Multicentre approach to epidemiological aspects of craniosynostosis in Germany.

We know of no current published data on the prevalence of craniosynostosis in Germany, so our objective in this study was to contribute to the limited knowledge of its epidemiology by assessing time trends, the frequency of prenatal diagnosis, and the timing of diagnosis and treatment. Data were collected in Saxony-Anhalt during the period 2000-17, and we designed a retrospective multicentre cohort study. The prevalence was 4.8 cases of craniosynostosis/10 000 births, and did not increase during that time. We compared the data of 91 patients with those of 273 controls. There were 75 boys and 16 girls (ratio 4.7:1). Fifty-one children had isolated craniosynostosis, consisting of 46 with a single-suture, and five with a multisuture, synostosis. Twenty-nine were associated with other congenital malformations, and 11 were syndromic. Three cases had been diagnosed prenatally, and 34 had skull deformities diagnosed immediately after birth at a mean (SD) age of 3.4 (4.7) months. The mean (SD) age at the time of first admission to hospital in one of the three surgical centres of Saxony-Anhalt was 5.9 (5.5) months, and 65 patients were operated on at a mean age of 9.1 (6.3) months. In contrast to published reports we found a prevalence of 4.8 cases of craniosynostosis/10 000 births that did not increase during the period 2000-16. Although we found a low prenatal detection rate, the diagnosis and treatment in this cohort study seemed timely.

Spin-orbit effects in optical spectra of gold-silver trimers.

Cationic gold-silver trimers are ideal model systems for the evaluation of relativistic electronic structure theories. The closed-shell triangles allow one to test density functional and wavefunction-based methods in their prediction of optical properties, as dependent on composition and symmetry. Here we present the gas-phase optical spectra of AgNAu3-N+ (N = 0-3) clusters recorded by longitudinal photodissociation spectroscopy in the photon energy range 1.9-4.4 eV. The experimental data are compared to excited electronic state calculations in the framework of all-electron range-separated time-dependent density functional and equation-of-motion coupled cluster theory using two-component as well as the spin-free scalar relativistic theories. In particular, it is shown that for mixed trimers scalar-relativistic corrections are insufficient and a two-component approach becomes obligatory for a correct description of optical response properties including both spin-orbit coupling and charge-transfer effects.

Pool-BCGA: a parallelised generation-free genetic algorithm for the ab initio global optimisation of nanoalloy clusters.

The Birmingham cluster genetic algorithm is a package that performs global optimisations for homo- and bimetallic clusters based on either first principles methods or empirical potentials. Here, we present a new parallel implementation of the code which employs a pool strategy in order to eliminate sequential steps and significantly improve performance. The new approach meets all requirements of an evolutionary algorithm and contains the main features of the previous implementation. The performance of the pool genetic algorithm is tested using the Gupta potential for the global optimisation of the Au10Pd10 cluster, which demonstrates the high efficiency of the method. The new implementation is also used for the global optimisation of the Au10 and Au20 clusters directly at the density functional theory level.

Influence of spin-orbit effects on structures and dielectric properties of neutral lead clusters.

Combining molecular beam electric deflection experiments and global optimization techniques has proven to be a powerful tool for resolving equilibrium structures of neutral metal and semiconductor clusters. Herein, we present electric molecular beam deflection experiments on PbN (N = 7-18) clusters. Promising structures are generated using the unbiased Birmingham Cluster Genetic Algorithm approach based on density functional theory. The structures are further relaxed within the framework of two-component density functional theory taking scalar relativistic and spin orbit effects into account. Quantum chemical results are used to model electric molecular beam deflection profiles based on molecular dynamics calculations. Comparison of measured and simulated beam profiles allows the assignment of equilibrium structures for the most cluster sizes in the examined range for the first time. Neutral lead clusters adopt mainly spherical geometries and resemble the structures of lead cluster cations apart from Pb10. Their growth pattern deviates strongly from the one observed for tin and germanium clusters.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

Exploring Flow, Factors, and Outcomes of Temporal Event Sequences with the Outflow Visualization.

