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Find video protocols related to scientific articles indexed in Pubmed.
Chronic myelogenous leukemia, version 1.2015.
J Natl Compr Canc Netw
PUBLISHED: 11-02-2014
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Chronic myelogenous leukemia (CML) is usually diagnosed in the chronic phase. Untreated chronic phase CML will eventually progress to advanced phase (accelerated or blast phase) CML. Tyrosine kinase inhibitors (TKIs) have been shown to induce favorable response rates in patients with accelerated and blast phase CML. The addition of TKIs to chemotherapy has also been associated with improved outcomes in patients with blast phase CML. Allogeneic hematopoietic stem cell transplant remains a potentially curative option for patients with advanced phase CML, although treatment with a course of TKIs will be beneficial as a bridge to transplant. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with advanced phase CML.
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Impact of copper overpressure on the synthesis of hexagonal boron nitride atomic layers.
ACS Appl Mater Interfaces
PUBLISHED: 09-22-2014
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Hexagonal boron nitride (h-BN) atomic layers are synthesized on polycrystalline copper foils via a novel chemical vapor deposition (CVD) process that maintains a vapor-phase copper overpressure during growth. Compared to h-BN films grown without a copper overpressure, this process results in a >10× reduction of 3-dimensional BN fullerene-like surface features, a reduction of carbon and oxygen contamination of 65% and 62%, respectively, an increase in h-BN grain size of >2×, and an 89% increase in electrical breakdown strength.
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Clinical and pathologic analysis of extramedullary tumors after hematopoietic stem cell transplantation.
Hum. Pathol.
PUBLISHED: 05-06-2014
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Clinical and pathologic analyses of 41 extramedullary biopsy/resection specimens of extramedullary tumors (EMTs) after hematopoietic stem cell transplantation (HSCT) were performed. The 41 EMT specimens were from 28 patients, with 11 having more than 1 consecutive EMT in different anatomic locations at different times post-HSCT. The median age at EMT diagnosis was 45 years (range, 17-73 years), and the male/female ratio was 17:11. The most common initial diagnosis was acute myeloid leukemia (21), followed by chronic myeloid leukemia with myeloid blast phase (2), primary myelofibrosis with acute leukemic transformation (1), acute lymphoblastic leukemia (2), mixed lineage T/myeloid leukemia (1), and plasma cell myeloma (1). All initial presentations were limited to bone marrow-only disease. Twenty patients had abnormal chromosomal karyotypes, whereas 6 had normal cytogenetics with their original disease. All patients received standard chemotherapy followed by allogeneic (27) or autologous (1) HSCT. The EMTs occurred 2 to 177 months (median, 16.5 months) after HSCT and were diagnosed as solid mass lesions as follows: skin and soft tissue (10), central nervous system and paraspinal tissue (9), breast (7), gastrointestinal tract (4), lymph node (4), genitourinary system (4), and mediastinum (3). Interestingly, all but 3 patients had negative bone marrows at the time their EMT was diagnosed, indicating that most EMTs presented as sole lesion of relapsed disease. The overall outcome was dismal for patients with EMT, with 20 (71%) of 28 patients deceased at 1 to 26 months after EMT diagnosis, with a median overall survival of only 6.5 months.
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An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.
Prehosp Emerg Care
PUBLISHED: 03-20-2014
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This report describes the development of an evidence-based guideline for external hemorrhage control in the prehospital setting. This project included a systematic review of the literature regarding the use of tourniquets and hemostatic agents for management of life-threatening extremity and junctional hemorrhage. Using the GRADE methodology to define the key clinical questions, an expert panel then reviewed the results of the literature review, established the quality of the evidence and made recommendations for EMS care. A clinical care guideline is proposed for adoption by EMS systems. Key words: tourniquet; hemostatic agents; external hemorrhage.
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Umbilical cord blood expansion with nicotinamide provides long-term multilineage engraftment.
J. Clin. Invest.
PUBLISHED: 01-07-2014
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Delayed hematopoietic recovery is a major drawback of umbilical cord blood (UCB) transplantation. Transplantation of ex vivo-expanded UCB shortens time to hematopoietic recovery, but long-term, robust engraftment by the expanded unit has yet to be demonstrated. We tested the hypothesis that a UCB-derived cell product consisting of stem cells expanded for 21 days in the presence of nicotinamide and a noncultured T cell fraction (NiCord) can accelerate hematopoietic recovery and provide long-term engraftment.
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EGFRvIII mCAR-modified T cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.
Clin. Cancer Res.
PUBLISHED: 12-18-2013
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Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. EGFRvIII is a constitutively activated mutant of the naturally occurring epidermal growth factor receptor and is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues.
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Chronic Myelogenous Leukemia, Version 1.2014.
J Natl Compr Canc Netw
PUBLISHED: 11-15-2013
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The 2014 NCCN Clinical Practice Guidelines in Oncology for Chronic Myelogenous Leukemia recommend quantitative reverse-transcription polymerase chain reaction (QPCR) standardized to International Scale (IS) as the preferred method for monitoring molecular response to tyrosine kinase inhibitor (TKI) therapy. A BCR-ABL1 transcript level of 10% or less (IS) is now included as the response milestone at 3 and 6 months. Change of therapy to an alternate TKI is recommended for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with imatinib. Continuing the same dose of TKI or switching to an alternate TKI are options for patients with BCR-ABL1 transcript levels greater than 10% (IS) at 3 months after primary treatment with dasatinib or nilotinib. The guidelines recommend 6-month evaluation with QPCR (IS) for patients with BCR-ABL1 transcript levels greater than 10% at 3 months. Monitoring with QPCR (IS) every 3 months is recommended for all patients, including those who meet response milestones at 3, 6, 12, and 18 months (BCR-ABL1 transcript level ?10% [IS] at 3 and 6 months, complete cytogenetic response at 12 and 18 months).
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ABSOLUTE CONFIGURATION AND BIOLOGICAL PROPERTIES OF ENANTIOMERS OF CFTR INHIBITOR BPO-27.
