michael WILLIAMS - Academia.edu (original) (raw)
Papers by michael WILLIAMS
The purpose of this study was to compare illness-related anxiety among participants in the Rituxi... more The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Illness-related anxiety was comparable between treatment arms at all time points (P > .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P < .001), regardless of treatment arm assignment. Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.
The journal of physical chemistry. B, Jan 12, 2013
Intermolecular vibrations of amino acid crystals occur in the THz, or far-infrared, region of the... more Intermolecular vibrations of amino acid crystals occur in the THz, or far-infrared, region of the electromagnetic spectrum. We have measured the THz and Raman spectra of DL-leucine as well as two polymorphs of DL-valine, the spectroscopic properties of which have not previously been compared. Theoretical modeling of intermolecular vibrations in hydrophobic amino acids is challenging because the van der Waals interactions between molecules are not accounted for in standard density functional theory. Therefore, to calculate the vibrational modes, we used a recently developed approach that includes these nonlocal electron correlation forces. We discuss methods for comparing results from different theoretical models using metrics other than calculated vibrational frequency and intensity, and we also report a new approach enabling concise comparison of vibrational modes that involve complicated mixtures of inter- and intramolecular displacements.
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2013
Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is both biologically ... more Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is both biologically and clinically heterogeneous. A variety of biomarkers, the achievement of minimal residual disease negativity after initial therapy, and the MCL International Prognostic Index (MIPI) are associated with patient outcome, although none has as yet been used for routine treatment stratification. Given the lack of widely accepted and standardized treatment approaches, clinical trial enrollment should always be considered for the initial therapy of MCL. Outside of the trial setting, younger and transplantation-eligible patients with newly diagnosed MCL who require treatment should first be considered for a rituximab+a high-dose cytarabine-containing regimen, followed by autologous stem cell transplantation consolidation in first remission. Symptomatic elderly and nontransplantation-eligible individuals typically receive rituximab+bendamustine, or R-CHOP (rituximab+cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone) followed by maintenance rituximab, the latter a treatment plan that has demonstrated extended response duration and survival. Promising early results for consolidation approaches with proteasome inhibitors and immunomodulatory drugs are now being tested in randomized clinical trials. The availability of highly active BCR signaling pathway inhibitors and cell death pathway modulation via BH3 mimetics, among other novel agents, promise to rapidly expand treatment options, change existing treatment paradigms, and further improve outcomes for MCL patients.
Journal of the American College of Cardiology, 2014
The aim of this study was to comprehensively review the epidemiology of aortic sclerosis (ASc) an... more The aim of this study was to comprehensively review the epidemiology of aortic sclerosis (ASc) and its association with cardiovascular events.
Proceedings of the National Academy of Sciences of the United States of America, 2014
Large commercial publishers sell bundled online subscriptions to their entire list of academic jo... more Large commercial publishers sell bundled online subscriptions to their entire list of academic journals at prices significantly lower than the sum of their á la carte prices. Bundle prices differ drastically between institutions, but they are not publicly posted. The data that we have collected enable us to compare the bundle prices charged by commercial publishers with those of nonprofit societies and to examine the types of price discrimination practiced by commercial and nonprofit journal publishers. This information is of interest to economists who study monopolist pricing, librarians interested in making efficient use of library budgets, and scholars who are interested in the availability of the work that they publish.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists, 2008
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improv... more In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. In low-tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.
