Science.gov

Sample records for minimal disease application

  1. Minimal change disease

    MedlinePlus

    ... seen under a very powerful microscope called an electron microscope. Minimal change disease is the most common ... biopsy and examination of the tissue with an electron microscope can show signs of minimal change disease.

  2. Minimal change disease

    MedlinePlus

    Minimal change nephrotic syndrome; Nil disease; Lipoid nephrosis; Idiopathic nephrotic syndrome of childhood ... which filter blood and produce urine. In minimal change disease, there is damage to the glomeruli. These ...

  3. Application of advanced cytometric and molecular technologies to minimal residual disease monitoring

    NASA Astrophysics Data System (ADS)

    Leary, James F.; He, Feng; Reece, Lisa M.

    2000-04-01

    Minimal residual disease monitoring presents a number of theoretical and practical challenges. Recently it has been possible to meet some of these challenges by combining a number of new advanced biotechnologies. To monitor the number of residual tumor cells requires complex cocktails of molecular probes that collectively provide sensitivities of detection on the order of one residual tumor cell per million total cells. Ultra-high-speed, multi parameter flow cytometry is capable of analyzing cells at rates in excess of 100,000 cells/sec. Residual tumor selection marker cocktails can be optimized by use of receiver operating characteristic analysis. New data minimizing techniques when combined with multi variate statistical or neural network classifications of tumor cells can more accurately predict residual tumor cell frequencies. The combination of these techniques can, under at least some circumstances, detect frequencies of tumor cells as low as one cell in a million with an accuracy of over 98 percent correct classification. Detection of mutations in tumor suppressor genes requires insolation of these rare tumor cells and single-cell DNA sequencing. Rare residual tumor cells can be isolated at single cell level by high-resolution single-cell cell sorting. Molecular characterization of tumor suppressor gene mutations can be accomplished using a combination of single- cell polymerase chain reaction amplification of specific gene sequences followed by TA cloning techniques and DNA sequencing. Mutations as small as a single base pair in a tumor suppressor gene of a single sorted tumor cell have been detected using these methods. Using new amplification procedures and DNA micro arrays it should be possible to extend the capabilities shown in this paper to screening of multiple DNA mutations in tumor suppressor and other genes on small numbers of sorted metastatic tumor cells.

  4. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

  5. On Modelling Minimal Disease Activity

    PubMed Central

    Jackson, Christopher H.; Su, Li; Gladman, Dafna D.

    2016-01-01

    Objective To explore methods for statistical modelling of minimal disease activity (MDA) based on data from intermittent clinic visits. Methods The analysis was based on a 2‐state model. Comparisons were made between analyses based on “complete case” data from visits at which MDA status was known, and the use of hidden model methodology that incorporated information from visits at which only some MDA defining criteria could be established. Analyses were based on an observational psoriatic arthritis cohort. Results With data from 856 patients and 7,024 clinic visits, analysis was based on virtually all visits, although only 62.6% provided enough information to determine MDA status. Estimated mean times for an episode of MDA varied from 4.18 years to 3.10 years, with smaller estimates derived from the hidden 2‐state model analysis. Over a 10‐year period, the estimated expected times spent in MDA episodes of longer than 1 year was 3.90 to 4.22, and the probability of having such an MDA episode was estimated to be 0.85 to 0.91, with longer times and greater probabilities seen with the hidden 2‐state model analysis. Conclusion A 2‐state model provides a useful framework for the analysis of MDA. Use of data from visits at which MDA status can not be determined provide more precision, and notable differences are seen in estimated quantities related to MDA episodes based on complete case and hidden 2‐state model analyses. The possibility of bias, as well as loss of precision, should be recognized when complete case analyses are used. PMID:26315478

  6. [Minimally Invasive Treatment of Esophageal Benign Diseases].

    PubMed

    Inoue, Haruhiro

    2016-07-01

    As a minimally invasive treatment of esophageal achalasia per-oral endoscopic myotomy( POEM) was developed in 2008. More than 1,100 cases of achalasia-related diseases received POEM. Success rate of the procedure was more than 95%(Eckerdt score improvement 3 points and more). No serious( Clavian-Dindo classification III b and more) complication was experienced. These results suggest that POEM becomes a standard minimally invasive treatment for achalasia-related diseases. As an off-shoot of POEM submucosal tumor removal through submucosal tunnel (per-oral endoscopic tumor resection:POET) was developed and safely performed. Best indication of POET is less than 5 cm esophageal leiomyoma. A novel endoscopic treatment of gastroesophageal reflux disease (GERD) was developed. Anti-reflux mucosectomy( ARMS) is nearly circumferential mucosal reduction of gastric cardia mucosa. ARMS is performed in 56 consecutive cases of refractory GERD. No major complications were encountered and excellent clinical results. Best indication of ARMS is a refractory GERD without long sliding hernia. Longest follow-up case is more than 10 years. Minimally invasive treatments for esophageal benign diseases are currently performed by therapeutic endoscopy. PMID:27440038

  7. Minimal residual disease in hypopigmented mycosis fungoides.

    PubMed

    Hsiao, Pa-Fan; Hsiao, Cheng-Hsiang; Tsai, Tsen-Fang; Jee, Shiou-Hwa

    2006-05-01

    We describe the case of a 13-year-old boy with stage I hypopigmented mycosis fungoides in whom minimal residual disease was detected with T-cell receptor gamma-polymerase chain reaction after the disease was in complete clinical remission. We further cloned and sequenced the T-cell receptor gamma-polymerase chain reaction product of the lesion in remission and found that the original T-cell clone still existed in decreased amounts. The patient was followed up for 3 1/2 years without any new lesions developing. The clinical significance of this residual malignant T-cell clone in mycosis fungoides remains to be elucidated. PMID:16631939

  8. The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

    PubMed

    Rivoire, Becky L; TerLouw, Stephen; Groathouse, Nathan A; Brennan, Patrick J

    2014-01-01

    True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial. PMID:24874086

  9. The Challenge of Producing Skin Test Antigens with Minimal Resources Suitable for Human Application against a Neglected Tropical Disease; Leprosy

    PubMed Central

    Rivoire, Becky L.; TerLouw, Stephen; Groathouse, Nathan A.; Brennan, Patrick J.

    2014-01-01

    True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial. PMID:24874086

  10. Minimal-change disease secondary to etanercept

    PubMed Central

    Koya, Mariko; Pichler, Raimund; Jefferson, J. Ashley

    2012-01-01

    Etanercept is a soluble tumor necrosis factor alpha (TNFα) receptor which is widely used in the treatment of rheumatoid arthritis, psoriasis and other autoimmune inflammatory disorders. It is known for its relative lack of nephrotoxicity; however, there are reports on the development of nephrotic syndrome associated with the treatment with TNFα antagonists. Here, we describe a patient with psoriasis who developed biopsy-proven minimal-change disease (MCD) shortly after initiating etanercept. Our case is unique in that the MCD resolved after discontinuation of this medication, notably without the use of corticosteroids, strongly suggesting a drug-related phenomenon. PMID:26019819

  11. Minimally invasive surgery for thyroid eye disease

    PubMed Central

    Naik, Milind Neilkant; Nair, Akshay Gopinathan; Gupta, Adit; Kamal, Saurabh

    2015-01-01

    Thyroid eye disease (TED) can affect the eye in myriad ways: proptosis, strabismus, eyelid retraction, optic neuropathy, soft tissue changes around the eye and an unstable ocular surface. TED consists of two phases: active, and inactive. The active phase of TED is limited to a period of 12–18 months and is mainly managed medically with immunosuppression. The residual structural changes due to the resultant fibrosis are usually addressed with surgery, the mainstay of which is orbital decompression. These surgeries are performed during the inactive phase. The surgical rehabilitation of TED has evolved over the years: not only the surgical techniques, but also the concepts, and the surgical tools available. The indications for decompression surgery have also expanded in the recent past. This article discusses the technological and conceptual advances of minimally invasive surgery for TED that decrease complications and speed up recovery. Current surgical techniques offer predictable, consistent results with better esthetics. PMID:26669337

  12. Technology applications for radioactive waste minimization

    SciTech Connect

    Devgun, J.S.

    1994-07-01

    The nuclear power industry has achieved one of the most successful examples of waste minimization. The annual volume of low-level radioactive waste shipped for disposal per reactor has decreased to approximately one-fifth the volume about a decade ago. In addition, the curie content of the total waste shipped for disposal has decreased. This paper will discuss the regulatory drivers and economic factors for waste minimization and describe the application of technologies for achieving waste minimization for low-level radioactive waste with examples from the nuclear power industry.

  13. Eliminating Hairy Cell Leukemia Minimal Residual Disease

    Cancer.gov

    In this trial, patients with hairy cell leukemia who have disease-related symptoms that require treatment will be randomly assigned to receive cladribine with either concurrent rituximab or rituximab at least 6 months after completing cladribine therapy.

  14. Prognostic relevance of minimal residual disease in colorectal cancer

    PubMed Central

    Bork, Ulrich; Grützmann, Robert; Rahbari, Nuh N; Schölch, Sebastian; Distler, Marius; Reissfelder, Christoph; Koch, Moritz; Weitz, Jürgen

    2014-01-01

    Presence of occult minimal residual disease in patients with colorectal cancer (CRC) has a strong prognostic impact on survival. Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC. Analysis of circulating tumor cells (CTC) in the blood is increasingly used in clinical practice for disease monitoring of CRC patients. In this review article the role of CTC, disseminated tumor cells (DTC) in the bone marrow and micrometastases and isolated tumor cells (ITC) in the lymph nodes will be discussed, including literature published until September 2013. Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood, DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes. Minimal residual disease could be used in the future to identify patient groups at risk, who might benefit from individualized treatment options. PMID:25132746

  15. Minimally invasive surgery for inflammatory bowel disease: Current perspectives.

    PubMed

    Shrestha, Badri

    2016-05-01

    The surgical management of complicated and recurrent inflammatory bowel disease (IBD), has remained a challenge. Minimally invasive surgery (MIS), in the form of laparoscopic resections, single port approach and robotic-assisted dissections in the management of IBD, have been examined in several prospective studies. All of them have shown advantages over open surgery in terms of reduction of physical trauma of surgery, recovery time, better cosmetic outcomes and shorter hospitalization. However, it is important to appreciate that not all patients with IBD are suitable for MIS, so a combination of both open and MIS should be adopted to achieve optimum outcomes. A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice. PMID:27158536

  16. Minimally invasive surgery for inflammatory bowel disease: Current perspectives

    PubMed Central

    Shrestha, Badri

    2016-01-01

    The surgical management of complicated and recurrent inflammatory bowel disease (IBD), has remained a challenge. Minimally invasive surgery (MIS), in the form of laparoscopic resections, single port approach and robotic-assisted dissections in the management of IBD, have been examined in several prospective studies. All of them have shown advantages over open surgery in terms of reduction of physical trauma of surgery, recovery time, better cosmetic outcomes and shorter hospitalization. However, it is important to appreciate that not all patients with IBD are suitable for MIS, so a combination of both open and MIS should be adopted to achieve optimum outcomes. A review on this subject performed by Neumann et al in this issue of World Journal of Gastrointestinal Pharmacology and Therapeutics have provided evidence in support of the contemporary practice of MIS in the management of IBD and the accompanying commentary further critically evaluates their application in clinical practice. PMID:27158536

  17. Monitoring of minimal residual disease in acute myeloid leukemia.

    PubMed

    Kern, Wolfgang; Haferlach, Claudia; Haferlach, Torsten; Schnittger, Susanne

    2008-01-01

    Two highly sensitive methods, multiparameter flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR), are increasingly used to monitor minimal residual disease (MRD) and to guide risk-adapted management in acute myeloid leukemia (AML). An independent prognostic impact has been demonstrated for MRD levels obtained by both methods. MFC has been found particularly useful for assessment of early clearance of malignant cells and after consolidation therapy. At the latter checkpoint, MRD levels quantified by RQ-PCR in AML with fusion genes also have the strongest prognostic power. In addition, highly predictive initial expression levels have been identified by RQ-PCR. Both methods are capable of early detection of relapse. Through the use of all available markers including NPM1 mutations and FLT3 mutations in addition to fusion genes, RQ-PCR-based MRD assessment is possible in more than half of patients, whereas MFC is applicable to most AML cases. With a sensitivity of 10(-4) (PML-RARA) to 10(-7) (patient-specific primers, FLT3 and NPM1 mutations), RQ-PCR is more sensitive in most cases. Large clinical trials will determine the exact role and place of immunologic and RQ-PCR-based monitoring of MRD in the therapy of patients with AML. PMID:18000811

  18. Minimally invasive approaches for the treatment of inflammatory bowel disease

    PubMed Central

    Zoccali, Marco; Fichera, Alessandro

    2012-01-01

    Despite significant improvements in medical management of inflammatory bowel disease, many of these patients still require surgery at some point in the course of their disease. Their young age and poor general conditions, worsened by the aggressive medical treatments, make minimally invasive approaches particularly enticing to this patient population. However, the typical inflammatory changes that characterize these diseases have hindered wide diffusion of laparoscopy in this setting, currently mostly pursued in high-volume referral centers, despite accumulating evidences in the literature supporting the benefits of minimally invasive surgery. The largest body of evidence currently available for terminal ileal Crohn’s disease shows improved short term outcomes after laparoscopic surgery, with prolonged operative times. For Crohn’s colitis, high quality evidence supporting laparoscopic surgery is lacking. Encouraging preliminary results have been obtained with the adoption of laparoscopic restorative total proctocolectomy for the treatment of ulcerative colitis. A consensus about patients’ selection and the need for staging has not been reached yet. Despite the lack of conclusive evidence, a wave of enthusiasm is pushing towards less invasive strategies, to further minimize surgical trauma, with single incision laparoscopic surgery being the most realistic future development. PMID:23239913

  19. The thrust minimization problem and its applications

    NASA Astrophysics Data System (ADS)

    Ivanyukhin, A. V.; Petukhov, V. G.

    2015-07-01

    An indirect approach to the optimization of trajectories with finite thrust based on Pontryagin's maximum principle is discussed. The optimization is aimed at calculating the minimum thrust for a point-to-point flight completed within a given interval of time with a constant exhaust velocity and a constant power. This may help calculate the region of existence of the optimum trajectory with thrust switching: it is evident that the latter problem may be solved if minimum thrust is lower than or equal to the available thrust in the problem with switching. A technique for calculating the optimum trajectories with a finite thrust by solving the problem of minimization of the thrust acceleration with a subsequent numerical continuation with respect to the mass flow towards the thrust minimization problem is proposed. This technique offers an opportunity to detect degeneracies associated with the lack of thrust or specific impulse. In effect, it allows one to calculate the boundaries of the region of existence of trajectories with thrust switching and thus makes it possible to automate the process of solving the problem of optimization of trajectories with thrust switching.

  20. Minimal Technologies Application Project: Planning and installation

    SciTech Connect

    Zellmer, S.D.; Hinchman, R.R.; Severinghaus, W.D.; Johnson, D.O.; Brent, J.J.

    1989-03-01

    Intensive and continuous tactical training during the last 35 years at the Hohenfels Training Area in West Germany has caused the loss of vegetative ground cover and has accelerated soil erosion rates, resulting in extensive environmental damage, safety hazards, and unrealistic training habitats. The objectives of this project are to develop and evaluate revegetation procedures for establishing adequate vegetative cover to control erosion at minimal costs and disruption to training activities. This project involved the development and installation of 12 revegetation procedures that combined four seedbed preparation methods and seeding options with three site-closure periods. In March 1987, the four seedbed preparation/seeding options and closure periods were selected, a study site design and location chosen, and specifications for the revegetation procedures developed. A German rehabilitation contractor attempted the specified seedbed preparation and seeding on the 13.5-ha site in June, but abnormally high rainfall, usually wet site conditions, and lack of adequate equipment prevented the contractor from completing six of the 12 planned procedures. Planning and execution of the project has nonetheless provided valuable information on the importance and use of soil analytical results, seed availability and cost data, contractor equipment requirements, and time required for planning future revegetation efforts. Continued monitoring of vegetative ground cover at the site for the next two years, combined with cost information, will provide necessary data to determine which of the six revegetation procedures is the most effective. These data will be used in planning future rehabilitation efforts on tactical training areas.

  1. Cord-Blood Transplantation in Patients with Minimal Residual Disease.

    PubMed

    Milano, Filippo; Gooley, Ted; Wood, Brent; Woolfrey, Ann; Flowers, Mary E; Doney, Kristine; Witherspoon, Robert; Mielcarek, Marco; Deeg, Joachim H; Sorror, Mohamed; Dahlberg, Ann; Sandmaier, Brenda M; Salit, Rachel; Petersdorf, Effie; Appelbaum, Frederick R; Delaney, Colleen

    2016-09-01

    Background The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. Methods In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). Results The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46). Conclusions Our data suggest that among patients with pretransplantation minimal

  2. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  3. Minimal change disease onset observed after bevacizumab administration

    PubMed Central

    Hanna, Ramy M.; Lopez, Eduardo; Wilson, James; Barathan, Shrinath; Cohen, Arthur H.

    2016-01-01

    This is a report of a patient with minimal change disease (MCD) onset after bevacizumab administration. A 72-year-old man with inoperable Grade 3 astrocytoma was treated with a combination of temozolomide and the vascular endothelial growth factor monoclonal antibody bevacizumab. After two biweekly treatments, he developed nephrotic syndrome. Despite cessation of bevacizumab, his renal function deteriorated and a renal biopsy disclosed MCD. Thereafter, he was started on high-dose oral prednisone and renal function immediately improved. Within weeks, the nephrotic syndrome resolved. Although rare, biologic agents can cause various glomerulopathies that can have important therapeutic implications. MCD should be considered in patients who develop nephrotic syndrome while exposed to antiangiogenic agents. PMID:26985375

  4. Minimal change disease onset observed after bevacizumab administration.

    PubMed

    Hanna, Ramy M; Lopez, Eduardo; Wilson, James; Barathan, Shrinath; Cohen, Arthur H

    2016-04-01

    This is a report of a patient with minimal change disease (MCD) onset after bevacizumab administration. A 72-year-old man with inoperable Grade 3 astrocytoma was treated with a combination of temozolomide and the vascular endothelial growth factor monoclonal antibody bevacizumab. After two biweekly treatments, he developed nephrotic syndrome. Despite cessation of bevacizumab, his renal function deteriorated and a renal biopsy disclosed MCD. Thereafter, he was started on high-dose oral prednisone and renal function immediately improved. Within weeks, the nephrotic syndrome resolved. Although rare, biologic agents can cause various glomerulopathies that can have important therapeutic implications. MCD should be considered in patients who develop nephrotic syndrome while exposed to antiangiogenic agents. PMID:26985375

  5. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  6. Minimal cut-set methodology for artificial intelligence applications

    SciTech Connect

    Weisbin, C.R.; de Saussure, G.; Barhen, J.; Oblow, E.M.; White, J.C.

    1984-01-01

    This paper reviews minimal cut-set theory and illustrates its application with an example. The minimal cut-set approach uses disjunctive normal form in Boolean algebra and various Boolean operators to simplify very complicated tree structures composed of AND/OR gates. The simplification process is automated and performed off-line using existing computer codes to implement the Boolean reduction on the finite, but large tree structure. With this approach, on-line expert diagnostic systems whose response time is critical, could determine directly whether a goal is achievable by comparing the actual system state to a concisely stored set of preprocessed critical state elements.

  7. Minimally invasive surgery for diaphragmatic diseases in neonates and infants.

    PubMed

    Fujishiro, Jun; Ishimaru, Tetsuya; Sugiyama, Masahiko; Arai, Mari; Suzuki, Keisuke; Kawashima, Hiroshi; Iwanaka, Tadashi

    2016-07-01

    Owing to recent advances in minimally invasive surgery (MIS), laparoscopic and thoracoscopic surgery have been gradually introduced for use in neonates and infants. This review focuses on two popular MIS procedures for diaphragmatic diseases in neonates and infants: congenital diaphragmatic hernia (CHD) repair and plication for diaphragmatic eventration. While several advantages of MIS are proposed for CDH repair in neonates, there are also some concerns, namely intraoperative hypercapnia and acidosis and a higher recurrence rate than open techniques. Thus, neonates with severe CDH, along with an unstable circulatory and respiratory status, may be unsuitable for MIS repair, and the use of selection criteria is, therefore, important in these patients. It is generally believed that a learning curve is associated with the higher recurrence rate. Contrary to CDH repair, no major disadvantages associated with the use of MIS for diaphragmatic eventration have been reported in the literature, other than technical difficulty. Thus, if technically feasible, all pediatric patients with diaphragmatic eventration requiring surgical treatment are potential candidates for MIS. Due to a shortage of studies on this procedure, the potential advantages of MIS compared to open techniques for diaphragmatic eventration, such as early recovery and more rapid extubation, need to be confirmed by further studies. PMID:27246508

  8. Minimal cut-set methodology for artificial intelligence applications

    SciTech Connect

    Weisbin, C.R.; de Saussure, G.; Barhen, J.; Oblow, E.M.; White, J.C.

    1984-01-01

    This paper suggests that given the considerable (and growing) literature of expert systems for diagnostics and maintenance, consideration of the theory of minimal cut sets should be most beneficial. The minimal cut-set approach uses disjunctive normal form in Boolean algebra and various Boolean operators to simplify very complicated tree structures composed of AND/OR gates. The simplification reduces the tree to an equivalent diagram displaying the smallest combinations of independent component failures which could result in the fault symbolized by the root of the tree and called the top event. This paper reviews minimal cut-set theory and illustrates its application with an example. Using this approach, expert diagnostic systems would have a tool in which, with minimum search, the description of fault causes is made clear and explicit, contributor sequences to a top event fault are easily quantified and ranked, and the probability of the top event is easily computed. Finally, the application of minimal cut sets to planning and problem solving is developed.

  9. Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study

    PubMed Central

    Cheminant, Morgane; Derrieux, Coralie; Touzart, Aurore; Schmit, Stéphanie; Grenier, Adrien; Trinquand, Amélie; Delfau-Larue, Marie-Hélène; Lhermitte, Ludovic; Thieblemont, Catherine; Ribrag, Vincent; Cheze, Stéphane; Sanhes, Laurence; Jardin, Fabrice; Lefrère, François; Delarue, Richard; Hoster, Eva; Dreyling, Martin; Asnafi, Vahid; Hermine, Olivier; Macintyre, Elizabeth

    2016-01-01

    Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management. PMID:26703963

  10. Minimal residual disease monitoring by 8-color flow cytometry in mantle cell lymphoma: an EU-MCL and LYSA study.

    PubMed

    Cheminant, Morgane; Derrieux, Coralie; Touzart, Aurore; Schmit, Stéphanie; Grenier, Adrien; Trinquand, Amélie; Delfau-Larue, Marie-Hélène; Lhermitte, Ludovic; Thieblemont, Catherine; Ribrag, Vincent; Cheze, Stéphane; Sanhes, Laurence; Jardin, Fabrice; Lefrère, François; Delarue, Richard; Hoster, Eva; Dreyling, Martin; Asnafi, Vahid; Hermine, Olivier; Macintyre, Elizabeth

    2016-03-01

    Quantification of minimal residual disease may guide therapeutic strategies in mantle cell lymphoma. While multiparameter flow cytometry is used for diagnosis, the gold standard method for minimal residual disease analysis is real-time quantitative polymerase chain reaction (RQ-PCR). In this European Mantle Cell Lymphoma network (EU-MCL) pilot study, we compared flow cytometry with RQ-PCR for minimal residual disease detection. Of 113 patients with at least one minimal residual disease sample, RQ-PCR was applicable in 97 (86%). A total of 284 minimal residual disease samples from 61 patients were analyzed in parallel by flow cytometry and RQ-PCR. A single, 8-color, 10-antibody flow cytometry tube allowed specific minimal residual disease assessment in all patients, with a robust sensitivity of 0.01%. Using this cut-off level, the true-positive-rate of flow cytometry with respect to RQ-PCR was 80%, whereas the true-negative-rate was 92%. As expected, RQ-PCR frequently detected positivity below this 0.01% threshold, which is insufficiently sensitive for prognostic evaluation and would ideally be replaced with robust quantification down to a 0.001% (10-5) threshold. In 10 relapsing patients, the transition from negative to positive by RQ-PCR (median 22.5 months before relapse) nearly always preceded transition by flow cytometry (4.5 months), but transition to RQ-PCR positivity above 0.01% (5 months) was simultaneous. Pre-emptive rituximab treatment of 2 patients at minimal residual disease relapse allowed re-establishment of molecular and phenotypic complete remission. Flow cytometry minimal residual disease is a complementary approach to RQ-PCR and a promising tool in individual mantle cell lymphoma therapeutic management. (clinicaltrials identifiers: 00209209 and 00209222). PMID:26703963

  11. Application of trajectory optimization principles to minimize aircraft operating costs

    NASA Technical Reports Server (NTRS)

    Sorensen, J. A.; Morello, S. A.; Erzberger, H.

    1979-01-01

    This paper summarizes various applications of trajectory optimization principles that have been or are being devised by both government and industrial researchers to minimize aircraft direct operating costs (DOC). These costs (time and fuel) are computed for aircraft constrained to fly over a fixed range. Optimization theory is briefly outlined, and specific algorithms which have resulted from application of this theory are described. Typical results which demonstrate use of these algorithms and the potential savings which they can produce are given. Finally, need for further trajectory optimization research is presented.

  12. Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies

    PubMed Central

    Ommen, Hans Beier

    2016-01-01

    Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon. PMID:26834951

  13. Energy minimization in medical image analysis: Methodologies and applications.

    PubMed

    Zhao, Feng; Xie, Xianghua

    2016-02-01

    Energy minimization is of particular interest in medical image analysis. In the past two decades, a variety of optimization schemes have been developed. In this paper, we present a comprehensive survey of the state-of-the-art optimization approaches. These algorithms are mainly classified into two categories: continuous method and discrete method. The former includes Newton-Raphson method, gradient descent method, conjugate gradient method, proximal gradient method, coordinate descent method, and genetic algorithm-based method, while the latter covers graph cuts method, belief propagation method, tree-reweighted message passing method, linear programming method, maximum margin learning method, simulated annealing method, and iterated conditional modes method. We also discuss the minimal surface method, primal-dual method, and the multi-objective optimization method. In addition, we review several comparative studies that evaluate the performance of different minimization techniques in terms of accuracy, efficiency, or complexity. These optimization techniques are widely used in many medical applications, for example, image segmentation, registration, reconstruction, motion tracking, and compressed sensing. We thus give an overview on those applications as well. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26186171

  14. Proposal for the standardization of flow cytometry protocols to detect minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Ikoma, Maura Rosane Valério; Beltrame, Miriam Perlingeiro; Ferreira, Silvia Inês Alejandra Cordoba Pires; Souto, Elizabeth Xisto; Malvezzi, Mariester; Yamamoto, Mihoko

    2015-01-01

    Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil. PMID:26670404

  15. Minimal residual disease: optimal methods, timing, and clinical relevance for an individual patient.

    PubMed

    Schrappe, Martin

    2012-01-01

    After approximately 20 years of development and after several prospective clinical trials, the detection of minimal residual disease (MRD) has emerged as part of state-of-the-art diagnostics to guide the majority of contemporary treatment programs both in pediatric and adult acute lymphoblastic leukemia (ALL). For ALL, several methods of MRD analysis are available, but 2 are widely applicable. One is based on the detection of aberrant expression of leukemia specific antigens by flow cytometry and the other one uses the specific rearrangements of the TCR or Ig genes, which can be detected by quantitative PCR in the DNA of leukemic cells. In some cases with known fusion genes such as BCR/ABL, RT-PCR can be used as a third method of identifying leukemic cells by analyzing RNA in patient samples. Clinical application of such sophisticated tools in the stratification and treatment of ALL requires reliable, reproducible, and quality-assured methods to ensure patient safety. PMID:23233572

  16. 78 FR 36196 - Draft Guidance for Industry: Biologics License Applications for Minimally Manipulated, Unrelated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for...: Biologics License Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord.../umbilical cord blood, for hematopoietic and immunologic reconstitution. The guidance document is intended...

  17. Minimally invasive surgery for inflammatory bowel disease: Review of current developments and future perspectives

    PubMed Central

    Neumann, Philipp-Alexander; Rijcken, Emile

    2016-01-01

    Patients with inflammatory bowel disease (IBD) comprise a population of patients that have a high likelihood of both surgical treatment at a young age and repetitive operative interventions. Therefore surgical procedures need to aim at minimizing operative trauma with best postoperative recovery. Minimally invasive techniques have been one of the major advancements in surgery in the last decades and are nowadays almost routinely performed in colorectal resections irrespective of underlying disease. However due to special disease related characteristics such as bowel stenosis, interenteric fistula, abscesses, malnutrition, repetitive surgeries, or immunosuppressive medications, patients with IBD represent a special cohort with specific needs for surgery. This review summarizes current evidence of minimally invasive surgery for patients with Crohn’s disease or ulcerative colitis and gives an outlook on the future perspective of technical advances in this highly moving field with its latest developments in single port surgery, robotics and trans-anal techniques. PMID:27158537

  18. Minimally invasive surgery for inflammatory bowel disease: Review of current developments and future perspectives.

    PubMed

    Neumann, Philipp-Alexander; Rijcken, Emile

    2016-05-01

    Patients with inflammatory bowel disease (IBD) comprise a population of patients that have a high likelihood of both surgical treatment at a young age and repetitive operative interventions. Therefore surgical procedures need to aim at minimizing operative trauma with best postoperative recovery. Minimally invasive techniques have been one of the major advancements in surgery in the last decades and are nowadays almost routinely performed in colorectal resections irrespective of underlying disease. However due to special disease related characteristics such as bowel stenosis, interenteric fistula, abscesses, malnutrition, repetitive surgeries, or immunosuppressive medications, patients with IBD represent a special cohort with specific needs for surgery. This review summarizes current evidence of minimally invasive surgery for patients with Crohn's disease or ulcerative colitis and gives an outlook on the future perspective of technical advances in this highly moving field with its latest developments in single port surgery, robotics and trans-anal techniques. PMID:27158537

  19. A minimally invasive microchip for transdermal injection/sampling applications.

    PubMed

    Strambini, Lucanos M; Longo, Angela; Diligenti, Alessandro; Barillaro, Giuseppe

    2012-09-21

    The design, fabrication, and characterization of a minimally invasive silicon microchip for transdermal injection/sampling applications are reported and discussed. The microchip exploits an array of silicon-dioxide hollow microneedles with density of one million needles cm(-2) and lateral size of a few micrometers, protruding from the front-side chip surface for one hundred micrometers, to inject/draw fluids into/from the skin. The microneedles are in connection with independent reservoirs grooved on the back-side of the chip. Insertion experiments of the microchip in skin-like polymers (agarose hydrogels with concentrations of 2% and 4% wt) demonstrate that the microneedles successfully withstand penetration without breaking, despite their high density and small size, according to theoretical predictions. Operation of the microchip with different liquids of biomedical interest (deionized water, NaCl solution, and d-glucose solution) at different differential pressures, in the range 10-100 kPa, highlights that the flow-rate through the microneedles is linearly dependent on the pressure-drop, despite the small section area (about 13 μm(2)) of the microneedle bore, and can be finely controlled from a few ml min(-1) up to tens of ml min(-1). Evaporation (at room temperature) and acceleration (up to 80 g) losses through the microneedles are also investigated to quantify the ability of the chip in storing liquids (drug to be delivered or collected fluid) in the reservoir, and result to be of the order of 70 nl min(-1) and 1300 nl min(-1), respectively, at atmospheric pressure and room temperature. PMID:22773092

  20. Application of Kick Minimization to the RTML 'Front End'

    SciTech Connect

    Tenenbaum, P.; /SLAC

    2007-02-03

    The ''front end'' of the ILC RTML constitutes the sections of the RTML which are upstream of the first RF cavity of the first stage bunch compressor: specifically, the SKEW, COLL, TURN, SPIN, and EMIT sections. Although in principle it should be easy to transport the beam through these sections with low emittance growth, since the energy spread of the beam is relatively low, in practice it is difficult because of the large number of betatron wavelengths and strong focusing, especially in the TURN section. We report here on the use of the Kick Minimization Method for limiting the emittance growth in the ''front end'' of the RTML. Kick Minimization (KM) is a steering method which balances two optima: minimization of the RMS measured orbit on the BPMs (often called 1:1 steering), and minimization of the RMS corrector strength [1]. The simulation program used for these studies is Lucretia [2].

