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Bio-based multilayer films were prepared by using the innovative nanolayer coextrusion process to produce films with a number of alternating layers varying from 3 to 2049. For the first time, a semicrystalline polymer was confined by another semicrystalline polymer by nanolayering in order to develop high barrier polyamide (PA11)/polylactic acid (PLA) films without compromising thermal stability and mechanical behavior. This process allows the preparation of nanostratified films with thin layers (down to nanometric thicknesses) in which a confinement effect can be induced. The stratified structure has been investigated, and the layer thicknesses have been measured. Barrier properties were successfully correlated to the microstructure, as well as the thermal behavior, and mechanical properties. The layer continuity was fully achieved for most of the films, but some layer breakups have been observed on the film with the thinnest PLA layer (2049-layers film). Coextruding PLA with PA11 has induced an increase in PLA crystallinity (from 4 to 16%) along with an increase in thermal stability of the multilayer films without impacting PA11 properties. Gas barrier properties were driven by the PLA confined layers due to the microstructural rearrangement by increasing crystallinity, whereas water barrier properties were governed by the PA11 confining layers due to its lower water affinity. As a consequence, a decrease of water permeability (up to 11 times less permeable for the 6M film) but an increase of gas barrier properties (barrier improvement factor (BIF) of 66% for the 0M film for N2and BIF of 36% for the 6M film for CO2for instance) were evidenced as the layer number was increased. This study paves the way for the development of ecofriendly materials with outstanding barrier performances and highlights the importance of nonmiscible polymers adhesion at melt state and additives presence.

Allogeneic chimeric antigen receptor (CAR) T holds the promise of taking this therapeutic approach to broader patient populations while avoiding the intensive manufacturing demands of autologous cell products. One limitation to delivering an allogeneic CAR T is T-cell receptor (TCR) driven toxicity. In this work, the expression of a peptide to interfere with TCR signaling was assessed for the generation of allogeneic CAR T cells. The expression of a truncated CD3ζ peptide was shown to incorporate into the TCR complex and to result in blunted TCR responses. When coexpressed with a natural killer group 2D (NKG2D) CAR, the allogeneic T cells (called CYAD-101) failed to induce graft-versus-host disease in mouse models while maintaining antitumor activity driven by the CAR in vitro and in vivo. Two clinical grade discrete batches of CYAD-101 cells were produced of single donor apheresis resulting in 48 billion CAR T cells sufficient for the entire dose-escalation phase of the proposed clinical trial. The 2 batches showed high consistency producing a predominantly CD4+T-cell population that displayed an effector/central memory phenotype with no evidence of exhaustion markers expression. These clinical grade CYAD-101 cells secreted cytokines and chemokines in response to ligands expressing target cells in vitro, demonstrating effector function through the CAR. Moreover, CYAD-101 cells failed to respond to TCR stimulation, indicating a lack of allogeneic potential. This bank of clinical grade, non–gene-edited, allogeneic CYAD-101 cells are used in the alloSHRINK clinical trial (NCT03692429).

Women with pathogenic germline BRCA1or BRCA2variants have a higher risk of breast cancer than in the general population. International guidelines recommend specific clinical and radiological breast follow-up. This specific breast screening program has already been shown to be of clinical benefit, but no information is available concerning the use of prognostic factors or specific survival to guide follow-up decisions. We evaluated “high-risk” screening in a retrospective single-center study of 520 women carrying pathogenic germline variants of the BRCA1or BRCA2gene treated for breast cancer between January 2000 and December 2016. We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N= 103), whereas the prevalent breast cancer group (PBCG) (N= 417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p< 0.00001), and N0 in 90% vs. 75% (p< 0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p< 0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p= 0.004) and more mastectomies (60% vs. 42% p< 0.0001) in the IBCG vs PBCG groups respectively. Overall and breast cancer-specific mortality were similar between the two groups. However, the patients in the IBCG had a significantly longer metastasis-free survival than those in the PBCG, at three years (96.9% [95% CI 93.5–100] vs. 92.30% [95% CI 89.8–94.9]; p= 0.02), suggesting a possible long-term survival advantage.

Training load may be an important factor underlying the (patho-)physiologic cardiovascular adaptations from endurance exercise. Yet quantifying training load remains challenging due to the complexity of its components (Frequency, Intensity, Time, and Type; F.I.T.T). This systematic review aims to evaluate how training load has been quantified in sports cardiology studies and to provide recommendations for how this can be improved.

