The subcoronary Toronto stentless versus supra-annular Perimount stented replacement aortic valve: Early clinical and hemodynamic results of a randomized comparison in 160 patients

BackgroundA stentless valve is expected to be hemodynamically superior to a stented valve. The aim of this study was to compare early postoperative hemodynamic function and clinical events in a randomized, prospective series of 160 stentless and stented biological replacement aortic valves.MethodsWe randomized 160 consecutive patients on 1 surgeon’s list to receive either a Toronto stentless porcine valve (St Jude Medical, Inc, St Paul, Minn) or a Perimount stented bovine pericardial valve (Edwards Lifesciences, Irvine, Calif). Echocardiography was performed at discharge, between 3 and 6 months, and at 1 year after surgery. Statistical analysis was performed by both intention to treat and actual valves implanted.ResultsThe mean labeled size of both designs of valve was 24.7. There were no statistically significant differences in results at any time interval or whether analysis was performed by actual valves implanted or intention to treat. At 3 to 6 months for the Toronto versus the Perimount valve, the effective orifice area was 1.58 versus 1.66 cm2, the mean pressure difference was 7.54 versus 7.42 mm Hg, and the peak velocity was 2.07 versus 2.0.1 m/s. There was no difference in mortality, regression of left ventricular hypertrophy, or complications other than paraprosthetic regurgitation at 12 months or on follow-up for a proportion of the sample to 8 years. The incidence of regurgitation through the valves was similar for Toronto (10%) and Perimount (13.8%) at 1 year, but mild paraprosthetic regurgitation was found in 5 patients with the Perimount valve and none with Toronto valves.ConclusionsThere were no significant differences in hemodynamic function or clinical events between the stented and stentless biological valves chosen for comparison in the early postoperative period or in preliminary follow-up to 5 years

Reducing image artefacts in concurrent TMS/fMRI by passive shimming

A significant problem in the concurrent application of transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) is the image artefact caused by the effect of the TMS-coil on the homogeneity of the static magnetic field (B0). The resulting field inhomogeneity can lead to spatial distortions and local signal loss in echo-planar (EP) images. Here we demonstrate that passive shimming using thin patches of austenitic stainless steel can reduce the effect of the TMS-coil on B0 by ~ 80%, thus essentially eliminating the associated artefact. Initially the effect of the TMS-coil on B0 was measured using the phase of gradient echo images. Consequently the ideal distribution for the steel was simulated using the magnetic properties of the steel and the effects of the TMS-coil. Finally we demonstrate the effect of two different implementations of the passive shim on a spherical phantom and in vivo

Brown Dwarfs in Young Moving Groups from Pan-STARRS1. I. AB Doradus

Substellar members of young ($\lesssim$150 Myr) moving groups are valuable benchmarks to empirically define brown dwarf evolution with age and to study the low-mass end of the initial mass function. We have combined Pan-STARRS1 (PS1) proper motions with optical$-$IR photometry from PS1, 2MASS and $\textit{WISE}$ to search for substellar members of the AB Dor Moving Group within $\approx$50 pc and with spectral types of late-M to early-L, corresponding to masses down to $\approx$30 M$_{Jup}$ at the age of the group ($\approx$125 Myr). Including both photometry and proper motions allows us to better select candidates by excluding field dwarfs whose colors are similar to young AB~Dor Moving Group members. Our near-IR spectroscopy has identified six ultracool dwarfs (M6$-$L4; $\approx$30$-$100 M$_{Jup}$) with intermediate surface gravities (INT-G) as candidate members of the AB Dor Moving Group. We find another two candidate members with spectra showing hints of youth but consistent with field gravities. We also find four field brown dwarfs unassociated with the AB Dor Moving Group, three of which have INT-G gravity classification. While signatures of youth are present in the spectra of our $\approx$125 Myr objects, neither their $J-K$ nor $W1-W2$ colors are significantly redder than field dwarfs with the same spectral types, unlike younger ultracool dwarfs. We also determined PS1 parallaxes for eight of our candidates and one previously identified AB Dor Moving Group candidate. Although radial velocities (and parallaxes, for some) are still needed to fully assess membership, these new objects provide valuable insight into the spectral characteristics and evolution of young brown dwarfs.Comment: ApJ, accepte

The Acquisition of Human B Cell Memory in Response to Plasmodium Falciparum Malaria

Immunity to Plasmodium falciparum (Pf), the most deadly agent of malaria, is only acquired after years of repeated infections and appears to wane rapidly without ongoing exposure. Antibodies (Abs) are central to malaria immunity, yet little is known about the B‐cell biology that underlies Pf‐specific humoral immunity. To address this gap in our knowledge we carried out a year‐long prospective study of the acquisition and maintenance of long‐lived plasma cells (LLPCs) and memory B cells (MBCs) in 225 individuals aged two to twenty‐five years in Mali, in an area of intense seasonal transmission. Using protein microarrays containing approximately 25% of the Pf proteome we determined that Pf‐specific Abs were acquired only gradually, in a stepwise fashion over years of Pf exposure. Pf‐specific Ab levels were significantly boosted each year during the transmission season but the majority of these Abs were short lived and were lost over the subsequent six month period of no transmission. Thus, we observed only a small incremental increase in stable Ab levels each year, presumably reflecting the slow acquisition LLPCs. The acquisition Pf‐specific MBCs mirrored the slow step‐wise acquisition of LLPCs. This slow acquisition of Pf‐specific LLPCs and MBCs was in sharp contrast to that of tetanus toxoid (TT)‐specific LLPCs and MBCs that were vi vi rapidly acquired and stably maintained following a single vaccination in individuals in this cohort. In addition to the development of normal MBCs we observed an expansion of atypical MBCs that are phenotypically similar to hyporesponsive FCRL4+ cells described in HIV‐infected individuals. Atypical MBC expansion correlated with cumulative exposure to Pf, and with persistent asymptomatic Pf‐infection in children, suggesting that the parasite may play a role in driving the expansion of atypical MBCs. Collectively, these observations provide a rare glimpse into the process of the acquisition of human B cell memory in response to infection and provide evidence for a selective deficit in the generation of Pf‐specific LLPCs and MBCs during malaria. Future studies will address the mechanisms underlying the slow acquisition of LLPCs and MBCs and the generation and function of atypical MBCs

