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Search Results: 1 - 10 of 584045 matches for " Matt D. A. Fletcher "
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Infraspinatus/Teres Minor Transfer Biceps In Situ Tenodesis Procedure: Initial Results of a Technique for Massive Cuff Tears
Matt D. A. Fletcher
ISRN Orthopedics , 2013, DOI: 10.1155/2013/646598
Abstract: Massive rotator cuff tears may not be primarily repairable with salvage options not necessarily providing acceptable results. Extrinsic tendon transfer is a significant undertaking with prolonged rehabilitation and variable outcome. A novel technique for the reconstruction of massive tears, not amenable to primary repair, by performing a transfer of the intrinsic posterior rotator cuff onto an intact, tenodesed long head of biceps tendon acting as a scaffold for the intrinsic transfer is described. The clinical results at short to medium term in 17 initial patients are presented. Encouraging results from this study suggest that this is a viable option for the management of massive rotator cuff tears with an intact posterior cuff with results equal or superior to other reconstructive techniques. 1. Introduction Rotator cuff pathology is a common problem, with tears causing a significant amount of time off work, pain, and loss of function. Tears can be graded according to a number of different systems, massive tears generally being considered the most difficult for surgical management. In the case of a massive tear with a retracted, deficient, or grossly degenerate tendon margin, direct primary repair is not possible. Present reconstructive options include medialisation of the supraspinatus footprint, margin convergence, subscapularis transfer, and extrinsic latissimus dorsi/teres major transfer. A novel technique for the primary reconstruction of a massive, retracted, and irreparable tear is described. This utilizes the infraspinatus and teres minor muscles, as well as an intact long head of biceps to create a new, postero-superior force couple with a more anatomic force transmission alignment of the transferred tendon compared to an extrinsic transfer. The transferred tendon acts as a humeral head depressor as well as force couple to facilitate return to normal shoulder kinematics. The procedure has the advantage of being performed as a primary operation and is easily accomplished in the deck-chair position. Recovery appears similar to simple rotator cuff repair, and postoperative pain is minimal. 2. Methods In deck-chair position, initial glenohumeral and subacromial arthroscopy is performed. Arthroscopic subacromial decompression is completed, and the cuff is inspected for a posterior cuff margin, and the presence of the long head of biceps. If amenable to reconstruction, an open approach to the shoulder is made. The presence of an irreparable rotator cuff tear is confirmed. The infraspinatus tendon is elevated by sharp dissection from the posterior
Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples
Laura E. MacConaill,Catarina D. Campbell,Sarah M. Kehoe,Adam J. Bass,Charles Hatton,Lili Niu,Matt Davis,Keluo Yao,Megan Hanna,Chandrani Mondal,Lauren Luongo,Caroline M. Emery,Alissa C. Baker,Juliet Philips,Deborah J. Goff,Michelangelo Fiorentino,Mark A. Rubin,Kornelia Polyak,Jennifer Chan,Yuexiang Wang,Jonathan A. Fletcher,Sandro Santagata,Gianni Corso,Franco Roviello,Ramesh Shivdasani,Mark W. Kieran,Keith L. Ligon,Charles D. Stiles,William C. Hahn,Matthew L. Meyerson,Levi A. Garraway
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007887
Abstract: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting.
Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma
Badreddin Edris,Jonathan A. Fletcher,Robert B. West,Matt van de Rijn,Andrew H. Beck
Sarcoma , 2012, DOI: 10.1155/2012/805614
Abstract: Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132’s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS.