MRI techniques and systems have evolved dramatically over recent years. These advances include higher field strengths, new techniques, faster gradients, improved coil technology, and more robust sequence protocols. This article reviews the most commonly used advanced MRI techniques, including diffusion-weighted imaging, magnetic resonance spectrography, diffusion tensor imaging, and cerebrospinal fluid flow tracking.

Three-dimensional printing has evolved dramatically in recent years and is now available for clinical use. Technical operations of 2 of the most common rapid prototyping processes (stereolithography and fused deposition modeling) and the steps involved in the creation of a prototype are discussed. Current applications in human neurosurgery including presurgical planning and educational opportunities are reviewed before focusing on the current applications in veterinary neurology.

A one-year-old alpine wether was presented for emergency evaluation of stranguria. Diagnostics identified a moderately distended bladder and mild dehydration. Preliminary lateral radiographs identified two metallic structures consistent with projectile pellets in the pelvic and perineal regions and no evidence of radiopaque uroliths. A tube cystostomy was performed, and a contrast urethrogram revealed one of the pellets in the perineal region was in proximity to the urethral obstruction. Subsequent radiography and ultrasound identified the pellet as being within the lumen of the urethra. Examination of the trichotomized skin revealed two scars, including a scar over the paralumbar fossa in the region of the urinary bladder suggestive of a projectile injury. The pellet was removed by a perineal urethrotomy. The patient was able to spontaneously urinate after urethrotomy, passed a tube cystostomy challenge two weeks after surgery, and was discharged. No complications were reported. While uncommon in the veterinary and comparative medical literature, clinicians should consider the potential for projectile pellets to migrate into the urinary tract after initial injury.

Recent innovations in Supercontinuum or white laser sources provide a very useful tool to probe nanomaterials physical and optical properties. Onera, The French Aerospace Lab, has developed a fast, in-line and comprehensive optical characterization method. From the combination of hyperspectral, polarized and angular measurements, physical properties of dense nanomaterials are to be retrieved. Based on achieved results, hyperspectral polarized scattering properties are discussed depending on microphysical properties. This technique is applied to a wide range of nanomaterials in suspensions: polymer, metal-oxide or metallic nanoparticles. It can be applied in various fields as chemical control, defence, atmospheric studies or aeronautical industry.

The European Defence Agency (EDA) launched the Active Imaging (ACTIM) study to investigate the potential of active imaging, especially that of spectral laser imaging. The work included a literature survey, the identification of promising military applications, system analyses, a roadmap and recommendations. Passive multi- and hyper-spectral imaging allows discriminating between materials. But the measured radiance in the sensor is difficult to relate to spectral reflectance due to the dependence on e.g. solar angle, clouds, shadows... In turn, active spectral imaging offers a complete control of the illumination, thus eliminating these effects. In addition it allows observing details at long ranges, seeing through degraded atmospheric conditions, penetrating obscurants (foliage, camouflage...) or retrieving polarization information. When 3D, it is suited to producing numerical terrain models and to performing geometry-based identification. Hence fusing the knowledge of ladar and passive spectral imaging will result in new capabilities. We have identified three main application areas for active imaging, and for spectral active imaging in particular: (1) long range observation for identification, (2) mid-range mapping for reconnaissance, (3) shorter range perception for threat detection. We present the system analyses that have been performed for confirming the interests, limitations and requirements of spectral active imaging in these three prioritized applications.

Onera, the French Aerospace Lab, develops and models active imaging systems to understand the relevant physical phenomena impacting on their performances. As a consequence, efforts have been done both on the propagation of a pulse through the atmosphere (scintillation and turbulence effects) and, on target geometries and their surface properties (radiometric and speckle effects). But these imaging systems must operate at night in all ambient illuminations and weather conditions in order to perform the strategic surveillance of the environment for various worldwide operations or to perform the enhanced navigation of an aircraft. Onera has implemented codes for 2D and 3D laser imaging systems. As we aim to image a scene even in the presence of rain, snow, fog or haze, Onera introduces such meteorological effects in these numerical models and compares simulated images with measurements provided by commercial imaging systems.

To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington’s disease (HD).