Journal of Proteome Research, 2015
Although significant progress has been made in the diagnosis and treatment of colorectal cancer (... more Although significant progress has been made in the diagnosis and treatment of colorectal cancer (CRC), it remains a leading cause of cancer death worldwide. Early identification and removal of polyps that may progress to overt CRC is the cornerstone of CRC prevention. Expression of the High Mobility Group A1 (HMGA1) gene is significantly elevated in CRCs as compared with adjacent, nonmalignant tissues. We investigated metabolic aberrations induced by HMGA1 overexpression in small intestinal and colonic epithelium using traveling wave ion mobility mass spectrometry (TWIMMS) in a transgenic model in which murine Hmga1 was misexpressed in colonic epithelium. To determine if these Hmga1-induced metabolic alterations in mice were relevant to human colorectal carcinogenesis, we also investigated tumors from patients with CRC and matched, adjacent, nonmalignant tissues. Multivariate statistical methods and manual comparisons were used to identify metabolites specific to Hmga1 and CRC. Statistical modeling of data revealed distinct metabolic patterns in Hmga1 transgenics and human CRC samples as compared with the control tissues. We discovered that 13 metabolites were specific for Hmga1 in murine intestinal epithelium and also found in human CRC. Several of these metabolites function in fatty acid metabolism and membrane composition. Although further validation is needed, our results suggest that high levels of HMGA1 protein drive metabolic alterations that contribute to CRC pathogenesis through fatty acid synthesis. These metabolites could serve as potential biomarkers or therapeutic targets.
Surgical technology international, 2004
The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common procedure performe... more The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common procedure performed for treatment of morbid obesity in the United States. The technique reported in this chapter requires mastering of extra-corporeal and intra-corporeal laparoscopic suturing, but is safe, cost effective, and technically feasible. Use of the straight needle eliminates the challenge of proper needle orientation encountered with a curved needle. The linear technique is used to construct the gastrojejunostomy because it is time saving and relatively simple. An endoscopic ruler and bougie are used to ensure a consistent pouch size and alimentary limb length. This chaper demonstrates the use of preoperative preparation, and a meticulous surgical technique using the linear stapler, to perform a combined total of more than 1800 cases.
Phytotherapy research : PTR, 2005
Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patie... more Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patients with coronary artery disease (CAD). Oxidant stress and increased systemic inflammation may contribute to this endothelial dysfunction. Aged garlic extract (AGE) contains antioxidant compounds and increases nitric oxide production and decreases the output of inflammatory cytokines from cultured cells. The aim of this study was to test the effect of treatment with AGE on brachial artery flow mediated endothelium-dependent dilation (FMD) and circulating markers of oxidative stress and systemic inflammation. The trial included 15 men with angiographically proven CAD in a randomized, placebo-controlled, cross-over design with 2-week treatment and washout periods. During AGE supplementation, FMD increased (44%) significantly (p = 0.04) from the baseline and mainly in men with lower baseline FMD. Levels of FMD at the end of AGE treatment were significantly (p = 0.03) higher compared with the corresponding levels at the end of placebo treatment when the variation in baseline body weight was taken into account. Markers of oxidant stress (plasma oxidized low density lipoprotein and peroxides), systemic inflammation (plasma C-reactive protein ad interleukin-6) and endothelial activation (VCAM-1) did not change significantly during the study. These data suggest that short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin. Whether improvement in endothelial function decreases the risk of future cardiovascular events remains to be determined.
Clinical advances in hematology & oncology : H&O, 2003
British journal of hospital medicine (London, England : 2005), 2006
British journal of hospital medicine (London, England : 2005), 2006
Missouri medicine
Crohn&amp... more Crohn's disease is a complex disease process causing transmural inflammation of the gastrointestinal tract, which produces a constellation of symptoms including abdominal pain, frequent loose stools, fistula formation, and extraintestinal manifestations. Biologic therapy, including tumor necrosis factor alpha inhibitors, are a growing class of agents, which have demonstrated efficacy in the treatment of moderate to severe Crohn's disease. Their indications for use have grown, as has the understanding of their associated safety concerns.
