Silicon detector dark matter results from the final exposure of CDMS II.

We report results of a search for weakly interacting massive particles (WIMPS) with the silicon detectors of the CDMS II experiment. This blind analysis of 140.2 kg day of data taken between July 2007 and September 2008 revealed three WIMP-candidate events with a surface-event background estimate of 0.41(-0.08)(+0.20)(stat)(-0.24)(+0.28)(syst). Other known backgrounds from neutrons and 206Pb are limited to <0.13 and <0.08 events at the 90% confidence level, respectively. The exposure of this analysis is equivalent to 23.4 kg day for a recoil energy range of 7-100 keV for a WIMP of mass 10 GeV/c2. The probability that the known backgrounds would produce three or more events in the signal region is 5.4%. A profile likelihood ratio test of the three events that includes the measured recoil energies gives a 0.19% probability for the known-background-only hypothesis when tested against the alternative WIMP+background hypothesis. The highest likelihood occurs for a WIMP mass of 8.6 GeV/c2 and WIMP-nucleon cross section of 1.9×10(-41) cm2.

Results from a low-energy analysis of the CDMS II germanium data.

We report results from a reanalysis of data from the Cryogenic Dark Matter Search (CDMS II) experiment at the Soudan Underground Laboratory. Data taken between October 2006 and September 2008 using eight germanium detectors are reanalyzed with a lowered, 2 keV recoil-energy threshold, to give increased sensitivity to interactions from weakly interacting massive particles (WIMPs) with masses below ∼10 GeV/c(2). This analysis provides stronger constraints than previous CDMS II results for WIMP masses below 9 GeV/c(2) and excludes parameter space associated with possible low-mass WIMP signals from the DAMA/LIBRA and CoGeNT experiments.

Dark matter search results from the CDMS II experiment.

Astrophysical observations indicate that dark matter constitutes most of the mass in our universe, but its nature remains unknown. Over the past decade, the Cryogenic Dark Matter Search (CDMS II) experiment has provided world-leading sensitivity for the direct detection of weakly interacting massive particle (WIMP) dark matter. The final exposure of our low-temperature germanium particle detectors at the Soudan Underground Laboratory yielded two candidate events, with an expected background of 0.9 +/- 0.2 events. This is not statistically significant evidence for a WIMP signal. The combined CDMS II data place the strongest constraints on the WIMP-nucleon spin-independent scattering cross section for a wide range of WIMP masses and exclude new parameter space in inelastic dark matter models.

Search for axions with the CDMS experiment.

We report on the first axion search results from the Cryogenic Dark Matter Search (CDMS) experiment at the Soudan Underground Laboratory. An energy threshold of 2 keV for electron-recoil events allows a search for possible solar axion conversion into photons or local galactic axion conversion into electrons in the germanium crystal detectors. The solar axion search sets an upper limit on the Primakov coupling g(agammagamma) of 2.4x10(-9) GeV-1 at the 95% confidence level for an axion mass less than 0.1 keV/c2. This limit benefits from the first precise measurement of the absolute crystal plane orientations in this type of experiment. The galactic axion search analysis sets a world-leading experimental upper limit on the axioelectric coupling g(aee) of 1.4x10(-12) at the 90% confidence level for an axion mass of 2.5 keV/c2.

Nosocomial transmission clusters and risk factors in Moraxella catarrhalis.

We report an objective examination of nosocomial transmission events derived from long-term (10-year) data from a single medical centre. Cluster analysis, based on the temporal proximity of genetically identical isolates of the respiratory pathogen Moraxella catarrhalis, identified 40 transmission events involving 33 of the 52 genotypes represented by multiple isolates. There was no evidence of highly transmissible or outbreak-prone genotypes. Although most clusters were small (mean size 3.6 isolates) and of short duration (median duration 25 days), clustering accounted for 38.7% of all isolates. Significant risk factors for clustering were multi-bed wards, and winter and spring season, but bacterial antibiotic resistance, manifested as the ability to produce a beta-lactamase was not a risk factor. The use of cluster analysis to identify transmission events and its application to long-term data demonstrate an approach to pathogen transmission that should find wide application beyond hospital populations.

n-3 polyunsaturated fatty acid supplementation reverses stress-induced modifications on brain monoamine levels in mice.

