Material flow cost accounting (MFCA) for the circular economy: An empirical study of the triadic relationship between MFCA, environmental performance, and the economic performance of Japanese companies.

The purpose of this study is to address the question of whether material flow cost accounting (MFCA) can contribute to the circular economy. Because MFCA is an environmental management accounting tool that simultaneously assesses company material and financial flows, it is expected to contribute to the circular economy by assisting companies to achieve both environmental and economic goals through resource efficiency. In short, the expected linkages between MFCA, company environmental and economic goals, and the circular economy are inputs, outputs, and outcomes. However, there is a lack of consensus regarding its potential, perhaps because of the scarcity of studies, with most being models and case studies without readily generalizable results. To address this gap, we analyze the triadic relationship between MFCA, environmental performance, and economic performance using a two-stage regression of data from Japanese listed companies. The main findings are as follows. Companies that implement MFCA more proactively are more likely to improve their environmental performance in terms of energy consumption, CO2 emissions, and waste produced. In turn, those that improve their environmental performance are also more likely to improve their productivity, while those that specifically improve environmental performance in terms of waste produced are also more likely to increase in profitability. Consequently, because MFCA can improve several aspects of environmental performance by saving resources, it can improve productivity by improving a range of environmental performance indicators. In particular, MFCA can improve company productivity and thereby profit, at least by reducing the amount of waste produced. This supports the view that MFCA is an effective tool to contribute to the circular economy.

Characterization and Benchmark of a Novel Capacitive and Fluidic Inclination Sensor.

In this paper, a fluidic capacitive inclination sensor is presented and compared to three types of silicon-based microelectromechanical system (MEMS) accelerometers. MEMS accelerometers are commonly used for tilt measurement. They can only be manufactured by large companies with clean-room technology due to the high requirements during assembly. In contrast, the fluidic sensor can be produced by small- and medium-sized enterprises (SMEs) as well, since only surface mount technologies (SMT) are required. Three different variants of the fluidic sensor were investigated. Two variants using stacked printed circuit boards (PCBs) and one variant with 3D-molded interconnect devices (MIDs) to form the sensor element are presented. Allan deviation, non-repeatability, hysteresis, and offset temperature stability were measured to compare the sensors. Within the fluidic sensors, the PCB variant with two sensor cavities performed best regarding all the measurement results except non-repeatability. Regarding bias stability, white noise, which was determined from the Allan deviation, and hysteresis, the fluidic sensors outperformed the MEMS-based sensors. The accelerometer Analog Devices ADXL355 offers slightly better results regarding offset temperature stability and non-repeatability. The MEMS sensors Bosch BMA280 and TDK InvenSense MPU6500 do not match the performance of fluidic sensors in any category. Their advantages are the favorable price and the smaller package. From the investigations, it can be concluded that the fluidic sensor is competitive in the targeted price range, especially for applications with extended requirements regarding bias stability, noise, and hysteresis.

Development and Proof of Concept of a Miniaturized MEMS Quantum Tunneling Accelerometer Based on PtC Tips by Focused Ion Beam 3D Nano-Patterning.

Most accelerometers today are based on the capacitive principle. However, further miniaturization for micro integration of those sensors leads to a poorer signal-to-noise ratio due to a small total area of the capacitor plates. Thus, other transducer principles should be taken into account to develop smaller sensors. This paper presents the development and realization of a miniaturized accelerometer based on the tunneling effect, whereas its highly sensitive effect regarding the tunneling distance is used to detect small deflections in the range of sub-nm. The spring-mass-system is manufactured by a surface micro-machining foundry process. The area of the shown polysilicon (PolySi) sensor structures has a size smaller than 100 µm × 50 µm (L × W). The tunneling electrodes are placed and patterned by a focused ion beam (FIB) and gas injection system (GIS) with MeCpPtMe3 as a precursor. A dual-beam system enables maximum flexibility for post-processing of the spring-mass-system and patterning of sharp tips with radii in the range of a few nm and initial distances between the electrodes of about 30-300 nm. The use of metal-organic precursor material platinum carbon (PtC) limits the tunneling currents to about 150 pA due to the high inherent resistance. The measuring range is set to 20 g. The sensitivity of the sensor signal, which depends exponentially on the electrode distance due to the tunneling effect, ranges from 0.4 pA/g at 0 g in the sensor operational point up to 20.9 pA/g at 20 g. The acceleration-equivalent thermal noise amplitude is calculated to be 2.4-3.4 mg/Hz. Electrostatic actuators are used to lead the electrodes in distances where direct quantum tunneling occurs.

