Total Pelvic Exenteration for Primary and Recurrent Malignancies

Contains fulltext : 81087.pdf (publisher's version ) (Open Access)INTRODUCTION: Complete resection is the most important prognostic factor in surgery for pelvic tumors. In locally advanced and recurrent pelvic malignancies, radical margins are sometimes difficult to obtain because of close relation to or growth in adjacent organs/structures. Total pelvic exenteration (TPE) is an exenterative operation for these advanced tumors and involves en bloc resection of the rectum, bladder, and internal genital organs (prostate/seminal vesicles or uterus, ovaries and/or vagina). METHODS: Between 1994 and 2008, a TPE was performed in 69 patients with pelvic cancer; 48 with rectal cancer (32 primary and 16 recurrent), 14 with cervical cancer (1 primary and 13 recurrent), 5 with sarcoma (3 primary and 2 recurrent), 1 with primary vaginal, and 1 with recurrent endometrial carcinoma. Ten patients were treated with neoadjuvant chemotherapy and 66 patients with preoperative radiotherapy to induce down-staging. Eighteen patients received IORT because of an incomplete or marginal complete resection. RESULTS: The median follow-up was 43 (range, 1-196) months. Median duration of surgery was 448 (range, 300-670) minutes, median blood loss was 6,300 (range, 750-21,000) ml, and hospitalization was 17 (range, 4-65) days. Overall major and minor complication rates were 34% and 57%, respectively. The in-hospital mortality rate was 1%. A complete resection was possible in 75% of all patients, a microscopically incomplete resection (R1) in 16%, and a macroscopically incomplete resection (R2) in 9%. Five-year local control for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 89%, 38%, and 64%, respectively. Overall survival after 5 years for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 66%, 8%, and 45%. CONCLUSIONS: Total pelvic exenteration is accompanied with considerable morbidity, but good local control and acceptable overall survival justifies the use of this extensive surgical technique in most patients, especially patients with primary locally advanced rectal cancer and recurrent cervical cancer

Spatiotemporal modeling of microbial metabolism

Background Microbial systems in which the extracellular environment varies both spatially and temporally are very common in nature and in engineering applications. While the use of genome-scale metabolic reconstructions for steady-state flux balance analysis (FBA) and extensions for dynamic FBA are common, the development of spatiotemporal metabolic models has received little attention. Results We present a general methodology for spatiotemporal metabolic modeling based on combining genome-scale reconstructions with fundamental transport equations that govern the relevant convective and/or diffusional processes in time and spatially varying environments. Our solution procedure involves spatial discretization of the partial differential equation model followed by numerical integration of the resulting system of ordinary differential equations with embedded linear programs using DFBAlab, a MATLAB code that performs reliable and efficient dynamic FBA simulations. We demonstrate our methodology by solving spatiotemporal metabolic models for two systems of considerable practical interest: (1) a bubble column reactor with the syngas fermenting bacterium Clostridium ljungdahlii; and (2) a chronic wound biofilm with the human pathogen Pseudomonas aeruginosa. Despite the complexity of the discretized models which consist of 900 ODEs/600 LPs and 250 ODEs/250 LPs, respectively, we show that the proposed computational framework allows efficient and robust model solution. Conclusions Our study establishes a new paradigm for formulating and solving genome-scale metabolic models with both time and spatial variations and has wide applicability to natural and engineered microbial systems

Ready for the road? A Socio-technical Investigation of Fire Safety Improvement Options for Lithium-ion Traction Batteries

Battery technology is crucial in the transition towards electric mobility. Lithium-ion batteries are conquering the market but are facing fire safety risks that might threaten further applications. In this study, we address the problem and potential solutions for traction batteries in the European Union area. We do so by taking a unique socio-technical system perspective. Therefore, a novel, mixed-method approach is applied, combining literature review; stakeholder interviews; Failure Mode, Mechanisms, and Event Analysis (FMMEA); and rapid prototyping. Our findings confirm that fire safety is an upcoming concern. Still, most stakeholders lack a full understanding of the problem. Improving safety is a shared responsibility among supply chain and societal stakeholders. For automotive applications, voluntary standard-setting on safety risks is an appropriate tool to improve fire safety, whereas for niche applications, a top-down approach setting regulations seems more suited. For both groups, the adaptation of battery pack designs to prevent thermal runaway propagation is shown to be promising from a technological, practical, and organizational perspective. The chosen mixed-method approach allowed for a holistic analysis of the problems and potential solutions. As such, it can serve as an empowerment strategy for stakeholders in the field, stimulating further discussion, agenda building, and action

