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Anxiety is a complex phenomenon: Its eliciting stimuli and circumstances, component behaviors, and functional consequences are only slowly coming to be understood. Here, we examine defense systems from field studies; laboratory studies focusing on experimental analyses of behavior; and, the fear conditioning literature, with a focus on the role of uncertainty in promoting an anxiety pattern that involves high rates of stimulus generalization and resistance to extinction. Respectively, these different areas provide information on evolved elicitors of defense (field studies); outline a defense system focused on obtaining information about uncertain threat (ethoexperimental analyses); and, provide a simple, well-researched, easily measured paradigm for analysis of nonassociative stress-enhanced fear conditioning (the SEFL). Results suggest that all of these—each of which is responsive to uncertainty—play multiple and interactive roles in anxiety. Brain system findings for some relevant models are reviewed, with suggestions that further analyses of current models may be capable of providing a great deal of additional information about these complex interactions and their underlying biology. [ABSTRACT FROM AUTHOR]

Treatment of small laryngeal cancerous lesions (T1 and T2) is based on partial endoscopic or open surgery and radiotherapy. In addition to the oncological imperative, these techniques must optimally preserve the functions of breathing, swallowing and phonation. To analyze the above functions in patients treated with supracricoid laryngectomy and reconstruction using infrahyoid muscle. Breathing, swallowing and phonation were analyzed in 37 patients treated in two institutes between 2005 and 2015. All patients undergoing the above type of reconstruction with a minimum 1 year's follow-up were included. Respiratory study noted any tracheotomy and measured peak inspiratory flow. Preservation of cricoarytenoid units and nasogastric intubation time, and DHI-30 self-administered questionnaire results were collected to analyze swallowing function. Phonation was assessed on the VHI-30 self-administered questionnaire. The rate of primary surgery without tracheotomy was 64.9% (13 patients), with rapid resumption of oral feeding (mean intubation time, 13 days). Mean VHI score was 28.3 and mean DHI 30 score 2.7. Mean peak inspiratory flow was 203.3 mL/min. Supracricoid laryngectomy with reconstruction using subhyoid muscle is an alternative technique for the treatment of small laryngeal cancerous lesions, providing uncomplicated functional outcome. [ABSTRACT FROM AUTHOR]

Cervical spondylodiscitis is a rare but severe complication of pharyngeal surgery. This multicenter retrospective study reported all patients in the database of the French head and neck tumor study group (GETTEC) affected by cervical spondylodiscitis after transoral robotic surgery (TORS) for malignant pharyngeal tumor from January 2010 to January 2017. To describe cases of post-TORS cervical spondylodiscitis, identify alarm signs, and determine optimal management of these potentially lethal complications. Seven patients from 6 centers were included. Carcinomas were located in the posterior pharyngeal wall. Tumor stage was T1 or T2. All patients had risk factors for spondylodiscitis. Mean time to diagnosis was 12.6 days. The interval between surgery and spondylodiscitis diagnosis ranged from 20 days to 4.5 months, for a mean 2.1 months. The most common symptom was neck pain (87%). Infections were polymicrobial; micro-organisms were isolated in 5 cases and managed by intravenous antibiotics, associated to medullary decompression surgery in 3 cases. Follow-up found favorable progression in 4 cases, and 3 deaths (mortality, 43%). This French multicenter study found elevated mortality in post-TORS spondylodiscitis, even in case of limited resection. Surgeons must be aware of this complication and alerted by persistent neck pain, fever, asthenia, impaired or delayed posterior pharyngeal wall wound healing or elevation of inflammatory markers. MRI is the most effective diagnostic radiological examination. [ABSTRACT FROM AUTHOR]

Specific defensive behaviors of rodents are shaped by features of the eliciting threat stimuli and situation. Threat scenarios confirmed these relationships in people, with results substantially replicated in 4 additional scenario studies. Subsequent human studies involve computer games measuring fear as flight from threat stimuli and anxiety as alternation between two threats. Stabilometric studies have shown reduction in sway (freezing) to inescapable (e.g. with gun pointed at subject) threatening photographs; but enhanced lateral sway (flight attempts) to escapable threats; (gun pointed away from subject). Relationships between threat ambiguity, risk assessment, and anxiety have been validated by identification of videos of facial expressions to ambiguous threats, as anxiety; and systematic biases toward threat stimuli by anxious individuals. Enhanced rumination, interpretable as unsuccessful risk assessment, is a dynamic component of both anxiety and depression, particularly in women. While there is less experimental work on defensive threat/attack, a transdiagnostic “Fear of Harm” phenotype of aggression associated with fear suggests that this is a component of pathological as well as normal human defensive behavior. [ABSTRACT FROM AUTHOR]