Mass-producible micro-optical elements by injection compression molding and focused ion beam structured titanium molding tools.

We demonstrate mass production compatible fabrication of polymer-based micro Fresnel lenses by injection compression molding. The extremely robust titanium-molding tool is structured with high precision by focused ion beam milling. In order to achieve optimal shape accuracy in the titanium we use an iterative design optimization. The inverse Fresnel lens structured into the titanium is transferred to polymers by injection compression molding, enabling rapid mass replication. We show that the optical performance of the molded diffractive Fresnel lenses is in good agreement with simulations, rendering our approach suitable for applications that require compact and high-quality optical elements in large numbers.

Functional and Degenerative Mitral Regurgitation: One Ring Fits All?

BACKGROUND: Three-dimensional saddle-shaped annuloplasty rings have been shown to create a larger surface of leaflet coaptation in mitral valve repair (MVR) for functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) which may increase repair durability. For the first time, this study reports mid-term results after MVR for DMR and FMR using a rigid three-dimensional ring (Profile 3D, Medtronic). METHODS: Between June 2009 and June 2012, 369 patients with DMR (n = 326) or FMR (n = 43) underwent MVR (mean age 62.3 ± 12.6 years). A total of 205 patients (55.6%) underwent isolated MVR and 164 patients (44.4%) a combined procedure. Follow-up examinations were performed in 94.9% (mean 4.9 ± 0.9 years). Echocardiographic assessment was complete in 93.2% (mean 4.3 ± 1.2 years). RESULTS: The 30-day mortality was 1.5% (5/326) for DMR (1.5% for isolated and 1.6% for combined procedures) and 9.3% (4/43) for FMR (0% for isolated and 10.5% for combined procedures). Survival at 6 years was 92.1 ± 1.9% for DMR (92.9 ± 2.6% for isolated and 90.7 ± 2.7% for combined procedures) and 66.4 ± 7.9% for FMR (80.0 ± 17.9% for isolated and 63.7 ± 8.9% for combined procedures). Cumulative risk for mitral valve-related reoperation at 6 years was 0% for FMR and 7.1 ± 1.5% for DMR. At echocardiographic follow-up, one patient presented with mitral regurgitation (MR) more than moderate. The only predictor of recurrent MR after MVR for DMR was residual mild MR at discharge. CONCLUSION: Repair of FMR with the three-dimensional Profile 3D annuloplasty ring shows excellent mid-term results with regard to recurrence of MR. In cases of DMR, the results are conforming to the current literature.

Inactivation of JNK2 as carcinogenic factor in colitis-associated and sporadic colorectal carcinogenesis.

We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis. We investigated expression of p-JNK2, p-JNK1-3, p21WAF1, γ-H2AX and Ki67 by immunohistochemistry in cases of quiescent UC (QUC), active UC (AUC), UC-dysplasia and UC-related colorectal carcinoma (UC-CRC). Comparison was made to normal healthy colorectal mucosa, sporadic adenoma and colorectal carcinoma (CRC), diverticulitis and Crohns disease (CD). We found p-JNK2 up-regulation in AUC and its early down-regulation in UC-CRC and CRC carcinogenesis. With down-regulated p-JNK2, p21WAF1 was also decreased. Ki67 was inversely expressed, showing increased proliferation early in UC-CRC and CRC carcinogenesis. p-JNK1-3 was increased in AUC and QUC. Less increased γ-H2AX in UC-CRC compared to CRC gave evidence that colitis-triggered inflammation masks DNA damage, thus contributing to neoplastic transformation. We hypothesize that JNK-dependent cell cycle arrest is important in AUC, while chronic inflammation causes dysregulated JNK activity in quiescent phase that may contribute to checkpoint override, promoting UC carcinogenesis. We suggest restoring p-JNK2 expression as a novel therapeutic strategy to early prevent the development of UC-related cancer.

DNA methylation in an engineered heart tissue model of cardiac hypertrophy: common signatures and effects of DNA methylation inhibitors.

DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 µM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray. A 7-day intervention sufficed to induce contractile dysfunction and significantly decrease promoter methylation of hypertrophy-associated upregulated genes such as Nppa (encoding ANP) and Acta1 (α-skeletal actin) in both intervention groups. To evaluate whether pathological consequences of AE are affected by inhibiting de novo DNA methylation we applied AE in the absence and presence of DNA methyltransferase (DNMT) inhibitors: 5-aza-2'-deoxycytidine (aza, 100 µM, nucleosidic inhibitor), RG108 (60 µM, non-nucleosidic) or methylene disalicylic acid (MDSA, 25 µM, non-nucleosidic). Aza had no effect on EHT function, but RG108 and MDSA partially prevented the detrimental consequences of AE on force, contraction and relaxation velocity. RG108 reduced AE-induced Atp2a2 (SERCA2a) promoter methylation. The results provide evidence for dynamic DNA methylation in cardiac hypertrophy and warrant further investigation of the potential of DNA methylation in the treatment of cardiac hypertrophy.

Is a Profiled Annuloplasty Ring Suitable for Repair of Degenerative Mitral Regurgitation? A Single-Center Experience Comprising 200 Patients.

Background Various devices have been proposed for ring annuloplasty in patients with degenerative mitral valve disease. This study reports for the first time midterm results with the rigid three-dimensional Medtronic Profile 3D (Medtronic, Minneapolis, Minnesota, United States) annuloplasty ring. Methods Between June 2009 and June 2011, 200 patients (mean age 61 ± 13 years, 70% male) with severe degenerative mitral regurgitation underwent mitral valve repair using the Medtronic Profile 3D annuloplasty ring. A total of 106 patients (53.0%) underwent isolated mitral valve repair and 94 patients (47.0%) underwent a concomitant procedure such as coronary artery bypass grafting (n = 21), tricuspid valve surgery (n = 49), AF ablation (n = 17), and aortic valve surgery (n = 13). The follow-up is 94.5% complete (mean 2.5 ± 0.5 years). Results Thirty-day mortality was 1.5%. Survival at 3 years was 97.1 ± 1.6% for isolated procedures and 92.4 ± 2.8% for combined procedures (p = 0.137). Freedom from mitral valve-related reoperation at 3 years was 97.1 ± 1.7% for isolated procedures and 95.5 ± 2.2% for combined procedures (p = 0.561). Seven patients (3.5%) required a mitral valve-related reoperation. Two of these reoperations were required for endocarditis, two for ring dehiscence, one for progression of the native disease (flail leaflet), one for leaflet suture dehiscence, and one for persistent systolic anterior motion. Conclusion The three-dimensional Medtronic Profile 3D annuloplasty ring is suitable for mitral valve repair for degenerative diseases. This saddle-shaped annuloplasty device provides excellent early results with a very good functional outcome at midterm either in isolated or combined procedures.

Repeated H2 O2 exposure drives cell cycle progression in an in vitro model of ulcerative colitis.

The production of hydrogen peroxide (H2 O2 ) drives tumourigenesis in ulcerative colitis (UC). Recently, we showed that H2 O2 activates DNA damage checkpoints in human colonic epithelial cells (HCEC) through c-Jun N-terminal Kinases (JNK) that induces p21(WAF1) . Moreover, caspases circumvented the G1/S and intra-S checkpoints, and cells accumulated in G2/M. The latter observation raised the question of whether repeated H2 O2 exposures alter JNK activation, thereby promoting a direct passage of cells from G2/M arrest to driven cell cycle progression. Here, we report that increased proliferation of repeatedly H2 O2 -exposed HCEC cells (C-cell cultures) was associated with (i) increased phospho-p46 JNK, (ii) decreased total JNK and phospho-p54 JNK and (iii) p21(WAF1) down-regulation. Altered JNK activation and p21(WAF1) down-regulation were accompanied by defects in maintaining G2/M and mitotic spindle checkpoints through adaptation, as well as by apoptosis resistance following H2 O2 exposure. This may cause increased proliferation of C-cell cultures, a defining initiating feature in the inflammation-carcinoma pathway in UC. We further suggest that dysregulated JNK activation is attributed to a non-apoptotic function of caspases, causing checkpoint adaptation in C-cell cultures. Additionally, loss of cell-contact inhibition and the overcoming of senescence, hallmarks of cancer, contributed to increased proliferation. Furthermore, there was evidence that p54 JNK inactivation is responsible for loss of cell-contact inhibition. We present a cellular model of UC and suggest a sinusoidal pattern of proliferation, which is triggered by H2 O2 -induced reactive oxygen species generation, involving an interplay between JNK activation/inactivation, p21(WAF1) , c-Fos, c-Jun/phospho-c-Jun, ATF2/phospho-ATF2, ß-catenin/TCF4-signalling, c-Myc, CDK6 and Cyclin D2, leading to driven cell cycle progression.