Event sequence data is common in many domains, ranging from electronic medical records (EMRs) to sports events. Moreover, such sequences often result in measurable outcomes (e.g., life or death, win or loss). Collections of event sequences can be aggregated together to form event progression pathways. These pathways can then be connected with outcomes to model how alternative chains of events may lead to different results. This paper describes the Outflow visualization technique, designed to (1) aggregate multiple event sequences, (2) display the aggregate pathways through different event states with timing and cardinality, (3) summarize the pathways' corresponding outcomes, and (4) allow users to explore external factors that correlate with specific pathway state transitions. Results from a user study with twelve participants show that users were able to learn how to use Outflow easily with limited training and perform a range of tasks both accurately and rapidly.

A low-magnetic-field soft gamma repeater.

Soft gamma repeaters (SGRs) and anomalous x-ray pulsars form a rapidly increasing group of x-ray sources exhibiting sporadic emission of short bursts. They are believed to be magnetars, that is, neutron stars powered by extreme magnetic fields, B ~ 10(14) to 10(15) gauss. We report on a soft gamma repeater with low magnetic field, SGR 0418+5729, recently detected after it emitted bursts similar to those of magnetars. X-ray observations show that its dipolar magnetic field cannot be greater than 7.5 × 10(12) gauss, well in the range of ordinary radio pulsars, implying that a high surface dipolar magnetic field is not necessarily required for magnetar-like activity. The magnetar population may thus include objects with a wider range of B-field strengths, ages, and evolutionary stages than observed so far.

Persephonella marina gen. nov., sp. nov. and Persephonella guaymasensis sp. nov., two novel, thermophilic, hydrogen-oxidizing microaerophiles from deep-sea hydrothermal vents.

Two thermophilic, strictly chemolithoautotrophic, microaerophilic, hydrogen-oxidizing members of the Bacteria designated strain EX-H1T and strain EX-H2T were isolated from two separate deep-sea hydrothermal vent sites at 9 degrees N 104 degrees W in the Pacific Ocean and Guaymas Basin. The motile 2-4-microm-long rods were Gram-negative and non-sporulating. The temperature range for growth was between 55 and 80 degrees C for EX- H1T (optimum at 73 degrees C) and 55-75 C for EX-H2T (optimum at 70 C). Both strains grew fastest at 2.5% (w/v) NaCl and at pH 6, although growth was observed from pH 4.7 to pH 7.5. EX-H1T and EX-H2T were able to use elemental sulfur, thiosulfate or hydrogen as an electron donor, and oxygen (2-3%, v/v) or nitrate as an electron acceptor. EX-H1T was also able to use elemental sulfur as an electron acceptor. EX-H1T and EX-H2T further differed in their genomic G+C content (38.5 and 37.4 mol%, respectively) and 16S rRNA sequences (4% difference). Maximum-likelihood analysis of the 16S rRNA phylogeny placed both isolates within the Aquificales as a distinct lineage and showed them to be only about 85% similar to Aquifex pyrophilus. On the basis of phenotypic and phylogenetic characteristics, it is proposed that EX-H1T and EX-H2T belong to a new genus within the Aquificales, namely Persephonella gen. nov. It is further proposed that EX-H1T be named Persephonella marina sp. nov., the type species of the genus, and that EX-H2T be named Persephonella guaymasensis sp. nov., a second species in this genus.

Biogeography and ecological setting of Indian Ocean hydrothermal vents.

Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.

A novel virus family, the Rudiviridae: Structure, virus-host interactions and genome variability of the sulfolobus viruses SIRV1 and SIRV2.

