eTRIKS Analytical Environment: A Modular High Performance Framework for Medical Data Analysis

Translational research is quickly becoming a science driven by big data. Improving patient care, developing personalized therapies and new drugs depend increasingly on an organization's ability to rapidly and intelligently leverage complex molecular and clinical data from a variety of large-scale partner and public sources. As analysing these large-scale datasets becomes computationally increasingly expensive, traditional analytical engines are struggling to provide a timely answer to the questions that biomedical scientists are asking. Designing such a framework is developing for a moving target as the very nature of biomedical research based on big data requires an environment capable of adapting quickly and efficiently in response to evolving questions. The resulting framework consequently must be scalable in face of large amounts of data, flexible, efficient and resilient to failure. In this paper we design the eTRIKS Analytical Environment (eAE), a scalable and modular framework for the efficient management and analysis of large scale medical data, in particular the massive amounts of data produced by high-throughput technologies. We particularly discuss how we design the eAE as a modular and efficient framework enabling us to add new components or replace old ones easily. We further elaborate on its use for a set of challenging big data use cases in medicine and drug discovery

Head orientation benefit to speech intelligibility in noise for cochlear implant users and in realistic listening conditions

Cochlear implant (CI) users suffer from elevated speech-reception thresholds and may rely on lip reading. Traditional measures of spatial release from masking quantify speech-reception-threshold improvement with azimuthal separation of target speaker and interferers and with the listener facing the target speaker. Substantial benefits of orienting the head away from the target speaker were predicted by a model of spatial release from masking. Audio-only and audio-visual speech-reception thresholds in normal-hearing (NH) listeners and bilateral and unilateral CI users confirmed model predictions of this head-orientation benefit. The benefit ranged 2–5 dB for a modest 30� orientation that did not affect the lip-reading benefit. NH listeners’ and CI users’ lip-reading benefit measured 3 and 5 dB, respectively. A head-orientation benefit of �2 dB was also both predicted and observed in NH listeners in realistic simulations of a restaurant listening environment. Exploiting the benefit of head orientation is thus a robust hearing tactic that would benefit both NH listeners and CI users in noisy listening conditions

Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades

The frontal eye field (FEF) and superior colliculus (SC) are thought to form two parallel systems for generating saccadic eye movements. The SC is thought classically to mediate reflex-like orienting movements. Thus it can be hypothesized that the FEF exerts a higher level control on a visual grasp reflex. To test this hypothesis we have studied the saccades of patients who have had discrete unilateral removals of frontal lobe tissue for the relief of intractable epilepsy. The responses of these patients were compared to those of normal subjects and patients with unilateral temporal lobe removals. Two tasks were used. In the first task the subject was instructed to look in the direction of a visual cue that appeared unexpectedly 12° to the left or right of a central fixation point (FP), in order to identify a patterned target that appeared 200 ms or more later. In the second “anti-saccade” task the subject was required to look not at the location of the cue but in the opposite direction, an equal distance from FP where after 200 ms or more the patterned target appeared. Three major observations have emerged from the present study. (a) Most frontal patients, with lesions involving both the dorsolateral and mesial cortex had long term difficulties in suppressing disallowed glances to visual stimuli that suddenly appeared in peripheral vision. (b) In such patients, saccades that were eventually directed away from the cue and towards the target were nearly always triggered by the appearance of the target itself irrespective of whether or not the “anti-saccade” was preceded by a disallowed glance. Those eye movements away from the cue were only rarely generated spontaneously across the blank screen during the cue-target time interval. (c) The latency of these visually-triggered saccades was very short (80–140 ms) compared to that of the correct saccades (170–200 ms) to the cue when the cue and target were on the same side, thereby suggesting that the structures removed in these patients normally trigger saccades after considerable computations have already been performed. The results support the view that the frontal lobes, particularly the dorsolateral region which contains the FEF and possibly the supplementary motor area contribute to the generation of complex saccadic eye-movement behaviour. More specifically, they appear to aid in suppressing unwanted reflex-like oculomotor activity and in triggering the appropriate volitional movements when the goal for the movement is known but not yet visible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46554/1/221_2004_Article_BF00235863.pd

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Real-Time TEM Imaging of the Formation of Crystalline Nanoscale Gaps

We present real-time transmission electron microscopy of nanogap formation by feedback controlled electromigration that reveals a remarkable degree of crystalline order. Crystal facets appear during feedback controlled electromigration indicating a layer-by-layer, highly reproducible electromigration process avoiding thermal runaway and melting. These measurements provide insight into the electromigration induced failure mechanism in sub-20 nm size interconnects, indicating that the current density at failure increases as the width decreases to approximately 1 nm

Variation in Treatment for Trapeziometacarpal Arthrosis

Background: Treatment recommendations for trapeziometacarpal (TMC) arthrosis are highly variable from surgeon to surgeon. This study addressed the influence of viewing radiographs on a decision to offer surgery for TMC arthrosis. Methods: In an online survey, 92 hand surgeons viewed clinical scenarios and were asked if they would offer surgery to 30 patients with TMC arthrosis. Forty-two observers were randomly assigned to review clinical information alone and 50 to review clinical information as well as radiographs. The degree of limitation of daily activities, time since diagnosis, prior treatment, pain with grind, crepitation with grind, and metacarpal adduction with metacarpophalangeal hyperextension were randomized for each patient scenario to determine the influence of these factors on offers of surgery. A cross-classified binary logistic multilevel regression analysis identified factors associated with surgeon offer of surgery. Results: Surgeons were more likely to offer surgery when they viewed radiographs (42% vs. 32%, P = 0.01). Other factors associated variation in offer of surgery included greater limitation of daily activities, symptoms for a year, prior splint or injection, deformity of the metacarpophalangeal joint. Factors not associated included limb dominance, prominence of the TMC joint, crepitation with the grind test, and pinch and grip strength. Conclusion: Surgeons that view radiographs are more likely to offer surgery to people with TMC arthrosis. Surgeons are also more likely to offer surgery when people do not adapt with time and nonoperative treatment. Given the notable influence of surgeon bias, and the potential for surgeon and patient impatience with the adaptation process, methods for increasing patient participation in the decision-making process merit additional attention and study

Localization of a 64-kDa phosphoprotein in the lumen between the outer and inner envelopes of pea chloroplasts

The identification and localization of a marker protein for the intermembrane space between the outer and inner chloroplast envelopes is described. This 64-kDa protein is very rapidly labeled by [γ-32P]ATP at very low (30 nM) ATP concentrations and the phosphoryl group exhibits a high turnover rate. It was possible to establish the presence of the 64-kDa protein in this plastid compartment by using different chloroplast envelope separation and isolation techniques. In addition comparison of labeling kinetics by intact and hypotonically lysed pea chloroplasts support the localization of the 64-kDa protein in the intermembrane space. The 64-kDa protein was present and could be labeled in mixed envelope membranes isolated from hypotonically lysed plastids. Mixed envelope membranes incorporated high amounts of 32P from [γ-32P]ATP into the 64-kDa protein, whereas separated outer and inner envelope membranes did not show significant phosphorylation of this protein. Water/Triton X-114 phase partitioning demonstrated that the 64-kDa protein is a hydrophilic polypeptide. These findings suggest that the 64-kDa protein is a soluble protein trapped in the space between the inner and outer envelope membranes. After sonication of mixed envelope membranes, the 64-kDa protein was no longer present in the membrane fraction, but could be found in the supernatant after a 110000 × g centrifugation