Comparative Gene Expression Profiling of Benign and Malignant Lesions Reveals Candidate Therapeutic Compounds for Leiomyosarcoma
Badreddin Edris,Jonathan A. Fletcher,Robert B. West,Matt van de Rijn,Andrew H. Beck
Sarcoma , 2012, DOI: 10.1155/2012/805614
Abstract: Leiomyosarcoma (LMS) is a malignant, soft-tissue tumor for which few effective therapies exist. Previously, we showed that there are three molecular subtypes of LMS. Here, we analyzed genes differentially expressed in each of the three LMS subtypes as compared to benign leiomyomas and then used the Connectivity Map (cmap) to calculate enrichment scores for the 1309 cmap drugs in order to identify candidate molecules with the potential to induce a benign, leiomyoma-like phenotype in LMS cells. 11 drugs were selected and tested for their ability to inhibit the growth of three human LMS cell lines. We identified two drugs with in vitro efficacy against LMS, one of which had a strongly negative enrichment score (Cantharidin) and the other of which had a strongly positive enrichment score (MG-132). Given MG-132’s strong inhibitory effect on LMS cell viability, we hypothesized that LMS cells may be sensitive to treatment with other proteasome inhibitors and demonstrated that bortezomib, a clinically-approved proteasome inhibitor not included in the original cmap screen, potently inhibited the viability of the LMS cell lines. These findings suggest that systematically linking LMS subtype-specific expression signatures with drug-associated expression profiles represents a promising approach for the identification of new drugs for LMS. 1. Introduction Leiomyosarcoma (LMS) is a malignant neoplasm of smooth muscle that accounts for approximately one quarter of all soft-tissue sarcomas. Most frequently, LMS occurs in the uterus or the retroperitoneum, but these tumors can also present in a number of soft tissues throughout the body. Current treatment protocols for LMS consist of surgery with adjuvant doxorubicin-based chemotherapy [1]. There are no effective targeted therapies available for this cancer. Previously, using gene expression profiling, array comparative hybridization, and immunohistochemistry, we identified three distinct biologic subtypes of LMS [2]. The presence of distinct biologic disease subtypes suggests that LMS subtypes may show differential drug responses. Leiomyoma (LM) is a benign smooth muscle neoplasm that, like its malignant counterpart LMS, frequently occurs in the uterus. While LM is a significant cause of hospitalizations for gynecological disorders and is the most frequent reason for hysterectomies among US women, these growths virtually never metastasize [3]. We hypothesize that genes differentially expressed between LMS subtypes and LM may provide insight into biological pathways driving malignant behavior in LMS and may facilitate
Interpretation of the angular dependence of the de Haas-van Alphen effect in MgB_2
A. Carrington,J. D. Fletcher,H. Harima
Physics , 2004, DOI: 10.1103/PhysRevB.71.174505
Abstract: We present detailed results for the amplitude and field dependence of the de Haas-van Alphen (dHvA) signal arising from the electron-like $\pi$ sheet of Fermi surface in MgB_2. Our data and analysis show that the dip in dHvA amplitude when the field is close to the basal plane is caused by a beat between two very similar dHvA frequencies and not a spin-zero effect as previously assumed. Our results imply that the Stoner enhancement factors in MgB_2 are small on both the Sigma and Pi sheets.
Magnetic fields in barred galaxies. II. Dynamo models
D. Moss,A. Shukurov,D. Sokoloff,R. Beck,A. Fletcher
Physics , 2001, DOI: 10.1051/0004-6361:20011343
Abstract: We study the generation and maintenance of large-scale magnetic fields in barred galaxies. We take a velocity field (with strong noncircular components) from a published gas dynamical simulation of Athanassoula (1992), and use this as input to a galactic dynamo calculation. Our work is largely motivated by recent high quality VLA radio observations of the barred galaxy NGC 1097, and we compare our results in detail with the regular magnetic fields deduced from these observations. We are able to reproduce most of the conspicuous large-scale features of the observed regular field, including the field structure in the central regions, by using a simple mean-field dynamo model in which the intensity of interstellar turbulence (more precisely, the turbulent diffusivity) is enhanced by a factor of 2-6 in the dust lanes and near the circumnuclear ring. We argue that magnetic fields can be dynamically important, and therefore should be included in models of gas flow in barred galaxies.
Low-Cost Mobile Phone Microscopy with a Reversed Mobile Phone Camera Lens
Neil A. Switz, Michael V. D'Ambrosio, Daniel A. Fletcher
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095330
Abstract: The increasing capabilities and ubiquity of mobile phones and their associated digital cameras offer the possibility of extending low-cost, portable diagnostic microscopy to underserved and low-resource areas. However, mobile phone microscopes created by adding magnifying optics to the phone's camera module have been unable to make use of the full image sensor due to the specialized design of the embedded camera lens, exacerbating the tradeoff between resolution and field of view inherent to optical systems. This tradeoff is acutely felt for diagnostic applications, where the speed and cost of image-based diagnosis is related to the area of the sample that can be viewed at sufficient resolution. Here we present a simple and low-cost approach to mobile phone microscopy that uses a reversed mobile phone camera lens added to an intact mobile phone to enable high quality imaging over a significantly larger field of view than standard microscopy. We demonstrate use of the reversed lens mobile phone microscope to identify red and white blood cells in blood smears and soil-transmitted helminth eggs in stool samples.