  1. Applications of minimal physiologically-based pharmacokinetic models

    PubMed Central

    Cao, Yanguang

    2012-01-01

    Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available. Such models depend on the quality of the drug disposition data and have vague biological features. An alternative minimal-physiologically-based PK (minimal-PBPK) modeling approach is proposed which inherits and lumps major physiologic attributes from whole-body PBPK models. The body and model are represented as actual blood and tissue usually total body weight) volumes, fractions (fd) of cardiac output with Fick’s Law of Perfusion, tissue/blood partitioning (Kp), and systemic or intrinsic clearance. Analyzing only blood or plasma concentrations versus time, the minimal-PBPK models parsimoniously generate physiologically-relevant PK parameters which are more easily interpreted than those from mam-millary models. The minimal-PBPK models were applied to four types of therapeutic agents and conditions. The models well captured the human PK profiles of 22 selected beta-lactam antibiotics allowing comparison of fitted and calculated Kp values. Adding a classical hepatic compartment with hepatic blood flow allowed joint fitting of oral and intravenous (IV) data for four hepatic elimination drugs (dihydrocodeine, verapamil, repaglinide, midazolam) providing separate estimates of hepatic intrinsic clearance, non-hepatic clearance, and pre-hepatic bioavailability. The basic model was integrated with allometric scaling principles to simultaneously describe moxifloxacin PK in five species with common Kp and fd values. A basic model assigning clearance to the tissue compartment well characterized plasma concentrations of six monoclonal antibodies in human subjects, providing good concordance of predictions with expected tissue kinetics. The proposed minimal-PBPK modeling approach offers an alternative and more rational basis for assessing PK than compartmental models. PMID:23179857

  2. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia

    PubMed Central

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-01-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348 PMID:26001791

  3. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies

    PubMed Central

    van der Velden, Vincent H. J.; Brüggemann, Monika; Orfao, Alberto

    2015-01-01

    Monitoring of minimal residual disease (MRD) has become routine clinical practice in frontline treatment of virtually all childhood acute lymphoblastic leukemia (ALL) and in many adult ALL patients. MRD diagnostics has proven to be the strongest prognostic factor, allowing for risk group assignment into different treatment arms, ranging from significant treatment reduction to mild or strong intensification. Also in relapsed ALL patients and patients undergoing stem cell transplantation, MRD diagnostics is guiding treatment decisions. This is also why the efficacy of innovative drugs, such as antibodies and small molecules, are currently being evaluated with MRD diagnostics within clinical trials. In fact, MRD measurements might well be used as a surrogate end point, thereby significantly shortening the follow-up. The MRD techniques need to be sensitive (≤10−4), broadly applicable, accurate, reliable, fast, and affordable. Thus far, flow cytometry and polymerase chain reaction (PCR) analysis of rearranged immunoglobulin and T-cell receptor genes (allele-specific oligonucleotide [ASO]-PCR) are claimed to meet these criteria, but classical flow cytometry does not reach a solid 10−4, whereas classical ASO-PCR is time-consuming and labor intensive. Therefore, 2 high-throughput technologies are being explored, ie, high-throughput sequencing and next-generation (multidimensional) flow cytometry, both evaluating millions of sequences or cells, respectively. Each of them has specific advantages and disadvantages. PMID:25999452

  4. Minimizing masses in explosively driven two-shockwave physics applications

    NASA Astrophysics Data System (ADS)

    Buttler, William; Cherne, Frank; Furlanetto, Michael; Payton, Jeremy; Stone, Joseph; Tabaka, Leonard; Vincent, Samuel

    2015-06-01

    We have experimentally investigated different two-shockwave high-explosives (HE) physics package designs to maximize the variability of the second shockwave peak stress, while minimizing the total HE load of the physics tool. A critical requirement is to also have a large radial diameter of the second shockwave to maintain its value as an HE driven two-shockwave drive. We have previously shown that we could vary the peak-stress of the second-shockwave with a 76 mm diameter HE lens driving different composite boosters of PBX 9501 and TNT. Here we report on our results with a 56- and 50-mm diameter HE lens driving Baritol. The results indicate that the 56-mm diameter HE lens works well, as does the Baritol, giving total HE loads of about 250 mg TNT equivalent explosives.

  5. Sensitive and Specific Measurement of Minimal Residual Disease in Acute Lymphoblastic Leukemia

    PubMed Central

    Morley, Alexander A.; Latham, Sue; Brisco, Michael J.; Sykes, Pamela J.; Sutton, Rosemary; Hughes, Elizabeth; Wilczek, Vicki; Budgen, Bradley; van Zanten, Katrina; Kuss, Bryone J.; Venn, Nicola C.; Norris, Murray D.; Crock, Catherine; Storey, Colin; Revesz, Tamas; Waters, Keith

    2009-01-01

    A sensitive and specific quantitative real-time polymerase chain reaction method, involving three rounds of amplification with two allele-specific oligonucleotide primers directed against an rearrangement, was developed to quantify minimal residual disease (MRD) in B-lineage acute lymphoblastic leukemia (ALL). For a single sample containing 10 μg of good quality DNA, MRD was quantifiable down to approximately 10−6, which is at least 1 log more sensitive than current methods. Nonspecific amplification was rarely observed. The standard deviation of laboratory estimations was 0.32 log units at moderate or high levels of MRD, but increased markedly as the level of MRD and the number of intact marker gene rearrangements in the sample fell. In 23 children with ALL studied after induction therapy, the mean MRD level was 1.6 × 10−5 and levels ranged from 1.5 × 10−2 to less than 10−7. Comparisons with the conventional one-round quantitative polymerase chain reaction method on 29 samples from another 24 children who received treatment resulted in concordant results for 22 samples and discordant results for seven samples. The sensitivity and specificity of the method are due to the use of nested polymerase chain reaction, one segment-specific and two allele-specific oligonucleotide primers, and the use of a large amount of good quality DNA. This method may improve MRD-based decisions on treatment for ALL patients, and the principles should be applicable to DNA-based MRD measurements in other disorders. PMID:19324989

  6. Selecting Map Projections in Minimizing Area Distortions in GIS Applications

    PubMed Central

    Yildirim, Faruk; Kaya, Ahmet

    2008-01-01

    Various software for Geographical Information Systems (GISs) have been developed and used in many different engineering projects. In GIS applications, map coverage is important in terms of performing reliable and meaningful queries. Map projections can be conformal, equal-area and equidistant. The goal of an application plays an important role in choosing one of those projections. Choosing the equal-area projection for an application in which area information is used (forestry, agriculture, ecosystem etc) reduces the amount of distortion on the area, but many users using GIS ignore this fact and continue to use applications with present map sheets no matter in what map projection it is. For example, extracting area information from data whose country system's map sheet is in conformal projection is relatively more distorted, compared to an equal-area projection one. The goal of this study is to make the best decision in choosing the most proper equal-area projection among the choices provided by ArcGIS 9.0, which is a popular GIS software package, and making a comparison on area errors when conformal projection is used. In this study, the area of parcels chosen in three different regions and geographic coordinates and whose sizes vary between 0.01 to 1,000,000 ha are calculated according to Transversal Mercator (TM, 3°), Universal Transversal Mercator (UTM, 6°) and 14 different equal-area projections existing in the ArcGIS 9.0 GIS software package. The parcel areas calculated with geographical coordinates are accepted as definite. The difference between the sizes calculated according to projection coordinates and real sizes of the parcels are determined. Consequently, the appropriate projections are decided for the areas smaller and equal than 1,000 ha and greater than 1,000 ha in the GIS software package.

  7. Minimal form factor digital-image sensor for endoscopic applications

    NASA Astrophysics Data System (ADS)

    Wäny, Martin; Voltz, Stephan; Gaspar, Fabio; Chen, Lei

    2009-02-01

    This paper presents a digital image sensor SOC featuring a total chip area (including dicing tolerances) of 0.34mm2 for endoscopic applications. Due to this extremely small form factor the sensor enables integration in endoscopes, guide wires and locater devices of less than 1mm outer diameter. The sensor embeds a pixel matrix of 10'000 pixels with a pitch of 3um x 3um covered with RGB filters in Bayer pattern. The sensor operates fully autonomous, controlled by an on chip ring oscillator and readout state machine, which controls integration AD conversion and data transmission, thus the sensor only requires 4 pin's for power supply and data communication. The sensor provides a frame rate of 40Frames per second over a LVDS serial data link. The endoscopic application requires that the sensor must work without any local power decoupling capacitances at the end of up to 2m cabling and be able to sustain data communication over the same wire length without deteriorating image quality. This has been achieved by implementation of a current mode successive approximation ADC and current steering LVDS data transmission. An band gap circuit with -40dB PSRR at the data frequency was implemented as on chip reference to improve robustness against power supply ringing due to the high series inductance of the long cables. The B&W versions of the sensor provides a conversion gain of 30DN/nJ/cm2 at 550nm with a read noise in dark of 1.2DN when operated at 2m cable. Using the photon transfer method according to EMVA1288 standard the full well capacity was determined to be 18ke-. According to our knowledge the presented work is the currently world smallest fully digital image sensor. The chip was designed along with a aspheric single surface lens to assemble on the chip without increasing the form factor. The extremely small form factor of the resulting camera permit's to provide visualization with much higher than state of the art spatial resolution in sub 1mm endoscopic

  8. Minimal Technologies Application Project, Hohenfels Training Area, Germany: Final report

    SciTech Connect

    Zellmer, S.D.; Hinchman, R.R.; Johnson, D.O. . Energy Systems Div.); Severinghaus, W.D. ); Brent, J.J. )

    1991-12-01

    At the US Army Hohenfels Training Area in Germany, more than 30 years of continuous and intensive tactical training has caused extensive environmental damage because of the loss of vegetative cover and accelerated soil erosion. A project was conducted to evaluate the cost-effectiveness and relative benefits of various revegetation procedures. These procedures involved amendment and seedbed preparation options that were combined with three different durations of site closure. The point-intercept method was used to measure the types and amounts of vegetation established and changes in the vegetative community. Over three growing seasons, applications of fertilizer and seed increased the percent grass, legume, and total vegetative cover. The duration of site closure had no influence on the types or amounts of ground cover established. Materials made up only 10% of the total cost of the fertilization and seeding operations. The results of the research indicate that less expensive methods of amendment application should be evaluated. The data also show that site closure is not practical, economical, or necessary. The results of this project suggest that a regular maintenance program consisting of seeding and fertilization is required to maintain adequate vegetative cover and control erosion on tactical training areas.

  9. Virtual reality applications in improving postural control and minimizing falls.

    PubMed

    Virk, Sumandeep; McConville, Kristiina M Valter

    2006-01-01

    Maintaining balance under all conditions is an absolute requirement for humans. Orientation in space and balance maintenance requires inputs from the vestibular, the visual, the proprioceptive and the somatosensory systems. All the cues coming from these systems are integrated by the central nervous system (CNS) to employ different strategies for orientation and balance. How the CNS integrates all the inputs and makes cognitive decisions about balance strategies has been an area of interest for biomedical engineers for a long time. More interesting is the fact that in the absence of one or more cues, or when the input from one of the sensors is skewed, the CNS "adapts" to the new environment and gives less weight to the conflicting inputs [1]. The focus of this paper is a review of different strategies and models put forward by researchers to explain the integration of these sensory cues. Also, the paper compares the different approaches used by young and old adults in maintaining balance. Since with age the musculoskeletal, visual and vestibular system deteriorates, the older subjects have to compensate for these impaired sensory cues for postural stability. The paper also discusses the applications of virtual reality in rehabilitation programs not only for balance in the elderly but also in occupational falls. Virtual reality has profound applications in the field of balance rehabilitation and training because of its relatively low cost. Studies will be conducted to evaluate the effectiveness of virtual reality training in modifying the head and eye movement strategies, and determine the role of these responses in the maintenance of balance. PMID:17946975

  10. Flow cytometric determination of leukemia-associated marker combinations for the study of minimal residual disease.

    PubMed

    Babusíková, O; Glasová, M; Kusenda, J; Koníková, E; Mésárosová, A

    1994-01-01

    To study the minimal residual disease in acute leukemia patients we used some marker combinations related either to the simultaneous surface membrane and cytoplasmic marker expression, or to the expression of atypical marker combinations, that are absent or extremely rare in normal hematopoietic cells. We investigated to which extent flow cytometric analysis of leukemia-associated marker combination may contribute to sensitive follow-up in patients with acute leukemia. For this purpose dilution experiments were performed, in which artificial mixtures of normal peripheral blood lymphocytes and leukemia cells from a patient with leukemia-associated phenotype were prepared and analyzed for double positive cells. Our results showed that the sensitivity of double color immunofluorescence assay was 3 in 10(4) cells. Sequential studies of residual disease were evaluated in five acute leukemia patients with leukemia-associated markers combinations at diagnosis. In three of them morphologic relapse was preceded by the immunologic detection of small amounts of leukemia cells, while in two other cases, in which no double positive cells for leukemia-associated markers were found, patients are still in hematologic remission. This approach to the study of minimal residual disease could be valuable in monitoring the efficiency of chemotherapy, as well as in evaluating the quality control of bone marrow before autografting. Furthermore, flow cytometric approach can efficiently complete other methods, which are used for more exact definition of remission in acute leukemia patients. PMID:7870213

  11. Peripheral blood minimal residual disease may replace bone marrow minimal residual disease as an immunophenotypic biomarker for impending relapse in acute myeloid leukemia.

    PubMed

    Zeijlemaker, W; Kelder, A; Oussoren-Brockhoff, Y J M; Scholten, W J; Snel, A N; Veldhuizen, D; Cloos, J; Ossenkoppele, G J; Schuurhuis, G J

    2016-03-01

    As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML. PMID:26373238

  12. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

    PubMed

    Kumar, Shaji; Paiva, Bruno; Anderson, Kenneth C; Durie, Brian; Landgren, Ola; Moreau, Philippe; Munshi, Nikhil; Lonial, Sagar; Bladé, Joan; Mateos, Maria-Victoria; Dimopoulos, Meletios; Kastritis, Efstathios; Boccadoro, Mario; Orlowski, Robert; Goldschmidt, Hartmut; Spencer, Andrew; Hou, Jian; Chng, Wee Joo; Usmani, Saad Z; Zamagni, Elena; Shimizu, Kazuyuki; Jagannath, Sundar; Johnsen, Hans E; Terpos, Evangelos; Reiman, Anthony; Kyle, Robert A; Sonneveld, Pieter; Richardson, Paul G; McCarthy, Philip; Ludwig, Heinz; Chen, Wenming; Cavo, Michele; Harousseau, Jean-Luc; Lentzsch, Suzanne; Hillengass, Jens; Palumbo, Antonio; Orfao, Alberto; Rajkumar, S Vincent; San Miguel, Jesus; Avet-Loiseau, Herve

    2016-08-01

    Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments. PMID:27511158

  13. Minimal Clinically Important Difference on Parkinson's Disease Sleep Scale 2nd Version

    PubMed Central

    Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Deli, Gabriella; Janszky, József; Komoly, Sámuel; Karádi, Kázmér; Kovács, Márton; Makkos, Attila; Faludi, Béla; Kovács, Norbert

    2015-01-01

    Background and Aims. The aim of the present study was to determine the estimates of minimal clinically important difference for Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score and dimensions. Methods. The subject population consisted of 413 PD patients. At baseline, MDS-UPDRS, Hoehn-Yahr Scale, Mattis Dementia Rating Scale, and PDSS-2 were assessed. Nine months later the PDSS-2 was reevaluated with the Patient-Reported Global Impression Improvement Scale. Both anchor-based techniques (within patients' score change method and sensitivity- and specificity-based method by receiver operating characteristic analysis) and distribution-based approaches (effect size calculations) were utilized to determine the magnitude of minimal clinically important difference. Results. According to our results, any improvements larger than −3.44 points or worsening larger than 2.07 points can represent clinically important changes for the patients. These thresholds have the effect size of 0.21 and −0.21, respectively. Conclusions. Minimal clinically important differences are the smallest change of scores that are subjectively meaningful to patients. Studies using the PDSS-2 as outcome measure should utilize the threshold of −3.44 points for detecting improvement or the threshold of 2.07 points for observing worsening. PMID:26539303

  14. A new multiple-drug applicator with minimal drug cross-talk, leakage, and consumption.

    PubMed

    Fujita, Yosuke; Shimomura, Takeshi; Hosoguchi, Masafumi; Kano, Masanobu; Fukurotani, Kenkichi; Tabata, Toshihide

    2010-04-01

    The relative effects of multiple drugs give an important clue to dissect a neuronal mechanism and to seek for a candidate neurotherapeutical agent. Here we have devised a "flute" applicator which can deliver several drugs to a neural cell preparation. The applicator stands by, cleaning itself with bath perfusate and delivers drugs only during test applications. This minimizes drug cross-talk in and leakage from the applicator and drug consumption. Using the applicator, we successfully compared the relative effects of widely different doses of an agonist in single neurons. The flute applicator would be a useful tool for pharmacological analyses. PMID:20060427

  15. Detection of minimal residual disease by polymerase chain reaction in patients with different hematologic diseases treated by bone marrow transplantation.

    PubMed

    Stuppia, L; Calabrese, G; Guanciali Franchi, P; Di Bartolomeo, P; Antonucci, A; Peila, R; Torlontano, G; Palka, G

    1993-02-01

    Thirteen male patients affected by different hematologic diseases who underwent bone marrow transplantation (BMT) with female donors were investigated by cytogenetic analysis and polymerase chain reaction (PCR) amplification of a DNA sequence specific for the Y chromosome. In six of these patients, PCR showed the presence of the Y chromosome-related sequence; in only three of these did cytogenetic analysis confirm the presence of mixed chimerism. In the remaining three patients, the results of the PCR were confirmed by in situ hybridization on cell nuclei with a probe for the alpha-satellite of the Y chromosome. We compare results obtained with the two methods and discuss the meaning of the minimal residual disease detected by PCR in patients submitted to BMT. PMID:8453609

  16. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL.

    PubMed

    Thompson, Philip A; Wierda, William G

    2016-01-21

    Deep remission and prolonged disease-free survival can be achieved with first-line chemoimmunotherapy (CIT), such as combined fludarabine, cyclophosphamide, and rituximab, in the majority of patients with chronic lymphocytic leukemia (CLL). More modest results are reported with less intense regimens like obinutuzumab plus chlorambucil. Clinical assessment has limited sensitivity in detecting residual disease responsible for subsequent relapse, even including morphologic bone marrow (BM) evaluation. Multicolor flow cytometry and polymerase chain reaction (PCR)-based methods can detect minimal residual disease (MRD) to a sensitivity of ≥1:10,000 (10(-4)). Achieving BM MRD-negative complete remission (CR) is associated with superior progression-free survival (PFS) and overall survival; MRD status is the single best posttreatment predictor of long-term outcomes after CIT. Newer oral B-cell receptor signaling pathway inhibitors are highly effective at controlling disease, but best monotherapy responses are typically partial remission, and patients must remain on treatment to maintain disease control. Therapeutic progress is still needed for CLL. We propose that targeting MRD provides opportunity to realize this progress. Achieving BM MRD-negative CR is a prerequisite for long-term unmaintained disease-free survival and potential for cure. We review available methodologies for detecting MRD and correlations with posttreatment outcomes. We discuss the potential utility of MRD to direct individualized therapy. Finally, we discuss the importance of MRD-negative status as a surrogate marker for longer PFS in clinical studies to allow more rapid determination of clinical benefit. PMID:26576865

  17. Minimally invasive treatment of pilonidal disease: crystallized phenol and laser depilation.

    PubMed

    Girgin, Mustafa; Kanat, Burhan Hakan; Ayten, Refik; Cetinkaya, Ziya; Kanat, Zekiye; Bozdağ, Ahmet; Turkoglu, Ahmet; Ilhan, Yavuz Selim

    2012-01-01

    Pilonidal disease has been treated surgically and by various other methods for many years. The most important problem associated with such treatment is recurrence, but cosmetic outcome is another important issue that cannot be ignored. Today, crystallized phenol is recognized as a treatment option associated with good medical and cosmetic outcomes. We hypothesized that the addition of laser depilation to crystallized phenol treatment of pilonidal disease might increase the rate of success, and this study aimed to determine if the hypothesis was true. Patients who were treated with crystallized phenol and 755-nm alexandrite laser depilation were retrospectively analyzed. In total, 42 (31 male and 11 female) patients were treated with crystallized phenol and alexandrite laser depilation and were followed up between January 2009 and January 2012. In all, 38 patients (90.5%) had chronic disease and 4 (9.5%) had recurrent disease. Among the patients, 26 (61.9%) recovered following 1 crystallized phenol treatment, and the remaining patients had complete remission following repeated treatment. Some patients needed multiple treatments, even up to 8 times. None of the patients had a recurrence during a mean 24 months (range, 6-30 months) of follow-up. Whatever method of treatment is used for pilonidal disease, hair cleaning positively affects treatment outcome. The present results support the hypothesis that the addition of laser depilation (which provides more permanent and effective depilation than other methods) to crystallized phenol treatment (a non-radical, minimally invasive method associated with very good cosmetic results) can increase the effectiveness of the treatment and also reduce the recurrence rate of the disease. PMID:23294066

  18. A New Approach to Rigid Body Minimization with Application to Molecular Docking*

    PubMed Central

    Mirzaei, Hanieh; Kozakov, Dima; Beglov, Dmitri; Paschalidis, Ioannis Ch.; Vajda, Sandor; Vakili, Pirooz

    2013-01-01

    Our work is motivated by energy minimization in the space of rigid affine transformations of macromolecules, an essential step in computational protein-protein docking. We introduce a novel representation of rigid body motion that leads to a natural formulation of the energy minimization problem as an optimization on the SO(3)×R3 manifold, rather than the commonly used SE(3). The new representation avoids the complications associated with optimization on the SE(3) manifold and provides additional flexibilities for optimization not available in that formulation. The approach is applicable to general rigid body minimization problems. Our computational results for a local optimization algorithm developed based on the new approach show that it is about an order of magnitude faster than a state of art local minimization algorithms for computational protein-protein docking. PMID:24763338

  19. Minimal residual disease monitoring: the new standard for treatment evaluation of haematological malignancies?

    PubMed

    Hauwel, Mathieu; Matthes, Thomas

    2014-01-01

    Minimal residual disease (MRD) refers to the small number of malignant cells that remain after therapy when the patient is in remission and shows no symptoms or overt signs of disease. Current treatment protocols for haematological malignancies allow most patients to obtain some form of MRD state, but cure seldom follows and in most cases fatal relapses occur sooner or later, leaving a bitter impression of having won a battle yet lost the war. MRD detection and quantification are used for evaluation of treatment efficiency, patient risk stratification and long-term outcome prediction. Whereas multicolour flow cytometry (MCFC) and polymerase chain reaction (PCR) based methods constitute the two most commonly used techniques for MRD detection, next generation sequencing will certainly be widely employed in the future. As MRD reflects the nature of the malignant disease itself, including its sensitivity to the drug regimens applied, it constitutes the ideal method for surveillance and patient follow-up. The morphological examination of peripheral blood or bone marrow smears, although still an indispensable part of routine laboratory testing, is clearly insufficient for patient management, and clinicians should not ask themselves whether to look for MRD or not, but how and when. PMID:24452390

  20. Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells.

    PubMed

    Tachtsidis, A; McInnes, L M; Jacobsen, N; Thompson, E W; Saunders, C M

    2016-08-01

    Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)-cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)-cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy-be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs. PMID:27189371

  1. Development of minimal residual disease-directed therapy in acute myeloid leukemia.

    PubMed

    Freeman, Sylvie D; Jovanovic, Jelena V; Grimwade, David

    2008-08-01

    The last three decades have seen major advances in understanding the genetic basis of acute myeloid leukemia (AML). Comprehensive molecular and cytogenetic analysis can distinguish biologically and prognostically distinct disease subsets that demand differing treatment approaches. Definition of these pretreatment characteristics coupled with morphological response to induction chemotherapy provides the framework for current risk-stratification schemes, aimed at identifying subgroups most (and least) likely to benefit from allogeneic transplant. However, since such parameters lack the precision to distinguish the individual patient likely to be cured with conventional therapy from those destined to relapse, there has been considerable interest in development of multiparameter flow cytometry, identifying leukemia-associated aberrant phenotypes, and real-time quantitative polymerase chain reaction (RQ-PCR) detecting leukemia-specific targets (eg, fusion gene transcripts, NPM1 mutation) or genes overexpressed in AML (eg, WT1), to provide a more precise measure of disease response. Minimal residual disease (MRD) monitoring has been shown to be a powerful independent prognostic factor and is now routinely used to guide therapy in patients with the acute promyelocytic leukemia (APL) subtype. We consider the challenges involved in extending this concept, to develop a more tailored personalized medicine approach to improve the management and outcome of other forms of AML. PMID:18692689

  2. Usability factors of mobile health application for chronic diseases

    NASA Astrophysics Data System (ADS)

    Zahra, Fatima; Hussain, Azham; Mohd, Haslina

    2016-08-01

    M-health has changed the conventional delivery system of health-care, permitting continuous, pervasive Health-care anywhere, anytime. Chronic disease apps are increasing, as many health workers, patients and clinicians already embracing smartphones in their comprehensive and diverse practices. There are lots of challenges and requirements that need to be addressed for mobile health applications to prevent or eliminate design problems and minimize potential threats for users, the proposed factors for chronic disease mobile applications can be used as a guide for app developers While, the usability testing, and evaluations of chronic disease apps have not yet touched the accuracy level of other web based applications. This study is being conducted to learn about challenges of m-health apps and to identify the factors that affect the usability of such applications.

  3. Accurate Sample Assignment in a Multiplexed, Ultrasensitive, High-Throughput Sequencing Assay for Minimal Residual Disease.

    PubMed

    Bartram, Jack; Mountjoy, Edward; Brooks, Tony; Hancock, Jeremy; Williamson, Helen; Wright, Gary; Moppett, John; Goulden, Nick; Hubank, Mike

    2016-07-01

    High-throughput sequencing (HTS) (next-generation sequencing) of the rearranged Ig and T-cell receptor genes promises to be less expensive and more sensitive than current methods of monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, the adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine the Ig heavy-chain gene HTS on the Illumina MiSeq platform for MRD. We identify errors associated with multiplexing that could potentially impact the accuracy of MRD analysis. We optimize a strategy that combines high-purity, sequence-optimized oligonucleotides, dual indexing, and an error-aware demultiplexing approach to minimize errors and maximize sensitivity. We present a probability-based, demultiplexing pipeline Error-Aware Demultiplexer that is suitable for all MiSeq strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally, using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 10(6) copies of specific leukemic MRD. PMID:27183494

  4. Update on Pharmaceutical and Minimally Invasive Management Strategies for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Rafii, Rokhsara; Albertson, Timothy E.; Louie, Samuel; Chan, Andrew L.

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a debilitating pulmonary disorder with systemic effects, and it is the fourth leading cause of death in the United States. COPD patients not only develop respiratory limitations, but can also demonstrate systemic wasting, features of depression, and can succumb to social isolation. Smoking cessation is crucial, and pharmacotherapy with bronchodilators is helpful in symptom management. Inhaled corticosteroids may be beneficial in some patients. In addition, pulmonary rehabilitation and palliative care are important components under the right clinical circumstance. This review highlights current guidelines and management strategies for COPD and emphasizes novel pharmacotherapy and minimally invasive (nonsurgical) lung-volume reduction interventions that may prove to be of significant benefit in the future. PMID:21660228

  5. Minimal residual disease of leukemia and the quality of cryopreserved human ovarian tissue in vitro.

    PubMed

    Asadi-Azarbaijani, Babak; Sheikhi, Mona; Nurmio, Mirja; Tinkanen, Helena; Juvonen, Vesa; Dunkel, Leo; Hovatta, Outi; Oskam, Irma C; Jahnukainen, Kirsi

    2016-03-01

    Auto-transplant of cryopreserved ovarian tissue in leukemia patients carries a risk to reintroduce malignant cells. Maturation of ovarian follicles in vitro is a promising strategy to overcome the leukemic cell contamination. The follicle development and survival in 14 cryopreserved ovarian tissues with leukemia-specific PCR marker was evaluated after 7 or 14 days culture. Minimal residual disease (MRD) quantification was assessed by real-time quantitative PCR in order to identify the MRD positive (n = 6) and negative (n = 8) samples and to monitor levels of MRD before and after culture. The morphology of ovarian follicles were studied by light microscopy. After culture, no statistical significant differences were detected in follicle densities between MRD positive- and negative samples. Ovarian MRD either decreased below undetectable or fluctuated near the baseline level after 7 and 14 days in culture. This study provides quantitative in vitro evidence that leukemia contamination does not affect the follicle survival in cryopreserved ovarian tissue. PMID:26122194

  6. Minimal Residual Disease by Next-Generation Sequencing: Pros and Cons.

    PubMed

    Avet-Loiseau, Herve

    2016-01-01

    The wealth of data recently generated highlights that minimal residual disease (MRD)-negative status can be achieved in a large proportion of patients. These studies, in addition to a meta-analysis, clearly suggest significant improvement in both event-free survival (EFS) and overall survival (OS) among those patients achieving MRD-negative status, especially with sensitivity of one cell in 1 million bone marrow cells. There is an evolving consensus that achieving MRD-negative status should become the ultimate goal of therapeutic intervention. Further future efforts should now be directed at determining how MRD status can be used to guide and personalize further therapy including type of consolidation and maintenance therapy. PMID:27249750

  7. WASTE MINIMIZATION FOR NON-AGRICULTURAL PESTICIDE APPLICATORS: EPA'S POLLUTION PREVENTION GUIDE

    EPA Science Inventory

    U.S. EPA's Office of Research and Development is preparing a guide to be published later this year for non-agricultural pesticide applicators which will provide specific information about waste minimization for pesticide users in industries such as commercial lawn care, structura...

