Real time, confocal imaging of Ca2+ waves in arterially perfused rat hearts

Objective: The aim of this study was to characterize the spatio-temporal dynamics of slow Ca2+ waves (SCW's) with cellular resolution in the arterially-perfused rat heart. Methods: Wister rat hearts were Langendorff-perfused with Tyrode solution containing bovine-albumine and Dextran. The heart was loaded with the Ca2+ sensitive dye Fluo-3 AM. Intracellular fluorescence changes reflecting changes in [Ca2+]i were recorded from subepicardial tissue layers using a slit hole confocal microscope with an image intensified video camera system at image rates of up to 50/s. Results: SCW's appeared spontaneously during cardiac rest or after trains of electrical stimuli. They were initiated preferentially in the center third of the cell and propagated to the cell borders, suggesting a relation between the cell nucleus and wave initiation. They were suppressed by Ca2+ transients and their probability of occurrence increased with the Ca2+ resting level. Propagation velocity within myocytes (40 to 180 μm/s) decreased with the resting Ca2+ level. Intercellular propagation was mostly confined to two or three cells and occurred bi-directionally. Intercellular unidirectional conduction block and facilitation of SCW's was occasionally observed. On average 10 to 20% of cells showed non-synchronized simultaneous SCW's within a given area in the myocardium. Conclusions: SCW's occurring at increased levels of [Ca2+]i in normoxic or ischemic conditions are mostly confined to two or three cells in the ventricular myocardium. Spatio-temporal summation of changes in membrane potential caused by individual SCW's may underlie the generation of triggered electrical ectopic impulse

Electrical and Mechanical Properties of Plated Ni/Cu Contacts for Si Solar Cells

AbstractPlated Ni/Cu/Ag contacts are an industrially feasible metallization approach for high efficiency c-Si solar cells with low surface doping concentrations (1018 cm-3 < ND < 1020 cm-3). The 2d-simulations of this work define the minimum requirements on the contact resistivity of metal contacts in a high efficiency solar cell design. The following experimental study of the contact resistivity of plated Ni/Cu/Ag contacts on lowly doped phosphorus emitter demonstrates low contact resistivities in the mΩcm2 regime, which enable solar cells with high fill factors. Furthermore, the paper analyzes the influence of the thermal silicidation process on pseudo-fill factor losses and on the mechanical contact adhesion. The contact adhesion is also studied with respect to the laser contact opening process. The results of this work demonstrate that the right choice of back-end processes enable plated Ni/Cu/Ag contacts with low contact resistivities in combination with high contact adhesions above 1 N/mm

Development and in-vitro characterization of an implantable flow sensing transducer for hydrocephalus

An implantable transducer for monitoring the flow of Cerebrospinal fluid (CSF) for the treatment of hydrocephalus has been developed which is based on measuring the heat dissipation of a local thermal source. The transducer uses passive telemetry at 13.56MHz for power supply and read out of the measured flow rate. The in vitro performance of the transducer has been characterized using artificial Cerebrospinal Fluid (CSF) with increased protein concentration and artificial CSF with 10% fresh blood. After fresh blood was added to the artificial CSF a reduction of flow rate has been observed in case that the sensitive surface of the flow sensor is close to the sedimented erythrocytes. An increase of flow rate has been observed in case that the sensitive surface is in contact with the remaining plasma/artificial CSF mix above the sediment which can be explained by an asymmetric flow profile caused by the sedimentation of erythrocythes having increased viscosity compared to artificial CSF. After removal of blood from artificial CSF, no drift could be observed in the transducer measurement which could be associated to a deposition of proteins at the sensitive surface walls of the packaged flow transducer. The flow sensor specification requirement of +−10% for a flow range between 2ml/h and 40ml/h. could be confirmed at test conditions of 37°

BariSurg trial: Sleeve gastrectomy versus Roux-en-Y gastric bypass in obese patients with BMI 35–60 kg/m2 – a multi-centre randomized patient and observer blind non-inferiority trial

