Prognostic and diagnostic value of EEG signal coupling measures in coma.

OBJECTIVE Our aim was to assess the diagnostic and predictive value of several quantitative EEG (qEEG) analysis methods in comatose patients. METHODS In 79 patients, coupling between EEG signals on the left-right (inter-hemispheric) axis and on the anterior-posterior (intra-hemispheric) axis was measured with four synchronization measures: relative delta power asymmetry, cross-correlation, symbolic mutual information and transfer entropy directionality. Results were compared with etiology of coma and clinical outcome. Using cross-validation, the predictive value of measure combinations was assessed with a Bayes classifier with mixture of Gaussians. RESULTS Five of eight measures showed a statistically significant difference between patients grouped according to outcome; one measure revealed differences in patients grouped according to the etiology. Interestingly, a high level of synchrony between the left and right hemisphere was associated with mortality on intensive care unit, whereas higher synchrony between anterior and posterior brain regions was associated with survival. The combination with the best predictive value reached an area-under the curve of 0.875 (for patients with post anoxic encephalopathy: 0.946). CONCLUSIONS EEG synchronization measures can contribute to clinical assessment, and provide new approaches for understanding the pathophysiology of coma. SIGNIFICANCE Prognostication in coma remains a challenging task. qEEG could improve current multi-modal approaches.

Structure of a mouse histone-encoding gene cluster

In addition to a previously described histone (H)-encoding H4 gene [Meier et al., Nucleic Acids Res. 17 (1989) 795], the mouse genomic DNA clone 53 contains two H3 genes, one functional and one partially deleted H2A gene, and one H2B gene. Clone 53 overlaps for 3 kb with MH143, another previously isolated mouse H-encoding clone [Yang et al., J. Biol. Chem. 262 (1987) 17118-17125], thus defining a 32-kb region of mouse chromosome 13 with a total of seven H-encoding genes. We have determined the nucleotide sequences and transcription start points of two genes coding for the H2A.1 and H3.2 proteins.

Cluster of Leptospirosis Acquired Through River Surfing in Switzerland

Background.  In Switzerland, leptospirosis is still considered as a travel-associated disease. After the surprising diagnosis of leptospirosis in a patient who was initially suspected as having primary human immunodeficiency virus infection, we recognized that acquisition of leptospirosis occurred through recreational activities and we identified additional affected individuals. Methods.  Detailed anamnesis, excluding occupational exposure, acquisition abroad, and pet contacts, enabled us to detect the source of infection and identify a cluster of leptospirosis. Convalescent sera testing was performed to confirm Leptospira infection. Microscopic agglutination tests were used to determine the infecting serovar. Results.  We identified a cluster of leptospirosis in young, previously healthy persons. Acquisition of leptospirosis was traced back to a surfing spot on a river in Switzerland (Reuss, Aargau). Clinical presentation was indistinct. Two of the 3 reported cases required hospitalization, and 1 case even suffered from meningitis. Serologic tests indicated infection with the serovar Grippotyphosa in all cases. With the exception of the case with meningitis, no antibiotics were administered, because leptospirosis was diagnosed after spontaneous resolution of most symptoms. Despite a prolonged period of convalescence in 2 cases, full recovery was achieved. Recent reports on beavers suffering from leptospirosis in this region underline the possible water-borne infection of the 3 cases and raise the question of potential wildlife reservoirs. Conclusions.  Insufficient awareness of caregivers, which may be promoted by the missing obligation to report human leptospirosis, combined with the multifaceted presentation of the disease result in significant underdiagnosis. More frequent consideration of leptospirosis as differential diagnosis is inevitable, particularly as veterinary data suggest re-emergence of the disease.

Charge exchange in cometary coma: Discovery of H- ions in the solar wind close to comet 67P/Churyumov-Gerasimenko

As Rosetta was orbiting comet 67P/Churyumov-Gerasimenko, the Ion and Electron Sensor detected negative particles with angular distributions like those of the concurrently measured solar wind protons but with fluxes of only about 10% of the proton fluxes and energies of about 90% of the proton energies. Using well-known cross sections and energy-loss data, it is determined that the fluxes and energies of the negative particles are consistent with the production of H- ions in the solar wind by double charge exchange with molecules in the coma.