ACS Med Chem Lett
PUBLISHED: 07-02-2013
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We previously reported benzopyrimido-pyrrolo-oxazinedione (BPO) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in a model of polycystic kidney disease. Here, we separated the enantiomers of lead compound BPO-27, (1), which contains a single chiral center, and determined their absolute configuration, activity and metabolic stability. Following separation by chiral supercritical fluid chromatography, the R enantiomer, as determined by x-ray crystallography, inhibited CFTR chloride conductance with IC50 ~ 4 nM, while S enantiomer was inactive. In vitro metabolic stability in hepatic microsomes showed both enantiomers as stable, with <5 % metabolism in 4 h. Following bolus interperitoneal administration in mice, serum (R)-1 decayed with t1/2 ~ 1.6 h and gave sustained therapeutic concentrations in kidney.
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Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study.
Lancet Neurol
PUBLISHED: 05-02-2013
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Seizure prediction would be clinically useful in patients with epilepsy and could improve safety, increase independence, and allow acute treatment. We did a multicentre clinical feasibility study to assess the safety and efficacy of a long-term implanted seizure advisory system designed to predict seizure likelihood and quantify seizures in adults with drug-resistant focal seizures.
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PDBStat: a universal restraint converter and restraint analysis software package for protein NMR.
J. Biomol. NMR
PUBLISHED: 04-22-2013
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The heterogeneous array of software tools used in the process of protein NMR structure determination presents organizational challenges in the structure determination and validation processes, and creates a learning curve that limits the broader use of protein NMR in biology. These challenges, including accurate use of data in different data formats required by software carrying out similar tasks, continue to confound the efforts of novices and experts alike. These important issues need to be addressed robustly in order to standardize protein NMR structure determination and validation. PDBStat is a C/C++ computer program originally developed as a universal coordinate and protein NMR restraint converter. Its primary function is to provide a user-friendly tool for interconverting between protein coordinate and protein NMR restraint data formats. It also provides an integrated set of computational methods for protein NMR restraint analysis and structure quality assessment, relabeling of prochiral atoms with correct IUPAC names, as well as multiple methods for analysis of the consistency of atomic positions indicated by their convergence across a protein NMR ensemble. In this paper we provide a detailed description of the PDBStat software, and highlight some of its valuable computational capabilities. As an example, we demonstrate the use of the PDBStat restraint converter for restrained CS-Rosetta structure generation calculations, and compare the resulting protein NMR structure models with those generated from the same NMR restraint data using more traditional structure determination methods. These results demonstrate the value of a universal restraint converter in allowing the use of multiple structure generation methods with the same restraint data for consensus analysis of protein NMR structures and the underlying restraint data.
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Computational capabilities of random automata networks for reservoir computing.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 04-16-2013
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This paper underscores the conjecture that intrinsic computation is maximal in systems at the "edge of chaos". We study the relationship between dynamics and computational capability in random Boolean networks (RBN) for reservoir computing (RC). RC is a computational paradigm in which a trained readout layer interprets the dynamics of an excitable component (called the reservoir) that is perturbed by external input. The reservoir is often implemented as a homogeneous recurrent neural network, but there has been little investigation into the properties of reservoirs that are discrete and heterogeneous. Random Boolean networks are generic and heterogeneous dynamical systems and here we use them as the reservoir. A RBN is typically a closed system; to use it as a reservoir we extend it with an input layer. As a consequence of perturbation, the RBN does not necessarily fall into an attractor. Computational capability in RC arises from a tradeoff between separability and fading memory of inputs. We find the balance of these properties predictive of classification power and optimal at critical connectivity. These results are relevant to the construction of devices which exploit the intrinsic dynamics of complex heterogeneous systems, such as biomolecular substrates.
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Myeloablative temozolomide enhances CD8? T-cell responses to vaccine and is required for efficacy against brain tumors in mice.
PLoS ONE
PUBLISHED: 02-05-2013
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Temozolomide (TMZ) is an alkylating agent shown to prolong survival in patients with high grade glioma and is routinely used to treat melanoma brain metastases. A prominent side effect of TMZ is induction of profound lymphopenia, which some suggest may be incompatible with immunotherapy. Conversely, it has been proposed that recovery from chemotherapy-induced lymphopenia may actually be exploited to potentiate T-cell responses. Here, we report the first demonstration of TMZ as an immune host-conditioning regimen in an experimental model of brain tumor and examine its impact on antitumor efficacy of a well-characterized peptide vaccine. Our results show that high-dose, myeloablative (MA) TMZ resulted in markedly reduced CD4(+), CD8(+) T-cell and CD4(+)Foxp3(+) TReg counts. Adoptive transfer of naïve CD8(+) T cells and vaccination in this setting led to an approximately 70-fold expansion of antigen-specific CD8(+) T cells over controls. Ex vivo analysis of effector functions revealed significantly enhanced levels of pro-inflammatory cytokine secretion from mice receiving MA TMZ when compared to those treated with a lower lymphodepletive, non-myeloablative (NMA) dose. Importantly, MA TMZ, but not NMA TMZ was uniquely associated with an elevation of endogenous IL-2 serum levels, which we also show was required for optimal T-cell expansion. Accordingly, in a murine model of established intracerebral tumor, vaccination-induced immunity in the setting of MA TMZ-but not lymphodepletive, NMA TMZ-led to significantly prolonged survival. Overall, these results may be used to leverage the side-effects of a clinically-approved chemotherapy and should be considered in future study design of immune-based treatments for brain tumors.
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Phase II trial of panobinostat, an oral pan-deacetylase inhibitor in patients with primary myelofibrosis, post-essential thrombocythaemia, and post-polycythaemia vera myelofibrosis.
Br. J. Haematol.
PUBLISHED: 01-16-2013
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Myelofibrosis (MF) is a Philadelphia chromosome-negative stem cell myeloproliferative neoplasm (MPN) associated with cytopenias, splenomegaly, constitutional symptoms, and poor prognosis. MF patients commonly express JAK2 V617F mutation and activation of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling. Agents targeting the JAK/STAT pathway have demonstrated efficacy in patients with MF. This study evaluated panobinostat, a pan-deacetylase inhibitor that depletes JAK2 V617F levels and JAK/STAT signalling in MPN cells, in patients with primary MF, post-essential thrombocythaemia MF, and post-polycythaemia vera MF. Patients received panobinostat 40 mg administered three times per week. Dose reductions were permitted for toxicities. The primary endpoint was response rate at 6 months using International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) consensus criteria. Analyses of peripheral blood cells from treated patients revealed that panobinostat inhibited JAK/STAT signalling, decreased inflammatory cytokine levels, and decreased JAK2 V617F allelic burden. However, panobinostat was poorly tolerated at the dose and schedule evaluated, and only 16 of 35 patients completed ?2 cycles of treatment. One patient (3%) achieved an IWG-MRT response. Common adverse events were thrombocytopenia (71.4%) and diarrhoea (80.0%). Although molecular correlative analyses suggested that panobinostat inhibits key intracellular targets, limited clinical activity was observed because of poor tolerance.