Clinical lymphoma, myeloma & leukemia, 2010
Mantle cell lymphoma (MCL) is regarded as an aggressive lymphoid malignancy that exhibits varied ... more Mantle cell lymphoma (MCL) is regarded as an aggressive lymphoid malignancy that exhibits varied clinical behavior and prognoses, reflecting the biologic heterogeneity of the disease. In most cases, patients with MCL achieve a shorter median survival compared with more common B-cell lymphomas, such as follicular lymphoma, and are less likely to achieve a durable response with chemotherapy. Currently, there is no defined standard of care for patients with MCL. Rituximab-containing immunochemotherapy strategies are commonly used, but the addition of rituximab to conventional induction chemotherapy has produced suboptimal responses that are relatively short-lived and have not resulted in a survival advantage. Further intensification of the chemotherapy component, including autologous stem cell transplantation, has increased response and survival rates but has not proven to be curative while being associated with higher toxicity. Clearly, there is a need for developing novel agents and strategies that will improve clinical outcomes for patients with MCL. Targeted therapies and new cytotoxic agents are showing great promise and may have a role in maintenance and/or initial therapy. This summary highlights current challenges in the management of MCL, and outlines expert perspectives, key questions, and future directions. For the third consecutive year, a panel of global experts in MCL assembled to deliberate on topical issues in MCL including advances in pathobiology, strategies for risk-adapted therapy, front-line treatment options, consolidation approaches, and novel therapeutic strategies. The proceedings of this workshop, held December 3, 2009 in New Orleans, LA, are summarized here. It must be emphasized that this synopsis is not meant to serve as an exhaustive review of MCL biology and management, but is a distillation of the expert discussions, highlighting key questions and future directions identified.
Pathology, Diagnosis, and Treatment, 2009
Opinion statement Mantle cell lymphoma is an aggressive non-Hodgkin’s lymphoma that remains incu... more Opinion statement Mantle cell lymphoma is an aggressive non-Hodgkin’s lymphoma that remains incurable with current chemotherapeutic approaches. Despite response rates to many regimens of 50% to 70%, the disease typically progresses after chemotherapy with a median survival time of approximately 3 years. There is no clear standard approach for treating mantle cell lymphoma, making it critical that appropriate patients be enrolled
Journal of Liquid Chromatography & Related Technologies - J LIQ CHROMATOGR RELAT TECHNO, 1980
A high pressure liquid chromatography (HPLC) system was developed, capable of resolving most 5′-n... more A high pressure liquid chromatography (HPLC) system was developed, capable of resolving most 5′-nucleotides and nucleotide-sugars present in liver tissue. Using three different extraction procedures, the recovery of the twelve major 5′-ribonucleotides from solutions of nucleotide standards, or liver samples, or isolated hepatocytes was compared. Nucleotides were obtained from acid extracts for HPLC analysis by adsorbing the nucleotides on charcoal, or precipitating the acid (perchloric acid) by KOH, or extracting the acid with alamine/ freon. The last two procedures were found to be superior to the charcoal adsorption procedure for recovering nucleotides from acid extracts. The recovery of nucleotides from either liver samples or isolated hepatocytes by these two procedures was similar; however, the recovery of nucleotides from standard solutions was slightly higher for the alamine/freon procedure than the KOH precipitation procedure.
Polymer Engineering and Science - POLYM ENG SCI, 1982
Measurements were made of linear viscoelastic properties and nonlinear stress-strain properties o... more Measurements were made of linear viscoelastic properties and nonlinear stress-strain properties of phase-separated styrene-butadiene-styrene (SBS) copolymers and their blends with several homopolymer polystyrenes (PS) and one random copolymer (SBR). Torsion pendulum testing yielded shear moduli G′, G″, and Rheovibron experiments produced tensile moduli E′, E″, over a 220°K range of temperature, both at low frequencies. For pure copolymers and their PS blends, G′ and E′ correlated quite well with the total PS content, but G″ and E″ were more sensitive to how the additive was distributed. Results suggest that a PS additive whose molecular weight (M) is less than that of the copolymer PS-block (Ms) causes expansion of both the interphase and the homogeneous PS-rich phase, while an additive with M > Ms mixes less well with these phases (probably forming separate domains of pure PS) and is less effective in enhancing the linear moduli. The blending with SBB produced reduction in G′ but a broad midrange peak in G″, suggesting that SBR was localized almost entirely within an expanded interphase. Tensile stress-strain data were obtained with an Material Testing System at room temperature. For PS blends, properties did not correlate well with the total PS content, the blends being always weaker than the SBS of the same overall composition. The amount of set also increased with PS content in the blends. Cyclic tests to increasing strain showed progressive structural alterations (as for the host SBS), with blend behavior resembling host properties more closely with each new cycle. When SBR was the additive, amounts as small as 1 percent reduced the curves by 15 percent. The yield stress was eliminated entirely with an addition of 10 percent SBR, but for all cases the set was the same. Results are discussed in terms of interphase force barriers to chain flow.