Background: Roux-en-Ygastric bypass (RYGB) and sleeve gastrectomy (SG) rank among the most frequently applied bariatric procedures worldwide due to their positive risk/benefit correlation. A systematic review revealed a similar excess weight loss (EWL) 2 years postoperatively between SG and RYGB. However, there is a lack of randomized controlled multi-centre trials comparing SG and RYGB, not only concerning EWL, but also in terms of remission of obesity-related co-morbidities, gastroesophageal reflux disease (GERD) and quality of life (QoL) in the mid- and long-term. Methods: The BariSurg trial was designed as a multi-centre, randomized controlled patient and observer blind trial. The trial protocol was approved by the corresponding ethics committees of the centres. To demonstrate EWL non-inferiority of SG compared to RYGB, power calculation was performed according to a non-inferiority study design. Morbidity, mortality, remission of obesity-related co-morbidities, GERD course and QoL are major secondary endpoints. 248 patients between 18 and 70 years, with a body mass index (BMI) between 35–60 kg/m2 and indication for bariatric surgery according to the most recent German S3-guidelines will be randomized. The primary and secondary endpoints will be assessed prior to surgery and afterwards at discharge and at the time points 3–6, 12, 24, 36, 48 and 60 months postoperatively. Discussion: With its five year follow-up, the BariSurg-trial will provide further evidence based data concerning the impact of SG and RYGB on EWL, remission of obesity-related co-morbidities, the course of GERD and QoL. Trial registration: The trial protocol has been registered in the German Clinical Trials Register DRKS0000476

Immediate surgery compared with short-course neoadjuvant gemcitabine plus capecitabine, FOLFIRINOX, or chemoradiotherapy in patients with borderline resectable pancreatic cancer (ESPAC5):a four-arm, multicentre, randomised, phase 2 trial