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Rapidly regulating platelet activity in vivo with an antidote controlled platelet inhibitor.
Mol. Ther.
PUBLISHED: 11-15-2011
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Millions of individuals are prescribed platelet inhibitors, such as aspirin and clopidogrel, to reduce their risk of thrombosis-related clinical events. Unfortunately many platelet inhibitors are contraindicated in surgical settings because of their inherent bleeding risk complicating the treatment of patients who require surgery. We describe the development of a potent antiplatelet agent, an RNA aptamer-termed Ch-9.14-T10 that binds von Willebrand factor (VWF) with high affinity and inhibits thrombosis in a murine carotid artery damage model. As expected, when this potent antiplatelet agent is administered, it greatly increases bleeding from animals that are surgically challenged. To improve this antiplatelet agents safety profile, we describe the generation of antidotes that can rapidly reverse the activity of Ch-9.14-T10 and limit blood loss from surgically challenged animals. Our work represents the first antidote controllable antiplatelet agent, which could conceivably lead to improved medical management of patients requiring antiplatelet medication who also need surgery.
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Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment.
Blood
PUBLISHED: 09-19-2011
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Imatinib mesylate treatment markedly reduces the burden of leukemia cells in chronic myelogenous leukemia (CML) patients. However, patients remain at risk for relapse on discontinuing treatment. We have previously shown that residual BCR-ABL(+) progenitors can be detected in CML patients within the first 2 years of imatinib treatment. However, reduced rates of relapse and continued decline of BCR-ABL levels with prolonged treatment, together with the ability of selected patients to maintain remission after discontinuing treatment, led us to investigate whether prolonged imatinib exposure resulted in reduction or elimination of BCR-ABL(+) stem cells. We evaluated BCR-ABL expression in CD34(+)CD38(+) (38(+)) committed progenitors and CD34(+)CD38(-) (38(-)) stem/primitive progenitor cells in samples from CML patients on imatinib treatment for at least 4 years with cytogenetic and molecular response. High levels of BCR-ABL expression were maintained over time in the 38(-) stem cell fraction. The absolute frequency of BCR-ABL(+) cells as determined by limiting dilution analysis was consistently higher in 38(-) compared with 38(+) cells. Transplantation into NOD/SCID-IL2R?-chain knockout mice demonstrated that BCR-ABL(+) cells had long-term in vivo repopulating capacity. These results directly demonstrate that BCR-ABL(+) stem cells persist in CML patients despite prolonged treatment with imatinib, and support ongoing efforts to target this population.
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Characterization of graphene films and transistors grown on sapphire by metal-free chemical vapor deposition.
ACS Nano
PUBLISHED: 09-14-2011
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We present a novel method for the direct metal-free growth of graphene on sapphire that yields high quality films comparable to that of graphene grown on SiC by sublimation. Graphene is synthesized on sapphire via the simple decomposition of methane at 1425-1600 °C. Film quality was found to be a strong function of growth temperature. The thickness, structure, interface characteristics, and electrical transport properties were characterized in order to understand the utility of this material for electronic devices. Graphene synthesized on sapphire is found to be strain relieved, with no evidence of an interfacial buffer layer. There is a strong correlation between the graphene structural quality and carrier mobility. Room temperature Hall effect mobility values were as high as 3000 cm(2)/(V s), while measurements at 2 K reached values of 10,500 cm(2)/(V s). These films also display evidence of the quantum Hall effect. Field effect transistors fabricated from this material had a typical current density of 200 mA/mm and transconductance of 40 mS/mm indicating that material performance may be comparable to graphene on SiC.
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Epitaxial graphene transistors: enhancing performance via hydrogen intercalation.
Nano Lett.
PUBLISHED: 08-04-2011
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We directly demonstrate the importance of buffer elimination at the graphene/SiC(0001) interface for high frequency applications. Upon successful buffer elimination, carrier mobility increases from an average of 800 cm(2)/(V s) to >2000 cm(2)/(V s). Additionally, graphene transistor current saturation increases from 750 to >1300 mA/mm, and transconductance improves from 175 mS/mm to >400 mS. Finally, we report a 10× improvement in the extrinsic current gain response of graphene transistors with optimal extrinsic current-gain cutoff frequencies of 24 GHz.
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Enhanced transport and transistor performance with oxide seeded high-? gate dielectrics on wafer-scale epitaxial graphene.
Nano Lett.
PUBLISHED: 08-04-2011
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We explore the effect of high-? dielectric seed layer and overlayer on carrier transport in epitaxial graphene. We introduce a novel seeding technique for depositing dielectrics by atomic layer deposition that utilizes direct deposition of high-? seed layers and can lead to an increase in Hall mobility up to 70% from as-grown. Additionally, high-? seeded dielectrics are shown to produce superior transistor performance relative to low-? seeded dielectrics and the presence of heterogeneous seed/overlayer structures is found to be detrimental to transistor performance, reducing effective mobility by 30-40%. The direct deposition of high-purity oxide seed represents the first robust method for the deposition of uniform atomic layer deposited dielectrics on epitaxial graphene that improves carrier transport.
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Monoclonal antibody blockade of IL-2 receptor ? during lymphopenia selectively depletes regulatory T cells in mice and humans.
Blood
PUBLISHED: 07-18-2011
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Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vaccine-driven immune responses and significantly reduces malignant growth in an established model of murine tumorigenesis. Unexpectedly, despite the improved antitumor efficacy engendered by TMZ-induced lymphopenia, there was a treatment related increase in the frequency of immunosuppressive regulatory T cells (T(Regs); P = .0006). Monoclonal antibody (mAb)-mediated inhibition of the high-affinity IL-2 receptor ? (IL-2R?/CD25) during immunotherapy in normal mice depleted T(Regs) (73% reduction; P = .0154) but also abolished vaccine-induced immune responses. However, during lymphodepletion, IL-2R? blockade decreased T(Regs) (93% reduction; P = .0001) without impairing effector T-cell responses, to augment therapeutic antitumor efficacy (66% reduction in tumor growth; P = .0024). Of clinical relevance, we also demonstrate that anti-IL-2R? mAb administration during recovery from lymphodepletive TMZ in patients with glioblastoma reduced T(Reg) frequency (48% reduction; P = .0061) while permitting vaccine-stimulated antitumor effector cell expansion. To our knowledge, this is the first report of systemic antibody-mediated T(Reg) depletion during lymphopenia and the consequent synergistic enhancement of vaccine-driven cellular responses, as well as the first demonstration that anti-IL-2R? mAbs function differentially in nonlymphopenic versus lymphopenic contexts.
