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For the clinical delivery of immunotherapies it is anticipated that cells will be cryopreserved and shipped to the patient where they will be thawed and administered. An established view in cellular cryopreservation is that following freezing, cells must be warmed rapidly (≤5 minutes) in order to maintain high viability. In this study we examine the interaction between the rate of cooling and rate of warming on the viability, and function of T cells formulated in a conventional DMSO based cryoprotectant and processed in conventional cryovials. The data obtained show that provided the cooling rate is −1 °C min−1 or slower, there is effectively no impact of warming rate on viable cell number within the range of warming rates examined (1.6 °C min−1 to 113 °C min−1). It is only following a rapid rate of cooling (−10 °C min−1) that a reduction in viable cell number is observed following slow rates of warming (1.6 °C min−1 and 6.2 °C min−1), but not rapid rates of warming (113 °C min−1 and 45 °C min−1). Cryomicroscopy studies revealed that this loss of viability is correlated with changes in the ice crystal structure during warming. At high cooling rates (−10 °C min−1) the ice structure appeared highly amorphous, and when subsequently thawed at slow rates (6.2 °C min−1 and below) ice recrystallization was observed during thaw suggesting mechanical disruption of the frozen cells. This data provides a fascinating insight into the crystal structure dependent behaviour during phase change of frozen cell therapies and its effect on live cell suspensions. Furthermore, it provides an operating envelope for the cryopreservation of T cells as an emerging industry defines formulation volumes and cryocontainers for immunotherapy products.

With the objective of improving MR endoluminal imaging of the colonic wall, electromagnetic simulations of different configurations of single-layer and double-layer, and double-turn endoluminal coil geometries were run. Indeed, during colon navigation, variations in coil orientation with respect to B0 are bound to occur, leading to impaired image acquisition due to a loss of signal uniformity. In this work, three typical coil orientations encountered during navigation were chosen and the resulting signal uniformity of the different geometries was investigated through the simulatedB1x,y/IRtvalues. Sampling this quantity over a circle of radius r enabled us to calculate the coefficient of variation (= standard deviation/mean) for this given distance. This procedure was repeated forr∈5;15 mm, which represents the region of interest in the colon. Our results show that single-loop and double-layer geometries could provide complementary solutions for improved signal uniformity. Finally, using four microelectromechanical system switches, we proposed the design of a reconfigurable endoluminal coil able to switch between those two geometries while also ensuring the active decoupling of the endoluminal coil during the RF transmission of an MR experiment.

PURPOSE To demonstrate the feasibility of integrating the magnetization transfer (MT) preparations required for inhomogeneous MT (ihMT) within an MPRAGE-style acquisition. Such a sequence allows for reduced power deposition and easy inclusion of other modules. METHODS An ihMT MPRAGE-style sequence (ihMTRAGE) was initially simulated to investigate acquisition of the 3D ihMT data sequentially, or in an interleaved manner. The ihMTRAGE sequence was implemented on a 3T clinical scanner to acquire ihMT data from the brain and spine. RESULTS Both simulations and in vivo data provided an ihMT signal that was significantly greater using a sequential ihMTRAGE acquisition, compared with an interleaved implementation. Comparison with a steady-state ihMT acquisition (defined as having one MT RF pulse between successive acquisition modules) demonstrated how ihMTRAGE allows for a reduction in average power deposition, or greater ihMT signal at equal average power deposition. Inclusion of a prospective motion-correction module did not significantly affect the ihMT signal obtained from regions of interest in the brain. The ihMTRAGE acquisition allowed combination with a spatial saturation module to reduce phase wrap artifacts in a cervical spinal cord acquisition. CONCLUSIONS Use of preparations necessary for ihMT experiments within an MPRAGE-style sequence provides a useful alternative for acquiring 3D ihMT data. Compared with our steady-state implementation, ihMTRAGE provided reduced power deposition, while allowing use of the maximum intensity from off-resonance RF pulses. The 3D ihMTRAGE acquisition allowed combination of other modules with the preparation necessary for ihMT experiments, specifically motion compensation and spatial saturation modules.

