Survival of patients managed in France for duodenal neuroendocrine tumors (D-NET): a 20-year multicenter cohort study from the GTE group: a cohort study.

INTRODUCTION: Duodenal neuroendocrine tumours (D-NETs) have a low incidence; however, their diagnosis has been increasing. Features such as tumour location, size, type, histological grade, and stage were used to adapt the treatment to either endoscopic (ER) or surgical (SR) resections. There is no consensus regarding the definitive treatment. The authors' study aimed to describe the management of non-metastatic, well-differentiated D-NETs in France and its impact on patient survival. METHODS: A registry-based multicenter study using prospectively collected data between 2000 and 2019, including all patients managed for non-metastatic G1 and G2 D-NETs, was conducted in the GTE group. RESULTS: A total of 153 patients were included. Fifty-eight benefited from an ER, and 95 had an SR. No difference in recurrence-free survival (RFS) was observed regardless of treatment type. There was no significant difference between the two groups (ER vs. SR) in terms of location, size, grade, or lymphadenopathy, regardless of the type of incomplete resection performed or regarding the pre-therapeutic assessment of lymph node invasion in imaging. The surgery allowed for significantly more complete resection (patients with R1 resection in the SR group: 9 vs. 14 in the ER group, P<0.001). Among the 51 patients with positive lymph node dissection after SR, tumour size was less than or equal to 1 cm in 25 cases. Surgical complications were more numerous (P=0.001). In the sub-group analysis of G1-G2 D-NETs between 11 and 19 mm, there was no significant difference in grade (P=0.977) and location (P=0.617) between the two groups (ER vs. SR). No significant difference was found in both morphological and functional imaging, focusing on the pre-therapeutic assessment of lymph node invasion (P=0.387). CONCLUSION: Regardless of the resection type (ER or SR) of G1-G2 non-metastatic D-NETs, as well as the type of management of incomplete resection, which was greater in the ER group, long-term survival results were similar between ER and SR. Organ preservation seems to be the best choice owing to the slow evolution of these tumours.

Association of palliative care management and survival after chemotherapy discontinuation in patients with advanced pancreatic adenocarcinoma: A retrospective single-centre observational study.

BACKGROUND: Palliative care (PC) is integrated into standard oncology care. However, its clinical impact at the end of life remains unclear in pancreatic adenocarcinoma (PA). We aimed to describe the end-of-life care pathway and to assess whether PC referral influences survival after chemotherapy discontinuation (CD) among advanced PA patients. METHODS: This retrospective single-centre observational study was conducted among deceased patients with advanced PA who had received chemotherapy between January 1, 2016, and December 31, 2021. Baseline characteristics, the timing of PC referral and events after CD were collected. The primary outcome was time from CD to death. RESULTS: Among the 148 included patients, 53.4% (n = 79) received PC, mostly late after the CD (n = 133, 89.9%), 16.9% (n = 25) received chemotherapy in the last 14 days of life and 75.6% died at the hospital. None received PC in the 8 weeks following the diagnosis. PC referral significantly increased PC department admissions (p < 0.001) and decreased medical unit admissions (p < 0.001). The median survival after the CD was 35 days (IQR: 19-64.5). PC referral was associated with increased survival after CD (HR: 0.65 [0.47-0.90], p = 0.010, Cox) and after adjusting (HR: 0.65 [0.42-0.99], p = 0.045, Cox). CONCLUSION: The study suggests that PC may be associated with longer survival after CD in advanced PA patients. However, PC is underused, and patients are referred late in their care pathway.

Anterior ischemic stroke: Comparison of two clinical outcome prediction scores through the investigation of cerebral collaterals using multiphase CT angiography.

PURPOSE: To compare the evaluation of collaterals on multiphase computed tomography (CT) angiography using the score proposed by the reference study by Menon et al. and the Alberta Stroke Program Early CT (ASPECT) score for the prediction of favorable clinical outcome in patients with anterior ischemic stroke (IS). MATERIALS AND METHODS: Retrospective single center study including 199 patients with anterior ischemic stroke and evaluated using multiphase CT angiography. Collaterals were assessed using the reference score and ASPECT score. The early clinical outcome [National Institute of Health Stroke Score (NIHSS) over day 1] and later clinical outcome [90-day modified Rankin Scale (mRS)] were collected. The primary analysis related to the association between collateral scores and clinical outcome. RESULTS: Collaterals are an independent predictive factor of favorable clinical outcome with the two scores, ranging from an odds ratio (OR) [95% confidence interval (CI)] = 1.84 [1.23; 2.76], P = 0.003 for the reference score to an OR [95% CI] = 2.63 [1.21; 5.73], p = 0.015 for the phase 3 ASPECT score. The phase 3 ASPECT score offers better sensitivity (Se) for the prediction of a favorable clinical outcome [Se = 95%, specificity (Sp) = 37% for a threshold of 7/7] than the reference score (Se = 83%, Sp = 47% for a threshold of 4/5). CONCLUSION: This study demonstrates the value of the ASPECT score in analyzing collaterals using multiphase CT angiography for the prediction of clinical outcome.