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Potent, metabolically stable benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR inhibitors for polycystic kidney disease.
J. Med. Chem.
PUBLISHED: 07-12-2011
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We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure-activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ-102, IC(50) ? 90 nM), we synthesized 16 PPQ analogues and 11 BPO analogues. The analogues were efficiently synthesized in 5-6 steps and 11-61% overall yield. Modification of 8 by bromine substitution at the 5-position of the furan ring, replacement of the secondary amine with an ether bridge, and carboxylation, gave 6-(5-bromofuran-2-yl)-7,9-dimethyl-8,10-dioxo-11-phenyl-7,8,9,10-tetrahydro-6H-benzo[b]pyrimido [4,5:3,4]pyrrolo [1,2-d][1,4]oxazine-2-carboxylic acid 42 (BPO-27), which fully inhibited CFTR with IC(50) ? 8 nM and, compared to 8, had >10-fold greater metabolic stability and much greater polarity/aqueous solubility. In an embryonic kidney culture model of PKD, 42 prevented cyst growth with IC(50) ? 100 nM. Benzopyrimido-pyrrolo-oxazinediones such as 42 are potential development candidates for antisecretory therapy of PKD.
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A phase I study in adults of clofarabine combined with high-dose melphalan as reduced-intensity conditioning for allogeneic transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-14-2011
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Clofarabine is a novel purine nucleoside analog with immunosuppressive and antileukemia activity. We performed a phase I study of the combination of clofarabine plus melphalan as a reduced-intensity conditioning regimen for allogeneic stem cell transplantation in patients with acute myelogenous leukemia. Patients over age 18 in complete remission or with active disease (up to 50% marrow blasts) who had a matched related or unrelated donor were eligible. The conditioning regimen consisted of escalating doses of clofarabine plus melphalan, followed by allogeneic stem cell transplantation. Sixteen patients (median age, 63 years) were treated at 3 dose levels; 4 of these patients had primary induction failure, and 3 were in first relapse. One patient at dose level 2 and 1 patient at dose level 3 died of multiorgan toxicity; no other dose-limiting toxicities were seen. All other patients at both doses of clofarabine studied demonstrated complete engraftment by day 30, with a median time to absolute neutrophil count recovery of 14 days, and 16 days for platelet recovery. With a median follow-up of 17 months, only 2 patients relapsed, and 4 patients died. Clofarabine plus melphalan at dose level 2 is a well-tolerated conditioning regimen with activity in patients with advanced acute myelogenous leukemia.
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Glutamatergic neurons in rodent models respond to nanoscale particulate urban air pollutants in vivo and in vitro.
Environ. Health Perspect.
PUBLISHED: 03-29-2011
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Inhalation of airborne particulate matter (PM) derived from urban traffic is associated with pathology in the arteries, heart, and lung; effects on brain are also indicated but are less documented.
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NCCN Task Force report: tyrosine kinase inhibitor therapy selection in the management of patients with chronic myelogenous leukemia.
J Natl Compr Canc Netw
PUBLISHED: 02-22-2011
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The advent of imatinib has dramatically improved outcomes in patients with chronic myelogenous leukemia (CML). It has become the standard of care for all patients with newly diagnosed chronic-phase CML based on its successful induction of durable responses in most patients. However, its use is complicated by the development of resistance in some patients. Dose escalation might overcome this resistance if detected early. The second-generation tyrosine kinase inhibitors (TKIs) dasatinib and nilotinib provide effective therapeutic options for managing patients resistant or intolerant to imatinib. Recent studies have shown that dasatinib and nilotinib provide quicker and potentially better responses than standard-dose imatinib when used as a first-line treatment. The goal of therapy for patients with CML is the achievement of a complete cytogenetic response, and eventually a major molecular response, to prevent disease progression to accelerated or blast phase. Selecting the appropriate TKI depends on many factors, including disease phase, primary or secondary resistance to TKI, the agents side effect profile and its relative effectiveness against BCR-ABL mutations, and the patients tolerance to therapy. In October 2010, NCCN organized a task force consisting of a panel of experts from NCCN Member Institutions with expertise in the management of patients with CML to discuss these issues. This report provides recommendations regarding the selection of TKI therapy for the management of patients with CML based on the evaluation of available published clinical data and expert opinion among the task force members.
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Temporal trends in motor vehicle and secondary organic tracers using in situ methylation thermal desorption GCMS.
Environ. Sci. Technol.
PUBLISHED: 11-24-2010
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Organic aerosol measurements with high temporal resolution can differentiate primary organic carbon (POC) from secondary organic carbon (SOC) and can be used to distinguish morning rush hour traffic emissions and subsequent photo-oxidation. In the current study, five hour filter samples were collected during the Summer Study for Organic Aerosols at Riverside (SOAR-1 in CA, USA) for analysis of organic molecular markers. To achieve the low detection limits required for the high temporal resolution data, a laboratory-based in situ methylation thermal desorption gas chromatography-mass spectrometry method was developed. This enabled the measurement of potential markers of SOC, including phthalic acid, along with markers for traffic emissions, including norhopane. The aromatic acids correlated well with unapportioned OC from a molecular marker chemical mass balance model (SOC-cmb; r(2) = 0.46-0.70) and SOC from the elemental carbon tracer method (SOC-ec; r(2) = 0.40-0.56). The aromatic acid/norhopane ratio increased substantially over the course of each day. The average mid-day phthalic acid ratio compared to previously published roadway emissions was a factor of 4 times higher, while the average 1,2,3-benzenetricarboxylic acid ratio was a factor of 40 times higher than roadway emissions. Using correlation plots of SOC-cmb and phthalic acid, it was estimated that 2.9 ± 0.6 ?g m(-3) SOC was associated with mid-day aromatic acid production in Riverside.