Non-apoptotic function of caspases in a cellular model of hydrogen peroxide-associated colitis.

Oxidative stress, caused by reactive oxygen species (ROS), is a major contributor to inflammatory bowel disease (IBD)-associated neoplasia. We mimicked ROS exposure of the epithelium in IBD using non-tumour human colonic epithelial cells (HCEC) and hydrogen peroxide (H2 O2 ). A population of HCEC survived H2 O2 -induced oxidative stress via JNK-dependent cell cycle arrests. Caspases, p21(WAF1) and γ-H2AX were identified as JNK-regulated proteins. Up-regulation of caspases was linked to cell survival and not, as expected, to apoptosis. Inhibition using the pan-caspase inhibitor Z-VAD-FMK caused up-regulation of γ-H2AX, a DNA-damage sensor, indicating its negative regulation via caspases. Cell cycle analysis revealed an accumulation of HCEC in the G1 -phase as first response to oxidative stress and increased S-phase population and then apoptosis as second response following caspase inhibition. Thus, caspases execute a non-apoptotic function by promoting cells through G1 - and S-phase by overriding the G1 /S- and intra-S checkpoints despite DNA-damage. This led to the accumulation of cells in the G2 /M-phase and decreased apoptosis. Caspases mediate survival of oxidatively damaged HCEC via γ-H2AX suppression, although its direct proteolytic inactivation was excluded. Conversely, we found that oxidative stress led to caspase-dependent proteolytic degradation of the DNA-damage checkpoint protein ATM that is upstream of γ-H2AX. As a consequence, undetected DNA-damage and increased proliferation were found in repeatedly H2 O2 -exposed HCEC. Such features have been associated with neoplastic transformation and appear here to be mediated by a non-apoptotic function of caspases. Overexpression of upstream p-JNK in active ulcerative colitis also suggests a potential importance of this pathway in vivo.

Direct Processing of PVD Hard Coatings via Focused Ion Beam Milling for Microinjection Molding.

Hard coatings can be applied onto microstructured molds to influence wear, form filling and demolding behaviors in microinjection molding. As an alternative to this conventional manufacturing procedure, "direct processing" of physical-vapor-deposited (PVD) hard coatings was investigated in this study, by fabricating submicron features directly into the coatings for a subsequent replication via molding. Different diamondlike carbon (DLC) and chromium nitride (CrN) PVD coatings were investigated regarding their suitability for focused ion beam (FIB) milling and microinjection molding using microscope imaging and areal roughness measurements. Each coating type was deposited onto high-gloss polished mold inserts. A specific test pattern containing different submicron features was then FIB-milled into the coatings using varied FIB parameters. The milling results were found to be influenced by the coating morphology and grain microstructure. Using injection-compression molding, the submicron structures were molded onto polycarbonate (PC) and cyclic olefin polymer (COP). The molding results revealed contrasting molding performances for the studied coatings and polymers. For CrN and PC, a sufficient replication fidelity based on AFM measurements was achieved. In contrast, only an insufficient molding result could be obtained for the DLC. No abrasive wear or coating delamination could be found after molding.

Adhesion-Induced Demolding Forces of Hard Coated Microstructures Measured with a Novel Injection Molding Tool.

The demolding of plastic parts remains a challenging aspect of injection molding. Despite various experimental studies and known solutions to reduce demolding forces, there is still not a complete understanding of the effects that occur. For this reason, laboratory devices and in-process measurement injection molding tools have been developed to measure demolding forces. However, these tools are mostly used to measure either frictional forces or demolding forces for a specific part geometry. Tools that can be used to measure the adhesion components are still the exception. In this study, a novel injection molding tool based on the principle of measuring adhesion-induced tensile forces is presented. With this tool, the measurement of the demolding force is separated from the actual ejection step of the molded part. The functionality of the tool was verified by molding PET specimens at different mold temperatures, mold insert conditions and geometries. It was demonstrated that once a stable thermal state of the molding tool was achieved, the demolding force could be accurately measured with a comparatively low force variance. A built-in camera was found to be an efficient tool for monitoring the contact surface between the specimen and the mold insert. By comparing the adhesion forces of PET molded on polished uncoated, diamond-like carbon and chromium nitride (CrN) coated mold inserts, it was found that a CrN coating reduced the demolding force by 98.5% and could therefore be an efficient solution to significantly improve demolding by reducing adhesive bond strength under tensile loading.