International audience; Purpose - The area of left ventricular (LV) pressure-strain loop (PSL) is used as an index of regional myocardial work. The purpose of the present work is to compare the main segmental PSL markers and the derived global work indices, when they are calculated using an estimated pressure signal or an observed pressure signal.Methods and results - In nine patients implanted with a bi-ventricular pace-maker (CRT), LV pressure was invasively measured in five conditions: CRT-off, LV-pacing, right ventricular-pacing and two different CRT-pacing. For each condition, systolic blood pressure was measured by brachial artery cuff-pressure and transthoracic echocardiography loops were recorded simultaneously. The error and relative root mean square error (rRMSE) between measured and estimated pressure were calculated for each patient and each configuration. Correlation coefficient (R2) and Bland-Altman (BA) analysis were performed for PSL area and work indices. A total of 43 different haemodynamic conditions were compared (774 segmental PSL). The global rRMSE between estimated and measured LV-pressure was 12.3 mmHg. The estimated and measured segmental LV-PSL were strongly correlated, with an R2 of 0.98. BA analysis shows that the mean bias for the estimation of segmental LV-PSL area is 86.0 mmHg.%. A significant bias effect with linearly increasing error with pressure values is observed. R2 ≥ 0.88 and a mean bias in BA analysis ≤41.4 mmHg.% was observed for the estimation of global myocardial work indices.Conclusion - The non-invasive estimation for LV pressure-strain loop area and the global myocardial work indices obtained from LV-PSL strongly correlates with invasive measurements.

Structural neuroimaging studies revealed a consistent pattern of volumetric reductions in both hippocampus (HC) and anterior cingulate cortex (ACC) of individuals with major depressive episode(s) (MDE). This study investigated HC and ACC volume differences in currently depressed individuals (n = 150), individuals with a past lifetime MDE history (n = 79) and healthy controls (n = 287).Non-demented individuals were recruited from a cohort of community-dwelling older adults (ESPRIT study). T1-weighted magnetic resonance images and FreeSurfer Software (automated method) were used. Concerning HC, a manual method of measurement dividing HC into head, body, and tail was also used. General Linear Model was applied adjusting for covariates.Current depression was associated with lower left posterior HC volume, using manual measurement, in comparison to healthy status. However, when we slightly changed sub-group inclusion criteria, results did not survive to correction for multiple comparisons.The finding of lower left posterior HC volume in currently depressed individuals but not in those with a past MDE compared to healthy controls could be related to brain neuroplasticity. Additionally, our results may suggest manual measures to be more sensitive than automated methods.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement N° 777657; Freezing is the most used bacterial cell preservation technique yet still a process that can be damaging and lead to cell death. Cryosensitivity greatly varies depending on considered species or strains. Fourier Transform Infra-Red (FTIR) spectroscopy is a powerful technique allowing biochemical characterization of major cellular components (lipids, proteins, polysaccharides). However, the exploitation of bacterial spectral features under native aqueous environments is challenging due to the strong absorption of water in the mid-IR region. The identification of cryoresistance markers has thus so far been mainly done using FTIR spectra of dried cells. In this study, three lactic acid bacteria strains were selected for their contrasting cryo-sensitivities. The objective was to combine two complementary approaches: a dynamic approach that measures evolution of peak positions in the lipid region of IR spectra as a function of temperature, and a novel approach using a FTIR microscope enabling higher spatial resolution of cells (~103 to 104 cells) in an aqueous environment. The most cryoresistant strain displayed a strikingly different membrane lipid phase transition compared to the other two: although phase transition happened very abruptly and at a low temperature (-14 °C), in gel phase, lipid membranes of the resistant strain maintained a higher degree of disorganization. These observations could be attributed to high unsaturated fatty acid content (>66% of C18:1). In addition to confirming the lipid membrane’s role in cryoresistance, this study has brought to light the potential role of other cellular components by removing the spectral contribution of water in spectra obtained with the FTIR microscope. This was achieved using a specially developed Matlab program, providing access to a large spectral region encompassing both the protein and carbohydrate regions (1800–975 cm-1). Good discrimination and visualization of population heterogeneity was observed, indicating that markers outside the lipid region must also contribute to cryoresistance

Increasingly more patients exposed to radiation from computed axial tomography (CT) will have a greater risk of developing tumors or cancer that are caused by cell mutation in the future. A minor dose level would decrease the number of these possible cases. However, this framework can result in medical specialists (radiologists) not being able to detect anomalies or lesions. This work explores a way of addressing these concerns, achieving the reduction of unnecessary radiation without compromising the diagnosis. We contribute with a novel methodology in the CT area to predict the precise radiation that a patient should be given to accomplish this goal. Specifically, from a real dataset composed of the dose data of over fifty thousand patients that have been classified into standardized protocols (skull, abdomen, thorax, pelvis, etc.), we eliminate atypical information (outliers), to later generate regression curves employing diverse well-known Machine Learning techniques. As a result, we have chosen the best analytical technique per protocol, a selection that was thoroughly carried out according to traditional dosimetry parameters to accurately quantify the dose level that the radiologist should apply in each CT test.