Anxiety and depression are highly prevalent behavior disorders, particularly in women. Recent preclinical work using animal models has been suboptimal in predicting the efficacy of drugs targeted at these conditions, suggesting a potential discrepancy between such models and the human disorders. Notably female animals tend to be equal to, or less responsive than, males in these tasks. A number of analyses suggest that mammalian defense patterns are complex: In addition to relatively discrete and immediate fight, flight, and freezing responses, a risk assessment pattern may occur in response to threat stimuli or situations with ambiguous elements. This pattern combines defensiveness with a number of cognition-linked behaviors such as sensory attention and orientation, approach, contact, and investigation of the potential threat. Studies measuring elements of this pattern suggest that female rats, and perhaps female mice, show higher levels than equivalent males. Higher female involvement may also occur in tasks involving learning/generalization/extinction of defensiveness to conditioned stimuli. Such findings are consonant with recent analyses of "female survival strategies" based on differential adaptiveness of cognitive components of defensiveness in females, due to the necessity of female care of offspring until they are independent. These data suggest the value of additional behavioral and functional analyses of cognitive aspects of defensive behavior; contributing to both an understanding of their underlying mechanisms, and providing more sensitive measures of drug responsivity for use with animal models. • Recent animal research involving models of anxiety-like or depression-like behaviors has been suboptimally effective at predicting drug effects on these human disorders. • Females are typically less responsive to threat than males in these models, in contrast to the higher rates of anxiety and depression in women. • Cognitive components of the defense pattern such as risk assessment, investigating and analyzing ambiguous threat, tend to show higher rates of responsivity in female rats and, possibly, mice. In models where these components are not evaluated, females may appear to show less defensiveness than males. • Additional analyses of the functions and behaviors involved in threat assessment may provide more precise information on neural and neurochemical systems of anxiety and depression, improving animal models of these disorders. [ABSTRACT FROM AUTHOR]

Over the 30 years since IBNS was founded, a central theme of "Translation" has emerged. This reflects increasing realization that mental disorders such as anxiety and depression are extremely widespread, expensive and painful to societies and individuals across the world. The Blanchard lab has been particularly involved in attempts to understand the evolutionary and functional mechanisms underlying defensive behaviors as a focal component of these disorders. This involved analysis of the relationships between threatening situations/stimuli, and the behaviors (flight, freezing, fight, and risk assessment) that respond to them, for rodents; and also attempts to link these relationships to human responsivity to similar threatening events: Linkages that are complicated by factors such as domestication and sex. In particular it is important to describe and characterize the organization of defensive patterns in people as well as nonhuman animals, and to understand how these patterns can become nonfunctional and pathological. • Improving translation of animal research to human psychopathology has been a major goal of behavioral neuroscience over the past 30 years. • The Blanchard lab focused on defensive behavior -an evolved, functional pattern of activities that provide optimum responsivity to threatening stimuli and situations. • These defenses range from relatively simple and immediate responses, to complex patterns seeking and assessing information relative to both threat and situation. • Although there is substantial consistency across mammalian species in the form/functions of many such defenses, sex differences and differences attributable to domestication complicate analyses animal models, and their translation to humans. • Behavioral Neuroscience research can facilitate understanding of these mechanisms \ and\their relationships to behavioral pathologies. [ABSTRACT FROM AUTHOR]

Abstract Objective Circumferential pharyngolaryngectomy is performed for advanced pharyngeal tumor or in a context of postradiation recurrence. Several free or pedicle flaps have been described for pharyngeal defect reconstruction, with choice at the surgeon's discretion. The aim of this study was to evaluate long-term swallowing function according to the type of flap used for reconstruction. Material and method A multicenter retrospective study was conducted from January to September 2016 within the French GETTEC head and neck tumor study group. All patients in remission after circumferential pharyngolaryngectomy were included and filled out the Deglutition Handicap Index (DHI) questionnaire and underwent swallowing function fiberoptic endoscopy assessment. 46 patients (39 men, 7 women) were included. Reconstruction used a tubularized forearm free flap (FFF group) in 19 cases, pectoralis major myocutaneous flap (PMMF group) in 15 cases and free jejunum flap (FJF group) in 12 cases. Results Mean DHI was 24: 20 in the FFF group, 23 in the FJF group and 25 in the PMMF group, without significant differences. 27 patients had normal swallowing, 9 mixed diet, 8 liquid diet and 3 were fed by gastrostomy. On endoscopy, free flaps (FJF and FFF) were associated with significantly greater rates of normal swallowing of saliva and yogurt than in the PMMF group (P = 0.04). Conclusion Type of flap reconstruction after circumferential pharyngolaryngectomy had no significant impact on postoperative swallowing function assessed on the self-administered DHI questionnaire. [ABSTRACT FROM AUTHOR]

Objective The present article is an update of the guideline of the French Society of Otorhinolaryngology and Head and Neck Surgery (SFORL) on the post-treatment follow-up of adult head and neck squamous cell carcinoma concerning screening for metastasis and metachronous esophageal and bronchial locations. Methods A multidisciplinary work-group was entrusted with a review of the literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the work-group members’ own experience. These were then reviewed by an editorial group independent of the work-group. A coordination meeting then finalized the guidelines. Guidelines were graded A, B, C or “expert opinion” according to decreasing level of evidence. [ABSTRACT FROM AUTHOR]

