Sacrificial Cladding with Brittle Materials for Blast Protection.

In the following work, sacrificial claddings filled with different brittle materials were investigated, from concrete foam to granular media. They were subjected to blast loading using an explosive driven shock tube, while a sensor measures the load transmission and a high speed camera records the compression of the core. From a macroscopic point of view, concrete foam and granular media can act efficiently as a crushable core but differs greatly in terms of energy dissipation mechanisms. To compare them, granular media was at first treated as a cellular material, and different key parameters (plateau stress, densification strain) were computed using the energy absorption efficiency methodology. The presented tests results, coupled with observation in literature, allow a better understanding on the crushing process of a granular media. In particular, granular media tend to work as a core even for low intensity load, contrary to more classical crushable core.

Penetration and propagation into biological matter and biological effects of high-power ultra-wideband pulses: a review.

Systems emitting ultra-wideband high power microwave (HP/UWB) pulses are developed for military and civilian applications. HP/UWB pulses typically have durations on the order of nanoseconds, rise times of picoseconds and amplitudes around 100 kV m(-1). This article reviews current research on biological effects from HP/UWB exposure. The different references were classified according to endpoints (cardiovascular system, central nervous system, behavior, genotoxicity, teratology …). The article also reviews the aspects of mechanisms of interactions and tissue damage as well as the numerical work that has been done for studying HP/UWB pulse propagation and pulse energy deposition inside biological tissues. The mechanisms proposed are the molecular conformation change, the modification of chemical reaction rates, membrane excitation and breakdown and direct electrical forces on cells or cell constituents, and the energy deposition. As regards the penetration of biological matter and the deposited energy, mainly computations were published. They have shown that the EM field inside the biological matter is strongly modified compared to the incident EM field and that the energy absorption for HP/UWB pulses occurs in the same way as for continuous waves. However, the energy carried by a HP/UWB pulse is very low and the deposited energy is low. The number of published studies dealing with the biological effects is small and only a few pointed out slight effects. It should be further noted that the animal populations used in the studies were not always large, the statistical analyses not always relevant and the teams involved in this research rather limited in number.

One milligram of lorazepam does not decrease anxiety induced by CCK-4 in healthy volunteers: investigation of neural correlates with BOLD MRI.

Benzodiazepine effects on cholecystokinin tetrapeptide (CCK-4)-induced panic attack (PA) in humans are incompletely characterized, in particular on the neurofunctional level. This work explores the effects of lorazepam on brain activity and behavioral and physiological symptoms related to CCK-4-induced PA in healthy volunteers. Twenty-one male volunteers received 1 mg of lorazepam or placebo orally, 2 hours before an injection of 0.9% saline solution followed by 50 µg of CCK-4 during functional magnetic resonance imaging (fMRI) and heart rate recording. Panic attacks were defined using the panic symptom scale (PSS). In addition, the Y1-STAI (state anxiety) and the Bond & Lader Visual Analogue Scale (VAS) were used. Eleven subjects were classified as panickers. CCK-4 induced behavioral anxiety and cardiovascular effects along with cerebral activation in anxiety-related brain regions. Overall, lorazepam did not significantly modify the anxiogenic and cardiovascular effects of CCK-4. Regarding CCK-4-induced brain activation, lorazepam did not reduce activity in the insulae and cingulate gyrus of panickers. One milligram of lorazepam was not sufficient to reverse strong panicogenic effects, but decreased brain activity in the case of mild anxiety.

The effect of aging on the inhibitory function in middle-aged subjects: a functional MRI study coupled with a color-matched Stroop task.

OBJECTIVE: The effects of aging on the inhibitory function are largely described in the neuroimaging literature but little data is available on the beginning of this age-related impairment. METHODS: In this study, we described the cortical activation of middle-aged (mean age +/- standard error to the mean, 51.7 +/- 3.1) subjects compared to young (26.8 +/- 3.4) and elderly subjects (62.8 +/- 3) while they performed a color-matched Stroop task during functional magnetic resonance imaging. The task consisted in identifying the printing color of a word regardless of its meaning. Three conditions were defined depending on the meaning of this word; neutral (no meaning), congruent (color name matching the printing color), incongruent (color name mismatching the printing color), with interference effect in the latter. RESULTS: Middle-aged subjects were as slow as elderly compared to young for all conditions and both were less accurate than young subjects during interference condition. Elderly showed an activity more bilateral and greater in the parietal lobule, the dorsolateral and ventrolateral prefrontal cortex (DLPFC, VLPFC) during both congruent and incongruent conditions compared to young. Middle-aged showed an intermediary level of activity between those of elderly and young subjects in the left DLPFC, VLPFC and parietal lobule only during incongruent condition. CONCLUSION: These results suggested that the age-related impairment of the inhibitory process could already occur around the age of 50 years and consist in an increase of the activity in the left prefrontal and parietal cortex before increasing more and becoming bilateral around the age of 60 years.