The aim of this study was to examine the effects of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on stress responses in mice subjected to an unpredictable chronic mild stress (UCMS) procedure. Stress-induced modifications in coat and aggressiveness were evaluated, and phospholipid PUFA profiles and monoamine levels were analyzed in the frontal cortex, hippocampus, and striatum. The results showed that repeated exposure to mild stressors induced degradation in the physical state of the coat, lowered body weight gain, and increased aggressiveness, without any effect of n-3 PUFA supplementation. The UCMS induced a significant decrease in the levels of norepinephrine in the frontal cortex and striatum, and a nonsignificant decrease in the hippocampus. The tissue levels of serotonin (5-HT) were 40% to 65% decreased in the three brain regions studied. Interestingly, the n-3 PUFA supplementation reversed this stress-induced reduction in 5-HT levels. These findings showed that supplementation in n-3 long-chain PUFAs might reverse certain effects of UCMS in cerebral structures involved in stress-related behaviors.

Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity.

Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-HT(1B) receptor (5-HT(1B)R), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT(1B)R (Htr1b(KO) mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1b(KO) mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1b(KO) mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1b(KO) mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT.

Neuropeptides in psychiatric diseases: an overview with a particular focus on depression and anxiety disorders.

This paper aimed at reviewing the involvement of neuropeptides in various psychiatric diseases, particularly in depression, and anxiety disorders. General features of neuropeptides are first described, including the history of their discovery, their definition, classification, biosynthesis, transport, release, inactivation, as well as their interaction with specific neuronal receptors. The differences with classical neurotransmitters are mentioned, as well as the different patterns of co-transmission. Finally, different mechanisms, both at the cellular and at the systemic level, are proposed that may explain the involvement of these molecules in various psychiatric diseases. Indeed, at the cellular level, a neuropeptide can be involved in a psychiatric disease, either because it is co-localized with a classical neurotransmitter involved in a disease, or because the neuropeptide-containing neuron projects on a target neuron involved in the disease. At the systemic level, a neuropeptide can play a direct role in the expression of a symptom of the disease. This is illustrated by different examples.

Effect of dorsal periaqueductal gray lesions on cardiovascular and behavioral responses to cat odor exposure in rats.

Previously we demonstrated Fos expression in the dorsal periaqueductal gray (DPAG) of the rat following cat odor exposure. Further work correlated the response to cat odor with a sustained blood pressure increase and deployment of defense behavior. It was therefore of interest to determine whether lesions of the DPAG would abolish these two effects of cat odor exposure. Male Wistar rats were given excitotoxic NMDA (N-methyl-D-aspartate) lesions of the DPAG and anterior tectum under halothane, then implanted with blood pressure telemetric probes. Sham lesions were made with saline. Rats were then exposed to cat odor with a hide option, followed 2 weeks later by re-exposure to cat odor without a hide option. Controls were exposed to rat odor in the same way. Trends toward attenuation in defense and cardiovascular indices were found in lesioned rats for cat odor exposure with a hide option, but these were not significant. Re-exposure to cat fur without a hide option enhanced the cardiovascular response and under these conditions, lesioned rats showed a significant change of the heart rate and locomotor activity response to cat fur. However, the blood pressure response was not significantly attenuated. Thus, the present results support the Fos data and indicate that the DPAG is involved in the expression of some but not all of the cardiovascular and behavioral components of the response to cat odor.

Effect of dorsal periaqueductal gray lesion on cardiovascular and behavioural responses to contextual conditioned fear in rats.