International audience; Aims - Cardiac resynchronization therapy (CRT) plays a pivotal role in the management of patients with heart failure (HF) and wide QRS complex. However, the treatment is plagued by numerous non-responders. Aim of the study is to evaluate the role myocardial work estimated by pressure-strain loops (PSLs) in the comprehension of physiological mechanisms associated with CRT and in the prediction of CRT response. Methods and results - Ninety-seven patients with symptomatic HF (ejection fraction: 27 ± 6%, QRS duration 164 ± 18 ms) undergoing CRT implantation according to current recommendations were retrospectively included in the study. Standard 2D and speckle tracking echocardiography were performed before CRT and at the 6-month follow-up (FU). PSL analysis allowed the calculation of global and regional myocardial constructive work (CW) and wasted work (WW). A > 15% reduction in left ventricular (LV) end-systolic volume at FU defined CRT-positive response (CRT-PR). At FU, 63 (65%) patients responded to CRT. Global CW (CWtot) was significantly increased in CRT-responders. At multivariate analysis, CWtot > 1057 mmHg% (OR 14.69, P = 0.005) and septal flash (OR 8.05, P = 0.004) were the only significant predictors of CRT-PR. CWtot was associated with the entity of CRT-induced myocardial remodelling in both ischaemic (r = -0.55, P

Cryopreservation-related stresses in Lactobacillus delbrueckii SUBSP. Bulgaricus: Global and multi-scale study. 55. Annual Meeting of the Society for Cryobiology

Interdependency of freezing and thawing rates on cryopreserved human t cells. 55. Annual Meeting of the Society for Cryobiology

Background Usability flaws in medication alerting systems may have a negative impact on clinical use and patient safety. In order to prevent the release of alerting systems that contain such flaws, it is necessary to provide designers and evaluators with evidence-based usability design principles. The objective of the present study was to develop a comprehensive, structured list of evidence-based usability design principles for medication alerting systems. Methods Nine sets of design principles for medication alerting systems were analyzed, summarized, and structured. We then matched the summarized principles with a list of usability flaws in order to determine the level of underlying evidence. Results Fifty-eight principles were summarized from the literature and two additional principles were defined, so that each flaw was matched with a principle. We organized the 60 summarized usability design principles into 6 meta-principles, 38 principles, and 16 sub-principles. Only 15 principles were not matched with a usability flaw. The 6 meta-principles respectively covered the improvement of the signal-to-noise ratio, the support for collaborative working, the fit with a clinician’s workflow, the data display, the transparency of the alerting system, and the actionable tools to be provided within an alert. Conclusions It is possible to develop an evidence-based, structured, comprehensive list of usability design principles that are specific to medication alerting systems and are illustrated by the corresponding usability flaws. This list represents an improvement over the current literature. Each principle is now associated with the best available evidence of its violation. This knowledge may help to improve the usability of medication alerting systems and, ultimately, decrease the harmful consequences of the systems’ usability flaws. Electronic supplementary material The online version of this article (10.1186/s12911-018-0615-9) contains supplementary material, which is available to authorized users.

International audience; The multi-modality cardiovascular imaging journal, European Heart Journal-Cardiovascular Imaging, was created in 2012. It has gained an impressive impact factor of 5.99 during its first 5 years and is now the most important imaging journal in Europe. The most important studies from the journal's fourth and fifth years will be highlighted in two reports. Part I of the review will focus on studies in myocardial function, myocardial ischaemia, and emerging techniques in cardiovascular imaging and Part II will focus on valvular heart diseases, heart failure, cardiomyopathies, and congenital heart diseases.