  8. 78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ...The Food and Drug Administration (FDA) is announcing the availability of a draft document entitled ``Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System'' dated June 2013.......

  9. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: A Clinical Evidence Review

    PubMed Central

    2016-01-01

    Background Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD). Poor event-free survival (EFS) as well as overall survival for those who are classified as MRD-positive have been substantiated in seminal studies demonstrating the prognostic value of MRD for EFS in the past few decades. This review sought to further elucidate the relationship between MRD and EFS by looking at relapse, the primary determinant of EFS and the biological mechanism through which MRD is thought to act. This evidence review aimed to ascertain whether MRD is an independent prognostic factor for relapse and to assess the effect of MRD-directed treatment on patient-important outcomes in childhood ALL. Methods Large prospective cohort studies with a priori multivariable analysis that includes potential confounders are required to draw confirmatory conclusions about the independence of a prognostic factor. Data on the prognostic value of MRD for relapse measured by molecular methods (polymerase chain reaction [PCR] of immunoglobulin or T-cell receptor rearrangements) or flow cytometry for leukemia-associated immunophenotypes or difference-from-normal approach were abstracted from included studies. Relevant data on relapse, EFS, and overall survival were abstracted from randomized controlled trials (RCTs) evaluating the effect of MRD-directed treatment. Results A total of 2,832 citations were reviewed, of which 12 studies were included in this

  10. Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

    PubMed

    Beldjord, Kheira; Chevret, Sylvie; Asnafi, Vahid; Huguet, Françoise; Boulland, Marie-Laure; Leguay, Thibaut; Thomas, Xavier; Cayuela, Jean-Michel; Grardel, Nathalie; Chalandon, Yves; Boissel, Nicolas; Schaefer, Beat; Delabesse, Eric; Cavé, Hélène; Chevallier, Patrice; Buzyn, Agnès; Fest, Thierry; Reman, Oumedaly; Vernant, Jean-Paul; Lhéritier, Véronique; Béné, Marie C; Lafage, Marina; Macintyre, Elizabeth; Ifrah, Norbert; Dombret, Hervé

    2014-06-12

    With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively. PMID:24740809

  11. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10(-3) a 10(-5)), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  12. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  13. Minimal residual disease monitoring and preemptive immunotherapy in myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Qin, Ya-Zhen; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-08-01

    This study investigated the efficacy of minimal residual disease (MRD) monitoring and MRD-directed preemptive immunotherapy in high-risk myelodysplastic syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (HSCT). MRD assessment consisted of Wilms' tumor gene 1 (WT1) detection with PCR and leukemia-associated immunophenotypic pattern examination with multiparameter flow cytometry (FCM). Post-HSCT, 31 patients were positive for WT1, and 8, for FCM; positivity for WT1 (18.6 vs. 6.1 %, P = 0.040) or FCM (62.5 vs. 3.6 %, P < 0.001) indicated a higher 2-year relapse rate. Twenty-one patients met our combined criteria for MRD, and the presence of MRD was associated with a higher 2-year relapse rate (27.3 vs. 4.5 %, P = 0.003). Preferentially expressed antigen of melanoma (PRAME) expression alone was not an appropriate MRD marker; however, it suggested that the MRD-positive patients may fail to respond to preemptive immunotherapy. In patients positive for both PRAME and MRD, the relapse rate was 60 % despite preemptive immunotherapy. Multivariate analysis confirmed the association between the increased relapse rate and positivity for both PRAME and MRD (hazard ratio = 42.8, P = 0.001). MRD monitoring predicted relapse in high-risk MDS post-HSCT patients, and PRAME- and MRD-positive patients did not benefit from preemptive immunotherapy. PMID:27302479

  14. New criteria for response assessment: role of minimal residual disease in multiple myeloma

    PubMed Central

    Paiva, Bruno; van Dongen, Jacques J. M.

    2015-01-01

    Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as acute lymphoblastic leukemia. In multiple myeloma (MM), the majority of patients will inevitably relapse despite achievement of progressively higher complete remission (CR) rates. Novel treatment protocols with inclusion of antibodies and small molecules might well be able to further increase remission rates and potentially also cure rates. Therefore, MRD diagnostics becomes essential to assess treatment effectiveness. This review summarizes reports from the past 2 decades, which demonstrate that persistent MRD by multiparameter flow cytometry, polymerase chain reaction, next-generation sequencing, and positron emission tomography/computed tomography, predicts significantly inferior survival among CR patients. We describe the specific features of currently available techniques for MRD monitoring and outline the arguments favoring new criteria for response assessment that incorporate MRD levels. Extensive data indicate that MRD information can potentially be used as biomarker to evaluate the efficacy of different treatment strategies, help on treatment decisions, and act as surrogate for overall survival. The time has come to address within clinical trials the exact role of baseline risk factors and MRD monitoring for tailored therapy in MM, which implies systematic usage of highly sensitive, cost-effective, readily available, and standardized MRD techniques. PMID:25838346

  15. Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction

    PubMed Central

    Rawstron, Andy C.; Gregory, Walter M.; de Tute, Ruth M.; Davies, Faith E.; Bell, Sue E.; Drayson, Mark T.; Cook, Gordon; Jackson, Graham H.; Morgan, Gareth J.; Child, J. Anthony

    2015-01-01

    The detection of minimal residual disease (MRD) in myeloma using a 0.01% threshold (10−4) after treatment is an independent predictor of progression-free survival (PFS), but not always of overall survival (OS). However, MRD level is a continuous variable, and the predictive value of the depth of tumor depletion was evaluated in 397 patients treated intensively in the Medical Research Council Myeloma IX study. There was a significant improvement in OS for each log depletion in MRD level (median OS was 1 year for ≥10%, 4 years for 1% to <10%, 5.9 years for 0.1% to <1%, 6.8 years for 0.01% to <0.1%, and more than 7.5 years for <0.01% MRD). MRD level as a continuous variable determined by flow cytometry independently predicts both PFS and OS, with approximately 1 year median OS benefit per log depletion. The trial was registered at www.isrctn.com as #68454111. PMID:25645353

  16. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

    SciTech Connect

    Lockwood, A.H.; Yap, E.W.; Rhoades, H.M.; Wong, W.H. )

    1991-03-01

    We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.

  17. Timing of foliar Zn application plays a vital role in minimizing Cd accumulation in wheat.

    PubMed

    Saifullah; Javed, Hina; Naeem, Asif; Rengel, Zed; Dahlawi, Saad

    2016-08-01

    Due to chemical and biochemical similarities between cadmium (Cd) and zinc (Zn), application of Zn may minimize Cd uptake by plants and ameliorate its toxicity. However, there is poor understanding of the comparative effectiveness of the foliar Zn application at different growth stages on Cd toxicity and accumulation in wheat. The present study was carried out to compare the effectiveness of foliarly applied Zn at different stages of plant growth to minimize Cd accumulation in wheat grains. Wheat (cv AARI-2011) was grown at three levels of soil Cd (0, 2.5, and 5.0 mg kg(-1)). Foliar application of Zn was carried out at either tillering, jointing, booting, heading, or grain filling stage using 0.05 % w/v aqueous solution of ZnSO4 · 7H2O. Increasing soil Cd had a negative effect on growth and yield attributes, including tiller production, root length and dry weight, plant height, 100-grain weight and grain and straw yield. Zinc foliar spray increased grain yield by increasing tiller production; importantly, an application at booting was more effective than at other stages. Foliarly applied Zn decreased Cd concentration in the roots, straw, and grain. Similar to grain yield, the largest decrease (74 %) in Cd concentration was associated with Zn foliar spray at booting. Grain yield was negatively related to grain Cd concentration which in turn showed a negative relationship with Zn concentration in leaves and grains. It is concluded that the booting stage is the suitable time for foliar application of Zn to (i) effectively minimize a Cd-induced loss in grain yield and (ii) decrease grain Cd concentration. PMID:27164881

  18. Evaluation of Minimal Residual Disease in Acute Myeloid Leukemia with NPM1 Marker

    PubMed Central

    Alizad Ghandforoush, Nasrin; Chahardouli, Bahram; Rostami, Shahrbano; Ghadimi, Habibeh; Ghasemi, Ali; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Nadali, Fatemeh

    2016-01-01

    Background: Minimal residual disease (MRD) tests provide early identification of hematologic relapse and timely management of acute myeloid leukemia (AML) patients. Approximately, 50% of AML patients do not have clonal chromosomal aberrations and categorize as a cytogenetically normal acute myeloid leukemia (CN-AML). About 60% of adult CN-AML has a mutation in exon 12 of NPM1 gene. This mutation is specific for malignant clone and potentially is a good marker of MRD. In this retrospective study, we set up a quantitative test for quantifying NPM1 type A mutation and AML patients carrying this mutation at the time of diagnosis, were followed-up. Materials and Methods : We prepared plasmids containing a cDNA fragment of NPM1 and ABL genes by PCR cloning. The plasmids were used to construct standard curves. Eleven patients were analyzed using established method. Serial PB and/or BM samples (n=71) were taken in 1-3 months intervals (mean 1.5-month intervals) and median follow-up duration after chemotherapy was 11 months (5-28.5 months). Results: In this study, we developed RNA-based RQ-PCR to quantitation of NPM1 mutation A with sensitivities of 10(-5). The percent of NPMmut/ABL level showed a range between 132 and 757 with median of 383.5 in samples at diagnosis. The median NPMmut transcript level log reduction was 3 logs. Relapse occurred in 54.5% of patients (n=6), all cases at diagnosis demonstrated the same mutation at relapse. In patients who experienced relapse, log reduction levels of NPM1 mRNA transcript after therapy were 4 (n=2), 3 (n=2) and 1 log (n=2). Totally, NPMmut level showed less than 5 log reduction in all of them, whereas this reduction was 5-6 logs in other patients. Conclusion: Despite the limitations of this study in terms of sample size and duration of follow-up, it showed the accuracy of set up for detection of mutation and this marker has worth for following-up at different stages of disease. Because of high frequency, stability, specificity

  19. IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

    SciTech Connect

    Duprez, Frederic; Madani, Indira; Morbee, Lieve; Bonte, Katrien; Deron, Philippe; Domjan, Vilmos; Boterberg, Tom; De Gersem, Werner; De Neve, Wilfried

    2012-05-01

    Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages were T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival

  20. Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis

    PubMed Central

    Fernandez-Juarez, Gema; Villacorta, Javier; Ruiz-Roso, Gloria; Panizo, Nayara; Martinez-Marín, Isabel; Marco, Helena; Arrizabalaga, Pilar; Díaz, Montserrat; Perez-Gómez, Vanessa; Vaca, Marco; Rodríguez, Eva; Cobelo, Carmen; Fernandez, Loreto; Avila, Ana; Praga, Manuel; Quereda, Carlos; Ortiz, Alberto

    2016-01-01

    Background Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. Methods Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. Results We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95

  1. Ecological applications for flood hazard minimization in the Siwaliks region of Nepal

    NASA Astrophysics Data System (ADS)

    Dhital, Y. P.; Tang, Q.

    2015-12-01

    Water-induced disaster problems including soil erosion, debris flow, landslides and flooding are common due to the unstable landscape of Siwaliks region of Nepal. Ecological applications especially focused on soil bioengineering techniques have been used in Nepal for nearly four decades to deal with erosion problems on slopes, in high way construction and riverbank stabilization. In this study, both vegetative check dams and wire net check dams along with vegetation were used for flood hazard minimization. After three growing seasons, the banks of the ephemeral stream were almost fully stabilized. Vegetation based solutions are found to be more effective than the mechanical methods of stream bank stabilization. Bamboo combinations for check dam construction and planting of bamboo behind check dam are both very useful for stream bank stabilization. Vegetation application on flood damaged bare ground was also found to be very successful. Furthermore, some plants species showed almost equal growth performances on both flood-affected and unaffected bare ground. However, more scientific implementation of ecological applications for flood hazard minimization in those affected areas is essential in future.

  2. Guidelines to come to minimized tensile strength loss upon cellulase application.

    PubMed

    Lenting, H B; Warmoeskerken, M M

    2001-08-23

    Application of cellulase technology in the textile production process often results in a certain loss of tensile strength along with the desired performance. In this paper guidelines are given how to come to minimization or even prevention of tensile strength loss. Part of the considerations is based on the hypothesis given in the accompanying paper (Lenting and Warmoeskerken, 2001, J. Biotechnol.) concerning the mechanism of interaction between cellulase action and applied shear force. Recommendations given concern the enzyme choice, process parameters and enzyme targeting. PMID:11500216

  3. Application of Sequential Quadratic Programming to Minimize Smart Active Flap Rotor Hub Loads

    NASA Technical Reports Server (NTRS)

    Kottapalli, Sesi; Leyland, Jane

    2014-01-01

    In an analytical study, SMART active flap rotor hub loads have been minimized using nonlinear programming constrained optimization methodology. The recently developed NLPQLP system (Schittkowski, 2010) that employs Sequential Quadratic Programming (SQP) as its core algorithm was embedded into a driver code (NLP10x10) specifically designed to minimize active flap rotor hub loads (Leyland, 2014). Three types of practical constraints on the flap deflections have been considered. To validate the current application, two other optimization methods have been used: i) the standard, linear unconstrained method, and ii) the nonlinear Generalized Reduced Gradient (GRG) method with constraints. The new software code NLP10x10 has been systematically checked out. It has been verified that NLP10x10 is functioning as desired. The following are briefly covered in this paper: relevant optimization theory; implementation of the capability of minimizing a metric of all, or a subset, of the hub loads as well as the capability of using all, or a subset, of the flap harmonics; and finally, solutions for the SMART rotor. The eventual goal is to implement NLP10x10 in a real-time wind tunnel environment.

  4. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    PubMed Central

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  5. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients.

    PubMed

    Paiva, Bruno; Cedena, Maria-Teresa; Puig, Noemi; Arana, Paula; Vidriales, Maria-Belen; Cordon, Lourdes; Flores-Montero, Juan; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Martinez-Lopez, Joaquin; Ocio, Enrique M; Hernandez, Miguel T; Teruel, Ana-Isabel; Rosiñol, Laura; Echeveste, María-Asunción; Martinez, Rafael; Gironella, Mercedes; Oriol, Albert; Cabrera, Carmen; Martin, Jesus; Bargay, Joan; Encinas, Cristina; Gonzalez, Yolanda; Van Dongen, Jacques J M; Orfao, Alberto; Bladé, Joan; Mateos, Maria-Victoria; Lahuerta, Juan José; San Miguel, Jesús F

    2016-06-23

    The value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10(-5); n = 54, 34%), MRD positive (between <10(-4) and ≥10(-5); n = 20, 12%), and MRD positive (≥10(-4); n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10(-4) and ≥10(-5) vs ≥10(-4) (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249

  6. Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready?

    PubMed

    Boyiadzis, Michael; Whiteside, Theresa L

    2016-06-01

    The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients' plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML. The rationale for developing exosome-based methodology for minimal residual disease detection is based on promising early observations. However, standards need to be established for evaluating exosome identity, isolation from body fluids, and assessment methods. The rapidly expanding knowledge of the exosome biology suggests that the exosome status as potential biomarkers may become clarified in the near future. PMID:27043038

  7. Prognostic Significance and Treatment Implications of Minimal Residual Disease Studies in Philadelphia-Negative Adult Acute Lymphoblastic Leukemia

    PubMed Central

    Spinelli, Orietta; Tosi, Manuela; Peruta, Barbara; Guinea Montalvo, Marie Lorena; Maino, Elena; Scattolin, Anna Maria; Parolini, Margherita; Viero, Piera; Rambaldi, Alessandro; Bassan, Renato

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is curable in about 40–50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. PMID:25237475

  8. Leukemia-associated marker combinations in acute leukemia suitable for detection of minimal residual disease.

    PubMed

    Babusíková, O; Mesárosová, A; Koníková, M; Kusenda, J; Glasová, M; Klobusická, M

    1993-01-01

    case (M3 according to FAB classification) an aberrant nuclear coexpression of TdT was observed. In one case of the last group an interesting antigen combination of CD4/CD34 present in AML with monocytic differentiation was observed. When 5 patients with leukemia-associated (aberrant) markers were again analyzed at relapse, the relevant antigen combinations were retained in all of them. In summary, 44 of 50 cases (88%) from our acute leukemia series studied for leukemia-associated antigen combination, both with surface membrane and cytoplasmic marker combinations and those with aberrant markers coexpression allow the detection of minimal residual disease. PMID:8272155

  9. Ice application to minimize pain in the split-thickness skin graft donor site.

    PubMed

    Akan, Mithat; Misirlioğlu, Aykut; Yildirim, Serkan; Cakir, Bariş; Taylan, Gaye; Aköz, Tayfun

    2003-01-01

    Reconstruction of tissue defects with skin grafts is one of the most used processes in soft tissue defects. While any part of the body can be used as a donor site of split-thickness skin grafts, the posterolateral thigh is the most used one. Pain in the graft donor site may be the primary concern of patients in the postoperative period. Various kinds of donor site dressings and procedures have been described for this purpose. The main goal of this practice is the fast recovery of the donor site. Nevertheless, avoiding infection, decreasing the pain in the donor site, and minimizing the cost should be considered. To minimize pain in the graft donor site, ice pack application, used for its local anesthetic effect, was utilized for patients postoperatively in our clinic. Thirty-six patients were included in this study between June 2001 and May 2002. Patients were divided into two groups, with 18 patients in-group I, to whom ice was applied, and 18 patients in group II, which was specified as the control group. The patients were evaluated according to the pain in the graft donor site. The visual analog scale (VAS) was used to evaluate the pain of the patients. The data were statistically evaluated with the Mann-Whitney U test procedure. In addition to this, infections, recovery periods, and cost benefit effects were also determined. The mean pain scores in the graft donor site were found to be quite low in patients in the group with ice application (p < 0.05). No significant difference was determined between the two groups when their pain scales were compared on the fourth and the fifth days (p > 0.05). Ice can be safely used in patients for whom donor site pain is the primary concern, with advantages such as ease of application, low cost (almost free), and a significant decrease in pain in the donor site. PMID:15058555

  10. Novel hydrogel application in minimally invasive surgical approaches to spontaneous intracranial hypotension. Report of 2 cases.

    PubMed

    Chai, Casey M; Banu, Matei A; Cobb, William; Mehta, Neel; Heier, Linda; Boockvar, John A

    2014-10-01

    The authors report 2 cases of orthostatic headaches associated with spontaneous intracranial hypotension (SIH) secondary to CSF leaks that were successfully treated with an alternative dural repair technique in which a tubular retractor system and a hydrogel dural sealant were used. The 2 patients, a 63-year-old man and a 45-year-old woman, presented with orthostatic headache associated with SIH secondary to suspected lumbar and lower cervical CSF leaks, respectively, as indicated by bony defects or epidural fluid collection. Epidural blood patch repair failed in both cases, but both were successfully treated with the minimally invasive application of a hydrogel dural sealant as a novel adjunct to traditional dural repair techniques. Both patients tolerated the procedure well. Moreover, SIH symptoms and MRI signs were completely resolved at 1-month follow-up in both patients. The minimally invasive dural repair procedure with hydrogel dural sealant described here offers a viable alternative in patients in whom epidural blood patches have failed, with obscure recalcitrant CSF leaks at the cervical as well as lumbar spinal level. The authors demonstrate that the adjuvant use of sealant is a safe and efficient repair method regardless of dural defect location. PMID:25084466

  11. Application of sonic-boom minimization concepts in supersonic transport design

    NASA Technical Reports Server (NTRS)

    Carlson, H. W.; Barger, R. L.; Mack, R. J.

    1973-01-01

    The applicability of sonic boom minimization concepts in the design of large supersonic transport airplanes capable of a 2500-nautical-mile range at a cruise Mach number of 2.7 is considered. Aerodynamics, weight and balance, and mission performance as well as sonic boom factors, have been taken into account. The results indicate that shock-strength nominal values of somewhat less than 48 newtons/sq m during cruise are within the realm of possibility. Because many of the design features are in direct contradiction to presently accepted design practices, further study of qualified airplane design teams is required to ascertain sonic boom shock strength levels actually attainable for practical supersonic transports.

  12. Minimizing the grid-resolution dependence of flow-routing algorithms for geomorphic applications

    NASA Astrophysics Data System (ADS)

    Pelletier, Jon D.

    2010-10-01

    The results of flow-routing methods currently used in the geomorphic literature depend on grid resolution. This poses a problem for landscape evolution models, which must be independent of grid resolution to the greatest extent possible. Here I illustrate a refinement of currently-used flow-routing algorithms that yields unit contributing areas (i.e. contributing areas per unit width of flow) with minimal grid-resolution effects. I illustrate the application of this method in idealized topography, in high-resolution Digital Elevation Models (DEMs) of real-world topography, and by integration into a landscape evolution model for ridge-and-valley topography. The landscape evolution model produces grid-resolution-independent results in a more straightforward way than previous models for this type of landscape.

  13. Minimizing crop damage through understanding relationships between pyrethrum phenology and ray blight disease severity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The most damaging foliar disease of pyrethrum in Australia is ray blight caused by Stagonosporopsis tanaceti. The probability of growers incurring economic losses caused by this disease has been substantially reduced by the implementation of a prophylactically-applied spring fungicide program. Th...

  14. Insights into Spared Memory Capacity in Amnestic MCI and Alzheimer's Disease via Minimal Interference

    ERIC Educational Resources Information Center

    Dewar, Michaela; Pesallaccia, Martina; Cowan, Nelson; Provinciali, Leandro; Della Sala, Sergio

    2012-01-01

    Impairment on standard tests of delayed recall is often already maximal in the aMCI stage of Alzheimer's Disease. Neuropathological work shows that the neural substrates of memory function continue to deteriorate throughout the progression of the disease, hinting that further changes in memory performance could be tracked by a more sensitive test…

  15. Applications of Metabolomics for Kidney Disease Research

    PubMed Central

    Wettersten, Hiromi I.; Weiss, Robert H.

    2013-01-01

    Metabolomics is one of the relative newcomers of the omics techniques and is likely the one most closely related to actual real-time disease pathophysiology. Hence, it has the power to yield not only specific biomarkers but also insight into the pathophysiology of disease. Despite this power, metabolomics as applied to kidney disease is still in its early adolescence and has not yet reached the mature stage of clinical application, i.e., specific biomarker and therapeutic target discovery. On the other hand, the insight gained from hints into what makes these diseases tick, as is evident from the metabolomics pathways which have been found to be altered in kidney cancer, are now beginning to bear fruit in leading to potential therapeutic targets. It is quite likely that, with greater numbers of clinical materials and with more investigators jumping into the field, metabolomics may well change the course of kidney disease research. PMID:23538740

  16. Using population viability criteria to assess strategies to minimize disease threats for an endangered carnivore.

    PubMed

    Doak, Daniel F; Bakker, Victoria J; Vickers, Winston

    2013-04-01

    Outbreaks of infectious disease represent serious threats to the viability of many vertebrate populations, but few studies have included quantitative evaluations of alternative approaches to the management of disease. The most prevalent management approach is monitoring for and rapid response to an epizootic. An alternative is vaccination of a subset of the free-living population (i.e., a "vaccinated core") such that some individuals are partially or fully immune in the event of an epizootic. We developed a simulation model describing epizootic dynamics, which we then embedded in a demographic simulation to assess these alternative approaches to managing rabies epizootics in the island fox (Urocyon littoralis), a species composed of only 6 small populations on the California Channel Islands. Although the monitor and respond approach was superior to the vaccinated-core approach for some transmission models and parameter values, this type of reactive management did not protect the population from rabies under many disease-transmission assumptions. In contrast, a logistically feasible program of prophylactic vaccination for part of the wild population yielded low extinction probabilities across all likely disease-transmission scenarios, even with recurrent disease introductions. Our use of a single metric of successful management-probability of extreme endangerment (i.e., quasi extinction)-to compare very different management approaches allowed an objective assessment of alternative strategies for controlling the threats posed by infectious disease outbreaks. PMID:23521669

  17. Global error minimization in image mosaicing using graph connectivity and its applications in microscopy

    PubMed Central

    Khurd, Parmeshwar; Grady, Leo; Oketokoun, Rafiou; Sundar, Hari; Gajera, Tejas; Gibbs-Strauss, Summer; Frangioni, John V.; Kamen, Ali

    2011-01-01

    Several applications such as multiprojector displays and microscopy require the mosaicing of images (tiles) acquired by a camera as it traverses an unknown trajectory in 3D space. A homography relates the image coordinates of a point in each tile to those of a reference tile provided the 3D scene is planar. Our approach in such applications is to first perform pairwise alignment of the tiles that have imaged common regions in order to recover a homography relating the tile pair. We then find the global set of homographies relating each individual tile to a reference tile such that the homographies relating all tile pairs are kept as consistent as possible. Using these global homographies, one can generate a mosaic of the entire scene. We derive a general analytical solution for the global homographies by representing the pair-wise homographies on a connectivity graph. Our solution can accommodate imprecise prior information regarding the global homographies whenever such information is available. We also derive equations for the special case of translation estimation of an X-Y microscopy stage used in histology imaging and present examples of stitched microscopy slices of specimens obtained after radical prostatectomy or prostate biopsy. In addition, we demonstrate the superiority of our approach over tree-structured approaches for global error minimization. PMID:22811964

  18. A 4-DOF haptic master using ER fluid for minimally invasive surgery system application

    NASA Astrophysics Data System (ADS)

    Oh, Jong-Seok; Han, Young-Min; Lee, Sang-Rock; Choi, Seung-Bok

    2013-04-01

    This paper presents a novel 4-degrees-of-freedom (4-DOF) haptic master using a electrorheological (ER) fluid which is applicable to minimally invasive surgery (MIS) systems. By adopting a controllable ER fluid, the master can easily generate 4-DOF repulsive forces with the advantages of a simple mechanism and continuous force control capability. The proposed master consists of two actuators: an ER spherical joint for 3-DOF rotational motion and an ER piston device for 1-DOF translational motion. The generated torque/force models are mathematically derived by analyzing the mechanism geometry and using the Bingham characteristics of an ER Fluid. The haptic master is optimally designed and manufactured based on the mathematical torque/force models. The repulsive torque/force responses are experimentally evaluated and expressed by the first-order and second-order dynamic equations for each motion. A sliding mode controller (SMC), which is known to be robust to uncertainties, is then designed and empirically implemented to achieve the desired torque/force trajectories. It is demonstrated by presenting torque/force tracking results of both rotational and translational motions that the proposed 4-DOF ER haptic master integrated with the SMC can provide an effective haptic control performance for MIS applications.

  19. Design and fabrication of an IPMC-embedded tube for minimally invasive surgery applications

    NASA Astrophysics Data System (ADS)

    Liu, Jiayu; Wang, Yanjie; Zhao, Dongxu; Zhang, Chi; Chen, Hualing; Li, Dichen

    2014-03-01

    Minimally Invasive Surgery (MIS) is receiving much attention for a number of reasons, including less trauma, faster recovery and enhanced precision. The traditional robotic actuators do not have the capabilities required to fulfill the demand for new applications in MIS. Ionic Polymer-Metal Composite (IPMC), one of the most promising smart materials, has extensive desirable characteristics such as low actuation voltage, large bending deformation and high functionality. Compared with traditional actuators, IPMCs can mimic biological muscle and are highly promising for actuation in robotic surgery. In this paper, a new approach which involves molding and integrating IPMC actuators into a soft silicone tube to create an active actuating tube capable of multi-degree-of-freedom motion is presented. First, according to the structure and performance requirements of the actuating tube, the biaxial bending IPMC actuators fabricated by using solution casting method have been implemented. The silicone was cured at a suitable temperature to form a flexible tube using molds fabricated by 3D Printing technology. Then an assembly based fabrication process was used to mold or integrate biaxial bending IPMC actuators into the soft silicone material to create an active control tube. The IPMC-embedded tube can generate multi-degree-of-freedom motions by controlling each IPMC actuator. Furthermore, the basic performance of the actuators was analyzed, including the displacement and the response speed. Experimental results indicate that IPMC-embedded tubes are promising for applications in MIS.

  20. Minimally Invasive Early Operative Treatment of Progressive Foot and Ankle Deformity Associated With Charcot-Marie-Tooth Disease.

    PubMed

    Boffeli, Troy J; Tabatt, Jessica A

    2015-01-01

    Charcot-Marie-Tooth disease is a neuromuscular disorder that commonly results in a predictable pattern of progressive bilateral lower extremity weakness, numbness, contracture, and deformity, including drop foot, loss of ankle eversion strength, dislocated hammertoes, and severe cavus foot deformity. Late stage reconstructive surgery will be often necessary if the deformity becomes unbraceable or when neuropathic ulcers have developed. Reconstructive surgery for Charcot-Marie-Tooth deformity is generally extensive and sometimes staged. Traditional reconstructive surgery involves a combination of procedures, including tendon lengthening or transfer, osteotomy, and arthrodesis. The described technique highlights our early surgical approach, which involves limited intervention before the deformity becomes rigid, severe, or disabling. We present 2 cases to contrast our early minimally invasive technique with traditional late stage reconstruction. Charcot-Marie-Tooth disease affects different muscles at various stages of disease progression. As 1 muscle becomes weak, the antagonist will overpower it and cause progressive deformity. The focus of the early minimally invasive approach is to decrease the forces that cause progressive deformity yet maintain function, where possible. Our goal has been to maintain a functional and braceable foot and ankle, with the hope of avoiding or limiting the extent of future major reconstructive surgery. The presented cases highlight the patient selection criteria, the ideal timing of early surgical intervention, the procedure selection criteria, and operative pearls. The early minimally invasive approach includes plantar fasciotomy, Achilles tendon lengthening, transfer of the peroneus longus to the fifth metatarsal, Hibbs and Jones tendon transfer, and hammertoe repair of digits 1 to 5. PMID:25131389

  1. MINIMIZING THE RISK OF PREGNANCY, SEXUALLY TRANSMITTED DISEASES, AND HIV AMONG INCARCERATED ADOLESCENT GIRLS

    PubMed Central

    ST LAWRENCE, JANET S.; SNODGRASS, C. EDWARD; ROBERTSON, ANGELA; BAIRD-THOMAS, CONNIE

    2010-01-01

    Delinquent girls are at elevated risk for unplanned pregnancy and sexually transmitted diseases when compared with non-delinquent peers. Participants—234 incarcerated female juveniles—completed demographic, individual, partner, peer, and family measures and were tested for sexually transmitted diseases. Disease rates were as follows: chlamydia (20%), gonorrhea (4%), and syphilis (1%). Stepwise multiple linear regression analysis assessed the relationship of the predictor variable sets with sexual risk. Demographic and individual variables had the strongest associations with risk. Peer, partner, or family variables did not account for significant additional variance. The results suggest that an intervention could be delivered during the window of opportunity during the girls’ incarceration, changing their knowledge, attitudes, and skills that are implicated in risky sexual behavior before they are released back into the community. PMID:20585415

  2. SU-E-J-167: Dosimetric Consequences From Minimal Displacements in APBI with SAVI Applicators

    SciTech Connect

    Chandrasekara, S; Dumitru, N; Hyvarinen, M; Pella, S

    2015-06-15

    Purpose: To determine the importance of providing proper solid immobilization in every fraction of treatment in APBI with brachytherapy. Methods: 125 patients treated with APBI brachytherapy with SAVI applicators at SFRO Boca Raton, from 2013–2015 were considered for this retrospective study. The CT scans of each patient, which were taken before each treatment, were imported in to the Oncentra treatment planning system. Then they were compared with the initial CT scan which was used for the initial plan. Deviation in displacements in reference to ribs and skin surface was measured and dosimetric evaluations respective to the initial image were performed. Results: Small deviations in displacements were observed from the SAVI applicator to the ribs and the skin surface. Dosimetric evaluations revealed, very small changes in the inter-fractionation position make significant differences in the maximum dose to critical organs. Additionally, the volume of the cavity also changed between fractions. As a Result, the maximum dose manifested variance between 10% and 32% in ribs and skin surface respectively. Conclusion: It appears that taking a CT scan before each treatment is necessary to minimize the risk of delivering undesired high doses to the critical organs. This study indicates, in 30% of the cases re-planning was necessary between treatments. We conclude that, treatment planning teams should evaluate the placement of the device by analyzing the CT images before each treatment and they must be prepared for re-planning if needed. This study also reveals the urgent need of improving the immobilization methods with APBI when treating with the SAVI applicator.