Contextual conditioned fear in the rat is characterized by a freezing immobility associated with a marked increase in blood pressure, a slow increase in heart rate, and ultrasonic vocalizations. A previous Fos study also revealed a marked activation of the ventrolateral part of the periaqueductal gray (VLPAG) and a much smaller activation of its dorsal part (DPAG). Recent chemical blockade experiments indicate that the main role of the VLPAG in the response is to impose the immobility necessary for the expression of the freezing component. We now test the role of the DPAG to see if its small activation (as revealed by Fos) is of any functional significance in the contextual fear response. Large N-methyl-D-aspartate (NMDA) excitotoxic lesions that destroyed most of the DPAG were made in 10 rats. Another group of 10 rats had sham lesions with saline. The animals were then implanted with blood pressure telemetric probes, fear conditioned, and finally tested. There was no significant difference in the amount of freezing and in the blood pressure response between the two groups. However, there was a complete abolition of ultrasonic vocalizations and a significantly greater increase in heart rate in the DPAG-lesioned group. The effect on vocalization and heart rate may be explained by lesion of adjacent structures: the lateral PAG and the superior colliculus (baroreflex alteration), respectively. Thus, most of DPAG appears to play little role in the expression of the contextual fear response.

Activation of ventrolateral medullary neurons projecting to spinal autonomic areas after chemical stimulation of the central nucleus of amygdala: a neuroanatomical study in the rat.

Several studies have shown that the central nucleus of amygdala is involved in cardiovascular regulation. The control of this function may be mediated by activation of the ventrolateral medulla neurons that project to preganglionic neurons located in the intermediolateral nucleus of the spinal cord. The aim of the present study was to examine whether stimulation of the central nucleus of amygdala activated ventrolateral medulla neurons projecting to the intermediolateral nucleus. For this purpose, the injection of a retrograde tracer, the cholera toxin b subunit (CTb), into the intermediolateral nucleus of the T2 segment was combined with immunohistochemical detection of Fos protein following chemical stimulation of the central nucleus of amygdala. Results showed that retrogradely labeled neurons were found throughout the ventrolateral medulla. Moreover, chemical stimulation of the central nucleus of amygdala induced: (1) a decrease of arterial blood pressure; (2) an expression of Fos protein mainly in sub-populations of neurons located in the intermediate and caudal parts of the ventrolateral medulla; (3) a significantly higher number of double labeled neurons (CTb-immunoreactive/Fos-immunoreactive) in the rostral part of the ventrolateral medulla than in the other parts of this region. These results show that the central nucleus of amygdala influences the activity of brainstem neurons projecting to the intermediolateral nucleus. Data were discussed in terms of descending amygdalofugal pathways involved in the hypotension.

Double immunocytochemistry for the detection of Fos protein in retrogradely identified neurons using cholera toxin B subunit.

The focus of this paper was to describe a method combining the neuroanatomical technique of retrograde transport of cholera toxin B subunit (CTB) with the technique of Fos functional labeling. This method allowed us to evaluate whether neurons identified by retrograde tracing were activated following chemical stimulation of another brain area. We have used this method at the light microscopic level to determine whether the stimulation of the rostral ventrolateral medulla activated retrogradely labeled adrenal sympathetic preganglionic neurons in the spinal cord. CTB-containing neurons, Fos immunoreactive neurons and double labeled neurons were observed in spinal autonomic areas. These results suggest that the rostral ventrolateral medulla exerts a descending activation upon identified adrenal preganglionic neurons. The method described in this protocol can be applied for other brain areas in order to establish if a given structure can activate an identified population of neurons linked with a particular target of central or peripheral nervous system.

Autonomic dysreflexia increases plasma adrenaline level in the chronic spinal cord-injured rat.

Autonomic dysreflexia (AD) occurs in up to 80% of quadriplegics and high paraplegics and is characterized by exaggerated sympathetic reflexes which induced paroxysmal hypertension. The aim of this study was to determine if plasma catecholamine levels increased during autonomic dysreflexia in the chronic spinal cord-injured (SCI) rats with special care to adrenaline. Catecholamine samples were collected before, during and 1 h after AD induced hypertension with colorectal distension. Results showed that plasma noradrenaline and adrenaline levels increased respectively 1.5-fold and 5-fold during AD in the chronic SCI rats. This suggests substantial roles for these two hormones in mediating the cardiovascular changes during AD. Knowledge of catecholamine levels during AD may thus aid in determining pathophysiology and potential pharmacologic treatments of this autonomic dysfunction.