Monthly Notices of the Royal Astronomical Society, 2014
We present an analysis of the H 2 emission-line gas kinematics in the inner 4 arcsec radius of si... more We present an analysis of the H 2 emission-line gas kinematics in the inner 4 arcsec radius of six nearby spiral galaxies, based on AO-assisted integral-field observations obtained in the K-band with SINFONI/VLT. Four of the six galaxies in our sample display ordered H 2 velocity fields, consistent with gas moving in the plane of the galaxy and rotating in the same direction as the stars. However, the gas kinematics is typically far from simple circular motion. We can classify the observed velocity fields into four different types of flows, ordered by increasing complexity: (1) circular motion in a disc (NGC 3351); (2) oval motion in the galaxy plane (NGC 3627 and NGC 4536); (3) streaming motion superimposed on circular rotation (NGC 4501); and (4) disordered streaming motions (NGC 4569 and NGC 4579). The H 2 velocity dispersion in the galaxies is usually higher than 50 km s −1 in the inner 1-2 arcsec radii. The four galaxies with ordered kinematics have v/σ < 1 at radii less than 40-80 pc. The radius at which v/σ = 1 is independent of the type of nuclear activity. While the low values of v/σ could be taken as an indication of a thick disc in the innermost regions of the galaxies, other lines of evidence (e.g. H 2 morphologies and velocity fields) argue for a thin disc interpretation in the case of NGC 3351 and NGC 4536. We discuss the implications of the high values of velocity dispersion for the dynamics of the gaseous disc and suggest caution when interpreting the velocity dispersion of ionized and warm tracers as being entirely dynamical. Understanding the nature and role of the velocity dispersion in the gas dynamics, together with the full 2D information of the gas, is essential for obtaining accurate black hole masses from gas kinematics.
Journal of the American Chemical Society, 2007
... a Reaction conditions: (a) hν, PhH; Fe 2 (CO) 9 , 64%; (b) DIBAL, Et 2 O, 0 °C to rt, 95%; (c... more ... a Reaction conditions: (a) hν, PhH; Fe 2 (CO) 9 , 64%; (b) DIBAL, Et 2 O, 0 °C to rt, 95%; (c) MnO 2 , CH 2 Cl ... (c) Freifelder, M. Practical Catalytic ... Carlos Gonza lez-Rodri guez, Luz Escalante, Jesu s A. Varela, Luis Castedo and Carlos Saa. Organic Letters 2009 11 (7), 1531-1533. ...
The purpose of this study was to compare illness-related anxiety among participants in the Rituxi... more The purpose of this study was to compare illness-related anxiety among participants in the Rituximab Extended Schedule or Retreatment Trial (RESORT) randomly assigned to maintenance rituximab (MR) versus rituximab re-treatment (RR). A secondary objective was to examine whether the superiority of MR versus RR on anxiety depended on illness-related coping style. Patients (N = 253) completed patient-reported outcome (PRO) measures at random assignment to MR or RR (baseline); at 3, 6, 12, 24, 36, and 48 months after random assignment; and at rituximab failure. PRO measures assessed illness-related anxiety and coping style, and secondary end points including general anxiety, worry and interference with emotional well-being, depression, and health-related quality of life (HRQoL). Patients were classified as using an active or avoidant illness-related coping style. Independent sample t tests and linear mixed-effects models were used to identify treatment arm differences on PRO end points and differences based on coping style. Illness-related anxiety was comparable between treatment arms at all time points (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05), regardless of coping style (active or avoidant). Illness-related anxiety and general anxiety significantly decreased over time on both arms. HRQoL scores were relatively stable and did not change significantly from baseline for both arms. An avoidant coping style was associated with significantly higher anxiety (18% and 13% exceeded clinical cutoff points at baseline and 6 months, respectively) and poorer HRQoL compared with an active coping style (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), regardless of treatment arm assignment. Surveillance until RR at progression was not associated with increased anxiety compared with MR, regardless of coping style. Avoidant coping was associated with higher anxiety and poorer HRQoL.
