Crowd Intelligence for the Classification of Fractures and Beyond

Medical diagnosis, like all products of human cognition, is subject to error. We tested the hypothesis that errors of diagnosis in the realm of fracture classification can be reduced by a consensus (group) diagnosis; and that digital imaging and Internet access makes feasible the compilation of a diagnostic consensus in real time.Twelve orthopaedic surgeons were asked to evaluate 20 hip radiographs demonstrating a femoral neck fracture. The surgeons were asked to determine if the fractures were displaced or not. Because no reference standard is available, the maximal accuracy of the diagnosis of displacement can be inferred from inter-observer reliability: if two readers disagree about displacement, one of them must be wrong. That method was employed here. Additionally, virtual reader groups of 3 and 5 individual members were amalgamated, with the response of those groups defined by majority vote. The purpose of this step was to see if increasing the number of readers would improve accuracy. In a second experiment, to study the feasibility of amassing a reader group on the Internet in real time, 40 volunteers were sent 10 periodic email requests to answer questions and their response times were assessed.The mean kappa coefficient for individual inter-observer reliability for the diagnosis of displacement was 0.69, comparable to prior published values. For 3-member virtual reader groups, inter-observer reliability was 0.77; and for 5-member groups, it was 0.80. In the experiment studying the feasibility of amassing a reader group in real time, the mean response time was 594 minutes. For all cases, a 9-member group (theoretically 99% accurate) was amassed in 135.8 minutes or less.Consensus may improve diagnosis. Amassing a group for this purpose on the Internet is feasible

Flow cytometry analysis of germinating Bacillus spores, using membrane potential dye

Germination of Bacillus anthracis spores is necessary for the transcription of plasmidic genes essential to the infection. Assessing germination potential is crucial to predict the risk associated with pathogenic Bacillus exposure. The aim of this study was to set up a viability assay based on membrane potential in order to predict the earliest germination event of spores. B. cereus and two strains of B. subtilis were used. The spores were isolated with a sodium bromide gradient. Approximately 107 spores were incubated at 37°C in tryptic soy broth (TSB). Aliquots were harvested at predetermined times and stained with 3,3'-dihexyloxacarbocyanine iodide [DiOC6(3)] or with bis-(1,3-dibutylbarbituric acid) trimethine oxonol [DiBAC4(3)]. Fluorescence characteristics were obtained using flow cytometry. The earliest detectable activation of membrane potential occurred after 15 min of incubation in TSB using DiOC6(3). Using DiBAC4(3), the earliest detectable signal was after 4 h of incubation. Control experiments using carbonyl cyanide m-chlorophenylhydrazone (CCCP)-treated spores did not show any change in the fluorescence intensity over time. Since no membrane potential and no germination were detected in CCCP-treated spores, the activation of membrane potential seems to be associated with germination. DiOC6(3) can be used as an early membrane potential indicator for spores. DiBAC4(3), by contrast, is not a early membrane potential marker

Geometric and algebraic classification of quadratic differential systems with invariant hyperbolas

Let QSH be the whole class of non-degenerate planar quadratic differential systems possessing at least one invariant hyperbola. We classify this family of systems, modulo the action of the group of real affine transformations and time rescaling, according to their geometric properties encoded in the configurations of invariant hyperbolas and invariant straight lines which these systems possess. The classification is given both in terms of algebraic geometric invariants and also in terms of affine invariant polynomials and it yields a total of 205 distinct such configurations. We have 162 configurations for the subclass QSH(η>0) of systems which possess three distinct real singularities at infinity, and 43 configurations for the subclass QSH(η=0) of systems which possess either exactly two distinct real singularities at infinity or the line at infinity filled up with singularities. The algebraic classification, based on the invariant polynomials, is also an algorithm which makes it possible to verify for any given real quadratic differential system if it has invariant hyperbolas or not and to specify its configuration of invariant hyperbolas and straight lines

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Arthroscopic proficiency: methods in evaluating competency

Abstract Background The current paradigm of arthroscopic training lacks objective evaluation oftechnical ability and its adequacy is concerning given the acceleratingcomplexity of the field. To combat insufficiencies, emphasis is shiftingtowards skill acquisition outside the operating room and sophisticatedassessment tools. We reviewed (1) the validity of cadaver and surgicalsimulation in arthroscopic training, (2) the role of psychomotor analysisand arthroscopic technical ability, (3) what validated assessment tools areavailable to evaluate technical competency, and (4) the quantification ofarthroscopic proficiency. Methods The Medline and Embase databases were searched for published articles in theEnglish literature pertaining to arthroscopic competence, arthroscopicassessment and evaluation and objective measures of arthroscopic technicalskill. Abstracts were independently evaluated and exclusion criteriaincluded articles outside the scope of knee and shoulder arthroscopy as wellas original articles about specific therapies, outcomes and diagnosesleaving 52 articles citied in this review. Results Simulated arthroscopic environments exhibit high levels of internal validityand consistency for simple arthroscopic tasks, however the ability totransfer complex skills to the operating room has not yet been established.Instrument and force trajectory data can discriminate between technicalability for basic arthroscopic parameters and may serve as useful adjunctsto more comprehensive techniques. There is a need for arthroscopicassessment tools for standardized evaluation and objective feedback oftechnical skills, yet few comprehensive instruments exist, especially forthe shoulder. Opinion on the required arthroscopic experience to obtainproficiency remains guarded and few governing bodies specify absolutequantities. Conclusions Further validation is required to demonstrate the transfer of complexarthroscopic skills from simulated environments to the operating room andprovide objective parameters to base evaluation. There is a deficiency ofvalidated assessment tools for technical competencies and little consensusof what constitutes a sufficient case volume within the arthroscopycommunity

A Simplified Method for the Aspiration of Bone Marrow from Patients Undergoing Hip and Knee Joint Replacement for Isolating Mesenchymal Stem Cells and In Vitro Chondrogenesis

The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon’s skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians.Peer Reviewe