Large-scale dust jets in the coma of 67P/Churyumov-Gerasimenko as seen by the OSIRIS instrument onboard Rosetta

Context. During the most recent perihelion passage in 2009 of comet 67P/Churyumov-Gerasimenko (67P), ground-based observations showed an anisotropic dust coma where jet-like features were detected at similar to 1.3 AU from the Sun. The current perihelion passage is exceptional as the Rosetta spacecraft is monitoring the nucleus activity since March 2014, when a clear dust coma was already surrounding the nucleus at 4.3 AU from the Sun. Subsequently, the OSIRIS camera also witnessed an outburst in activity between April 27 and 30, and since mid-July, the dust coma at rh similar to 3.7-3.6 AU preperihelion is clearly non-isotropic, pointing to the existence of dust jet-like features. Aims. We aim to ascertain on the nucleus surface the origin of the dust jet-like features detected as early as in mid-July 2014. This will help to establish how the localized comet nucleus activity compares with that seen in previous apparitions and will also help following its evolution as the comet approaches its perihelion, at which phase most of the jets were detected from ground-based observations. Determining these areas also allows locating them in regions on the nucleus with spectroscopic or geomorphological distinct characteristics. Methods. Three series of dust images of comet 67P obtained with the Wide Angle Camera (WAC) of the OSIRIS instrument onboard the Rosetta spacecraft were processed with different enhancement techniques. This was made to clearly show the existence of jet-like features in the dust coma, whose appearance toward the observer changed as a result of the rotation of the comet nucleus and of the changing observing geometry from the spacecraft. The position angles of these features in the coma together with information on the observing geometry, nucleus shape, and rotation, allowed us to determine the most likely locations on the nucleus surface where the jets originate from. Results. Geometrical tracing of jet sources indicates that the activity of the nucleus of 67P gave rise during July and August 2014 to large-scale jet-like features from the Hapi, Hathor, Anuket, and Aten regions, confirming that active regions may be present on the nucleus localized at 60. northern latitude as deduced from previous comet apparitions. There are also hints that large-scale jets observed from the ground are possibly composed, at their place of origin on the nucleus surface, of numerous small-scale features.

Dust measurements in the coma of comet 67P/Churyumov-Gerasimenko inbound to the Sun

Critical measurements for understanding accretion and the dust/gas ratio in the solar nebula, where planets were forming 4.5 billion years ago, are being obtained by the GIADA (Grain Impact Analyser and Dust Accumulator) experiment on the European Space Agency's Rosetta spacecraft orbiting comet 67P/Churyumov-Gerasimenko. Between 3.6 and 3.4 astronomical units inbound, GIADA and OSIRIS (Optical, Spectroscopic, and Infrared Remote Imaging System) detected 35 outflowing grains of mass 10(-10) to 10(-7) kilograms, and 48 grains of mass 10(-5) to 10(-2) kilograms, respectively. Combined with gas data from the MIRO (Microwave Instrument for the Rosetta Orbiter) and ROSINA (Rosetta Orbiter Spectrometer for Ion and Neutral Analysis) instruments, we find a dust/gas mass ratio of 4 +/- 2 averaged over the sunlit nucleus surface. A cloud of larger grains also encircles the nucleus in bound orbits from the previous perihelion. The largest orbiting clumps are meter-sized, confirming the dust/gas ratio of 3 inferred at perihelion from models of dust comae and trails.

