Science.gov

Sample records for minimal disease application

  1. 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 ...

  2. 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.

  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 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

  9. 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

  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

    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

  4. 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

  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

    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

  10. 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

  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. 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

  17. 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

  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 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

  6. 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

  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 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  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. 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

  19. 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

  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 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

  5. 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

  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. 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.

  18. 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.

  19. 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

  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. 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

  5. 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

  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. 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

  20. 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

  1. 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

  2. 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

  3. 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

  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. 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

  10. 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

  11. 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

  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. 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

  15. 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

  16. 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

  17. 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

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  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. 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

  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. 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.

  7. 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

  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 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

  13. 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

  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. 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.

  20. 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

  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. 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

  7. 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.

  8. [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

  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

    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

  19. 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

  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 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

  3. 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

  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. 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

  13. 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

  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. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  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. 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.

  12. 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.

  13. 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

  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. 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

  18. 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

  19. 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

  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

  11. Neurostimulation in Alzheimer's disease: from basic research to clinical applications.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Tezzon, Frediano; Christova, Monica; Schwenker, Kerstin; Golaszewski, Stefan; Trinka, Eugen; Brigo, Francesco

    2015-05-01

    The development of different methods of brain stimulation provides a promising therapeutic tool with potentially beneficial effects on subjects with impaired cognitive functions. We performed a systematic review of the studies published in the field of neurostimulation in Alzheimer's disease (AD), from basic research to clinical applications. The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD. Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients. PMID:25721941

  12. Strategies for minimizing nosocomial measles transmission.

    PubMed Central

    Biellik, R. J.; Clements, C. J.

    1997-01-01

    As a result of the highly contagious nature of measles before the onset of rash, nosocomial transmission will remain a threat until the disease is eradicated. However, a number of strategies can minimize its nosocomial spread. It is therefore vital to maximize awareness among health care staff that an individual with measles can enter a health facility at any time and that a continual risk of the nosocomial transmission of measles exists. The present review makes two groups of recommendations: those which are generally applicable to all countries, and certain additional recommendations which may be suitable only for industrialized countries. PMID:9342896

  13. Minimally invasive radioguided parathyroidectomy.

    PubMed

    Costello, D; Norman, J

    1999-07-01

    The last decade has been characterized by an emphasis on minimizing interventional techniques, hospital stays, and overall costs of patient care. It is clear that most patients with sporadic HPT do not require a complete neck exploration. We now know that a minimal approach is appropriate for this disease. Importantly, the MIRP technique can be applied to most patients with sporadic HPT and can be performed by surgeons with modest advanced training. The use of a gamma probe as a surgical tool converts the sestamibi to a functional and anatomical scan eliminating the need for any other preoperative localizing study. Quantification of the radioactivity within the removed gland eliminates the need for routine frozen section histologic examination and obviates the need for costly intraoperative parathyroid hormone measurements. This radioguided technique allows the benefit of local anesthesia, dramatically reduces operative times, eliminates postoperative blood tests, provides a smaller scar, requires minimal time spent in the hospital, and almost assures a rapid, near pain-free recovery. This combination is beneficial to the patient whereas helping achieve a reduction in overall costs. PMID:10448697

  14. Minimization and Mitigation of Wire EDM Cutting Errors in the Application of the Contour Method of Residual Stress Measurement

    NASA Astrophysics Data System (ADS)

    Ahmad, Bilal; Fitzpatrick, Michael E.

    2016-01-01

    The contour method of residual stress measurement relies on the careful application of wire electro-discharge machining (WEDM) for the cutting stage. Changes in material removal rates during the cut lead to errors in the final calculated values of residual stress. In this study, WEDM cutting parameters have been explored to identify the optimum conditions for contour method residual stress measurements. The influence of machine parameters on the surface roughness and cutting artifacts in the contour cut is discussed. It has been identified that the critical parameter in improving the surface finish is the spark pulse duration. A typical cutting artifact and its impact on measured stress values have been identified and demonstrated for a contour cut in a welded marine steel. A procedure is presented to correct contour displacement data from the influence of WEDM cutting artifacts, and is demonstrated on the correction of a measured weld residual stress. The corrected contour method improved the residual stress magnitude up to 150 MPa. The corrected contour method results were validated by X-ray diffraction, incremental center hole drilling, and neutron diffraction.

  15. Tailoring the optimal control cost function to a desired output: application to minimizing phase errors in short broadband excitation pulses

    NASA Astrophysics Data System (ADS)

    Skinner, Thomas E.; Reiss, Timo O.; Luy, Burkhard; Khaneja, Navin; Glaser, Steffen J.

    2005-01-01

    The de facto standard cost function has been used heretofore to characterize the performance of pulses designed using optimal control theory. The freedom to choose new, creative quality factors designed for specific purposes is demonstrated. While the methodology has more general applicability, its utility is illustrated by comparison to a consistently chosen example—broadband excitation. The resulting pulses are limited to the same maximum RF amplitude used previously and tolerate the same variation in RF homogeneity deemed relevant for standard high-resolution NMR probes. Design criteria are unchanged: transformation of Iz → Ix over resonance offsets of ±20 kHz and RF variability of ±5%, with a peak RF amplitude equal to 17.5 kHz. However, the new cost effectively trades a small increase in residual z magnetization for improved phase in the transverse plane. Compared to previous broadband excitation by optimized pulses (BEBOP), significantly shorter pulses are achievable, with only marginally reduced performance. Simulations transform Iz to greater than 0.98 Ix, with phase deviations of the final magnetization less than 2°, over the targeted ranges of resonance offset and RF variability. Experimental performance is in excellent agreement with the simulations.

  16. Aqueous cationic, anionic and non-ionic multi-walled carbon nanotubes, functionalised with minimal framework damage, for biomedical application

    PubMed Central

    Chen, Shu; Hu, Sheng; Smith, Elizabeth F.; Ruenraroengsak, Pakatip; Thorley, Andrew J.; Menzel, Robert; Goode, Angela E.; Ryan, Mary P.; Tetley, Teresa D.; Porter, Alexandra E.; Shaffer, Milo S. P.

    2014-01-01

    The use of a thermochemical grafting approach provides a versatile means to functionalise as-synthesised, bulk multi-walled carbon nanotubes (MWNTs) without altering their inherent structure. The associated retention of properties is desirable for a wide range of commercial applications, including for drug delivery and medical purposes; it is also pertinent to studies of intrinsic toxicology. A systematic series of water-compatible MWNTs, with diameter around 12 nm have been prepared, to provide structurally-equivalent samples predominantly stabilised by anionic, cationic, or non-ionic groups. The surface charge of MWNTs was controlled by varying the grafting reagents and subsequent post-functionalisation modifications. The degree of grafting was established by thermal analysis (TGA). High resolution transmission electron microscope (HRTEM) and Raman measurements confirmed that the structural framework of the MWNTs was unaffected by the thermochemical treatment, in contrast to a conventional acid-oxidised control which was severely damaged. The effectiveness of the surface modification was demonstrated by significantly improved solubility and stability in both water and cell culture medium, and further quantified by zeta-potential analysis. The grafted MWNTs exhibited relatively low bioreactivity on human immortal alveolar epithelial type 1-like cells (TT1) following 24h exposure as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) and lactate dehydrogenase release (LDH) assays. The exposure of TT1 cells to MWNTs suppressed the release of the inflammatory mediators, interleukin 6 (IL-6) and interleukin 8 (IL-8). TEM cell uptake studies indicated efficient cellular entry of MWNTs into TT1 cells, via a range of mechanisms. Cationic MWNTs showed a more substantial interaction with TT1 cell membranes than anionic MWNTs, demonstrating a surface charge effect on cell uptake. PMID:24631251

  17. Minimally invasive pancreatic surgery – a review

    PubMed Central

    Damoli, Isacco; Ramera, Marco; Paiella, Salvatore; Marchegiani, Giovanni; Bassi, Claudio

    2015-01-01

    During the past 20 years the application of a minimally invasive approach to pancreatic surgery has progressively increased. Distal pancreatectomy is the most frequently performed procedure, because of the absence of a reconstructive phase. However, middle pancreatectomy and pancreatoduodenectomy have been demonstrated to be safe and feasible as well. Laparoscopic distal pancreatectomy is recognized as the gold standard treatment for small tumors of the pancreatic body-tail, with several advantages over the traditional open approach in terms of patient recovery. The surgical treatment of lesions of the pancreatic head via a minimally invasive approach is still limited to a few highly experienced surgeons, due to the very challenging resection and complex anastomoses. Middle pancreatectomy and enucleation are indicated for small and benign tumors and offer the maximum preservation of the parenchyma. The introduction of a robotic platform more than ten years ago increased the interest of many surgeons in minimally invasive treatment of pancreatic diseases. This new technology overcomes all the limitations of laparoscopic surgery, but actual benefits for the patients are still under investigation. The increased costs associated with robotic surgery are under debate too. This article presents the state of the art of minimally invasive pancreatic surgery. PMID:26240612

  18. Minimally invasive mediastinal surgery

    PubMed Central

    Melfi, Franca M. A.; Mussi, Alfredo

    2016-01-01

    In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a “no-touch” technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally

  19. Minimally invasive mediastinal surgery.

    PubMed

    Melfi, Franca M A; Fanucchi, Olivia; Mussi, Alfredo

    2016-01-01

    In the past, mediastinal surgery was associated with the necessity of a maximum exposure, which was accomplished through various approaches. In the early 1990s, many surgical fields, including thoracic surgery, observed the development of minimally invasive techniques. These included video-assisted thoracic surgery (VATS), which confers clear advantages over an open approach, such as less trauma, short hospital stay, increased cosmetic results and preservation of lung function. However, VATS is associated with several disadvantages. For this reason, it is not routinely performed for resection of mediastinal mass lesions, especially those located in the anterior mediastinum, a tiny and remote space that contains vital structures at risk of injury. Robotic systems can overcome the limits of VATS, offering three-dimensional (3D) vision and wristed instrumentations, and are being increasingly used. With regards to thymectomy for myasthenia gravis (MG), unilateral and bilateral VATS approaches have demonstrated good long-term neurologic results with low complication rates. Nevertheless, some authors still advocate the necessity of maximum exposure, especially when considering the distribution of normal and ectopic thymic tissue. In recent studies, the robotic approach has shown to provide similar neurological outcomes when compared to transsternal and VATS approaches, and is associated with a low morbidity. Importantly, through a unilateral robotic technique, it is possible to dissect and remove at least the same amount of mediastinal fat tissue. Preliminary results on early-stage thymomatous disease indicated that minimally invasive approaches are safe and feasible, with a low rate of pleural recurrence, underlining the necessity of a "no-touch" technique. However, especially for thymomatous disease characterized by an indolent nature, further studies with long follow-up period are necessary in order to assess oncologic and neurologic results through minimally invasive

  20. The ZOOM minimization package

    SciTech Connect

    Fischler, Mark S.; Sachs, D.; /Fermilab

    2004-11-01

    A new object-oriented Minimization package is available for distribution in the same manner as CLHEP. This package, designed for use in HEP applications, has all the capabilities of Minuit, but is a re-write from scratch, adhering to modern C++ design principles. A primary goal of this package is extensibility in several directions, so that its capabilities can be kept fresh with as little maintenance effort as possible. This package is distinguished by the priority that was assigned to C++ design issues, and the focus on producing an extensible system that will resist becoming obsolete.

  1. Waste minimization handbook, Volume 1

    SciTech Connect

    Boing, L.E.; Coffey, M.J.

    1995-12-01

    This technical guide presents various methods used by industry to minimize low-level radioactive waste (LLW) generated during decommissioning and decontamination (D and D) activities. Such activities generate significant amounts of LLW during their operations. Waste minimization refers to any measure, procedure, or technique that reduces the amount of waste generated during a specific operation or project. Preventive waste minimization techniques implemented when a project is initiated can significantly reduce waste. Techniques implemented during decontamination activities reduce the cost of decommissioning. The application of waste minimization techniques is not limited to D and D activities; it is also useful during any phase of a facility`s life cycle. This compendium will be supplemented with a second volume of abstracts of hundreds of papers related to minimizing low-level nuclear waste. This second volume is expected to be released in late 1996.

  2. Prospective long-term minimal residual disease monitoring using RQ-PCR in RUNX1-RUNX1T1-positive acute myeloid leukemia: results of the French CBF-2006 trial.

    PubMed

    Willekens, Christophe; Blanchet, Odile; Renneville, Aline; Cornillet-Lefebvre, Pascale; Pautas, Cécile; Guieze, Romain; Ifrah, Norbert; Dombret, Hervé; Jourdan, Eric; Preudhomme, Claude; Boissel, Nicolas

    2016-03-01

    In t(8;21)(q22;q22) acute myeloid leukemia, the prognostic value of early minimal residual disease assessed with real-time quantitative polymerase chain reaction is the most important prognostic factor, but how long-term minimal residual disease monitoring may contribute to drive individual patient decisions remains poorly investigated. In the multicenter CBF-2006 study, a prospective monitoring of peripheral blood and bone marrow samples was performed every 3 months and every year, respectively, for 2 years following intensive chemotherapy in 94 patients in first complete remission. A complete molecular remission was defined as a (RUNX1-RUNX1T1/ABL1)×100 ≤ 0.001%. After the completion of consolidation therapy, a bone marrow complete molecular remission was observed in 30% of the patients, but was not predictive of subsequent relapse. Indeed, 8 patients (9%) presented a positive bone marrow minimal residual disease for up to 2 years of follow-up while still remaining in complete remission. Conversely, a peripheral blood complete molecular remission was statistically associated with a lower risk of relapse whatever the time-point considered after the completion of consolidation therapy. During the 2-year follow-up, the persistence of peripheral blood complete molecular remission was associated with a lower risk of relapse (4-year cumulative incidence, 8.2%), while molecular relapse confirmed on a subsequent peripheral blood sample predicted hematological relapse (4-year cumulative incidence, 86.9%) within a median time interval of 3.9 months. In t(8;21)(q22;q22) acute myeloid leukemia, minimal residual disease monitoring on peripheral blood every 3 months allows for the prediction of hematological relapse, and to identify patients who could potentially benefit from intervention therapy. (ClinicalTrials.gov ID #NCT00428558). PMID:26635039

  3. Waste Minimization Crosscut Plan

    SciTech Connect

    Not Available

    1992-05-13

    On November 27, 1991, the Secretary of Energy directed that a Department of Energy (DOE) crosscut plan for waste minimization (WMin) be prepared and submitted by March 1, 1992. This Waste Minimization Crosscut Plan responds to the Secretary`s direction and supports the National Energy Strategy (NES) goals of achieving greater energy security, increasing energy and economic efficiency, and enhancing environmental quality. It provides a DOE-wide planning framework for effective coordination of all DOE WMin activities. This Plan was jointly prepared by the following Program Secretarial Officer (PSO) organizations: Civilian Radioactive Waste Management (RW); Conservation and Renewable Energy (CE); Defense Programs (DP); Environmental Restoration and Waste Management (EM), lead; Energy Research (ER); Fossil Energy (FE); Nuclear Energy (NE); and New Production Reactors (NP). Assistance and guidance was provided by the offices of Policy, Planning, and Analysis (PE) and Environment, Safety and Health (EH). Comprehensive application of waste minimization within the Department and in both the public and private sectors will provide significant benefits and support National Energy Strategy goals. These benefits include conservation of a substantial proportion of the energy now used by industry and Government, improved environmental quality, reduced health risks, improved production efficiencies, and longer useful life of disposal capacity. Taken together, these benefits will mean improved US global competitiveness, expanded job opportunities, and a better quality of life for all citizens.