Lateralized deficit of response inhibition in early-onset schizophrenia

Background. The ability to inhibit inappropriate or unwanted actions is a key element of executive control. The existence of executive function deficits in schizophrenia is consistent with frontal lobe theories of the disorder. Relatively few studies have examined response inhibition in schizophrenia, and none in adolescent patients with early-onset schizophrenia (EOS). Methods. Twenty-one adolescents with the onset of clinically impairing psychosis before 19 years of age and 16 matched controls performed a stop-signal task to assess response inhibition. The patients with EOS were categorized as paranoid (n=10) and undifferentiated subtypes (n=11). The undifferentiated group had higher levels of negative symptomatology. Stop-signal reaction time (SSRT) and go-signal reaction time (Go-RT) were analysed with respect to hand of response. Results. The undifferentiated early-onset patients had significantly longer SSRTs, indicative of poor response inhibition, for the left hand compared to the paranoid early-onset patients and control participants. No differences existed for inhibitory control with the right hand. The three groups did not differ in Go-RT. Conclusions. Our results indicate a specific lateralized impairment of response inhibition in patients with undifferentiated, but not paranoid, EOS. These findings are consistent with reports of immature frontostriatal networks in EOS and implicate areas such as the pre-motor cortex and supplementary motor area (SMA) that are thought to play a role in both voluntary initiation and inhibition of movement

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

Objective: To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design: Opportunistic addition to an established randomised double blind placebo controlled trial. Setting: Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants: 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of “psychological” adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results: 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 P=0.03). The number of psychological adverse events—such as fatigue, stress, anxiety, and insomnia—that participants reported at their usual monthly appointments was significantly higher after the earthquake (χ2 P=0.007) but did not differ between treatment groups. Conclusion: In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical Trials Registry (anzctr.org.au) ACTRN1260900048622

Towards More Precise Survey Photometry for PanSTARRS and LSST: Measuring Directly the Optical Transmission Spectrum of the Atmosphere

Motivated by the recognition that variation in the optical transmission of the atmosphere is probably the main limitation to the precision of ground-based CCD measurements of celestial fluxes, we review the physical processes that attenuate the passage of light through the Earth's atmosphere. The next generation of astronomical surveys, such as PanSTARRS and LSST, will greatly benefit from dedicated apparatus to obtain atmospheric transmission data that can be associated with each survey image. We review and compare various approaches to this measurement problem, including photometry, spectroscopy, and LIDAR. In conjunction with careful measurements of instrumental throughput, atmospheric transmission measurements should allow next-generation imaging surveys to produce photometry of unprecedented precision. Our primary concerns are the real-time determination of aerosol scattering and absorption by water along the line of sight, both of which can vary over the course of a night's observations.Comment: 41 pages, 14 figures. Accepted PAS

Phenyl Saligenin Phosphate Induced Caspase-3 and c-Jun N-Terminal Kinase Activation in Cardiomyocyte-Like Cells

At present, little is known about the effect(s) of organophosphorous compounds (OPs) on cardiomyocytes. In this study we have investigated the effects of phenyl saligenin phosphate (PSP), two organophosphorothioate insecticides (diazinon and chlorpyrifos) and their acutely toxic metabolites (diazoxon and chlorpyrifos oxon) on mitotic and differentiated H9c2 cardiomyoblasts. OP-induced cytotoxicity was assessed by monitoring MTT reduction, LDH release and caspase-3 activity. Cytotoxicity was not observed with diazinon, diazoxon or chlorpyrifos oxon (48 h exposure; 200 μM). Chlorpyrifos-induced cytotoxicity was only evident at concentrations >100 μM. In marked contrast, PSP displayed pronounced cytotoxicity towards mitotic and differentiated H9c2 cells. PSP triggered the activation of JNK1/2, but not ERK1/2, p38 MAPK or PKB, suggesting a role for this pro-apoptotic protein kinase in PSP-induced cell death. The JNK1/2 inhibitor SP 600125 attenuated PSP-induced caspase-3 and JNK1/2 activation, confirming the role of JNK1/2 in PSP-induced cytotoxicity. Fluorescently labelled PSP (dansylated PSP) was used to identify novel PSP binding proteins. Dansylated PSP displayed cytotoxicity towards differentiated H9c2 cells. 2D-gel electrophoresis profiles of cells treated with dansylated PSP (25 μM) were used to identify proteins fluorescently labelled with dansylated PSP. Proteomic analysis identified tropomyosin, heat shock protein β-1 and nucleolar protein 58 as novel protein targets for PSP. In summary, PSP triggers cytotoxicity in differentiated H9c2 cardiomyoblasts via JNK1/2-mediated activation of caspase-3. Further studies are required to investigate whether the identified novel protein targets of PSP play a role in the cytotoxicity of this OP, which is usually associated with the development of OP-induced delayed neuropathy