The journal of physical chemistry. B, Jan 12, 2013
Intermolecular vibrations of amino acid crystals occur in the THz, or far-infrared, region of the... more Intermolecular vibrations of amino acid crystals occur in the THz, or far-infrared, region of the electromagnetic spectrum. We have measured the THz and Raman spectra of DL-leucine as well as two polymorphs of DL-valine, the spectroscopic properties of which have not previously been compared. Theoretical modeling of intermolecular vibrations in hydrophobic amino acids is challenging because the van der Waals interactions between molecules are not accounted for in standard density functional theory. Therefore, to calculate the vibrational modes, we used a recently developed approach that includes these nonlocal electron correlation forces. We discuss methods for comparing results from different theoretical models using metrics other than calculated vibrational frequency and intensity, and we also report a new approach enabling concise comparison of vibrational modes that involve complicated mixtures of inter- and intramolecular displacements.
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2013
Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is both biologically ... more Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is both biologically and clinically heterogeneous. A variety of biomarkers, the achievement of minimal residual disease negativity after initial therapy, and the MCL International Prognostic Index (MIPI) are associated with patient outcome, although none has as yet been used for routine treatment stratification. Given the lack of widely accepted and standardized treatment approaches, clinical trial enrollment should always be considered for the initial therapy of MCL. Outside of the trial setting, younger and transplantation-eligible patients with newly diagnosed MCL who require treatment should first be considered for a rituximab+a high-dose cytarabine-containing regimen, followed by autologous stem cell transplantation consolidation in first remission. Symptomatic elderly and nontransplantation-eligible individuals typically receive rituximab+bendamustine, or R-CHOP (rituximab+cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone) followed by maintenance rituximab, the latter a treatment plan that has demonstrated extended response duration and survival. Promising early results for consolidation approaches with proteasome inhibitors and immunomodulatory drugs are now being tested in randomized clinical trials. The availability of highly active BCR signaling pathway inhibitors and cell death pathway modulation via BH3 mimetics, among other novel agents, promise to rapidly expand treatment options, change existing treatment paradigms, and further improve outcomes for MCL patients.
Journal of the American College of Cardiology, 2014
The aim of this study was to comprehensively review the epidemiology of aortic sclerosis (ASc) an... more The aim of this study was to comprehensively review the epidemiology of aortic sclerosis (ASc) and its association with cardiovascular events.
Proceedings of the National Academy of Sciences of the United States of America, 2014
Large commercial publishers sell bundled online subscriptions to their entire list of academic jo... more Large commercial publishers sell bundled online subscriptions to their entire list of academic journals at prices significantly lower than the sum of their á la carte prices. Bundle prices differ drastically between institutions, but they are not publicly posted. The data that we have collected enable us to compare the bundle prices charged by commercial publishers with those of nonprofit societies and to examine the types of price discrimination practiced by commercial and nonprofit journal publishers. This information is of interest to economists who study monopolist pricing, librarians interested in making efficient use of library budgets, and scholars who are interested in the availability of the work that they publish.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists, 2008
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improv... more In low-tumor burden follicular lymphoma (FL), maintenance rituximab (MR) has been shown to improve progression-free survival when compared with observation. It is not known whether MR provides superior long-term disease control compared with re-treatment rituximab (RR) administered on an as-needed basis. E4402 (RESORT) was a randomized clinical trial designed to compare MR against RR. Eligible patients with previously untreated low-tumor burden FL received four doses of rituximab, and responding patients were randomly assigned to either RR or MR. Patients receiving RR were eligible for re-treatment at each disease progression until treatment failure. Patients assigned to MR received a single dose of rituximab every 3 months until treatment failure. The primary end point was time to treatment failure. Secondary end points included time to first cytotoxic therapy, toxicity, and health-related quality of life (HRQOL). A total of 289 patients were randomly assigned to RR or MR. With a median follow-up of 4.5 years, the estimated median time to treatment failure was 3.9 years for patients receiving RR and 4.3 years for those receiving MR (P = .54). Three-year freedom from cytotoxic therapy was 84% for those receiving RR and 95% for those receiving MR (P = .03). The median number of rituximab doses was four patients receiving RR and 18 for those receiving MR. There was no difference in HRQOL. Grade 3 to 4 toxicities were infrequent in both arms. In low-tumor burden FL, a re-treatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.