The unenveloped, stiff-rod-shaped, linear double-stranded DNA viruses SIRV1 and SIRV2 from Icelandic Sulfolobus isolates form a novel virus family, the Rudiviridae. The sizes of the genomes are 32. 3 kbp for SIRV1 and 35.8 kbp for SIRV2. The virions consist of a tube-like superhelix formed by the DNA and a single basic 15.8-kD DNA-binding protein. The tube carries a plug and three tail fibers at each end. One turn of the DNA-protein superhelix measures 4.3 nm and comprises 16.5 turns of B DNA. The linear DNA molecules appear to have covalently closed hairpin ends. The viruses are not lytic and are present in their original hosts in carrier states. Both viruses are quite stable in these carrier states. In several laboratory hosts SIRV2 was invariant, but SIRV1 formed many different variants that completely replaced the wild-type virus. Some of these variants were still variable, whereas others were stable. Up to 10% nucleotide substitution was found between corresponding genome fragments of three variants. Some variants showed deletions. Wild-type SIRV1, but not SIRV2, induces an SOS-like response in Sulfolobus. We propose that wild-type SIRV1 is unable to propagate in some hosts but surmounts this host range barrier by inducing a host response effecting extensive variation of the viral genome.

Virtual reality exposure therapy for PTSD Vietnam Veterans: a case study.

Virtual reality (VR) integrates real-time computer graphics, body tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion. VR exposure (VRE) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder (PTSD). This report presents the results of the first Vietnam combat veteran with PTSD to have been treated with VRE. The patient was exposed to two virtual environments, a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle. The patient experienced a 34% decrease on clinician-rated PTSD and a 45% decrease on self-rated PTSD. Treatment gains were maintained at 6-month follow-up.

A virtual environment for the treatment of chronic combat-related post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is one of the most disabling psychopathological conditions affecting the veteran population. An estimated 830,000 U.S. veterans currently have symptoms of chronic combat-related PTSD. No therapeutic approach has proven to be consistently effective in the management of combat-related PTSD. Behavior therapies with an exposure element have proven more effective than most other types of treatment, but a significant number of patients do not seem to benefit from them, possibly because of difficulties imagining, visualizing, or describing their traumatic experiences. In this article, we describe Virtual Vietnam, a set of two virtual environments we have developed for the treatment of combat-related PTSD, and its use as one component of a comprehensive treatment program.

Viruses, plasmids and other genetic elements of thermophilic and hyperthermophilic Archaea.

We review and update the work on genetic elements, e.g., viruses and plasmids (exluding IS elements and transposons) in the kingdom Crenarchaeota (Thermoproteales and Sulfolobales) and the orders Thermococcales and Thermoplasmales in the kingdom Euryarchaeota of the archael domain, including unpublished data from our laboratory. The viruses of Crenarchaeota represent four novel virus families. The Fuselloviridae represented by SSVI of S. shibatae and relatives in other Sulfolobus strains have the form of a tailed spindle. The envelope is highly hydrophobic. The DNA is double-stranded and circular. Members of this group have also been found in Methanococcus and Haloarcula. The Lipothrivciridae (e.g., T TV1 to 3) have the form of flexible filaments. They have a core containing linear double-stranded DNA and DNA-binding proteins which is wrapped into a lipid membrane. The "Bacilloviridae" (e.g., TTV4 and SIRV) are stiff rods lacking this membrane, but also featuring linear double-stranded DNA and DNA-binding proteins. Both virus types carry on both ends structures involved in the attachment to receptors. Both types are represented in Thermoproteus and Sulfolobus. The droplet-formed novel Sulfolobus virus SNDV represents the "Guttaviridae" containing circular double-stranded DNA. Though head and tail viruses distantly resembling T phages or lambdoid phages were seen electronmicroscopically in solfataric water samples, no such virus has so far been isolated. SSV1 is temperate, TTV1 causes lysis after induction, the other viruses found so far exist in carrier states. The hosts of all but TTV1 survive virus production. We discuss the implications of the nature of these viruses for understanding virus evolution. The plasmids found so far range in size from 4.5 kb to about 40 kb. Most of them occur in high copy number, probably due to the way of their detection. Most are cryptic, pNOB8 is conjugative, the widespread pDL10 alleviates in an unknown way autotrophic growth of its host Desulfurolobus by sulfur reduction. The plasmid pTIK4 appears to encode a killer function. pNOB8 has been used as a vector for the transfer of the lac S (beta-galactosidase) gene into a mutant of S. solfataricus.