International audience; OBJECTIVE: The aim of this study was to test a new automated hepatic volumetry technique by comparing the accuracies and postprocessing times of manual and automated liver volume segmentation methods in a patient population undergoing orthotopic liver transplantation so that liver volume could be determined on pathology as the standard of reference. CONCLUSION: Both manual and automated multiphase MDCT-based volume measurements were strongly correlated to liver volume (Pearson correlation coefficient, r = 0.87 [p < 0.0001] and 0.90 [p < 0.0001], respectively). Automated multiphase segmentation was significantly more rapid than manual segmentation (mean time, 16 ± 5 [SD] and 86 ± 3 seconds, respectively; p = 0.01). Overall, automated liver volumetry based on multiphase CT acquisitions is feasible and more rapid than manual segmentation.

Introduction The Comprehensive in vitro Proarrhythmia Assay (C i PA) is a nonclinical Safety Pharmacology paradigm for discovering electrophysiological mechanisms that are likely to confer proarrhythmic liability to drug candidates intended for human use. Topics covered Key talks delivered at the ‘C i PA on my mind’ session, held during the 2015 Annual Meeting of the Safety Pharmacology Society (SPS), are summarized. Issues and potential solutions relating to crucial constituents [ e.g. , biological materials (ion channels and pluripotent stem cell-derived cardiomyocytes), study platforms, drug solutions, and data analysis] of C i PA core assays are critically examined. Discussion In order to advance the C i PA paradigm from the current testing and validation stages to a research and regulatory drug development strategy, systematic guidance by C i PA stakeholders is necessary to expedite solutions to pending and newly arising issues. Once a study protocol is proved to yield robust and reproducible results within and across laboratories, it can be implemented as qualified regulatory procedure.

International audience

Cryopreservation is key for delivery of cellular therapies, however the key physical and biological events during cryopreservation are poorly understood. This study explored the entire cooling range, from membrane phase transitions above 0°C to the extracellular glass transition at -123°C, including an endothermic event occurring at -47°C that we attributed to the glass transition of the intracellular compartment. An immortalised, human suspension cell line (Jurkat) was studied, using the cryoprotectant dimethyl sulfoxide. Fourier transform infrared spectroscopy was used to determine membrane phase transitions and differential scanning calorimetry to analyse glass transition events. Jurkat cells were exposed to controlled cooling followed by rapid, uncontrolled cooling to examine biological implications of the events, with post-thaw viable cell number and functionality assessed up to 72 h post-thaw. The intracellular glass transition observed at -47°C corresponded to a sharp discontinuity in biological recovery following rapid cooling. No other physical events were seen which could be related to post-thaw viability or performance significantly. Controlled cooling to at least -47°C during the cryopreservation of Jurkat cells, in the presence of dimethyl sulfoxide, will ensure an optimal post-thaw viability. Below -47°C, rapid cooling can be used. This provides an enhanced physical and biological understanding of the key events during cryopreservation and should accelerate the development of optimised cryobiological cooling protocols.

The European PREMIUM project aims at proposing new eco-friendly strategies to preserve lactic acid bacteria (LAB). One approach considered is the development of new protective agents in order to allow the application of more aggressive drying processes than freeze-drying. Recently, oligosaccharides such as fructo-oligosaccharides and galacto-oligosaccharides have been reported as promising molecules for protecting LAB. It is generally assumed in the literature that direct interaction between membrane and protective agent is important to stabilize membrane during water removal. The ability of oligosaccharides to interact with bacterial membrane will be dependent not only on their sugar composition but also on the lipid membrane composition. The objective of this study is to develop a simplified lipid model representative of bacterial membrane to investigate the specific interaction between oligosaccharides and lipids. The membrane of two strains of lactic acid bacteria exhibiting different freezing resistances and extremely low survival to freeze-drying were fully characterized to determine lipid composition and lipid phase transition. Lipid membrane models of various level of complexity were subsequently designed: i) liposomes and monolayers from bacterial lipid extracts; ii) liposomes from lipid extracts enriched with standard lipids, and ii) liposomes and monolayers made from two standard lipids. The standard lipids were chosen in accordance with the predominant lipids present within the bacterial membrane. The biophysical properties of these models were determined using Fourier Transform Infrared spectroscopy (lipid phase transition) and Langmuir isotherms (surface pressure area isotherms). Two binary lipid models satisfactorily representing the two bacterial strains according to their biophysical properties were set up and could thus be further used to investigate specific interaction between lipid and oligosaccharides.