Journal of Proteome Research, 2015
Although significant progress has been made in the diagnosis and treatment of colorectal cancer (... more Although significant progress has been made in the diagnosis and treatment of colorectal cancer (CRC), it remains a leading cause of cancer death worldwide. Early identification and removal of polyps that may progress to overt CRC is the cornerstone of CRC prevention. Expression of the High Mobility Group A1 (HMGA1) gene is significantly elevated in CRCs as compared with adjacent, nonmalignant tissues. We investigated metabolic aberrations induced by HMGA1 overexpression in small intestinal and colonic epithelium using traveling wave ion mobility mass spectrometry (TWIMMS) in a transgenic model in which murine Hmga1 was misexpressed in colonic epithelium. To determine if these Hmga1-induced metabolic alterations in mice were relevant to human colorectal carcinogenesis, we also investigated tumors from patients with CRC and matched, adjacent, nonmalignant tissues. Multivariate statistical methods and manual comparisons were used to identify metabolites specific to Hmga1 and CRC. Statistical modeling of data revealed distinct metabolic patterns in Hmga1 transgenics and human CRC samples as compared with the control tissues. We discovered that 13 metabolites were specific for Hmga1 in murine intestinal epithelium and also found in human CRC. Several of these metabolites function in fatty acid metabolism and membrane composition. Although further validation is needed, our results suggest that high levels of HMGA1 protein drive metabolic alterations that contribute to CRC pathogenesis through fatty acid synthesis. These metabolites could serve as potential biomarkers or therapeutic targets.
Surgical technology international, 2004
The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common procedure performe... more The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common procedure performed for treatment of morbid obesity in the United States. The technique reported in this chapter requires mastering of extra-corporeal and intra-corporeal laparoscopic suturing, but is safe, cost effective, and technically feasible. Use of the straight needle eliminates the challenge of proper needle orientation encountered with a curved needle. The linear technique is used to construct the gastrojejunostomy because it is time saving and relatively simple. An endoscopic ruler and bougie are used to ensure a consistent pouch size and alimentary limb length. This chaper demonstrates the use of preoperative preparation, and a meticulous surgical technique using the linear stapler, to perform a combined total of more than 1800 cases.
Phytotherapy research : PTR, 2005
Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patie... more Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patients with coronary artery disease (CAD). Oxidant stress and increased systemic inflammation may contribute to this endothelial dysfunction. Aged garlic extract (AGE) contains antioxidant compounds and increases nitric oxide production and decreases the output of inflammatory cytokines from cultured cells. The aim of this study was to test the effect of treatment with AGE on brachial artery flow mediated endothelium-dependent dilation (FMD) and circulating markers of oxidative stress and systemic inflammation. The trial included 15 men with angiographically proven CAD in a randomized, placebo-controlled, cross-over design with 2-week treatment and washout periods. During AGE supplementation, FMD increased (44%) significantly (p = 0.04) from the baseline and mainly in men with lower baseline FMD. Levels of FMD at the end of AGE treatment were significantly (p = 0.03) higher compared with the corresponding levels at the end of placebo treatment when the variation in baseline body weight was taken into account. Markers of oxidant stress (plasma oxidized low density lipoprotein and peroxides), systemic inflammation (plasma C-reactive protein ad interleukin-6) and endothelial activation (VCAM-1) did not change significantly during the study. These data suggest that short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin. Whether improvement in endothelial function decreases the risk of future cardiovascular events remains to be determined.