  4. Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications.

    PubMed

    Hua, Yinan; Nair, Sreejayan

    2015-02-01

    Cardiovascular disease is the leading cause of death in the U.S. and other developed countries. Metabolic syndrome, including obesity, diabetes/insulin resistance, hypertension and dyslipidemia is a major threat for public health in the modern society. It is well established that metabolic syndrome contributes to the development of cardiovascular disease collective called as cardiometabolic disease. Despite documented studies in the research field of cardiometabolic disease, the underlying mechanisms are far from clear. Proteases are enzymes that break down proteins, many of which have been implicated in various diseases including cardiac disease. Matrix metalloproteinase (MMP), calpain, cathepsin and caspase are among the major proteases involved in cardiac remodeling. Recent studies have also implicated proteases in the pathogenesis of cardiometabolic disease. Elevated expression and activities of proteases in atherosclerosis, coronary heart disease, obesity/insulin-associated heart disease as well as hypertensive heart disease have been documented. Furthermore, transgenic animals that are deficient in or over-express proteases allow scientists to understand the causal relationship between proteases and cardiometabolic disease. Mechanistically, MMPs and cathepsins exert their effect on cardiometabolic diseases mainly through modifying the extracellular matrix. However, MMP and cathepsin are also reported to affect intracellular proteins, by which they contribute to the development of cardiometabolic diseases. On the other hand, activation of calpain and caspases has been shown to influence intracellular signaling cascade including the NF-κB and apoptosis pathways. Clinically, proteases are reported to function as biomarkers of cardiometabolic diseases. More importantly, the inhibitors of proteases are credited with beneficial cardiometabolic profile, although the exact molecular mechanisms underlying these salutary effects are still under investigation. A better

  5. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    PubMed Central

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  6. Applications of laser in ischemic heart disease in China

    NASA Astrophysics Data System (ADS)

    Chen, Mingzhe; Zhang, Yongzhen

    1999-09-01

    Current data demonstrate that laser coronary angioplasty is most useful in complex lesions not well suited for percutaneous transluminal coronary angioplasty (PTCA). It is not `stand-alone' procedure, and should be considered an adjunct to PTCA or stenting. To date, there are not data supporting reduction of restenosis. Direct myocardial revascularization (DMR), either transmyocardial revascularization (TMR) or percutaneous (catheter-based) myocardial revascularization (PMR), uses laser to create channels between ischemic myocardium and left ventricular cavity. Candidates include patients with chronic, severe, refractory angina and those unable to undergo angioplasty or bypass surgery because conduits or acceptable target vessels are lacking. Although the mechanisms of action of DMR have not yet been clearly elucidated, but several theories have been proposed, including channel patency, angiogenesis, and denervation. TMR, typically requiring open thoracotomy, is effective for improving myocardial perfusion and reducing angina. Pilot studies demonstrate that clinical application of PMR is feasible and safe and effective for decreasing angina. Late sequelae also remain to be determined. An ongoing randomized clinical trial is comparing PMR with conventional medical therapy in patients with severe, refractory angina and disease unamenable to angioplasty or bypass surgery.

  7. Identification of follicular lymphoma by polymerase chain reaction amplification of the t(14;18) translocation: An improved method for staging of malignancy and detection of minimal residual disease

    SciTech Connect

    La Spada, A.R.; Lakey, C.; Hanke, D.C.

    1994-09-01

    60 to 85% of follicular non-Hodgkin`s lymphomas have a reciprocal translocation between chromosomes 14 and 18 (t(14q21;18q32)). As a result of this translocation, the joining region of the immunoglobulin heavy chain gene (J{sub H}) on chromosome 14 is juxtaposed to the bcl-2 gene on chromosome 18. Polymerase chain reaction (PCR) amplification across the translocation breakpoint may be used to detect follicular lymphoma cells in the peripheral blood and bone marrow, as morphological examination for lymphoma cells is extremely insensitive. We performed PCR assays with a universal J{sub H} primer and pairs of major breakpoint region (MBR) primers or minor cluster region (MCR) primers from the bcl-2 gene. PCR products were then visualized on ethidium-stained agarose gels, along with size markers and appropriate positive and negative controls. We began by comparing the PCR assay to Southern blot analysis and found that Southern blot analysis detected 9 translocations in 24 follicular lymphomas (37.5%), while PCR amplification detected 13 (58.3%), making it the more sensitive technique. By using adjacent MBR and MCR primer pairs in the PCR assay, we were also able to attain very high specificities (>95%). As detection of minimal residual disease after therapy is likely important for the prognosis and further management of these patients, we decided to use our PCR assay to evaluate peripheral blood stem cell preparations from patients undergoing autologous bone marrow transplantation. Of the 26 patients analyzed thus far, 4 (15%) have been found positive for MBR translocations. These results indicate that PCR amplification of the t(14;18) translocation is a sensitive and specific method for detection of follicular lymphoma cells, and therefore has potential application as a tool not only for the staging but also for the management of this malignancy.

  8. Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications

    PubMed Central

    Hua, Yinan; Nair, Sreejayan

    2014-01-01

    Cardiovascular disease is the leading cause of death in the U.S. and other developed country. Metabolic syndrome, including obesity, diabetes/insulin resistance, hypertension and dyslipidemia is major threat for public health in the modern society. It is well established that metabolic syndrome contributes to the development of cardiovascular disease collective called as cardiometabolic disease. Despite documented studies in the research field of cardiometabolic disease, the underlying mechanisms are far from clear. Proteases are enzymes that break down proteins, many of which have been implicated in various diseases including cardiac disease. Matrix metalloproteinase (MMP), calpain, cathepsin and caspase are among the major proteases involved in cardiac remodeling. Recent studies have also implicated proteases in the pathogenesis of cardiometabolic disease. Elevated expression and activities of proteases in atherosclerosis, coronary heart disease, obesity/insulin-associated heart disease as well as hypertensive heart disease have been documented. Furthermore, transgenic animals that are deficient in or overexpress proteases allow scientists to understand the causal relationship between proteases and cardiometabolic disease. Mechanistically, MMPs and cathepsins exert their effect on cardiometabolic diseases mainly through modifying the extracellular matrix. However, MMP and cathepsin are also reported to affect intracellular proteins, by which they contribute to the development of cardiometabolic diseases. On the other hand, activation of calpain and caspases has been shown to influence intracellular signaling cascade including the NF-κB and apoptosis pathways. Clinically, proteases are reported to function as biomarkers of cardiometabolic diseases. More importantly, the inhibitors of proteases are credited with beneficial cardiometabolic profile, although the exact molecular mechanisms underlying these salutary effects are still under investigation. A better

  9. Esophagectomy - minimally invasive

    MedlinePlus

    Minimally invasive esophagectomy; Robotic esophagectomy; Removal of the esophagus - minimally invasive; Achalasia - esophagectomy; Barrett esophagus - esophagectomy; Esophageal cancer - esophagectomy - laparoscopic; Cancer of the ...

  10. Development and Application of Chronic Disease Risk Prediction Models

    PubMed Central

    Oh, Sun Min; Stefani, Katherine M.

    2014-01-01

    Currently, non-communicable chronic diseases are a major cause of morbidity and mortality worldwide, and a large proportion of chronic diseases are preventable through risk factor management. However, the prevention efficacy at the individual level is not yet satisfactory. Chronic disease prediction models have been developed to assist physicians and individuals in clinical decision-making. A chronic disease prediction model assesses multiple risk factors together and estimates an absolute disease risk for the individual. Accurate prediction of an individual's future risk for a certain disease enables the comparison of benefits and risks of treatment, the costs of alternative prevention strategies, and selection of the most efficient strategy for the individual. A large number of chronic disease prediction models, especially targeting cardiovascular diseases and cancers, have been suggested, and some of them have been adopted in the clinical practice guidelines and recommendations of many countries. Although few chronic disease prediction tools have been suggested in the Korean population, their clinical utility is not as high as expected. This article reviews methodologies that are commonly used for developing and evaluating a chronic disease prediction model and discusses the current status of chronic disease prediction in Korea. PMID:24954311

  11. A minimal connected network of transcription factors regulated in human tumors and its application to the quest for universal cancer biomarkers.

    PubMed

    Essaghir, Ahmed; Demoulin, Jean-Baptiste

    2012-01-01

    A universal cancer biomarker candidate for diagnosis is supposed to distinguish, within a broad range of tumors, between healthy and diseased patients. Recently published studies have explored the universal usefulness of some biomarkers in human tumors. In this study, we present an integrative approach to search for potential common cancer biomarkers. Using the TFactS web-tool with a catalogue of experimentally established gene regulations, we could predict transcription factors (TFs) regulated in 305 different human cancer cell lines covering a large panel of tumor types. We also identified chromosomal regions having significant copy number variation (CNV) in these cell lines. Within the scope of TFactS catalogue, 88 TFs whose activity status were explained by their gene expressions and CNVs were identified. Their minimal connected network (MCN) of protein-protein interactions forms a significant module within the human curated TF proteome. Functional analysis of the proteins included in this MCN revealed enrichment in cancer pathways as well as inflammation. The ten most central proteins in MCN are TFs that trans-regulate 157 known genes encoding secreted and transmembrane proteins. In publicly available collections of gene expression data from 8,525 patient tissues, 86 genes were differentially regulated in cancer compared to inflammatory diseases and controls. From TCGA cancer gene expression data sets, 50 genes were significantly associated to patient survival in at least one tumor type. Enrichment analysis shows that these genes mechanistically interact in common cancer pathways. Among these cancer biomarker candidates, TFRC, MET and VEGFA are commonly amplified genes in tumors and their encoded proteins stained positive in more than 80% of malignancies from public databases. They are linked to angiogenesis and hypoxia, which are common in cancer. They could be interesting for further investigations in cancer diagnostic strategies. PMID:22761861

  12. iPS cell technologies: significance and applications to CNS regeneration and disease

    PubMed Central

    2014-01-01

    In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enormous increase in interest regarding the application of iPS cell technologies to medical science, in particular for regenerative medicine and human disease modeling. In this review article, we outline the current status of applications of iPS technology to cell therapies (particularly for spinal cord injury), as well as neurological disease-specific iPS cell research (particularly for Parkinson’s disease and Alzheimer’s disease). Finally, future directions of iPS cell research are discussed including a) development of an accurate assay system for disease-associated phenotypes, b) demonstration of causative relationships between genotypes and phenotypes by genome editing, c) application to sporadic and common diseases, and d) application to preemptive medicine. PMID:24685317

  13. IRIS: A database application system for diseases identification using FTIR spectroscopy

    NASA Astrophysics Data System (ADS)

    Arshad, Ahmad Zulhilmi; Munajat, Yusof; Ibrahim, Raja Kamarulzaman Raja; Mahmood, Nasrul Humaimi

    2015-05-01

    Infrared information on diseases identification system (IRIS) is an application for diseases identification and analysis by using Fourier transform infrared (FTIR) spectroscopy. This is the preliminary step to gather information from the secondary data which was extracted from recognized various research and scientific paper, which are combined into a single database as in IRIS for our purpose of study. The importance of this database is to examine the fingerprint differences between normal and diseases cell or tissue. With the implementation of this application is it hopes that the diseases identification using FTIR spectroscopy would be more reliable and may assist either physicians, pathologists, or researchers to diagnose the certain type of disease efficiently.

  14. [Ultrasound and color Doppler applications in chronic kidney disease].

    PubMed

    Meola, Mario; Petrucci, Ilaria

    2012-01-01

    Chronic kidney disease (CKD) encompasses all clinical features and complications during the progression of various kidney conditions towards end-stage renal disease. These conditions include immune and inflammatory diseases such as primary and HCV-related glomerulonephritis; infectious diseases such as pyelonephritis with or without reflux and tuberculosis; vascular diseases such as chronic ischemic nephropathy; hereditary and congenital diseases such as polycystic disease and congenital cystic dysplasia; metabolic diseases including diabetes and hyperuricemia; and systemic diseases (collagen disease, vasculitis, myeloma). During the progression of CKD, ultrasound imaging can differentiate the nature of the renal damage in only 50-70% of cases. Infact, the end-stage kidney appears shrunken, reduced in volume (Ø <9 cm), unstructured, amorphous, with acquired cystic degeneration (small and multiple cysts involving the cortex and medulla) or nephrocalcinosis, but there are rare exceptions, such as polycystic kidney disease, diabetic nephropathy, and secondary inflammatory nephropathies. The main difficulties in the differential diagnosis are encountered in multifactorial CKD, which is commonly presented to the nephrologist at stage 4-5, when the kidney is shrunken, unstructured and amorphous. As in acute renal injury and despite the lack of sensitivity, ultrasonography is essential for assessing the progression of the renal damage and related complications, and for evaluating all conditions that increase the risk of CKD, such as lithiasis, recurrent urinary tract infections, vesicoureteral reflux, polycystic kidney disease and obstructive nephropathy. The timing and frequency of ultrasound scans in CKD patients should be evaluated case by case. In this review we will consider the morphofunctional features of the kidney in all nephropathies that may lead to progressive CKD. PMID:23229668

  15. [Application for Lifestyle disease by iPS cells technologies].

    PubMed

    Takashima, Yasuhiro

    2016-03-01

    Currently it is less advanced to understand the pathology of lifestyle disease by using iPS cells because there is partly less direct connection between life style disease and iPS cells. So much more scientists focus on regenerative medicine such as beta cells therapy using iPS cells technologies. It will be indeed a powerful tool to generate beta cells from iPS cells as even in type2 diabetes patients, hyposecretion of insulin from beta cells in pancreas is one of causes. Another reason is complexity of the pathology of life style disease. There are a lot of reasons to cause lifestyle disease. Lifestyle diseases include cancer, chronic liver disease, Type 2 diabetes, heart disease, metabolic syndrome, chronic renal failure, stroke, and obesity. Since obesity is one of major causes of lifestyle diseases, we want to focus on adipogenesis from iPS cells in this review. We analysed and established the differentiation protocol into adipocytes from mouse ES cells and human iPS cells. The other point in this review is the starting pluripotent cells for differentiation. Quality of pluripotent stem cells are one of most critical factors to succeed in getting well-differentiated cells. Recently, we have developed new naive human pluripotent stem cells (PSC),"Reset cells". Naive PSC have more similar to human epibast cells than conventional human PSC. They will be more ideal cells for differentiation because of their hypomethylated status and earlier stage of development. PMID:26923982

  16. Preparation and characterization of semi-refined kappa carrageenan-based edible film for nano coating application on minimally processed food

    NASA Astrophysics Data System (ADS)

    Manuhara, Godras Jati; Praseptiangga, Danar; Muhammad, Dimas Rahadian Aji; Maimuni, Bawani Hindami

    2016-02-01

    Shorter and easier processing of semi-refined kappa carrageenan extracted from Euchema cottonii red seaweed result in cheaper price of the polysaccharide. In this study, edible film was prepared from the semi-refined carrageenan without any salt addition. The effect of the carrageenan concentration (1.0, 1.5, and 2.0% w/v) on physical and mechanical properties of the edible film was studied. Edible film thickness and tensile strength increased but elongation at break and water vapor transmission rate (WVTR) decreased as the concentration increased. Based on the characteristic of the edible film, formulation using 2% carrageenan was recommended. The edible film demonstrated the characteristic as follow: 0.054 mm thickness, 21.14 MPa tensile strength, 12.36% elongation at break, and 9.56 g/m2.hour WVTR. It was also noted the carrageenan-based edible film indicated potential physical and mechanical characteristics for nano coating applications on minimally processed food.