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Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma.
Clin. Cancer Res.
PUBLISHED: 11-03-2010
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To establish feasibility, maximum tolerated dose (MTD), and potential efficacy of ablative dose total marrow irradiation (TMI) delivered by helical tomotherapy in patients with multiple myeloma (MM).
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Alcohol consumption and cancer risk: understanding possible causal mechanisms for breast and colorectal cancers.
Evid Rep Technol Assess (Full Rep)
PUBLISHED: 11-01-2010
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The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers.
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A covariance NMR toolbox for MATLAB and OCTAVE.
J. Magn. Reson.
PUBLISHED: 08-17-2010
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The Covariance NMR Toolbox is a new software suite that provides a streamlined implementation of covariance-based analysis of multi-dimensional NMR data. The Covariance NMR Toolbox uses the MATLAB or, alternatively, the freely available GNU OCTAVE computer language, providing a user-friendly environment in which to apply and explore covariance techniques. Covariance methods implemented in the toolbox described here include direct and indirect covariance processing, 4D covariance, generalized indirect covariance (GIC), and Z-matrix transform. In order to provide compatibility with a wide variety of spectrometer and spectral analysis platforms, the Covariance NMR Toolbox uses the NMRPipe format for both input and output files. Additionally, datasets small enough to fit in memory are stored as arrays that can be displayed and further manipulated in a versatile manner within MATLAB or OCTAVE.
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Epitaxial graphene materials integration: effects of dielectric overlayers on structural and electronic properties.
ACS Nano
PUBLISHED: 04-27-2010
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We present the integration of epitaxial graphene with thin film dielectric materials for the purpose of graphene transistor development. The impact on epitaxial graphene structural and electronic properties following deposition of Al(2)O(3), HfO(2), TiO(2), and Ta(2)O(5) varies based on the choice of dielectric and deposition parameters. Each dielectric film requires the use of a nucleation layer to ensure uniform, continuous coverage on the graphene surface. Graphene quality degrades most severely following deposition of Ta(2)O(5), while the deposition if TiO(2) appears to improve the graphene carrier mobility. Finally, we discuss the potential of dielectric stack engineering for improved transistor performance.
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Inconsolable night-time awakening: beyond night terrors.
J Dev Behav Pediatr
PUBLISHED: 04-24-2010
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Sophia is a 3-year-old girl who was brought to her pediatrician by her parents who were concerned about inconsolable night-time awakening. Her mother indicated that she has frequent (>6), early nocturnal awakenings accompanied by screaming and crying lasting up to 1 hour since her birth. These episodes increased in intensity and frequency in the past year since the birth of her brother. With a bedtime routine (a cup of water by bedside with a washcloth and touching mothers nose, chin, and cheeks), Sophia falls asleep easily; however, within 1 hour she awakes screaming and flailing unaware of her surroundings and unable to be comforted. There are no tonic-clonic movements. Prior interventions, including a sleep coach and "letting Sophia cry it out," did not change her sleep pattern. Sophias mother reports that she needs to be on a specific daily routine including set times for awakening, activity, snacks, naps, and meals. Diversion from the routine and separation from her mother results in a tantrum (kicking, hitting, screaming, and inconsolability) often lasting more than 30 minutes. Sophia was born after an uncomplicated 37-week gestation. Neonatal hyperbilirubinemia required readmission for 24 hours of phototherapy; serum bilirubin levels were performed daily for 3 weeks after discharge. At 6 weeks, daily episodes of screaming, inconsolability, forceful vomiting, and inability to sleep led to a diagnosis of gastroesophageal reflux. Medication trials were not successful, but the symptoms resolved by 5 months. Formula intolerance and difficulty swallowing and chewing different textures of solid food occurred in the first year. Occupational therapy was of "no benefit"; Sophia was overwhelmed by the activity and took a long time to warm up to the therapist. Her texture aversion resolved by 2 years of age. She prefers one-on-one play and has minimal interactions with other children. She has met all her developmental milestones appropriately and has no other health issues. Sophia lives with her parents and infant brother. There is a maternal family history of insomnia and sleep walking and a paternal history of sleeping walking. Her mother adheres to a strict daily schedule. Sleep deprivation, differences parent child-rearing practices, social isolation, and lack of quality parent time were all identified by the mother as significant marital stressors. During the office visit, Sophia required 30 minutes to warm up and smile, and over 60 minutes before she spoke her first word. Physical examination was normal (including growth measurements) and the developmental examination was age-appropriate. Upon completion of the assessment, she was engaging, playful, and cooperative with the pediatrician.
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It looks like autism: caution in diagnosis.
J Dev Behav Pediatr
PUBLISHED: 04-24-2010
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CASE 1: At 3 years of age, Billy was seen by his pediatrician for a well child visit. Spontaneous speech was limited during the visit. He did not interact with the pediatrician and attempts to play with Billy resulted in oppositional behavior. About 3 months after the visit, Billys parents requested a developmental evaluation; he was diagnosed with autism by means of an observational measure and a parent interview. Billy was born full term after an uncomplicated labor, delivery and postnatal period. Motor milestones were normal. His parents recalled that he used his finger to point to an object prior to using words. He spoke several single words by his first birthday and used phrases before age 2 years. Billy was described as often having difficulty with transitions, but he is happy and outgoing in familiar situations. At 3 years old, when he started preschool, Billy did not speak to either the teacher or other children. This pattern of refusal to speak persists. His parents report that he talks to them and one uncle using complete sentences with clear speech. Billy prefers to repeat activities and is reluctant to try activities. He frequently plays with the same toy cars placing them in a neat line and becomes upset if things are not done in the same way. An uncle has Asperger syndrome. CASE 2: Juan, a 3 year old Mexican-American boy, was referred by his preschool teacher because "he does not interact with other children or use language at an age-appropriate level." He prefers to play alone, resists participation in group activities at preschool, and does not share as well as other students according to his teacher. Expressive language with speech is rarely seen in preschool. In contrast, at home he plays interactively, shares toys with his older brother and speaks in short, clear sentences. In preschool, English is spoken exclusively. At home, Spanish is the primary language. Prenatal and birth histories were uneventful. Motor and social milestones were achieved art the expected times. He spoke his first word at 18 months and 2-word phrases at 2 years. Currently, he speaks in full sentences with pleurals and pronouns. He follows commands and recently had a normal audiogram. His parents, who speak English with ease, are concerned about the teachers observations at school. The physical examination was normal; the developmental and behavioral assessments were conducted by an English speaking clinician. Juan played interactively with toys while demonstrating curiosity, showing and joint attention. There was no speech production during a 30 minute period although he did follow directions. When a Spanish speaking clinician assumed responsibility for the assessment, Juans speech production increased significantly. He told a story about his drawing and talked about the family dog and his brother. He had good eye contact and appropriate pragmatic speech when the dialogue was in Spanish.
