The word-length effect in acquired alexia, and real and virtual hemianopia

A word-length effect is often described in pure alexia, with reading time proportional to the number of letters in a word. Given the frequent association of right hemianopia with pure alexia, it is uncertain whether and how much of the word-length effect may be attributable to the hemifield loss. To isolate the contribution of the visual field defect, we simulated hemianopia in healthy subjects with a gaze-contingent paradigm during an eye-tracking experiment. We found a minimal word-length effect of 14 ms/letter for full-field viewing, which increased to 38 ms/letter in right hemianopia and to 31 ms/letter in left hemianopia. We found a correlation between mean reading time and the slope of the word-length effect in hemianopic conditions. The 95% upper prediction limits for the word-length effect were 51 ms/letter in subjects with full visual fields and 161 ms/letter with simulated right hemianopia. These limits, which can be considered diagnostic criteria for an alexic word-length effect, were consistent with the reading performance of six patients with diagnoses based independently on perimetric and imaging data: two patients with probable hemianopic dyslexia, and four with alexia and lesions of the left fusiform gyrus, two with and two without hemianopia. Two of these patients also showed reduction of the word-length effect over months, one with and one without a reading rehabilitation program. Our findings clarify the magnitude of the word-length effect that originates from hemianopia alone, and show that the criteria for a word-length effect indicative of alexia differ according to the degree of associated hemifield loss.

Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes

Eosinophilia is an important indicator of various neoplastic and nonneoplastic conditions. Depending on the underlying disease and mechanisms, eosinophil infiltration can lead to organ dysfunction, clinical symptoms, or both. During the past 2 decades, several different classifications of eosinophilic disorders and related syndromes have been proposed in various fields of medicine. Although criteria and definitions are, in part, overlapping, no global consensus has been presented to date. The Year 2011 Working Conference on Eosinophil Disorders and Syndromes was organized to update and refine the criteria and definitions for eosinophilic disorders and to merge prior classifications in a contemporary multidisciplinary schema. A panel of experts from the fields of immunology, allergy, hematology, and pathology contributed to this project. The expert group agreed on unifying terminologies and criteria and a classification that delineates various forms of hypereosinophilia, including primary and secondary variants based on specific hematologic and immunologic conditions, and various forms of the hypereosinophilic syndrome. For patients in whom no underlying disease or hypereosinophilic syndrome is found, the term hypereosinophilia of undetermined significance is introduced. The proposed novel criteria, definitions, and terminologies should assist in daily practice, as well as in the preparation and conduct of clinical trials.

What is the evidence supporting the prevention of osteoarthritis and improved femoral coverage after shelf procedure for Legg-Calvé-Perthes disease?

The evidence supporting continued use of shelf acetabuloplasty in Legg-Calvé-Perthes disease (LCPD) is not well-defined, and there is controversy regarding the long-term benefits related to clinical and functional improvement.

Learning from failure--rationale and design for a study about discontinuation of randomized trials (DISCO study)

Background Randomized controlled trials (RCTs) may be discontinued because of apparent harm, benefit, or futility. Other RCTs are discontinued early because of insufficient recruitment. Trial discontinuation has ethical implications, because participants consent on the premise of contributing to new medical knowledge, Research Ethics Committees (RECs) spend considerable effort reviewing study protocols, and limited resources for conducting research are wasted. Currently, little is known regarding the frequency and characteristics of discontinued RCTs. Methods/Design Our aims are, first, to determine the prevalence of RCT discontinuation for specific reasons; second, to determine whether the risk of RCT discontinuation for specific reasons differs between investigator- and industry-initiated RCTs; third, to identify risk factors for RCT discontinuation due to insufficient recruitment; fourth, to determine at what stage RCTs are discontinued; and fifth, to examine the publication history of discontinued RCTs. We are currently assembling a multicenter cohort of RCTs based on protocols approved between 2000 and 2002/3 by 6 RECs in Switzerland, Germany, and Canada. We are extracting data on RCT characteristics and planned recruitment for all included protocols. Completion and publication status is determined using information from correspondence between investigators and RECs, publications identified through literature searches, or by contacting the investigators. We will use multivariable regression models to identify risk factors for trial discontinuation due to insufficient recruitment. We aim to include over 1000 RCTs of which an anticipated 150 will have been discontinued due to insufficient recruitment. Discussion Our study will provide insights into the prevalence and characteristics of RCTs that were discontinued. Effective recruitment strategies and the anticipation of problems are key issues in the planning and evaluation of trials by investigators, Clinical Trial Units, RECs and funding agencies. Identification and modification of barriers to successful study completion at an early stage could help to reduce the risk of trial discontinuation, save limited resources, and enable RCTs to better meet their ethical requirements.

The transcription factor encyclopedia

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field.

Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field

Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders.

Mending The Mind With Dharma

Anxiety, depression, and tragedy are all unavoidable aspects of existence that we find ourselves grappling with at some point in our lives. In those darker moments we often look beyond ourselves for a means to cope with our struggles in the hopes of transcending into enhanced states of being. The world¿s religions have provided various answers to problems of mental and physical affliction. Across cultures and throughout history, numerous techniques for ¿mending the mind¿ have emerged, conditioned by a number of factors, including the normative values of a society as well as the scientific advances and technologies available for therapeutic application. Buddhism encompasses a broad tradition of beliefs, practices, and philosophies that, taken together, aim at eliminating suffering from the human experience. It is suggested that anyone who comes to understand and practice Buddhist teachings¿Dharma¿will rise out of the life of suffering and into a condition of awakening or nirvana. With this as an intended goal, a person who is unfulfilled in their life or who is experiencing feelings of depression will, it might be assumed, find great potential in turning to Buddhism as means for alleviation of these states. In contemporary western society, however, the most common route for eliminating emotional distress is to take antidepressant medication, which aims for immediate relief of the negative feelings and experiences that arise from depression. As I will argue, while this may be a successful approach to masking unwanted feelings, it in fact fails to treat the actual roots or cause of the undesirable experiences. Moreover, such a ¿therapeutic¿ approach lacks any aspect geared towards developing a consistently rewarding lifestyle. I will argue that the incorporation of Dharma¿both a set of ideas and as a form of practices¿into daily routines and modes of thinking provides the means for a balanced lifestyle, allowing the individual to relieve suffering and depression in a manner that the narrow scope of western medicine cannot provide.

