2,440 research outputs found

    Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints

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    Recent advances in cardiovascular magnetic resonance (CMR) now allow the accurate and reproducible measurement of many aspects of cardiac and vascular structure and function, with prognostic data emerging for several key imaging biomarkers. These biomarkers are increasingly used in the evaluation of new drugs, devices and lifestyle modifications for the prevention and treatment of cardiovascular disease. This review outlines a conceptual framework for the application of imaging biomarkers to clinical trials, highlights several important CMR techniques which are in use in randomised studies, and reviews certain aspects of trial design, conduct and interpretation in relation to the use of CMR

    TMS demonstrates that both right and left superior temporal sulci are important for facial expression recognition

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    Prior studies demonstrate that a face-responsive region in the posterior superior temporal sulcus (pSTS) is involved in facial expression recognition. Although this region can be identified in both hemispheres, studies more commonly report it in the right hemisphere. However, the extent to which expression recognition is lateralised in pSTS remains unclear. In the current study, we used transcranial magnetic stimulation (TMS) to systematically compare the causal contribution of the right pSTS (rpSTS) with the left pSTS (lpSTS) during facial expression recognition. TMS was delivered over the functionally localised rpSTS, lpSTS and the control vertex site while participants (N = 30) performed an expression matching task and a control object matching task. TMS delivered over the rpSTS impaired expression recognition more than TMS delivered over the lpSTS. Crucially, TMS delivered over the rpSTS and lpSTS impaired task performance more than TMS delivered over the control site. TMS had no effect on the control task. This causally demonstrates that while task disruption was greater in the rpSTS, both the rpSTS and the lpSTS were engaged in facial expression recognition. Our results indicate that cognitive functions that are seemingly lateralised in neuroimaging studies, still rely on computations performed in both hemispheres for optimum task performance

    Harmful algal blooms of the Southern Benguela current: A review and appraisal of monitoring from 1989 to 1997

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    The Benguela upwelling system is subjected to blooms of harmful and toxic algae, the incidence and consequences of which are documented here. Red tides are common and usually attributed to members of the Dinophyceae, most of which are non-toxic. The incidence of these blooms varies spatially, with most blooms confined to the area west of Cape Agulhas. Cape Point forms the natural divide for species that dominate blooms of the west coast of South Africa as opposed to those that dominate the South Coast. Blooms occur most commonly fromJanuary to May, during the latter half of the upwelling season. Each red tide is associated with synoptic weather patterns, which dictate the onshore and offshore movement of dinoflagellate-dominated frontal blooms. There is also interannual variation, thought to be related to weather pattern changes. The harmful effects of highbiomass, non-toxic blooms include die-offs resulting from anoxia or hypoxia. Other effects of high biomassblooms include those that may cause mechanical or physical damage or those that may alter the foodweb. Recently, a bloom of the very small pelagophyte, Aureococcus anophagefferens, referred to as brown tide, in Saldanha Bay and Langebaan Lagoon resulted in growth arrest in both oysters and mussels. Toxic species cause mass mortalities of fish, shellfish, marine mammals, seabirds and other animals. Human illness is caused by contaminated seafood when toxic phytoplankton are filtered from the water by shellfish that accumulate toxins to levels thatare potentially lethal to humans and other consumers. Of these shellfish poisoning syndromes, Paralytic (PSP) and Diarrhetic Shellfish Poisoning (DSP) are common in the Benguela. Confirmed cases of PSP have beenattributed to the dinoflagellate Alexandrium catenella. Although shellfish are usually only marginally affected, in extreme cases of poisoning, mussel mortalities have been observed, and in most instances these have been attributed to blooms of A. catenella. Sardine Sardinops sagax mortalities in St Helena Bay have also been attributed to the ingestion of this PSP-producing dinoflagellate. Monitoring has revealed the presence of Dinophysis acuminata, D. fortii, D. hastata, D. tripos and D. rotundata, all of which have been reported to cause DSP. The dinoflagellate Gymnodiniun cf. mikimotoi, has been implicated in a type of Neurotoxic Shellfish Poisoning and human skin and respiratory irritations have been attributed to aerosol toxins produced by this species

    Electronic Structure and Lattice dynamics of NaFeAs

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    The similarity of the electronic structures of NaFeAs and other Fe pnictides has been demonstrated on the basis of first-principle calculations. The global double-degeneracy of electronic bands along X-M and R-A direction indicates the instability of Fe pnictides and is explained on the basis of a tight-binding model. The de Haas-van Alphen parameters for the Fermi surface (FS) of NaFeAs have been calculated. A QM=(1/2,1/2,0)\mathbf{Q}_{M}=(1/2,1/2,0) spin density wave (SDW) instead of a charge density wave (CDW) ground state is predicted based on the calculated generalized susceptibility χ(q)\chi(\mathbf{q}) and a criterion derived from a restricted Hatree-Fock model. The strongest electron-phonon (e-p) coupling has been found to involve only As, Na z-direction vibration with linear-response calculations. A possible enhancement mechanism for e-p coupling due to correlation is suggested