Clinical advances in hematology & oncology : H&O, 2003
British journal of hospital medicine (London, England : 2005), 2006
British journal of hospital medicine (London, England : 2005), 2006
Missouri medicine
Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease is a complex disease process causing transmural inflammation of the gastrointestinal tract, which produces a constellation of symptoms including abdominal pain, frequent loose stools, fistula formation, and extraintestinal manifestations. Biologic therapy, including tumor necrosis factor alpha inhibitors, are a growing class of agents, which have demonstrated efficacy in the treatment of moderate to severe Crohn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Their indications for use have grown, as has the understanding of their associated safety concerns.
Clinical lymphoma, myeloma & leukemia, 2010
Mantle cell lymphoma (MCL) is regarded as an aggressive lymphoid malignancy that exhibits varied ... more Mantle cell lymphoma (MCL) is regarded as an aggressive lymphoid malignancy that exhibits varied clinical behavior and prognoses, reflecting the biologic heterogeneity of the disease. In most cases, patients with MCL achieve a shorter median survival compared with more common B-cell lymphomas, such as follicular lymphoma, and are less likely to achieve a durable response with chemotherapy. Currently, there is no defined standard of care for patients with MCL. Rituximab-containing immunochemotherapy strategies are commonly used, but the addition of rituximab to conventional induction chemotherapy has produced suboptimal responses that are relatively short-lived and have not resulted in a survival advantage. Further intensification of the chemotherapy component, including autologous stem cell transplantation, has increased response and survival rates but has not proven to be curative while being associated with higher toxicity. Clearly, there is a need for developing novel agents and strategies that will improve clinical outcomes for patients with MCL. Targeted therapies and new cytotoxic agents are showing great promise and may have a role in maintenance and/or initial therapy. This summary highlights current challenges in the management of MCL, and outlines expert perspectives, key questions, and future directions. For the third consecutive year, a panel of global experts in MCL assembled to deliberate on topical issues in MCL including advances in pathobiology, strategies for risk-adapted therapy, front-line treatment options, consolidation approaches, and novel therapeutic strategies. The proceedings of this workshop, held December 3, 2009 in New Orleans, LA, are summarized here. It must be emphasized that this synopsis is not meant to serve as an exhaustive review of MCL biology and management, but is a distillation of the expert discussions, highlighting key questions and future directions identified.
Pathology, Diagnosis, and Treatment, 2009
Opinion statement Mantle cell lymphoma is an aggressive non-Hodgkin’s lymphoma that remains incu... more Opinion statement Mantle cell lymphoma is an aggressive non-Hodgkin’s lymphoma that remains incurable with current chemotherapeutic approaches. Despite response rates to many regimens of 50% to 70%, the disease typically progresses after chemotherapy with a median survival time of approximately 3 years. There is no clear standard approach for treating mantle cell lymphoma, making it critical that appropriate patients be enrolled
Journal of Liquid Chromatography & Related Technologies - J LIQ CHROMATOGR RELAT TECHNO, 1980
A high pressure liquid chromatography (HPLC) system was developed, capable of resolving most 5′-n... more A high pressure liquid chromatography (HPLC) system was developed, capable of resolving most 5′-nucleotides and nucleotide-sugars present in liver tissue. Using three different extraction procedures, the recovery of the twelve major 5′-ribonucleotides from solutions of nucleotide standards, or liver samples, or isolated hepatocytes was compared. Nucleotides were obtained from acid extracts for HPLC analysis by adsorbing the nucleotides on charcoal, or precipitating the acid (perchloric acid) by KOH, or extracting the acid with alamine/ freon. The last two procedures were found to be superior to the charcoal adsorption procedure for recovering nucleotides from acid extracts. The recovery of nucleotides from either liver samples or isolated hepatocytes by these two procedures was similar; however, the recovery of nucleotides from standard solutions was slightly higher for the alamine/freon procedure than the KOH precipitation procedure.
