Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Safe and prolonged survival with long-term exposure to pomalidomide in relapsed/refractory myeloma.

BACKGROUND: The IFM2009-02 trial studied pomalidomide (4 mg daily, 21/28 versus 28/28) and dexamethasone in very advanced relapsed or refractory multiple myeloma (RRMM). We observed that 40% of patients had a prolonged progression-free survival (PFS) and subsequently overall survival (OS). We sought to analyze the characteristics of these patients and study the effect of long exposure to pomalidomide. DESIGN: We separated the studied population into two groups: 3 months to 1 year (<1 year) and more than 1 year (≥1 year) of treatment with pomalidomide and dexamethasone based on clinical judgment and historical control studies. We then analyzed the characteristics of patients according to duration of treatment. RESULTS: The overall response rate (ORR) for the <1-year group was 43%, the median PFS 4.6 months [95% confidence interval (95% CI) 3.8-6.4] with only 6% at 12 months, and the median OS was 15 months (11.7-20.3) and 40% at 18 months. For the ≥1-year group, the response rate and survival were strikingly different, ORR at 83%, median PFS 20.7 months (14.7-35.4), median OS not reached, and 91% at 18 months. CONCLUSION: Pomalidomide and dexamethasone favored prolonged and safe exposure to treatment in 40% of heavily treated and end-stage RRMM, a paradigm shift in the natural history of RRMM characterized with a succession of shorter disease-free intervals and ultimately shorter survival. Although an optimization of pomalidomide-dexamethasone regimen is warranted in advanced RRMM, we claim that pomalidomide has proven once more to change the natural history of myeloma in this series, which should be confirmed in a larger study.

[Text Comprehensibility of Hospital Report Cards]. / Verständlichkeit der Texte von Qualitätsvergleichen zu Krankenhausleistungen.

Objectives: Recently, the number of hospital report cards that compare quality of hospitals and present information from German quality reports has greatly increased. Objectives of this study were to a) identify suitable methods for measuring the readability and comprehensibility of hospital report cards, b) to obtain reliable information on the comprehensibility of texts for laymen, c) to give recommendations for improvements and d) to recommend public health actions. Methods: The readability and comprehensibility of the texts were tested with a) a computer-aided evaluation of formal text characteristics (readability indices Flesch (German formula) and 1. Wiener Sachtextformel formula), b) an expert-based heuristic analysis of readability and comprehensibility of texts (counting technical terms and analysis of text simplicity as well as brevity and conciseness using the Hamburg intelligibility model) and c) a survey of subjects about the comprehensibility of individual technical terms, the assessment of the comprehensibility of the presentations and the subjects' decisions in favour of one of the 5 presented clinics due to the better quality of data. In addition, the correlation between the results of the text analysis with the results from the survey of subjects was tested. Results: The assessment of texts with the computer-aided evaluations showed poor comprehensibility values. The assessment of text simplicity using the Hamburg intelligibility model showed poor comprehensibility values (-0.3). On average, 6.8% of the words used were technical terms. A review of 10 technical terms revealed that in all cases only a minority of respondents (from 4.4% to 39.1%) exactly knew what was meant by each of them. Most subjects (62.4%) also believed that unclear terms worsened their understanding of the information offered. The correlation analysis showed that presentations with a lower frequency of technical terms and better values for the text simplicity were better understood. Conclusion: The determination of the frequency of technical terms and the assessment of text simplicity using the Hamburg intelligibility model were suitable methods to determine the readability and comprehensibility of presentations of quality indicators. The analysis showed predominantly poor comprehensibility values and indicated the need to improve the texts of report cards.

Subthreshold Ξ

Results on the production of the double strange cascade hyperon Ξ^{-} are reported for collisions of p(3.5 GeV)+Nb, studied with the High Acceptance Di-Electron Spectrometer (HADES) at SIS18 at GSI Helmholtzzentrum for Heavy-Ion Research, Darmstadt. For the first time, subthreshold Ξ^{-} production is observed in proton-nucleus interactions. Assuming a Ξ^{-} phase-space distribution similar to that of Λ hyperons, the production probability amounts to P_{Ξ^{-}}=[2.0±0.4(stat)±0.3(norm)±0.6(syst)]×10^{-4} resulting in a Ξ^{-}/(Λ+Σ^{0}) ratio of P_{Ξ^{-}}/P_{Λ+Σ^{0}}=[1.2±0.3(stat)±0.4(syst)]×10^{-2}. Available model predictions are significantly lower than the measured Ξ^{-} yield.

Juvenile play experience does not affect nicotine sensitization and voluntary consumption of nicotine in adult rats.