Primary and secondary detoxification in severe flecainide intoxication.

Since experience with primary and secondary detoxification in severe flecainide intoxications is limited, 2 different cases of flecainide intoxications are reported. In the first case, with plasma concentrations of 6500 ng/ml (therapeutic range: 200-980 ng/ml), the patient survived with a pacemaker and catecholamine support. In the second case, hemoperfusion terminated the need for emergency resuscitation during the initial phase, but was unsuccessful 3 h later. Even with a lower plasma concentration the patient died. Both patients had rapid onset of symptoms due to the very good bioavailability of the drug. Although it may be a rare intoxication, it is dangerous because of its quick onset and its efficiency in altering the cardiac stability. We recommend the prophylactic use of a pacemaker and gastric suction. The usefulness of hemoperfusion has not yet been proven.

cAMP- and diacylglycerol-mediated pathways elevate cytosolic free calcium concentration via dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels in normal rat anterior pituitary cells.

The effect of 8-bromocyclic AMP (8-Br-cAMP) and phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, on cytosolic free calcium concentration ([Ca2+]i) in normal rat anterior pituitary cells was examined. [Ca2+]i was monitored directly by the fluorescent indicator fura-2. 8-Br-cAMP as well as PMA elevated [Ca2+]i in a concentration-dependent manner. Forskolin (10 mumol/l), which activates adenylate cyclase, and 1-oleoyl-2-acetyl-glycerol (10 mumol/l), another activator of protein kinase C, also increased [Ca2+]i. Both the 8-Br-cAMP (2 mmol/l)- and the PMA (100 nmol/l)-induced increase in [Ca2+]i was dependent on the presence of extracellular calcium and could be inhibited by the calcium channel blockers Mg2+ and nifedipine, but not by omega-conotoxin (100 nmol/l). The half-maximally inhibitory concentrations of Mg2+ and nifedipine were about 12 mmol/l and 160 nmol/l, respectively, for the [Ca2+]i response to 8-Br-cAMP (2 mmol/l), and were about 6 mmol/l and 400 nmol/l, respectively, for the PMA (100 nmol/l)-induced increase in [Ca2+]i. The sodium channel blocker tetrodotoxin (5 mumol/l) or PMA (100 nmol/l) on [Ca2+]i. After pretreatment for 3 min with PMA (100 nmol/l), the subsequent K+ (100 mmol/l)- or arachidonic acid (3 mumol/l)-induced increase in [Ca2+]i was decreased by about 50%. By contrast, pretreatment (3 min) with 8-Br-cAMP (2-10 mmol/l) markedly enhanced the subsequent [Ca2+]i response to K+ (100 mmol/l), and left the effect of arachidonic acid (3 mumol/l) on [Ca2+]i unimpaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination.

The effect of dynorphin A-(1-13) (Dyn A-(1-13] and other opioids on the cytosolic free calcium concentration [(Ca2+]i) in rat anterior pituitary cells was examined using the fluorescent indicator fura-2. A commercial synthetic Dyn A-(1-13) preparation elevated [Ca2+]i. Results, which were obtained with receptor antagonists, and in LHRH receptor radioligand binding studies as well as by HPLC combined with LHRH radioimmunoassay, strongly suggest that this effect of the dynorphin preparation was due to contamination with a LHRH-like compound. Dyn A-(1-13), purified by HPLC, as well as Dyn A-(2-13), [Leu5]enkephalin, beta-endorphin, morphine, or U50,488H had no effect on [Ca2+]i. LHRH caused a rapid increase in [Ca2+]i by about 50 nM which was blocked by the LHRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6] LHRH.