Test-retest reliability of a functional MRI anticipatory anxiety paradigm in healthy volunteers.

PURPOSE: To evaluate the reproducibility of neural activations induced by an anticipatory anxiety provocation challenge in healthy volunteers. MATERIALS AND METHODS: Fourteen healthy male volunteers participated in two separate functional MRI (fMRI) sessions in which they underwent a paradigm based on anticipation of aversive transcutaneous electrical nerve stimulations. This paradigm consisted of alternating presentation of red circles associated with the likelihood that aversive stimuli may be given and blue circles during which the subjects knew that no shock could be given. Anxiety state was compared before the fMRI sessions and during the threat periods using clinical scales (Hamilton, STAI-Y1), the Bond and Lader Visual Analogue Scale, and self-rating scales of apprehension and stimulus aversivity. RESULTS: The selected paradigm induced anticipatory anxiety of moderate intensity as suggested by clinical scales and apprehension rating, without any habituation to the somatosensory stimulus across sessions. Compared to rest periods, threat of the aversive stimulus induced clear brain activation in anticipatory anxiety-related areas: frontal/prefrontal cortex, insula, lentiform nucleus, temporal pole, and cingulate cortex. Anxiety symptoms and cerebral activity were reproducible across sessions. CONCLUSION: The fMRI paradigm and its assessment method include all criteria to speed up the evaluation and the development of new anxiolytics.

Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety.

The main objective of this work was to study the functional markers of the clinical response to cholecystokinin tetrapeptide (CCK-4). Twelve healthy male subjects were challenged with CCK-4 and simultaneously underwent functional magnetic resonance imaging (fMRI) recording. Since anticipatory anxiety (AA) is an intrinsic part of panic disorder, a behavioral paradigm, using the threat of being administered a second injection of CCK-4, has been developed to investigate induced AA. The study was composed of three fMRI scans according to an open design. During first and second scan, subjects were injected with placebo and CCK-4, respectively. The third scan was the AA challenge. CCK-4 administration induced physiological and psychological symptoms of anxiety that met the criteria for a panic attack in 8 subjects, as well as cerebral activation in anxiety-related brain regions. Clinical and physiological response intensity was consistent with cerebral activity extent and robustness. fMRI proved more sensitive than clinical assessment in evidencing the effects of the AA challenge. The latter induced brain activation, different from that obtained on CCK-4 and during placebo injection, that was likely related to anxiety. The method applied in this study is suitable for the study of anxiety using fMRI.

Human models as tools in the development of psychotropic drugs.

Despite the growing means devoted to research and development (R α D) and refinements in the preclinical stages, the efficiency of central nervous system (CMS) drug development is disappointing. Many drugs reach patient studies with an erroneous therapeutic indication andlor in incorrect doses. Apart from the first clinical studies, which are conducted in healthy volunteers and focus only on safety, iolerability, and pharmacokinetics, drug development mostly relies on patient studies. Psychiatric disorders are characterized by heterogeneity and a high rate of comorbidity. It is becoming increasingly difficult to recruit patients for clinical trials and there are many confounding factors in this population, for example, those related to treatments. In order to keep patient exposure and financial expenditure to a minimum, it is important to avoid ill-designed and inconclusive studies. This risk could be minimized by gathering pharmacodynamic data earlier in development and considering that the goal of a phase 1 plan is to reach patient studies with clear ideas about the compound's pharmacodynamic profile, its efficacy in the putative indication (proof of concept), and pharmacokinetic/pharmacodynamic relationships, in addition to safety, tolerability, and pharmacokinetics. Human models in healthy volunteers may be useful tools for this purpose, but their use necessitates a global adaptation of the phase scheme, favoring pharmacodynamic assessments without neglecting safety. We are engaged in an R α D program aimed to adapt existing models and develop new paradigms suitable for early proof of concept substantiation.