362 research outputs found

    A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

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    Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory ( p<0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required. © 2013 Elsevier Ltd

    Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms

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    A scanning electron microscope survey was initiated to determine if the previously reported findings of “dinosaurian soft tissues” could be identified in situ within the bones. The results obtained allowed a reinterpretation of the formation and preservation of several types of these “tissues” and their content. Mineralized and non-mineralized coatings were found extensively in the porous trabecular bone of a variety of dinosaur and mammal species across time. They represent bacterial biofilms common throughout nature. Biofilms form endocasts and once dissolved out of the bone, mimic real blood vessels and osteocytes. Bridged trails observed in biofilms indicate that a previously viscous film was populated with swimming bacteria. Carbon dating of the film points to its relatively modern origin. A comparison of infrared spectra of modern biofilms with modern collagen and fossil bone coatings suggests that modern biofilms share a closer molecular make-up than modern collagen to the coatings from fossil bones. Blood cell size iron-oxygen spheres found in the vessels were identified as an oxidized form of formerly pyritic framboids. Our observations appeal to a more conservative explanation for the structures found preserved in fossil bone

    A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

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    BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

    The Effects of Twitter Sentiment on Stock Price Returns

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    Social media are increasingly reflecting and influencing behavior of other complex systems. In this paper we investigate the relations between a well-know micro-blogging platform Twitter and financial markets. In particular, we consider, in a period of 15 months, the Twitter volume and sentiment about the 30 stock companies that form the Dow Jones Industrial Average (DJIA) index. We find a relatively low Pearson correlation and Granger causality between the corresponding time series over the entire time period. However, we find a significant dependence between the Twitter sentiment and abnormal returns during the peaks of Twitter volume. This is valid not only for the expected Twitter volume peaks (e.g., quarterly announcements), but also for peaks corresponding to less obvious events. We formalize the procedure by adapting the well-known "event study" from economics and finance to the analysis of Twitter data. The procedure allows to automatically identify events as Twitter volume peaks, to compute the prevailing sentiment (positive or negative) expressed in tweets at these peaks, and finally to apply the "event study" methodology to relate them to stock returns. We show that sentiment polarity of Twitter peaks implies the direction of cumulative abnormal returns. The amount of cumulative abnormal returns is relatively low (about 1-2%), but the dependence is statistically significant for several days after the events

    Reinforcement learning or active inference?

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    This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain

    Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

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    The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

    Treating Cancer as an Infectious Disease—Viral Antigens as Novel Targets for Treatment and Potential Prevention of Tumors of Viral Etiology

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    Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers.Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC) and Hepatitis B-associated hepatocellular carcinoma (HCC) by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188)Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies.This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer

    Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study

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    <p>Abstract</p> <p>Background</p> <p>Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing.</p> <p>Methods/Design</p> <p>A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use.</p> <p>Discussion</p> <p>This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.</p

    Genetic Structure of the Polymorphic Metrosideros (Myrtaceae) Complex in the Hawaiian Islands Using Nuclear Microsatellite Data

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    Five species of Metrosideros (Myrtaceae) are recognized in the Hawaiian Islands, including the widespread M. polymorpha, and are characterized by a multitude of distinctive, yet overlapping, habit, ecological, and morphological forms. It remains unclear, despite several previous studies, whether the morphological variation within Hawaiian Metrosideros is due to hybridization, genetic polymorphism, phenotypic plasticity, or some combination of these processes. The Hawaiian Metrosideros complex has become a model system to study ecology and evolution; however this is the first study to use microsatellite data for addressing inter-island patterns of variation from across the Hawaiian Islands.Ten nuclear microsatellite loci were genotyped from 143 individuals of Metrosideros. We took advantage of the bi-parental inheritance and rapid mutation rate of these data to examine the validity of the current taxonomy and to investigate whether Metrosideros plants from the same island are more genetically similar than plants that are morphologically similar. The Bayesian algorithm of the program structure was used to define genetic groups within Hawaiian Metrosideros and the closely related taxon M. collina from the Marquesas and Austral Islands. Several standard and nested AMOVAs were conducted to test whether the genetic diversity is structured geographically or taxonomically.The results suggest that Hawaiian Metrosideros have dynamic gene flow, with genetic and morphological diversity structured not simply by geography or taxonomy, but as a result of parallel evolution on islands following rampant island-island dispersal, in addition to ancient chloroplast capture. Results also suggest that the current taxonomy requires major revisions in order to reflect the genetic structure revealed in the microsatellite data
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