Juvenile play experiences promote behavioral flexibility in rats. If other early positive experiences, such as tactile stimulation, are given prior to exposure to psychostimulants, the behavioral response to the drug is attenuated. The objective of the present study was to determine if the experience of juvenile play behavior would attenuate the response to nicotine. Two experiments were conducted: (1) behavioral sensitization to nicotine exposure, and (2) voluntary consumption of nicotine. For both experiments, rats were reared either with three same-sex peers (play group) or one adult (no play group) during their juvenile period. Then, as adults, half of each group was exposed to repeated injections of nicotine and the other half to saline. Prior play experience had no effect on behavioral sensitization or on voluntary consumption of nicotine. It remains to be determined whether juvenile experience with play influences the rewarding properties of nicotine in social contexts as adults.

Remimazolam sedation for awake tracheal intubation.

We present a case of a 55-year-old woman presenting for an elective minor procedure. Following a previous anaesthetic, a 'can't intubate, can't oxygenate' incident had been documented. She had since undergone awake tracheal intubation for procedures requiring general anaesthesia. We were able to safely facilitate awake tracheal intubation using remimazolam for sedation. Remimazolam is a novel ultra-short acting benzodiazepine with similar pharmacodynamic effects to its parent compound midazolam, having minimal cardiovascular or respiratory effects and offering excellent anxiolysis and amnesia. It has a significantly shorter duration of action than midazolam, making it a valuable sedative agent for awake tracheal intubation. The patient remained stable throughout the procedure, with minimal effects on the respiratory and cardiovascular systems. The quality of sedation was reported as highly satisfactory by both the patient and the team.

Does prenatal nicotine exposure alter the brain's response to nicotine in adolescence? A neuroanatomical analysis.

This study examined changes in dendritic morphology and spine density in multiple brain regions [Zilles' areas: (i) the Cg3 region of the anterior cingulate cortex or the medial prefrontal cortex, layer III (Cg3); (ii) the dorsal agranular insular cortex, layer III (AID); (iii) the PAR I region of the parietal cortex, layer III (Par1) and (iv) the nucleus accumbens (NAc)]of Long-Evans rats following exposure to nicotine prenatally, in late adolescence, or both prenatally and in adolescence. Prenatal nicotine exposure induced enduring changes in neuroanatomical organisation that varied between male and female offspring, with males exhibiting increased dendritic complexity of neurons in AID and NAc whereas females experienced increased dendritic complexity in Par1 but decreased dendritic complexity of neurons in NAc. Similarly, nicotine given in late adolescence dramatically reorganised neural circuitry of both male and female offspring, with males exhibiting decreased dendritic complexity of neurons in Par1 and Cg3 but increased dendritic complexity in AID, and females exhibiting decreased dendritic complexity in Cg3 and NAc but increased complexity in AID. Exposure to nicotine both prenatally and in adolescence produced few neuroanatomical parameters that demonstrated a prenatal experience × adolescent drug administration interaction. Females showed additive effects in Par1, Cg3 and NAc whereas males demonstrated additive effects only in AID. Thus, the timing of nicotine exposure produced differential effects on cerebral organisation in a regionally specific manner.

Effects of rat prenatal exposure to valproic acid on behaviour and neuro-anatomy.

Autism is a highly debilitating disorder that has recently displayed a dramatic rise in incidence. In order to realistically study preventative and remedial strategies, it is important that we develop and understand useful animal models of the disorder. The purpose of this study was to investigate the efficacy of the prenatal valproic acid (VPA) rat model of autism by examining the neuro-anatomical and behavioural outcomes of offspring exposed to this paradigm. The VPA-treated rats exhibited behavioural changes in the delayed non-match-to-sample task, novel object recognition, activity box, and Whishaw tray reaching task. Anatomically, there was a reduction in brain weight and cortical thickness, along with decreased dendritic branching in the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC), and decreased spine density in the mPFC, OFC, and cerebellum. Behavioural and anatomical findings from this study produced reliable results indicating that prenatal VPA exposure may be a viable model for the study of autism in rats.

Difficult airways: a 3D printing study with virtual fibreoptic endoscopy.

Head and neck cancer patients present unique airway challenges, and oropharyngeal, laryngeal, and hypopharyngeal tumours considerably distort and narrow the anatomy of the airway. We describe the use of 3D augmented reality software combined with 3D printed models to assess the anatomy of difficult airways and to assist in the formulation of the most optimal airway management strategy in such patients. The reported patients had computed tomograms (CT) of the neck prior to their anaesthetic and surgical management. DICOM files of the respective scans were imported to 3D rendering software (OsiriX, Pixmeo). We constructed volume rendered models for initial assessment of the airway then generated serial surface rendered models to create a virtual endoscopic path of the airway to simulate the fibreoptic approach. To further facilitate the study of difficult airways we have subsequently printed 3D models of those that were most difficult using rapid prototyping. Head and neck tumours significantly distort the airway. Thorough study of the relevant anatomy prior to airway management for operating reasons enhances communication between the surgeon and anaesthetist, and aids selection of the most appropriate intubation approach. In conclusion, this paper highlights a useful and novel pre-assessment strategy that allows a virtual, visual, 3-dimensional assessment of the airway anatomy combined with 3D modelling and 3D printing. This enables the airway specialist, anaesthetist, and head and neck surgeon to anticipate any critical steps and adjust the plan accordingly.