  17. [Application of iodine metabolism analysis methods in thyroid diseases].

    PubMed

    Han, Jian-hua; Qiu, Ling

    2013-08-01

    The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases. PMID:23987480

  18. Osteopathic manipulative treatment: novel application to dermatological disease.

    PubMed

    Campbell, Shannon M; Winkelmann, Richard R; Walkowski, Stevan

    2012-10-01

    Dermatological diseases, such as dysesthesia syndromes, stasis dermatoses, and hyperhidrosis are difficult to treat due to their complex etiologies. Current theories suggest these diseases are caused by physiological imbalances, such as nerve impingement, localized tissue congestion, and impaired autonomic regulation. Osteopathic manipulative therapy targets these physiological dysfunctions and may serve as a beneficial therapeutic option. Osteopathic manipulative therapy techniques include high velocity low amplitude, muscle energy, counterstrain, myofascial release, craniosacral, and lymphatic drainage. An osteopathic manipulative therapy technique is chosen based on its physiological target for a particular disease. Osteopathic manipulative therapy may be useful alone or in combination with standard therapeutic options. However, due to the lack of standardized trials supporting the efficacy of osteopathic manipulative therapy treatment for dermatological disease, randomized, well-controlled studies are necessary to confirm its therapeutic value. PMID:23125887

  19. Application of 5-ALA for differential diagnostics of stomach diseases

    NASA Astrophysics Data System (ADS)

    Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

    2001-01-01

    59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

  20. Cell biomechanics and its applications in human disease diagnosis

    NASA Astrophysics Data System (ADS)

    Nematbakhsh, Yasaman; Lim, Chwee Teck

    2015-04-01

    Certain diseases are known to cause changes in the physical and biomechanical properties of cells. These include cancer, malaria, and sickle cell anemia among others. Typically, such physical property changes can result in several fold increases or decreases in cell stiffness, which are significant and can result in severe pathology and eventual catastrophic breakdown of the bodily functions. While there are developed biochemical and biological assays to detect the onset or presence of diseases, there is always a need to develop more rapid, precise, and sensitive methods to detect and diagnose diseases. Biomechanical property changes can play a significant role in this regard. As such, research into disease biomechanics can not only give us an in-depth knowledge of the mechanisms underlying disease progression, but can also serve as a powerful tool for detection and diagnosis. This article provides some insights into opportunities for how significant changes in cellular mechanical properties during onset or progression of a disease can be utilized as useful means for detection and diagnosis. We will also showcase several technologies that have already been developed to perform such detection and diagnosis.

  1. Prototype early warning system for heart disease detection using Android Application.

    PubMed

    Zennifa, Fadilla; Fitrilina; Kamil, Husnil; Iramina, Keiji

    2014-01-01

    Heart Disease affects approximately 70 million people worldwide where most people do not even know the symptoms. This research examines the prototype of early warning system for heart disease by android application. It aims to facilitate users to early detect heart disease which can be used independently. To build the application in android phone, variable centered intelligence rule system (VCIRS) as decision makers and pulse sensor - Arduino as heart rate detector were applied in this study. Moreover, in Arduino, the heart rate will become an input for symptoms in Android Application. The output of this system is the conclusion statement of users diagnosed with either coronary heart disease, hypertension heart disease, rheumatic heart disease or do not get any kind of heart disease. The result of diagnosis followed by analysis of the value of usage variable rate (VUR) rule usage rate (RUR) and node usage rate (NUR) that shows the value of the rule that will increase when the symptoms frequently appear. This application was compared with the medical analysis from 35 cases of heart disease and it showed concordance between diagnosis from android application and expert diagnosis of the doctors. PMID:25570737

  2. [Minimally invasive breast surgery].

    PubMed

    Mátrai, Zoltán; Gulyás, Gusztáv; Kunos, Csaba; Sávolt, Akos; Farkas, Emil; Szollár, András; Kásler, Miklós

    2014-02-01

    Due to the development in medical science and industrial technology, minimally invasive procedures have appeared in the surgery of benign and malignant breast diseases. In general , such interventions result in significantly reduced breast and chest wall scars, shorter hospitalization and less pain, but they require specific, expensive devices, longer surgical time compared to open surgery. Furthermore, indications or oncological safety have not been established yet. It is quite likely, that minimally invasive surgical procedures with high-tech devices - similar to other surgical subspecialties -, will gradually become popular and it may form part of routine breast surgery even. Vacuum-assisted core biopsy with a therapeutic indication is suitable for the removal of benign fibroadenomas leaving behind an almost invisible scar, while endoscopically assisted skin-sparing and nipple-sparing mastectomy, axillary staging and reconstruction with latissimus dorsi muscle flap are all feasible through the same short axillary incision. Endoscopic techniques are also suitable for the diagnostics and treatment of intracapsular complications of implant-based breast reconstructions (intracapsular fluid, implant rupture, capsular contracture) and for the biopsy of intracapsular lesions with uncertain pathology. Perception of the role of radiofrequency ablation of breast tumors requires further hands-on experience, but it is likely that it can serve as a replacement of surgical removal in a portion of primary tumors in the future due to the development in functional imaging and anticancer drugs. With the reduction of the price of ductoscopes routine examination of the ductal branch system, guided microdochectomy and targeted surgical removal of terminal ducto-lobular units or a "sick lobe" as an anatomical unit may become feasible. The paper presents the experience of the authors and provides a literature review, for the first time in Hungarian language on the subject. Orv. Hetil

  3. Modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.

    PubMed

    Oraby, Tamer; Vasilyeva, Olga; Krewski, Daniel; Lutscher, Frithjof

    2014-01-01

    Behavior and habitat of wildlife animals change seasonally according to environmental conditions. Mathematical models need to represent this seasonality to be able to make realistic predictions about the future of a population and the effectiveness of human interventions. Managing and modeling disease in wild animal populations requires particular care in that disease transmission dynamics is a critical consideration in the etiology of both human and animal diseases, with different transmission paradigms requiring different disease risk management strategies. Since transmission of infectious diseases among wildlife depends strongly on social behavior, mechanisms of disease transmission could also change seasonally. A specific consideration in this regard confronted by modellers is whether the contact rate between individuals is density-dependent or frequency-dependent. We argue that seasonal behavior changes could lead to a seasonal shift between density and frequency dependence. This hypothesis is explored in the case of chronic wasting disease (CWD), a fatal disease that affects deer, elk and moose in many areas of North America. Specifically, we introduce a strategic CWD risk model based on direct disease transmission that accounts for the seasonal change in the transmission dynamics and habitats occupied, guided by information derived from cervid ecology. The model is composed of summer and winter susceptible-infected (SI) equations, with frequency-dependent and density-dependent transmission dynamics, respectively. The model includes impulsive birth events with density-dependent birth rate. We determine the basic reproduction number as a weighted average of two seasonal reproduction numbers. We parameterize the model from data derived from the scientific literature on CWD and deer ecology, and conduct global and local sensitivity analyses of the basic reproduction number. We explore the effectiveness of different culling strategies for the management of CWD

  4. Perspectives on Systems Biology Applications in Diabetic Kidney Disease

    PubMed Central

    Komorowsky, Claudiu V.; Brosius, Frank C.; Pennathur, Subramaniam; Kretzler, Matthias

    2012-01-01

    Diabetic kidney disease (DKD) is a microvascular complication of type 1 and 2 diabetes with a devastating impact on individuals with the disease, their families and society as a whole. DKD is the single most frequent cause of incident chronic kidney disease (CKD) cases and accounts for over 40% of the population with end stage renal disease (ESRD). Contributing factors for the high prevalence are the increase in obesity and subsequent diabetes combined with an improved long–term survival with diabetes. Environment and genetic variations contribute to DKD susceptibility and progressive loss of kidney function. How the molecular mechanisms of genetic and environmental exposures interact during DKD initiation and progression are the focus of ongoing research efforts. The development of standardized, unbiased high throughput profiling technologies of human DKD samples opens new avenues in capturing the multiple layers of DKD pathobiology. These techniques routinely interrogate analytes on a genome–wide scale generating comprehensive DKD associated fingerprints. Linking the molecular fingerprints to deep clinical phenotypes may ultimately elucidate the intricate molecular interplay in a disease stage and subtype specific manner. This insight will form the basis for accurate prognosis and facilitate targeted therapeutic interventions. In this review, we present ongoing efforts from large scale data integration translating “–omics” research efforts into improved and individualized health care in DKD. PMID:22733404

  5. Potential application of lithium in Parkinson's and other neurodegenerative diseases

    PubMed Central

    Lazzara, Carol A.; Kim, Yong-Hwan

    2015-01-01

    Lithium, the long-standing hallmark treatment for bipolar disorder, has recently been identified as a potential neuroprotective agent in neurodegeneration. Here we focus on introducing numerous in vitro and in vivo studies that have shown lithium treatment to be efficacious in reducing oxidative stress and inflammation, increasing autophagy, inhibiting apoptosis, and decreasing the accumulation of α-synulcein, with an emphasis on Parkinson's disease. A number of biological pathways have been shown to be involved in causing these neuroprotective effects. The inhibition of GSK-3β has been the mechanism most studied; however, other modes of action include the regulation of apoptotic proteins and glutamate excitotoxicity as well as down-regulation of calpain. This review provides a framework of the neuroprotective effects of lithium in neurodegenerative diseases and the putative mechanisms by which lithium provides the protection. Lithium-only treatment may not be a suitable therapeutic option for neurodegenerative diseases due to inconsistent efficacy and potential side-effects, however, the use of low dose lithium in combination with other potential or existing therapeutic compounds may be a promising approach to reduce symptoms and disease progression in neurodegenerative diseases. PMID:26578864

  6. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics

    PubMed Central

    Rai, Aswathy N.; Epperson, William B.; Nanduri, Bindu

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional genomics methods such as microarrays, RNA-seq, and proteomics are helpful. In this review, we summarize the progress made in our understanding of BRD using functional genomics approaches. We also discuss some of the available bioinformatics resources for analyzing high-throughput data, in the context of biological pathways and molecular interactions. Although resources for studying host response to infection are avail-able, the corresponding information is lacking for majority of BRD pathogens, impeding progress in identifying diagnostic signatures for BRD using functional genomics approaches. PMID:26526746

  7. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics.

    PubMed

    Rai, Aswathy N; Epperson, William B; Nanduri, Bindu

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional genomics methods such as microarrays, RNA-seq, and proteomics are helpful. In this review, we summarize the progress made in our understanding of BRD using functional genomics approaches. We also discuss some of the available bioinformatics resources for analyzing high-throughput data, in the context of biological pathways and molecular interactions. Although resources for studying host response to infection are avail-able, the corresponding information is lacking for majority of BRD pathogens, impeding progress in identifying diagnostic signatures for BRD using functional genomics approaches. PMID:26526746

  8. Momentum-based morphometric analysis with application to Parkinson's disease

    NASA Astrophysics Data System (ADS)

    Chen, Jingyun; Khan, Ali R.; McKeown, Martin J.; Beg, Mirza F.

    2011-03-01

    We apply the initial momentum shape representation of diffeomorphic metric mapping from a template region of interest (ROI) to a given ROI as a morphometic marker in Parkinson's disease. We used a three-step segmentation-registrationmomentum process to derive feature vectors from ROIs in a group of 42 subjects consisting of 19 Parkinson's Disease (PD) subjects and 23 normal control (NC) subjects. Significant group differences between PD and NC subjects were detected in four basal ganglia structures including the caudate, putamen, thalamus and globus pallidus. The magnitude of regionally significant between-group differences detected ranged between 34-75%. Visualization of the different structural deformation pattern between-groups revealed that some parts of basal ganglia structure actually hypertrophy, presumably as a compensatory response to more widespread atrophy. Our results of both hypertrophy and atrophy in the same structures further demonstrate the importance of morphological measures as opposed to overall volume in the assessment of neurodegenerative disease.

  9. Applications of systems approaches in the study of rheumatic diseases

    PubMed Central

    Kim, Ki-Jo; Lee, Saseong

    2015-01-01

    The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features. PMID:25750554

  10. Progress in Mining the Human Proteome for Disease Applications

    PubMed Central

    2011-01-01

    Abstract Currently available technologies allow in-depth analysis of multiple facets of the proteome that have clinical relevance and that complement current genomics-based approaches. Although some progress has been made in our knowledge of the human proteome in health and in disease, there is an urgent need to chart a coherent road map with clearly defined milestones to guide proteomics efforts. Areas of emphasis include: (1) building resources, (2) filling gaps in our understanding of biological variation, and (3) systematically characterizing proteome alterations that occur in well-defined disease states, all of which require an organized and collaborative effort. PMID:21375461

  11. Preclinical testing of radiopharmaceuticals for novel applications in HIV, bacterial and fungal infectious diseases.

    PubMed

    Shah, M; Garg, G; Dadachova, E

    2015-09-01

    Antibiotics, antifungal and antiviral medications have traditionally been used in the management of infections. Due to widespread emergence of resistance to antimicrobial medications, and their side effects, there is a growing need for alternative approaches for management of such conditions. Antibiotic resistant bacterial pathogens are on the rise. A cure has not been achieved for viral infections like AIDS, while fungal and parasitic infections are constant threats to the health of general public. The incidence of opportunistic infections in immunocompromised individuals like HIV patients, patients receiving high dose steroids, chemotherapy patients, and organ transplant recipients is on the rise. Radioimmunotherapy (RIT) has the potential to be a suitable and viable therapeutic modality in the arena of infection management. Provided the target-associated antigen is expressed by the target cells and minimally or not expressed by other tissues, selective targeting of radiation to target sites can be theoretically accomplished with relative sparing normal tissues from radiation exposure. In our laboratory we successfully demonstrated the effectiveness of RIT for treating infectious diseases. We targeted murine cryptococcosis with a mAb to the Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213 ((213)Bi) or Rhenium-188 ((188)Re). We subsequently extended the applicability of RIT for treating bacterial and viral infections. One of the advantages of using RIT to treat infections as opposed to cancer is that, in contrast to tumor cells, cells expressing microbial antigens are antigenically very different from host tissues and thus provide the potential for exquisite specificity and low cross-reactivity. Ever increasing incidence of infectious pathologies, exhaustion of antimicrobial possibilities and rising drug resistance calls for use of alternative and novel therapeutic options and we believe RIT is the need of the hour to combat these

  12. Minimally invasive aortic valve surgery.

    PubMed

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-09-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  13. Minimally invasive aortic valve surgery

    PubMed Central

    Castrovinci, Sebastiano; Emmanuel, Sam; Moscarelli, Marco; Murana, Giacomo; Caccamo, Giuseppa; Bertolino, Emanuela Clara; Nasso, Giuseppe; Speziale, Giuseppe; Fattouch, Khalil

    2016-01-01

    Aortic valve disease is a prevalent disorder that affects approximately 2% of the general adult population. Surgical aortic valve replacement is the gold standard treatment for symptomatic patients. This treatment has demonstrably proven to be both safe and effective. Over the last few decades, in an attempt to reduce surgical trauma, different minimally invasive approaches for aortic valve replacement have been developed and are now being increasingly utilized. A narrative review of the literature was carried out to describe the surgical techniques for minimally invasive aortic valve surgery and report the results from different experienced centers. Minimally invasive aortic valve replacement is associated with low perioperative morbidity, mortality and a low conversion rate to full sternotomy. Long-term survival appears to be at least comparable to that reported for conventional full sternotomy. Minimally invasive aortic valve surgery, either with a partial upper sternotomy or a right anterior minithoracotomy provides early- and long-term benefits. Given these benefits, it may be considered the standard of care for isolated aortic valve disease. PMID:27582764

  14. Developments in renal pharmacogenomics and applications in chronic kidney disease

    PubMed Central

    Padullés, Ariadna; Rama, Inés; Llaudó, Inés; Lloberas, Núria

    2014-01-01

    Chronic kidney disease (CKD) has shown an increasing prevalence in the last century. CKD encompasses a poor prognosis related to a remarkable number of comorbidities, and many patients suffer from this disease progression. Once the factors linked with CKD evolution are distinguished, it will be possible to provide and enhance a more intensive treatment to high-risk patients. In this review, we focus on the emerging markers that might be predictive or related to CKD progression physiopathology as well as those related to a different pattern of response to treatment, such as inhibitors of the renin–angiotensin system (including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers; the vitamin D receptor agonist; salt sensitivity hypertension; and progressive kidney-disease markers with identified genetic polymorphisms). Candidate-gene association studies and genome-wide association studies have analyzed the genetic basis for common renal diseases, including CKD and related factors such as diabetes and hypertension. This review will, in brief, consider genotype-based pharmacotherapy, risk prediction, drug target recognition, and personalized treatments, and will mainly focus on findings in CKD patients. An improved understanding will smooth the progress of switching from classical clinical medicine to gene-based medicine. PMID:25206311

  15. MicroRNAs and Their Applications in Kidney Diseases

    PubMed Central

    Badal, Shawn S.; Danesh, Farhad R.