Role of Ca2+-activated Cl- current during proarrhythmic early after depolarizations in sheep and human ventricular myocytes

OBJECTIVES: The proarrhythmic early afterdepolarizations (EADs) during phase-2 of the cardiac action potential (phase-2 EADs) are associated with secondary Ca2+-release of the sarcoplasmic reticulum. This makes it probable that the Ca2+-activated Cl- current [ICl(Ca)] is present during phase-2 EADs. Activation of ICl(Ca) during phase-2 of the action potential will result in an outwardly directed, repolarizing current and may thus be expected to prevent excessive depolarization of phase-2 EADs. The present study was designed to test this hypothesis. METHODS AND RESULTS: The contribution of ICl(Ca) during phase-2 EADs was studied in enzymatically isolated sheep and human ventricular myocytes using the patch-clamp methodology. EADs were induced by a combination of a low stimulus frequency (0.5 Hz) and exposure to 1 microm noradrenaline. In sheep myocytes, the ICl(Ca) blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.5 mm) abolished phase-1 repolarization of the action potential in all myocytes tested. This indicates that ICl(Ca) is present in all sheep myocytes. However, DIDS had no effect on phase-2 EAD characteristics. In human myocytes, DIDS neither affected phase-1 repolarization nor phase-2 EAD characteristics. CONCLUSION: In sheep ventricular myocytes, but not in human ventricular myocytes, ICl(Ca) contributes to phase-1 repolarization of the action potential. In both sheep and human myocytes, ICl(Ca) plays a limited role during phase-2 EAD

Possible mechanisms of the protective effect of pretreatment with anipamil in ischemic-reperfused isolated rat hearts.

Rats were given anipamil (5 mg/kg) or glucose, intraperitoneally twice daily for 5 days. During this period the mean arterial blood pressure and heart rate were measured daily. The heart was then isolated and perfused. Energy metabolism and intracellular pH were monitored by 31P nuclear magnetic resonance spectroscopy during 30 minutes of ischemia followed by 30 minutes of reperfusion, with a simultaneous isovolumetric measurement of left ventricular contraction. Myocardial norepinephrine and glycogen were assayed immediately after excision of the heart, after 15 minutes oxygenated perfusion, at the end of ischemia and at the end of reperfusion. Metabolic and functional recovery during reperfusion were significantly better in hearts pretreated with anipamil (p less than 0.0005 vs controls). However, protection was not preceded by an effect on mean arterial pressure or heart rate in vivo, or a negative inotropic effect during control perfusion of the isolated hearts. There was no energy sparing effect during ischemia; but intracellular pH during ischemia stabilized at a higher level (p less than 0.0005 vs controls). Myocardial norepinephrine and glycogen stores were not decreased by pretreatment with anipamil, and their release or degradation due to ischemia and reperfusion were also not different from controls. Commonly known mechanisms of myocardial protection by calcium antagonists fail to explain the protection by pretreatment with anipamil as observed in our experiments, and alternative mechanisms are to be considered

The fate of soil organic carbon upon erosion, transport and deposition in agricultural landscapes - A review of different concepts