Objectives A 10-year retrospective study investigated factors for survival and laryngeal preservation in advanced laryngeal, hypopharyngeal or epilaryngeal neoplasia. Material and method Two hundred and forty-six patients with advanced cancer of the larynx (17.48%), hypopharynx (48.78%) or epilarynx (33.74%) undergoing primary organ-sparing treatment were included from 1998 to 2008. Treatment comprised chemotherapy followed by radiation therapy for 92.68% of patients, isolated radiation therapy for 1.6% and concomitant or sequential radiation-chemotherapy for 5.7%. General health status, history and tumor status were recorded. Factors influencing survival were analyzed by Kaplan-Meier estimator, log-rank test and Cox models. Results Median overall survival of the population was 2.3 years and median laryngeal preservation 0.99 years in male patients and 2 years in female patients. Survival correlated significantly with body mass index (BMI; P = 0.0004), WHO performance status ( P = 0.0064), alcohol consumption ( P = 0.0004) and cessation ( P < 0.0001) and also T stage ( P = 0.0038), initial laryngeal mobility ( P = 0.0002) and post-chemotherapy assessment ( P < 0.0001). Survival with functional larynx correlated with baseline BMI at first consultation ( P = 0.016), baseline WHO grade ( P = 0.0005), laryngeal mobility ( P < 0.0001), T staging ( P = 0.0009), and T and/or N chemotherapy response to a classical organ preservation protocol ( P < 0.0001). Conclusion Over and above established criteria, the present study highlighted the importance of general health and nutritional status during treatment. [ABSTRACT FROM AUTHOR]

Introduction Osteoradionecrosis (ORN) is a severe, generally irreversible complication of radiotherapy due to failure of healing. The pentoxifylline-tocopherol combination decreases the superficial fibrosis induced by radiotherapy. Potentiation by Clodronate (PENTOCLO) appears to be effective in ORN of the mandible. The objectives of this study were to evaluate the efficacy and safety of PENTOCLO to treat osteoradionecrosis of the mandible. Methods Retrospective study of 27 patients with a mean age of 65 ± 12 years, managed for ORN of the mandible secondary to irradiation for head and neck cancer, treated by the PENTOCLO protocol between January 2010 and March 2011. The primary endpoint was regression of exposed bone until complete healing. Assessment was both clinical (measurement of mucosal ulceration) and radiological (panoramic dental x-rays) before treatment, after antibiotic-corticosteroid combination therapy for one month (M1), and then after 3, 6, 12 months of PENTOCLO. Results An improvement of mucosal ulceration was observed in 16/21 patients after 3 months and in 12/17 patients after 6 months of PENTOCLO. Healing was obtained in 16 patients. Median healing time was 82 days (range: 32–266), and was shorter after surgery and radiotherapy (49 days) and longer after chemoradiotherapy (169 days). Radiological healing was achieved later than clinical healing with improvement in 9 out of 20 patients at 3 months. The safety and efficacy of treatment were evaluated by intraoral clinical examination, and assessment of feeding, weight and analgesic consumption. No patient discontinued treatment because of adverse effects. Conclusion The PENTOCLO protocol achieved clinical and radiological regression of ORN with, in parallel, a reduction of the indications for major surgery. These preliminary results need to be confirmed by prospective studies comprising quality of life assessment. [ABSTRACT FROM AUTHOR]

Objectives The authors present the section of the guidelines of the French Otorhinolaryngology Head and Neck Surgery Society (SFORL) for the management of somatic pain induced by head and neck cancer treatment concerning management of pain following radiation therapy and chemotherapy. Methods A multidisciplinary work group was entrusted with a literature review. Guidelines were drawn up based on the articles retrieved and the group members' experience. They were read over by an editorial group independent of the work group. A coordination meeting drew up the final version. Guidelines were graded A, B or C or as expert opinion in decreasing order of level of evidence. Results Particular care should be given to detection and early adapted treatment of pain induced by radiation therapy and/or chemotherapy, to improve quality of life in head and neck cancer patients. [ABSTRACT FROM AUTHOR]

Objective To present the guidelines of the French Oto-Rhino-Laryngology – Head and Neck Surgery Society (SFORL) concerning the management of somatic pain induced by the treatment of head and neck cancer, and in particular the management of early and late post-surgical pain. Methods A multidisciplinary work group conducted a review of the scientific literature on the study topic. An editorial group subsequently read the resulting guidelines before validation. Results It is recommended to prevent onset of pain caused by malpositioning on the operating table, as well as pain related to postoperative care. During surgery, it is recommended to spare nerve and muscle structures as far as possible to limit painful sequelae. Management of early postoperative pain upon tumor resection and flap harvesting sites requires patient-controlled analgesia by morphine pump. Physical therapy is recommended after flap harvesting to minimize painful sequelae. Conclusion Preventive and curative measures should be undertaken for appropriate management of post-surgical pain in the treatment of head and neck cancers. [ABSTRACT FROM AUTHOR]

