Reinstating the Novelty P3

P300 (or P3) is a major positive complex in the human event-related potential, occurring some 300 ms after stimulus onset, and long thought to be the cortical correlate of the Orienting Reflex, our automatic attention-grabbing response to a novel stimulus. The Novelty P3 was the third P3 subcomponent discovered (after P3a and P3b) and appeared promising in its sensitivity to stimulus novelty, the defining characteristic of the Orienting Reflex. But some 15 years later it was claimed to be indistinguishable from the previously-discovered P3a. This led to a decline in interest in the field and confused nomenclature, with some studies using P3a and Novelty P3 interchangeably. However, recent similar studies have again reported three subcomponents of the P3. Further, using single-stimulus habituation paradigms, in addition to P3a and P3b, a later decrementing P3 subcomponent has been reported, and recently labelled HabP3 to avoid contention. We report three studies to resolve this chaotic situation, arguing for identification of the late subcomponent following the P3a and P3b as the Novelty P3. Reinstatement of the Novelty P3 as the central index of the Orienting Reflex will have widespread impact in a range of theoretical, practical, and clinical areas involving novelty processing and attention

CHEMICALLY MODIFIED PHOTOSYNTHETIC BACTERIAL REACTION CENTERS: CIRCULAR DICHROISM, RAMAN RESONANCE, LOW TEMPERATURE ABSORPTION, FLUORESCENCE AND ODMR SPECTRA AND POLYPEPTIDE COMPOSITION OF BOROHYDRIDE TREATED REACTION CENTERS FROM Rhodobacter sphaeroides R26

Reaction centers from Rhodobacter sphaeroides have been modified by treatment with sodium borohydride similar to the original procedure [Ditson et al., Biochim. Biophys. Acta 766, 623 (1984)], and investigated spectroscopically and by gel electrophoresis. (1) Low temperature (1.2 K) absorption, fluorescence, absorption- and fluorescence-detected ODMR, and microwave-induced singlet-triplet absorption difference spectra (MIA) suggest that the treatment produces a spectroscopically homogeneous preparation with one of the ‘additional’ bacteriochlorophylls being removed. The modification does not alter the zero field splitting parameters of the primary donor triplet (TP870). (2) From the circular dichroism and Raman resonance spectra in the1500–1800 cm-1 region, the removed pigment is assigned to BchlM, e.g. the "extra" Bchl on the "inactive" M-branch. (3) A strong coupling among all pigment molecules is deduced from the circular dichroism spectra, because pronounced band-shifts and/or intensity changes occur in the spectral components assigned to all pigments. This is supported by distinct differences among the MIA spectra of untreated and modified reaction centers, as well as by Raman resonance. (4) The modification is accompanied by partial proteolytic cleavage of the M-subunit. The preparation is thus spectroscopically homogeneous, but biochemically heterogenous

Commitment to Breastfeeding in the Context of Phenylketonuria

Objective: To describe the meaning and importance of breastfeeding to mothers of infants with phenylketonuria (PKU). Design: Qualitative description. Setting: Mothers from the United States and Canada were recruited from the PKU Listserv and interviewed by telephone. Participants: Ten breastfeeding mothers with infants who had PKU and were younger than age 36 months. Methods: Mothers’ thoughts, decisions, and experiences of breastfeeding their infants with PKU were collected through telephone interviews. Interviews were transcribed verbatim, and data were analyzed using thematic descriptive analysis in the context of PKU. Results: Participants felt that that breastfeeding an infant with PKU was the healthiest choice and was therefore worth the labor. These women believed that this was what a loving mother would choose. As they continued to breastfeed their infants after diagnosis, the views of the participants changed. Initially they saw PKU as a disorder and felt that their infants were ill; later they felt that their infants were healthy in spite of PKU. Normal could mean a breastfeeding infant with PKU. Conclusion: Findings demonstrate the importance mothers attribute to breastfeeding and their willingness to invest considerable effort to breastfeed. Health care providers working with these mothers should help them strategize for success

Total lung capacity by plethysmography and high-resolution computed tomography in COPD

Jamie L Garfield, Nathaniel Marchetti, John P Gaughan, Robert M Steiner, Gerard J CrinerDepartment of Pulmonary and Critical Care Medicine and Department of Radiology, Temple University School of Medicine, Philadelphia, Pennsylvania, USAAim: To characterize and compare total lung capacity (TLC) measured by plethysmography with high-resolution computed tomography (HRCT), and to identify variables that predict the difference between the two modalities.Methods: Fifty-nine consecutive patients referred for the evaluation of COPD were retrospectively reviewed. Patients underwent full pulmonary function testing and HRCT within 3 months. TLC was obtained by plethysmography as per American Thoracic Society/European Respiratory Society standards and by HRCT using custom software on 0.75 and 5 mm thick contiguous slices performed at full inspiration (TLC).Results: TLC measured by plethysmography correlated with TLC measured by inspiratory HRCT (r = 0.92, P < 0.01). TLC measured by plethysmography was larger than that determined by inspiratory HRCT in most patients (mean of 6.46 ± 1.28 L and 5.34 ± 1.20 L respectively, P < 0.05). TLC measured by both plethysmography and HRCT correlated significantly with indices of airflow obstruction (forced expiratory volume in 1 second/forced vital capacity [FVC] and FVC%), static lung volumes (residual volume, percent predicted [RV%], total lung capacity, percent predicted [TLC%], functional residual capacity, percent predicted [FRC%], and inspiratory capacity, percent predicted), and percent emphysema. TLC by plethysmography and HRCT both demonstrated significant inverse correlations with diffusion impairment. The absolute difference between TLC measured by plethysmography and HRCT increased as RV%, TLC%, and FRC% increased. Gas trapping (RV% and FRC%) independently predicted the difference in TLC between plethysmography and HRCT.Conclusion: In COPD, TLC by plethysmography can be up to 2 L greater than inspiratory HRCT. Gas trapping independently predicts patients for whom TLC by plethysmography differs significantly from HRCT.Keywords: lung capacity, plethysmography, high-resolution computed tomography, gas trapping, lung volume measurement error

Evaluation of miglustat as maintenance therapy after enzyme therapy in adults with stable type 1 Gaucher disease: a prospective, open-label non-inferiority study.