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Max: concern with social skills, language and excessive TV viewing in a 3 year old.
J Dev Behav Pediatr
PUBLISHED: 04-24-2010
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Max is a 3-year-old healthy boy who was brought to the pediatricians office by his mother for frequent temper tantrums at home. His teachers at the Montessori school are concerned about his communication skills. He is very talkative with his peers, but he constantly speaks about Thomas the Tank Engine. His peers seem to be uninterested in his repetitive stories. His teachers believe that Max has difficulty separating fantasy and reality. At home, his mother describes Max as "difficult to control." When placed in time-out, he hits, kicks and scratches his mother. He has a large vocabulary, but mostly speaks in phrases directly from cartoons. For example, he repeats a particular phrase from a program in which the main character grows in size with fury every time he gets angry and says, "I hate it, leave me alone." Before this exposure, the mother reports that her son had never used the word "hate." Max watches 5 hours of childrens programs on television every day; he is not exposed to any news programs. Frequently, he watches the same episode of a program many times. Maxs mother believes that he can watch as much TV as he wants as long as it is "good programming," so he only watches PBS kids shows and the Disney channel.
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Effective targeting of quiescent chronic myelogenous leukemia stem cells by histone deacetylase inhibitors in combination with imatinib mesylate.
Cancer Cell
PUBLISHED: 03-19-2010
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Imatinib mesylate (IM) induces remission in chronic myelogenous leukemia (CML) patients but does not eliminate leukemia stem cells (LSCs), which remain a potential source of relapse. Here we investigated the ability of HDAC inhibitors (HDACis) to target CML stem cells. Treatment with HDACis combined with IM effectively induced apoptosis in quiescent CML progenitors resistant to elimination by IM alone, and eliminated CML stem cells capable of engrafting immunodeficient mice. In vivo administration of HDACis with IM markedly diminished LSCs in a transgenic mouse model of CML. The interaction of IM and HDACis inhibited genes regulating hematopoietic stem cell maintenance and survival. HDACi treatment represents an effective strategy to target LSCs in CML patients receiving tyrosine kinase inhibitors.
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Geophysical detection of relict metasomatism from an Archean (approximately 3.5 Ga) subduction zone.
Science
PUBLISHED: 12-08-2009
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When plate tectonics started on Earth has been uncertain, and its role in the assembly of early continents is not well understood. By synthesizing coincident seismic and electrical profiles, we show that subduction processes formed the Archean Slave craton in Canada. The spatial overlap between a seismic discontinuity and a conductive anomaly at approximately 100 kilometers depth, in conjunction with the occurrence of mantle xenoliths rich in secondary minerals representative of a metasomatic front, supports cratonic assembly by subduction and accretion of lithospheric fragments. Although evidence of cratonic assembly is rarely preserved, these results suggest that plate tectonics was operating as early as Paleoarchean times, approximately 3.5 billion years ago (Ga).
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Sensitivity and bias of molecular marker-based aerosol source apportionment models to small conltibutions of coal combustion soot.
Environ. Sci. Technol.
PUBLISHED: 11-20-2009
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Carbonaceous atmospheric particulate matter (PM25) collected in the midwestern United States revealed that soot emissions from incomplete coal combustion were important sources of several organic molecular markers used in source apportionment studies. Despite not constituting a major source of organic carbon in the PM25, coal soot was an important source of polyaromatic hydrocarbons, hopanes, and elemental carbon. These marker compounds are becoming widely used for source apportionment of atmospheric organic PM, meaning that significant emissions of these marker compounds from unaccounted sources such as coal soot could bias apportionment results. This concept was demonstrated using measurements of atmospheric PM collected on a 1-in-6 day schedule at three monitoring sites in Ohio: Mingo Junction (near Steubenville), Cincinnati, and Cleveland. Impacts of coal sootwere measured to be significant at Mingo Junction and small at Cleveland and Cincinnati. As a result, biases in apportionment results were substantial at Mingo Junction and insignificant at Cleveland and Cincinnati. Misapportionments of organic carbon mass at Mingo Junction were significant when coal soot was detected in the particulate samples as identified bythe presence of picene, but when coal soot was not included in the model: gasoline engines (+8% to +58% of OC), smoking engines (0% to -17% of OC), biomass combustion (+1% to +11% of OC), diesel engines (-1% to -2% of OC), natural gas combustion (0% to -2% of OC), and unapportioned OC (0% to -47% of OC). These results suggest that the role of coal soot in source apportionment studies needs to be better examined in many parts of the United States and other parts of the world.
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A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens.
Blood
PUBLISHED: 11-19-2009
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Combination tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant in patients conditioned with a fractionated total body irradiation-based regimen has shown encouraging results. We studied this prophylaxis combination in 85 patients receiving a matched-sibling transplant conditioned with 3 different regimens:fludarabine-melphalan (n = 46); total body irradiation-etoposide (n = 28), and busulfan-cyclophosphamide (n = 11). The conditioning regimens were completed on day -4. Sirolimus and tacrolimus were started on day -3 to avoid overlap with conditioning therapy. All patients engrafted, with a median time to neutrophil engraftment of 15 days. The cumulative incidence of acute GVHD grades II to IV and III to IV was 43% and 19%, respectively, with no significant difference by conditioning regimen. The 2-year cumulative incidence of chronic GVHD was 46%. With a median follow-up of 26 months, disease-free survival was 58% and overall survival, 66%. The day-100 and 2-year nonrelapse mortality was 4.8% and 10.2%, respectively. The overall incidence of thrombotic microangiopathy was 19%, and it was significantly higher with busulfan/cyclophosphamide (55%, P = .005). Tacrolimus plus sirolimus is an effective combination for acute GVHD prophylaxis and is associated with very low nonrelapse mortality. Thrombotic microangiopathy is a significant complication with this regimen, particularly in patients receiving busulfan/cyclophosphamide.