Objectives The authors present the guidelines of the French Oto-Rhino-Laryngology- Head and Neck Surgery Society (Société française d'oto-rhino-laryngologie et de chirurgie de la face et du cou [SFORL]) for the management of somatic pain induced by head-and-neck cancer treatment, and in particular the instruments needed for the definition and initial assessment of the various types of pain. Methods A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. Results The priority is to eliminate tumoral recurrence when pain reappears or changes following head-and-neck cancer treatment. Neuropathic pain screening instruments and pain assessment scales should be used to assess pain intensity and treatment efficacy. Functional rehabilitation sessions should be prescribed to reduce musculoskeletal pain and prevent ankylosis and postural disorder. Psychotherapy and mind-body therapy, when available, should be provided in case of chronic pain. In case of recalcitrant complex pain, referral should be made to a multidisciplinary pain structure. Conclusion The management of somatic pain induced by head-and-neck cancer treatment above all requires identifying and assessing the intensity of the various types of pain involved, their functional impact and their emotional component. [ABSTRACT FROM AUTHOR]

Summary: Objective: Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. Method: Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. Study centres: CLCC François-Baclesse and CHU de Caen. Patients: Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). Results: In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. Conclusion: In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%. [Copyright &y& Elsevier]

Highlights: [•] The health care burden of psychopathologies demands research relevant to solutions. [•] Animal models of psychopathologies are a weak link in the translatability of such research. [•] Their weakness reflects the lack of an adequate conception of the organization of behavior. [•] The adaptive functions of behavior may enable identification of cross-species parallels. [•] Permitting cross-talk between model and psychopathology that aids understanding of both. [ABSTRACT FROM AUTHOR]

Abstract: We present a comprehensive study on the controlled phase synthesis and thermal decomposition of Cd(BH2)4, a material for solid state hydrogen storage obtained via the metathesis reaction of LiBH4 with CdCl2. By adjusting the stochiometry of the reactants and controlling the mechanical milling vial temperature, we have isolated the tetragonal (P42mn) low temperature phase and the cubic () high temperature phase of the cadmium borohydride. Cd(BH2)4 has a low thermodynamic stability and decomposes with fast kinetic at 348K, when heated at 1Kmin−1 against a backpressure of 1bar H2. A semi-quantitative analysis reveals that the decomposition gases are composed of 1:1 H2 +B2H6 and that only Cd remains as solid crystalline phase. [Copyright &y& Elsevier]

Abstract: BTBR T+tf/J (BTBR) mice show abnormal social, communicatory, and repetitive/stereotyped behaviors paralleling many of the symptoms of autism spectrum disorders. BTBR also show agenesis of the corpus callosum (CC) suggesting major perturbations of growth or guidance factors in the dorsal forebrain . Heparan sulfate (HS) is a polysaccaride found in the brain and other animal tissues. It binds to a wide variety of ligands and through these ligands modulates a number of biological processes, including cell proliferation and differentiation, migration and guidance. It is aggregated on fractal-like structures (fractones) in the subventricular zone (SVZ), that may be visualized by laminin immunoreactivity (LAM-ir), as well as by HS immunoreactivity (HS-ir). We report that the lateral ventricles of BTBR mice were drastically reduced in area compared to C57BL/6J (B6) mice while the BTBR SVZ was significantly shorter than that of B6. In addition to much smaller fractones for BTBR, both HS and LAM-ir associated with fractones were significantly reduced in BTBR, and their anterior–posterior distributions were also altered. Finally, the ratio of HS to LAM in individual fractones was significantly higher in BTBR than in B6 mice. These data, in agreement with other findings linking HS to callosal development, suggest that variations in the quantity and distribution of HS in the SVZ of the lateral ventricles may be important modulators of the brain structural abnormalities of BTBR mice, and, potentially, contribute to the behavioral pathologies of these animals. [Copyright &y& Elsevier]

Abstract: BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors, showing deficiencies in social behaviors; reduced or unusual ultrasonic vocalizations in conspecific situations; and enhanced, repetitive self-grooming.Recent studies have described their behaviors in a seminatural visible burrow system (VBS); a Social Proximity Test in which avoidance of a conspecific is impossible; and in an object approach and investigation test evaluating attention to specific objects and potential stereotypies in the order of approaching/investigating objects. VBS results confirmed strong BTBR avoidance of conspecifics and in the Social Proximity Test, BTBR showed dramatic differences in several close-in behaviors, including specific avoidance of a nose-to-nose contact that may potentially be related to gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a Three-Chamber Test, and some additional behaviors – but not nose to nose avoidance – in the Social Proximity Test. BTBR also showed higher levels of preference for particular objects, and higher levels of sequences investigating 3- or 4-objects in the same order. Heparan sulfate (HS) associated with fractal structures in the subventricular zone of the lateral ventricles was severely reduced in BTBR. HS may modulate the functions of a range of growth and guidance factors during development, and HS abnormalities are associated with relevant brain (callosal agenesis) and behavioral (reductions in sociality) changes; suggesting the value of examination of the dynamics of the HS system in the context of autism. [Copyright &y& Elsevier]