    Dual-site TMS demonstrates causal functional connectivity between the left and right posterior temporal sulci during facial expression recognition

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    Abstract Background Neuroimaging studies suggest that facial expression recognition is processed in the bilateral posterior superior temporal sulcus (pSTS). Our recent repetitive transcranial magnetic stimulation (rTMS) study demonstrates that the bilateral pSTS is causally involved in expression recognition, although involvement of the right pSTS is greater than involvement of the left pSTS. Objective/Hypothesis: In this study, we used a dual-site TMS to investigate whether the left pSTS is functionally connected to the right pSTS during expression recognition. We predicted that if this connection exists, simultaneous TMS disruption of the bilateral pSTS would impair expression recognition to a greater extent than unilateral stimulation of the right pSTS alone. Methods Participants attended two TMS sessions. In Session 1, participants performed an expression recognition task while rTMS was delivered to the face-sensitive right pSTS (experimental site), object-sensitive right lateral occipital complex (control site) or no rTMS was delivered (behavioural control). In Session 2, the same experimental design was used, except that continuous theta-burst stimulation (cTBS) was delivered to the left pSTS immediately before behavioural testing commenced. Session order was counter-balanced across participants. Results In Session 1, rTMS to the rpSTS impaired performance accuracy compared to the control conditions. Crucially in Session 2, the size of this impairment effect doubled after cTBS was delivered to the left pSTS. Conclusions Our results provide evidence for a causal functional connection between the left and right pSTS during expression recognition. In addition, this study further demonstrates the utility of the dual-site TMS for investigating causal functional links between brain regions

    Transcranial Magnetic Stimulation and the Understanding of Behavior

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    The development of the use of transcranial magnetic stimulation (TMS) in the study of psychological functions has entered a new phase of sophistication. This is largely due to an increasing physiological knowledge of its effects and to its being used in combination with other experimental techniques. This review presents the current state of our understanding of the mechanisms of TMS in the context of designing and interpreting psychological experiments. We discuss the major conceptual advances in behavioral studies using TMS. There are meaningful physiological and technical achievements to review, as well as a wealth of new perceptual and cognitive experiments. In doing so we summarize the different uses and challenges of TMS in mental chronometry, perception, awareness, learning, and memory

    Mate choice for nonadditive genetic benefits and the maintenance of genetic diversity in song sparrows

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    The lek paradox asserts that strong directional selection via female choice should deplete additive genetic variation in fitness and consequently any benefit to females expressing the preference. Recently, we have provided a novel resolution to the paradox by showing that nonadditive genetic effects such as overdominance can be inherited from parent to offspring, and populations with females that express a mating preference for outbred males maintain higher genetic variation than populations with females that mate randomly. Here, we test our dynamic model using empirical data previously published from a small island population of song sparrows (Melospiza melodia). The model assumes that fitness and male trait expression display overdominance effects. The results demonstrate that female choice for outbred males mediated by directional selection on song repertoire size provides a heritable benefit to offspring through reduced inbreeding depression. Within the population, we estimate the heritability of the inbreeding coefficient to be 0.18 +/- 0.08 (SD). Furthermore, we show that mate choice for outbred males increases fitness-related genetic variation in the population by 12% and thereby reduces inbreeding depression by 1% per generation in typical years and upwards of 15% in severe years. Thus, mate choice may help to stave off population extinction in this and other small populations

    Regulation of Membrane Targeting of the G Protein-coupled Receptor Kinase 2 by Protein Kinase A and Its Anchoring Protein AKAP79

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    The beta 2 adrenergic receptor (beta 2AR) undergoes desensitization by a process involving its phosphorylation by both protein kinase A (PKA) and G protein-coupled receptor kinases (GRKs). The protein kinase A-anchoring protein AKAP79 influences beta 2AR phosphorylation by complexing PKA with the receptor at the membrane. Here we show that AKAP79 also regulates the ability of GRK2 to phosphorylate agonist-occupied receptors. In human embryonic kidney 293 cells, overexpression of AKAP79 enhances agonist-induced phosphorylation of both the beta 2AR and a mutant of the receptor that cannot be phosphorylated by PKA (beta 2AR/PKA-). Mutants of AKAP79 that do not bind PKA or target to the beta 2AR markedly inhibit phosphorylation of beta 2AR/PKA-. We show that PKA directly phosphorylates GRK2 on serine 685. This modification increases Gbeta gamma subunit binding to GRK2 and thus enhances the ability of the kinase to translocate to the membrane and phosphorylate the receptor. Abrogation of the phosphorylation of serine 685 on GRK2 by mutagenesis (S685A) or by expression of a dominant negative AKAP79 mutant reduces GRK2-mediated translocation to beta 2AR and phosphorylation of agonist-occupied beta 2AR, thus reducing subsequent receptor internalization. Agonist-stimulated PKA-mediated phosphorylation of GRK2 may represent a mechanism for enhancing receptor phosphorylation and desensitization
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