An AFM-Based Stiffness Clamp for Dynamic Control of Rigidity
Kevin D. Webster,Ailey Crow,Daniel A. Fletcher
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0017807
Abstract: Atomic force microscopy (AFM) has become a powerful tool for measuring material properties in biology and imposing mechanical boundary conditions on samples from single molecules to cells and tissues. Constant force or constant height can be maintained in an AFM experiment through feedback control of cantilever deflection, known respectively as a ‘force clamp’ or ‘position clamp’. However, stiffness, the third variable in the Hookean relation F = kx that describes AFM cantilever deflection, has not been dynamically controllable in the same way. Here we present and demonstrate a ‘stiffness clamp’ that can vary the apparent stiffness of an AFM cantilever. This method, employable on any AFM system by modifying feedback control of the cantilever, allows rapid and reversible tuning of the stiffness exposed to the sample in a way that can decouple the role of stiffness from force and deformation. We demonstrated the AFM stiffness clamp on two different samples: a contracting fibroblast cell and an expanding polyacrylamide hydrogel. We found that the fibroblast, a cell type that secretes and organizes the extracellular matrix, exhibited a rapid, sub-second change in traction rate (dF/dt) and contraction velocity (dx/dt) in response to step changes in stiffness between 1–100 nN/μm. This response was independent of the absolute contractile force and cell height, demonstrating that cells can react directly to changes in stiffness alone. In contrast, the hydrogel used in our experiment maintained a constant expansion velocity (dx/dt) over this range of stiffness, while the traction rate (dF/dt) changed with stiffness, showing that passive materials can also behave differently in different stiffness environments. The AFM stiffness clamp presented here, which is applicable to mechanical measurements on both biological and non-biological samples, may be used to investigate cellular mechanotransduction under a wide range of controlled mechanical boundary conditions.
Uncovering the components of the Francisella tularensis virulence stealth strategy
Bradley D. Jones,Jed A. Rasmussen,Joshua R. Fletcher
Frontiers in Cellular and Infection Microbiology , 2014, DOI: 10.3389/fcimb.2014.00032
Abstract: Over the last decade, studies on the virulence of the highly pathogenic intracellular bacterial pathogen Francisella tularensis have increased dramatically. The organism produces an inert LPS, a capsule, escapes the phagosome to grow in the cytosol (FPI genes mediate phagosomal escape) of a variety of host cell types that include epithelial, endothelial, dendritic, macrophage, and neutrophil. This review focuses on the work that has identified and characterized individual virulence factors of this organism and we hope to highlight how these factors collectively function to produce the pathogenic strategy of this pathogen. In addition, several recent studies have been published characterizing F. tularensis mutants that induce host immune responses not observed in wild type F. tularensis strains that can induce protection against challenge with virulent F. tularensis. As more detailed studies with attenuated strains are performed, it will be possible to see how host models develop acquired immunity to Francisella. Collectively, detailed insights into the mechanisms of virulence of this pathogen are emerging that will allow the design of anti-infective strategies.
Damping of the de Haas-van Alphen oscillations in the superconducting state of MgB_2
J. D. Fletcher,A. Carrington,S. M. Kazakov,J. Karpinski
Physics , 2004, DOI: 10.1103/PhysRevB.70.144501
Abstract: The de Haas-van Alphen (dHvA) signal arising from orbits on the $\pi$ Fermi surface sheet of the two-gap superconductor MgB$_2$ has been observed in the vortex state below $H_{c2}$. An extra attenuation of the dHvA signal, beyond those effects described in the conventional Lifshitz-Kosevich expression, is seen due to the opening of the superconducting gap. Our data show that the $\pi$ band gap is still present up to $H_{c2}$. The data are compared to current theories of dHvA oscillations in the superconducting state which allow us to extract estimates for the evolution of the $\pi$ band gap with magnetic field. Contrary to results for other materials, we find that the most recent theories dramatically underestimate the damping in MgB$_2$.
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