Abstract: Risk assessment is a pattern of activities involved in detection and analysis of threat stimuli and the situations in which the threat is encountered. It is a core process in the choice of specific defenses, such as flight, freezing, defensive threat and defensive attack, that counter the threat and minimize the danger it poses. This highly adaptive process takes into account important characteristics, such as type and location (including distance from the subject) of the threat, as well as those (e.g. presence of an escape route or hiding place) of the situation, combining them to predict which specific defense is optimal with that particular combination of threat and situation. Risk assessment is particularly associated with ambiguity either of the threat stimulus or of the outcome of available defensive behaviors. It is also crucial in determining that threat is no longer present, permitting a return to normal, nondefensive behavior. Although risk assessment has been described in detail in rodents, it is also a feature of human defensive behavior, particularly in association with ambiguity. Rumination may be a specifically human form of risk assessment, more often expressed by women, and highly associated with anxiety. Risk assessment behaviors respond to drugs effective against generalized anxiety disorder; however, flight, a dominant specific defense in many common situations, shows a pharmacological response profile closer to that of panic disorder. Risk assessment and flight also appear to show some consistent differences in terms of brain regional activation patterns, suggesting a potential biological differentiation of anxiety and fear/panic systems. An especially intriguing possibility is that mirror neurons may respond to some of the same types of situational differences that are analyzed during risk assessment, suggesting an additional functional role for these neurons. [Copyright &y& Elsevier]

Abstract: Most of percutaneous coronary interventions are performed on stabilized patients. Although these procedures have recently been challenged for this type of patient following the publication of the recent Courage study in 2007 (which in fact has only confirmed previous studies), their efficacy is now well established for lowering the frequency of episodes of angina and increasing the performance under load in stabilized high risk patients. In practice, the evaluation of patients (case by case) is essential to establish their risk (low, intermediate or high) in order to offer the most suitable treatment. The aim of this paper is to overview the indications, limitations and results of coronary angioplasties performed in stabilized patients in France in 2009. [Copyright &y& Elsevier]

Abstract: In rodents, where chemical signals play a particularly important role in determining intraspecies interactions including social dominance and intersexual relationships, various studies have shown that behavior is sensitive to conspecific odor cues. Mice use urinary scent marks for communication with individual conspecifics in many social contexts. Urinary scent involves genetic information about individuals such as species, sex, and individual identity as well as metabolic information such as social dominance, and reproductive and health status, which are mediated by chemical proteins in scent marks including the major histocompatibility complex and the major urinary proteins. The odor of the predator which can be considered to be a threatening signal for the prey also modulate mouse behavior in which scent marking is suppressed in response to the cat odor exposure in mice. These odorant chemicals are detected and recognized through two olfactory bulbs, the role of which in detection of chemosignals with biological relevant appears to be differential, but partly overlapped. Mice deposit scent marks toward conspecifics to maintain their social relationships, and inhibit scent marking in a context where natural predator, cat odor is contained. This suppression of scent marking is long-lasting (for at least 7 days) and context-dependent, while the odorant signaling to conspecifics tends to appear frequently (over 24h but less than 7 days intervals) depending on the familiarity of each signal-recipient. It has been discussed that scent marking is a communicative behavior associated with territoriality toward conspecifics, indicating that the social signaling within species are sensitive to predator odor cues in terms of vulnerability to predation risk. [Copyright &y& Elsevier]

Abstract: The reduction reaction of VCl3 mixed with LiAlD4 is studied for different ball-mill energies. From low to high ball-milling energies VCl3 is reduced by the formation of Li–V–Cl metastables phases, LiCl and free Al and V or Al–V phases. It is also shown that the enhancement of the kinetics reaches a limit with increased ball-mill energy. From measurements of the released hydrogen with a Sieverts apparatus and X-ray and neutron diffraction, it is shown that even under mild conditions, at or close to room temperature, the two first steps of the decomposition of VCl3-enhanced LiAlD4 occurs during the first weeks after milling at temperatures in the range 20–50°C. [Copyright &y& Elsevier]

Abstract: Rats incorporate circa 22kHz ultrasonic alarm cries into their defense pattern in response to a predator threat. These calls are dependent on conspecific presence, show gender differences, and tend to be emitted from a place of relative safety. Rats emit sonic defensive threat vocalizations when approached by a potential threat. These are emitted regardless of conspecific presence, and increase as a function of threat proximity, eventually culminating in defensive attack at close distances. Ample data from field studies suggest a similar division of vocalizations into alarm or warning cries, and defensive threat vocalizations, although both are often subsumed under the rubric of “alarm cries”. A clear distinction between these types of calls is necessary for proper analysis of the evolutionary mechanisms responsible for the development and maintenance of each of them. Furthermore, the integration of data from field studies and laboratory experiments may prove useful in evaluation of the relationship between each type of cry and emotional (fear or anxiety-like) states in mammals. [Copyright &y& Elsevier]