  3. Minimally invasive surgery using mini anterior incision for thyroid diseases: a prospective cohort study

    PubMed Central

    Sabuncuoglu, Mehmet Zafer; Sabuncuoglu, Aylin; Sozen, Isa; Benzin, Mehmet Fatih; Cakir, Tugrul; Cetin, Recep

    2014-01-01

    Aim: Minimally invasive surgical techniques have attracted interest in all surgical specialties since 1980. The thyroidectomy technique requires meticulous surgical dissection, absolute hemostasis, en bloc tumor resection and adequate visualization of the operative field, all of which can be accomplished with minimally invasive techniques. Methods: The study group comprised all patients undergoing MITS from its introduction in 2010 until July 2012. All data were prospectively recorded in the Elbistan Hospital and Suleyman Demirel University in Turkey. This study was designed to demonstrate our experience with mini-incision-technique in thyroidectomy. Results: Over the 2-year period, 37 patients underwent bilateral MITS procedures. The procedure made with a small (2.5 cm) anterior incision made above the isthmus. The final diagnoses were benign multinodular goitre (37%), follicular adenoma (28%) incidental carcinoma (11%), Hashimoto’s thyroiditis (15%), Hurtle cell adenoma (5%), subacute thyroiditis (3%), residual thyroid-non carcinoma (2%), simple cyst (1%), diffuse hyperplasia (1%) and other (1%). Of the carcinomas, 80% were papillary thyroid cancer, 13% were follicular, and the remaining 7% were Hurtle cell carcinomas. We dont need to extend our incision in any cases. Two patients had temporary recurrent laryngeal nevre paresis and one patient had temporary hypocalcemia. Conclusions: It is not easy to demonstrate the advantages of MIT over conventional and video-assisted surgery. The main complications, such as nerve injury, hypoparathyroidism, or hemorrhage, are the same as in other surgical approaches. MIT has demonstrated advantages over conventional open approaches for both hemi- and total thyroidectomy and the benefits do not depend on the open or video-assisted approach. The anterior mini-incision approach can be performed with an operative time and postoperative complication profile equivalent to conventional thyroidectomy while providing excellent

  4. Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in myeloma.

    PubMed

    Compagno, Mara; Mantoan, Barbara; Astolfi, Monica; Boccadoro, Mario; Ladetto, Marco

    2005-01-01

    The evaluation of minimal residual disease (MRD) is critical in the evaluation of treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative evaluation of MRD now has a 10-yr-long history, but it remains a relatively sophisticated procedure. More recently, real-time quantitative approaches have also been developed. These approaches allow a very effective monitoring of disease but introduce additional complexity and costs to the procedure. This chapter describes how we currently perform real-time polymerase chain reaction (PCR) in MM. Compared to the first description of the assay in June 2000, significant improvements have been made. Although real-time PCR is the main focus of the chapter, most of the information suitable for a proper setup of a qualitative approach is also provided. PMID:15968100

  5. Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia.

    PubMed

    Pettit, Kristen; Stock, Wendy; Walter, Roland B

    2016-07-01

    Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD-based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation. PMID:27269126

  6. Minimally Invasive Multilevel Percutaneous Pedicle Screw Fixation for Lumbar Spinal Diseases

    PubMed Central

    Son, Seong; Park, Chan Woo; Kim, Woo Kyung

    2012-01-01

    Objective There are rare reports on the result of multilevel (≥3 levels) percutaneous pedicle screw fixation (PPF). The purpose of this study was to report the clinical experiences for multilevel PPF of the lumbar spine. Methods A total of 17 patients of lumbar spinal disease (7 degenerative diseases, 6 infectious diseases, and 4 traumatic instabilities) underwent neural decompression and multilevel PPF. There were 8 men and 9 women with a mean age of 61.4 years (range, 25-84) and a mean follow-up period of 23.2 months (range, 13-48). The average PPF level was 3.7. A retrospective review of clinical, radiological, and surgical data was conducted. Results "Excellent" or "good" clinical results were obtained in 15 patients (88.2%) according to the Odom's criteria. The average improvement of visual analogue scale was 5.2 points (from 9.3 to 4.1), and the average improvement of Oswestry Disability Index was 36.2 (from 71.2 to 35.0) at the last visit (p<0.05). The fusion rate was 88.2%, but, screw loosening was occurred in 2 patients, and adjacent segmental degeneration was occurred in 2 patients. There was no statistical significance in the change of total lumbar lordotic angle. The average operation time was 5.9 hours, with an estimated blood loss of 550 ml and bed rest duration of 2.0 days. Conclusion Although the current study examined a small sample with relatively short term follow up periods, our study results demonstrate that multilevel PPF is feasible and safe for selective lumbar spinal diseases. PMID:25983845

  7. Minimal interference beam size/profile measurement techniques applicable to the Collider

    SciTech Connect

    Nexsen, W.; Dutt, S.; Kauffmann, S.; Lebedev, V.; Maschke, A.; Mokhov, N.; Richardson, R.; Tsyganov, E.; Zinchenko, A.

    1993-05-01

    The imaging of synchrotron radiation (SR) has been suggested as a technique for providing a continuous, non-interfering monitor of the beam profile in the Collider rings at the Superconducting Super Collider. A closer examination has raised questions concerning the applicability of SR imaging in this case because of the diffraction broadening of the image, the requirements for axial space and location in the lattice, and the complexity of the system. We have surveyed the known, alternative, minimal interference techniques for measuring beam size and have evaluated them for possible Collider usage. We conclude that of the approaches that appear feasible, all require at least some development for our usage and that the development of an electron beam probe offers the best promise. We recommend that flying wires be used for cross-checking and calibrating the electron beam probe diagnostic and for luminosity measurements when the highest accuracy is required, but flying wires should not be used as the primary diagnostic because of their limited lifetime.

  8. Investigation of subclinical atherosclerosis in psoriatic arthritis patients with minimal disease activity.

    PubMed

    Yilmazer, Baris; Sahin, Tayfun; Unlu, Berrin Öztaş; Kir, Hale Maral; Cefle, Ayse

    2015-08-01

    The aim of this study was to investigate the presence of subclinical atherosclerosis among psoriatic arthritis (PsA) patients without any cardiovascular disease (CVD) or traditional cardiovascular risk factors through measurement of endothelial function and carotid intima-media thickness (IMT) and correlated with disease-related risk factors. Twenty patients with PsA according to classification criteria for psoriatic arthritis and 20 age- and sex-matched controls were included. Patients with risk factors for cardiovascular disease were excluded. Carotid IMT was measured using two-dimensional carotid ultrasonography (USG). Endothelial function was determined by measuring flow-mediated endothelial-dependent vasodilatation (FMD %) and nitrate-induced dilatation (NID %) using brachial artery USG. Additionally, serum asymmetric dimethylarginine (ADMA) level was obtained using ELISA methodology. In this cross-sectional study, FMD % was significantly more decreased among PsA patients versus control group [mean 11 % (median (range) %10.5 (8-15 %)] and mean 13.2 % [median (range) 12, 8 % (8.1-17.6 %), respectively; p = 0.01]. There was no significant difference in NID %, ADMA level and mean IMT or maximum IMT results. FMD % did not show a significant correlation with clinical and laboratory data of PsA patients. This study showed that endothelial dysfunction may be present in PsA patients with no CVD and traditional cardiovascular risk factors. The study findings lend support to the previous reports that suggested a potential relationship between PsA and atherosclerotic disorders. PMID:25669439

  9. Comparison between qualitative and real-time polymerase chain reaction to evaluate minimal residual disease in children with acute lymphoblastic leukemia

    PubMed Central

    Paula, Francisco Danilo Ferreira; Elói-Santos, Silvana Maria; Xavier, Sandra Guerra; Ganazza, Mônica Aparecida; Jotta, Patricia Yoshioka; Yunes, José Andrés; Viana, Marcos Borato; Assumpção, Juliana Godoy

    2015-01-01

    Introduction Minimal residual disease is an important independent prognostic factor that can identify poor responders among patients with acute lymphoblastic leukemia. Objective The aim of this study was to analyze minimal residual disease using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements by conventional polymerase chain reaction followed by homo-heteroduplex analysis and to compare this with real-time polymerase chain reaction at the end of the induction period in children with acute lymphoblastic leukemia. Methods Seventy-four patients diagnosed with acute lymphoblastic leukemia were enrolled. Minimal residual disease was evaluated by qualitative polymerase chain reaction in 57 and by both tests in 44. The Kaplan–Meier and multivariate Cox methods and the log-rank test were used for statistical analysis. Results Nine patients (15.8%) were positive for minimal residual disease by qualitative polymerase chain reaction and 11 (25%) by real-time polymerase chain reaction considering a cut-off point of 1 × 10−3 for precursor B-cell acute lymphoblastic leukemia and 1 × 10−2 for T-cell acute lymphoblastic leukemia. Using the qualitative method, the 3.5-year leukemia-free survival was significantly higher in children negative for minimal residual disease compared to those with positive results (84.1% ± 5.6% versus 41.7% ± 17.3%, respectively; p-value = 0.004). There was no significant association between leukemia-free survival and minimal residual disease by real-time polymerase chain reaction. Minimal residual disease by qualitative polymerase chain reaction was the only variable significantly correlated to leukemia-free survival. Conclusion Given the difficulties in the implementation of minimal residual disease monitoring by real-time polymerase chain reaction in most treatment centers in Brazil, the qualitative polymerase chain reaction strategy may be a cost-effective alternative. PMID:26670399

  10. Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease

    PubMed Central

    Ravichandran, Rajeswari; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Mukherjee, Shayanti; Ramakrishna, Seeram

    2012-01-01

    Myocardial infarction (MI) is characterized by heart-wall thinning, myocyte slippage, and ventricular dilation. The injury to the heart-wall muscle after MI is permanent, as after an abundant cell loss the myocardial tissue lacks the intrinsic capability to regenerate. New therapeutics are required for functional improvement and regeneration of the infarcted myocardium, to overcome harmful diagnosis of patients with heart failure, and to overcome the shortage of heart donors. In the past few years, myocardial tissue engineering has emerged as a new and ambitious approach for treating MI. Several left ventricular assist devices and epicardial patches have been developed for MI. These devices and acellular/cellular cardiac patches are employed surgically and sutured to the epicardial surface of the heart, limiting the region of therapeutic benefit. An injectable system offers the potential benefit of minimally invasive release into the myocardium either to restore the injured extracellular matrix or to act as a scaffold for cell delivery. Furthermore, intramyocardial injection of biomaterials and cells has opened new opportunities to explore and also to augment the potentials of this technique to ease morbidity and mortality rates owing to heart failure. This review summarizes the growing body of literature in the field of myocardial tissue engineering, where biomaterial injection, with or without simultaneous cellular delivery, has been pursued to enhance functional and structural outcomes following MI. Additionally, this review also provides a complete outlook on the tissue-engineering therapies presently being used for myocardial regeneration, as well as some perceptivity into the possible issues that may hinder its progress in the future. PMID:23271906

  11. Partial Sum Minimization of Singular Values in Robust PCA: Algorithm and Applications.

    PubMed

    Oh, Tae-Hyun; Tai, Yu-Wing; Bazin, Jean-Charles; Kim, Hyeongwoo; Kweon, In So

    2016-04-01

    Robust Principal Component Analysis (RPCA) via rank minimization is a powerful tool for recovering underlying low-rank structure of clean data corrupted with sparse noise/outliers. In many low-level vision problems, not only it is known that the underlying structure of clean data is low-rank, but the exact rank of clean data is also known. Yet, when applying conventional rank minimization for those problems, the objective function is formulated in a way that does not fully utilize a priori target rank information about the problems. This observation motivates us to investigate whether there is a better alternative solution when using rank minimization. In this paper, instead of minimizing the nuclear norm, we propose to minimize the partial sum of singular values, which implicitly encourages the target rank constraint. Our experimental analyses show that, when the number of samples is deficient, our approach leads to a higher success rate than conventional rank minimization, while the solutions obtained by the two approaches are almost identical when the number of samples is more than sufficient. We apply our approach to various low-level vision problems, e.g., high dynamic range imaging, motion edge detection, photometric stereo, image alignment and recovery, and show that our results outperform those obtained by the conventional nuclear norm rank minimization method. PMID:26353362

  12. Minimization of Radiation Exposure due to Computed Tomography in Inflammatory Bowel Disease

    PubMed Central

    Mc Laughlin, Patrick D.; O'Connor, Owen J.; O'Neill, Siobhán B.; Shanahan, Fergus; Maher, Michael M.

    2012-01-01

    Patient awareness and concern regarding the potential health risks from ionizing radiation have peaked recently (Coakley et al., 2011) following widespread press and media coverage of the projected cancer risks from the increasing use of computed tomography (CT) (Berrington et al., 2007). The typical young and educated patient with inflammatory bowel disease (IBD) may in particular be conscious of his/her exposure to ionising radiation as a result of diagnostic imaging. Cumulative effective doses (CEDs) in patients with IBD have been reported as being high and are rising, primarily due to the more widespread and repeated use of CT (Desmond et al., 2008). Radiologists, technologists, and referring physicians have a responsibility to firstly counsel their patients accurately regarding the actual risks of ionizing radiation exposure; secondly to limit the use of those imaging modalities which involve ionising radiation to clinical situations where they are likely to change management; thirdly to ensure that a diagnostic quality imaging examination is acquired with lowest possible radiation exposure. In this paper, we synopsize available evidence related to radiation exposure and risk and we report advances in low-dose CT technology and examine the role for alternative imaging modalities such as ultrasonography or magnetic resonance imaging which avoid radiation exposure. PMID:22577571

  13. Learning impairment by minimal cortical injury in a mouse model of Alzheimer's disease.

    PubMed

    Zou, Jingyu; Wang, Min; Uchiumi, Osamu; Shui, Yuan; Ishigaki, Yasuhito; Liu, Xiaoyan; Tajima, Nobuyoshi; Akai, Takuya; Iizuka, Hideaki; Kato, Nobuo

    2016-04-15

    Brain injury accelerates amyloid-β (Aβ) deposits and exacerbates Alzheimer's disease (AD). Accumulation of intracellular soluble Aβ impairs cognition prior to emergence of Aβ plaques. However, it is not known whether brain injury affects learning impairment attributable to intracellular soluble Aβ. We made a small injury by injecting glutamate into the parietal cortex in 3xTg AD mice of 4-5 months old, at which age soluble Aβ is accumulated without Aβ deposits. The size of glutamate-induced lesion was significantly larger than that of saline-injected control lesion. We reduced the relative difficulty of Morris water maze (MWM) task by repeating it twice, so that saline-injected 3xTg mice could perform as well as wild-type control mice. Under this condition, glutamate-injected 3xTg mice exhibited learning deficits. DNA microarray analysis revealed that 3 genes are upregulated, with one gene downregulated, more than 2 folds in the hippocampus. These 4 genes do not appear to be involved directly in learning but may be a part of signal cascade triggered by glutamate-induced small injury. Hippocampal content of soluble Aβ1-42 was increased in the glutamate 3xTg group. Facilitation of large-conductance calcium-activated potassium (BK) channel accompanied learning recovery in the saline-control 3xTg group in agreement with our previous reports, in which learning deficits attributable to intracellular Aβ were alleviated by facilitating BK channels. However, BK channel remained suppressed in the glutamate 3xTg group. It is suggested that glutamate-induced injury worsens learning by enhancing the toxicity of soluble Aβ or increasing its content per se. PMID:26876740

  14. POLLUTION BALANCE METHOD AND THE DEMONSTRATION OF ITS APPLICATION TO MINIMIZING WASTE IN A BIOCHEMICAL PROCESS

    EPA Science Inventory

    In this study, we introduced several modifications to the WAR (waste reduction) algorithm developed earlier. hese modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. esign hierarchy was formulated to promote appropriat...

  15. POLLUTION BALANCE METHOD AND THE DEMONSTRATION OF ITS APPLICATION TO MINIMIZING WASTE IN A BIOCHEMICAL PROCESS

    EPA Science Inventory

    In this study, we introduced several modifications to the WAR (waste reduction) algorithm developed earlier. These modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. A design hierarchy was formulated to promote appro...

  16. A clofarabine-based bridging regimen in patients with relapsed ALL and persistent minimal residual disease (MRD).

    PubMed

    Gossai, N; Verneris, M R; Karras, N A; Gorman, M F; Patel, N J; Burke, M J

    2014-03-01

    In patients with relapsed ALL, minimal residual disease (MRD) identified prior to allogeneic hematopoietic cell transplantation (HCT) is a strong predictor of relapse. We report our experience using a combination of reduced-dosing clofarabine, CY and etoposide as a 'bridge' to HCT in eight patients with high risk or relapsed ALL and pre-HCT MRD. All patients had detectable MRD (>0.01%, flow cytometry) at the start of therapy with all eight achieving MRD reduction following one cycle. The regimen was well tolerated with seven grade 3/4 toxicities occurring among four of the eight patients. Five patients (62.5%) are alive, one died from relapse (12.5%) and two from transplant-related mortality (25%). The combination of reduced-dose clofarabine, CY and etoposide as bridging therapy appears to be well tolerated in patients with relapsed ALL and is effective in reducing pre-HCT MRD. PMID:24317126

  17. Comparative analysis between RQ-PCR and digital-droplet-PCR of immunoglobulin/T-cell receptor gene rearrangements to monitor minimal residual disease in acute lymphoblastic leukaemia.

    PubMed

    Della Starza, Irene; Nunes, Vittorio; Cavalli, Marzia; De Novi, Lucia Anna; Ilari, Caterina; Apicella, Valerio; Vitale, Antonella; Testi, Anna Maria; Del Giudice, Ilaria; Chiaretti, Sabina; Foà, Robin; Guarini, Anna

    2016-08-01

    Real-time quantitative polymerase chain reaction (RQ-PCR) is a standardized tool for minimal residual disease (MRD) monitoring in acute lymphoblastic leukaemia (ALL). The applicability of this technology is limited by the need of a standard curve based on diagnostic DNA. The digital droplet PCR (ddPCR) technology has been recently applied to various medical fields, but its use in MRD monitoring is under investigation. In this study, we analysed 50 ALL cases by both methods in two phases: in the first, we established analytical parameters to investigate the applicability of this new technique; in the second, we analysed MRD levels in 141 follow-up (FU) samples to investigate the possible use of ddPCR for MRD monitoring in ALL patients. We documented that ddPCR has sensitivity and accuracy at least comparable to those of RQ-PCR. Overall, the two methods gave concordant results in 124 of the 141 analysed MRD samples (88%, P = 0·94). Discordant results were found in 12% borderline cases. The results obtained prove that ddPCR is a reliable method for MRD monitoring in ALL, with the advantage of quantifying without the need of the calibration curves. Its application in a cohort of patients with a longer FU will conclusively define its clinical predictive value. PMID:27172403

  18. Stochastic quasi-Newton method: Application to minimal model for proteins

    NASA Astrophysics Data System (ADS)

    Chau, C. D.; Sevink, G. J. A.; Fraaije, J. G. E. M.

    2011-01-01

    Knowledge of protein folding pathways and inherent structures is of utmost importance for our understanding of biological function, including the rational design of drugs and future treatments against protein misfolds. Computational approaches have now reached the stage where they can assess folding properties and provide data that is complementary to or even inaccessible by experimental imaging techniques. Minimal models of proteins, which make possible the simulation of protein folding dynamics by (systematic) coarse graining, have provided understanding in terms of descriptors for folding, folding kinetics, and folded states. Here we focus on the efficiency of equilibration on the coarse-grained level. In particular, we applied a new regularized stochastic quasi-Newton (S-QN) method, developed for accelerated configurational space sampling while maintaining thermodynamic consistency, to analyze the folding pathway and inherent structures of a selected protein, where regularization was introduced to improve stability. The adaptive compound mobility matrix B in S-QN, determined by a factorized secant update, gives rise to an automated scaling of all modes in the protein, in particular an acceleration of protein domain dynamics or principal modes and a slowing down of fast modes or “soft” bond constraints, similar to lincs/shake algorithms, when compared to conventional Langevin dynamics. We used and analyzed a two-step strategy. Owing to the enhanced sampling properties of S-QN and increased barrier crossing at high temperatures (in reduced units), a hierarchy of inherent protein structures is first efficiently determined by applying S-QN for a single initial structure and T=1>Tθ, where Tθ is the collapse temperature. Second, S-QN simulations for several initial structures at very low temperature (T=0.01

  19. Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

    PubMed Central

    YAMAMOTO, NOBUYUKI; KOZAKI, AIKO; HARTOMO, TRI BUDI; YANAI, TOMOKO; HASEGAWA, DAIICHIRO; KAWASAKI, KEIICHIRO; KOSAKA, YOSHIYUKI; MATSUO, MASAFUMI; HIRASE, SATOSHI; MORI, TAKESHI; HAYAKAWA, AKIRA; IIJIMA, KAZUMOTO; NISHIO, HISAHIDE; NISHIMURA, NORIYUKI

    2015-01-01

    Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients. PMID:26722317

  20. Expression of Wilms tumor gene in high risk neuroblastoma: complementary marker to tyrosine hydroxylase for detection of minimal residual disease

    PubMed Central

    Chou, Pauline M.; Olszewski, Marie; Rademaker, Alfred W.; Khan, Sana

    2015-01-01

    Background Neuroblastoma (NB) is an enigmatic tumor that often presents with metastatic disease at diagnosis and it is this aggressive propensity which places it among the deadliest pediatric tumors despite intensive multimodal therapy including hematopoietic stem cell transplantation (HSCT). We have previously demonstrated that Wilms tumor 1 gene (WT1) is a surrogate marker of proliferation in leukemia. To determine the potential association between WT1 and a known marker of NB, tyrosine hydroxylase (TH) in this high risk group of patients. Methods A total of 141 random samples from 34 patients were obtained, at diagnosis (n=27), during therapy (n=95), in clinical remission (n=13), and at the time of relapse (n=6). Quantitative RT-PCR was used for the evaluation of the level of gene expression using specific primers. Results Although similar gene expressions were demonstrated in both controls when evaluating both genes, significant difference was found at each clinical time point. Furthermore, when comparing patient samples from diagnosis to clinical remission and diagnosis to clinical relapse, individual gene expression varied. WT1 demonstrated significance (P=0.0002) and insignificance (P=0.06) whereas TH remained non-significant (P=0.2, P=0.09) respectively. Conclusions WT1 gene is indicative of cellular proliferation in NB and for this reason it can be adjuvant to TH for the detection minimal residual disease (MRD). PMID:26835379

  1. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

    PubMed

    Tie, Jeanne; Wang, Yuxuan; Tomasetti, Cristian; Li, Lu; Springer, Simeon; Kinde, Isaac; Silliman, Natalie; Tacey, Mark; Wong, Hui-Li; Christie, Michael; Kosmider, Suzanne; Skinner, Iain; Wong, Rachel; Steel, Malcolm; Tran, Ben; Desai, Jayesh; Jones, Ian; Haydon, Andrew; Hayes, Theresa; Price, Tim J; Strausberg, Robert L; Diaz, Luis A; Papadopoulos, Nickolas; Kinzler, Kenneth W; Vogelstein, Bert; Gibbs, Peter

    2016-07-01

    Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence. PMID:27384348

  2. Next-generation sequencing of FLT3 internal tandem duplications for minimal residual disease monitoring in acute myeloid leukemia

    PubMed Central

    Hélevaut, Nathalie; Rodriguez, Céline; Quief, Sabine; Sebda, Shéhérazade; Renneville, Aline; Nibourel, Olivier; Rousselot, Philippe; Gruson, Bérengère; Dombret, Hervé; Castaigne, Sylvie; Preudhomme, Claude

    2015-01-01

    Minimal Residual Disease (MRD) detection can be used for early intervention in relapse, risk stratification, and treatment guidance. FLT3 ITD is the most common mutation found in AML patients with normal karyotype. We evaluated the feasibility of NGS with high coverage (up to 2.4.106 PE fragments) for MRD monitoring on FLT3 ITD. We sequenced 37 adult patients at diagnosis and various times of their disease (64 samples) and compared the results with FLT3 ITD ratios measured by fragment analysis. We found that NGS could detect variable insertion sites and lengths in a single test for several patients. We also showed mutational shifts between diagnosis and relapse, with the outgrowth of a clone at relapse different from that dominant at diagnosis. Since NGS is scalable, we were able to adapt sensitivity by increasing the number of reads obtained for follow-up samples, compared to diagnosis samples. This technique could be applied to detect biological relapse before its clinical consequences and to better tailor treatments through the use of FLT3 inhibitors. Larger cohorts should be assessed in order to validate this approach. PMID:26078355

  3. Minimal residual disease negativity in elderly patients with acute myeloid leukemia may indicate different postremission strategies than in younger patients.

    PubMed

    Buccisano, F; Maurillo, L; Piciocchi, A; Del Principe, M I; Sarlo, C; Cefalo, M; Ditto, C; Di Veroli, A; De Santis, G; Irno Consalvo, M; Fraboni, D; Panetta, P; Palomba, P; Attrotto, C; Del Poeta, G; Sconocchia, G; Lo-Coco, F; Amadori, S; Venditti, A

    2015-08-01

    In the present analysis, we evaluated whether in elderly acute myeloid leukemia (AML) patients (>60 years), minimal residual disease (MRD) assessed by flow cytometry may have a role in guiding choice of postremission strategies. We analyzed 149 young and 61 elderly adults who achieved morphological CR after induction course of EORTC/GIMEMA protocols. Elderly patients reached a postconsolidation MRD negative status less frequently than younger ones (11 vs 28 %, p = 0.009). MRD negativity resulted in a longer 5-year disease-free survival (DFS) both in elderly (57 vs 13 %, p = 0.0197) and in younger patients (56 vs 31 %, p = 0.0017). Accordingly, 5-year cumulative incidence of relapse (CIR) of both elderly (83 vs 42 %, p = 0.045) and younger patients (59 vs 24 % p = NS) who were MRD positive doubled that of MRD negative ones. Nevertheless, CIR of MRD negative elderly patients was twofold higher than that of younger MRD negative ones (42 vs 24 %, p = NS). In conclusion, elderly patients in whom chemotherapy yields a MRD negative CR have duration of DFS and rate of CIR significantly better than those who remain MRD positive. Nonetheless, the high CIR rate observed in the elderly suggests that MRD negativity might have different therapeutic implications in this population than in the younger counterpart. PMID:25869029

  4. Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

    PubMed Central

    Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

    2016-01-01

    Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

  5. High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment.

    PubMed

    Logan, Aaron C; Gao, Hong; Wang, Chunlin; Sahaf, Bita; Jones, Carol D; Marshall, Eleanor L; Buño, Ismael; Armstrong, Randall; Fire, Andrew Z; Weinberg, Kenneth I; Mindrinos, Michael; Zehnder, James L; Boyd, Scott D; Xiao, Wenzhong; Davis, Ronald W; Miklos, David B

    2011-12-27

    The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing (HTS) for disease-specific IGH sequence quantification. To achieve accurate MRD quantification, we developed a systematic bioinformatic methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during IGH-HTS. We then compared the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide PCR for MRD quantification in 28 samples collected from 6 CLL patients following allogeneic HCT. Using amplimer libraries generated with consensus primers from patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454 pyrosequencing to be 10(-5), with a high correlation between quantification by allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire reconstitution after HCT-information not provided by the other MRD methods. IGH-HTS using consensus primers will broaden the availability of MRD quantification in CLL and other B cell malignancies, and this approach has potential for quantitative evaluation of immune diversification following transplant and nontransplant therapies. PMID:22160699

  6. Metabolic syndrome and its relationship with the achievement of minimal disease activity state in psoriatic arthritis patients: an observational study.

    PubMed

    Costa, Luisa; Caso, Francesco; Ramonda, Roberta; Del Puente, Antonio; Cantarini, Luca; Darda, Md Abud; Caso, Paolo; Lorenzin, Mariagrazia; Fiocco, Ugo; Punzi, Leonardo; Scarpa, Raffaele

    2015-02-01

    The aim of the study was to evaluate the influence of metabolic syndrome (MetS) on achieving minimal disease activity (MDA) in psoriatic arthritis (PsA) patients treated with anti-tumor necrosis factor (TNF)-α with a follow-up period of 24 months. A cohort of PsA patients was assessed at the University Federico II of Naples and at University of Padova. For the aim of the present study, patients' data were collected at baseline (T0), at 12 months (T1) and at 24 months (T2). Assessment of metabolic and disease activity parameters was performed at each visit. The NCEP-ACT III criteria were used to identify subjects with MetS and the MDA criteria to evaluate the disease activity. On the basis of the exclusion and inclusion criteria, 330 subjects were included in the study; 134 patients (40.7%) were classified as not having MetS and 196 (59.3%) as having MetS. An inverse association was found between presence of metabolic syndrome and the probability of achieving MDA. Univariate analysis indicated that patients with metabolic syndrome were less likely to achieve MDA than patients without metabolic syndrome (OR 0.45, p < 0.001). This inverse association remained statistically significant in the multivariate regression model (OR 0.56, p < 0.001). Metabolic syndrome is associated with a lower probability of achieving MDA in PsA patients in therapy with anti-TNF-α. PMID:25395342

  7. High-throughput VDJ sequencing for quantification of minimal residual disease in chronic lymphocytic leukemia and immune reconstitution assessment

    PubMed Central

    Logan, Aaron C.; Gao, Hong; Wang, Chunlin; Sahaf, Bita; Jones, Carol D.; Marshall, Eleanor L.; Buño, Ismael; Armstrong, Randall; Fire, Andrew Z.; Weinberg, Kenneth I.; Mindrinos, Michael; Zehnder, James L.; Boyd, Scott D.; Xiao, Wenzhong; Davis, Ronald W.; Miklos, David B.