Real-time monitoring of a microbial electrolysis cell using an electrical equivalent circuit model.

Efforts in developing microbial electrolysis cells (MECs) resulted in several novel approaches for wastewater treatment and bioelectrosynthesis. Practical implementation of these approaches necessitates the development of an adequate system for real-time (on-line) monitoring and diagnostics of MEC performance. This study describes a simple MEC equivalent electrical circuit (EEC) model and a parameter estimation procedure, which enable such real-time monitoring. The proposed approach involves MEC voltage and current measurements during its operation with periodic power supply connection/disconnection (on/off operation) followed by parameter estimation using either numerical or analytical solution of the model. The proposed monitoring approach is demonstrated using a membraneless MEC with flow-through porous electrodes. Laboratory tests showed that changes in the influent carbon source concentration and composition significantly affect MEC total internal resistance and capacitance estimated by the model. Fast response of these EEC model parameters to changes in operating conditions enables the development of a model-based approach for real-time monitoring and fault detection.

Long-term performance of a microbial electrolysis cell operated with periodic disconnection of power supply.

This study describes a new approach for achieving stable long-term performance and maximizing the removal of chemical oxygen demand (COD) in a Microbial Electrolysis Cell (MEC). In the proposed approach, the MEC power supply is periodically disconnected, e.g. at a frequency of 0.1-0.5 Hz and a duty cycle of 90-95%. To evaluate the impact of such periodic power supply disconnection (on/off mode) on MEC performance, experiments were carried out in two flow-through MECs with activated granular carbon electrodes. The on/off operating strategy was applied to one MEC, while the other one was operated at a fixed voltage (control MEC). Long-term on/off operation resulted in progressive increase in COD removal efficiency (from 80% to 90%) and MEC current over time, while the control MEC showed stable but inferior performance. Furthermore, by changing the operating strategies and applying the on/off approach to the control MEC, its COD removal was increased from 78% to 83% and internal resistance decreased. The proposed on/off mode of operation can be used to develop a high-rate MEC-based wastewater treatment system.

Type, intensity and duration of daily physical activities performed by adults with spinal cord injury.

STUDY DESIGN: Secondary analysis of cross-sectional data. OBJECTIVES: To describe and compare (1) self-reported intensities and durations of specific types of daily physical activities and (2) minutes per day spent on daily physical activities across key demographic groups. SETTING: Community (Ontario, Canada). METHODS: Participants were 695 adults with spinal cord injury (SCI; 76% male, Mage=46.81±13.41 years, Myears post injury=15.19±11.10 years). Daily activities were assessed over the telephone using the Physical Activity Recall Assessment for People with SCI. Multivariate analyses of variance (MANOVA) were computed to test for differences in intensities and durations of different daily activities (objective 1) and between-group differences in minutes per day of daily activities (objective 2). RESULTS: Overall, participants reported 127.92±142.79 min per day of daily physical activities with significantly more time spent in mild intensity (78.93±104.62 min per day) than moderate- (40.23±68.71 min per day) or heavy-intensity activities (8.75±24.53 min per day). Four patterns emerged with respect to type, duration and intensity, with some activities being typically performed at lighter or heavier intensities than others. There were significant differences in minutes per day of activity intensity and duration between groups based on education, injury severity and mode of mobility (P<0.05). CONCLUSION: Given that some groups were more likely to engage in moderate-heavy-intensity activities, and some activities were more likely to be performed at moderate-heavy intensities, interventions that target key groups to increase certain daily activities may be one strategy to enhance overall physical activity participation among people with SCI.

Limitations in ionization-induced compression of femtosecond laser pulses due to spatio-temporal couplings.

It was recently proposed that ionization-induced self-compression could be used as an effective method to further compress femtosecond laser pulses propagating freely in a gas jet [He et al., Phys. Rev. Lett. 113, 263904 2014]. Here, we address the question of the homogeneity of the self-compression process and show experimentally that homogeneous self-compression down to 12fs can be obtained by finding the appropriate focusing geometry for the laser pulse. Simulations are used to reproduce the experimental results and give insight into the self-compression process and its limitations. Simulations suggest that the ionization process induces spatio-temporal couplings which lengthen the pulse duration at focus, possibly making this method ineffective for increasing the laser peak intensity.