Creatine supplementation is an established ergogenic aid in sports and is now claimed to have therapeutical applications in a variety of diseases. The available literature mainly covers the short-term (one to several weeks) effects of creatine supplementation on skeletal muscle function in health and disease, which is of little help to evaluate the long-term (two or more months) potential of creatine as a drug in chronic disorders, such as neurodegenerative diseases or muscular dystrophies. Recent findings in healthy humans indicate that the beneficial effect on muscle function and muscle total creatine content may disappear when creatine is continuously ingested for more than two or three months. The mechanism for this habituation to chronic creatine exposure is poorly understood. The primary purpose of the present review article is to critically evaluate the available evidence for long-term efficacy of creatine administration and to hypothesize about ways to optimize creatine administration regimens.

As shown by M.~Fliess, the input/output behavior of nonlinear analytical dynamical systems can be encoded symbolically in a noncommutative formal power series. For nonlinear dynamical systems, this gives an equivalent of the Laplace transform. Here, we consider the inverse problem: is it possible, for a given input/output behavior, to compute effectively its symbolic description, starting from some finite panels of input/output data? More specifically, we present here several ways for effective computation of the terms of generating series, taking as data the jets of some input at time 0 and the jets at time 0 of the corresponding output. We restrict ourselves to the theoretical case of numerically exact data. First, we present a commutative approach based on the representation of the output as an analytic expansion on the basis of the shuffle algebra. Then we present a noncommutative combinatorial approach based on the analysis of recurrence relations via Chen series and its successive derivatives. In this way, we obtain a very compact and efficient identification software. These results may have at least two types of applications (not yet developed). First, we can use the results as an aid in real identification software. This would also allow us to test a real process, in order to decide whether it reflects the behavior of some unknown causal analytic functional. Bibliography: 9 titles.

The effect of creatine and caffeine supplementation on muscle torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmaxwere measured during an exercise test consisting of 30 intermittent contractions of musculus quadriceps (2 s stimulation, 2 s rest) that were induced by electrical stimulation. According to a double-blind randomized crossover design, subjects (n= 10) performed the exercise test before (pretest) and after (posttest) creatine supplementation (Cr, 4 × 5 g/day, 4 days), short-term caffeine intake (Caf, 5 mg · kg−1· day−1, 3 days), creatine supplementation + short-term caffeine intake (Cr+Caf), acute caffeine intake (ACaf, 5 mg/kg) or placebo. Compared with placebo, Cr shortened RT by ∼5% (P< 0.05). Conversely, Caf increased RT (+∼10%, P< 0.05), in particular as RT increased because of fatigue. RT was not significantly changed by either Cr+Caf or ACaf. Tmaxand CT were similar during all experimental conditions. Initial Tmaxwas ∼20% of voluntary maximal isometric contraction force, which was not different between treatments. It is concluded that Caf intake (3 days) prolongs muscle RT and by this action overrides the shortening of RT due to creatine supplementation.

We report experimental measurements of the extinction in a suspension of dielectric spheres. We find that the model originally introduced by Keller is in good agreement with the data provided that nonlocal effects are properly taken into account. We also find that the simple criterion establishing the regime of independent scattering previously introduced is not consistent with our data.

A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n= 10) or placebo (P, n= 9) intake. The exercise protocol consisted of two bouts (Aand B) of maximal contractions, separated by 15 s of rest. Bouts AandBconsisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3–5 h of rest between exercise sessions. Blood samples were collected before and after bouts Aand Band 24 h afterbout B. Knee-extension power outputs were ∼10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations (P< 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects (n= 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by ∼25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.

1We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects.2A double‐blind trial was performed in young healthy volunteers (n=22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee‐extension rehabilitation programme (3 sessions week−1, 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin).3Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross‐sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee‐extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters.4Immobilization decreased quadriceps muscle CSA (∼10 %) and Wmax(∼25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmaxrecovered at a faster rate in CR than in P (P< 0.05for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P< 0.05), whilst MRF4 protein expression was increased in CR but not in P (P< 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r=0.73, P< 0.05).5It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine‐induced change in MRF4 and myogenin expression.