Erosion and deposition redistribute large quantities of sediment and soil organic carbon (SOC) in agricultural landscapes. In the perspective of global carbon cycling, the coupling between erosion processes and the fate of SOC is of particular interest. However, different concepts have been proposed to assess the impact of erosion-induced lateral and vertical carbon fluxes. On landscape scale, this resulted in contrasting conclusions if agricultural soils represent either a carbon sink or source. The large global area of arable soil and generally high erosion rates, make these insights important. In this review, we aim to give an overview of the different conceptual relations described governing C dynamics at sites of erosion, along the transport pathway and at depositional sites and the current state of knowledge on the fate of SOC upon erosion, transport and deposition in agricultural landscapes.The impact of erosion on SOC dynamics differs for sites of erosion, deposition and during transport, with further influences by agricultural practices (e.g. tillage and fertilisation). Controlling processes are the detachment of sediment and SOC, net primary production resulting in dynamic replacement and changes in mineralisation upon transport and deposition due to aggregate breakdown and deep burial, respectively. However, the exact magnitude and dominance of these processes are debated, resulting in a controversy whether arable land functions as a sink or source for atmospheric CO2. Global estimations range between a net sink strength of 0.06-1 versus a source of 0.27-1.14GtCyr-1 for agricultural soils.An eco-geomorphologic approach, which encompasses physical- and biological-driven factors (e.g. spatio-temporal variation in biological, geomorphological and biological processes, environmental conditions, mineralisation, and net primary production) is of importance to balance the carbon budget and ascertain sink or source formation at landscape scale. High spatio-temporal variability on process-scale imposes constrains, to measure and model the fate of SOC upon erosion, with limited quantitative data available. Prospective research across the landscape (eroding sites, transport pathway, and depositional sites) should include all relevant processes at broad temporal and spatial scales. Definitive resolution of the sink/source controversy lies in further eco-geomorphologic research on the fate of SOC, focussing on long-term and spatial extensive monitoring studies, combined with advanced measuring, modelling and extrapolation techniques to cover broad spatio-temporal SOC dynamics. Ascertainment of carbon dynamics in agricultural landscapes provides important insights to balance the carbon budget and finally holds the answer on sink/source formation

The fate of soil organic carbon upon erosion, transport and deposition in agricultural landscapes - A review of different concepts

Erosion and deposition redistribute large quantities of sediment and soil organic carbon (SOC) in agricultural landscapes. In the perspective of global carbon cycling, the coupling between erosion processes and the fate of SOC is of particular interest. However, different concepts have been proposed to assess the impact of erosion-induced lateral and vertical carbon fluxes. On landscape scale, this resulted in contrasting conclusions if agricultural soils represent either a carbon sink or source. The large global area of arable soil and generally high erosion rates, make these insights important. In this review, we aim to give an overview of the different conceptual relations described governing C dynamics at sites of erosion, along the transport pathway and at depositional sites and the current state of knowledge on the fate of SOC upon erosion, transport and deposition in agricultural landscapes.The impact of erosion on SOC dynamics differs for sites of erosion, deposition and during transport, with further influences by agricultural practices (e.g. tillage and fertilisation). Controlling processes are the detachment of sediment and SOC, net primary production resulting in dynamic replacement and changes in mineralisation upon transport and deposition due to aggregate breakdown and deep burial, respectively. However, the exact magnitude and dominance of these processes are debated, resulting in a controversy whether arable land functions as a sink or source for atmospheric CO2. Global estimations range between a net sink strength of 0.06-1 versus a source of 0.27-1.14GtCyr-1 for agricultural soils.An eco-geomorphologic approach, which encompasses physical- and biological-driven factors (e.g. spatio-temporal variation in biological, geomorphological and biological processes, environmental conditions, mineralisation, and net primary production) is of importance to balance the carbon budget and ascertain sink or source formation at landscape scale. High spatio-temporal variability on process-scale imposes constrains, to measure and model the fate of SOC upon erosion, with limited quantitative data available. Prospective research across the landscape (eroding sites, transport pathway, and depositional sites) should include all relevant processes at broad temporal and spatial scales. Definitive resolution of the sink/source controversy lies in further eco-geomorphologic research on the fate of SOC, focussing on long-term and spatial extensive monitoring studies, combined with advanced measuring, modelling and extrapolation techniques to cover broad spatio-temporal SOC dynamics. Ascertainment of carbon dynamics in agricultural landscapes provides important insights to balance the carbon budget and finally holds the answer on sink/source formation