    2014-01-01

    MicroRNAs (miRNAs) are short, non-coding RNAs that employ classic Watson-Crick base-pairing to identify their target genes, ultimately resulting in destabilizing their target mRNAs and/or inhibiting their translation. The role of miRNAs in a wide-range of human diseases, including those afflicting the kidney, has been intensely investigated. However there is still a vast dearth of knowledge regarding their specific mode of action and therapeutic effects in various kidney diseases. This review discusses the latest efforts to further our understanding of the basic biology of miRNAs, their impact on various kidney diseases and their potential as novel biomarkers and therapeutic agents. We initially provide an overview of miRNA biology and the canonical pathway implicated in their biogenesis. We will then discuss commonly employed experimental strategies for miRNA research and highlight some of the newly described state-of-the-art technologies to identify miRNAs and their target genes. Finally, we will carefully examine the emerging role of miRNAs in the pathogenesis of various kidney diseases. PMID:24928414

  16. The current clinical revolution. Applications of gene therapy in treatment of disease.

    PubMed

    Worden, M

    1994-05-01

    A major technological revolution is on the horizon that promises cures for inherited diseases such as cystic fibrosis, sickle cell anemia, muscular dystrophy, hemophilia, leukocyte-adhesion deficiency, and Gaucher's disease. This revolutionary technology also promises effective treatments for acquired diseases such as cancer and AIDS. The technique is gene therapy and it has already been used in humans. Some applications raise ethical considerations that not only affect the individual who is treated but have implications for future generations as well. PMID:10134065

  17. Application of laser technology in treatment of diseases of the external genitals

    NASA Astrophysics Data System (ADS)

    Wilczak, Maciej; Wozniak, Jakub; Sajdak, Stefan; Opala, Tomasz; Rabiega, Dorota

    2000-11-01

    Lasersurgery is the very profitable method of treatment of diseases of external sexual organs, with regard to high efficiency and little relapses. Lasersurgery is recommended especially for pregnant women considering possibility of physiological childbirth. We prefer laser CO2 in connexion with colposcope in treatment of diseases of external sexual organs. The application of this method is limited by the high cost of equipment.

  18. Minimally Invasive Surgery in Gastrointestinal Cancer: Benefits, Challenges, and Solutions for Underutilization

    PubMed Central

    Gusani, Niraj J.; Kimchi, Eric T.; Kavic, Stephen M.

    2014-01-01

    Background and Objectives: After the widespread application of minimally invasive surgery for benign diseases and given its proven safety and efficacy, minimally invasive surgery for gastrointestinal cancer has gained substantial attention in the past several years. Despite the large number of publications on the topic and level I evidence to support its use in colon cancer, minimally invasive surgery for most gastrointestinal malignancies is still underused. Methods: We explore some of the challenges that face the fusion of minimally invasive surgery technology in the management of gastrointestinal malignancies and propose solutions that may help increase the utilization in the future. These solutions are based on extensive literature review, observation of current trends and practices in this field, and discussion made with experts in the field. Results: We propose 4 different solutions to increase the use of minimally invasive surgery in the treatment of gastrointestinal malignancies: collaboration between surgical oncologists/hepatopancreatobiliary surgeons and minimally invasive surgeons at the same institution; a single surgeon performing 2 fellowships in surgical oncology/hepatopancreatobiliary surgery and minimally invasive surgery; establishing centers of excellence in minimally invasive gastrointestinal cancer management; and finally, using robotic technology to help with complex laparoscopic skills. Conclusions: Multiple studies have confirmed the utility of minimally invasive surgery techniques in dealing with patients with gastrointestinal malignancies. However, training continues to be the most important challenge that faces the use of minimally invasive surgery in the management of gastrointestinal malignancy; implementation of our proposed solutions may help increase the rate of adoption in the future. PMID:25489209

  19. Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases

    PubMed Central

    Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

    2015-01-01

    Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9. PMID:26501275

  20. Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases.

    PubMed

    Ishida, Kentaro; Gee, Peter; Hotta, Akitsu

    2015-01-01

    Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9. PMID:26501275

  1. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association

    PubMed Central

    Roumier, Christophe; Cheok, Meyling; Marceau-Renaut, Alice; Nibourel, Olivier; Geffroy, Sandrine; Helevaut, Nathalie; Rousselot, Philippe; Gruson, Bérengère; Gardin, Claude; Chretien, Marie-Lorraine; Sebda, Shéhérazade; Figeac, Martin; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Castaigne, Sylvie; Dombret, Hervé; Renneville, Aline; Preudhomme, Claude

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis. PMID:26486081

  2. Clinical application of next-generation sequencing for Mendelian diseases.

    PubMed

    Jamuar, Saumya Shekhar; Tan, Ene-Choo

    2015-01-01

    Over the past decade, next-generation sequencing (NGS) has led to an exponential increase in our understanding of the genetic basis of Mendelian diseases. NGS allows for the analysis of multiple regions of the genome in one single reaction and has been shown to be a cost-effective and efficient tool in investigating patients with Mendelian diseases. More recently, NGS has been successfully deployed in the clinics, with a reported diagnostic yield of ~25 %. However, recommendations on clinical implementation of NGS are still evolving with numerous key challenges that impede the widespread use of genetics in everyday medicine. These challenges include when to order, on whom to order, what type of test to order, and how to interpret and communicate the results, including incidental findings, to the patient and family. In this review, we discuss these challenges and suggest guidelines on implementing NGS in the routine clinical workflow. PMID:26076878

  3. OSCILLATION MECHANICS OF THE RESPIRATORY SYSTEM: APPLICATIONS TO LUNG DISEASE

    PubMed Central

    Kaczka, David W.; Dellacá, Raffaele L.

    2011-01-01

    Since its introduction in the 1950s, the forced oscillation technique (FOT) and the measurement of respiratory impedance have evolved into powerful tools for the assessment of various mechanical phenomena in the mammalian lung during health and disease. In this review, we highlight the most recent developments in instrumentation, signal processing, and modeling relevant to FOT measurements. We demonstrate how FOT provides unparalleled information on the mechanical status of the respiratory system compared to more widely-used pulmonary function tests. The concept of mechanical impedance is reviewed, as well as the various measurement techniques used to acquire such data. Emphasis is placed on the analysis of lower, physiologic frequency ranges (typically less than 10 Hz) that are most sensitive to normal physical processes as well as pathologic structural alterations. Various inverse modeling approaches used to interpret alterations in impedance are also discussed, specifically in the context of three common respiratory diseases: asthma, chronic obstructive pulmonary disease, and acute lung injury. Finally, we speculate on the potential role for FOT in the clinical arena. PMID:22011237

  4. Parkinson's Disease Sleep Scale 2: application in an Italian population.

    PubMed

    Arnaldi, Dario; Cordano, Christian; De Carli, Fabrizio; Accardo, Jennifer; Ferrara, Michela; Picco, Agnese; Tamburini, Tiziano; Brugnolo, Andrea; Abbruzzese, Giovanni; Nobili, Flavio

    2016-02-01

    Sleep disturbances and nocturnal disabilities are common in Parkinson's Disease (PD). The PD sleep scale, second version (PDSS-2), has been proposed as a helpful tool for measuring sleep disorders in PD. We aimed to validate the Italian version of the PDSS-2. One hundred and twenty-three consecutive PD outpatients (76 males) were evaluated by means of PDSS-2, Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Parkinson's Disease Quality of Life Questionnaire (self-administered scales), Unified Parkinson's Disease Rating (motor section) and Hoehn and Yahr Scales, and Mini Mental State Examination. PDSS-2 internal consistency was satisfactory (Cronbach's α: 0.77) with significant item to total score correlation and high intra-class correlation coefficient for test-retest reliability (0.943). Total PDSS-2 score was correlated with the scores on all other clinical scales. The factor analysis identified five factors, related to five areas of nocturnal disturbances, similarly as the original PDSS-2. The five factors mainly reflected: (1) nocturnal movement-related problems, (2) quality of sleep, (3) dreaming distress, (4) fragmentation of sleep and (5) insomnia symptoms. The PDSS-2 scale has confirmed its usefulness in evaluating sleep problems in Italian PD patients. PMID:26520846

  5. Iowa Commercial Pesticide Applicator Manual, Category 1C: Agricultural Crop Disease Control. CS-11.

    ERIC Educational Resources Information Center

    Nyvall, Robert F.; Ryan, Stephen O.

    This manual provides information needed to meet specific standards for certification as a pesticide applicator. It summarizes the economically important diseases of field and forage crops such as corn, soybeans and alfalfa. Special attention is given to pesticide application methods and safety. (CS)

  6. Integration of apple rootstock genotype with reduced Brassica seed meal application rates for replant disease control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pre-plant soil application of Brassica seed meal (SM) formulations can provide fumigant level control of apple replant disease. However, due to high cost of the SM treatment relative to non-tarped soil fumigation, reduced application rates would likely accelerate commercial adoption of this technolo...

  7. Therapeutic applications of mesenchymal stroma cells in pediatric diseases: current aspects and future perspectives.

    PubMed

    Habib, Hamid S; Halawa, Taher F; Atta, Hazem M

    2011-11-01

    Mesenchymal stem cells or stroma cells (MSCs) were recently proven to play various therapeutic roles when used in clinical trials to control various inflammatory, neoplastic and immunologic diseases in children. Clinical trials show some promising results, particularly in diseases where conventional therapy is still ineffective. However, experimental studies sometimes show conflicting results. This review aims to assess the current therapeutic role of MSCs in the control of several pediatric diseases and elaborate on their future applications by reviewing published studies. A review of published studies on this subject based on Pubmed and Medical Subject Heading databases, with search for all relevant articles focusing on results of clinical trials to evaluate the clinical applications of MSCs. The review includes documentation of positive as well as negative applications of MSCs focused on pediatric diseases. MSCs have important immunosuppressive and antifibrotic effects that need to be employed to help patients with diseases for which no conventional management has proven to be effective. They may be also be used as an adjuvant to conventional therapeutic modalities to consolidate recovery. This review sheds light on the significance of the use of MSCs for the treatment of various pediatric diseases and focuses on promising applications. Most of the reported studies agree about the favorable use of MSCs in various diseases; however, more clinical trials, involving larger numbers of patients, need to be conducted in order to refine the outcome of the therapeutic methods and establish standardized protocols. PMID:22037754

  8. Tuberculosis Diagnosis: Relevancy of Veterinary Applications to Human Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Veterinary applications of tuberculosis (TB) tests may provide insight into the diagnostic potential and technical development of emerging tests for human TB. Interferon (IFN)-gamma release assays (IGRA) were developed initially for bovine TB eradication programs. As the test relies on functional le...

  9. Graphical Neuroimaging Informatics: Application to Alzheimer’s Disease

    PubMed Central

    Bowman, Ian; Joshi, Shantanu H.; Greer, Vaughan

    2013-01-01

    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

  10. Applications of luminescent systems to infectious disease methodology

    NASA Technical Reports Server (NTRS)

    Picciolo, G. L.; Chappelle, E. W.; Deming, J. W.; Mcgarry, M. A.; Nibley, D. A.; Okrend, H.; Thomas, R. R.

    1976-01-01

    The characterization of a clinical sample by a simple, fast, accurate, automatable analytical measurement is important in the management of infectious disease. Luminescence assays offer methods rich with options for these measurements. The instrumentation is common to each assay, and the investment is reasonable. Three general procedures were developed to varying degrees of completeness which measure bacterial levels by measuring their ATP, FMN and iron porphyrins. Bacteriuria detection and antibiograms can be determined within half a day. The characterization of the sample for its soluble ATP, FMN or prophyrins was also performed.

  11. Induced pluripotent stem cells in Alzheimer's disease: applications for disease modeling and cell-replacement therapy.

    PubMed

    Yang, Juan; Li, Song; He, Xi-Biao; Cheng, Cheng; Le, Weidong

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in those over the age of 65. While a numerous of disease-causing genes and risk factors have been identified, the exact etiological mechanisms of AD are not yet completely understood, due to the inability to test theoretical hypotheses on non-postmortem and patient-specific research systems. The use of recently developed and optimized induced pluripotent stem cells (iPSCs) technology may provide a promising platform to create reliable models, not only for better understanding the etiopathological process of AD, but also for efficient anti-AD drugs screening. More importantly, human-sourced iPSCs may also provide a beneficial tool for cell-replacement therapy against AD. Although considerable progress has been achieved, a number of key challenges still require to be addressed in iPSCs research, including the identification of robust disease phenotypes in AD modeling and the clinical availabilities of iPSCs-based cell-replacement therapy in human. In this review, we highlight recent progresses of iPSCs research and discuss the translational challenges of AD patients-derived iPSCs in disease modeling and cell-replacement therapy. PMID:27184028

  12. Application of multispectral systems for the diagnosis of plant diseases

    NASA Astrophysics Data System (ADS)

    Feng, Jie; Liao, Ningfang; Wang, Guolong; Luo, Yongdao; Liang, Minyong

    2008-03-01

    Multispectral imaging technique combines space imaging and spectral detecting. It can obtain the spectral information and image information of object at the same time. Base on this concept, A new method proposed multispectral camera system to demonstrated plant diseases. In this paper, multispectral camera was used as image capturing device. It consists of a monochrome CCD camera and 16 narrow-band filters. The multispectral images of Macbeth 24 color patches are captured under the illumination of incandescent lamp in this experiment The 64 spectral reflectances of each color patches are calculated using Spline interpolation from 400 to 700nm in the process. And the color of the object is reproduced from the estimated spectral reflectance. The result for reproduction is contrast with the color signal using X-rite PULSE spectrophotometer. The average and maximum ΔΕ * ab are 9.23 and 12.81. It is confirmed that the multispectral system realizes the color reproduction of plant diseases from narrow-band multispectral image.