A description and estimate of very low-intensity activity and inactive awake time in community-dwelling adults with chronic spinal cord injury.

STUDY DESIGN: Secondary analysis of cross-sectional data. OBJECTIVES: To estimate the amount of very low-intensity activity (VLPA) or inactive daily awake time that people with spinal cord injury (SCI) engage in and to determine correlates of VLPA/inactivity in this population. SETTING: Community (Ontario, Canada). METHODS: Participants with SCI (n=695; Mage=47 years; Myears post-injury=15 years, 76% men) completed telephone interviews. Demographic details and injury-related characteristics were self-reported. Total daily physical activity (for example, mild, moderate and heavy intensity) was measured using the Physical Activity Recall Assessment for People with SCI (PARA-SCI). VLPA/inactivity was calculated by subtracting total daily physical activity time from daily awake time. Correlates of VLPA/inactivity were assessed using a hierarchical linear regression where demographic variables were entered on the first step and injury-related characteristics were entered second. RESULTS: Participants reported VLPA/inactivity for approximately 768±169 min per day, or 84%, of their awake time. The regression model predicting VLPA/inactivity was not significant. CONCLUSION: People with SCI spend the majority of their awake time in VLPA/inactivity. However, VLPA/inactivity did not differ as a function of demographic or injury-related variables, suggesting that all segments of the SCI population could benefit from strategies to reduce inactivity.

Active Living Leaders Training Program for adults with spinal cord injury: a pilot study.

STUDY DESIGN: Quasi-experimental pre-post design with 6-month follow-up. OBJECTIVES: Active Living Leaders Training Program (ALLTP) equips individuals with knowledge and skills to encourage those with spinal cord injury (SCI) to increase their leisure-time physical activity (LTPA). The purpose of this pilot study was to, first, (i) evaluate participants' perceptions of the relevance/usefulness of ALLTP material/presentation, (ii) examine changes in participants' self-efficacy to promote LTPA, (iii) identify program components associated with greater self-efficacy and, second, measure participants' use of ALLTP skills and resources over the subsequent 6 months. SETTING: Canada. METHODS: Six SCI fitness trainers and six adults with SCI completed the three sections of ALLTP and, after each section, provided feedback. Six months later, participants' use of resources and skills was assessed. Means, standard deviations, repeated measures analysis of variance and Pearson's correlations were computed. RESULTS: Relevance/usefulness of the program was rated favorably. Self-efficacy to speak about and encourage LTPA remained high throughout the ALLTP and was positively correlated with the relevance/usefulness of program content and presentation. At follow-up, participants had discussed LTPA with an average of seven people with disabilities and reported using at least one skill and resource from the ALLTP during those discussions. CONCLUSIONS: Users had positive perceptions of ALLTP and reported using the training to promote LTPA to others with disabilities. Participant feedback has been used to improve ALLTP. ALLTP can now be used to train people with SCI and SCI fitness trainers to promote LTPA to others with disabilities.

Investigation of cyano-bridged coordination nanoparticles Gd(3+)/[Fe(CN)6](3-)/D-mannitol as T1-weighted MRI contrast agents.

Cyano-bridged Gd(3+)/[Fe(CN)6](3-) coordination polymer nanoparticles of 3-4 nm stabilized with D-mannitol presenting a high r1 relaxivity value of 11.4 mM(-1) s(-1) were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.

²°¹Tl⁺-labelled Prussian blue nanoparticles as contrast agents for SPECT scintigraphy.

Prussian blue (PB) and its analogues on the nanometric scale are exciting nano-objects that combine the advantages of molecular-based materials and nanochemistry. Herein, we demonstrate that ultra-small PB nanoparticles of 2-3 nm can be easily labelled with radioactive (201)Tl(+) to obtain new nanoprobes as radiotracers for 201-thallium-based imaging.

In vivo quantitative NMR imaging of fruit tissues during growth using Spoiled Gradient Echo sequence.