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Generalized indirect covariance NMR formalism for establishment of multidimensional spin correlations.
J Phys Chem A
PUBLISHED: 10-09-2009
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Multidimensional nuclear magnetic resonance (NMR) experiments measure spin-spin correlations, which provide important information about bond connectivities and molecular structure. However, direct observation of certain kinds of correlations can be very time-consuming due to limitations in sensitivity and resolution. Covariance NMR derives correlations between spins via the calculation of a (symmetric) covariance matrix, from which a matrix-square root produces a spectrum with enhanced resolution. Recently, the covariance concept has been adopted to the reconstruction of nonsymmetric spectra from pairs of 2D spectra that have a frequency dimension in common. Since the unsymmetric covariance NMR procedure lacks the matrix-square root step, it does not suppress relay effects and thereby may generate false positive signals due to chemical shift degeneracy. A generalized covariance formalism is presented here that embeds unsymmetric covariance processing within the context of the regular covariance transform. It permits the construction of unsymmetric covariance NMR spectra subjected to arbitrary matrix functions, such as the square root, with improved spectral properties. This formalism extends the domain of covariance NMR to include the reconstruction of nonsymmetric NMR spectra at resolutions or sensitivities that are superior to the ones achievable by direct measurements.
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Correlating Raman spectral signatures with carrier mobility in epitaxial graphene: a guide to achieving high mobility on the wafer scale.
Nano Lett.
PUBLISHED: 09-02-2009
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We report a direct correlation between carrier mobility and Raman topography of epitaxial graphene (EG) grown on silicon carbide (SiC). We show the Hall mobility of material on SiC(0001) is highly dependent on thickness and monolayer strain uniformity. Additionally, we achieve high mobility epitaxial graphene (18100 cm(2)/(V s) at room temperature) on SiC(0001) and show that carrier mobility depends strongly on the graphene layer stacking.
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NCCN task force report: molecular markers in leukemias and lymphomas.
J Natl Compr Canc Netw
PUBLISHED: 07-29-2009
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The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkins lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.
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A comparison of summertime secondary organic aerosol source contributions at contrasting urban locations.
Environ. Sci. Technol.
PUBLISHED: 06-24-2009
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Primary and secondary sources contributing to atmospheric organic aerosol during the months of July and August were quantitatively assessed in three North American urban areas: Cleveland, Ohio, and Detroit, Michigan, in the Midwest region and Riverside, California, in the Los Angeles Air Basin. Organic molecular marker species unique to primary aerosol sources and secondarytracers derived from isoprene, alpha-pinene, beta-caryophyllene, and toluene were measured using gas chromatography-mass spectrometry. Source contributions from motor vehicles, biomass burning, vegetative detritus, and secondary organic aerosol (SOA) were estimated using chemical mass balance (CMB) modeling. In Cleveland, primary sources accounted for 37 +/- 2% of ambient organic carbon, measured biogenic and anthropogenic secondary sources contributed 46 +/- 6%, and other unknown sources contributed 17 +/- 4%. Similarly, Detroit aerosol was determined to be 44 +/- 5% primary and 37 +/- 3% secondary, while 19 +/- 7% was unaccounted for by measured sources. In Riverside, 21 +/- 3% of organic carbon came from primary sources, 26 +/- 5% was attributed to measured secondary sources, and 53 +/- 3% came from other sources that were expected to be secondary in nature. The comparison of samples across these two regions demonstrated that summertime SOA in the Midwestern United States was substantially different from the summertime SOA in the Los Angeles Air Basin and indicated the need to exert caution when generalizing about the sources and nature of SOA across different urban areas. Furthermore, the results of this study suggestthatthe contemporary understanding of SOA sources and formation mechanisms is satisfactory to explainthe majority of SOA in the Midwest Additional SOA sources and mechanisms of formation are needed to explain the majority of SOA in the Los Angeles Air Basin.
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External fixator clamp reuse degrades clamp mechanical performance.
Vet Surg
PUBLISHED: 06-23-2009
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To determine the effects of clamp reuse for the Kirschner-Ehmer (KE); Securos; and the IMEX-SK clamp.
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Improved outcomes using tacrolimus/sirolimus for graft-versus-host disease prophylaxis with a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplant as treatment of myelofibrosis.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-22-2009
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Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) regimens is a potentially curative treatment for patients (patients) with myelofibrosis (MF), as we and others have reported. Nonrelapse mortality (NRM) from graft-versus-host disease (GVHD) and other complications has limited the success of this approach. As part of an ongoing prospective research study at City of Hope, a combination of tacrolimus/sirolimus +/- methotrexate (MTX) for GVHD prophylaxis has become the standard treatment for our allogeneic HCT patients. In this report, we present results for 23 consecutive patients, including extended follow up for 9 patients previously reported who received cyclosporine (CsA)/mycophenolate moffetil (MMF)+/-MTX, and the current series of 14 patients who received tacrolimus/sirolimus+/-MTX, and evaluate the impact of the GVHD prophylaxis regimen on the outcomes. Median follow-up for alive patients was 29.0 months (9.5-97.0). The estimated 2-year overall survival (OS) for the CsA/MMF cohort was 55.6% (confidence interval 36.0, 71.3), and for the tacrolimus/sirolimus cohort it was 92.9% (63.3, 98.8) (P=.047). The probability of grade III or IV acute GVHD (aGVHD) was 60% for the CsA/MMF patients, and 10% for the tacrolimus/sirolimus group (P=.0102). No significant differences were seen for grade II to IV aGVHD in the 2 groups. We conclude that the combination of tacrolimus/sirolimus+/-MTX for GVHD prophylaxis in the setting of RIC HCT for MF appears to reduce the incidence of severe aGVHD and NRM, and leads to improved OS compared to CSA/MMF+/-MTX.
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Reduced-intensity conditioning followed by peripheral blood stem cell transplantation for adult patients with high-risk acute lymphoblastic leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-10-2009
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Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT); however, it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine (Flu)/melphalan (Mel) prior to allogeneic peripheral blood stem cell transplantation (PBSCT) between 6/14/02 and 6/15/07 at the City of Hope. Indications for the RIC regimen were: (1) aged 50 years or older (42%), (2) compromised organ function (54%), or (3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival (OS) and disease-free survival (DFS) at 2 years was 61.5%. Relapse incidence was 21.1% and nonrelapse mortality (NRM) was 21.5% at 2 years. Chronic graft-versus-host (cGVHD) developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source, or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant.