BACKGROUND: Previous studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy. METHODS: Adult type 1 Gaucher disease patients stabilized during at least 3 years of previous enzyme therapy were included in this 2-year, prospective, open-label non-inferiority study. The primary endpoint was percent change from baseline in liver volume. Secondary endpoints included changes in spleen volume, hemoglobin concentration and platelet count. RESULTS: Forty-two patients were enrolled (mean±SD age, 45.1±12.7 years; previous enzyme therapy duration 9.5±4.0 years). Median (range) exposure to miglustat 100 mg t.i.d. was 658 (3-765) days. Twenty-one patients discontinued treatment prematurely; 13 due to adverse events, principally gastrointestinal. The upper 95% confidence limit of mean percent change in liver volume from baseline to end of treatment was below the non-inferiority margin of 10% (-1.1%; 95%CI -6.0, 3.9%). Mean (95%CI) changes in spleen volume, hemoglobin concentration and platelet count were 102 (24,180) mL, -0.95 (-1.38, -0.53) g/dL and -44.1 (-57.6, -30.7) ×109/L, respectively. CONCLUSIONS: The primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy. Several patients showed a gradual deterioration in some disease manifestations, suggesting that miglustat could maintain clinical stability, but not in all patients. Miglustat demonstrated a predictable profile of safety and tolerability that was consistent with that reported in previous clinical trials and experience in clinical practice. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00319046.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Magnetohydrodynamics of the Weakly Ionized Solar Photosphere

We investigate the importance of ambipolar diffusion and Hall currents for high-resolution comprehensive ('realistic') photospheric simulations. To do so we extended the radiative magnetohydrodynamics code \emph{MURaM} to use the generalized Ohm's law under the assumption of local thermodynamic equilibrium. We present test cases comparing analytical solutions with numerical simulations for validation of the code. Furthermore, we carried out a number of numerical experiments to investigate the impact of these neutral-ion effects in the photosphere. We find that, at the spatial resolutions currently used (5-20 km per grid point), the Hall currents and ambipolar diffusion begin to become significant -- with flows of 100 m/s in sunspot light bridges, and changes of a few percent in the thermodynamic structure of quiet-Sun magnetic features. The magnitude of the effects is expected to increase rapidly as smaller-scale variations are resolved by the simulations.Comment: accepted Ap

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

Neuronal correlates of cognitive control are altered in women with endometriosis and chronic pelvic pain

Endometriosis is a debilitating women's health condition and is the most common cause of chronic pelvic pain. Impaired cognitive control is common in chronic pain conditions, however, it has not yet been investigated in endometriosis. The aim of this study was to explore the neuronal correlates of cognitive control in women with endometriosis. Using a cross-sectional study design with data collected at a single time-point, event-related potentials were elicited during a cued continuous performance test from 20 women with endometriosis (mean age = 28.5 ± 5.2 years) and 20 age- and gender-matched controls (mean age = 28.5 ± 5.2 years). Event-related potential components were extracted and P3 component amplitudes were derived with temporal principal components analysis. Behavioral and ERP outcomes were compared between groups and subjective pain severity was correlated with ERP component amplitudes. No significant behavioral differences were seen in task performance between the groups (all p > 0.094). Target P3b (all p < 0.034) and SW (all p < 0.040), and non-target early P3a (eP3a; all p < 0.023) and late P3a (lP3a; all p < 0.035) amplitudes were smaller for the endometriosis compared to the healthy control group. Lower non-target eP3a (p < 0.001), lP3a (p = 0.013), and SW (p = 0.019) amplitudes were correlated with higher pain severity scores. Findings suggest that endometriosis-associated chronic pelvic pain is linked to alterations in stimulus-response processing and inhibitory control networks, but not impaired behavioral performance, due to compensatory neuroplastic changes in overlapping cognitive control and pain networks

On the Origin of the Treponematoses: A Phylogenetic Approach

For 500 years, controversy has raged around the origin of T. pallidum subsp. pallidum, the bacterium responsible for syphilis. Did Christopher Columbus and his men introduce this pathogen into Renaissance Europe, after contracting it during their voyage to the New World? Or does syphilis have a much older history in the Old World? This paper represents the first attempt to use a phylogenetic approach to solve this question. In addition, it clarifies the evolutionary relationships between the pathogen that causes syphilis and the other T. pallidum subspecies, which cause the neglected tropical diseases yaws and endemic syphilis. Using a collection of pathogenic Treponema strains that is unprecedented in size, we show that yaws appears to be an ancient infection in humans while venereal syphilis arose relatively recently in human history. In addition, the closest relatives of syphilis-causing strains identified in this study were found in South America, providing support for the Columbian theory of syphilis's origin