Injection Molding of Encapsulated Diffractive Optical Elements.

Microstructuring techniques, such as laser direct writing, enable the integration of microstructures into conventional polymer lens systems and may be used to generate advanced functionality. Hybrid polymer lenses combining multiple functions such as diffraction and refraction in a single component become possible. In this paper, a process chain to enable encapsulated and aligned optical systems with advanced functionality in a cost-efficient way is presented. Within a surface diameter of 30 mm, diffractive optical microstructures are integrated in an optical system based on two conventional polymer lenses. To ensure precise alignment between the lens surfaces and the microstructure, resist-coated ultra-precision-turned brass substrates are structured via laser direct writing, and the resulting master structures with a height of less than 0.002 mm are replicated into metallic nickel plates via electroforming. The functionality of the lens system is demonstrated through the production of a zero refractive element. This approach provides a cost-efficient and highly accurate method for producing complicated optical systems with integrated alignment and advanced functionality.

Narrow band imaging for detection of dysplasia in colitis: a randomized controlled trial.

OBJECTIVES: In ulcerative colitis surveillance, chromoendoscopy improves dysplasia detection 3 ­ 5-fold compared with white light endoscopy (WLE). The aim of this study was to investigate whether narrow band imaging (NBI) can improve dysplasia detection compared with WLE. METHODS: This was a randomized, parallel-group trial. A total of 220 patients were needed to be recruited to detect a threefold increase in dysplasia detection. In all, 112 patients with long-standing ulcerative colitis were randomized to colonoscopic extubation with NBI (56) or WLE (56) (1:1 ratio) at two tertiary endoscopy units in the United Kingdom. Targeted biopsies of suspicious areas and quadrantic random biopsies every 10 cm were taken in both groups. The primary outcome measure was the proportion of patients with at least one area of dysplasia detected. In a prespecified mid-point analysis, the criteria for trial discontinuation were met and the trial was stopped and analyzed at this point. RESULTS: There was no difference in the primary outcome between the two groups, with 5 patients having at least one dysplastic lesion in each group (odds ratio (OR) 1.00, 95 % confidence interval (95 % CI) 0.27 ­ 3.67, P = 1.00). This remained unchanged when adjusted for other variables (OR 0.69, 95 % CI 0.16 ­ 2.96, P = 0.62). Overall, dysplasia detection was 9 % in each arm. Yield of dysplasia from random nontargeted biopsies was 1 / 2,707 (0.04 % ). CONCLUSIONS: Overall, in this multicenter parallel-group trial, there was no difference in dysplasia detection when using NBI compared with high-definition WLE colonoscopy. Random background biopsies were ineffective in detecting dysplasia.

Use of PtC Nanotips for Low-Voltage Quantum Tunneling Applications.

The use of focused ion and focused electron beam (FIB/FEB) technology permits the fabrication of micro- and nanometer scale geometries. Therefore, FIB/FEB technology is a favorable technique for preparing TEM lamellae, nanocontacts, or nanowires and repairing electronic circuits. This work investigates FIB/FEB technology as a tool for nanotip fabrication and quantum mechanical tunneling applications at a low tunneling voltage. Using a gas injection system (GIS), the Ga-FIB and FEB technology allows both additive and subtractive fabrication of arbitrary structures. Using energy dispersive X-ray spectroscopy (EDX), resistance measurement (RM), and scanning tunneling microscope (STM)/spectroscopy (STS) methods, the tunneling suitability of the utilized metal-organic material-platinum carbon (PtC) is investigated. Thus, to create electrode tips with radii down to 15 nm, a stable and reproducible process has to be developed. The metal-organic microstructure analysis shows suitable FIB parameters for the tunneling effect at high aperture currents (260 pA, 30 kV). These are required to ensure the suitability of the electrodes for the tunneling effect by an increased platinum content (EDX), a low resistivity (RM), and a small band gap (STM). The STM application allows the imaging of highly oriented pyrolytic graphite (HOPG) layers and demonstrates the tunneling suitability of PtC electrodes based on high FIB aperture currents and a low tunneling voltage.

