are difficult to image with poor baseline LVOT images or Doppler studies, or where there is poor interobserver reproducibility.

Redefining how chemicals are sold and used is an emerging trend in the manufacturing sector. This shift entails a fundamental restructuring of supplier-customer transactions from a volume and sales orientation to a service orientation. This restructured relationship between chemical suppliers and their customers has yielded reduced costs, improved quality, and streamlined chemical handling. With the right set of incentives, the service-based contracting can also enhance environmental performance through pollution prevention. The Chemical Strategies Partnership is working with electronics manufacturing companies to adapt this new supplier-customer model to the electronics industry to improve environmental performance while reducing costs and increasing efficiency.

SUMMARY Administration of 1 i.u./24h of adrenocorticotrophic hormone (Cortrophin ZN, ACTH) to hypophysectomized—castrated rats significantly increased sebum production to the level of that in castrated rats with intact pituitaries. The incidence of mitoses in the sebaceous glands was also significantly increased. Neither the preputial glands nor the seminal vesicles showed any response. No significant increase in sebum production in hypophysectomized—castrated rats could be detected 24 days after giving implants releasing 0·2 or 0·6 mg testosterone/24 h, although sebaceous mitoses were significantly increased in both instances. Concomitant administration of both ACTH and testosterone raised sebum production to the same extent as ACTH alone, and raised the incidence of sebaceous mitoses to a level equal to that produced by ACTH plus testosterone. It is concluded that the sebaceous glands respond—either directly or indirectly as the result of stimulation of the adrenal cortex—to ACTH and that this response is less dependent on the presence of the pituitary than is the action of testosterone. ACTH does not itself facilitate the response of the sebaceous glands to testosterone.