  13. Clinical Applications of Mesenchymal Stem Cells in Chronic Diseases

    PubMed Central

    Sitzia, Clementina; Erratico, Silvia; Torrente, Yvan

    2014-01-01

    Extraordinary progress in understanding several key features of stem cells has been made in the last ten years, including definition of the niche, and identification of signals regulating mobilization and homing as well as partial understanding of the mechanisms controlling self-renewal, commitment, and differentiation. This progress produced invaluable tools for the development of rational cell therapy protocols that have yielded positive results in preclinical models of genetic and acquired diseases and, in several cases, have entered clinical experimentation with positive outcome. Adult mesenchymal stem cells (MSCs) are nonhematopoietic cells with multilineage potential to differentiate into various tissues of mesodermal origin. They can be isolated from bone marrow and other tissues and have the capacity to extensively proliferate in vitro. Moreover, MSCs have also been shown to produce anti-inflammatory molecules which can modulate humoral and cellular immune responses. Considering their regenerative potential and immunoregulatory effect, MSC therapy is a promising tool in the treatment of degenerative, inflammatory, and autoimmune diseases. It is obvious that much work remains to be done to increase our knowledge of the mechanisms regulating development, homeostasis, and tissue repair and thus to provide new tools to implement the efficacy of cell therapy trials. PMID:24876848

  14. Application of plant impedance for diagnosing plant disease

    NASA Astrophysics Data System (ADS)

    Xu, Huirong; Jiang, Xuesong; Zhu, Shengpan; Ying, Yibin

    2006-10-01

    Biological cells have components acting as electrical elements that maintain the health of the cell by regulation of the electrical charge content. Plant impedance is decided by the state of plant physiology and pathology. Plant physiology and pathology can be studies by measuring plant impedance. The effect of Cucumber Mosaic Virus red bean isolate (CMV-RB) on electrical resistance of tomato leaves was studied by the method of impedance measurement. It was found that the value of resistance of tomato leaves infected with CMV-RB was smaller than that in sound plant leaves. This decrease of impedances in leaf tissue was occurred with increased severity of disease. The decrease of resistance of tomato leaves infected with CMV-RB could be detected by electrical resistance detecting within 4 days after inoculation even though significant visible differences between the control and the infected plants were not noted, so that the technique for measurement of tomato leaf tissue impedance is a rapid, clever, simple method on diagnosis of plant disease.

  15. Current Progress in Nanotechnology Applications for Diagnosis and Treatment of Kidney Diseases

    PubMed Central

    Lee, Sue Hyun; Lee, Jung Bok; Bae, Min Soo; Balikov, Daniel A.; Hwang, Amy; Boire, Timothy C.; Kwon, Il Keun; Sung, Hak-Joon

    2016-01-01

    Significant progress has been made in nanomedicine, primarily in the form of nanoparticles, for theranostic applications to various diseases. A variety of materials, both organic and inorganic, have been used to develop nanoparticles with promise to achieve improved efficacy in medical applications as well as reduced systemic side effects compared to current standard of care medical practices. In particular, this article highlights the recent development and application of nanoparticles for diagnosing and treating nephropathologies. PMID:26121684

  16. Prebiotic Supplementation has Only Minimal Effects on Growth Efficiency, Intestinal Health and Disease Resistance of Westslope Cutthroat Trout Oncorhynchus clarkii lewisi Fed 30% Soybean Meal

    PubMed Central

    Sealey, Wendy M.; Conley, Zachariah B.; Bensley, Molly

    2015-01-01

    Prebiotics have successfully been used to prevent infectious diseases in aquaculture and there is an increasing amount of literature that suggests that these products can also improve alternative protein utilization and digestion. Therefore, the objective of this study was to examine whether prebiotic supplementation increased the growth efficiency, intestinal health, and disease resistance of cutthroat trout fed a high level of dietary soybean meal. To achieve this objective, juvenile Westslope cutthroat trout (Oncorhynchus clarkii lewisi) were fed a practical type formulation with 0 or 30% dietary soybean meal with or without the commercial prebiotic (Grobiotic-A) prior to experimental exposure to Flavobacterium psychrophilum. Juvenile Westslope cutthroat trout (initial weight 7.8 g/fish ±SD of 0.5 g) were stocked at 30 fish/tank in 75 L tanks with six replicate tanks per diet and fed their respective diets for 20 weeks. Final weights of Westslope cutthroat trout were affected by neither dietary soybean meal inclusion level (P = 0.9582) nor prebiotic inclusion (P = 0.9348) and no interaction was observed (P = 0.1242). Feed conversion ratios were similarly not affected by soybean meal level (P = 0.4895), prebiotic inclusion (P = 0.3258) or their interaction (P = 0.1478). Histological examination of the distal intestine of Westslope cutthroat trout demonstrated increases in inflammation due to both increased soybean meal inclusion level (P = 0.0038) and prebiotic inclusion (P = 0.0327) without significant interaction (P = 0.3370). Feeding dietary soybean meal level at 30% increased mortality of F. psychrophilum cohabitation challenged Westslope cutthroat trout (P = 0.0345) while prebiotic inclusion tended to decrease mortality (P = 0.0671). These results indicate that subclinical alterations in intestinal inflammation levels due to high dietary inclusion levels of soybean meal could predispose Westslope cutthroat

  17. Prebiotic Supplementation has Only Minimal Effects on Growth Efficiency, Intestinal Health and Disease Resistance of Westslope Cutthroat Trout Oncorhynchus clarkii lewisi Fed 30% Soybean Meal.

    PubMed

    Sealey, Wendy M; Conley, Zachariah B; Bensley, Molly

    2015-01-01

    Prebiotics have successfully been used to prevent infectious diseases in aquaculture and there is an increasing amount of literature that suggests that these products can also improve alternative protein utilization and digestion. Therefore, the objective of this study was to examine whether prebiotic supplementation increased the growth efficiency, intestinal health, and disease resistance of cutthroat trout fed a high level of dietary soybean meal. To achieve this objective, juvenile Westslope cutthroat trout (Oncorhynchus clarkii lewisi) were fed a practical type formulation with 0 or 30% dietary soybean meal with or without the commercial prebiotic (Grobiotic-A) prior to experimental exposure to Flavobacterium psychrophilum. Juvenile Westslope cutthroat trout (initial weight 7.8 g/fish ±SD of 0.5 g) were stocked at 30 fish/tank in 75 L tanks with six replicate tanks per diet and fed their respective diets for 20 weeks. Final weights of Westslope cutthroat trout were affected by neither dietary soybean meal inclusion level (P = 0.9582) nor prebiotic inclusion (P = 0.9348) and no interaction was observed (P = 0.1242). Feed conversion ratios were similarly not affected by soybean meal level (P = 0.4895), prebiotic inclusion (P = 0.3258) or their interaction (P = 0.1478). Histological examination of the distal intestine of Westslope cutthroat trout demonstrated increases in inflammation due to both increased soybean meal inclusion level (P = 0.0038) and prebiotic inclusion (P = 0.0327) without significant interaction (P = 0.3370). Feeding dietary soybean meal level at 30% increased mortality of F. psychrophilum cohabitation challenged Westslope cutthroat trout (P = 0.0345) while prebiotic inclusion tended to decrease mortality (P = 0.0671). These results indicate that subclinical alterations in intestinal inflammation levels due to high dietary inclusion levels of soybean meal could predispose Westslope cutthroat

  18. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    PubMed

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  19. Application of multispectral reflectance for early detection of tomato disease

    NASA Astrophysics Data System (ADS)

    Xu, Huirong; Zhu, Shengpan; Ying, Yibin; Jiang, Huanyu

    2006-10-01

    Automatic diagnosis of plant disease is important for plant management and environmental preservation in the future. The objective of this study is to use multispectral reflectance measurements to make an early discrimination between the healthy and infected plants by the strain of tobacco mosaic virus (TMV-U1) infection. There were reflectance changes in the visible (VIS) and near infrared spectroscopy (NIR) between the healthy and infected plants. Discriminant models were developed using discriminant partial least squares (DPLS) and Mahalanobis distance (MD). The DPLS models had a root mean square error of calibration (RMSEC) of 0.397 and correlation coefficient (r) of 0.59 and the MD model correctly classified 86.7% healthy plants and up to 91.7% infected plants.

  20. Gene editing and its application for hematological diseases.

    PubMed

    Osborn, Mark J; Belanto, Joseph J; Tolar, Jakub; Voytas, Daniel F

    2016-07-01

    The use of precise, rationally designed gene-editing nucleases allows for targeted genome and transcriptome modification, and at present, four major classes of nucleases are being employed: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. Each reagent shares the ability to recognize and bind a target sequence of DNA. Depending on the properties of the reagent, the DNA can be cleaved on one or both strands, or epigenetic changes can be mediated. These novel properties can impact hematological disease by allowing for: (1) direct modification of hematopoietic stem/progenitor cells (HSPCs), (2) gene alteration of hematopoietic lineage committed terminal effectors, (3) genome engineering in non-hematopoietic cells with reprogramming to a hematopoietic phenotype, and (4) transcriptome modulation for gene regulation, modeling, and discovery. PMID:27233509

  1. [AM and its application in plant disease prevention of Chinese medicinal herbs cultivation].

    PubMed

    Xiao, Wenjuan; Yang, Guang; Chen, Meilan; Guo, Lanpin; Wang, Min

    2011-02-01

    To study the beneficial effect of AMF from the utilization achievement in the agroforestry research, we discuss the application of AM in medicinal plant disease prevention and control. This paper summarized the type of medicinal plant disease, the influence of plant disease and the commonly used prevention method in production. As for the adverse consequences caused by plant's non-infectious and infectious diseases, AM has some improvement function. Something will affect the function of AM in the prevention of medicinal plant disease, for example, the relationship between AMF and the plants, the quantity, the time and the environmental factors about AMF inoculation and so on. In order to achieve the useful effect of AM in the prevention of medicinal plant disease, we should choose the suitable condition during production in practice to carry on the vaccination. PMID:21585020

  2. Application of Infrared and Raman Spectroscopy for the Identification of Disease Resistant Trees.

    PubMed

    Conrad, Anna O; Bonello, Pierluigi

    2015-01-01

    New approaches for identifying disease resistant trees are needed as the incidence of diseases caused by non-native and invasive pathogens increases. These approaches must be rapid, reliable, cost-effective, and should have the potential to be adapted for high-throughput screening or phenotyping. Within the context of trees and tree diseases, we summarize vibrational spectroscopic and chemometric methods that have been used to distinguish between groups of trees which vary in disease susceptibility or other important characteristics based on chemical fingerprint data. We also provide specific examples from the literature of where these approaches have been used successfully. Finally, we discuss future application of these approaches for wide-scale screening and phenotyping efforts aimed at identifying disease resistant trees and managing forest diseases. PMID:26779211

  3. Application of Infrared and Raman Spectroscopy for the Identification of Disease Resistant Trees

    PubMed Central

    Conrad, Anna O.; Bonello, Pierluigi

    2016-01-01

    New approaches for identifying disease resistant trees are needed as the incidence of diseases caused by non-native and invasive pathogens increases. These approaches must be rapid, reliable, cost-effective, and should have the potential to be adapted for high-throughput screening or phenotyping. Within the context of trees and tree diseases, we summarize vibrational spectroscopic and chemometric methods that have been used to distinguish between groups of trees which vary in disease susceptibility or other important characteristics based on chemical fingerprint data. We also provide specific examples from the literature of where these approaches have been used successfully. Finally, we discuss future application of these approaches for wide-scale screening and phenotyping efforts aimed at identifying disease resistant trees and managing forest diseases. PMID:26779211

  4. A Novel, Minimally-Invasive Approach to Repair Degenerative Disk Disease in an Ovine Model Using Injectable Polymethyl-Methacrylate and Bovine Collagen (PMMA/BC)

    PubMed Central

    Feldman, Erica; Narayan, Anisha; Taylor, William

    2016-01-01

    Background : The natural, inflammatory repair processes of an injured intervertebral degenerative disc can propagate further injury and destruction. While there are many different treatment modalities of the pain related to degenerative disc disease, none are actually reparative in nature. Treatment strategies to repair a degenerative disc without inducing a destructive inflammatory milieu have been elusive.  Purpose: The purpose of this experiment is to discover the feasibility of reconstructing an injured intervertebral disc using an injected, inert polymer as the foundation for endogenous collagen growth. Study Design: In this ovine model of six subjects in total, we introduce a modality where a large inert polymer, polymethyl methacrylate (PMMA), in conjunction bovine collagen (BC) is injected into the intervertebral disc. Following six months of observation, histologic specimens were evaluated macroscopically and microscopically for evidence of a benefit of the injectable PMMA/BC. Methods: We obtained six merino sheep for this study. Concentric injuries were made to four of their lumbar intervertebral discs. Two of those levels were treated with a percutaneous injection of 0.3 cc of PMMA/BC. The remaining lumbar levels were left untreated and were our controls. After six months, all subjects were sacrificed. Their four levels were extracted and were examined macroscopically and microscopically. Results: All subjects tolerated the lumbar injury and percutaneous injection of PMMA/BC well. After the six month interval, all subjects have demonstrated an intact architecture of their lumbar disc height at the macroscopic and microscopic level. Microscopically, there was no evidence of external migration of the PMMA/BC microspheres, nor was there any evidence of an inflammatory response by its presence. Notably, the PMMA/BC microspheres were well-incorporated into the concentric disc tears and had undergone endogenous collagen formation in its environment

  5. Lasers in minimally invasive periodontal and peri-implant therapy.

    PubMed

    Mizutani, Koji; Aoki, Akira; Coluzzi, Donald; Yukna, Raymond; Wang, Chen-Ying; Pavlic, Verica; Izumi, Yuichi

    2016-06-01

    Laser therapy has the potential to be an effective, minimally invasive procedure in periodontal therapy. The aim of the present review was to survey the relevant literature on the clinical application of lasers as a minimally invasive treatment for periodontitis and peri-implant disease. Currently, there are a large number of published clinical studies and case reports that evaluate the adjunctive use of diode, carbon dioxide, neodymium-doped yttrium aluminium garnet (Nd:YAG), erbium-doped yttrium aluminium garnet (Er:YAG) and erbium, chromium-doped: yttrium, scandium, gallium, garnet (Er,Cr:YSGG) lasers or antimicrobial photodynamic therapy for nonsurgical and minimally invasive surgical treatment of periodontal pockets. These procedures are expected not only to control inflammation but also to provide biostimulation effects with photonic energy. Recent meta-analyses did not show statistically significant differences in pocket reduction and clinical attachment gain compared with mechanical debridement alone, although limited positive effects of adjunctive laser therapy were reported. At present, systematic literature approaches suggest that more evidence-based studies need to be performed to support the integration of various laser therapies into the treatment of periodontal and peri-implant diseases. The disparity between previous statistical analyses and individual successful clinical outcomes of laser applications might reveal the necessity of developing optimal laser-treatment modalities of different wavelengths and better-defined indications for each protocol. PMID:27045437

