Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls.

BackgroundAuditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.MethodsASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.ResultsG-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.DiscussionThe excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies

Super-orbital re-entry in Australia - laboratory measurement, simulation and flight observation

There are large uncertainties in the aerothermodynamic modelling of super-orbital re-entry which impact the design of spacecraft thermal protection systems (TPS). Aspects of the thermal environment of super-orbital re-entry flows can be simulated in the laboratory using arc- and plasma jet facilities and these devices are regularly used for TPS certification work [5]. Another laboratory device which is capable of simulating certain critical features of both the aero and thermal environment of super-orbital re-entry is the expansion tube, and three such facilities have been operating at the University of Queensland in recent years[10]. Despite some success, wind tunnel tests do not achieve full simulation, however, a virtually complete physical simulation of particular re-entry conditions can be obtained from dedicated flight testing, and the Apollo era FIRE II flight experiment [2] is the premier example which still forms an important benchmark for modern simulations. Dedicated super-orbital flight testing is generally considered too expensive today, and there is a reluctance to incorporate substantial instrumentation for aerothermal diagnostics into existing missions since it may compromise primary mission objectives. An alternative approach to on-board flight measurements, with demonstrated success particularly in the ‘Stardust’ sample return mission, is remote observation of spectral emissions from the capsule and shock layer [8]. JAXA’s ‘Hayabusa’ sample return capsule provides a recent super-orbital reentry example through which we illustrate contributions in three areas: (1) physical simulation of super-orbital re-entry conditions in the laboratory; (2) computational simulation of such flows; and (3) remote acquisition of optical emissions from a super-orbital re entry event

Early bilingual experience is associated with change detection ability in adults.

To adapt to their more varied and unpredictable (language) environments, infants from bilingual homes may gather more information (sample more of their environment) by shifting their visual attention more frequently. However, it is not known whether this early adaptation is age-specific or lasts into adulthood. If the latter, we would expect to observe it in adults who acquired their second language early, not late, in life. Here we show that early bilingual adults are faster at disengaging attention to shift attention, and at noticing changes between visual stimuli, than late bilingual adults. In one experiment, participants were presented with the same two visual stimuli; one changed (almost imperceptibly), the other remained the same. Initially, participants looked at both stimuli equally; eventually, they fixated more on the changing stimulus. This shift in looking occurred in the early but not late bilinguals. It suggests that cognitive processes adapt to early bilingual experiences

Is mere exposure enough? The effects of bilingual environments on infant cognitive development.

Bilinguals purportedly outperform monolinguals in non-verbal tasks of cognitive control (the 'bilingual advantage'). The most common explanation is that managing two languages during language production constantly draws upon, and thus strengthens, domain-general inhibitory mechanisms (Green 1998 Biling. Lang. Cogn. 1, 67-81. (doi:10.1017/S1366728998000133)). However, this theory cannot explain why a bilingual advantage has been found in preverbal infants (Kovacs & Mehler 2009 Proc. Natl Acad. Sci. USA 106, 6556-6560. (doi:10.1073/pnas.0811323106)). An alternative explanation is needed. We propose that exposure to more varied, less predictable (language) environments drive infants to sample more by placing less weight on consolidating familiar information in order to orient sooner to (and explore) new stimuli. To confirm the bilingual advantage in infants and test our proposal, we administered four gaze-contingent eye-tracking tasks to seven- to nine-month-old infants who were being raised in either bilingual (n = 51) or monolingual (n = 51) homes. We could not replicate the finding by Kovacs and Mehler that bilingual but not monolingual infants inhibit learned behaviour (experiment 1). However, we found that infants exposed to bilingual environments do indeed explore more than those exposed to monolingual environments, by potentially disengaging attention faster from one stimulus in order to shift attention to another (experiment 3) and by switching attention more frequently between stimuli (experiment 4). These data suggest that experience-driven adaptations may indeed result in infants exposed to bilingual environments switching attention more frequently than infants exposed to a monolingual environment

Gauss Composition for P^1, and the universal Jacobian of the Hurwitz space of double covers

We investigate the universal Jacobian of degree n line bundles over the Hurwitz stack of double covers of P^1 by a curve of genus g. Our main results are: the construction of a smooth, irreducible, universally closed (but not separated) moduli compactification of this universal Jacobian; a description of the global geometry and moduli properties of these stacks; and a computation of the Picard groups of these stacks in the cases when n-g is even. An important ingredient of our work is the parametrization of line bundles on double covers by binary quadratic forms. This parametrization generalizes the classical number theoretic correspondence between ideal classes of quadratic rings and integral binary quadratic forms, which in particular gives the group law on integral binary quadratic forms first discovered by Gauss.Comment: mathematical and expositional updates and improvements, 29 pages, 5 figure

Palladium und Kupfer-katalysierte Domino- und Multikomponentenreaktionen auf Basis der Kupplungs-Isomerisierungs-Reaktion