Rotating dust particles in the coma of comet 67P/Churyumov-Gerasimenko

Context. During September and October 2014, the OSIRIS cameras onboard the ESA Rosetta mission detected millions of single particles. Many of these dust particles appear as long tracks (due to both the dust proper motion and the spacecraft motion during the exposure time) with a clear brightness periodicity. Aims. We interpret the observed periodic features as a rotational and translational motion of aspherical dust grains. Methods. By counting the peaks of each track, we obtained statistics of a rotation frequency. We compared these results with the rotational frequency predicted by a model of aspherical dust grain dynamics in a model gas flow. By testing many possible sets of physical conditions and grain characteristics, we constrained the rotational properties of dust grains. Results. We analyzed on the motion of rotating aspherical dust grains with different cross sections in flow conditions corresponding to the coma of 67P/Churyumov-Gerasimenko qualitatively and quantitatively. Based on the OSIRIS observations, we constrain the possible physical parameters of the grains.

Identification of a conserved cluster in the RH domain of GRK critical for activation by GPCRs

One of the most critical aspects of G Protein Coupled Receptors (GPCRs) regulation is their rapid and acute desensitization following agonist stimulation. Phosphorylation of these receptors by GPCR kinases (GRK) is a major mechanism of desensitization. Considerable evidence from studies of rhodopsin kinase and GRK2 suggests there is an allosteric docking site for the receptor distinct from the GRK catalytic site. While the agonist-activated GPCR appears crucial for GRK activation, the molecular details of this interaction remain unclear. Recent studies suggested an important role for the N- and C-termini and domains in the small lobe of the kinase domain in allosteric activation; however, neither the mechanism of action of that site nor the RH domain contributions have been elucidated. To search for the allosteric site, we first indentified evolutionarily conserved sites within the RH and kinase domains presumably deterministic of protein function employing evolutionary trace (ET) methodology and crystal structures of GRK6. Focusing on a conserved cluster centered on helices 3, 9, and 10 in the RH domain, key residues of GRK5 and 6 were targeted for mutagenesis and functional assays. We found that a number of double mutations within helices 3, 9, and 10 and the N-terminus markedly reduced (50–90%) the constitutive phosphorylation of the β-2 Adrenergic Receptor (β2AR) in intact cells and phosphorylation of light-activated rhodopsin (Rho*) in vitro as compared to wild type (WT) GRK5 or 6. Based on these results, we designed peptide mimetics of GRK5 helix 9 both computationally and through chemical modifications with the goal of both confirming the importance of helix 9 and developing a useful inhibitor to disrupt the GPCR-GRK interaction. Several peptides were found to block Rho* phosphorylation by GRK5 including the native helix 9 sequence, Peptide Builder designed-peptide preserving only the key ET residues, and chemically locked helices. Most peptidomimetics showed inhibition of GRK5 activity greater than 80 % with an IC50 of ∼ 30 µM. Alanine scanning of helix 9 has further revealed both essential and non-essential residues for inhibition. Importantly, substitution of Arg 169 by an alanine in the native helix 9-based peptide gave an almost complete inhibition at 30 µM with an IC50 of ∼ 10 µM. In summary we report a previously unrecognized crucial role for the RH domain of GRK5 and 6, and the subsequent identification of a lead peptide inhibitor of protein-protein interaction with potential for specific blockade of GPCR desensitization. ^

Kawasaki syndrome: Cluster analysis of incident cases presenting to a pediatric tertiary care hospital in Texas from January 1, 2005 to December 31, 2009