The effect of oral creatine supplementation on high-intensity exercise performance has been extensively studied over the past ten years and its ergogenic potential in young healthy subjects is now well documented. Recently, research has shifted from performance evaluation towards elucidating the mechanisms underlying enhanced muscle functional capacity after creatine supplementation. In this review, we attempt to summarise recent advances in the understanding of potential mechanisms of action of creatine supplementation at the level of skeletal muscle cells. By increasing intracellular creatine content, oral creatine ingestion conceivably stimulates operation of the creatine kinase (CK)/phosphocreatine (PCr) system, which in turn facilitates muscle relaxation. Furthermore, evidence is accumulating to suggest that creatine supplementation can beneficially impact on muscle protein and glycogen synthesis. Thus, muscle hypertrophy and glycogen supercompensation a1'e candidate factors to explain the ergogenic potential of creatine ingestion. Additional issues discussed in this review are the fibre-type specificity of muscle creatine metabolism, the identification of responders versus non-responders to creatine intake, and the scientific background concerning potential side effects of creatine supplementation.

OP ‘T EIJNDE, B., and P. HESPEL. Short-term creatine supplementation does not alter the hormonal response to resistance training. Med. Sci. Sports Exerc., Vol. 33, No. 3, 2001, pp. 449–453.

A nephelometer is presented that theoretically requires no absolute calibration. This instrument is used for determining the particle-size distribution of various scattering media (aerosols, fogs, rocket exhausts, engine plumes, and the like) from angular static light-scattering measurements. An inverse procedure is used, which consists of a least-squares method and a regularization scheme based on numerical filtering. To retrieve the distribution function one matches the experimental data with theoretical patterns derived from Mie theory. The main principles of the inverse method are briefly presented, and the nephelometer is then described with the associated partial calibration procedure. Finally, the whole granulometer system (inverse method and nephelometer) is validated by comparison of measurements of scattering media with calibrated monodisperse or known size distribution functions.

A search procedure based on a least-squares method including a regularization scheme constructed from numerical filtering is presented. This method, with the addition of a nephelometer, can be used to determine the particle-size distributions of various scattering media (aerosols, fogs, rocket exhausts, motor plumes) from angular static light-scattering measurements. For retrieval of the distribution function, the experimental data are matched with theoretical patterns derived from Mie theory. The method is numerically investigated with simulated data, and the performance of the inverse procedure is evaluated. The results show that the retrieved distribution function is quite reliable, even for strong levels of noise.

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 × 5 g/day; n= 8) or placebo (n= 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by ∼20% (P< 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT (r= 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.

The effect of short-term calcium antagonism with felodipine on blood pressure and on plasma catecholamines, renin, and aldosterone was studied in 10 normal volunteers at rest and during incremental bicycle exercise. At rest, diastolic blood pressure was slightly increased during felodipine treatment, whereas systolic pressure and heart rate were not significantly changed. The plasma noradrenaline concentration and plasma renin activity were increased during felodipine treatment; the plasma adrenaline and aldosterone concentrations, on the contrary, were not significantly changed. The rises in plasma renin activity, plasma aldosterone, and plasma adrenaline and noradrenaline concentrations produced by exercise were not significantly affected by felodipine. It is concluded that the rise in plasma renin activity during calcium antagonism with felodipine is not accompanied by a significant increase in plasma aldosterone. Furthermore, the present data suggest that, at least during exercise, calcium antagonism does not interfere with the mechanisms underlying the exercise-induced activation of renin and aldosterone release.

Summary: The intracellular concentrations of sodium [Na+] and potassium [K+] and the water content in human erythrocytes were investigated in 21 male runners before and after a marathon. From 2 to 5 min after the race, the intra-erythrocyte [K+] was significantly decreased (p<0.001) by 7% whereas the plasma [K+], intra-erythrocyte [Na+] and the erythrocyte water content were unchanged. The change in the intra-erythrocyte [K+] observed immediately after the marathon, was negatively correlated with the race time (r=−0.44;p<0.05). Furthermore, the change in the plasma [K+] (r=−0.64;p<0.001) and the amount of K+ excreted in the urine during the race (r=0.54;p<0.05) were also, respectively, negatively and positively correlated with the race time. It is concluded that during prolonged physical exercise the erythrocytes could serve as a kind of K+ reservoir that is drained with increasing magnitude of body K+ loss. This might explain why in the faster marathon runners, in whom the urinary K+ loss is smaller and the K+ intake is greater than in the slower runners during race, the intra-erythrocyte [K+] is unchanged after a marathon whereas in the slower runners it is decreased.