  6. Clinical Applications of Molecular Biology for Infectious Diseases

    PubMed Central

    Speers, David J

    2006-01-01

    Molecular biological methods for the detection and characterisation of microorganisms have revolutionised diagnostic microbiology and are now part of routine specimen processing. Polymerase chain reaction (PCR) techniques have led the way into this new era by allowing rapid detection of microorganisms that were previously difficult or impossible to detect by traditional microbiological methods. In addition to detection of fastidious microorganisms, more rapid detection by molecular methods is now possible for pathogens of public health importance. Molecular methods have now progressed beyond identification to detect antimicrobial resistance genes and provide public health information such as strain characterisation by genotyping. Treatment of certain microorganisms has been improved by viral resistance detection and viral load testing for the monitoring of responses to antiviral therapies. With the advent of multiplex PCR, real-time PCR and improvements in efficiency through automation, the costs of molecular methods are decreasing such that the role of molecular methods will further increase. This review will focus on the clinical utility of molecular methods performed in the clinical microbiology laboratory, illustrated with the many examples of how they have changed laboratory diagnosis and therefore the management of infectious diseases. PMID:16886046

  7. Clinical application of stem cell therapy in Parkinson's disease.

    PubMed

    Politis, Marios; Lindvall, Olle

    2012-01-01

    Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce long-lasting symptomatic relief without side effects while counteracting PD progression. PMID:22216957

  8. Anaesthesia for minimally invasive surgery

    PubMed Central

    Dec, Marta

    2015-01-01

    Minimally invasive surgery (MIS) is rising in popularity. It offers well-known benefits to the patient. However, restricted access to the surgical site and gas insufflation into the body cavities may result in severe complications. From the anaesthetic point of view MIS poses unique challenges associated with creation of pneumoperitoneum, carbon dioxide absorption, specific positioning and monitoring a patient to whom the anaesthetist has often restricted access, in a poorly lit environment. Moreover, with refinement of surgical procedures and growing experience the anaesthetist is presented with patients from high-risk groups (obese, elderly, with advanced cardiac and respiratory disease) who once were deemed unsuitable for the laparoscopic technique. Anaesthetic management is aimed at getting the patient safely through the procedure, minimizing the specific risks arising from laparoscopy and the patient's coexisting medical problems, ensuring quick recovery and a relatively pain-free postoperative course with early return to normal function. PMID:26865885

  9. Beyond Oncology – Application of HPMA Copolymers in Non-cancerous Diseases

    PubMed Central

    Liu, Xin-Ming; Miller, Scott C.; Wang, Dong

    2009-01-01

    Macromolecular drug conjugates have been developed to improve the efficacy and safety profile of various therapeutic agents for many years. Among them, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates are the most extensively studied delivery platforms for the effective treatment of cancer. In recent years, the applications of HPMA copolymers for the treatment of a broader range of non-cancerous diseases have also been explored. This review highlights the recent developments in the rational design, synthesis, and evaluation of novel HPMA copolymer-drug conjugates for non-cancerous diseases, such as musculoskeletal diseases, infectious diseases and spinal cord injury. The translation potential of these applications are also briefly discussed. PMID:19909776

  10. TOWARD MINIMALLY ADHESIVE SURFACES UTILIZING SILOXANES

    EPA Science Inventory

    Three types of siloxane-based network polymers have been investigated for their surface properties towards potential applications as minimally adhesive coatings. A filled poly(dimethylsiloxane) (PDMS) elastomer, RTV it, has been studied to determine surface weldability and stabil...

  11. Amaranth oil application for coronary heart disease and hypertension.

    PubMed

    Martirosyan, Danik M; Miroshnichenko, Lidia A; Kulakova, Svetlana N; Pogojeva, Ala V; Zoloedov, Vladimir I

    2007-01-01

    Cardiovascular disease (CVD) is the Nation's leading killer for both men and women among all racial and ethnic groups. Development and progression of CVD is linked to the presence of risk factors such as hyperlipidemia, hypertension, obesity, and diabetes mellitus. It is known that cholesterol is an indicator of increased risk of heart attack and stroke. Low-density cholesterol (LDL) above 130 mg/dl high-density cholesterol (HDL) cholesterol below 35 mg/dl and total blood cholesterol above 200 mg/dl are indicators of problematic cholesterol. Proper ranges of cholesterol are important in the prevention of CVD. It has been suggested that a reduction in the consumption of saturated and an increase in unsaturated fatty acids is beneficial and prevents CVD. Amaranth grain contains tocotrienols and squalene compounds, which are known to affect cholesterol biosynthesis. The cholesterol precursors squalene, lanosterol and other methyl sterols, reflect cholesterol synthesis 123, whereas plant sterols and cholestanol, a metabolite of cholesterol, reflect the efficiency of cholesterol absorption in normal and hyperlipidemic populations 456. Qureshi with co-authors 7 showed that feeding of chickens with amaranth oil decreases blood cholesterol levels, which are supported by the work of others 8. Previously, we have shown that Amaranth oil modulates the cell membrane fluidity 9 and stabilized membranes that could be one reason as to why it is beneficial to those who consume it. It is known that in hypertension, the cell membrane is defective and hence, the movement of the Na and K ions across the cell membranes could defective that could contribute to the development of increase in blood pressure. Based on these properties of amaranth oil we hypothesize that it could be of significant benefit for patients with CVD. PMID:17207282

  12. Amaranth oil application for coronary heart disease and hypertension

    PubMed Central

    Martirosyan, Danik M; Miroshnichenko, Lidia A; Kulakova, Svetlana N; Pogojeva, Ala V; Zoloedov, Vladimir I

    2007-01-01

    Cardiovascular disease (CVD) is the Nation's leading killer for both men and women among all racial and ethnic groups. Development and progression of CVD is linked to the presence of risk factors such as hyperlipidemia, hypertension, obesity, and diabetes mellitus. It is known that cholesterol is an indicator of increased risk of heart attack and stroke. Low-density cholesterol (LDL) above 130 mg/dl high-density cholesterol (HDL) cholesterol below 35 mg/dl and total blood cholesterol above 200 mg/dl are indicators of problematic cholesterol. Proper ranges of cholesterol are important in the prevention of CVD. It has been suggested that a reduction in the consumption of saturated and an increase in unsaturated fatty acids is beneficial and prevents CVD. Amaranth grain contains tocotrienols and squalene compounds, which are known to affect cholesterol biosynthesis. The cholesterol precursors squalene, lanosterol and other methyl sterols, reflect cholesterol synthesis [1-3], whereas plant sterols and cholestanol, a metabolite of cholesterol, reflect the efficiency of cholesterol absorption in normal and hyperlipidemic populations [4-6]. Qureshi with co-authors [7] showed that feeding of chickens with amaranth oil decreases blood cholesterol levels, which are supported by the work of others [8]. Previously, we have shown that Amaranth oil modulates the cell membrane fluidity [9] and stabilized membranes that could be one reason as to why it is beneficial to those who consume it. It is known that in hypertension, the cell membrane is defective and hence, the movement of the Na and K ions across the cell membranes could defective that could contribute to the development of increase in blood pressure. Based on these properties of amaranth oil we hypothesize that it could be of significant benefit for patients with CVD. PMID:17207282

  13. Lyme disease and conservation

    USGS Publications Warehouse

    Ginsberg, H.

    1994-01-01

    Lyme disease is a tick-borne illness that is wide-spread in North America, especially in the northeastern and northcentral United States. This disease could negatively influence efforts to conserve natural populations in two ways: (1) the disease could directly affect wild animal health; and (2) tick control efforts could adversely affect natural populations and communities. Lyme disease affects several domestic animals, but symptoms have been reported in only a few wild species. Direct effects of Lyme disease on wild animal populations have not been reported, but the disease should be considered as a possible cause in cases of unexplained population declines in endemic areas. Methods available to manage ticks and Lyme disease include human self-protection techniques, manipulation of habitats and hosts species populations, biological control, and pesticide applications. The diversity of available techniques allows selection of approaches to minimize environmental effects by (1) emphasizing personal protection techniques, (2) carefully targeting management efforts to maximize efficiency, and (3) integrating environmentally benign techniques to improve management while avoiding broad-scale environmentally destructive approaches. The environmental effects of Lyme disease depend, to a large extent, on the methods chosen to minimize human exposure to infected ticks. Conservation biologists can help design tick management programs that effectively lower the incidence of human Lyme disease while simultaneously minimizing negative effects on natural populations.

  14. Mucosal immunization application to allergic disease: sublingual immunotherapy.

    PubMed

    Frati, Franco; Moingeon, Philippe; Marcucci, Francesco; Puccinelli, Paola; Sensi, Laura; Di Cara, Giuseppe; Incorvaia, Cristoforo

    2007-01-01

    Sublingual immunotherapy (SLIT) is an effective and safe treatment for respiratory allergy, and its mechanism of action currently is investigated with increasing attention. Studies of pharmacokinetics showed that allergen extracts administered via the sublingual route are not directly absorbed by the oral mucosa but are long retained at mucosal level, where the allergen molecules are captured by dendritic cells and, following their migration in the draining lymph nodes, presented to T cells. This seems to be the pivotal factor underlying the mechanisms of action of SLIT, at least for the long-term effects, and for the short-term efficacy, observed with ultrarush or coseasonal treatment, a down-regulation of mast cells resulting in hyporeactivity at the peak of the pollen season may be suggested. Regarding the clinically established long-lasting effects, the core mechanism is likely to consist of T regulatory (Treg) cell activation. In particular, Treg cells differentiate from naive T cells after application of soluble antigens to the mucosae, a crucial factor being the tolerogenic function of dendritic cells, and exert a suppressive effect on both Th1 and Th2 responses. Moreover, at least for the type 1 cells (Treg1), a production of IL-10 with consequent down-modulation of the immune response has been reported. Another characteristic of sublingual immunization is the absence of effectors cells, viz., mast cells, basophils, and eosinophils, in the oral mucosa of allergic subjects, which account for the excellent tolerability of SLIT. PMID:17390755

  15. Study of Mobile GIS Application on the Field of GPR in the Road Disease Detection

    NASA Astrophysics Data System (ADS)

    Liao, Q.; Yang, F.

    2013-12-01

    With the reflection principle of pulsed electromagnetic waves, ground penetrating radar (GPR) is available to measure depth of the pavement layer, reflecting different hidden danger underground. Currently, GPR has been widely used in road engineering with the constantly improved ability of detection and diagnosis to road diseases. The sum of road disease data of a region, a city, and even a wider range will be a very informative database, so we need a more convenient way to achieve data query intuitively. As mobile internet develops continuously, application of mobile terminal device plays a more important role in information platform. Mobile GIS, with smartphone as its terminal, is supported by the mobile Internet, GPS or base station as its positioning method. In this article, based on Android Platform and using C/S pattern, the LBS application of road diseases information which integrates Baidu Map API and database technology was discussed. After testing, it can display and query the real-time and historical road diseases data, the classification of data on a phone intuitively and easily. Because of the location technique and high portability of smart phone, the spot investigations of road diseases become easier. Though, the system needs further improvement, especially with the improving of the mobile phone performance, the system can also add the function of analysis to the disease data, thus forming a set of service system with more applicable.

  16. Eleventh annual Department of Energy low-level waste management conference. Volume 3: Waste characterization, waste reduction and minimization, prototype licensing application

    SciTech Connect

    1989-11-01

    Thirteen papers are presented in volume 3. The seven papers on waste characterization discuss sampling, analysis, and certification techniques for low-level radioactive wastes. Three papers discuss US DOE waste minimization policies and regulations, Y-12 Plant`s reduction of chlorinated solvents, and C-14 removal from spent resins. The last three papers discuss the licensing studies for earth-mounded concrete bunkers for LLW disposal. Papers have been processed separately for inclusion on the data base.

  17. Minimally Invasive Valve Surgery

    PubMed Central

    Pope, Nicolas H.; Ailawadi, Gorav

    2014-01-01

    Cardiac valve surgery is life saving for many patients. The advent of minimally invasive surgical techniques has historically allowed for improvement in both post-operative convalescence and important clinical outcomes. The development of minimally invasive cardiac valve repair and replacement surgery over the past decade is poised to revolutionize the care of cardiac valve patients. Here, we present a review of the history and current trends in minimally invasive aortic and mitral valve repair and replacement, including the development of sutureless bioprosthetic valves. PMID:24797148

  18. [Application of spatial relative risk estimation in communicable disease risk evaluation].

    PubMed

    Zhang, Yewu; Guo, Qing; Wang, Xiaofeng; Yu, Meng; Su, Xuemei; Dong, Yan; Zhang, Chunxi

    2015-05-01

    This paper summaries the application of adaptive kernel density algorithm in the spatial relative risk estimation of communicable diseases by using the reported data of infectious diarrhea (other than cholera, dysentery, typhoid and paratyphoid) in Ludian county and surrounding area in Yunnan province in 2013. Statistically significant fluctuations in an estimated risk function were identified through the use of asymptotic tolerance contours, and finally these data were visualized though disease mapping. The results of spatial relative risk estimation and disease mapping showed that high risk areas were in southeastern Shaoyang next to Ludian. Therefore, the spatial relative risk estimation of disease by using adaptive kernel density algorithm and disease mapping technique is a powerful method in identifying high risk population and areas. PMID:26080648

  19. Applications of metabolomics for kidney disease research: from biomarkers to therapeutic targets.

    PubMed

    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

  20. The application of biomarkers in clinical trials for motor neuron disease

    PubMed Central

    Ganesalingam, Jeban; Bowser, Robert

    2010-01-01

    The interest and research into disease-related biomarkers has greatly accelerated over the last 10 years. The potential clinical benefits for disease-specific biomarkers include a more rapid and accurate disease diagnosis, and potential reduction in size and duration of clinical drug trials, which would speed up drug development. The application of biomarkers into the clinical arena of motor neuron disease should both determine if a drug hits its proposed target and whether the drug alters the course of disease. This article will highlight the progress made in discovering suitable biomarker candidates from a variety of sources, including imaging, neurophysiology and proteomics. For biomarkers to have clinical utility, specific criteria must be satisfied. While there has been tremendous effort to discover biomarkers, very few have been translated to the clinic. The bottlenecks in the biomarker pipeline will be highlighted as well as lessons that can be learned from other disciplines, such as oncology. PMID:20406070

  1. Autologous bone marrow concentrate: review and application of a novel intra-articular orthobiologic for cartilage disease.

    PubMed

    Sampson, Steven; Botto-van Bemden, Angie; Aufiero, Danielle

    2013-09-01

    Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow

  2. Optimal time-points for minimal residual disease monitoring change on the basis of the method used in patients with acute myeloid leukemia who underwent allogeneic stem cell transplantation: a comparison between multiparameter flow cytometry and Wilms' tumor 1 expression.

    PubMed

    Rossi, Giovanni; Carella, Angelo Michele; Minervini, Maria Marta; di Nardo, Francesco; Waure, Chiara de; Greco, Michele Mario; Merla, Emanuela; Cillis, Giovanni Pio de; Di Renzo, Nicola; Melpignano, Angela; Capalbo, Silvana; Palumbo, Gaetano; Pisapia, Giovanni; Cascavilla, Nicola

    2015-02-01

    Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p=0.006 and p=0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p=0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used. PMID:25498507

  3. Pre-transplant achievement of negativity in minimal residual disease and French-American-British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients.