Die Kupplungs-Isomerisierungs-Reaktion (KIR), eine schnelle Sonogashira-Alkinylierung von elektronenziehenden Halogeniden und Propargylalkoholen gefolgt von einer basenkatalysierten Carbinol-Allenol-Enon-Isomerisierung, stellt einen milden und effizienten Zugang zu Chalkonen dar. Innerhalb der vorliegenden Arbeit konnten neue Dominoreaktionen entwickelt werden, die methodische Erweiterungen der KIR darstellen. Es ist gelungen die zwingend notwendige Akzeptorfunktionalität in situ mittels einer intramolekularen Carbopalladierungsreaktion zu erzeugen. Terminale Acetylene reagieren mit N-Iodphenylalkinylamiden in einer Carbopalladierungs-Sonogashira-Alkinylierungs-Dominosequenz zu Inylidendihydroindolonen; der Alkinsäureiodphenylester konnte mit 4 Anisylpropargylalkohol in einer Insertions-Kupplungs-Isomerisierungs-Reaktion zum Oxobutenylidenbenzofuranon umgesetzt werden. Entgegen dem Postulat, dass intramolekulare 5-exo-dig-Cyclisierungsreaktionen streng syn-stereospezifisch verlaufen, wurden die Inylidendihydroindolone als E/Z-Doppelbindungsisomere und das Oxobutenylidenbenzofuranon anti-stereoselektiv als Z Isomer erhalten. Neben der Einbindung eines metallorganischen Insertionsereignisses konnte zudem die irreversible Allenol-Enon-Tautomerie durch die Inkorporation von Propargylethern anstelle der entsprechenden Alkohole erfolgreich unterbunden werden. Das bislang elusive, hoch reaktive Allenintermediat kann jetzt in einer kinetisch und thermodynamisch kontrollierten intramolekularen Abfangreaktion adressiert werden. Die Insertions-KI-Diels-Alder-Dominoreaktion der Akzeptoren bzw. mit Propargylallylethern liefert die bislang unbekannte, stark fluoreszierende Substanzklasse der Spirobenzofuranone und Spiroindolone in moderaten bis guten Ausbeuten. DFT- und MP2-Rechnungen der konkurrierenden produktbildenden Schritte der intramolekularen Diels-Alder-Reaktion vs. der Claisen-Umlagerung des Vinylallenylallyletherintermediats zeigen sowohl eine kinetische als auch thermodynamische Präferenz der [4+2]-Cycloaddition. Mit der Erkenntnis dieser Molecular-Modeling Studien konnten die elektronische Natur und die sterischen Eigenschaften der Akzeptor- und Alkinkomponente so modifiziert werden, dass nun eine Claisen-Umlagerung als Folgereaktion das Intermediat adressiert. Die Kupplungs-Isomerisierungs-Claisen-Dominoreaktion von elektronenarmen Arylhalogeniden bzw. aromatischen Säurechloriden mit Propargyltritylethern zeigt eine bemerkenswerte Dichotomie im finalen Schritt und resultiert, als Folge selbst kleinster elektronisch diverser Substituenteneffekte, in der Bildung von Tricyclooctenen, Chalkone, 1H-Iso¬chro¬menen und Indanen. Die Sonogashira-Reaktion von terminalen Phenylacetylenen mit N-Iodphenylalkinylamiden bzw. Alkinsäureiodphenylestern liefert in einer Carbopalladierungs-Alkinylierungs-Reaktion die entsprechenden internen vinylogen Alkinoylderivate. Erfolgt die Umsetzung der in situ generierten Alkinoylester bzw. -amide mit primären oder sekundären Aminen im Sinne einer Aza-Michael-Addition, ist ein eleganter Zugang zu vinylogen Enaminocarbonsäureestern und -amiden geschaffen. Unter Verwendung der hier vorgestellten Insertions-Sonogashira-Aminovinylierungs-Dreikomponentenreaktion können im Ein-Topf-Verfahren maßgeschneiderte orangefarben bis rot fluoreszierende Push-Pull-Chromophore und in guten bis exzellenten Ausbeuten erhalten werden

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Polyclonal mucosa-associated invariant T cells have unique innate functions in bacterial infection

Mucosa-associated invariant T (MAIT) cells are a unique population of αβ T cells in mammals that reside preferentially in mucosal tissues and express an invariant Vα paired with limited Vβ T-cell receptor (TCR) chains. Furthermore, MAIT cell development is dependent upon the expression of the evolutionarily conserved major histocompatibility complex (MHC) class Ib molecule MR1. Using in vitro assays, recent studies have shown that mouse and human MAIT cells are activated by antigen-presenting cells (APCs) infected with diverse microbes, including numerous bacterial strains and yeasts, but not viral pathogens. However, whether MAIT cells play an important, and perhaps unique, role in controlling microbial infection has remained unclear. To probe MAIT cell function, we show here that purified polyclonal MAIT cells potently inhibit intracellular bacterial growth of Mycobacterium bovis BCG in macrophages (MΦ) in coculture assays, and this inhibitory activity was dependent upon MAIT cell selection by MR1, secretion of gamma interferon (IFN-γ), and an innate interleukin 12 (IL-12) signal from infected MΦ. Surprisingly, however, the cognate recognition of MR1 by MAIT cells on the infected MΦ was found to play only a minor role in MAIT cell effector function. We also report that MAIT cell-deficient mice had higher bacterial loads at early times after infection compared to wild-type (WT) mice, demonstrating that MAIT cells play a unique role among innate lymphocytes in protective immunity against bacterial infection