Nondestructive studies of physiological processes in agronomic products require increasingly higher spatial and temporal resolutions. Nuclear Magnetic Resonance (NMR) imaging is a non-invasive technique providing physiological and morphological information on biological tissues. The aim of this study was to design a robust and accurate quantitative measurement method based on NMR imaging combined with contrast agent (CA) for mapping and quantifying water transport in growing cherry tomato fruits. A multiple flip-angle Spoiled Gradient Echo (SGE) imaging sequence was used to evaluate the intrinsic parameters maps M0 and T1 of the fruit tissues. Water transport and paths flow were monitored using Gd(3+)/[Fe(CN)6](3-)/D-mannitol nanoparticles as a tracer. This dynamic study was carried out using a compartmental modeling. The CA was preferentially accumulated in the surrounding tissues of columella and in the seed envelopes. The total quantities and the average volume flow of water estimated are: 198 mg, 1.76 mm(3)/h for the columella and 326 mg, 2.91 mm(3)/h for the seed envelopes. We demonstrate in this paper that the NMR imaging technique coupled with efficient and biocompatible CA in physiological medium has the potential to become a major tool in plant physiology research.

Pulse-width modulated external resistance increases the microbial fuel cell power output.

This study describes MFC operation with a pulse-width modulated connection of the external resistor (R-PWM mode) at low and high frequencies. Analysis of the output voltage profiles acquired during R-PWM tests showed the presence of slow and fast dynamic components, which can be described by a simple equivalent circuit model suitable for process control applications. At operating frequencies above 100 Hz a noticeable improvement in MFC performance was observed with the power output increase of 22-43% as compared to MFC operation with a constant external resistance.

An investigation of seasonal variation in leisure-time physical activity in persons with spinal cord injury.

STUDY DESIGN: Secondary cross-sectional analyses of a cohort. OBJECTIVES: To examine seasonal variation in total moderate-to-vigorous leisure-time physical activity (MV-LTPA), exercise and sport participation in a cohort of individuals with spinal cord injury (SCI). SETTING: Community (Ontario, Canada). METHODS: Participants with SCI (n=695) completed telephone interviews regarding their involvement in MV-LTPA along with social cognitive predictors of MV-LTPA. Logistic regression was used to predict the impact of season on participation in MV-LTPA, exercise and sport. Hierarchical linear regression was used to examine seasonal variation in min per day of MV-LTPA in the active sub-cohort (n=342) with a specific focus on exercise (for example, wheeling), and sport (for example, sledge hockey). RESULTS: Logistic regressions revealed that season did not predict whether participants engaged in MV-LTPA, exercise or sport. Linear regressions revealed that individuals in the active sub-cohort who completed the questionnaire during the winter reported engaging in less MV-LTPA than those who were interviewed in summer (ßsummer=0.14, P<0.05). This pattern was observed for exercise (ßsummer=0.16, P<0.05; R2 change=0.018) but not for sport (ßsummer=0.076, P=0.68; R2 change=0.014). CONCLUSION: Individuals with SCI report less exercise and total LTPA accrued during the winter months; sport was found to be an exception to this case.

Identification of critical infection parameters to control helper-dependent adenoviral vector production.

Helper-dependent adenoviral vectors (HDVs) are the most promising adenoviral vectors for gene therapy treatments as well as vaccination strategies. However, the lack of a robust and efficient strategy to produce the HDV at high titers constitutes a major obstacle hindering the use of this promising technology at the clinical level. The HDV production requires a double infection of a recombinase-expressing HEK293 cell line with the HDV and a helper virus (HV). To limit the contamination of viral HDV lots by HV, encapsidation of HV is prevented by the recombinase action. A real-time quantitative PCR assay was developed to accurately characterize the contamination of the final product by HV. Infection strategies to enhance the HDV yield and reduce the contamination by HV were investigated. The multiplicity of infection (MOI) was identified as a critical parameter to simultaneously improve the HDV yield and reduce the contamination by HV. HDV-to-HV MOI ratio dictated the HDV yield whereas the HV accumulation was controlled by the MOI of HV. Delaying infection with the HV did not improve the HDV yield.

From the first to the third generation adenoviral vector: what parameters are governing the production yield?

Human adenoviral viral vector serotype 5 (AdV) is presently the primary viral vector used in gene therapy trials. Advancements in AdV process development directly contribute to the clinical application and commercialization of the AdV gene delivery technology. Notably, the development of AdV production in suspension culture has driven the increase in AdV volumetric and specific productivity, therefore providing large quantities of AdV required for clinical studies. This review focuses on detailing the viral, cell and cell culture parameters governing the productivity of the three generations of AdV vectors.

An efficient and scalable process for helper-dependent adenoviral vector production using polyethylenimine-adenofection.