Abstract: Deficits in social interaction are primary characteristics of autism, which has strong genetic components. Genetically manipulated mouse models may provide a useful research tool to advance the investigation of genes associated with autism. To identify these genes using mouse models, behavioral assays for social relationships in the background strains must be developed. The present study examined colony formation in groups of one male and three female mice (Experiment 1) and, groups of three male mice (Experiment 2) of the C57BL/6J strain in a semi-natural visible burrow system. For adult mixed-sex colonies, 4-h observations during both the dark and light cycles for 15 days demonstrated day-dependent increases in huddling together in the chamber accompanied by decreased frequencies of active social behaviors. Sequential analyses of social interactions indicated that approaches to the back of the approached animal typically elicited flight, while approaches to the front of the approached animal failed to do so. This was seen for female to female, and for female to male approaches, as well as male to female approaches, strongly counterindicating a view that rear approach/flight specifically reflects female responsivirity to unwanted male sexual approach. For adult male colonies, similar protocols found that these social behaviors were similar to those of adult mixed-sex colonies. These findings suggest two potentially useful measures of eusocial behavior in mice, of possible value for genetic mouse models of autism; that is, huddling together and approaches to the front but not the back, of conspecifics. [Copyright &y& Elsevier]

Abstract: The isothermal decompositions of pure LiAlD4 and LiAlD4 ball-milled with VCl3 and have been studied by synchrotron X-ray diffraction. The changes of the different phases are examined during the decomposition and the activation energies and kinetics parameters are derived. Two periods of decomposition are observed. The first is an induction period governed by the nucleation of new phases. The second is the main decomposition period where the apparent activation energies and the kinetics are affected by the additives. VCl3 appears to be a better additive in regard of decreasing the apparent activation energy and enhancing the kinetics of the decomposition. [Copyright &y& Elsevier]

Abstract: Exposure of rats to a cat elicits Fos activity in a number of brain areas or structures. Based on hodological relationships of these, Canteras has proposed a medial hypothalamic defense system, with input from several forebrain sites. Both electrolytic and neurotoxic lesions of the dorsal premammillary nucleus, which shows the strongest Fos response to cat exposure, produce striking decrements in a number of defensive behaviors to a cat or to cat odor stimuli, but do not have a major effect on either postshock freezing, or responsivity to the odor of a female in estrus. Neurotoxic lesions of the medial amygdala produce decrements in defensiveness to predator stimuli, particularly odor stimuli, that are consistent with a view of this structure as involved with allomonal cues. While dorsal hippocampal lesions had little effect on responsivity to predator stimuli, neurotoxic lesions of the ventral hippocampus reduced freezing and enhanced a variety of nondefensive behaviors to both cat odor and footshock, with similar reductions in defensiveness during context conditioning tests for cat odor, cat exposure and footshock. These results support the view that the dorsal premammillary nucleus is strongly and selectively involved in control of responsivity to predator stimuli. Structures with important input into the medial hypothalamic defense system appear also to be functionally involved with antipredator defensive behaviors, and these lesion studies may suggest specific hypotheses as to the particular defense functions of different areas. [Copyright &y& Elsevier]

Previous studies have shown that electrolytic lesions of the dorsal premammillary nucleus (PMd) produce robust reductions in responsivity of rats to the presence of a live predator as well as to its odor, suggesting a critical role for the PMd in the modulation of defense. The present study investigated whether disruptions in defensive responding were specific to predators or if they may indicate a more general deficit in responding to pheromonal odors. Sexually naive male rats with bilateral ibotenic acid lesions of the PMd were exposed to the odor of a female rat in estrus as well as to the presence of cat odor, and, a live cat.PMd lesions produced a dramatic reduction in freezing and avoidance to the cat odor; and, reductions in freezing, enhanced activity and risk assessment to cat exposure. However, PMd lesions produced no changes in response to the presentation of the female odorant. These results confirm earlier findings of attenuation in defensiveness following electrolytic PMd lesions while extending these findings to suggest that the reduced defensiveness occurs specifically in response to predatory odors. [Copyright &y& Elsevier]

Thermal desorption spectroscopy and X-ray diffraction experiments show that ball-milling of LiAlD4 in presence of VCl3 or TiCl3·1/3(AlCl3) can reduce its thermal decomposition temperatures by 60 and 50 °C, respectively. However, some partial decomposition of LiAlD4 into Li3AlD6, Al and D2 occurs during the mechanical processing: 80% for TiCl3·1/3(AlCl3), 40% for VCl3. LiCl is formed during the ball-milling, this suggests the reduction of the additives by LiAlD4. The localisations of Ti or V atoms are not yet determined. [Copyright &y& Elsevier]