Polymer Engineering and Science - POLYM ENG SCI, 1982
Measurements were made of linear viscoelastic properties and nonlinear stress-strain properties o... more Measurements were made of linear viscoelastic properties and nonlinear stress-strain properties of phase-separated styrene-butadiene-styrene (SBS) copolymers and their blends with several homopolymer polystyrenes (PS) and one random copolymer (SBR). Torsion pendulum testing yielded shear moduli G′, G″, and Rheovibron experiments produced tensile moduli E′, E″, over a 220°K range of temperature, both at low frequencies. For pure copolymers and their PS blends, G′ and E′ correlated quite well with the total PS content, but G″ and E″ were more sensitive to how the additive was distributed. Results suggest that a PS additive whose molecular weight (M) is less than that of the copolymer PS-block (Ms) causes expansion of both the interphase and the homogeneous PS-rich phase, while an additive with M > Ms mixes less well with these phases (probably forming separate domains of pure PS) and is less effective in enhancing the linear moduli. The blending with SBB produced reduction in G′ but a broad midrange peak in G″, suggesting that SBR was localized almost entirely within an expanded interphase. Tensile stress-strain data were obtained with an Material Testing System at room temperature. For PS blends, properties did not correlate well with the total PS content, the blends being always weaker than the SBS of the same overall composition. The amount of set also increased with PS content in the blends. Cyclic tests to increasing strain showed progressive structural alterations (as for the host SBS), with blend behavior resembling host properties more closely with each new cycle. When SBR was the additive, amounts as small as 1 percent reduced the curves by 15 percent. The yield stress was eliminated entirely with an addition of 10 percent SBR, but for all cases the set was the same. Results are discussed in terms of interphase force barriers to chain flow.
Monthly Notices of the Royal Astronomical Society, 2014
We present an analysis of the H 2 emission-line gas kinematics in the inner 4 arcsec radius of si... more We present an analysis of the H 2 emission-line gas kinematics in the inner 4 arcsec radius of six nearby spiral galaxies, based on AO-assisted integral-field observations obtained in the K-band with SINFONI/VLT. Four of the six galaxies in our sample display ordered H 2 velocity fields, consistent with gas moving in the plane of the galaxy and rotating in the same direction as the stars. However, the gas kinematics is typically far from simple circular motion. We can classify the observed velocity fields into four different types of flows, ordered by increasing complexity: (1) circular motion in a disc (NGC 3351); (2) oval motion in the galaxy plane (NGC 3627 and NGC 4536); (3) streaming motion superimposed on circular rotation (NGC 4501); and (4) disordered streaming motions (NGC 4569 and NGC 4579). The H 2 velocity dispersion in the galaxies is usually higher than 50 km s −1 in the inner 1-2 arcsec radii. The four galaxies with ordered kinematics have v/σ < 1 at radii less than 40-80 pc. The radius at which v/σ = 1 is independent of the type of nuclear activity. While the low values of v/σ could be taken as an indication of a thick disc in the innermost regions of the galaxies, other lines of evidence (e.g. H 2 morphologies and velocity fields) argue for a thin disc interpretation in the case of NGC 3351 and NGC 4536. We discuss the implications of the high values of velocity dispersion for the dynamics of the gaseous disc and suggest caution when interpreting the velocity dispersion of ionized and warm tracers as being entirely dynamical. Understanding the nature and role of the velocity dispersion in the gas dynamics, together with the full 2D information of the gas, is essential for obtaining accurate black hole masses from gas kinematics.
Journal of the American Chemical Society, 2007
... a Reaction conditions: (a) hν, PhH; Fe 2 (CO) 9 , 64%; (b) DIBAL, Et 2 O, 0 °C to rt, 95%; (c... more ... a Reaction conditions: (a) hν, PhH; Fe 2 (CO) 9 , 64%; (b) DIBAL, Et 2 O, 0 °C to rt, 95%; (c) MnO 2 , CH 2 Cl ... (c) Freifelder, M. Practical Catalytic ... Carlos Gonza lez-Rodri guez, Luz Escalante, Jesu s A. Varela, Luis Castedo and Carlos Saa. Organic Letters 2009 11 (7), 1531-1533. ...