Background: Despite almost 40 years of research into the etiology of Kawasaki Syndrome (KS), there is little research published on spatial and temporal clustering of KS cases. Previous analysis has found significant spatial and temporal clustering of cases, therefore cluster analyses were performed to substantiate these findings and provide insight into incident KS cases discharged from a pediatric tertiary care hospital. Identifying clusters from a single institution would allow for prospective analysis of risk factors and potential exposures for further insight into KS etiology. ^ Methods: A retrospective study was carried out to examine the epidemiology and distribution of patients presenting to Texas Children’s Hospital in Houston, Texas, with a diagnosis of Acute Febrile Mucocutaneous Lymph Node Syndrome (MCLS) upon discharge from January 1, 2005 to December 31, 2009. Spatial, temporal, and space-time cluster analyses were performed using the Bernoulli model with case and control event data. ^ Results: 397 of 102,761 total patients admitted to Texas Children’s Hospital had a principal or secondary diagnosis of Acute Febrile MCLS upon over the 5 year period. Demographic data for KS cases remained consistent with known disease epidemiology. Spatial, temporal, and space-time analyses of clustering using the Bernoulli model demonstrated no statistically significant clusters. ^ Discussion: Despite previous findings of spatial-temporal clustering of KS cases, there were no significant clusters of KS cases discharged from a single institution. This implicates the need for an expanded approach to conducting spatial-temporal cluster analysis and KS surveillance given the limitations of evaluating data from a single institution.^

El cluster vitivinícola mendocino

Si bien en el campo de las políticas públicas nacionales la desregulación total de las distintas fases de la cadena vitivinícola emerge como el principal rasgo distintivo de los años noventa, en los principales ámbitos provinciales vinculados con el complejo han ido irrumpiendo algunas políticas y acciones regulatorias tendientes a alentar la reconversión productiva del sector, a promover el consumo y, fundamentalmente, la exportación de los distintos productos vitivinícolas. Un claro ejemplo de ello lo brinda el Tratado celebrado entre las Provincias de Mendoza y San Juan en el mes de noviembre de 1994 (ya en el mes de junio de dicho año, habían suscripto un Acta por la que se proponían realizar esfuerzos comunes en el ordenamiento de la industria vitivinícola), luego convertido en leyes provinciales por ambas cámaras legislativas.Por lo expuesto, el presente trabajo busca analizar el contexto y las causas que llevaron a la aplicación y continuidad del mencionado Acuerdo Interprovincial. Además, se pretende evaluar los resultados obtenidos por el mismo, y la situación actual del problema de sobreoferta de vinos. Los objetivos generales de la investigación son: -Analizar la importancia del cluster vitivinícola para la economía de la provincia de Mendoza y para Argentina misma. -Describir la evolución del sector y evaluar su condición de cluster productivo. En cuanto a los objetivos específicos, se mencionan: -Conocer la teoría referida al concepto de cluster productivo, y verificar si el sector en cuestión puede considerarse como tal. -Analizar las causas y consecuencias que tuvo la implementación del acuerdo interprovincial entre Mendoza y San Juan en el cluster mendocino. -Conocer el contexto que llevó a plantear el acuerdo, y los objetivos que perseguía. -Analizar si el acuerdo fue o no una buena medida para corregir los problemas que se presentaban en el momento y si cumplió sus objetivos. Comparar con las demás medidas barajadas para solucionar el mismo problema del sector (sobreexistencias vínicas).

Assamblages and cluster analysis from DSDP Hole 22-214 of the eastern Indian Ocean

Multivariate analyses of latest Pliocene through Holocene benthic foraminifera from 61 samples from Deep-Sea Drilling Project (DSDP) Site 214, eastem Indian Ocean were carried out. The 46 highest ranked species were used in R-mode factor analysis which has enabled to the identification of three environmentally significant assemblages at Site 214. Assemblage 1 is characterized by Uvigerina hispido-costata, Osangularia culter , Gavelinopsis lobatulus, Cibicides wuellerstorfi and Karreriella baccata as principal species. This assemblage is inferred to reflect high-energy, well-oxygenated and probably low-organic carbon deep-sea environment at Site 214. Assemblage 2 is defined principally by Globocassidulina pacifica and U. proboscidea and is considered to indicate an organic carbon-rich environment which resulted from high surface productivity irrespective of dissolved oxygen content. Assemblage 3 is marked by Oridorsalis umbonatus, Textularia lythostrota, Hoeglundina elegans, Pyrgo murrhina, and Pullenia quinqueloba as principal species. This assemblage is inferred to indicate a low-organic carbon environment with high pore water oxygen concentration leading to better preservation of deep-sea sediments.