    2011-01-01

    The primary cause of poor outcome following allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) is disease recurrence. Detection of increasing minimal residual disease (MRD) following HCT may permit early intervention to prevent clinical relapse; however, MRD quantification remains an uncommon diagnostic test because of logistical and financial barriers to widespread use. Here we describe a method for quantifying CLL MRD using widely available consensus primers for amplification of all Ig heavy chain (IGH) genes in a mixture of peripheral blood mononuclear cells, followed by high-throughput sequencing (HTS) for disease-specific IGH sequence quantification. To achieve accurate MRD quantification, we developed a systematic bioinformatic methodology to aggregate cancer clone sequence variants arising from systematic and random artifacts occurring during IGH-HTS. We then compared the sensitivity of IGH-HTS, flow cytometry, and allele-specific oligonucleotide PCR for MRD quantification in 28 samples collected from 6 CLL patients following allogeneic HCT. Using amplimer libraries generated with consensus primers from patient blood samples, we demonstrate the sensitivity of IGH-HTS with 454 pyrosequencing to be 10−5, with a high correlation between quantification by allele-specific oligonucleotide PCR and IGH-HTS (r = 0.85). From the same dataset used to quantify MRD, IGH-HTS also allowed us to profile IGH repertoire reconstitution after HCT—information not provided by the other MRD methods. IGH-HTS using consensus primers will broaden the availability of MRD quantification in CLL and other B cell malignancies, and this approach has potential for quantitative evaluation of immune diversification following transplant and nontransplant therapies. PMID:22160699

  8. Comparison of Glomerular Transcriptome Profiles of Adult-Onset Steroid Sensitive Focal Segmental Glomerulosclerosis and Minimal Change Disease

    PubMed Central

    Ren, Hong; Liu, Jian; Zhang, Weijia; Wei, Chengguo; Xu, Jing; Zhang, Wen; Li, Xiao; Wang, Weiming; Lv, Danfeng; He, John Cijiang; Chen, Nan

    2015-01-01

    Objective To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Methods We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis. Results Analysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys. Conclusions This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases. PMID:26536600

  9. Application of the Flexible CO2 Laser in Minimally Invasive Laminectomies: Technical Note.

    PubMed

    Hussain, Namath S; Perez-Cruet, Mick

    2016-01-01

    Background Minimally invasive laminectomy is a very effective surgical method for treating lumbar stenosis. However, this technique can be technically difficult, especially in patients suffering from severe stenosis. The contralateral decompression from a unilateral approach can result in durotomy during removal of the hypertrophied ligamentum flavum. This complication can be difficult to treat through a small working channel. Objective To detail our group's operative experience with the CO2 laser and discuss our results and previous studies in the literature reporting results.  Methods The CO2 laser (Omniguide, Boston, MA) was investigated in the surgical ablation of the contralateral ligamentum flavum during minimally invasive laminectomies. Forty levels have been investigated thus far. The amount of voltage needed to adequately desiccate and remove the ligamentum flavum safely as well as the effectiveness of this technique were investigated. Results The contralateral ligamentum flavum could be removed effectively using the 9 to 11 watt continuous wavelength (10,600 nanometer) power setting on the CO2 laser. Shrinkage of the contralateral ligamentum flavum facilitated its removal using a number 2 Kerrison Punch. No durotomies occurred, and the use of the laser did not significantly lengthen operative times.  Conclusions The CO2 laser appears to be a useful tool in the armamentarium of instruments available to the minimally invasive spine surgeon and may help to reduce the incidence of durotomies when performing minimally invasive laminectomies. PMID:27433407

  10. Advancing the field of pharmaceutical risk minimization through application of implementation science best practices.

    PubMed

    Smith, Meredith Y; Morrato, Elaine

    2014-08-01

    Regulators are increasingly mandating the use of pharmaceutical risk-minimization programs for a variety of medicinal products. To date, however, evaluations of these programs have shown mixed results and relatively little attention has been directed at diagnosing the specific factors contributing to program success or lack thereof. Given the growing use of these programs in many different patient populations, it is imperative to understand how best to design, deliver, disseminate, and assess them. In this paper, we argue that current approaches to designing, implementing, and evaluating risk-minimization programs could be improved by applying evidence- and theory-based 'best practices' from implementation science. We highlight commonly encountered challenges and gaps in the design, implementation, and evaluation of pharmaceutical risk-minimization initiatives and propose three key recommendations to address these issues: (1) risk-minimization program design should utilize models and frameworks that guide what should be done to produce successful outcomes and what questions should be addressed to evaluate program success; (2) intervention activities and tools should be theoretically grounded and evidence based; and (3) evaluation plans should incorporate a mixed-methods approach, pragmatic trial designs, and a range of outcomes. Regulators, practitioners, policy makers, and researchers are encouraged to apply these best practices in order to improve the public health impact of this important regulatory tool. PMID:25005707

  11. Application of the Flexible CO2 Laser in Minimally Invasive Laminectomies: Technical Note

    PubMed Central

    Perez-Cruet, Mick

    2016-01-01

    Background Minimally invasive laminectomy is a very effective surgical method for treating lumbar stenosis. However, this technique can be technically difficult, especially in patients suffering from severe stenosis. The contralateral decompression from a unilateral approach can result in durotomy during removal of the hypertrophied ligamentum flavum. This complication can be difficult to treat through a small working channel. Objective To detail our group’s operative experience with the CO2 laser and discuss our results and previous studies in the literature reporting results.  Methods The CO2 laser (Omniguide, Boston, MA) was investigated in the surgical ablation of the contralateral ligamentum flavum during minimally invasive laminectomies. Forty levels have been investigated thus far. The amount of voltage needed to adequately desiccate and remove the ligamentum flavum safely as well as the effectiveness of this technique were investigated. Results The contralateral ligamentum flavum could be removed effectively using the 9 to 11 watt continuous wavelength (10,600 nanometer) power setting on the CO2 laser. Shrinkage of the contralateral ligamentum flavum facilitated its removal using a number 2 Kerrison Punch. No durotomies occurred, and the use of the laser did not significantly lengthen operative times.  Conclusions The CO2 laser appears to be a useful tool in the armamentarium of instruments available to the minimally invasive spine surgeon and may help to reduce the incidence of durotomies when performing minimally invasive laminectomies. PMID:27433407

  12. Pollution balance method and the demonstration of its application to minimizing waste in a biochemical process

    SciTech Connect

    Hilaly, A.K.; Sikdar, S.K.

    1995-06-01

    In this study, the authors introduced several modifications to the WAR (waste reduction) algorithm developed earlier. These modifications were made for systematically handling sensitivity analysis and various tasks of waste minimization. A design hierarchy was formulated to promote appropriate waste reduction tasks at designated levels of the hierarchy. A sensitivity coefficient was used to measure the relative impacts of process variables on the pollution index of a process. The use of the WAR algorithm was demonstrated by a fermentation process for making penicillin.

  13. Minimal residual disease assessed by multi-parameter flow cytometry is highly prognostic in adult patients with acute lymphoblastic leukaemia.

    PubMed

    Ravandi, Farhad; Jorgensen, Jeffrey L; O'Brien, Susan M; Jabbour, Elias; Thomas, Deborah A; Borthakur, Gautam; Garris, Rebecca; Huang, Xuelin; Garcia-Manero, Guillermo; Burger, Jan A; Ferrajoli, Alessandra; Wierda, William; Kadia, Tapan; Jain, Nitin; Wang, Sa A; Konoplev, Sergei; Kebriaei, Partow; Champlin, Richard E; McCue, Deborah; Estrov, Zeev; Cortes, Jorge E; Kantarjian, Hagop M

    2016-02-01

    The prognostic value of minimal residual disease (MRD) assessed by multi-parameter flow cytometry (MFC) was investigated among 340 adult patients with B-cell acute lymphoblastic leukaemia (B-ALL) treated between 2004 and 2014 using regimens including the hyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine) backbone. Among them, 323 (95%) achieved complete remission (CR) and were included in this study. Median age was 52 years (range, 15-84). Median white blood cell count (WBC) was 9·35 × 10(9) /l (range, 0·4-658·1 ×1 0(9) /l). MRD by MFC was initially assessed with a sensitivity of 0·01%, using a 15-marker, 4-colour panel and subsequently a 6-colour panel on bone marrow specimens obtained at CR achievement and at approximately 3 month intervals thereafter. MRD negative status at CR was associated with improved disease-free survival (DFS) and overall survival (OS) (P = 0·004 and P = 0·03, respectively). Similarly, achieving MRD negative status at approximately 3 and 6 months was associated with improved DFS (P = 0·004 and P < 0·0001, respectively) and OS (P = 0·004 and P < 0·0001, respectively). Multivariate analysis including age, WBC at presentation, cytogenetics (standard versus high risk) and MRD status at CR, 3 and 6 months, indicated that MRD negative status at CR was an independent predictor of DFS (P < 0·05). Achievement of an MRD negative state assessed by MFC is an important predictor of DFS and OS in adult patients with ALL. PMID:26492205

  14. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    PubMed

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p=0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p=0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. PMID:26598032

  15. Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis

    PubMed Central

    Garin, Eduardo H.; Reiser, Jochen; Cara-Fuentes, Gabriel; Wei, Changli; Matar, Dany; Wang, Heiman; Alachkar, Nada; Johnson, Richard J.

    2014-01-01

    Background Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. Methods One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 were measured by ELISA. Glomeruli were stained for CD80. Results After abatacept, urinary CD80 became undetectable with concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in one patient with primary FSGS and in two recurrent FSGS subjects despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. One patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before abatacept. After Abatacept, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. Conclusion These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since urinary CD80 is only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria. PMID:25239302

  16. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission.

    PubMed

    Cowan, Andrew J; Stevenson, Philip A; Cassaday, Ryan D; Graf, Solomon A; Fromm, Jonathan R; Wu, David; Holmberg, Leona A; Till, Brian G; Chauncey, Thomas R; Smith, Stephen D; Philip, Mary; Orozco, Johnnie J; Shustov, Andrei R; Green, Damian J; Libby, Edward N; Bensinger, William I; Shadman, Mazyar; Maloney, David G; Press, Oliver W; Gopal, Ajay K

    2016-02-01

    Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission after induction chemotherapy, with the best results for patients in complete remission (CR). We hypothesized that evaluation of minimal residual disease (MRD) before ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011 with pretransplantation MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11; 14) by PCR or positive flow cytometry from blood or bone marrow, was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached, with 82% survival at 5 years, whereas for the MRD-positive patients, median OS was 3.01 years (hazard ratio [HR], 4.04; P = .009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75% PFS at 5 years, whereas for MRD-positive patients, it was 2.38 years (HR, 3.69; P = .002). MRD positivity is independently associated with poor outcomes after ASCT for MCL patients in CR. PMID:26348890

  17. Minimal Change Disease as a Secondary and Reversible Event of a Renal Transplant Case with Systemic Lupus Erythematosus

    PubMed Central

    Gkrouzman, Elena; Kirou, Kyriakos A.; Seshan, Surya V.; Chevalier, James M.

    2015-01-01

    Secondary causes of minimal change disease (MCD) account for a minority of cases compared to its primary or idiopathic form and provide ground for consideration of common mechanisms of pathogenesis. In this paper we report a case of a 27-year-old Latina woman, a renal transplant recipient with systemic lupus erythematosus (SLE), who developed nephrotic range proteinuria 6 months after transplantation. The patient had recurrent acute renal failure and multiple biopsies were consistent with MCD. However, she lacked any other features of the typical nephrotic syndrome. An angiogram revealed a right external iliac vein stenosis in the region of renal vein anastomosis, which when restored resulted in normalization of creatinine and relief from proteinuria. We report a rare case of MCD developing secondary to iliac vein stenosis in a renal transplant recipient with SLE. Additionally we suggest that, in the event of biopsy-proven MCD presenting as an atypical nephrotic syndrome, alternative or secondary, potentially reversible, causes should be considered and explored. PMID:26351598

  18. Current applications of lasers in heart disease

    NASA Astrophysics Data System (ADS)

    Lee, Garrett; Chan, Ming C.; Mason, Dean T.

    1993-03-01

    Although the laser has been in existence for abut 30 years, its application in heart disease has only been examined in the past decade. Much attention has been given its exciting potential in treating coronary artery disease. Transmitted through a catheter comprised of one or more thin optical fibers which can be threaded nonsurgically into the coronary artery, the laser can ablate atherosclerotic plaque that obstructs the artery and diminishes blood flow to the myocardium. In clinical studies, the laser can treat some obstructive lesions that are not suitable for balloon angioplasty (i.e., long and diffuse lesions, very tight stenoses, ostial lesions, calcified lesions). In patients who failed balloon angioplasty due to severe dissection or abrupt closure, the laser may seal up the dissections and restore antegrade blood flow. In addition, the laser may have other applications and treatment modalities that are still under investigation. It may ablate ectopic ventricular foci, or terminate supraventricular tachyrhythmia by destroying the heart's abnormal conduction pathways. It can cut the hypertrophied septum that is associated with left ventricular outflow tract obstruction, or create a channel in the atrial septum as a palliative procedure in newborns with transposition of the great vessels. It may provide a wider orifice for blood flow within the heart in infants with pulmonary outflow obstruction and in adults with aortic valvular stenosis. It is also capable of fusing small thin-walled blood vessels together. Further, a more intriguing possibility is its use to bore several tiny channels in the myocardium to allow oxygenated blood from within the ventricular chamber to perfuse the ischemic heart tissue.

  19. Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases.

    PubMed

    Good, R A

    2000-07-01

    With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and

  20. [Operation of cross-section and extravasal correction of the femoral vein valves in varicose disease using minimal access].

    PubMed

    Tsukanov, Iu T; Tsukanov, A Iu

    2002-02-01

    Taking into account the heightened demands of patients for the quality of life the aesthetics of upper incisions in varicose disease gains significance. The authors adduce the depiction of the procedure and results of application of two original operations: cross-sectomy with application of public approach and extravasal correction of femoral vein valves using proper fascial tunics by inguinal mini-access. Endosurgical manipulations are performed inside operative space, created by hook-elevator with endoillumination, permitting to reduce cutaneous incision and remove it to aesthetically less significant zones. The 2 cm long incision in the hair-bearing part of public region in inside and horizontal direction was applied in cross-sectomy. The transverse cutaneous incision 2-2.5 cm long 6-7 cm down inguinal ligamentum and medially about femoral vessels projection was proposed for valvuloplasty. Cross-sectomy using mini-access was done in 49 patients, valvuloplasty of femoral vein--in 41. Estimation of immediate and late follow-up results witnesses, that elaborated endosurgical procedures of cross-sectomy and valvuloplasty of femoral vein in patients with varicose disease using mini-access corresponds to aesthetical demands of modern phlebology. PMID:12024722

  1. Davidon-Broyden rank-one minimization methods in Hilbert space with application to optimal control problems

    NASA Technical Reports Server (NTRS)

    Straeter, T. A.

    1972-01-01

    The Davidon-Broyden class of rank one, quasi-Newton minimization methods is extended from Euclidean spaces to infinite-dimensional, real Hilbert spaces. For several techniques of choosing the step size, conditions are found which assure convergence of the associated iterates to the location of the minimum of a positive definite quadratic functional. For those techniques, convergence is achieved without the problem of the computation of a one-dimensional minimum at each iteration. The application of this class of minimization methods for the direct computation of the solution of an optimal control problem is outlined. The performance of various members of the class are compared by solving a sample optimal control problem. Finally, the sample problem is solved by other known gradient methods, and the results are compared with those obtained with the rank one quasi-Newton methods.

  2. How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

    PubMed Central

    Béné, Marie C.; Kaeda, Jaspal S.

    2009-01-01

    Resistance to therapeutic agents is a major factor in the failure of cancer treatments. In leukemia, the resistant cells remaining in the bone marrow and/or peripheral blood constitute minimal residual disease and are detectable by highly sensitive assays when the patient appears to be in complete remission. Early detection of the expansion of residual cells permits clinical intervention with the aim of reversing the proliferation of resistant leukemic cells. Therefore, accurate and precise measurement of minimal residual disease can greatly enhance optimization of oncology patients' clinical management. This notion is supported by a large body of data among chronic myeloid leukemia patients, but minimal residual disease detection and monitoring is increasingly applied to other types of leukemia, and is starting to be a factor in decision-making for some therapeutic trials in childhood acute lymphoblastic leukemia. Here, from the solid ground of minimal residual disease detection in chronic myeloid leukemia, the current state of the art and development of molecular techniques in other leukemias and the growing field of multiparameter flow cytometry are reviewed in two separate parts reporting on the respective advances, advantages and pitfalls of these emerging methods. PMID:19586938

  3. Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis

    PubMed Central

    Volejnikova, Jana; Mejstrikova, Ester; Valova, Tatana; Reznickova, Leona; Hodonska, Ladislava; Mihal, Vladimir; Sterba, Jaroslav; Jabali, Yahia; Prochazkova, Daniela; Blazek, Bohumir; Hak, Jiri; Cerna, Zdenka; Hrusak, Ondrej; Stary, Jan; Trka, Jan; Fronkova, Eva

    2011-01-01

    Background Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. Design and Methods In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. Results We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04–8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10−4 was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69±7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥10−2, intermediate-risk: <10−2 and ≥10−4, standard-risk: <10−4) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. Conclusions Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic

  4. Improved minimal residual disease detection by targeted quantitative polymerase chain reaction in Nucleophosmin 1 type a mutated acute myeloid leukemia.

    PubMed

    Pettersson, Louise; Levéen, Per; Axler, Olof; Dvorakova, Dana; Juliusson, Gunnar; Ehinger, Mats

    2016-10-01

    Multicolor flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are important independent techniques to determine minimal residual disease (MRD) in acute myeloid leukemia (AML). MFC is the standard method, but may be unreliable. Therefore, MFC-based determination of MRD with an RQ-PCR-based approach targeting the nucleophosmin 1 (NPM1) type A mutation was set out to compare. Since most current NPM1 RQ-PCR MRD protocols suffer from clear definitions of quantifiability, we sought to define quantifiability in a reproducible and standardized manner. The limit of quantifiability of our RQ-PCR protocol for the NPM1 type A mutation varied between 0.002% and 0.04% residual leukemic cells depending on the features of the standard curve for each PCR experiment. The limit of detection was close to 0.001% leukemic cells. The limit of detection by MFC ranged from 0.01% to 1% depending on the phenotype of the leukemic cells as compared with non-leukemic bone marrow cells. Forty-five MRD samples from 15 patients using both NPM1 mutation specific RQ-PCR and MFC were analyzed. In 32 of the 45 samples (71%), an MRD-signal could be detected with RQ-PCR. A quantifiable NPM1 mutation signal was found in 15 samples (33%) (range 0.003%-2.6% leukemic cells). By contrast, only two follow-up samples (4%) showed residual leukemic cells (0.04% and 0.3%, respectively) by MFC. Thus, RQ-PCR of the NPM1 type A mutation was more sensitive and reliable than MFC for determination of MRD, which might have clinical implications. © 2016 Wiley Periodicals, Inc. PMID:27191933

  5. Application of edible coating with starch and carvacrol in minimally processed pumpkin.

    PubMed

    Santos, Adriele R; da Silva, Alex F; Amaral, Viviane C S; Ribeiro, Alessandra B; de Abreu Filho, Benicio A; Mikcha, Jane M G

    2016-04-01

    The present study evaluated the effect of an edible coating of cassava starch and carvacrol in minimally processed pumpkin (MPP). The minimal inhibitory concentration (MIC) of carvacrol against Escherichia coli, Salmonella enterica serotype Typhimurium, Aeromonas hydrophila, and Staphylococcus aureus was determined. The edible coating that contained carvacrol at the MIC and 2 × MIC was applied to MPP, and effects were evaluated with regard to the survival of experimentally inoculated bacteria and autochthonous microflora in MPP. Total titratable acidity, pH, weight loss, and soluble solids over 7 days of storage under refrigeration was also analyzed. MIC of carvacrol was 312 μg/ml. Carvacrol at the MIC reduced the counts of E. coli and S. Typhimurium by approximately 5 log CFU/g. A. hydrophila was reduced by approximately 8 log CFU/g, and S. aureus was reduced by approximately 2 log CFU/g on the seventh day of storage. Carvacrol at the 2 × MIC completely inhibited all isolates on the first day of Storage. coliforms at 35 °C and 45 °C were not detected (< 3 MPN/g) with either treatment on all days of shelf life. The treatment groups exhibited a reduction of approximately 2 log CFU/g in psychrotrophic counts compared with controls on the last day of storage. Yeast and mold were not detected with either treatment over the same period. The addition of carvacrol did not affect total titratable acidity, pH, or soluble solids and improved weight loss. The edible coating of cassava starch with carvacrol may be an interesting approach to improve the safety and microbiological quality of MPP. PMID:27413224

  6. Next-generation sequencing for minimal residual disease monitoring in acute myeloid leukemia patients with FLT3-ITD or NPM1 mutations.

    PubMed

    Thol, Felicitas; Kölking, Britta; Damm, Frederik; Reinhardt, Katarina; Klusmann, Jan-Henning; Reinhardt, Dirk; von Neuhoff, Nils; Brugman, Martijn H; Schlegelberger, Brigitte; Suerbaum, Sebastian; Krauter, Jürgen; Ganser, Arnold; Heuser, Michael

    2012-07-01

    Systematic assessment of minimal residual disease (MRD) in acute myeloid leukemia (AML) patients has been hampered by lack of a reliable, uniform MRD marker applicable to all patients. We evaluated next-generation sequencing (NGS) for MRD assessment in AML patients (n = 80 samples). The ability of NGS technologies to generate thousands of clonal sequences makes it possible to determine the allelic ratio of sequence variants. Using NGS, we were able to determine the allelic ratio of different FLT3-internal tandem duplication (ITD) clones within one patient sample, in addition to resolution of FLT3-ITD insertion site, length, and sequence in a single analysis. Furthermore, NGS allowed us to study emergence of clonal dominance. Parallel assessment of MRD by NGS and quantitative real-time polymerase chain reaction in NPM1 mutated patients was concordant in 95% of analyzed samples (n = 38). The frequency of mutated alleles was linearly quantified by NGS. As NGS sensitivity is scalable depending on sequence coverage, it reflects a highly flexible and reliable tool to assess MRD in leukemia patients. PMID:22454318

  7. Application of the microbiological method DEFT/APC to detect minimally processed vegetables treated with gamma radiation

    NASA Astrophysics Data System (ADS)

    Araújo, M. M.; Duarte, R. C.; Silva, P. V.; Marchioni, E.; Villavicencio, A. L. C. H.

    2009-07-01

    Marketing of minimally processed vegetables (MPV) are gaining impetus due to its convenience, freshness and apparent health effect. However, minimal processing does not reduce pathogenic microorganisms to safe levels. Food irradiation is used to extend the shelf life and to inactivate food-borne pathogens. In combination with minimal processing it could improve safety and quality of MPV. A microbiological screening method based on the use of direct epifluorescent filter technique (DEFT) and aerobic plate count (APC) has been established for the detection of irradiated foodstuffs. The aim of this study was to evaluate the applicability of this technique in detecting MPV irradiation. Samples from retail markets were irradiated with 0.5 and 1.0 kGy using a 60Co facility. In general, with a dose increment, DEFT counts remained similar independent of the irradiation while APC counts decreased gradually. The difference of the two counts gradually increased with dose increment in all samples. It could be suggested that a DEFT/APC difference over 2.0 log would be a criteria to judge if a MPV was treated by irradiation. The DEFT/APC method could be used satisfactorily as a screening method for indicating irradiation processing.

  8. Minimizing errors from linear and nonlinear weights of WENO scheme for broadband applications with shock waves

    NASA Astrophysics Data System (ADS)

    Arshed, Ghulam M.; Hoffmann, Klaus A.

    2013-08-01

    Improvements in the numerical algorithm for the dynamics of flows that involve discontinuities and broadband fluctuations simultaneously are proposed. These two flow features suggest numerical strategies of a paradoxical nature because the discontinuities demand dissipation, and the small-scale smooth features require the opposite. There may be several ways to approach such a complicated issue, but the natural choice is a numerical technique that can adjust adaptively with flow regimes. The weighted essentially non-oscillatory (WENO) scheme may be this choice. However, there are two sources of dissipation associated with the WENO procedure: the upwind optimal stencil and the nonlinear adaption mechanism. The current work suggests a robust and comprehensive treatment for the minimization of dissipation error from these two sources. The optimization technique, which is guided by restriction on the linear optimal weights derived from stability and consistency requirement, is used to delay the dissipation of the upwind optimal stencil to those wavenumbers for which the dispersion error is large. The parallel advantage of this technique is the improvement of the dispersion property. Nevertheless, optimization decreases the formal order of accuracy of the optimal stencil from fifth order to third order. This loss of accuracy is derived by Taylor series expansion. Using Taylor-series expansion and WENO procedure, the third-order accuracy is verified in the smooth region, except at the critical point of order two, where the order of accuracy reduces to at least second order. This possible loss of accuracy at the second-order critical point is restored in an attempt to reduce the dissipation induced by the nonlinear adaptive weights. Modification of the nonlinear weights to reduce the dissipation is introduced by redefining them with an additional smoothness indicator. Other suggestions to minimize the dissipation of the nonlinear weights are also reviewed. The numerical

  9. Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

    NASA Technical Reports Server (NTRS)

    Manchester, John I.; Shibata, Masayuki; Setlik, Robert F.; Ornstein, Rick L.; Rein, Robert

    1993-01-01

    A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at the ab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar to ab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.

  10. Unconstrained and Constrained Minimization, Linear Scaling, and the Grassmann Manifold: Theory and Applications

    SciTech Connect

    RACZKOWSKI,DAVID; FONG,C.Y.; SCHULTZ,PETER A.; LIPPERT,ROSS A.; STECHEL,E.B.

    2000-07-19

    An unconstrained minimization algorithm for electronic structure calculations using density functional for systems with a gap is developed to solve for nonorthogonal Wannier-like orbitals in the spirit of E. B. Stechel, A. R. Williams, and P. J. Feibelman, Phys. Rev. B 49, 10,008 (1994). The search for the occupied sub-space is a Grassmann conjugate gradient algorithm generalized from the algorithm of A. Edelman, T.A. Arias, and S. T. Smith, SIAM J. on Matrix Anal. Appl. 20, 303 (1998). The gradient takes into account the nonorthogonality of a local atom-centered basis, gaussian in their implementation. With a localization constraint on the Wannier-like orbitals, well-constructed sparse matrix multiplies lead to O(N) scaling of the computationally intensive parts of the algorithm. Using silicon carbide as a test system, the accuracy, convergence, and implementation of this algorithm as a quantitative alternative to diagonalization are investigated. Results up to 1,458 atoms on a single processor are presented.

  11. Control of an ER haptic master in a virtual slave environment for minimally invasive surgery applications

    NASA Astrophysics Data System (ADS)

    Han, Young-Min; Choi, Seung-Bok

    2008-12-01

    This paper presents the control performance of an electrorheological (ER) fluid-based haptic master device connected to a virtual slave environment that can be used for minimally invasive surgery (MIS). An already developed haptic joint featuring controllable ER fluid and a spherical joint mechanism is adopted for the master system. Medical forceps and an angular position measuring device are devised and integrated with the joint to establish the MIS master system. In order to embody a human organ in virtual space, a volumetric deformable object is used. The virtual object is then mathematically formulated by a shape-retaining chain-linked (S-chain) model. After evaluating the reflection force, computation time and compatibility with real-time control, the haptic architecture for MIS is established by incorporating the virtual slave with the master device so that the reflection force for the object of the virtual slave and the desired position for the master operator are transferred to each other. In order to achieve the desired force trajectories, a sliding mode controller is formulated and then experimentally realized. Tracking control performances for various force trajectories are evaluated and presented in the time domain.

  12. Three-chip LED illumination system for laparoscopy and minimal access surgery applications

    NASA Astrophysics Data System (ADS)

    Ye, Bin; Wang, Liqiang; Duan, Huilong

    2010-11-01

    Light-emitting diodes (LEDs) bring great flexibility in color choice and high luminous efficacy design for biomedical illumination. Based on the state-of-the-art LED chips, a three-chip LED illumination system was developed specially for laparoscopy and minimal access surgery. White light is produced by mixing three specific wavelengths of amber red, true green and blue, and then coupled into a fiber-optic light guide with 2mm diameter. The whole device has a compact size of 145mm × 92mm × 84 mm which is more suitable than a conventional xenon lamp source for portable endoscopes. The illuminance and color characteristic of the three-chip model were analyzed, compared to those of traditional light source. A maximum illuminance of 1960 lux was obtained at the distance of 100 mm, with the average current of 450 mA of the LEDs. Additionally, a simulation environment had been set up to find out the performance of the endo-illuminator in the specific circumstance, which was closer distance and crawl space. Experiments showed that images taken under the three-chip LED illumination had better contrast and saturation. With the temperature of 31.5 degrees Celsius at the end of the fiber bundle, the endo-illuminator is also a cold light source.

  13. Novel/non-conventional manure application practices to minimize environmental impacts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Livestock manure can supply essential crop nutrients and contribute to improved soil quality. However, conventional surface broadcast application can result in adverse environmental effects from NH3 volatilization, odor, and runoff losses of nutrients and pathogens. Incorporation of manure by tillag...

  14. [Application of precision medicine in obesity and metabolic disease surgery].

    PubMed

    Wang, Cunchuan; Gao, Zhiguang

    2016-01-01

    The U. S. A. president Obama called for a new initiative to fund precision medicine during his State of Union Address on January 20th, 2015, which meant that the human medicine enters a new era. The meaning of "precision medicine" is significantly similar to the concept of precision obesity and metabolic disease surgery, which was proposed by the author in early August 2011. Nowadays, obesity and metabolic disease surgery has been transformed from open surgery to laparoscopic surgery, the extensive mode to the precision mode. The key value concept is to minimize postoperative complication, minimize postoperative hospital stay and obtain the best effect of weight loss by accurate preoperative assessment, delicate operation, excellent postoperative management and scientific follow-up. The precision obesity and metabolic disease surgery has more development space in the future. PMID:26797833

  15. Fast extraction of minimal paths in 3D images and applications to virtual endoscopy.

    PubMed

    Deschamps, T; Cohen, L D

    2001-12-01

    The aim of this article is to build trajectories for virtual endoscopy inside 3D medical images, using the most automatic way. Usually the construction of this trajectory is left to the clinician who must define some points on the path manually using three orthogonal views. But for a complex structure such as the colon, those views give little information on the shape of the object of interest. The path construction in 3D images becomes a very tedious task and precise a priori knowledge of the structure is needed to determine a suitable trajectory. We propose a more automatic path tracking method to overcome those drawbacks: we are able to build a path, given only one or two end points and the 3D image as inputs. This work is based on previous work by Cohen and Kimmel [Int. J. Comp. Vis. 24 (1) (1997) 57] for extracting paths in 2D images using Fast Marching algorithm. Our original contribution is twofold. On the first hand, we present a general technical contribution which extends minimal paths to 3D images and gives new improvements of the approach that are relevant in 2D as well as in 3D to extract linear structures in images. It includes techniques to make the path extraction scheme faster and easier, by reducing the user interaction. We also develop a new method to extract a centered path in tubular structures. Synthetic and real medical images are used to illustrate each contribution. On the other hand, we show that our method can be efficiently applied to the problem of finding a centered path in tubular anatomical structures with minimum interactivity, and that this path can be used for virtual endoscopy. Results are shown in various anatomical regions (colon, brain vessels, arteries) with different 3D imaging protocols (CT, MR). PMID:11731307

  16. Human hematopoietic cell lines: a model system for study of minimal residual disease detection technique in acute leukemia.