Catastrophic Flooding In North-Central Pennsylvania: Geomorphic Findings From The September 2011 Event And Their Significance To

Tropical Storm Lee produced 25-36 cm of rainfall in north-central Pennsylvania on September 4th through 8th of 2011. Loyalsock Creek, Muncy Creek, and Fishing Creek experienced catastrophic flooding resulting in new channel formation, bank erosion, scour of chutes, deposition/reworking of point bars and chute bars, and reactivation of the floodplain. This study was created to investigate aspects of both geomorphology and sedimentology by studying the well-exposed gravel deposits left by the flood, before these features are removed by humans or covered by vegetation. By recording the composition of gravel bars in the study area and creating lithofacies models, it is possible to understand the 2011 flooding. Surficial clasts on gravel bars are imbricated, but the lack of imbrication and high matrix content of sediments at depth suggests that surface imbrication of the largest clasts took place during hyperconcentrated flow (40-70% sediment concentration). The imbricated clasts on the surface are the largest observed within the bars. The lithofacies recorded are atypical for mixed-load stream lithofacies and more similar to glacial outburst flood lithofacies. This paper suggests that the accepted lithofacies model for mixed-load streams with gravel bedload may not always be useful for interpreting depositional systems. A flume study, which attempted to duplicate the stratigraphy recorded in the field, was run in order to better understand hyperconcentrated flows in the study area. Results from the study in the Bucknell Geology Flume Laboratory indicate that surficial imbrication is possible in hyperconcentrated conditions. After flooding the flume to entrain large amounts of sand and gravel, deposition of surficially imbricated gravel with massive or upward coarsening sedimentology occurred. Imbrication was not observed at depth. These experimental flume deposits support our interpretation of the lithofacies discovered in the field. The sizes of surficial gravel bar clasts show clear differences between chute and point bars. On point bars, gravels fine with increasing distance from the channel. Fining also occurs at the downstream end of point bars. In chute deposits, dramatic fining occurs down the axis of the chute, and lateral grain sizes are nearly uniform. Measuring the largest grain size of sandstone clasts at 8-11 kilometer intervals on each river reveals anomalies in the downstream fining trends. Gravel inputs from bedrock outcrops, tributaries, and erosion of Pleistocene outwash terraces may explain observed variations in grain size along streams either incised into the Appalachian Plateau or located near the Wisconsinan glacial boundary. Atomic Mass Spectrometry (AMS) radiocarbon dating of sediment from recently scoured features on Muncy Creek and Loyalsock Creek returned respective ages of 500 BP and 2490 BP. These dates suggest that the recurrence interval of the 2011 flooding may be several hundred to several thousand years. This geomorphic interval of recurrence is much longer then the 120 year interval calculated by the USGS using historical stream gauge records.

Aleatory Sovereignty and the Rule of Sensitive Spaces

Addressing life in borders and refugee camps requires understanding the way these spaces are ruled, the kinds of problems rule poses for the people who live there, and the abilities of inhabitants to remake their own lives. Recent literature on such spaces has been influenced by Agamben's notion of sovereignty, which reduces these spaces and their residents to abstractions. We propose an alternate framework focused on what we call aleatory sovereignty, or rule by chance. This allows us to see camps and borders not only as the outcomes of humanitarian projects but also of anxieties about governance and rule; to see their inhabitants not only as abject recipients of aid, but also as individuals who make decisions and choices in complex conditions; and to show that while the outcome of projects within such spaces is often unpredictable, the assumptions that undergird such projects create regular cycles of implementation and failure.

A Stable Niche Assumption-Free Test of Ecological Divergence

Understanding the impact of geological events on diversification processes is central to evolutionary ecology. The recent amalgamation between ecological niche models (ENMs) and phylogenetic analyses has been used to estimate historical ranges of modern lineages by projecting current ecological niches of organisms onto paleoclimatic reconstructions. A critical assumption underlying this approach is that niches are stable over time. Using Notophthalmus viridescens (eastern newt), in which four ecologically diverged subspecies are recognized, we introduce an analytical framework free from the niche stability assumption to examine how refugial retreat and subsequent postglacial expansion have affected intraspecific ecological divergence. We found that the current subspecies designation was not congruent with the phylogenetic lineages. Thus, we examined ecological niche overlap between the refugial and modern populations, in both subspecies and lineage, by creating ENMs independently for modern and estimated last glacial maximum (LGM) newt populations, extracting bioclimate variables by randomly generated points, and conducting principal component analyses. Our analyses consistently showed that when tested as a hypothesis, rather than used as an assumption, the niches of N. viridescens lineages have been unstable since the LGM (both subspecies and lineages). There was greater ecological niche differentiation among the subspecies than the modern phylogenetic lineages, suggesting that the subspecies, rather than the phylogenetic lineages, is the unit of the current ecological divergence. The present study found little evidence that the LGM refugial retreat caused the currently observed ecological divergence and suggests that ecological divergence has occurred during postglacial expansion to the current distribution ranges.