Functional development of prefrontal cortex in rats continues into adolescence.

Bilateral removal of the sulcal prefrontal cortex in rats at 60 days of age and older results in aphagia and adipsia, but removal of this area before 60 days of age does not affect food or water regulation. Apparently the development of the role of this neocortical region in feeding and drinking continues well beyond the time of weaning in the rat.

Affective behavior in patients with localized cortical excisions: role of lesion site and side.

The perception of emotion in verbal and facial expression, and the spontaneous production of conversational speech were studied in patients with unilateral focal excisions of frontal, temporal, or parieto-occipital cortex. Lesions of the left hemisphere impaired the matching of verbal descriptions to appropriate verbal categories of emotional states, whereas with lesions of the right hemisphere, the matching of different faces displaying similar emotional states was impaired. The effects of lesions of both left and right hemisphere occurred regardless of the locus of the lesion. On the other hand, frontal-lobe lesions had differential effects upon unsolicited talking; lesions of the left frontal lobe virtually abolished this behavior, whereas lesions of the right frontal lobe produced excessive talking. These data suggest that the nature of the behavioral stimulus as well as the locus and side of damage must be considered in the study of the neural basis of affective behavior.

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Chronic inhibition of cyclooxygenase-2 induces dendritic hypertrophy and limited functional improvement following motor cortex stroke.

The cyclooxygenase-2 (COX-2) enzyme is part of the inflammatory pathway and is induced within the brain by a variety of pathological events, including ischemia. Pharmacological agents that inhibit COX-2 have been found to be neuroprotective in a number of injury models, and long-term administration of these drugs has been shown to induce plastic changes in the brain. In the current experiment, we investigated the effectiveness of stimulating cortical plasticity following stroke injury through the administration of the COX-2 inhibitor drug NS398. Furthermore, we determined whether the induced plastic changes improved functional outcome following motor cortex stroke. Chronic drug administration was found to induce dendritic hypertrophy in cells in the parietal cortex, and this anatomical change was associated with the animals making significantly more reach attempts, as well as successful reaches during a skilled reaching task. Additional motor tests however revealed that the treatment did not affect the level of motor recovery, as the animals showed chronic impairments in the Schallert cylinder, and the forepaw inhibition tasks. Short-term administration of the drug, immediately following the stroke did not induce any dendritic changes, nor was it found to improve behavioral performance on any of the motor tasks. Based on these results we conclude that the plastic changes that are induced by long-term COX-2 inhibitor administration provide some benefit to functional outcome following ischemic cortical injury.

Enriched environment improves motor function in intact and unilateral dopamine-depleted rats.

Previous studies have suggested that experience and environmental conditions can affect the progression and severity of symptoms in Parkinson's disease. Furthermore, earlier reports have indicated that enriched environment promotes the survival of dopaminergic grafts in a rat model of Parkinson's disease. Here we investigated whether environmental enrichment affects normal motor function and the severity of dopamine depletion in a rat model of Parkinson's disease. Adult female Long-Evans rats were pre-trained and tested daily in a skilled reaching task. One group of rats was placed in an enriched environment while one group was housed under standard conditions. During this time period, reaching success of animals exposed to the enriched environment improved as compared with animals living in standard housing. The animals remained in the two housing conditions for six weeks prior to receiving unilateral infusion of the neurotoxin 6-hydroxydopamine into the nigrostriatal bundle. The daily behavioral testing continued up to four weeks after lesion. The observations showed that rats housed in an enriched environment significantly improved in reaching success during the first three weeks after lesion as compared with rats housed in the standard condition. Qualitative movement analysis, drug-induced rotation and histological findings indicate that compensatory processes in particular might have accounted for the behavioral improvements. These data are discussed in relation to possible mechanisms of experience-dependent modulation of the pathology of Parkinson's disease.

Experience-dependent amelioration of motor impairments in adulthood following neonatal medial frontal cortex injury in rats is accompanied by motor map expansion.