    PubMed

    Koníková, E; Kusenda, J; Babusíková, O; Glasová, M

    1995-01-01

    these surface and cytoplasmic marker combinations minor neoplastic cell populations could be detected. Human hematopoietic cell lines could serve as a reliable model system for monitoring minimal residual disease in acute leukemia patients. PMID:8552200

  17. Cost-minimization analysis of sublingual immunotherapy versus subcutaneous immunotherapy for house dust mite respiratory allergic disease in Denmark.

    PubMed

    Rønborg, Steen; Johnsen, Claus R; Theilgaard, Sune; Winther, Anders; Hahn-Pedersen, Julie; Andreasen, Jakob Nørgaard; Olsen, Jens

    2016-08-01

    Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT. PMID:26909663

  18. Application of a generalized minimal residual method to 2D unsteady flows

    NASA Technical Reports Server (NTRS)

    Hixon, Ray; Sankar, L. N.

    1992-01-01

    A generalized minimum residual scheme (GMRES), previously developed for solving nonlinear and linear systems of equations, has been applied to the numerical solution of 2D unsteady compressible flows. It is found that the use of GMRES significantly increases the time step that may be used, compared to noniterative implicit schemes. The feasibility of reducing the memory requirements of the GMRES scheme using a multigrid strategy has also been explored. Several sample steady and unsteady viscous flow applications are presented.

  19. Minimally invasive drug delivery to the cochlea through application of nanoparticles to the round window membrane.

    PubMed

    Buckiová, Daniela; Ranjan, Sanjeev; Newman, Tracey A; Johnston, Alexander H; Sood, Rohit; Kinnunen, Paavo K J; Popelář, Jiří; Chumak, Tetyana; Syka, Josef

    2012-09-01

    Direct drug delivery to the cochlea is associated with the risk of irreversible damage to the ear. In this study, liposome and polymersome nanoparticles (NPs), both formed from amphiphilic molecules (lipids in liposomes and block copolymers in polymersomes), were tested as potential tools for drug delivery to the cochlea via application onto the round window membrane in adult mice (strain C3H). One day after round window membrane application, both types of NPs labeled with fluorescent markers were identified in the spiral ganglion in all cochlear turns without producing any distinct morphological or functional damage to the inner ear. NPs were detected, although to a lesser extent, in the organ of Corti and the lateral wall. The potential of liposome and polymersome NPs as therapeutic delivery systems into the cochlea via the round window membrane was evaluated using disulfiram, a neurotoxic agent, as a model payload. Disulfiram-loaded NP delivery resulted in a significant decrease in the number of spiral ganglion cells starting 2 days postapplication, with associated pronounced hearing loss reaching 20-35 dB 2 weeks postapplication as assessed through auditory brainstem responses. No changes in hair cell morphology and function (as assessed by recording otoacoustic emissions) were detected after disulfiram-loaded NP application. No effects were observed in controls where solution of free disulfiram was similarly administered. The results demonstrate that liposome and polymersome NPs are capable of carrying a payload into the inner ear that elicits a biological effect, with consequences measurable by a functional readout. PMID:22475648

  20. Applications of supercritical fluid technology to pollution prevention and waste minimization

    SciTech Connect

    Turner, R.J.

    1995-10-01

    One approach to the prevention of pollution and the reduction of worker exposure from conventional solvents is the use of less hazardous substitutes. One of the more novel substitutes is carbon dioxide. Although carbon dioxide is a gas at ordinary conditions, it can be liquified by application of pressure. In its supercritical state, it exhibits good solvent properties. Separation of the carbon dioxide from the extracted materials can be accomplished by pressure reduction, adsorption onto activated carbon, or with a membrane process, e.g., decaffeination of coffee. This paper presents a brief overview of the university and federal laboratory collaborative efforts focusing on processes using supercritical carbon dioxide as a substitute for hazardous solvents. The SCCO2 technology applications under this program include extraction of natural pharmaceutical materials, phase-transfer catalysis, solvent replacement in chemical synthesis, temperature-solubility relationships, and separation of organic materials from soils and slurries. A paper on the extraction of heavy metals with SCCO2 was presented by Ataai et.al. at the 87th National Meeting, A&WMA. This work is also supported by the EPA.

  1. Disease resistance: Molecular mechanisms and biotechnological applications

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This special issue “Disease resistance: molecular mechanisms and biotechnological applications” contains 11 review articles and four original research papers. Research in the area of engineering for disease resistance continues to progress although only 10% of the transgenic plants registered for ...

  2. Assessing the effectiveness of manure application timing options to minimize P loss from fields

    NASA Astrophysics Data System (ADS)

    Archibald, J. A.; Fuka, D. R.; Schneider, R.; Easton, Z. M.; Walter, M. T.

    2015-12-01

    It is widely understood that spreading manure before a large runoff event causes water quality problems downstream. Phosphorus (P) is a pollutant that is particularly susceptible to these types of events, as P is often disproportionately transported in overland runoff. While the benefit of avoiding the intersection of manure and runoff is unmistakable, it is less clear what length of time is needed between manure application and runoff, and also, what types of predictions can be most effective (i.e. what is the benefit of runoff predictions over simple rain predictions?). In this study, we model the effect of prediction type and avoidance window size on resultant P export. This research aims to help land managers optimize the needs of their crops with water protection goals in the age of increasing online decision support tool options.

  3. Optimizing convergence rates of alternating minimization reconstruction algorithms for real-time explosive detection applications

    NASA Astrophysics Data System (ADS)

    Bosch, Carl; Degirmenci, Soysal; Barlow, Jason; Mesika, Assaf; Politte, David G.; O'Sullivan, Joseph A.

    2016-05-01

    X-ray computed tomography reconstruction for medical, security and industrial applications has evolved through 40 years of experience with rotating gantry scanners using analytic reconstruction techniques such as filtered back projection (FBP). In parallel, research into statistical iterative reconstruction algorithms has evolved to apply to sparse view scanners in nuclear medicine, low data rate scanners in Positron Emission Tomography (PET) [5, 7, 10] and more recently to reduce exposure to ionizing radiation in conventional X-ray CT scanners. Multiple approaches to statistical iterative reconstruction have been developed based primarily on variations of expectation maximization (EM) algorithms. The primary benefit of EM algorithms is the guarantee of convergence that is maintained when iterative corrections are made within the limits of convergent algorithms. The primary disadvantage, however is that strict adherence to correction limits of convergent algorithms extends the number of iterations and ultimate timeline to complete a 3D volumetric reconstruction. Researchers have studied methods to accelerate convergence through more aggressive corrections [1], ordered subsets [1, 3, 4, 9] and spatially variant image updates. In this paper we describe the development of an AM reconstruction algorithm with accelerated convergence for use in a real-time explosive detection application for aviation security. By judiciously applying multiple acceleration techniques and advanced GPU processing architectures, we are able to perform 3D reconstruction of scanned passenger baggage at a rate of 75 slices per second. Analysis of the results on stream of commerce passenger bags demonstrates accelerated convergence by factors of 8 to 15, when comparing images from accelerated and strictly convergent algorithms.

  4. Management considerations to minimize environmental impacts of arsenic following monosodium methylarsenate (MSMA) applications to turfgrass.

    PubMed

    Mahoney, Denis J; Gannon, Travis W; Jeffries, Matthew D; Matteson, Audrey R; Polizzotto, Matthew L

    2015-03-01

    Monosodium methylarsenate (MSMA) is an organic arsenical herbicide currently utilized in turfgrass and cotton systems. In recent years, concerns over adverse impacts of arsenic (As) from MSMA applications have emerged; however, little research has been conducted in controlled field experiments using typical management practices. To address this knowledge gap, a field lysimeter experiment was conducted during 2012-2013 to determine the fate of As following MSMA applications to a bareground and an established turfgrass system. Arsenic concentrations in soil, porewater, and aboveground vegetation, were measured through one yr after treatment. Aboveground vegetation As concentration was increased compared to nontreated through 120 d after initial treatment (DAIT). In both systems, increased soil As concentrations were observed at 0-4 cm at 30 and 120 DAIT and 0-8 cm at 60 and 365 DAIT, suggesting that As was bound in shallow soil depths. Porewater As concentrations in MSMA-treated lysimeters from a 30-cm depth (22.0-83.8 μg L(-1)) were greater than those at 76-cm depth (0.4-5.1 μg L(-1)). These results were combined with previous research to devise management considerations in systems where MSMA is utilized. MSMA should not be applied if rainfall is forecasted within 7 DAIT and/or in areas with shallow water tables. Further, disposing of MSMA-treated turfgrass aboveground vegetation in a confined area - a common management practice for turfgrass clippings - may be of concern due to As release to surface water or groundwater as the vegetation decomposes. Finally, long-term MSMA use may cause soil As accumulation and thus downward migration of As over time; therefore, MSMA should be used in rotation with other herbicides. PMID:25556868

  5. The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer's disease: relationship to episodic and semantic memory impairment.

    PubMed

    Perry, R J; Watson, P; Hodges, J R

    2000-01-01

    The development of cholinergic therapies for Alzheimer's disease (AD) has highlighted the importance of understanding the role of attentional deficits and the relationship between attention and memory in the earliest stages of the disease. Variability in the tasks used to examine aspects of attention, and in the disease severity, between studies makes it difficult to determine which aspects of attention are affected earliest in AD, and how attentional impairment is related to other cognitive modules. We tested 27 patients in the early stages of the disease on the basis of the MMSE (minimal 24-30 corresponding to minimal cognitive impairment, very mild or possible AD in other classifications; and mild 18-23) on a battery of attentional tests aimed to assess sustained, divided, and selective attention, plus tests of episodic memory, semantic memory, visuoperceptual and visuospatial function, and verbal short-term memory. Although the mildly demented group were impaired on all attentional tests, the minimally impaired group showed a preserved ability to sustain attention, and to divide attention based on a dual-task paradigm. The minimally demented group had particular problems with response inhibition and speed of attentional switching. Examination of the relationship between attention and other cognitive domains showed impaired episodic memory in all patients. Deficits in attention were more prevalent than deficits in semantic memory suggesting that they occur at an earlier stage and the two were partially independent. Impairment in visuoperceptual and visuospatial functions and verbal short-term memory were the least common. Although attention is impaired early in AD, 40% of our patients showed deficits in episodic memory alone, confirming that amnesia may be the only cognitive deficit in the earliest stages of sporadic AD. PMID:10678692

  6. Evolutionary perspectives on wildlife disease: concepts and applications

    PubMed Central

    Vander Wal, Eric; Garant, Dany; Pelletier, Fanie

    2014-01-01

    Wildlife disease has the potential to cause significant ecological, socioeconomic, and health impacts. As a result, all tools available need to be employed when host–pathogen dynamics merit conservation or management interventions. Evolutionary principles, such as evolutionary history, phenotypic and genetic variation, and selection, have the potential to unravel many of the complex ecological realities of infectious disease in the wild. Despite this, their application to wildlife disease ecology and management remains in its infancy. In this article, we outline the impetus behind applying evolutionary principles to disease ecology and management issues in the wild. We then introduce articles from this special issue on Evolutionary Perspectives on Wildlife Disease: Concepts and Applications, outlining how each is exemplar of a practical wildlife disease challenge that can be enlightened by applied evolution. Ultimately, we aim to bring new insights to wildlife disease ecology and its management using tools and techniques commonly employed in evolutionary ecology. PMID:25469154

  7. Analysis of the application of decontamination technologies to radioactive metal waste minimization using expert systems

    SciTech Connect

    Bayrakal, S.

    1993-09-30

    Radioactive metal waste makes up a significant portion of the waste currently being sent for disposal. Recovery of this metal as a valuable resource is possible through the use of decontamination technologies. Through the development and use of expert systems a comparison can be made of laser decontamination, a technology currently under development at Ames Laboratory, with currently available decontamination technologies for applicability to the types of metal waste being generated and the effectiveness of these versus simply disposing of the waste. These technologies can be technically and economically evaluated by the use of expert systems techniques to provide a waste management decision making tool that generates, given an identified metal waste, waste management recommendations. The user enters waste characteristic information as input and the system then recommends decontamination technologies, determines residual contamination levels and possible waste management strategies, carries out a cost analysis and then ranks, according to cost, the possibilities for management of the waste. The expert system was developed using information from literature and personnel experienced in the use of decontamination technologies and requires validation by human experts and assignment of confidence factors to the knowledge represented within.

  8. Minimization of thermal impact by application of electrode cooling in a co-linear PEF treatment chamber.

    PubMed

    Meneses, Nicolas; Jaeger, Henry; Knorr, Dietrich

    2011-10-01

    A co-linear pulsed electric field (PEF) treatment chamber was analyzed and optimized considering electrical process conditions, temperature, and retention of heat-sensitive compounds during a continuous PEF treatment of peach juice. The applicability of a jacket heat-exchanger device surrounding the ground electrode was studied in order to provide active cooling and to avoid temperature peaks within the treatment chamber thus reducing the total thermal load to which the product is exposed. Simulation of the PEF process was performed using a finite element method prior to experimental verification. Inactivation of polyphenoloxydase (PPO) and peroxidase (POD) as well as the degradation of ascorbic acid (AA) in peach juice was quantified and used as indirect indicators for the temperature distribution. Peaks of product temperature within the treatment chamber were reduced, that is, from 98 to 75 °C and retention of the indicators PPO, POD, and AA increased by more than 10% after application of the active electrode cooling device. Practical Application:  The co-linear PEF treatment chamber is widely used for continuous PEF treatment of liquid products and also suitable for industrial scale application; however, Joule heating in combination with nonuniform electric field distribution may lead to unwanted thermal effects. The proposed design showed potential to reduce the thermal load, to which the food is exposed, allowing the retention of heat-sensitive components. The design is applicable at laboratory or industrial scale to perform PEF trials avoiding temperature peaks, which is also the basis for obtaining inactivation kinetic models with minimized thermal impact on the kinetic variables. PMID:22417588

  9. Potential applications of catestatin in cardiovascular diseases.

    PubMed

    Zhao, Yilin; Zhu, Dan

    2016-08-01

    Catestatin (CST) was first named in 1997 for its catecholamine-inhibitory activity. It was discovered as a potent inhibitor of catecholamine secretion and as a regulator of histamine release. Accumulating evidence shows that CST is involved with cardiovascular diseases; however, whether CST is a protective factor for these conditions and the mechanisms by which such actions may be mediated are not well understood. In this article, we review recent basic research and clinical trials in the study of CST and summarize the association of CST with cardiovascular diseases. We review data obtained from MedLine via PubMed and from our own investigations. PMID:27415768

  10. Metabolomics: Applications and Promise in Mycobacterial Disease.

    PubMed

    Mirsaeidi, Mehdi; Banoei, Mohammad Mehdi; Winston, Brent W; Schraufnagel, Dean E

    2015-09-01

    Until recently, the study of mycobacterial diseases was trapped in culture-based technology that is more than a century old. The use of nucleic acid amplification is changing this, and powerful new technologies are on the horizon. Metabolomics, which is the study of sets of metabolites of both the bacteria and host, is being used to clarify mechanisms of disease, and can identify changes leading to better diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic profiles are arrays of biochemical products of genes in their environment. These complex patterns are biomarkers that can allow a more complete understanding of cell function, dysfunction, and perturbation than genomics or proteomics. Metabolomics could herald sweeping advances in personalized medicine and clinical trial design, but the challenges in metabolomics are also great. Measured metabolite concentrations vary with the timing within a condition, the intrinsic biology, the instruments, and the sample preparation. Metabolism profoundly changes with age, sex, variations in gut microbial flora, and lifestyle. Validation of biomarkers is complicated by measurement accuracy, selectivity, linearity, reproducibility, robustness, and limits of detection. The statistical challenges include analysis, interpretation, and description of the vast amount of data generated. Despite these drawbacks, metabolomics provides great opportunity and the potential to understand and manage mycobacterial diseases. PMID:26196272

  11. Applications of Doppler ultrasound in clinical vascular disease

    NASA Technical Reports Server (NTRS)

    Barnes, R. W.; Hokanson, D. E.; Sumner, D. S.; Strandness, D. E., Jr.

    1975-01-01

    Doppler ultrasound has become the most useful and versatile noninvasive technique for objective evaluation of clinical vascular disease. Commercially available continuous-wave instruments provide qualitative and quantitative assessment of venous and arterial disease. Pulsed Doppler ultrasound was developed to provide longitudinal and transverse cross-sectional images of the arterial lumen with a resolution approaching that of conventional X-ray techniques. Application of Doppler ultrasound in venous, peripheral arterial, and cerebrovascular diseases is reviewed.

  12. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases.

    PubMed

    Ma, Yiyangzi; Shi, Na; Li, Mengtao; Chen, Fei; Niu, Haitao

    2015-08-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

  13. Applications of Next-generation Sequencing in Systemic Autoimmune Diseases

    PubMed Central

    Ma, Yiyangzi; Shi, Na; Li, Mengtao; Chen, Fei; Niu, Haitao

    2015-01-01

    Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogenesis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body’s immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases. PMID:26432094

  14. Human Pluripotent Stem Cells: Applications and Challenges in Neurological Diseases

    PubMed Central

    Hibaoui, Youssef; Feki, Anis

    2012-01-01

    The ability to generate human pluripotent stem cells (hPSCs) holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery, and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises, and challenges of hPSC applications in human neurological disease modeling and therapies. PMID:22934023

  15. Graphical neuroimaging informatics: application to Alzheimer's disease.

    PubMed

    Van Horn, John Darrell; Bowman, Ian; Joshi, Shantanu H; Greer, Vaughan

    2014-06-01

    The Informatics Visualization for Neuroimaging (INVIZIAN) framework allows one to graphically display image and meta-data information from sizeable collections of neuroimaging data as a whole using a dynamic and compelling user interface. Users can fluidly interact with an entire collection of cortical surfaces using only their mouse. In addition, users can cluster and group brains according in multiple ways for subsequent comparison using graphical data mining tools. In this article, we illustrate the utility of INVIZIAN for simultaneous exploration and mining a large collection of extracted cortical surface data arising in clinical neuroimaging studies of patients with Alzheimer's Disease, mild cognitive impairment, as well as healthy control subjects. Alzheimer's Disease is particularly interesting due to the wide-spread effects on cortical architecture and alterations of volume in specific brain areas associated with memory. We demonstrate INVIZIAN's ability to render multiple brain surfaces from multiple diagnostic groups of subjects, showcase the interactivity of the system, and showcase how INVIZIAN can be employed to generate hypotheses about the collection of data which would be suitable for direct access to the underlying raw data and subsequent formal statistical analysis. Specifically, we use INVIZIAN show how cortical thickness and hippocampal volume differences between group are evident even in the absence of more formal hypothesis testing. In the context of neurological diseases linked to brain aging such as AD, INVIZIAN provides a unique means for considering the entirety of whole brain datasets, look for interesting relationships among them, and thereby derive new ideas for further research and study. PMID:24203652

  16. Application of ozone in the treatment of periodontal disease

    PubMed Central

    Srikanth, Adusumilli; Sathish, Manthena; Sri Harsha, Anumolu Venkatanaga

    2013-01-01

    Gingivitis and periodontitis are most common inflammatory diseases of supporting tissues of teeth. Role of microbial etiology and host response in progression of gingival and periodontal diseases has been well established. Because of the beneficial biological effects of ozone, due to its antimicrobial and immunostimulating effect, it is well indicated in the treatment of gingival and periodontal diseases. The objective of this article is to provide a general review about clinical applications of ozone in treatment of periodontal diseases and to summarize the available in vitro and in vivo studies in Periodontics in which ozone has been used. PMID:23946585

  17. A comparison of MyoD1 and fetal acetylcholine receptor expression in childhood tumors and normal tissues: implications for the molecular diagnosis of minimal disease in rhabdomyosarcomas.

    PubMed

    Gattenloehner, S; Dockhorn-Dworniczak, B; Leuschner, I; Vincent, A; Müller-Hermelink, H K; Marx, A

    1999-11-01

    Detection of minimal residual disease or micrometastases in rhabdomyosarcoma (RMS) has been an unresolved problem in 70 to 80% of RMS patients. In patients with alveolar type RMS, which harbors chromosomal translocations and produces tumor-specific fusion products, polymerase chain reaction (PCR)-based diagnosis is clear-cut. In the more frequent embryonal RMS, however, no such PCR-based marker has been described. Recently it has been suggested that the PCR-based detection of MyoD1 may be a valuable adjunct in the diagnosis of minimal disease in embryonal RMS. We report here that MyoD1 mRNA is not specific for RMS, but can be amplified from ex vivo samples of many other childhood tumors and some normal tissues. By contrast, simultaneous amplification of alpha and gamma subunit message of the fetal type acetylcholine receptor (AChR), by a novel duplex PCR, and the quantification of both transcripts resulting in a alpha/gammaAChR ratio <1 was 100% sensitive in alveolar (n = 8) and embryonal (n = 10) RMS. Moreover, gammaAChR was not detected in other childhood (n = 27) or adult tumors (n = 12), or normal tissues, except thymus. The high sensitivity and specificity of the method were confirmed by the successful detection of five cases of cytologically or molecularly verified RMS bone marrow micrometastases among 47 bone marrow samples from childhood tumor patients. By contrast, MyoD1 showed no amplification because of its low level of transcription. We conclude that mRNA of the fetal type AChR is a more specific and (about 100 times) more sensitive marker for the molecular detection of RMS than MyoD1, and thus appears to be a promising candidate for the detection of minimal disease in RMS lacking tumor-specific translocations. PMID:11272905

  18. Optimized oral cholera vaccine distribution strategies to minimize disease incidence: A mixed integer programming model and analysis of a Bangladesh scenario.

    PubMed

    Smalley, Hannah K; Keskinocak, Pinar; Swann, Julie; Hinman, Alan

    2015-11-17

    In addition to improved sanitation, hygiene, and better access to safe water, oral cholera vaccines can help to control the spread of cholera in the short term. However, there is currently no systematic method for determining the best allocation of oral cholera vaccines to minimize disease incidence in a population where the disease is endemic and resources are limited. We present a mathematical model for optimally allocating vaccines in a region under varying levels of demographic and incidence data availability. The model addresses the questions of where, when, and how many doses of vaccines to send. Considering vaccine efficacies (which may vary based on age and the number of years since vaccination), we analyze distribution strategies which allocate vaccines over multiple years. Results indicate that, given appropriate surveillance data, targeting age groups and regions with the highest disease incidence should be the first priority, followed by other groups primarily in order of disease incidence, as this approach is the most life-saving and cost-effective. A lack of detailed incidence data results in distribution strategies which are not cost-effective and can lead to thousands more deaths from the disease. The mathematical model allows for what-if analysis for various vaccine distribution strategies by providing the ability to easily vary parameters such as numbers and sizes of regions and age groups, risk levels, vaccine price, vaccine efficacy, production capacity and budget. PMID:26458806

  19. Current applications of nanoparticles in infectious diseases.

    PubMed

    Zazo, Hinojal; Colino, Clara I; Lanao, José M

    2016-02-28

    For decades infections have been treated easily with drugs. However, in the 21st century, they may become lethal again owing to the development of antimicrobial resistance. Pathogens can become resistant by means of different mechanisms, such as increasing the time they spend in the intracellular environment, where drugs are unable to reach therapeutic levels. Moreover, drugs are also subject to certain problems that decrease their efficacy. This requires the use of high doses, and frequent administrations must be implemented, causing adverse side effects or toxicity. The use of nanoparticle systems can help to overcome such problems and increase drug efficacy. Accordingly, there is considerable current interest in their use as antimicrobial agents against different pathogens like bacteria, virus, fungi or parasites, multidrug-resistant strains and biofilms; as targeting vectors towards specific tissues; as vaccines and as theranostic systems. This review begins with an overview of the different types and characteristics of nanoparticles used to deliver drugs to the target, followed by a review of current research and clinical trials addressing the use of nanoparticles within the field of infectious diseases. PMID:26772877

  20. RESEARCH NOTE FROM COLLABORATION: NNLC: non-negative least chi-square minimization and application to HPGe detectors

    NASA Astrophysics Data System (ADS)

    Désesquelles, P.; Ha, T. M. H.; Korichi, A.; LeBlanc, F.; Petrache, C. M.; AGATA Collaboration

    2009-03-01

    A new method is proposed for the problem of solving chi-square minimization with a positive solution. This method is embodied in an evolution of the popular NNLS algorithm. Its efficiency with respect to residue minimization is illustrated by the improvement it permits on the location of gamma-interactions inside an AGATA HPGe detector.

  1. Application of the Chick Embryo Chorioallantoic Membrane in Neurosurgery Disease

    PubMed Central

    Yuan, Yong-Jie; Xu, Kan; Wu, Wei; Luo, Qi; Yu, Jin-Lu

    2014-01-01

    The chick embryo chorioallantoic membrane (CAM) is a highly vascularized extraembryonic membrane. Because of its ease of accessibility, extensive vascularization and immunodeficient environment, the CAM has been broadly used in the oncology, biology, pharmacy, and tissue regeneration research. The present review summarizes the application of the CAM in neurosurgery disease research. We focused on the use of the CAM as an assay for the research of glioma, vascular anomalies, Moyamoya Disease, and the blood-brain barrier. PMID:25419173

  2. Theory of protein misfolding and applications to misfolding diseases

    NASA Astrophysics Data System (ADS)

    Plotkin, Steven S.

    2009-03-01

    Physics-based algorithms can predict the misfolding mechanisms of proteins involved in aggregation-related diseases, including ALS and the Prion diseases. Predictions based on such an algorithm that we have developed, which employs both atomistic interactions and surface-area based coarse-graining, have been recently verified by immunological assays and point to diagnostic and therapeutic applications. I will describe the results of our misfolding theory, and discuss future directions towards drug research.

  3. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  4. Application of regenerative medicine for kidney diseases.

    PubMed

    Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  5. Application of Regenerative Medicine for Kidney Diseases

    PubMed Central

    Fukui, Akira; Kobayashi, Eiji

    2007-01-01

    Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF). The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application. PMID:19279698

  6. Study on application of optical clearing technique in skin diseases

    NASA Astrophysics Data System (ADS)

    Shan, Hao; Liang, Yanmei; Wang, Jingyi; Li, Yan

    2012-11-01

    So far, the study of the optical clearing is almost always about healthy tissue. However, the ultimate goal is to detect diseases for clinical application. Optical clearing on diseased skins is explored. The effect is evaluated by applying a combined liquid paraffin and glycerol mixed solution on several kinds of diseased skins in vitro. Scanning experiments from optical coherence tomography show that it has different effects among fibroma, pigmented nevus, and seborrheic keratosis. Based on the results, we conclude that different skin diseases have different compositions and structures, and their optical parameters and biological characteristics should be different, which implies that the optical clearing technique may have selectivity and may not be suitable for all kinds of skin diseases.

  7. [Clinical applications of arterial spin labeling technique in brain diseases].

    PubMed

    Wang, Li; Zheng, Gang; Zhao, Tiezhu; Guo, Chao; Li, Lin; Lu, Guangming

    2013-02-01

    Arterial spin labeling (ASL) technique is a kind of perfusion functional magnetic resonance imaging method that is based on endogenous contrast, and it can measure cerebral blood flow (CBF) noninvasively. The ASL technique has advantages of noninvasiveness, simplicity and relatively lower costs so that it is more suitable for longitudinal studies compared with previous perfusion methods, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), CT and the contrast agent based magnetic resonance perfusion imaging. This paper mainly discusses the current clinical applications of ASL in brain diseases as cerebrovascular diseases, brain tumors, Alzheimer's disease and epilepsy, etc. PMID:23488163

  8. Safely Increase the Minimally Invasive Hysterectomy Rate: A Novel Three-Tiered Preoperative Categorization System Can Predict the Difficulty for Benign Disease

    PubMed Central

    Andryjowicz, Esteban; Wray, Teresa B; Reinaldo Ruiz, V; Rudolf, James; Noroozkhani, Sara; Crowder, Sandra; Slezak, Jeff M

    2015-01-01

    Context: A nonlaparotomic route is recommended for hysterectomy for benign indications. Objective: 1) Predict the difficulty of hysterectomy to treat benign disease as measured by operative time and risk of laparotomy, 2) confirm the safety and quality of increasing our minimally invasive hysterectomy (MIH) rate, and 3) determine whether the assistant’s experience affected the likelihood of an MIH being performed in equally difficult hysterectomies. Design: All hysterectomies for benign disease performed at the Kaiser Permanente Fontana Medical Center in Fontana, CA, in 2012 were reviewed for length of surgery, length of stay, complications, and readmissions. A three-tiered category system was developed from four preoperative parameters (body mass index, number of vaginal deliveries, clinical uterine size, and history of major abdominal surgery) to anticipate length and difficulty of surgery. Main Outcome Measures: Rates of MIH, complications, and readmissions as well as length of surgery and length of stay for similarly difficult hysterectomies. These outcomes were compared with surgeons’ and assistants’ experience. Results: Of 576 hysterectomies performed for benign disease, 89% were MIH with a 3% complication rate and 4% readmission rate. An increase in the hysterectomy category was statistically significantly associated with longer surgery times and a higher percentage of laparotomy. With the most experienced assistants, the MIH rate was 98%. Conclusions: Using 4 preoperative parameters, the average operating time for hysterectomy for benign disease can be predicted. A higher hysterectomy category predicts a more difficult surgery. Our center has increased its MIH rate to 89% while maintaining safety. PMID:26222092

  9. Optimal Effect of Phenol Block in the Sciatic Nerve of Rats: Standardization of Minimized Dosage and Duration of Application.

    PubMed

    Lin, Chuan-Chao; Chang, Chein-Wei; Tsai, Su-Ju

    2015-08-31

    The phenol nerve block has been widely used in clinical practice for spasticity reduction, but the correlation between the dosage of phenol and its effectiveness has seldom been discussed. The objective was to determine the optimal duration of phenol in contact with the nervous tissue and to investigate the dose-response relationship of 5% aqueous phenol solution by percutaneous nerve block in rats. Group I (n = 8) received sciatic nerve block by bathing the nerves in phenol solution, and group II (n = 40) by injecting phenol percutaneously. Group IIa to IId received different volumes (0.80, 0.16, 0.08 and 0.04 ml) and group IIe received normal saline. Compound muscle action potential (CMAP) was measured pre-injection and at 90 and 270 sec after injection and after surgical exposure of the nerves. The duration of CMAP reduced by 10%, 25%, 50%, 75% and 100% after phenol injection was also recorded. The mean latency for the evoked response to subside in direct phenol application (group I) and percutaneous nerve block (group IIa) were 73.5 ± 5.9 and 62.4 ± 7.6 sec, respectively. There was no statistical difference for the time periods in the blocking effect elicited by phenol solution between these two methods. Ninety sec was set as the optimal duration for phenol to produce complete conduction blockage. Higher volume of phenol produced more significant blocking effect at 90 and 270 sec after injection. Percutaneous injection with 0.16 ml of phenol solution had the same blocking effect as 0.8 ml. The continuous injection model for percutaneous phenol block indeed used significantly more phenol than actually needed. Clinically, the progressive injection model can be used to minimize injection volume. PMID:26211647

  10. Mycobacterium ulcerans causes minimal pathogenesis and colonization in Medaka (Oryzias latipes): An experimental fish model of disease transmission

    PubMed Central

    Mosi, Lydia; Mutoji, Nadine K.; Basile, Fritz A; Donnell, Robert; Jackson, Kathrine L.; Spangenberg, Thomas; Kishi, Yoshito; Ennis, Don G.; Small, Pamela L.C.