Impact of EEG-vigilance on brain glucose uptake measured with [(18)F]FDG and PET in patients with depressive episode or mild cognitive impairment.

INTRODUCTION: [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) is a well-established method for the examination of the cerebral glucose metabolism of patients with affective disorder or memory impairment. An understudied question is how far results are influenced by interindividual differences in central nervous arousal as assessed with electroencephalogram (EEG-vigilance) during the PET recording. Building upon previous neuroimaging studies, we supposed an association between EEG-vigilance and normalized brain [(18)F]FDG-uptake (nFDGu) as measured by [(18)F]FDG-PET. For the first time, the present study exploratively investigated this association in a routine diagnostic work-up. MATERIALS AND METHODS: Simultaneous 31-channel EEG and [(18)F]FDG-PET under resting conditions were acquired from 14 patients with depressive episode or mild cognitive impairment (MCI). EEG-vigilance was automatically classified by using the VIGALL algorithm (Vigilance Algorithm Leipzig). A nonparametric voxelwise simple linear regression with vigilance measure as predictor and nFDGu as criterion was performed using the Statistical nonParametric Mapping toolbox. RESULTS: The main finding was a significant negative correlation between vigilance measure and nFDGu in bilateral frontal and temporal regions, bilateral cingulate gyrus and right thalamus with vigilance-related changes of nFDGu between 17.1 and 44.4%. DISCUSSION: Simultaneous EEG and [(18)F]FDG-PET under resting conditions revealed that brain regions associated with EEG-vigilance partly overlapped with regions of impaired nFDGu in depression and MCI, as reported by previous studies. Vigilance-related changes of nFDGu were about the same magnitude as disease-related metabolic changes in patients with affective disorder or memory impairment as reported in previous studies. Therefore, our data suggest that differences in EEG-vigilance might influence alterations of nFDGu in disorders such as depression or MCI. Whether this possible impact of vigilance on nFDGu should be taken into account during the routine diagnostic application of [(18)F]FDG-PET has to be explored in future studies with larger patient groups.

Dynamic patient position changes during colonoscope withdrawal increase adenoma detection: a randomized, crossover trial.

BACKGROUND: Colonoscopy has a miss rate for adenomas that may partly relate to poor visualization of the colonic surface. Dynamic position changes during colonoscope withdrawal can improve luminal distension. OBJECTIVE: To assess whether position changes also improve adenoma and polyp detection. DESIGN: Randomized crossover clinical trial. SETTING: Academic endoscopy unit. PATIENTS: This study involved 130 patients who presented for routine colonoscopy. INTERVENTION: Examination either entirely in the left lateral position followed by position changes (cecum to hepatic flexure, left lateral; transverse colon, supine; splenic flexure and descending colon, right lateral) or vice versa. After both examinations, polyps were removed for histopathology. MAIN OUTCOME MEASUREMENTS: Proportion of patients with ≥1 polyp or adenoma detected between the hepatic flexure and the sigmoid-descending colon junction. Luminal distension was measured on a scale of 1 to 5: 1, total collapse; 5, fully distended. RESULTS: At least 1 adenoma was detected in 34% of patients in colon areas in which the patient position differed from left lateral (transverse colon, splenic flexure, descending colon) compared with 23% examined with the patient in the left lateral position alone (P = .01). At least 1 polyp was detected in 52% of patients with position changes versus 34% of patients examined in the left lateral position alone (P < .001). Adenoma and polyp detection were positively correlated with an improved distension score (correlation coefficient, 0.12; P < .001). Adenomas were detected in 16% of colon areas with adequate distension scores (4 and 5) compared with 7% of those with borderline or nondiagnostic scores (1-3; P < .001). LIMITATIONS: Single-operator study. CONCLUSION: Dynamic position changes during colonoscope withdrawal significantly improved polyp and adenoma detection. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00234650).

Expression profiles of HMGB1 on B-CLL related leukocytes contribute to prediction of relapse.