Safety requirements for adenoviral gene therapy protocols have led to the development of the third generation of vectors commonly called helper-dependent adenoviral vectors (HDVs). HDVs have demonstrated a high therapeutic potential; however, the poor efficiency and reliability of the actual production process hampers further large-scale clinical evaluation of this new vector. The current HDV production methods involve a preliminary rescue step through transfection of adherent cell cultures by an HDV plasmid followed by a helper adenovirus (HV) infection. Amplification by serial co-infection of complementary cells allows an increase in the HDV titer. Using a HEK293 FLP/frt cell system in suspension culture, an alternative protocol to the current transfection/infection procedure was evaluated. In this work, the adenofection uses the HDV plasmid linked to the HV with the help of polyethylenimine (PEI) and has shown to outperform standard protocols by producing higher HDV yield. The influence of complex composition on the HDV production was examined by a statistical design. The optimized adenofection and amplification conditions were successively performed to generate HDV at the 3 L bioreactor scale. Following only two serial co-infection passages, up to 1.44 x 10(8) HDV infectious units/mL of culture were generated, which corresponded to 26% of the total particles produced. This production strategy, realized in cell suspension culture, reduced process duration and therefore the probability of vector recombination by introducing a cost-effective transfection protocol, ensuring production of high-quality vector stock.

A predictive nutritional model for plant cells and hairy roots.

A structured nutritional model is proposed to describe growth and nutritional behavior of Eschscholtzia californica suspension cells and Catharanthus roseus and Daucus carota hairy roots in in vitro culture. The model describes the cells specific growth rate from concentration of intracellular nutrients such as inorganic phosphate (Pi), nitrogen sources (NO(3) (-) and NH(4) (+)) and sugars. Two-level Michaelis-Menten kinetics are used to describe Pi and NO(3) (-) uptake and simple Michaelis-Menten kinetics for description of sugars uptake. Model parameters for each cell line were calibrated using data from batch cultures. The predictive capacity of the model was tested using data from medium exchange hairy root cultures. The model describes growth and nutritional behavior for the cell and hairy root lines. A sensitivity analysis was performed to identify critical model parameters and effect of initial conditions. The cell and hairy roots lines are also compared from their kinetic parameters. The kinetic model is efficient for describing and predicting growth and nutritional behaviors of suspension cells and hairy roots.

Dynamic flux cartography of hairy roots primary metabolism.

A dynamic model for plant cell and hairy root primary metabolism is presented. The model includes nutrient uptake (Pi, sugars, nitrogen sources), the glycolysis and pentose phosphate pathways, the TCA cycle, amino acid biosynthesis, respiratory chain, biosynthesis of cell building blocks (structural hexoses, organic acids, lipids, and organic phosphated molecules). The energy shuttles (ATP, ADP) and cofactors (NAD/H, NADP/H) are also included. The model describes the kinetics of 44 biochemical reactions (fluxes) of the primary metabolism of plant cells and includes 41 biochemical species (metabolites, nutrients, biomass components). Multiple Michaelis-Menten type kinetics are used to describe biochemical reaction rates. Known regulatory phenomena on metabolic pathways are included using sigmoid switch functions. A visualization framework showing fluxes and metabolite concentrations over time is presented. The visualization of fluxes and metabolites is used to analyze simulation results from Catharanthus roseus hairy root 50 d batch cultures. The visualization of the metabolic system allows analyzing split ratios between pathways and flux time-variations. For carbon metabolism, the cells were observed to have relatively high and stable fluxes for the central carbon metabolism and low and variable fluxes for anabolic pathways. For phosphate metabolism, a very high free intracellular Pi turnover rate was observed with higher flux variations than for the carbon metabolism. Nitrogen metabolism also exhibited large flux variations. The potential uses of the model are also discussed.

ADM1 application for tuning and performance analysis of a multi-model observer-based estimator.

Anaerobic digestion model no.1 (ADM1) was used for tuning and performance analysis of the multi-model observer based estimator (mmOBE). The mmOBE was based on the variable structure model (VSM) of the anaerobic digestion model, which consists of several local submodels, each of which describes a typical process state. Depending on the hydraulic retention time, ADM1 simulated the methanogenic, organic overload, and acidogenic states of the process. These simulations allowed for optimising tunable parameters of the mmOBE. Owing to relatively slow process dynamics, a data acquisition interval as large as one day was sufficient to obtain acceptable accuracy. The simulations of mmOBE performance showed excellent rate of mmOBE convergence to ADM1 outputs. Moreover, mmOBE successfully estimated key kinetic parameters, such as maximal transformation rates of CODs, VFAs, and methane. These estimations can be used in the development of the advanced knowledge-based process system, which uses both available measurements and estimations of key kinetic parameters for extended diagnosis of failures and process trend analysis.