Corticotropin-releasing factor (CRF) and its receptor subtypes have been implicated in endocrine and behavioral responsivity to stress and emotion, including fear, anxiety, and aggression. SSR125543A is a new nonpeptide selective antagonist at the CRF1 receptor that has been shown to produce an anxiolytic-like effect in a number of animal models of anxiety. The present study investigated effects of an oral dose of 10, or 30 mg/kg of SSR125543A on aggressive behaviors of resident male Syrian hamsters toward male intruders. The high dose (30 mg/kg) of the CRF1 receptor antagonist produced a higher latency to bite and lower lateral attack frequencies and chase durations, indicating a reduction in aggression toward intruders in resident hamsters. The same dose of SSR125543A also enhanced frequency and duration of olfactory investigation, indicating that neither avoidance of the opponent nor deficiency in social activity is responsible for the reduction in aggression seen in these animals. [Copyright &y& Elsevier]

The advantages of using predator-related odor stimuli to study emotional responses in laboratory tests depend on whether such stimuli do elicit a relatively complete pattern of emotionality. This has been confirmed for cat fur/skin odor stimuli, which elicit a range of defensive behaviors in rats that may be reduced by anxiolytic drugs, produce residual anxiety-like behavior in the elevated plus maze and support rapid aversive conditioning to the context in which they were encountered. Although the synthetic fox fecal odor, trimethylthiazoline (TMT), elicits avoidance similar to that seen in response to cat fur/skin odor, this avoidance does not respond to anxiolytic drugs. In addition, TMT does not produce residual anxiety-like behaviors in the elevated plus maze, nor does it support conditioning.As natural cat feces also elicit avoidance but fail to support conditioning, it is possible that the ability of a predator-related odor to serve as an effective unconditioned stimulus (US) relates to its predictive status with reference to the actual presence of the predator. Avoidance per se may reflect that a stimulus is aversive but not necessarily capable of eliciting an emotional response. This view is consonant with findings in a Mouse Defense Test Battery (MDTB) measuring a wide range of defensive responses to predator exposure. A contextual defense measure that may reflect either conditioned or residual but unconditioned emotional responses was almost never reduced by drug effects unless these also reduced risk assessment or defensive threat/attack measures. However, reductions in contextual defense without changes in flight/avoidance measures were much more common.These findings suggest that flight/avoidance, although it obviously may occur as one component of a full pattern of defensive and emotional behaviors, is also somewhat separable from the others. When—as appears to be the case with TMT—it is the major or perhaps only consistent defensive behavior elicited, this may reflect a stimulus that is aversive or noxious but with little ability to predict the presence of threat or danger. That such stimuli fail to support rapid aversive conditioning suggests the need for a reanalysis of the characteristics required for an effective aversive US. [Copyright &y& Elsevier]

We evaluated the benefits of automation on the technical performance of a new automated cell culture incubator, the AUTOCELL 200, developed by Jouan SA. In addition, we assessed the potential interference of the embedded mechanical parts on cell culture growth. We measured a throughput of 150 plates loaded per hour, and 120 plates unloaded per hour, which is compatible with an external robotic handler. The mean time of robotic gate opening was 7 s. The gate pathway minimized climate disturbances inside the incubator. For CO2, we used a delay between opening events of 1 min. Biological assay results did not demonstrate a significant difference between the automated incubator and a traditional manual incubator, but we concluded that automation using the AUTOCELL 200 could provide meaningful benefits for cell culture. [ABSTRACT FROM AUTHOR]

Paul MacLean''s work has exemplified and encouraged an approach in which natural behaviors are elicited and investigated in laboratory settings. Our own experiences with bringing natural behaviors into the laboratory indicate that this is best achieved by providing the social and environmental stimuli necessary to support these behaviors and by an initial process of ethological/observational analysis of them. Examples discussed in support of these suggestions include the development of more natural habitats, including visible burrow systems (VBS), for fossorial rodents such as rats and mice; analysis of aggressive and defensive behaviors among social groups in such habitats and to introduced predators; and the development of defense test batteries in which individual defensive behaviors may be elicited through manipulations of threat and environmental stimuli.These situations have proved useful in analysis of the effects of drugs active against anxiety-related psychopathologies. However, an equally important use for them is in the analysis of normal defensive and aggressive behaviors. Detailed analysis of natural behaviors in socially and environmentally adequate situations provides an important link between molecular findings and both normal and pathological behavior patterns. Investigation of natural behaviors in adequate stimulus contexts does not represent an antiexperimental stance but one that supplements and enhances the generalizability of more conventional experimental laboratory approaches. [Copyright &y& Elsevier]