Expression of Fos protein in adrenal preganglionic neurons following chemical stimulation of the rostral ventrolateral medulla of the rat.

The ventrolateral medulla is known to be involved in the regulation of arterial blood pressure, especially via its connections with sympathetic preganglionic neurons (SPNs) mainly located in the intermediolateral nucleus of the spinal cord. It has been shown that stimulation of the rostral part of the ventrolateral medulla (RVLM) elicits a release of catecholamines from the adrenal medulla. The aim of the present study was to demonstrate the existence of a functional pathway between the RVLM and adrenal SPNs using the combination of a retrograde tract tracing technique (cholera toxin B subunit) with the immunohistochemical detection of Fos protein following the chemical stimulation of RVLM. The data obtained showed that: (1) chemical stimulation of the RVLM induced Fos immunoreactivity in the intermediolateral nucleus and particularly in SPNs projecting to the adrenal medulla; (2) along the thoracic segments T2-T12, 26.1% of retrogradely identified adrenal SPNs were Fos-immunoreactive with the greatest percentage (30.9%) in the T8 segment. These results favored a functional control of the RVLM on adrenal SPNs which may contribute to a substantial activation of the cardiovascular system via the release of adrenal catecholamines.

[Interobserver variation of the Global Assessment Scale. Study of 59 patients at admission to a general adult psychiatric unit]. / Etude de la fidélité interjuges du score EGF. Application à 59 patients lors de leur admission dans un pavillon de psychiatrie générale adulte.

UNLABELLED: In France, an analysis of the evaluation of psychiatric activity was done by a work group representing thirteen hospitals spread over the entire country. The group just recently published their final report in the form of an experimentation protocol for the description of psychiatric activity. The proposed methodology leads to some modifications of the existing data collection based on individual patient information sheets "fiche par patient", more particularly concerning new items such as the Global Assessment Scale (GAS or Axis V of DSM III-R): our first impression was that this new type of evaluation seemed to us somewhat subjective. We therefore decided to analyze the reliability of the score established by psychiatrists not familiar with its use. In the beginning the GAS score was evaluated in clinical cases (patients seen at their admission by two or three psychiatrists and scored afterwards independently), then in theoretical cases (34 cases types taken from the Health-Sickness Rating Scale of Luborsky) with the objective to improve the consensus between clinicians. RESULTS: The clinical case studies made in an adult psychiatry pavilion permitted evaluating 59 patients at admission, of which 25 by three judges and respectively 40, 28 and 41 by pairs. The global accuracy of the score obtained with the clinical cases seems satisfactory for a discipline such as psychiatry (Kappa of Cohen's coefficient = 0.51, p < 0.001 for 25 patients by three judges--Kappa = 0.45, p < 0.001 for the 109 pairs of evaluations). The more detailed study of the classes obtained a satisfactory consensus for the scores below 40 and above 60 (K = 0.46 to 0.59) but not entirely satisfactory for the scores in the mid range of the scale between 40 and 60 (K = 0.22 to 0.29) which represents 39% of the patients in the study; this is improved by grouping into larger classes this part of the scale and it is therefore advisable to use it that way. For the 34 theoretical cases taken from the Luborsky HSRS evaluated independently by three judges the results obtained are clearly not as good (global Kappa = 0.29, p < 0.01). That is perhaps due to the fact that these "case types" don't use the descriptive patient models generally used in France. Keeping in mind that the mid range of the scale should be interpreted prudently, the GAS scale can nevertheless be credited with a certain global objectivity in the case of neutral study. Would it be the same if the GAS study could influence the allocation of resources? Taking into account all the clinical practices in mental health, the question of how all the data of this type evaluation could be recorded and updated should also examined.