Alcohol affects neuronal substrates of response inhibition but not of perceptual processing of stimuli signalling a stop response

Alcohol impairs inhibitory control, including the ability to terminate an initiated action. While there is increasing knowledge about neural mechanisms involved in response inhibition, the level at which alcohol impairs such mechanisms remains poorly understood. Thirty-nine healthy social drinkers received either 0.4g/kg or 0.8g/kg of alcohol, or placebo, and performed two variants of a Visual Stop-signal task during acquisition of functional magnetic resonance imaging (fMRI) data. The two task variants differed only in their instructions: in the classic variant (VSST), participants inhibited their response to a “Go-stimulus” when it was followed by a “Stop-stimulus”. In the control variant (VSST_C), participants responded to the “Go-stimulus” even if it was followed by a “Stop-stimulus”. Comparison of successful Stop-trials (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage groups enabled the identification of alcohol effects on functional neural circuits supporting inhibitory behaviour and error processing. Alcohol impaired inhibitory control as measured by the Stop-signal reaction time, but did not affect other aspects of VSST performance, nor performance on the VSST_C. The low alcohol dose evoked changes in neural activity within prefrontal, temporal, occipital and motor cortices. The high alcohol dose evoked changes in activity in areas affected by the low dose but importantly induced changes in activity within subcortical centres including the globus pallidus and thalamus. Alcohol did not affect neural correlates of perceptual processing of infrequent cues, as revealed by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises the inhibitory control of action by modulating cortical regions supporting attentional, sensorimotor and action-planning processes. At higher doses the impact of alcohol also extends to affect subcortical nodes of fronto-basal ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have little impact on the early visual processing of infrequent perceptual cues. These observations clarify clinically-important effects of alcohol on behaviour

Three-Dimensional Human iPSC-Derived Artificial Skeletal Muscles Model Muscular Dystrophies and Enable Multilineage Tissue Engineering

Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice. Pathological cellular hallmarks of incurable forms of severe muscular dystrophy could be modeled with high fidelity using this 3D platform. Finally, we show generation of fully human iPSC-derived, complex, multilineage muscle models containing key isogenic cellular constituents of skeletal muscle, including vascular endothelial cells, pericytes, and motor neurons. These results lay the foundation for a human skeletal muscle organoid-like platform for disease modeling, regenerative medicine, and therapy development

Understanding the attitudes of the elderly towards enrolment into cancer clinical trials

BACKGROUND: The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials. METHODS: The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials. RESULTS: Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making. CONCLUSION: Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials

Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level

An adolescent with both Wegener's Granulomatosis and chronic blastomycosis

We report a case of Wegener's Granulomatosis (WG) associated with blastomycosis. This appears to be the first case report of WG co-existing with a tissue proven blastomycosis infection. The temporal correlation of the two conditions suggests that blastomycosis infection (and therefore possibly other fungal infections), may trigger the systemic granulomatous vasculitis in a predisposed individual; a provocative supposition warranting further study

Heterostructured electrode with concentration gradient shell for highly efficient oxygen reduction at low temperature

Heterostructures of oxides have been widely investigated in optical, catalytic and electrochemical applications, because the heterostructured interfaces exhibit pronouncedly different transport, charge, and reactivity characteristics compared to the bulk of the oxides. Here we fabricated a three-dimensional (3D) heterostructured electrode with a concentration gradient shell. The concentration gradient shell with the composition of Ba0.5-xSr0.5-yCo0.8Fe0.2O3-δ (BSCF-D) was prepared by simply treating porous Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) backbone with microwave-plasma. Electrochemical impedance spectroscopy reveals that the oxygen surface exchange rate of the BSCF-D is enhanced by ~250% that of the pristine BSCF due to the appearance of the shell. The heterostructured electrode shows an interfacial resistance as low as 0.148 Ω cm2 at 550°C and an unchanged electrochemical performance after heating treatment for 200 h. This method offers potential to prepare heterostructured oxides not only for electrochemical devices but also for many other applications that use ceramic materials

The evolution of tooth wear indices

Tooth wear—attrition, erosion and abrasion—is perceived internationally as an ever-increasing problem. Clinical and epidemiological studies, however, are difficult to interpret and compare due to differences in terminology and the large number of indices that have been developed for diagnosing, grading and monitoring dental hard tissue loss. These indices have been designed to identify increasing severity and are usually numerical. Some record lesions on an aetiological basis (e.g. erosion indices), others record lesions irrespective of aetiology (tooth wear indices); none have universal acceptance, complicating the evaluation of the true increase in prevalence reported. This article considers the ideal requirements for an erosion index. It reviews the literature to consider how current indices have evolved and discusses if these indices meet the clinical and research needs of the dental profession

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Does egg deposition by herbivorous pine sawflies affect transcription of sesquiterpene synthases in pine?

Scots pine (Pinus sylvestris; Pinaceae, Pinales) is known to defend against egg deposition by herbivorous sawflies by changing its terpenoid volatile blend. The oviposition-induced pine odor attracts egg parasitoids that kill the sawfly eggs. Here, we investigated whether sawfly egg deposition activates genes encoding pine terpene synthases by extracting mRNA from oviposition-induced P. sylvestris. Three new sesquiterpene synthases, PsTPS 1, PsTPS 2, and PsTPS 3, were isolated that were shown on heterologous expression in Escherichia coli to produce (E)-β-caryophyllene and α-humulene (PsTPS 1), 1(10),5-germacradiene-4-ol (PsTPS 2), and longifolene and α-longipinene (PsTPS 3) as their principal products. Quantitative RT-PCR analyses revealed that transcript levels of PsTPS 1 and PsTPS 2 were significantly higher in oviposition-induced twigs that were attractive to the parasitoids than in non-attractive, artificially damaged twigs. Thus, our results demonstrate a specific transcription response to egg deposition, distinct from that caused by artificial wounding. Transcripts of PsTPS 3 did not change in response to egg deposition. The transcript levels of PsTPS 1, PsTPS 2, and PsTPS 3 were also determined in relation to time after egg deposition, since pine odor is attractive to the parasitoid only 72 h after egg deposition. Transcription rates of PsTPS 1 and PsTPS 2 were significantly enhanced only 72 h after egg deposition, thus matching the timing of odor attractiveness, while for PsTPS 3, enhanced transcription was not detected at any time period studied after egg deposition. The ecological significance of the oviposition-induced increase of sesquiterpene synthase transcripts is discussed