BACKGROUND: The High Mobility Group Box 1 (HMGB1) is a nuclear protein that is frequently overexpressed in hematologic diseases and might be of relevance in immunogenic cancer control thus correlating with patients' (pts.) prognosis in diseases such as acute myeloid, acute lymphatic and chronic lymphocytic leukemia. MATERIALS AND METHODS: Expression profiles of blasts from AML (n = 21), ALL (n = 16) and of B-lymphocytes of CLL (n = 9) pts. were analyzed for surface expression of HMGB1 using flow cytometry. Expression was quantified and correlated with clinically and prognostically relevant markers. RESULTS: Expression profiling of HMGB1 in blasts of AML and ALL subtypes did not show differences between primary vs. secondary disease development and gender related differences. In ALL pts. however, age groups at initial diagnosis between ≥20 vs. <20 years were compared and showed significant differences (≥20 vs. <20 years; 89% vs. 49%, p  <0.05) with higher expression in higher age. In AML and CLL these differences were not visible. To evaluate the prognostic significance of HMGB1 expression, expression quantity was correlated with established and prognostic classification systems (in AML ELN, in ALL GMALL) and probability to relapse. No significant correlation was seen in these entities. However, when AML pts. were analyzed for remission rates after first anthracycline based induction therapy, in those who did not experience a complete remission significantly enhanced HMGB1 surface expression was seen (98 vs. 94%; p < 0.05; n = 20). Furthermore, for CLL it was shown that higher HMGB1 expression was found in pretreated patients with relapsed or/and refractory disease (1 vs. more relapses; 94 vs. 98%; p  <0.05; n = 9). CONCLUSION: HMGB1 is frequently expressed in hematologic malignancies. In this study it was shown that HMGB1 surface expression on AML blasts can be used as predictors for treatment response. In CLL it may be a marker for advanced disease. In order to implement this marker in FACS routine it could be a useful and practical tool for prognostic assessment and treatment planning.

Results after Repair of Functional Tricuspid Regurgitation with a Three-Dimensional Annuloplasty Ring.

BACKGROUND: Tricuspid valve (TV) repair is the recommended treatment for severe functional tricuspid regurgitation (fTR) in patients undergoing left-sided surgery. For this purpose, a wide range of annuloplasty devices differing in form and flexibility are available. This study reports the results using a three-dimensional annuloplasty ring (Medtronic, Contour 3D Ring) for TV repair and analysis of risk factors. METHODS: A cohort of 468 patients who underwent TV repair (TVr) with a concomitant cardiac procedure from December 2010 to January 2017 was retrospectively analyzed. RESULTS: At follow-up, 96.1% of patients had no/trivial or mild TR. The 30-day mortality was 4.7%; it significantly differed between electively performed operations (2.7%) and urgent/emergent operations (11.7%). Risk factors for recurrent moderate and severe TR were LVEF < 50%, TAPSE < 16 mm, and moderate mitral valve (MV) regurgitation at follow-up. Preoperatively reduced renal function lead to a higher 30-day and overall mortality. Reoperation of the TV was required in six patients (1.6%). Risk factors for TV related reoperations were preoperative TV annulus over 50 mm and an implanted permanent pacemaker. CONCLUSIONS: TVr with the Contour 3D annuloplasty ring shows low TR recurrence and reoperation rates. Risk-factor analysis for the recurrence of TR revealed the importance of left- and right-ventricular function.

Expression of Surface-associated 82 kDa proMMP-9 in Lymphatic Leukemia Blast Cells Differentially Correlates With Prognosis.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) degrade extracellular matrix and process regulatory proteins. Recently, a membrane-bound 82kDa variant of proMMP-9 identified on myeloid blasts was shown to be associated with prognosis. PATIENTS AND METHODS: To investigate the role of 82kDa proMMP-9 with acute lymphoblastic leukemia (ALL) and chronic lymphoid leukemia (CLL), we performed flow-cytometry analysis of expression on ALL blasts (n=18) and CLL lymphocytes (n=21) from blood and correlated data with clinical parameters. RESULTS: In ALL, mature B-linear blasts expressed higher levels of 82kDa proMMP-9 compared to T-linear blasts. Elevated levels of 82kDa proMMP-9 were found in elderly patients and at patients with relapse. No correlation was observed on blood cells and extramedullary disease. In CLL, the 82kDa proMMP-9 expression did not correlate with any of the clinical parameters. CONCLUSION: Our findings suggest that higher levels of 82kDa proMMP-9 expression on blast cells may correlate with a more unfavorable ALL-subtype. Further studies are required to clarify the prognostic role of the 82kDa pro-MMP-9 expression.