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New approved dasatinib regimen available for clinical use.
Expert Rev Anticancer Ther
PUBLISHED: 03-12-2009
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Dasatinib, a tyrosine kinase inhibitor of BCR-ABL, was originally approved for the second-line treatment of any-phase chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia at a dosage of 70 mg twice daily. In chronic-phase (CP) CML resistant to first-line imatinib, this regimen is more efficacious than high-dose imatinib. A Phase III study of CP CML has now shown that dasatinib 100 mg once daily is therapeutically noninferior to 70 mg twice daily and has an improved safety profile. Patients receiving dasatinib 100 mg once daily suffered significantly fewer thrombocytopenia (grade 3-4) and pleural effusion (all grades) events than those receiving dasatinib 70 mg twice daily. Fewer patients receiving dasatinib 100 mg once daily also required dose interruption/reduction or discontinuation. The recommended regimen for dasatinib in patients with CP disease and who are resistant or intolerant to primary therapy with imatinib is now 100 mg once daily.
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Epidural analgesia and laparoscopic technique do not reduce incidence of prolonged ileus in elective colon resections.
Am. J. Surg.
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This study evaluated the incidence and risk factors for prolonged ileus in patients undergoing elective colon resection.
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Congenital hypothyroidism caused by excess prenatal maternal iodine ingestion.
J. Pediatr.
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We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized.
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Reduced intensity allogeneic hematopoietic stem cell transplantation for MDS using tacrolimus/sirolimus-based GVHD prophylaxis.
Leuk. Res.
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We report a consecutive series of 59 patients with MDS who underwent reduced-intensity hematopoietic stem cell transplantation (RI-HSCT) with fludarabine/melphalan conditioning and tacrolimus/sirolimus-based GVHD prophylaxis. Two-year OS, EFS, and relapse incidences were 75.1%, 65.2%, and 20.9%, respectively. The cumulative incidence of non-relapse mortality at 100 days, 1 year, and 2 years was 3.4%, 8.5%, and 10.5%, respectively. The incidence of grade II-IV acute GVHD was 35.4%; grade III-IV was 18.6%. Forty of 55 evaluable patients developed chronic GVHD; of these 35 were extensive grade. This RI-HSCT protocol produces encouraging outcomes in MDS patients, and tacrolimus/sirolimus-based GVHD prophylaxis may contribute to that promising result.
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Integration of hexagonal boron nitride with quasi-freestanding epitaxial graphene: toward wafer-scale, high-performance devices.
ACS Nano
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Hexagonal boron nitride (h-BN) is a promising dielectric material for graphene-based electronic devices. Here we investigate the potential of h-BN gate dielectrics, grown by chemical vapor deposition (CVD), for integration with quasi-freestanding epitaxial graphene (QFEG). We discuss the large scale growth of h-BN on copper foil via a catalytic thermal CVD process and the subsequent transfer of h-BN to a 75 mm QFEG wafer. X-ray photoelectron spectroscopy (XPS) measurements confirm the absence of h-BN/graphitic domains and indicate that the film is chemically stable throughout the transfer process, while Raman spectroscopy indicates a 42% relaxation of compressive stress following removal of the copper substrate and subsequent transfer of h-BN to QFEG. Despite stress-induced wrinkling observed in the films, Hall effect measurements show little degradation (<10%) in carrier mobility for h-BN coated QFEG. Temperature dependent Hall measurements indicate little contribution from remote surface optical phonon scattering and suggest that, compared to HfO(2) based dielectrics, h-BN can be an excellent material for preserving electrical transport properties. Graphene transistors utilizing h-BN gates exhibit peak intrinsic cutoff frequencies >30 GHz (2.4× that of HfO(2)-based devices).
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Solution NMR structure of the ribosomal protein RP-L35Ae from Pyrococcus furiosus.
Proteins
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The ribosome consists of small and large subunits each composed of dozens of proteins and RNA molecules. However, the functions of many of the individual protomers within the ribosome are still unknown. In this article, we describe the solution NMR structure of the ribosomal protein RP-L35Ae from the archaeon Pyrococcus furiosus. RP-L35Ae is buried within the large subunit of the ribosome and belongs to Pfam protein domain family PF01247, which is highly conserved in eukaryotes, present in a few archaeal genomes, but absent in bacteria. The protein adopts a six-stranded anti-parallel ?-barrel analogous to the "tRNA binding motif" fold. The structure of the P. furiosus RP-L35Ae presented in this article constitutes the first structural representative from this protein domain family.
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Substrate considerations for graphene synthesis on thin copper films.
Nanotechnology
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Chemical vapor deposition on copper substrates is a primary technique for synthesis of high quality graphene films over large areas. While well-developed processes are in place for catalytic growth of graphene on bulk copper substrates, chemical vapor deposition of graphene on thin films could provide a means for simplified device processing through the elimination of the layer transfer process. Recently, it was demonstrated that transfer-free growth and processing is possible on SiO(2). However, the Cu/SiO(2)/Si material system must be stable at high temperatures for high quality transfer-free graphene. This study identifies the presence of interdiffusion at the Cu/SiO(2) interface and investigates the influence of metal (Ni, Cr, W) and insulating (Si(3)N(4), Al(2)O(3), HfO(2)) diffusion barrier layers on Cu-SiO(2) interdiffusion, as well as graphene structural quality. Regardless of barrier choice, we find the presence of Cu diffusion into the silicon substrate as well as the presence of Cu-Si-O domains on the surface of the copper film. As a result, we investigate the choice of a sapphire substrate and present evidence that it is a robust substrate for synthesis and processing of high quality, transfer-free graphene.
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The Expanded FindCore Method for Identification of a Core Atom Set for Assessment of Protein Structure Prediction.
Proteins
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Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (D.A. Snyder and G.T. Montelione PROTEINS 2005;59:673-686) is a superimposition independent method for identifying a core atom set, and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an "Expanded FindCore" atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines "expanded core atom sets" that match an experts intuition of which parts of the structure are sufficiently well-defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. © Proteins 2013;. © 2013 Wiley Periodicals, Inc.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.