Arachidonic acid elevates cytosolic free calcium concentration in rat anterior pituitary cells.

Arachidonic acid is liberated from phospholipids by various hypothalamic releasing hormones and may be involved in stimulus-secretion coupling in rat adenohypophysis. In the present study, the effect of exogenous arachidonic acid on calcium homeostasis in rat anterior pituitary cells was investigated in vitro. Arachidonic acid markedly stimulated the release of various anterior pituitary hormones (beta-endorphin, luteinizing hormone, growth hormone). Arachidonic acid (10 mumol/l) decreased the initial rate of 45Ca2+ uptake. In cells prelabelled with 45Ca2+, arachidonic acid (10 mumol/l) decreased the exchangeable cell calcium content and increased the rate of 45Ca2+ extrusion. Cytosolic free calcium concentration [( Ca2+]i) was measured with the fluorescent indicator fura-2. Arachidonic acid markedly elevated [Ca2+]i. The concentration dependency of this effect (1 mumol/l and above) was similar to that on hormone secretion. Arachidonic acid (6 mumol/l) elevated [Ca2+]i by about 300 nmol/l, and arachidonic acid (10 mumol/l) raised [Ca2+]i into the micromolar range. The effect of arachidonic acid (3 mumol/l) on [Ca2+]i was not influenced by inhibitors of arachidonic acid metabolism (nordihydroguaiaretic acid, BW755C). In Ca2+-free media (Ca2+ omitted, EGTA 2 mmol/l), the effect of arachidonic acid (3 mumol/l) on [Ca2+]i was almost unimpaired, whereas the effect of arachidonic acid (10 mumol/l) was reduced. Thus, the secretagogue arachidonic acid induces calcium mobilization and an increase in cytosolic free calcium concentration. These actions further qualify arachidonic acid as a potential intracellular mediator of stimulus-induced hormone secretion from rat adenohypophysis.

Effect of prostaglandin E2 on ACTH and beta-endorphin release from rat adenohypophysis in vitro after secretagogues which can mimic various first or second messengers.

The purpose of the present study was to further characterize the inhibition by prostaglandin E2 (PGE2) of adrenocorticotropin (ACTH) and beta-endorphin release from rat anterior pituitary fragments in vitro. Peptide hormone release was induced by vasopressin, which initiates secretion via cell surface receptors, or by secretagogues which can mimic various post-receptor mechanisms and the effect of PGE2 was examined. Concentration-response curves of the effect of vasopressin on the release of beta-endorphin-like (beta-End-IR) and ACTH-like immunoreactivity (ACTH-IR) were constructed in the absence or presence of a fixed concentration of PGE2. The concentration-response curve of vasopressin was shifted to the right about 8-fold by PGE2 (1 mumol/l) without altering the maximum effect. PGE2 (60 nmol/l-1 mumol/l) markedly reduced beta-End-IR release induced by 8-bromoadenosine-3',5'-cyclic-monophosphate (8Br-cAMP) (1 mmol/l). Omission of Ca2+ from the incubation medium did not prevent PGE2-induced inhibition of 8Br-cAMP-evoked secretion. 4 beta-Phorbol, 12 beta-myristate, 13 alpha-acetate (PMA) stimulated beta-End-IR and ACTH-IR release in a concentration-dependent manner. This effect was not blocked by indometacin or eicosatetraynoic acid. PG E2 (greater than 100 nmol/l) reduced PMA (100 nmol/l)-elicited secretion by about 50%. PG E2 (1 mumol/l) almost halved beta-End-IR release caused by K+ (30 mmol/l). After pre-incubation in Ca2+-free medium, re-introduction of Ca2+ (1.3 mmol/l) elicited beta-End-IR release. This response was abolished by PG E2 (1 mumol/l). The addition of Ba2+ (10 mmol/l) to a Ca2+-free medium markedly enhanced beta-End-IR release.(ABSTRACT TRUNCATED AT 250 WORDS)