    2012-01-01

    Mycobacterium ulcerans causes Buruli ulcer in humans, a progressive ulcerative epidermal lesion due to the mycolactone toxin produced by the bacterium. Molecular analysis of M. ulcerans reveals it is closely related to M. marinum, a pathogen of both fish and man. Molecular evidence from diagnostic PCR assays for the insertion sequence IS2404 suggests an association of M. ulcerans with fish. However, fish infections by M. ulcerans have not been well documented and IS2404 has been found in other mycobacteria. We have thus, employed two experimental approaches to test for M. ulcerans in fish. We show here for the first time that M. ulcerans with or without the toxin does not mount acute or chronic infections in Japanese Medaka “Oryzias latipes” even at high doses. Moreover, M. ulcerans-infected medaka do not exhibit any visible signs of infection nor disease and the bacteria do not appear to replicate over time. In contrast, similar high doses of the wild-type M. marinum or a mycolactone producing M. marinum “DL” strain are able to mount an acute disease with mortality in medaka. Although these results would suggest that M. ulcerans does not mount infections in fish we have evidence that CLC macrophages from goldfish are susceptible to mycolactones. PMID:22465732

  11. Minimal Reduplication

    ERIC Educational Resources Information Center

    Kirchner, Jesse Saba

    2010-01-01

    This dissertation introduces Minimal Reduplication, a new theory and framework within generative grammar for analyzing reduplication in human language. I argue that reduplication is an emergent property in multiple components of the grammar. In particular, reduplication occurs independently in the phonology and syntax components, and in both cases…

  12. A review of disease progression models of Parkinson's disease and applications in clinical trials.

    PubMed

    Venuto, Charles S; Potter, Nicholas B; Ray Dorsey, E; Kieburtz, Karl

    2016-07-01

    Quantitative disease progression models for neurodegenerative disorders are gaining recognition as important tools for drug development and evaluation. In Parkinson's disease (PD), several models have described longitudinal changes in the Unified Parkinson's Disease Rating Scale (UPDRS), one of the most utilized outcome measures for PD trials assessing disease progression. We conducted a literature review to examine the methods and applications of quantitative disease progression modeling for PD using a combination of key words including "Parkinson disease," "progression," and "model." For this review, we focused on models of PD progression quantifying changes in the total UPDRS scores against time. Four different models reporting equations and parameters have been published using linear and nonlinear functions. The reasons for constructing disease progression models of PD thus far have been to quantify disease trajectories of PD patients in active and inactive treatment arms of clinical trials, to quantify and discern symptomatic and disease-modifying treatment effects, and to demonstrate how model-based methods may be used to design clinical trials. The historical lack of efficiency of PD clinical trials begs for model-based simulations in planning for studies that result in more informative conclusions, particularly around disease modification. © 2016 International Parkinson and Movement Disorder Society. PMID:27226141

  13. [Application of artificial neural networks in infectious diseases].

    PubMed

    Xu, Jun-fang; Zhou, Xiao-nong

    2011-02-28

    With the development of information technology, artificial neural networks has been applied to many research fields. Due to the special features such as nonlinearity, self-adaptation, and parallel processing, artificial neural networks are applied in medicine and biology. This review summarizes the application of artificial neural networks in the relative factors, prediction and diagnosis of infectious diseases in recent years. PMID:21823326

  14. Taxonomic minimalism.

    PubMed

    Beattle, A J; Oliver, I

    1994-12-01

    Biological surveys are in increasing demand while taxonomic resources continue to decline. How much formal taxonomy is required to get the job done? The answer depends on the kind of job but it is possible that taxonomic minimalism, especially (1) the use of higher taxonomic ranks, (2) the use of morphospecies rather than species (as identified by Latin binomials), and (3) the involvement of taxonomic specialists only for training and verification, may offer advantages for biodiversity assessment, environmental monitoring and ecological research. As such, formal taxonomy remains central to the process of biological inventory and survey but resources may be allocated more efficiently. For example, if formal Identification is not required, resources may be concentrated on replication and increasing sample sizes. Taxonomic minimalism may also facilitate the inclusion in these activities of important but neglected groups, especially among the invertebrates, and perhaps even microorganisms. PMID:21236933

  15. Development and Feasibility Testing of Image-Guided Minimally Invasive Tissue for Diagnosis Treatment of Benign and Malignant Breast Disease

    NASA Technical Reports Server (NTRS)

    Jeffrey, Stefanie S.

    1999-01-01

    Dr. Robert Mah and Dr. Stefanie Jeffrey worked on the development of the NASA Smart Probe in its application as a device to measure and interpret physiologic and image-based parameters of breast tissue. To date the following has been achieved: 1 . Choice of candidate sensors to be tested in breast tissue. 2. Preliminary designs for probe tip, specifically use of different tip shapes, cutting edges, and sensor configuration. 3. Design of sonographic guidance system. 4. Design of data extraction and analysis tool using scanned information of images of the breast tissue to provide a higher dimension of information for breast tissue characterization and interpretation. 5. Initial ex-vivo (fruit and tofu) and in-vivo (rodent) testing to confirm unique substance and tissue characterization by the Smart Probe software.

  16. Minimal residual disease quantification using consensus primers and high-throughput IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia

    PubMed Central

    Logan, A C; Zhang, B; Narasimhan, B; Carlton, V; Zheng, J; Moorhead, M; Krampf, M R; Jones, C D; Waqar, A N; Faham, M; Zehnder, J L; Miklos, D B

    2013-01-01

    Quantification of minimal residual disease (MRD) following allogeneic hematopoietic cell transplantation (allo-HCT) predicts post-transplant relapse in patients with chronic lymphocytic leukemia (CLL). We utilized an MRD-quantification method that amplifies immunoglobulin heavy chain (IGH) loci using consensus V and J segment primers followed by high-throughput sequencing (HTS), enabling quantification with a detection limit of one CLL cell per million mononuclear cells. Using this IGH–HTS approach, we analyzed MRD patterns in over 400 samples from 40 CLL patients who underwent reduced-intensity allo-HCT. Nine patients relapsed within 12 months post-HCT. Of the 31 patients in remission at 12 months post-HCT, disease-free survival was 86% in patients with MRD <10−4 and 20% in those with MRD ⩾10−4 (relapse hazard ratio (HR) 9.0; 95% confidence interval (CI) 2.5–32; P<0.0001), with median follow-up of 36 months. Additionally, MRD predicted relapse at other time points, including 9, 18 and 24 months post-HCT. MRD doubling time <12 months with disease burden ⩾10−5 was associated with relapse within 12 months of MRD assessment in 50% of patients, and within 24 months in 90% of patients. This IGH–HTS method may facilitate routine MRD quantification in clinical trials. PMID:23419792

  17. Self-reported adherence to a home-based exercise program among patients affected by psoriatic arthritis with minimal disease activity.

    PubMed

    Chimenti, Maria Sole; Triggianese, Paola; Conigliaro, Paola; Santoro, Matteo; Lucchetti, Ramona; Perricone, Roberto

    2014-11-01

    More than half of all patients with psoriatic arthritis (PsA) exhibit progressive erosive arthritis, associated with severe functional impairment and psychosocial disability. Biologics have been suggested to be more effective in inducing minimal disease activity" (MDA) than disease-modifying antirheumatic drugs (DMARDs). Behavioral patient education appears to be more effective in encouraging patients to increase their physical activity (PA) levels. The aim of the study was to evaluate the benefits of home-based exercises program on disease activity and quality of life in MDA-PsA patients treated with an anti-tumor necrosis factor (TNF) and DMARD therapy. We observed a self-reported adherence rate to home-based exercise of 76.6% and data showed the impact of the exercise program on self-reported health and mental assessment. A positive relationship between patient and therapist is crucial, influencing the quality of the performance, the emotional support, and increasing motivation in PsA patients. PMID:25381979

  18. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics

    PubMed Central

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  19. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics.

    PubMed

    Mahla, Ranjeet Singh

    2016-01-01

    Regenerative medicine, the most recent and emerging branch of medical science, deals with functional restoration of tissues or organs for the patient suffering from severe injuries or chronic disease. The spectacular progress in the field of stem cell research has laid the foundation for cell based therapies of disease which cannot be cured by conventional medicines. The indefinite self-renewal and potential to differentiate into other types of cells represent stem cells as frontiers of regenerative medicine. The transdifferentiating potential of stem cells varies with source and according to that regenerative applications also change. Advancements in gene editing and tissue engineering technology have endorsed the ex vivo remodelling of stem cells grown into 3D organoids and tissue structures for personalized applications. This review outlines the most recent advancement in transplantation and tissue engineering technologies of ESCs, TSPSCs, MSCs, UCSCs, BMSCs, and iPSCs in regenerative medicine. Additionally, this review also discusses stem cells regenerative application in wildlife conservation. PMID:27516776

  20. Analysis of a waste-minimization program for nonhazardous solid wastes utilizing source-reduction and recycling techniques and its application to Air Force installations. Master's thesis

    SciTech Connect

    McDermott, B.G.

    1991-09-01

    This nation has fallen victim to its own excessive behavior and has created an overabundance of trash, referred to in this thesis as Nonhazardous Solid Waste (NSW). This situation has created environmental and health problems that can no longer be ignored. All types of communities are affected including Air Force installations. Unfortunately, the AF does not currently have a long term waste management policy or program regarding NHSW minimization. This research concentrates on the application of a NHSW minimization program for AF installations using the two most preferred methods, source reduction and recycling. The development of a comprehensive waste minimization program using the techniques described is the most effective and efficient way to decrease the solid waste burden. The construction and implementation of these programs is not easy, especially for an organization as complex and diverse as the AF. However, the payoffs from a well planned and executed program far outweigh any costs.

  1. [TREATMENT OF POST-SPONDYLODESIS, ADJACENT-SEGMENT DISEASE WITH MINIMALLY INVASIVE, ANTEROLATERAL SURGERY ON THE LUMBAR SPINE: IS THERE IS NO NEED FOR DORSAL OPERATION?].

    PubMed

    Schwarcz, Attila; Szakály, Péter; Büki, András; Dóczi, Tamás

    2015-07-30

    Adjacent segment disease (ASD) occurs with a probability of 30% in the lumbar spine following spinal fusion surgery. Usually advanced degenerative changes happen cranially to the fused lumbar segment. Thus, secondary spinal instability, stenosis, spodylolisthesis, foraminal stenosis can lead to the recurrence of the pain not always amenable to conservative measures. A typical surgical solution to treat ASD consists of posterior revision surgery including decompression, change or extension of the instrumentation and fusion to the rostral level. It results in a larger operation with considerable risk of complications. We present a typical case of ASD treated surgically with a new minimally invasive method not yet performed in Hungary. We use anterolateral abdominal muscle splitting approach to reach the lumbar spine through the retroperitoneum. A discectomy is performed by retracting the psoas muscle dorsally. The intervertebral bony fusion is achieved by implanting a cage with large volume that is stuffed with autologous bone or tricalcium phosphate. A cage with large volume results in excellent annulus fibrosus tension, immediate stability and provides large surface for bony fusion. A stand-alone cage construct can be supplemented with lateral screw/rod/plate fixation. The advantage of the new technique for the treatment of ASD includes minimal blood loss, short operation time, significantly less postoperative pain and much lower complication rate. PMID:26380422

  2. Metabolomics and Its Application to Acute Lung Diseases.

    PubMed

    Stringer, Kathleen A; McKay, Ryan T; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a "snapshot" in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and

  3. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  4. Minimally invasive retroperitoneal pancreatic necrosectomy in necrotising pancreatitis.

    PubMed

    Shelat, V G; Diddapur, R K

    2007-08-01

    With the marriage of surgery and technology, applications of minimal access surgery are increasing exponentially. Pancreatic diseases are no exception. Minimally invasive retroperitoneal pancreatic necrosectomy (MIRP), or percutaneous video-assisted necrosectomy, is a new technique to debride the necrotic pancreas. We report a 51- year-old male patient who successfully underwent MIRP for infected pancreatic necrosis, and briefly review of literature. PMID:17657370

  5. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study

    PubMed Central

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

    2016-01-01

    In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10−5). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10−4) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10−6). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL. PMID:26639181

  6. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

    PubMed

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P

    2016-04-01

    In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL. PMID:26639181

  7. Bone Marrow Minimal Residual Disease Was an Early Response Marker and a Consistent Independent Predictor of Survival After Anti-GD2 Immunotherapy

    PubMed Central

    Cheung, Nai-Kong V.; Ostrovnaya, Irina; Kuk, Deborah; Cheung, Irene Y.

    2015-01-01

    Purpose Immunotherapy is a standard of care for children with high-risk neuroblastoma, where bone marrow (BM) is the predominant metastatic site. Early response markers of minimal residual disease (MRD) in the BM that are also predictive of survival could help individualize patient therapies. Patients and Methods After achieving first remission (n = 163), primary refractory disease (n = 102), or second remission (n = 95), children with stage 4 neuroblastoma received anti-GD2 3F8 antibody immunotherapy. BM MRD before 3F8 treatment and after cycle 2 (postMRD) was measured using a four-marker panel (B4GALNT1, PHOX2B, CCND1, and ISL1) by quantitative reverse transcription polymerase chain reaction. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Prognostic variables were tested in both univariable and multivariable analyses, and MRD markers were further assessed individually and in combination as binary composite (postMRD: 0 and 1) and as equal sum (postMRDSum: 0 to 4) using the Cox regression models, and their predictive accuracy was determined by the concordance index. Results When BM was evaluated after cycle 2, individual markers were highly predictive of PFS and OS. The prediction accuracy improved when they were combined in postMRDSum. A multivariable model taking into account all the variables significant in the univariable analyses identified postMRDSum to be independently predictive of PFS and OS. When the model for OS also included missing killer immunoglobulin-like receptor ligand, human antimouse antibody response, and the enrollment disease status, the concordance index was 0.704. Conclusion BM MRD after two cycles of immunotherapy was confirmed as an early response marker and a consistent independent predictor of survival. PMID:25559819

  8. Interferon-α: A Potentially Effective Treatment for Minimal Residual Disease in Acute Leukemia/Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Mo, Xiao-Dong; Zhang, Xiao-Hui; Xu, Lan-Ping; Wang, Yu; Yan, Chen-Hua; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2015-11-01

    In this prospective clinical study, the safety and efficacy of preemptive interferon-α (IFN-α) treatment were investigated and compared with preemptive donor lymphocyte infusion (DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). Patients undergoing allogeneic HSCT were eligible if they had acute leukemia or myelodysplastic syndrome and were MRD-positive after HSCT. Patients who were able to receive DLI were assigned to a preemptive DLI group (n = 45); patients who could not or did not agree to receive DLI after HSCT received preemptive IFN-α. A total of 22 patients received preemptive IFN-α; the median treatment duration was 35 days (range, 4 to 180 days). Seven patients relapsed, and 1 patient died from severe pneumonia. The 1-year cumulative incidence of chronic graft-versus-host disease (cGVHD) after intervention was 90.9% for the IFN-α group and 62.9% for the DLI group (P < .001). MRD status after preemptive intervention was comparable in the 2 groups, and the 1-year cumulative incidence of relapse after intervention was 27.3% for the IFN-α group and 35.6% for the DLI group (P = .514). The 1-year cumulative incidence of nonrelapse mortality after intervention was 4.5% for the IFN-α group and 4.4% for the DLI group (P = .985). The 1-year probability of disease-free survival after intervention was 68.2% for the IFN-α group and 60.0% for the DLI group (P = .517). In multivariate analysis, early-onset MRD, persistent MRD after intervention, and absence of cGVHD after intervention were significantly associated with poorer clinical outcomes. Thus, preemptive IFN-α may be a potential alternative for MRD-positive patients who cannot receive preemptive DLI after HSCT. PMID:26116088

  9. A Threshold-Minimization Scheme for Exploring the Energy Landscape of Biomolecules: Application to a Cyclic Peptide and a Disaccharide.

    PubMed

    Neelamraju, Sridhar; Johnston, Roy L; Schön, J Christian

    2016-05-10

    We present a scheme, called the threshold-minimization method, for globally exploring the energy landscapes of small systems of biomolecular interest where typical exploration moves always require a certain degree of subsequent structural relaxation in order to be efficient, e.g., systems containing small or large circular carbon chains such as cyclic peptides or carbohydrates. We show that using this threshold-minimization method we can not only reproduce the global minimum and relevant local minima but also overcome energetic barriers associated with different types of isomerism for the example of a cyclic peptide, cyclo-(Gly)4. We then apply the new method to the disaccharide α-d-glucopyranose-1-2-β-d-fructofuranose, report energetically preferred configurations and barriers to boat-chair isomerization in the glucopyranosyl ring, and discuss the energy landscape. PMID:27049524

  10. Minimization of the root of a quadratic functional under a system of affine equality constraints with application to portfolio management

    NASA Astrophysics Data System (ADS)

    Landsman, Zinoviy

    2008-10-01

    We present an explicit closed form solution of the problem of minimizing the root of a quadratic functional subject to a system of affine constraints. The result generalizes Z. Landsman, Minimization of the root of a quadratic functional under an affine equality constraint, J. Comput. Appl. Math. 2007, to appear, see , articles in press, where the optimization problem was solved under only one linear constraint. This is of interest for solving significant problems pertaining to financial economics as well as some classes of feasibility and optimization problems which frequently occur in tomography and other fields. The results are illustrated in the problem of optimal portfolio selection and the particular case when the expected return of finance portfolio is certain is discussed.

  11. A two-dimensional cascade solution using minimized surface singularity density distributions - with application to film cooled turbine blades

    NASA Technical Reports Server (NTRS)

    Mcfarland, E.; Tabakoff, W.; Hamed, A.

    1977-01-01

    An investigation of the effects of coolant injection on the aerodynamic performance of cooled turbine blades is presented. The coolant injection is modeled in the inviscid irrotational adiabatic flow analysis through the cascade using the distributed singularities approach. The resulting integral equations are solved using a minimized surface singularity density criteria. The aerodynamic performance was evaluated using this solution in conjunction with an existing mixing theory analysis. The results of the present analysis are compared with experimental measurements in cold flow tests.

  12. Ultrasound treatment of neurological diseases - current and emerging applications.

    PubMed

    Leinenga, Gerhard; Langton, Christian; Nisbet, Rebecca; Götz, Jürgen

    2016-03-01

    Like cardiovascular disease and cancer, neurological disorders present an increasing challenge for an ageing population. Whereas nonpharmacological procedures are routine for eliminating cancer tissue or opening a blocked artery, the focus in neurological disease remains on pharmacological interventions. Setbacks in clinical trials and the obstacle of access to the brain for drug delivery and surgery have highlighted the potential for therapeutic use of ultrasound in neurological diseases, and the technology has proved useful for inducing focused lesions, clearing protein aggregates, facilitating drug uptake, and modulating neuronal function. In this Review, we discuss milestones in the development of therapeutic ultrasound, from the first steps in the 1950s to recent improvements in technology. We provide an overview of the principles of diagnostic and therapeutic ultrasound, for surgery and transient opening of the blood-brain barrier, and its application in clinical trials of stroke, Parkinson disease and chronic pain. We discuss the promising outcomes of safety and feasibility studies in preclinical models, including rodents, pigs and macaques, and efficacy studies in models of Alzheimer disease. We also consider the challenges faced on the road to clinical translation. PMID:26891768

  13. Application of Induced Pluripotent Stem Cells in Liver Diseases

    PubMed Central

    Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

    2014-01-01

    Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

  14. miRNAs: roles and clinical applications in vascular disease.

    PubMed

    Jamaluddin, Md Saha; Weakley, Sarah M; Zhang, Lidong; Kougias, Panagiotis; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2011-01-01

    miRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease. PMID:21171923

  15. miRNAs: roles and clinical applications in vascular disease

    PubMed Central

    Jamaluddin, Md Saha; Weakley, Sarah M; Zhang, Lidong; Kougias, Panagiotis; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2011-01-01

    miRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease. PMID:21171923

  16. Comparison between Three Promising ß-emitting Radionuclides, 67Cu, 47Sc and 161Tb, with Emphasis on Doses Delivered to Minimal Residual Disease

    PubMed Central

    Champion, Christophe; Quinto, Michele A.; Morgat, Clément; Zanotti-Fregonara, Paolo; Hindié, Elif

    2016-01-01

    PURPOSE: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy β- emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of 67Cu, 47Sc and 161Tb to irradiate small tumors. METHODS: The absorbed dose deriving from a homogeneous distribution of 67Cu, 47Sc or 161Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including β- spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm3, which would result in a dose of 160 Gy if totally absorbed. RESULTS: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, 161Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with 67Cu, 14.8 Gy with 47Sc and 44.5 Gy with 161Tb. Auger and conversion electrons accounted for 71% of 161Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by 161Tb was 4.1 times higher than that from 67Cu and 8.1 times that from 47Sc. CONCLUSION: 161Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy β- emission and low-energy conversion and Auger electrons. Therefore 161Tb might be a better candidate than 67Cu and 47Sc for treating minimal residual disease in a clinical setting. PMID:27446495

  17. Influenza SIRS with Minimal Pneumonitis

    PubMed Central

    Erramilli, Shruti; Mannam, Praveen; Manthous, Constantine A.

    2016-01-01

    Although systemic inflammatory response syndrome (SIRS) is a known complication of severe influenza pneumonia, it has been reported very rarely in patients with minimal parenchymal lung disease. We here report a case of severe SIRS, anasarca, and marked vascular phenomena with minimal or no pneumonitis. This case highlights that viruses, including influenza, may cause vascular dysregulation causing SIRS, even without substantial visceral organ involvement.

  18. Minimal cosmography

    NASA Astrophysics Data System (ADS)

    Piazza, Federico; Schücker, Thomas

    2016-04-01

    The minimal requirement for cosmography—a non-dynamical description of the universe—is a prescription for calculating null geodesics, and time-like geodesics as a function of their proper time. In this paper, we consider the most general linear connection compatible with homogeneity and isotropy, but not necessarily with a metric. A light-cone structure is assigned by choosing a set of geodesics representing light rays. This defines a "scale factor" and a local notion of distance, as that travelled by light in a given proper time interval. We find that the velocities and relativistic energies of free-falling bodies decrease in time as a consequence of cosmic expansion, but at a rate that can be different than that dictated by the usual metric framework. By extrapolating this behavior to photons' redshift, we find that the latter is in principle independent of the "scale factor". Interestingly, redshift-distance relations and other standard geometric observables are modified in this extended framework, in a way that could be experimentally tested. An extremely tight constraint on the model, however, is represented by the blackbody-ness of the cosmic microwave background. Finally, as a check, we also consider the effects of a non-metric connection in a different set-up, namely, that of a static, spherically symmetric spacetime.

  19. Minimally Invasive Radiofrequency Devices.

    PubMed

    Sadick, Neil; Rothaus, Kenneth O

    2016-07-01

    This article reviews minimally invasive radiofrequency options for skin tightening, focusing on describing their mechanism of action and clinical profile in terms of safety and efficacy and presenting peer-reviewed articles associated with the specific technologies. Treatments offered by minimally invasive radiofrequency devices (fractional, microneedling, temperature-controlled) are increasing in popularity due to the dramatic effects they can have without requiring skin excision, downtime, or even extreme financial burden from the patient's perspective. Clinical applications thus far have yielded impressive results in treating signs of the aging face and neck, either as stand-alone or as postoperative maintenance treatments. PMID:27363771

  20. LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Polarisation splitting of laser beams by large angles with minimal reflection losses

    NASA Astrophysics Data System (ADS)

    Davydov, B. L.

    2006-05-01

    New crystal anisotropic prisms for splitting orthogonally polarised components of laser radiation by large angles with minimal reflection losses caused by the Brewster refraction and total internal reflection of polarised waves from the crystal—air interface are considered and the method for their calculation is described. It is shown that, by assembling glue-free combinations of two or three prisms, thermally stable beamsplitters can be fabricated, which are free from the beam astigmatism and the wave dispersion of the output angles of the beams. The parameters and properties of new beamsplitters are presented in a convenient form in figures and tables.

  1. [Atypical BCR-ABL transcripts in patients with chronic myeloid leukemia--the scheme for the diagnosis and monitoring of minimal residual disease].

    PubMed

    Link-Lenczowska, Dorota; Sacha, Tomasz; Zawada, Magdalena; Czekalska, Sylwia; Florek, Izabela; Skotnicki, Aleksander B

    2014-01-01

    More than 95% of patients with detected translocation t(9;22), is characterized by the fusion between exons e13 or e14 of BCR gene, which are located in major breakpoint cluster region (M-bcr) and exon a2 of ABL gene. These fusions are described as b2a2 (e13a2) and b3a2 (e14a2). Other fusions of exons e1, e6, e8, e12, e19, e20 of BCR gene with exons a2 or a3 of ABL gene occur very rarely and lead to formation of so called unusual fusion BCR-ABL genes. The aim of this study is to describe long-term observations of the occurrence and routine procedure in the diagnosis of atypical variants of the fusion gene BCR-ABL in a population of patients with chronic myeloid leukemia (CML). It was found that the vast majority of patients with detected BCR-ABL transcripts were b3a2 and b2a2. Other detected variants, which are described as rare were: e1a2, b2a3, b3a3, c3a2, e6a2, e6a3. At the stage of diagnosis as well as during monitoring of the effects of treatment, molecular methods which are based on polymerase chain reaction were used (multiplex RT-PCR, nested RT-PCR, RQ-PCR). Multiplex RT-PCR reaction gave possibility to detect variants of the fusion BCR-ABL gene in one reaction and was crucial in the selection of appropriate test used for further monitoring of the disease and the effectiveness of treatment. This paper proposes a scheme for dealing with the diagnosis and monitoring of minimal residual disease (MRD) in patients with CML treated with tyrosine kinase inhibitors (TKIs) in the presence of rare fusion of the BCR and ABL genes. PMID:25248240

  2. Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus

    PubMed Central

    Lim, Min Hyuk; Oh, Tae Jung; Choi, Karam; Lee, Jung Chan

    2016-01-01

    Background The oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans. Methods Plasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups. Results The insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group. Conclusion The oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans. PMID:27273909

  3. Quantification of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL) using amplicon-fusion-site polymerase chain reaction (AFS-PCR)

    PubMed Central

    2012-01-01

    The amplification of putative oncogenes is a common finding within the genome of various cancer types. Identification and further targeting of specific junction sites within the sequence of genomic amplicons (amplicon fusion sites, AFS) by PCR (AFS-PCR) is suitable for quantification of minimal residual disease (MRD). This approach has recently been developed and described for MYCN amplified neuroblastomas. To compare AFS-PCR directly to routinely used MRD diagnostic strategies, we mapped the amplified genomic regions (ampGR) of an iAMP21-amplicon in high resolution of a patient with acute lymphoblastic leukemia (ALL). Successfully, we established AFS-PCR covering junction sites between ampGR within the iAMP21-amplicon. Quantification of MRD by AFS-PCR was directly comparable to IgH/TCR based real time quantitative PCR and fluorescence activated cell sorting (FACS) analysis in consecutive bone marrow (BM) specimens. Our data give an additional proof of concept of AFS-PCR for quantification of MRD. The method could be taken into account for ALL patients with genomic amplifications as alternative MRD diagnostic, if no or qualitatively poor Ig/TCR-PCRs are available. PMID:23210797

  4. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report

    PubMed Central

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from simple steatosis to inflammation leading to fibrosis, cirrhosis, and even hepatocellular carcinoma. With the progressive epidemics of obesity and diabetes, major risk factors in the development and pathogenesis of NAFLD, the prevalence of NAFLD and its associated complications including liver failure and hepatocellular carcinoma is expected to increase by 2030 with an enormous health and economic impact. We present a patient who developed Hepatocellular carcinoma (HCC) from nonalcoholic steatohepatitis (NASH) cirrhosis. Due to morbid obesity, she was not an optimal transplant candidate and was not initially listed. After attempts for lifestyle modifications failed to lead to weight reduction, a transarterial embolization of the left gastric artery was performed. This is the sixth such procedure in humans in literature. Subsequently she had a meaningful drop in BMI from 42 to 36 over the following 6 months ultimately leading to her being listed for transplant. During this time, the left hepatic HCC was treated with chemoembolization without evidence of recurrence. In this article, we wish to highlight the use of minimally invasive percutaneous endovascular therapies such as transarterial chemoembolization (TACE) in the comprehensive management of the NAFLD spectrum and percutaneous transarterial embolization of the left gastric artery (LGA), a novel method, for the management of obesity. PMID:26629307

  5. Minimally invasive percutaneous endovascular therapies in the management of complications of non-alcoholic fatty liver disease (NAFLD): A case report.

    PubMed

    Salsamendi, Jason; Pereira, Keith; Kang, Kyungmin; Fan, Ji

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of disorders from simple steatosis to inflammation leading to fibrosis, cirrhosis, and even hepatocellular carcinoma. With the progressive epidemics of obesity and diabetes, major risk factors in the development and pathogenesis of NAFLD, the prevalence of NAFLD and its associated complications including liver failure and hepatocellular carcinoma is expected to increase by 2030 with an enormous health and economic impact. We present a patient who developed Hepatocellular carcinoma (HCC) from nonalcoholic steatohepatitis (NASH) cirrhosis. Due to morbid obesity, she was not an optimal transplant candidate and was not initially listed. After attempts for lifestyle modifications failed to lead to weight reduction, a transarterial embolization of the left gastric artery was performed. This is the sixth such procedure in humans in literature. Subsequently she had a meaningful drop in BMI from 42 to 36 over the following 6 months ultimately leading to her being listed for transplant. During this time, the left hepatic HCC was treated with chemoembolization without evidence of recurrence. In this article, we wish to highlight the use of minimally invasive percutaneous endovascular therapies such as transarterial chemoembolization (TACE) in the comprehensive management of the NAFLD spectrum and percutaneous transarterial embolization of the left gastric artery (LGA), a novel method, for the management of obesity. PMID:26629307

  6. Evaluation of allogeneic transplantation in first or later minimal residual disease - negative remission following adult-inspired therapy for acute lymphoblastic leukemia.