    PubMed

    Ma, Liyuan; Hao, Siguo; Diong, Colin; Goh, Yeow-Tee; Gopalakrishnan, Sathish; Ho, Aloysius; Hwang, William; Koh, Liang-Piu; Koh, Mickey; Lim, Zi-Yi; Loh, Yvonne; Poon, Michelle; Tan, Lip-Kun; Tan, Patrick; Linn, Yeh-Ching

    2015-05-01

    To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome. PMID:25139689

  4. Prostate resection - minimally invasive

    MedlinePlus

    ... are: Erection problems (impotence) No symptom improvement Passing semen back into your bladder instead of out through ... Whelan JP, Goeree L. Systematic review and meta-analysis of transurethral resection of the prostate versus minimally ...

  5. Minimizing Shortness of Breath

    MedlinePlus

    ... Top Doctors in the Nation Departments & Divisions Home Health Insights Stress & Relaxation Breathing and Relaxation Minimizing Shortness of Breath ... Management Assess Your Stress Coping Strategies Identifying ... & Programs Health Insights Doctors & Departments Research & Science Education & Training Make ...

  6. Minimally invasive hip replacement

    MedlinePlus

    ... Smits SA, Swinford RR, Bahamonde RE. A randomized, prospective study of 3 minimally invasive surgical approaches in total hip arthroplasty: comprehensive gait analysis. J Arthroplasty . 2008;23:68-73. PMID: 18722305 ...

  7. Minimal Orderings Revisited

    SciTech Connect

    Peyton, B.W.

    1999-07-01

    When minimum orderings proved too difficult to deal with, Rose, Tarjan, and Leuker instead studied minimal orderings and how to compute them (Algorithmic aspects of vertex elimination on graphs, SIAM J. Comput., 5:266-283, 1976). This paper introduces an algorithm that is capable of computing much better minimal orderings much more efficiently than the algorithm in Rose et al. The new insight is a way to use certain structures and concepts from modern sparse Cholesky solvers to re-express one of the basic results in Rose et al. The new algorithm begins with any initial ordering and then refines it until a minimal ordering is obtained. it is simple to obtain high-quality low-cost minimal orderings by using fill-reducing heuristic orderings as initial orderings for the algorithm. We examine several such initial orderings in some detail.

  8. Minimalism. Clip and Save.

    ERIC Educational Resources Information Center

    Hubbard, Guy

    2002-01-01

    Provides background information on the art movement called "Minimalism" discussing why it started and its characteristics. Includes learning activities and information on the artist, Donald Judd. Includes a reproduction of one of his art works and discusses its content. (CMK)

  9. Minimally Invasive Forefoot Surgery in France.

    PubMed

    Meusnier, Tristan; Mukish, Prikesht

    2016-06-01

    Study groups have been formed in France to advance the use of minimally invasive surgery. These techniques are becoming more frequently used and the technique nuances are continuing to evolve. The objective of this article was to advance the awareness of the current trends in minimally invasive surgery for common diseases of the forefoot. The percutaneous surgery at the forefoot is less developed at this time, but also will be discussed. PMID:27261810

  10. Future of Minimally Invasive Colorectal Surgery.

    PubMed

    Whealon, Matthew; Vinci, Alessio; Pigazzi, Alessio

    2016-09-01

    Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics. PMID:27582647

  11. Conventional and pretargeted radioimmunotherapy using bismuth-213 to target and treat non-Hodgkin lymphomas expressing CD20: a preclinical model toward optimal consolidation therapy to eradicate minimal residual disease

    PubMed Central

    Park, Steven I.; Shenoi, Jaideep; Pagel, John M.; Hamlin, Don K.; Wilbur, D. Scott; Orgun, Nural; Kenoyer, Aimee L.; Frayo, Shani; Axtman, Amanda; Bäck, Tom; Lin, Yukang; Fisher, Darrell R.; Gopal, Ajay K.; Green, Damian J.

    2010-01-01

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 minutes, tumor uptake for 1F5(scFv)4SA was 16.5% ± 7.0% injected dose per gram compared with 2.3% ± .9% injected dose per gram for the control FP. Mice treated with anti-CD20 PRIT and 600 μCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared with controls (mean tumor volume .01 ± .02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared with 23 days for the control FP (P < .0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT. PMID:20702781

  12. Conventional and Pretargeted Radioimmunotherapy Using Bismuth-213 to Target and Treat Non-Hodgkin Lymphomas Expressing CD20: A Preclinical Model toward Optimal Consolidation Therapy to Eradicate Minimal Residual Disease.

    SciTech Connect

    Park, Steven I.; Shenoi, Jaideep; Pagel, John M.; Hamlin, Donald K.; Wilbur, D. Scott; Orgun, Nural; Kenoyer, Aimee L.; Frayo, Shani; Axtman, Amanda; Back, Tom; Lin, Yukang; Fisher, Darrell R.; Gopal, Ajay K.; Green, Damian J.; Press, Oliver W.

    2010-11-18

    Radioimmunotherapy (RIT) with α-emitting radionuclides is an attractive approach for the treatment of minimal residual disease (MRD) because the short path lengths and high energies of α-particles produce optimal cytotoxicity at small target sites while minimizing damage to surrounding normal tissues. Pretargeted RIT (PRIT) using antibody-streptavidin (Ab-SA) constructs and radiolabeled biotin allows rapid, specific localization of radioactivity at tumor sites, making it an optimal method to target α-emitters with short half-lives, such as bismuth-213 (213Bi). Athymic mice bearing Ramos lymphoma xenografts received anti-CD20 1F5(scFv)4SA fusion protein (FP), followed by a dendrimeric clearing agent and [213Bi]DOTA-biotin. After 90 min, tumor uptake for 1F5(scFv)4SA was 16.5 ± 7.0 % injected dose per gram (ID/g) compared with 2.3 ± 0.9 % ID/g for the control FP. Mice treated with anti-CD20 PRIT and 600 µCi [213Bi]DOTA-biotin exhibited marked tumor growth delays compared to controls (mean tumor volume 0.01 ± 0.02 vs. 203.38 ± 83.03 mm3 after 19 days, respectively). The median survival for the 1F5(scFv)4SA group was 90 days compared to 23 days for the control FP (p<0.0001). Treatment was well tolerated, with no treatment-related mortalities. This study demonstrates the favorable biodistribution profile and excellent therapeutic efficacy attainable with 213Bi-labeled anti-CD20 PRIT.

  13. Applications of Nanotechnology in Diagnostics and Therapeutics of Alzheimer's and Parkinson's Disease.

    PubMed

    Soursou, Georgia; Alexiou, Athanasios; Ashraf, Ghulam Md; Siyal, Asad Ali; Mushtaq, Gohar; Kamal, Mohammad A

    2015-01-01

    In this paper, an extended review analysis has been presented concerning the developments in brain drug delivery through new and efficient applications of nanotechnology. Modern nanotechnological approaches for the diagnosis and treatment of Alzheimer's and Parkinson's diseases are described along with simultaneous analysis of safety and practical clinical usage of these strategies. PMID:26560322

  14. Imaging and minimally invasive aortic valve replacement

    PubMed Central

    Loor, Gabriel

    2015-01-01

    Cardiovascular imaging has been the most important tool allowing for innovation in cardiac surgery. There are now a variety of approaches available for treating aortic valve disease, including standard sternotomy, minimally invasive surgery, and percutaneous valve replacement. Minimally invasive cardiac surgery relies on maximizing exposure within a limited field of view. The complexity of this approach is increased as the relationship between the great vessels and the bony thorax varies between individuals. Ultimately, the success of minimally invasive surgery depends on appropriate choices regarding the type and location of the incision, cannulation approach, and cardioprotection strategy. These decisions are facilitated by preoperative imaging, which forms the focus of this review. PMID:25694979

  15. Minimally invasive procedures

    PubMed Central

    Baltayiannis, Nikolaos; Michail, Chandrinos; Lazaridis, George; Anagnostopoulos, Dimitrios; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Kioumis, Ioannis; Pitsiou, Georgia; Katsikogiannis, Nikolaos; Tsakiridis, Kosmas; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

    2015-01-01

    Minimally invasive procedures, which include laparoscopic surgery, use state-of-the-art technology to reduce the damage to human tissue when performing surgery. Minimally invasive procedures require small “ports” from which the surgeon inserts thin tubes called trocars. Carbon dioxide gas may be used to inflate the area, creating a space between the internal organs and the skin. Then a miniature camera (usually a laparoscope or endoscope) is placed through one of the trocars so the surgical team can view the procedure as a magnified image on video monitors in the operating room. Specialized equipment is inserted through the trocars based on the type of surgery. There are some advanced minimally invasive surgical procedures that can be performed almost exclusively through a single point of entry—meaning only one small incision, like the “uniport” video-assisted thoracoscopic surgery (VATS). Not only do these procedures usually provide equivalent outcomes to traditional “open” surgery (which sometimes require a large incision), but minimally invasive procedures (using small incisions) may offer significant benefits as well: (I) faster recovery; (II) the patient remains for less days hospitalized; (III) less scarring and (IV) less pain. In our current mini review we will present the minimally invasive procedures for thoracic surgery. PMID:25861610

  16. Minimally invasive procedures on the lumbar spine.

    PubMed

    Skovrlj, Branko; Gilligan, Jeffrey; Cutler, Holt S; Qureshi, Sheeraz A

    2015-01-16

    Degenerative disease of the lumbar spine is a common and increasingly prevalent condition that is often implicated as the primary reason for chronic low back pain and the leading cause of disability in the western world. Surgical management of lumbar degenerative disease has historically been approached by way of open surgical procedures aimed at decompressing and/or stabilizing the lumbar spine. Advances in technology and surgical instrumentation have led to minimally invasive surgical techniques being developed and increasingly used in the treatment of lumbar degenerative disease. Compared to the traditional open spine surgery, minimally invasive techniques require smaller incisions and decrease approach-related morbidity by avoiding muscle crush injury by self-retaining retractors, preventing the disruption of tendon attachment sites of important muscles at the spinous processes, using known anatomic neurovascular and muscle planes, and minimizing collateral soft-tissue injury by limiting the width of the surgical corridor. The theoretical benefits of minimally invasive surgery over traditional open surgery include reduced blood loss, decreased postoperative pain and narcotics use, shorter hospital length of stay, faster recover and quicker return to work and normal activity. This paper describes the different minimally invasive techniques that are currently available for the treatment of degenerative disease of the lumbar spine. PMID:25610845

  17. Applications of Complex Systems Science in Obesity and Noncommunicable Chronic Disease Research1234

    PubMed Central

    Wang, Youfa; Xue, Hong; Esposito, Layla; Joyner, Michael J.; Bar-Yam, Yaneer; Huang, Terry T.-K.

    2014-01-01

    Interest in the application of systems science (SS) to obesity and noncommunicable chronic disease (NCD) research has been growing rapidly over the past decade as the epidemic of obesity and NCDs continues to grow globally. This article summarizes the key messages of the presentations made in the special symposium “Applications of Complex Systems Science in Obesity and Noncommunicable Chronic Disease Research,” held during the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014. Invited leaders from various fields presented cutting-edge aspects of the applications of SS in public health research, with a focus on obesity and NCDs. In addition, the symposium was capped with a discussion on funding opportunities from the NIH. The speakers described the nature of SS, how it could be applied to biomedical and public health research, lessons from SS to inform obesity and NCD interventions, and the promises, challenges, and recommendations going forward. PMID:25469401

  18. Application of artificial photoperiod in fish: a factor that increases susceptibility to infectious diseases?

    PubMed

    Valenzuela, Ariel; Campos, Victor; Yañez, Francisco; Alveal, Katherine; Gutiérrez, Pamela; Rivas, Meyling; Contreras, Nancy; Klempau, Alfredo; Fernandez, Italo; Oyarzun, Ciro

    2012-08-01

    This paper describes and evaluates the mortality associated with the potential stressor effect induced by application of artificial photoperiods in rainbow trout (Oncorhynchus mykiss). After application of artificial photoperiods, high mortalities of trout subjected to this management were recorded (36% in LD 14:10 and 25% in LD 24:0) as compared to controls (7%). The recorded signology related to diseased trout included darkening, lethargy and erratic swimming. Among the morphological changes, skin lesions and ulcerative-type necrosis could be observed. Blood tests, histopathology and isolation of pathogens identified as Flavobacterium psychrophilum, associated with Aeromonas, Pseudomonas and Saprolegnia sp., were performed. The application of artificial photoperiods suggests that fish may be more susceptible to opportunistic diseases; thus, it is advisable to emphasize preventive measures in fish subjected to this management. PMID:22160663

  19. DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

    PubMed Central

    Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

    2014-01-01

    Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

  20. Future perspectives of Smartphone applications for rheumatic diseases self-management.

    PubMed

    Azevedo, Ana Rita Pereira; de Sousa, Hugo Manuel Lopes; Monteiro, Joaquim António Faria; Lima, Aurea Rosa Nunes Pereira

    2015-03-01

    Rheumatic diseases (RD) self-management interventions are designed to improve health-related quality of life, health care utilization, and perceived self-efficacy. Despite these demonstrated good results, there are several issues that hinder or render less appealing these interventions. One economically and socially viable solution is exploiting the potential of Smartphone technology. This potential comes from Smartphones pervasive presence in actual society, combined with the advantages of being personal, intuitive, and computationally powerful, with capability to support applications and assist its user throughout different activities of daily living and environments persistently. With their global acceptance increasing quickly, there is a great opportunity for mobile health in using Smartphone applications for RD self-management. Besides the potential of such applications, research on the development and evaluation of such applications is in the early stages. Therefore, it is important to foresee its future applicability in order to meet the needs of the twenty-first century. PMID:25168866

  1. Short Message Service (SMS) Applications for Disease Prevention in Developing Countries

    PubMed Central

    Suggs, L. Suzanne; Odermatt, Peter

    2012-01-01

    Background The last decade has witnessed unprecedented growth in the number of mobile phones in the developing world, thus linking millions of previously unconnected people. The ubiquity of mobile phones, which allow for short message service (SMS), provides new and innovative opportunities for disease prevention efforts. Objective The aim of this review was to describe the characteristics and outcomes of SMS interventions for disease prevention in developing countries and provide recommendations for future work. Methods A systematic search of peer-reviewed and gray literature was performed for papers published in English, French, and German before May 2011 that describe SMS applications for disease prevention in developing countries. Results A total of 34 SMS applications were described, among which 5 had findings of an evaluation reported. The majority of SMS applications were pilot projects in various levels of sophistication; nearly all came from gray literature sources. Many applications were initiated by the project with modes of intervention varying between one-way or two-way communication, with or without incentives, and with educative games. Evaluated interventions were well accepted by the beneficiaries. The primary barriers identified were language, timing of messages, mobile network fluctuations, lack of financial incentives, data privacy, and mobile phone turnover. Conclusion This review illustrates that while many SMS applications for disease prevention exist, few have been evaluated. The dearth of peer-reviewed studies and the limited evidence found in this systematic review highlight the need for high-quality efficacy studies examining behavioral, social, and economic outcomes of SMS applications and mobile phone interventions aimed to promote health in developing country contexts. PMID:22262730

  2. Current neuroimaging techniques in Alzheimer's disease and applications in animal models

    PubMed Central

    Zhang, Linda; Chang, Raymond Chuen-Chung; Chu, Leung-Wing; Mak, Henry Ka-Fung

    2012-01-01

    With Alzheimer’s disease (AD) quickly becoming the most costly disease to society, and with no disease-modifying treatment currently, prevention and early detection have become key points in AD research. Important features within this research focus on understanding disease pathology, as well as finding biomarkers that can act as early indicators and trackers of disease progression or potential treatment. With the advances in neuroimaging technology and the development of new imaging techniques, the search for cheap, noninvasive, sensitive biomarkers becomes more accessible. Modern neuroimaging techniques are able to cover most aspects of disease pathology, including visualization of senile plaques and neurofibrillary tangles, cortical atrophy, neuronal loss, vascular damage, and changes in brain biochemistry. These methods can provide complementary information, resulting in an overall picture of AD. Additionally, applying neuroimaging to animal models of AD could bring about greater understanding in disease etiology and experimental treatments whilst remaining in vivo. In this review, we present the current neuroimaging techniques used in AD research in both their human and animal applications, and discuss how this fits in to the overall goal of understanding AD. PMID:23133824

  3. Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility.