One of the most common, and disruptive, neurological symptoms following neonatal brain injury is a motor impairment. Neonatal medial frontal cortical lesions in rats produce enduring motor impairments, and it is thought that lesion-induced abnormal cortical morphology and connectivity may underlie the motor deficits. In order to investigate the functional consequences of the lesion-induced anatomical abnormalities in adulthood, we used intracortical microstimulation to determine the neurophysiologic organization of motor maps within the lesion hemisphere. In addition, groups of neonatal lesion rats were given reach training or complex housing rehabilitation in adulthood and then mapped with intracortical microstimulation. The results demonstrate that neonatal medial frontal cortex lesions produce motor deficits in adulthood that are associated with abnormal motor maps. Further, adult behavioral treatment promoted partial recovery that was supported by reorganization of the motor maps whereby there were increases in the size of the forelimb motor maps. The experience-induced expansion of the forelimb motor maps in adulthood provides a neural mechanism for the experience-dependent improvements in motor performance.

Differential expression of basic fibroblast growth factor-2 in the developing rat brain.

Basic fibroblast growth factor-2 is a trophic molecule involved in a number of functions within the CNS, including the regulation of CNS responses to injury. Prior studies suggest that rats recover differently from injury inflicted to different regions and at different ages throughout development, and that basic fibroblast growth factor-2 may, at least in part, underlie this phenomenon. In the present study, we describe the distribution of basic fibroblast growth factor-2 at postnatal days 0, 2, 6, 10, 12, 14, 18, 21 and 30 in the indusium griseum, the external capsule, the hippocampus, the medial prefrontal cortex, the motor cortex, the rostral migratory stream, and the subventricular zone. Our results suggest a differential temporal and spatial expression of basic fibroblast growth factor-2 throughout development, which may explain the differential recovery observed from cortical lesions inflicted at different time points after birth.

[Legionellosis due to Legionella gormanii fortuitously found in a man with chronic lymphocytic leukemia: a case study and literature review]. / Légionellose à Legionella gormanii de découverte fortuite et leucémie lymphoïde chronique: à propos d'un cas et revue de la littérature.

Legionellosis due to other species than Legionella pneumophila is rarely described in human cases. It has been reported in immunocompromised patients with respiratory symptoms of pneumonia. We report a case of legionellosis in an immunocompromised 54-year-old man hospitalized for a blood transfusion. A routine pulmonary X- Ray was made and then a bronchoalveolar lavage was collected in which Legionella gormanii was identified. The diagnostic of legionellosis must be considered in all immunocompromised patients presenting with any pulmonary symptoms.

Chronic stress induces persistent changes in global DNA methylation and gene expression in the medial prefrontal cortex, orbitofrontal cortex, and hippocampus.

Chronic stress is associated with a plethora of cognitive symptoms such as emotional dysregulation and impaired executive function that have been attributed to modifications in neuroanatomy in the orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and hippocampus (HPC). While many studies have examined stress-induced changes in neuronal morphology, synaptic plasticity, and cellular function, there has been little investigation into persistent changes in gene expression that may be responsible for the maintenance of these changes. This study exposed adult rats to a chronic stressor and then examined changes in mRNA gene expression in the OFC, mPFC and HPC following a two-week withdrawal period. mRNA bio-sequencing results revealed sex- and region-dependent changes. Surprisingly the greatest changes in gene expression were found in the OFC, and similar to anatomical studies, analysis of gene changes with Ingenuity Pathway Analysis software demonstrated that the mPFC and OFC exhibited contrasting activation of canonical pathways and functional networks. The HPC demonstrated the largest degree of sex-dependent change in gene expression. In general, chronic stress induced persistent changes in gene expression in the three brain regions we examined and these changes could be associated with the commonly reported cognitive symptoms. The current study highlights the region- and sex-dependent nature of the brain's response to chronic stress and the difficulty we face when attempting to develop treatment options.

Basic fibroblast growth factor stimulates functional recovery after neonatal lesions of motor cortex in rats.

Rats were given bilateral lesions of the motor cortex on the tenth day of life, and then received a daily subcutaneously injection of either basic fibroblast growth factor (FGF-2) or vehicle for 7 consecutive days. In adulthood, they were trained and assessed on a skilled forelimb reaching task. Although all lesion groups were impaired at skilled reaching, the postnatal day 10-lesioned group that received FGF-2 was less impaired than the lesion group that received the vehicle. Furthermore, the lesioned rats that received FGF-2 showed a filling of the lesion cavity with tissue, whereas the lesioned vehicle-treated rats still had a prominent lesion cavity. The functionality of the tissue filling the cavity, tissue surrounding it, and tissue from the motor cortex (in control rats) was assessed using intracortical microstimulation, and showed that stimulation of some sites from the filled cavity could evoke movement. The rats were perfused and processed for Golgi-Cox staining. Medium spiny neurons from the striatum were drawn and analyzed, and the results suggest that postnatal day 10 lesions of the motor cortex induced an increase in the length and complexity of these cells compared with those of non-lesioned rats. Our results suggest that FGF-2 may play an important role in recovery from early brain damage.