BackgroundPatients with borderline resectable pancreatic ductal adenocarcinoma have relatively low resection rates and poor survival despite the use of adjuvant chemotherapy. The aim of our study was to establish the feasibility and efficacy of three different types of short-course neoadjuvant therapy compared with immediate surgery.MethodsESPAC5 (formerly known as ESPAC-5f) was a multicentre, open label, randomised controlled trial done in 16 pancreatic centres in two countries (UK and Germany). Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, biopsy proven pancreatic ductal adenocarcinoma in the pancreatic head, and were staged as having a borderline resectable tumour by contrast-enhanced CT criteria following central review. Participants were randomly assigned by means of minimisation to one of four groups: immediate surgery; neoadjuvant gemcitabine and capecitabine (gemcitabine 1000 mg/m2 on days 1, 8, and 15, and oral capecitabine 830 mg/m2 twice a day on days 1-21 of a 28-day cycle for two cycles); neoadjuvant FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, folinic acid given according to local practice, and fluorouracil 400 mg/m2 bolus injection on days 1 and 15 followed by 2400 mg/m2 46 h intravenous infusion given on days 1 and 15, repeated every 2 weeks for four cycles); or neoadjuvant capecitabine-based chemoradiation (total dose 50·4 Gy in 28 daily fractions over 5·5 weeks [1·8 Gy per fraction, Monday to Friday] with capecitabine 830 mg/m2 twice daily [Monday to Friday] throughout radiotherapy). Patients underwent restaging contrast-enhanced CT at 4-6 weeks after neoadjuvant therapy and underwent surgical exploration if the tumour was still at least borderline resectable. All patients who had their tumour resected received adjuvant therapy at the oncologist's discretion. Primary endpoints were recruitment rate and resection rate. Analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN, 89500674, and is complete.FindingsBetween Sept 3, 2014, and Dec 20, 2018, from 478 patients screened, 90 were randomly assigned to a group (33 to immediate surgery, 20 to gemcitabine plus capecitabine, 20 to FOLFIRINOX, and 17 to capecitabine-based chemoradiation); four patients were excluded from the intention-to-treat analysis (one in the capecitabine-based chemoradiotherapy withdrew consent before starting therapy and three [two in the immediate surgery group and one in the gemcitabine plus capecitabine group] were found to be ineligible after randomisation). 44 (80%) of 55 patients completed neoadjuvant therapy. The recruitment rate was 25·92 patients per year from 16 sites; 21 (68%) of 31 patients in the immediate surgery and 30 (55%) of 55 patients in the combined neoadjuvant therapy groups underwent resection (p=0·33). R0 resection was achieved in three (14%) of 21 patients in the immediate surgery group and seven (23%) of 30 in the neoadjuvant therapy groups combined (p=0·49). Surgical complications were observed in 29 (43%) of 68 patients who underwent surgery; no patients died within 30 days. 46 (84%) of 55 patients receiving neoadjuvant therapy were available for restaging. Six (13%) of 46 had a partial response. Median follow-up time was 12·2 months (95% CI 12·0-12·4). 1-year overall survival was 39% (95% CI 24-61) for immediate surgery, 78% (60-100) for gemcitabine plus capecitabine, 84% (70-100) for FOLFIRINOX, and 60% (37-97) for capecitabine-based chemoradiotherapy (p=0·0028). 1-year disease-free survival from surgery was 33% (95% CI 19-58) for immediate surgery and 59% (46-74) for the combined neoadjuvant therapies (hazard ratio 0·53 [95% CI 0·28-0·98], p=0·016). Three patients reported local disease recurrence (two in the immediate surgery group and one in the FOLFIRINOX group). 78 (91%) patients were included in the safety set and assessed for toxicity events. 19 (24%) of 78 patients reported a grade 3 or worse adverse event (two [7%] of 28 patients in the immediate surgery group and 17 [34%] of 50 patients in the neoadjuvant therapy groups combined), the most common of which were neutropenia, infection, and hyperglycaemia.InterpretationRecruitment was challenging. There was no significant difference in resection rates between patients who underwent immediate surgery and those who underwent neoadjuvant therapy. Short-course (8 week) neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Neoadjuvant chemotherapy with either gemcitabine plus capecitabine or FOLFIRINOX had the best survival compared with immediate surgery. These findings support the use of short-course neoadjuvant chemotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma.FundingCancer Research UK

Diagnosis of Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis by Measurement of microRNA Abundance in Blood and Tissue

A solid process for diagnosis could have a substantial impact on the successful treatment of pancreatic cancer, for which currently mortality is nearly identical to incidence. Variations in the abundance of all microRNA molecules from peripheral blood cells and pancreas tissues were analyzed on microarrays and in part validated by real-time PCR assays. In total, 245 samples from two clinical centers were studied that were obtained from patients with pancreatic ductal adenocarcinoma or chronic pancreatitis and from healthy donors. Utilizing the minimally invasive blood test, receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) analysis demonstrated very high sensitivity and specificity of a distinction between healthy people and patients with either cancer or chronic pancreatitis; respective AUC values of 0.973 and 0.950 were obtained. Confirmative and partly even more discriminative diagnosis could be performed on tissue samples with AUC values of 1.0 and 0.937, respectively. In addition, discrimination between cancer and chronic pancreatitis was achieved (AUC = 0.875). Also, several miRNAs were identified that exhibited abundance variations in both tissue and blood samples. The results could have an immediate diagnostic value for the evaluation of tumor reoccurrence in patients, who have undergone curative surgical resection, and for people with a familial risk of pancreatic cancer

Interface Study on Laser-structured Plated Contacts for Silicon Solar Cells

Plating of a Ni-Cu stack on laser-structured passivation layer openings is a low-cost metallization approach for silicon solar cells. This work investigates the correlation of microscopic interface properties and contact resistance and mechanical adhesion. Advanced micro characterization methods are applied. Based on the results a model is introduced on how to realize adhesion. The results indicate an important influence of interfacial oxide on the contact resistance and its decrease during post-plating annealing