    PubMed

    Cassaday, Ryan D; Alan Potts, D; Stevenson, Philip A; Bar, Merav; Georges, George E; Shustov, Andrei R; Sorror, Mohamed L; Wood, Brent L; Delaney, Colleen; Doney, Kristine C; Storb, Rainer F; Sandmaier, Brenda M

    2016-09-01

    Comparisons without hematopoietic cell transplantation (HCT) to myeloablative (MAC) or reduced-intensity HCT (RIC) for adults with acute lymphoblastic leukemia (ALL) in first minimal-residual-disease negative remission (MRD(Neg) CR1) are limited. Further, the importance of MRD(Neg) following salvage therapy (MRD(Neg) CR2+) is unknown. We evaluated 89 patients in MRD(Neg) CR1 after adult-inspired treatment: 33 received MAC (12 Philadelphia chromosome [Ph]+), 17 received RIC (13 Ph+), and 39 Deferred HCT (3 Ph+). Three-year overall survival (OS) estimates for MAC, RIC, and Deferred HCT were 71%, 69%, and 68%, while 3-year event-free survival (EFS) estimates were 65%, 54%, and 28%, respectively. Further, HCT in MRD(Neg) CR1 performed similarly to MRD(Neg) CR2+: 3-year OS estimates were 70% and 69%, and 3-year EFS estimates were 62% and 62%, respectively. In conclusion, adults with ALL in MRD(Neg) CR1 following adult-inspired therapy had similar OS with or without HCT, and HCT in MRD(Neg) CR2 + can yield long-term survival. PMID:27002921

  7. Risk Factors for Metabolic Syndrome Independently Predict Arterial Stiffness and Endothelial Dysfunction in Patients With Chronic Kidney Disease and Minimal Comorbidity

    PubMed Central

    Lilitkarntakul, Pajaree; Dhaun, Neeraj; Melville, Vanessa; Kerr, Debbie; Webb, David J.; Goddard, Jane

    2012-01-01

    OBJECTIVE Metabolic syndrome (MS) is common in patients with chronic kidney disease (CKD), but its contribution to arterial stiffness and endothelial dysfunction in CKD is not well defined. We hypothesized that risk factors for MS would independently predict arterial stiffness and endothelial dysfunction in CKD patients. RESEARCH DESIGN AND METHODS Risk factors for MS, carotid-femoral pulse wave velocity (CF-PWV) and flow-mediated dilation (FMD) as measures of arterial stiffness and endothelial dysfunction, respectively, were assessed in 113 minimally comorbid CKD patients and in 23 matched control subjects. RESULTS CF-PWV correlated with systolic blood pressure (SBP), waist circumference, and plasma glucose (r2 = 0.25, 0.09, and 0.09; P < 0.01 for all). FMD correlated with SBP (r2 = 0.09; P < 0.01) and waist circumference (r2 = 0.03; P < 0.05). CF-PWV increased progressively (r2 = 0.07; P < 0.01) with increasing number of risk factors for MS. In multiple linear regression, SBP and waist circumference were independent determinants of CF-PWV, whereas only SBP predicted FMD. CONCLUSIONS The number of MS risk factors is an important determinant of arterial stiffness in CKD patients irrespective of the degree of renal impairment. Although BP remains the major determinant of arterial stiffness and endothelial dysfunction, waist circumference independently predicts arterial stiffness. MS risk factors, particularly abdominal girth, are potential targets for future interventional studies in patients with CKD. PMID:22648437

  8. Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia.

    PubMed

    Buccisano, Francesco; Maurillo, Luca; Spagnoli, Alessandra; Del Principe, Maria Ilaria; Fraboni, Daniela; Panetta, Paola; Ottone, Tiziana; Consalvo, Maria Irno; Lavorgna, Serena; Bulian, Pietro; Ammatuna, Emanuele; Angelini, Daniela F; Diamantini, Adamo; Campagna, Selenia; Ottaviani, Licia; Sarlo, Chiara; Gattei, Valter; Del Poeta, Giovanni; Arcese, William; Amadori, Sergio; Lo Coco, Francesco; Venditti, Adriano

    2010-09-30

    A total of 143 adult acute myeloid leukemia (AML) patients with available karyotype (K) and FLT3 gene mutational status were assessed for minimal residual disease (MRD) by flow cytometry. Twenty-two (16%) patients had favorable, 115 (80%) intermediate, and 6 (4%) poor risk K; 19 of 129 (15%) carried FLT3-ITD mutation. Considering postconsolidation MRD status, patients with good/intermediate-risk K who were MRD(-) had 4-year relapse-free survival (RFS) of 70% and 63%, and overall survival (OS) of 84% and 67%, respectively. Patients with good- and intermediate-risk K who were MRD(+) had 4-year RFS of 15% and 17%, and OS of 38% and 23%, respectively (P < .001 for all comparisons). FLT3 wild-type patients achieving an MRD(-) status, had a better outcome than those who remained MRD(+) (4-year RFS, 54% vs 17% P < .001; OS, 60% vs 23%, P = .002). Such an approach redefined cytogenetic/genetic categories in 2 groups: (1) low-risk, including good/intermediate K-MRD(-) with 4-year RFS and OS of 58% and 73%, respectively; and (2) high risk, including poor-risk K, FLT3-ITD mutated cases, good/intermediate K-MRD(+) categories, with RFS and OS of 22% and 17%, respectively (P < .001 for all comparisons). In AML, the integrated evaluation of baseline prognosticators and MRD improves risk-assessment and optimizes postremission therapy. PMID:20548095

  9. Diagnostic Applications of Cone-Beam CT for Periodontal Diseases

    PubMed Central

    AlJehani, Yousef A.

    2014-01-01

    Objectives. This paper aims to review the diagnostic application of cone beam computed tomography (CBCT) in the field of periodontology. Data. Original articles that reported on the use of CBCT for periodontal disease diagnosis were included. Sources. MEDLINE (1990 to January 2014), PubMed (using medical subject headings), and Google Scholar were searched using the following terms in different combinations: “CBCT,” “volumetric CT,” “periodontal disease ,” and “periodontitis.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Conclusions. Bony defects, caters, and furcation involvements seem to be better depicted on CBCT, whereas bone quality and periodontal ligament space scored better on conventional intraoral radiography. CBCT does not offer a significant advantage over conventional radiography for assessing the periodontal bone levels. PMID:24803932

  10. Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232.

    PubMed

    Borowitz, Michael J; Wood, Brent L; Devidas, Meenakshi; Loh, Mignon L; Raetz, Elizabeth A; Salzer, Wanda L; Nachman, James B; Carroll, Andrew J; Heerema, Nyla A; Gastier-Foster, Julie M; Willman, Cheryl L; Dai, Yunfeng; Winick, Naomi J; Hunger, Stephen P; Carroll, William L; Larsen, Eric

    2015-08-20

    Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children's Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in subjects randomized in a 2 × 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD ≥0.1% or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD <0.01% had a 5-year event-free survival (EFS) of 87% ± 1% vs 74% ± 4% for those with MRD 0.01% to 0.1%; increasing MRD amounts was associated with progressively worse outcome. Subjects converting from MRD positive to negative by end consolidation had a relatively favorable 79% ± 5% 5-year disease-free survival vs 39% ± 7% for those with MRD ≥0.01%. Although HD-MTX was superior to C-MTX, MRD retained prognostic significance in both groups (86% ± 2% vs 58% ± 4% for MRD-negative vs positive C-MTX subjects; 88% ± 2% vs 68% ± 4% for HD-MTX subjects). Intensified therapy given to subjects with MRD >0.1% did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1% to 1% MRD crossing those with 0.01% to 0.1% MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome. This trial was registered at www.clinicaltrials.gov as #NCT00075725. PMID:26124497

  11. Pharmacogenomics: Application to the Management of Cardiovascular Disease

    PubMed Central

    Johnson, JA; Cavallari, LH; Beitelshees, AL; Lewis, JP; Shuldiner, AR; Roden, DM

    2011-01-01

    The past decade has seen substantial advances in cardiovascular pharmacogenomics. Genetic determinants of response to clopidogrel and warfarin have been defined, resulting in changes to the product labels for these drugs that suggest the use of genetic information as a guide for therapy. Genetic tests are available, as are guidelines for incorporation of genetic information into patient-care decisions. These guidelines and the literature supporting them are reviewed herein. Significant advances have also been made in the pharmacogenomics of statin-induced myopathy and the response to β-blockers in heart failure, although the clinical applications of these findings are less clear. Other areas hold promise, including the pharmacogenomics of antihypertensive drugs, aspirin, and drug-induced long-QT syndrome (diLQTS). The potential value of pharmacogenomics in the discovery and development of new drugs is also described. In summary, pharmacogenomics has current applications in the management of cardiovascular disease, with clinically relevant data continuing to mount. PMID:21918509

  12. An application of genetic algorithms to the network reconfiguration in distribution for loss minimization and load balancing problem (part 2)

    SciTech Connect

    Choi, D.S.; Hasegawa, Jun; Kim, C.S.

    1995-12-31

    Network reconfiguration in distribution system is realized by changing the status of sectionalizing switches, and is usually done for loss reducing or for load balancing in the system. This paper presents a new method which applies a genetic algorithm for determining which sectionalizing switch to operate in order to solve the distribution system loss minimization reconfiguration problem. In addition, the proposed method introduces a new limited life feature for performing natural selection of individuals. Simulations were carried out in order to verify the effectiveness of the proposed method. These results showed that the proposed method is effective in dealing with the problems of homogeneity and genetic drift associated with the population in the initial state.

  13. Application of the method of data reconciliation for minimizing uncertainty of the weight function in the multicriteria optimization model

    NASA Astrophysics Data System (ADS)

    Mendecka, Barbara; Kozioł, Joachim

    2015-03-01

    The multicriteria decision process consists of five main steps: definition of the optimisation problem, determination of the weight structure of the decision criteria, design of the evaluation matrix, selection of the optimal evaluation method and ranking of solutions. It is often difficult to obtain the optimal solution to a multicriterion problem. The main reason is the subjective element of the model - the weight functions of the decision criteria. Expert opinions are usually taken into account in their determination. The aim of this article is to present a novel method of minimizing the uncertainty of the weights of the decision criteria using Monte Carlo simulation and method of data reconciliation. The proposed method is illustrated by the example of multicriterion social effectiveness evaluation for electric power supply to a building using renewable energy sources.

  14. Is demography destiny? Application of machine learning techniques to accurately predict population health outcomes from a minimal demographic dataset.

    PubMed

    Luo, Wei; Nguyen, Thin; Nichols, Melanie; Tran, Truyen; Rana, Santu; Gupta, Sunil; Phung, Dinh; Venkatesh, Svetha; Allender, Steve

    2015-01-01

    For years, we have relied on population surveys to keep track of regional public health statistics, including the prevalence of non-communicable diseases. Because of the cost and limitations of such surveys, we often do not have the up-to-date data on health outcomes of a region. In this paper, we examined the feasibility of inferring regional health outcomes from socio-demographic data that are widely available and timely updated through national censuses and community surveys. Using data for 50 American states (excluding Washington DC) from 2007 to 2012, we constructed a machine-learning model to predict the prevalence of six non-communicable disease (NCD) outcomes (four NCDs and two major clinical risk factors), based on population socio-demographic characteristics from the American Community Survey. We found that regional prevalence estimates for non-communicable diseases can be reasonably predicted. The predictions were highly correlated with the observed data, in both the states included in the derivation model (median correlation 0.88) and those excluded from the development for use as a completely separated validation sample (median correlation 0.85), demonstrating that the model had sufficient external validity to make good predictions, based on demographics alone, for areas not included in the model development. This highlights both the utility of this sophisticated approach to model development, and the vital importance of simple socio-demographic characteristics as both indicators and determinants of chronic disease. PMID:25938675

  15. Progress on conformal microwave array applicators for heating chestwall disease

    NASA Astrophysics Data System (ADS)

    Stauffer, P. R.; Maccarini, P. F.; Juang, T.; Jacobsen, S. K.; Gaeta, C. J.; Schlorff, J. L.; Milligan, A. J.

    2007-02-01

    Previous studies have reported the computer modeling, CAD design, and theoretical performance of single and multiple antenna arrays of Dual Concentric Conductor (DCC) square slot radiators driven at 915 and 433 MHz. Subsequently, practical CAD designs of microstrip antenna arrays constructed on thin and flexible printed circuit board (PCB) material were reported which evolved into large Conformal Microwave Array (CMA) sheets that could wrap around the surface of the human torso for delivering microwave energy to large areas of superficial tissue. Although uniform and adjustable radiation patterns have been demonstrated from multiple element applicators radiating into simple homogeneous phantom loads, the contoured and heterogeneous tissue loads typical of chestwall recurrent breast cancer have required additional design efforts to achieve good coupling and efficient heating from the increasingly larger conformal array applicators used to treat large area contoured patient anatomy. Thus recent work has extended the theoretical optimization of DCC antennas to improve radiation efficiency of each individual aperture and reduce mismatch reflections, radiation losses, noise, and cross coupling of the feedline distribution network of large array configurations. Design improvements have also been incorporated into the supporting bolus structure to maintain effective coupling of DCC antennas into contoured anatomy and to monitor and control surface temperatures under the entire array. New approaches for non-invasive monitoring of surface and sub-surface tissue temperatures under each independent heat source are described that make use of microwave radiometry and flexible sheet grid arrays of thermal sensors. Efforts to optimize the clinical patient interface and move from planar rectangular shapes to contoured vest applicators that accommodate entire disease in a larger number of patients are summarized. By applying heat more uniformly to large areas of contoured anatomy

  16. An image-intensive ePR for image-guided minimally invasive spine surgery applications including real-time intra-operative image acquisition, archival, and display

    NASA Astrophysics Data System (ADS)

    Documet, Jorge R.; Le, Anh; Liu, Brent; Huang, H. K.; Chiu, John

    2009-02-01

    Recent developments in medical imaging informatics have improved clinical workflow in Radiology enterprise but gaps remain in the clinical workflow from diagnosis to surgical treatment through post-operative follow-up. One solution to bridge this gap is the development of an electronic patient record (ePR) that integrates key imaging and informatics data during the pre, intra, and post-operative phases of clinical workflow. We present an ePR system based on standards and tailored to the clinical application for image-guided minimally invasive spinal surgery (MISS). The ePR system has been implemented in a clinical environment for a half-year.

  17. Minimal Identifiable Disease and the Role of Conditioning Intensity in Hematopoietic Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Evolving from Myelodysplastic Syndrome.

    PubMed

    Festuccia, Moreno; Deeg, H Joachim; Gooley, Theodore A; Baker, Kelsey; Wood, Brent L; Fang, Min; Sandmaier, Brenda M; Scott, Bart L

    2016-07-01

    Allogeneic hematopoietic cell transplantation (HCT) is the only known treatment with curative potential for myelodysplastic syndrome, but relapse is a major cause of failure. We studied results in 289 patients transplanted between June 2004 and December 2013. Minimal identifiable disease (MID) markers pre-HCT were determined by multiparameter flow cytometry (MFC) and cytogenetics on marrow aspirates. The impact of MID on outcome after low- and high-intensity conditioning HCT was determined. Among 287 assessable patients, 68 (23.7%) had more than 5% marrow blasts at HCT; 219 patients were in morphologic remission but 154 (53.7%) were MID positive, whereas 65 (22.6%) were MID negative. The impact of MID on outcome was significantly different between patients who received low-intensity conditioning and patients who received a high-intensity regimen. The impact of conditioning intensity differed across the various MID categories. In particular, the risk of overall mortality was higher with low-intensity than with high-intensity regimens for patients who were positive for MID by cytogenetics regardless of positivity by MFC (HR, 1.67 if MFC positive/cytogenetics positive, HR, 7.23 if MFC negative/cytogenetics positive). On the other hand, patients who were MID negative by both MFC and cytogenetics had similar risks of mortality with low- and high-intensity regimens (HR, .99). The main factor responsible for mortality after low-intensity conditioning in MID-positive patients was relapse. The presence of MID should be considered when deciding on conditioning intensity because it identifies subgroups of patients who may benefit from high- or low-intensity conditioning. PMID:27064057

  18. Estimation of molecular upper remission limit for monitoring minimal residual disease in peripheral blood of acute myeloid leukemia patients by WT1 expression

    PubMed Central

    POLÁK, JAROSLAV; HÁJKOVÁ, HANA; MAALAUFOVÁ-SOUKUPOVÁ, JACQUELINE; MARKOVÁ, JANA; ŠÁLEK, CYRIL; SCHWARZ, JIŘÍ; HAŠKOVEC, CEDRIK

    2012-01-01

    To date, approximately one half of acute myeloid leukaemia (AML) patients do not have a suitable specific molecular marker for monitoring minimal residual disease (MRD). The Wilm’s tumour gene (WT1) has been suggested as a possible molecular marker of MRD in AML. The expression of WT1 in peripheral blood (PB) was measured using quantitative real-time reverse transcription-polymerase chain reaction in peripheral leukocytes from 151 patients with AML at diagnosis. WT1 expression was significantly elevated, i.e. up to 3 orders of magnitude in the majority (80%) of AML patients at diagnosis compared to the PB of healthy donors. Sequence samples of the long-term followed-up AML patients treated with chemotherapy and/or allogeneic bone marrow transplantation were analysed for WT1 expression. The results revealed that the hematological relapses were preceded (median, 1.8 months) by an increase in WT1 gene expression. For the practical utility of this gene as a molecular marker of relapse, it was necessary to determine an upper remission limit, crossing which would signal hematological relapse. The upper remission limit was determined in our set of patients to be 0.02 WT1/ABL. The AML patients who consequently relapsed crossed this upper remission limit; however, those in permanent remission did not. Therefore, this upper remission limit could be taken as the border of molecular relapse of AML patients. Moreover, insufficient decline of WT1 expression under the upper remission limit following induction and/or consolidation therapy was associated with markedly high risk of relapse. The results show that our upper remission limit can be taken as the border of molecular relapse of AML patients and WT1 levels following initial therapy as a beneficial prognostic marker. PMID:22969857

  19. Minimal hepatic glucose-6-phosphatase-α activity required to sustain survival and prevent hepatocellular adenoma formation in murine glycogen storage disease type Ia

    PubMed Central

    Lee, Young Mok; Kim, Goo-Young; Pan, Chi-Jiunn; Mansfield, Brian C.; Chou, Janice Y.

    2015-01-01

    Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. In a previous 70–90 week-study, we showed that a recombinant adeno-associated virus (rAAV) vector-mediated gene transfer that restores more than 3% of wild-type hepatic G6Pase-α activity in G6pc−/− mice corrects hepatic G6Pase-α deficiency with no evidence of HCA. We now examine the minimal hepatic G6Pase-α activity required to confer therapeutic efficacy. We show that rAAV-treated G6pc−/− mice expressing 0.2% of wild-type hepatic G6Pase-α activity suffered from frequent hypoglycemic seizures at age 63–65 weeks but mice expressing 0.5–1.3% of wild-type hepatic G6Pase-α activity (AAV-LL mice) sustain 4–6 h of fast and grow normally to age 75–90 weeks. Despite marked increases in hepatic glycogen accumulation, the AAV-LL mice display no evidence of hepatic abnormalities, hepatic steatosis, or HCA. Interprandial glucose homeostasis is maintained by the G6Pase-α/glucose-6-phosphate transporter (G6PT) complex, and G6PT-mediated microsomal G6P uptake is the rate-limiting step in endogenous glucose production. We show that hepatic G6PT activity is increased in AAV-LL mice. These findings are encouraging for clinical studies of G6Pase-α gene-based therapy for GSD-Ia. PMID:26937391

  20. Minimization of the Vibration Energy of Thin-Plate Structures and the Application to the Reduction of Gearbox Vibration

    NASA Technical Reports Server (NTRS)

    Inoue, Katsumi; Krantz, Timothy L.

    1995-01-01

    While the vibration analysis of gear systems has been developed, a systematic approach to the reduction of gearbox vibration has been lacking. The technique of reducing vibration by shifting natural frequencies is proposed here for gearboxes and other thin-plate structures using the theories of finite elements, modal analysis, and optimization. A triangular shell element with 18 degrees of freedom is developed for structural and dynamic analysis. To optimize, the overall vibration energy is adopted as the objective function to be minimized at the excitation frequency by varying the design variable (element thickness) under the constraint of overall constant weight. Modal analysis is used to determine the sensitivity of the vibration energy as a function of the eigenvalues and eigenvectors. The optimum design is found by the gradient projection method and a unidimensional search procedure. By applying the computer code to design problems for beams and plates, it was verified that the proposed method is effective in reducing vibration energy. The computer code is also applied to redesign the NASA Lewis gear noise rig test gearbox housing. As one example, only the shape of the top plate is varied, and the vibration energy levels of all the surfaces are reduced, yielding an overall reduction of 1/5 compared to the initial design. As a second example, the shapes of the top and two side plates are varied to yield an overall reduction in vibration energy of 1/30.

  1. Application of optical spectroscopic techniques for disease diagnosis

    NASA Astrophysics Data System (ADS)

    Saha, Anushree

    Optical spectroscopy, a truly non-invasive tool for remote diagnostics, is capable of providing valuable information on the structure and function of molecules. However, most spectroscopic techniques suffer from drawbacks, which limit their application. As a part of my dissertation work, I have developed theoretical and experimental methods to address the above mentioned issues. I have successfully applied these methods for monitoring the physical, chemical and biochemical parameters of biomolecules involved in some specific life threatening diseases like lead poisoning and age-related macular degeneration (AMD). I presented optical studies of melanosomes, which are one of the vital organelles in the human eye, also known to be responsible for a disease called age-related macular degeneration (AMD), a condition of advanced degeneration which causes progressive blindness. I used Raman spectroscopy, to first chemically identify the composition of melanosome, and then monitor the changes in its functional and chemical behavior due to long term exposure to visible light. The above study, apart from explaining the role of melanosomes in AMD, also sets the threshold power for lasers used in surgeries and other clinical applications. In the second part of my dissertation, a battery of spectroscopic techniques was successfully applied to explore the different binding sites of lead ions with the most abundant carrier protein molecule in our circulatory system, human serum albumin. I applied optical spectroscopic tools for ultrasensitive detection of heavy metal ions in solution which can also be used for lead detection at a very early stage of lead poisoning. Apart from this, I used Raman microspectroscopy to study the chemical alteration occurring inside a prostate cancer cell as a result of a treatment with a low concentrated aqueous extract of a prospective drug, Nerium Oleander. The experimental methods used in this study has tremendous potential for clinical

  2. Minimizing the Risk of Disease Transmission in Emergency Settings: Novel In Situ Physico-Chemical Disinfection of Pathogen-Laden Hospital Wastewaters.

    PubMed

    Sozzi, Emanuele; Fabre, Kerline; Fesselet, Jean-François; Ebdon, James E; Taylor, Huw

    2015-01-01

    'Coalition for Cholera Prevention and Control' recently highlighted the research as meriting serious consideration and further study. Further applications of the method to other emergency settings are being actively explored by the authors through discussion with the World Health Organization with regards to the ongoing Ebola outbreak in West Africa, and with the UK-based NGO Oxfam with regards to excreta-borne disease management in the Philippines and Myanmar, as a component of post-disaster incremental improvements to local sanitation chains. PMID:26110821

  3. Minimizing the Risk of Disease Transmission in Emergency Settings: Novel In Situ Physico-Chemical Disinfection of Pathogen-Laden Hospital Wastewaters

    PubMed Central

    Sozzi, Emanuele; Fabre, Kerline; Fesselet, Jean-François; Ebdon, James E.; Taylor, Huw

    2015-01-01

    ‘Coalition for Cholera Prevention and Control’ recently highlighted the research as meriting serious consideration and further study. Further applications of the method to other emergency settings are being actively explored by the authors through discussion with the World Health Organization with regards to the ongoing Ebola outbreak in West Africa, and with the UK-based NGO Oxfam with regards to excreta-borne disease management in the Philippines and Myanmar, as a component of post-disaster incremental improvements to local sanitation chains. PMID:26110821

  4. Three-dimensional elastic image registration based on strain energy minimization: application to prostate magnetic resonance imaging.

    PubMed

    Zhang, Bao; Arola, Dwayne D; Roys, Steve; Gullapalli, Rao P

    2011-08-01

    The use of magnetic resonance (MR) imaging in conjunction with an endorectal coil is currently the clinical standard for the diagnosis of prostate cancer because of the increased sensitivity and specificity of this approach. However, imaging in this manner provides images and spectra of the prostate in the deformed state because of the insertion of the endorectal coil. Such deformation may lead to uncertainties in the localization of prostate cancer during therapy. We propose a novel 3-D elastic registration procedure that is based on the minimization of a physically motivated strain energy function that requires the identification of similar features (points, curves, or surfaces) in the source and target images. The Gauss-Seidel method was used in the numerical implementation of the registration algorithm. The registration procedure was validated on synthetic digital images, MR images from prostate phantom, and MR images obtained on patients. The registration error, assessed by averaging the displacement of a fiducial landmark in the target to its corresponding point in the registered image, was 0.2 ± 0.1 pixels on synthetic images. On the prostate phantom and patient data, the registration errors were 1.0 ± 0.6 pixels (0.6 ± 0.4 mm) and 1.8 ± 0.7 pixels (1.1 ± 0.4 mm), respectively. Registration also improved image similarity (normalized cross-correlation) from 0.72 ± 0.10 to 0.96 ± 0.03 on patient data. Registration results on digital images, phantom, and prostate data in vivo demonstrate that the registration procedure can be used to significantly improve both the accuracy of localized therapies such as brachytherapy or external beam therapy and can be valuable in the longitudinal follow-up of patients after therapy. PMID:20552248

  5. Immunological GABAergic interactions and therapeutic applications in autoimmune diseases.

    PubMed

    Prud'homme, Gérald J; Glinka, Yelena; Wang, Qinghua

    2015-11-01

    Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. However, it is also produced in other sites; notably by pancreatic β cells and immune cells. The function of GABA in the immune system is at an early stage of study, but it exerts inhibitory effects that are relevant to autoimmune diseases. The study of GABAergic interactions in the immune system has centered on three main aspects: 1) the expression of GABA and the relevant GABAergic molecular machinery; 2) the in vitro response of immune cells; and 3) therapeutic applications in autoimmune diseases. T cells and macrophages can produce GABA, and express all the components necessary for a GABAergic response. There are two types of GABA receptors, but lymphocytes appear to express only type A (GABAAR); a ligand-gated chloride channel. Other immune cells may also express the type B receptor (GABABR); a G-protein coupled receptor. Activation of GABA receptors on T cells and macrophages inhibits responses such as production of inflammatory cytokines. In T cells, GABA blocks the activation-induced calcium signal, and it also inhibits NF-κB activation. In preclinical models, therapeutic application of GABA, or GABAergic (agonistic) drugs, protects against type 1 diabetes (T1D), experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and contact dermatitis. In addition, GABA exerts anti-apoptotic and proliferative effects on islet β cells, which may be applicable to islet transplantation. Autoimmunity against glutamic acid decarboxylase 65 (GAD65; synthesizes GABA) occurs in T1D. Antigen therapy of T1D with GAD65 or proinsulin in mice has protective effects, which are markedly enhanced by combined GABA therapy. Clinically, autoantibodies against GAD65 and/or GABA receptors play a pathogenic role in several neurological conditions, including stiff person syndrome (SPS), some forms of encephalitis, and autoimmune epilepsy. GABAergic drugs are widely used in

  6. Herbal Products: Benefits, Limits, and Applications in Chronic Liver Disease

    PubMed Central

    Del Prete, Anna; Scalera, Antonella; Iadevaia, Maddalena Diana; Miranda, Agnese; Zulli, Claudio; Gaeta, Laura; Tuccillo, Concetta; Federico, Alessandro; Loguercio, Carmelina

    2012-01-01

    Complementary and alternative medicine soughts and encompasses a wide range of approaches; its use begun in ancient China at the time of Xia dynasty and in India during the Vedic period, but thanks to its long-lasting curative effect, easy availability, natural way of healing, and poor side-effects it is gaining importance throughout the world in clinical practice. We conducted a review describing the effects and the limits of using herbal products in chronic liver disease, focusing our attention on those most known, such as quercetin or curcumin. We tried to describe their pharmacokinetics, biological properties, and their beneficial effects (as antioxidant role) in metabolic, alcoholic, and viral hepatitis (considering that oxidative stress is the common pathway of chronic liver diseases of different etiology). The main limit of applicability of CAM comes from the lacking of randomized, placebo-controlled clinical trials giving a real proof of efficacy of those products, so that anecdotal success and personal experience are frequently the driving force for acceptance of CAM in the population. PMID:22991573

  7. Breath Analysis in Disease Diagnosis: Methodological Considerations and Applications

    PubMed Central

    Lourenço, Célia; Turner, Claire

    2014-01-01

    Breath analysis is a promising field with great potential for non-invasive diagnosis of a number of disease states. Analysis of the concentrations of volatile organic compounds (VOCs) in breath with an acceptable accuracy are assessed by means of using analytical techniques with high sensitivity, accuracy, precision, low response time, and low detection limit, which are desirable characteristics for the detection of VOCs in human breath. “Breath fingerprinting”, indicative of a specific clinical status, relies on the use of multivariate statistics methods with powerful in-built algorithms. The need for standardisation of sample collection and analysis is the main issue concerning breath analysis, blocking the introduction of breath tests into clinical practice. This review describes recent scientific developments in basic research and clinical applications, namely issues concerning sampling and biochemistry, highlighting the diagnostic potential of breath analysis for disease diagnosis. Several considerations that need to be taken into account in breath analysis are documented here, including the growing need for metabolomics to deal with breath profiles. PMID:24957037

  8. A simple strategy for implementing standard reference terminologies in a distributed healthcare delivery system with minimal impact to existing applications.

    PubMed

    Bouhaddou, Omar; Lincoln, Michael J; Maulden, Sarah; Murphy, Holli; Warnekar, Pradnya; Nguyen, Viet; Lam, Siew; Brown, Steven H; Frankson, Ferdinand J; Crandall, Glen; Hughes, Carla; Sigley, Roger; Insley, Marcia; Graham, Gail

    2006-01-01

    The Veterans Administration (VA) has adopted an ambitious program to standardize its clinical terminology to comply with industry-wide standards. The VA is using commercially available tools and in-house software to create a high-quality reference terminology system. The terminology will be used by current and future applications with no planned disruption to operational systems. The first large customer of the group is the national VA Health Data Repository (HDR). Unique enterprise identifiers are assigned to each standard term, and a rich network of semantic relationships makes the resulting data not only recognizable, but highly computable and reusable in a variety of applications, including decision support and data sharing with partners such as the Department of Defense (DoD). This paper describes the specific methods and approaches that the VA has employed to develop and implement this innovative program in existing information system. The goal is to share with others our experience with key issues that face our industry as we move toward an electronic health record for every individual. PMID:17238306

  9. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

    PubMed

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-01-01

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02-5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL. PMID:27427275

  10. Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL

    PubMed Central

    Dawidowska, Małgorzata; Kosmalska, Maria; Sędek, Łukasz; Szczepankiewicz, Aleksandra; Twardoch, Magdalena; Sonsala, Alicja; Szarzyńska-Zawadzka, Bronisława; Derwich, Katarzyna; Lejman, Monika; Pawelec, Katarzyna; Obitko-Płudowska, Agnieszka; Pawińska-Wąsikowska, Katarzyna; Kwiecińska, Kinga; Kołtan, Andrzej; Dyla, Agnieszka; Grzeszczak, Władysław; Kowalczyk, Jerzy R.; Szczepański, Tomasz; Ziętkiewicz, Ewa; Witt, Michał

    2016-01-01

    Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07–5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05–3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02–5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28–12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61–28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL. PMID:27427275