Lesions of the dorsal premammillary nucleus (PMd) have been reported to produce dramatic reductions in responsivity of rats to a live cat. Such lesions provide a means of analyzing the potentially differential neural systems involved in different defensive behaviors, and the relationship between these systems and concepts such as anxiety. Rats with bilateral electrolytic lesions of the PMd were run in an elevated plus maze (EPM), exposed first to cat odor and then to a live cat, and assessed for postshock freezing and locomotion. PMd lesions produced a dramatic reduction in freezing, avoidance, and stretch attend to the cat odor stimulus, and reduction in freezing, with greater activity, and enhanced stretch approach to cat exposure. However, PMd lesions had minimal effects in the EPM, and postshock freezing scores were unchanged. These results confirm earlier findings of reduced defensiveness of PMd-lesioned rats to a cat, extending the pattern of reduced defensiveness to cat odor stimuli as well, but also suggest that such lesions have few effects on nonolfactory threat stimuli. [Copyright &y& Elsevier]

Ticlopidine or clopidogrel combined with aspirin decrease major cardiac events (Mace) after PTCA with stent implantation. It has not be proven yet that pretreatment by T or C was superior to conventional post-treatment, especially in unstable patients. The aim of the present study was to determine the influence of thienopyridine pretreatment on the risk of Mace (death, Q wave myocardial infarction, need for repeat PTCA or surgery, angina recurrence, stent thrombosis) during the hospitalization period in a population prospectively included in 2 multicentre registries of patients undergoing placement of a S670® or S7® stent (Medtronic) implanted in native coronary arteries (≥3.0 mm). Among the 2929 patients included into the registries, 1205 had unstable angina (41 %). 50,2% of the patients were pretreated by T or C (T = 15.7%, C = 34.5%); 85.5% received aspirin before the procedure; definition of pretreatment was the administration of drug at least 6 hours before stent implantation. GPIIb-IIIa antagonists were administered in only 13.9% of patients. Mace were observed in 2% of the patients. Factors correlated with Mace by univariate and multivariate analyses were: age >73 years (RR: 2.37; 95 % CI: 1.05–5.36, P < 0.037) , previous myocardial infarction (RR: 2.56; 95% CI: 1.08–6.11, P <0.034), pretreatment by T or C (RR: 0.389; 95% CI: 0.16-0.95, P < 0.038). In patients who did not receive GPIIb-IIIa antagonists, age >73, and pretreatment by T or C were the only independent predictors of Mace. [Copyright &y& Elsevier]

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABAA–benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABAA–benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. [Copyright &y& Elsevier]

Preparative Scale Supercritical Fluid Chromatography is emerging as a powerful alternative to HPLC for the purification and separation of complex chemical reaction mixtures. Advantages include greatly reduced solvent usage (and thus lower cost and environmental impact), higher throughput, and in some cases higher resolution. While there are commercially available prep SFC instruments, none currently offer all the features desired by many medicinal chemists engaged in the drug discovery process. These include: the ability to collect an unlimited number of fractions per sample with high recovery and negligible carryover, fully automated capacity to collect several hundred fractions, and the ability to collect fractions into the same disposable test tubes and racks which are already employed in HPLC. This article describes the customization of a preparatory scale SFC system purchased from Berger Instruments, Inc., Newark, DE. (a subsidiary Mettler-Toledo International, Inc., of Greifensee, Switzerland) in order to provide these capabilities. [ABSTRACT FROM AUTHOR]

Objectives To assess the long term clinical impact of coronary artery disease (CAD) distribution in patients undergoing transcatheter aortic valve replacement (TAVR) using the FRench Aortic National CoreValve and Edwards (FRANCE-2) registry. Background CAD is common in patients undergoing TAVR. However, the impact of CAD distribution before TAVR on short and long-term prognosis remains unclear. Methods FRANCE-2 is a national French registry including all consecutive TAVR performed between 2010 and 2012 in 34 centres. Three-year mortality was assessed in relation to CAD status. CAD was define as at least one coronary stenosis > 50%. Results A total of 4201 patients were enrolled in the registry. For the present analysis, we excluded patients with a history of coronary artery bypass. CAD was reported in 1252 patients (30%). Half of patient presented with coronary multivessel disease. CAD extent was associated with an increase in cardiovascular risk-profile and in Logistic Euroscore (from 19.3 ± 12.8% to 21.9 ± 13.5%, P < 0.001). Mortality at 30 days and 3 years was 9% and 44% respectively in the overall population. In multivariate analyses, neither the presence nor the extent of CAD was associated with mortality at 3 years (presence of CAD: HR 0.90; 95% CI 0.78 to 1.07). Significant lesion of the left anterior descending (LAD) was associated with higher 3-year mortality (HR 1.42; 95% CI 1.10 to 1.87). Similar results were found after propensity score matching (428 patients per group). Conclusions CAD is not associated with decreased short and long-term survival in patients undergoing TAVR. The potential deleterious effect of LAD disease on long-term survival suggests the need for revascularization before or at the time of TAVR. [ABSTRACT FROM AUTHOR]