    PubMed Central

    Kodavanti, U P; Costa, D L; Bromberg, P A

    1998-01-01

    The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S. renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies. Images Figure 2 PMID:9539009

  4. Feasibility and Acceptability of Utilizing a Smartphone Based Application to Monitor Outpatient Discharge Instruction Compliance in Cardiac Disease Patients around Discharge from Hospitalization

    PubMed Central

    Layton, Aimee M.; Whitworth, James; Peacock, James; Bartels, Matthew N.; Jellen, Patricia A.; Thomashow, Byron M.

    2014-01-01

    The purpose of this study was to determine the feasibility and acceptability of utilizing a smartphone based application to monitor compliance in patients with cardiac disease around discharge. For 60 days after discharge, patients' medication compliance, physical activity, follow-up care, symptoms, and reading of education material were monitored daily with the application. 16 patients were enrolled in the study (12 males, 4 females, age 55 ± 18 years) during their hospital stay. Five participants were rehospitalized during the study and did not use the application once discharged. Seven participants completed 1–30 days and four patients completed >31 days. For those 11 patients, medication reminders were utilized 37% (1–30-day group) and 53% (>31-day group) of the time, education material was read 44% (1–30) and 53% (>31) of the time, and physical activity was reported 25% (1–30) and 42% (>31) of the time. Findings demonstrated that patients with stable health utilized the application, even if only minimally. Patients with decreased breath sounds by physical exam and who reported their health as fair to poor on the day of discharge were less likely to utilize the application. Acceptability of the application to report health status varied among the stable patients. PMID:25574165

  5. A model for developing job rotation schedules that eliminate sequential high workloads and minimize between-worker variability in cumulative daily workloads: Application to automotive assembly lines.

    PubMed

    Yoon, Sang-Young; Ko, Jeonghan; Jung, Myung-Chul

    2016-07-01

    The aim of study is to suggest a job rotation schedule by developing a mathematical model in order to reduce cumulative workload from the successive use of the same body region. Workload assessment using rapid entire body assessment (REBA) was performed for the model in three automotive assembly lines of chassis, trim, and finishing to identify which body part exposed to relatively high workloads at workstations. The workloads were incorporated to the model to develop a job rotation schedule. The proposed schedules prevent the exposure to high workloads successively on the same body region and minimized between-worker variance in cumulative daily workload. Whereas some of workers were successively assigned to high workload workstation under no job rotation and serial job rotation. This model would help to reduce the potential for work-related musculoskeletal disorders (WMSDs) without additional cost for engineering work, although it may need more computational time and relative complex job rotation sequences. PMID:26995031

  6. Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI)

    PubMed Central

    2014-01-01

    Abstract Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation. PMID:25006452

  7. Repair of congenital heart disease with associated pulmonary hypertension in children: what are the minimal investigative procedures? Consensus statement from the Congenital Heart Disease and Pediatric Task Forces, Pulmonary Vascular Research Institute (PVRI).

    PubMed

    Lopes, Antonio Augusto; Barst, Robyn J; Haworth, Sheila Glennis; Rabinovitch, Marlene; Al Dabbagh, Maha; Del Cerro, Maria Jesus; Ivy, Dunbar; Kashour, Tarek; Kumar, Krishna; Harikrishnan, S; D'Alto, Michele; Thomaz, Ana Maria; Zorzanelli, Leína; Aiello, Vera D; Mocumbi, Ana Olga; Santana, Maria Virginia T; Galal, Ahmed Nasser; Banjar, Hanaa; Tamimi, Omar; Heath, Alexandra; Flores, Patricia C; Diaz, Gabriel; Sandoval, Julio; Kothari, Shyam; Moledina, Shahin; Gonçalves, Rilvani C; Barreto, Alessandra C; Binotto, Maria Angélica; Maia, Margarida; Al Habshan, Fahad; Adatia, Ian

    2014-06-01

    Standardization of the diagnostic routine for children with congenital heart disease associated with pulmonary arterial hypertension (PAH-CHD) is crucial, in particular since inappropriate assignment to repair of the cardiac lesions (e.g., surgical repair in patients with elevated pulmonary vascular resistance) may be detrimental and associated with poor outcomes. Thus, members of the Congenital Heart Disease and Pediatric Task Forces of the Pulmonary Vascular Research Institute decided to conduct a survey aimed at collecting expert opinion from different institutions in several countries, covering many aspects of the management of PAH-CHD, from clinical recognition to noninvasive and invasive diagnostic procedures and immediate postoperative support. In privileged communities, the vast majority of children with congenital cardiac shunts are now treated early in life, on the basis of noninvasive diagnostic evaluation, and have an uneventful postoperative course, with no residual PAH. However, a small percentage of patients (older at presentation, with extracardiac syndromes or absence of clinical features of increased pulmonary blood flow, thus suggesting elevated pulmonary vascular resistance) remain at a higher risk of complications and unfavorable outcomes. These patients need a more sophisticated diagnostic approach, including invasive procedures. The authors emphasize that decision making regarding operability is based not only on cardiac catheterization data but also on the complete diagnostic picture, which includes the clinical history, physical examination, and all aspects of noninvasive evaluation. PMID:25006452

  8. About the ZOOM minimization package

    SciTech Connect

    Fischler, M.; Sachs, D.; /Fermilab

    2004-11-01

    A new object-oriented Minimization package is available for distribution in the same manner as CLHEP. This package, designed for use in HEP applications, has all the capabilities of Minuit, but is a re-write from scratch, adhering to modern C++ design principles. A primary goal of this package is extensibility in several directions, so that its capabilities can be kept fresh with as little maintenance effort as possible. This package is distinguished by the priority that was assigned to C++ design issues, and the focus on producing an extensible system that will resist becoming obsolete.

  9. Small Non-coding RNAs Associated with Viral Infectious Diseases of Veterinary Importance: Potential Clinical Applications

    PubMed Central

    Samir, Mohamed; Pessler, Frank

    2016-01-01

    MicroRNAs (miRNAs) represent a class of small non-coding RNA (sncRNA) molecules that can regulate mRNAs by inducing their degradation or by blocking translation. Considering that miRNAs are ubiquitous, stable, and conserved across animal species, it seems feasible to exploit them for clinical applications. Unlike in human viral diseases, where some miRNA-based molecules have progressed to clinical application, in veterinary medicine, this concept is just starting to come into view. Clinically, miRNAs could represent powerful diagnostic tools to pinpoint animal viral diseases and/or prognostic tools to follow up disease progression or remission. Additionally, the possible consequences of miRNA dysregulation make them potential therapeutic targets and open the possibilities to use them as tools to generate viral disease-resistant livestock. This review presents an update of preclinical studies on using sncRNAs to combat viral diseases that affect pet and farm animals. Moreover, we discuss the possibilities and challenges of bringing these bench-based discoveries to the veterinary clinic. PMID:27092305

  10. Ways To Minimize Bullying.

    ERIC Educational Resources Information Center

    Mueller, Mary Ellen; Parisi, Mary Joy

    This report delineates a series of interventions aimed at minimizing incidences of bullying in a suburban elementary school. The social services staff was scheduled to initiate an anti-bullying incentive in fall 2001 due to the increased occurrences of bullying during the prior year. The target population consisted of third- and fourth-grade…

  11. Periodic minimal surfaces

    NASA Astrophysics Data System (ADS)

    Mackay, Alan L.

    1985-04-01

    A minimal surface is one for which, like a soap film with the same pressure on each side, the mean curvature is zero and, thus, is one where the two principal curvatures are equal and opposite at every point. For every closed circuit in the surface, the area is a minimum. Schwarz1 and Neovius2 showed that elements of such surfaces could be put together to give surfaces periodic in three dimensions. These periodic minimal surfaces are geometrical invariants, as are the regular polyhedra, but the former are curved. Minimal surfaces are appropriate for the description of various structures where internal surfaces are prominent and seek to adopt a minimum area or a zero mean curvature subject to their topology; thus they merit more complete numerical characterization. There seem to be at least 18 such surfaces3, with various symmetries and topologies, related to the crystallographic space groups. Recently, glyceryl mono-oleate (GMO) was shown by Longley and McIntosh4 to take the shape of the F-surface. The structure postulated is shown here to be in good agreement with an analysis of the fundamental geometry of periodic minimal surfaces.

  12. Minimally invasive pancreatic surgery.

    PubMed

    Yiannakopoulou, E

    2015-12-01

    Minimally invasive pancreatic surgery is feasible and safe. Laparoscopic distal pancreatectomy should be widely adopted for benign lesions of the pancreas. Laparoscopic pancreaticoduodenectomy, although technically demanding, in the setting of pancreatic ductal adenocarcinoma has a number of advantages including shorter hospital stay, faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. Furthermore, it seems that progression-free survival is longer in patients undergoing laparoscopic pancreaticoduodenectomy in comparison with those undergoing open pancreaticoduodenectomy. Minimally invasive middle pancreatectomy seems appropriate for benign or borderline tumors of the neck of the pancreas. Technological advances including intraoperative ultrasound and intraoperative fluorescence imaging systems are expected to facilitate the wide adoption of minimally invasive pancreatic surgery. Although, the oncological outcome seems similar with that of open surgery, there are still concerns, as the majority of relevant evidence comes from retrospective studies. Large multicenter randomized studies comparing laparoscopic with open pancreatectomy as well as robotic assisted with both open and laparoscopic approaches are needed. Robotic approach could be possibly shown to be less invasive than conventional laparoscopic approach through the less traumatic intra-abdominal handling of tissues. In addition, robotic approach could enable the wide adoption of the technique by surgeon who is not that trained in advanced laparoscopic surgery. A putative clinical benefit of minimally invasive pancreatic surgery could be the attenuated surgical stress response leading to reduced morbidity and mortality as well as lack of the detrimental immunosuppressive effect especially for the oncological patients. PMID:26530291

  13. The Minimal Era

    ERIC Educational Resources Information Center

    Van Ness, Wilhelmina

    1974-01-01

    Described the development of Minimal Art, a composite name that has been applied to the scattering of bland, bleak, non-objective fine arts painting and sculpture forms that proliferated slightly mysteriously in the middle 1960's as Pop Art began to decline. (Author/RK)

  14. Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Application of Metabolomics

    PubMed Central

    He, Xuyun; Ji, Guang; Jia, Wei; Li, Houkai

    2016-01-01

    Gut microbiota are intricately involved in the development of obesity-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance. In the current review, we discuss the role of gut microbiota in the development of NAFLD by focusing on the mechanisms of gut microbiota-mediated host energy metabolism, insulin resistance, regulation of bile acids and choline metabolism, as well as gut microbiota-targeted therapy. We also discuss the application of a metabolomic approach to characterize gut microbial metabotypes in NAFLD. PMID:26999104

  15. Metabolomics in Plants and Humans: Applications in the Prevention and Diagnosis of Diseases

    PubMed Central

    Gomez-Casati, Diego F.; Zanor, Maria I.; Busi, María V.

    2013-01-01

    In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health. PMID:23986911

  16. An Experimental Approach to Controllably Vary Protein Oxidation While Minimizing Electrode Adsorption for Boron-Doped Diamond Electrochemical Surface Mapping Applications

    PubMed Central

    McClintock, Carlee S; Hettich, Robert L.

    2012-01-01

    Oxidative protein surface mapping has become a powerful approach for measuring the solvent accessibility of folded protein structures. A variety of techniques exist for generating the key reagent – hydroxyl radicals – for these measurements; however, these approaches range significantly in their complexity and expense of operation. This research expands upon earlier work to enhance the controllability of boron-doped diamond (BDD) electrochemistry as an easily accessible tool for producing hydroxyl radicals in order to oxidize a range of intact proteins. Efforts to modulate oxidation level while minimizing the adsorption of protein to the electrode involved the use of relatively high flow rates to reduce protein residence time inside the electrochemical flow chamber. Additionally, a different cell activation approach using variable voltage to supply a controlled current allowed us to precisely tune the extent of oxidation in a protein-dependent manner. In order to gain perspective on the level of protein adsorption onto the electrode surface, studies were conducted to monitor protein concentration during electrolysis and gauge changes in the electrode surface between cell activation events. This report demonstrates the successful use of BDD electrochemistry for greater precision in generating a target number of oxidation events upon intact proteins. PMID:23210708

  17. Is minimally invasive application by intramedullary osteosynthesis in comparison with volar plating real benefit in the treatment of distal radius fractures?

    PubMed Central

    Vlček, Martin; Jaganjac, Edib; Pech, Jan; Jonáš, David; Kebrle, Radek

    2014-01-01

    Purpose of the study: Can minimally invasive intramedullary osteosynthesis of distal radius fractures provide better therapeutic results than multidirectional locking plates. Retrospective study of 68 patients operated for distal radius fractures, 18 were treated with intramedullary X-screw (XSCR) fixation and 50 with the multidirectional angle-stable plate system (APTUS). The evaluation at 1-year follow-up included functional status of the wrist and hand, and radiographic findings. In the XSCR group, the functional outcomes of the treated extremity did not achieve values comparable with those of the uninjured side in any of the parameters measured. The radiographic findings did not meet the requirements of successful healing due to failure to restore an anatomical volar tilt in 22.2% cases. In the APTUS group, comparable values of the injured and the uninjured side were achieved in radial deviation, ulnar deviation, pronation, supination and grip strength. The radiographic criteria of successful healing were met by all fractures treated by locking plate osteosynthesis. Implant migration associated with secondary displacement of bone fragments was recorded in 33.3 % of the XSCR patients and only in 4.0 % of the APTUS patients. The overall evaluation show that intramedullary osteosynthesis does not produce better treatment outcomes compared with plate osteosynthesis in indicated types of fractures. PMID:24856379

  18. Application of remote thermal imaging and night vision technology to improve endangered wildlife resource management with minimal animal distress and hazard to humans

    NASA Astrophysics Data System (ADS)

    Lavers, C.; Franks, K.; Floyd, M.; Plowman, A.

    2005-01-01

    Advanced electromagnetic sensor systems more commonly associated with the hightech military battlefield may be applied to remote surveillance of wildlife. The first comprehensive study of a wide global variety of Near Infra Red (NIR) and thermal wildlife portraits are presented with this technology: for mammals, birds and other animals. The paper illustrates the safety aspects afforded to zoo staff and personnel in the wild during the day and night from potentially lethal and aggressive animals, and those difficult to approach normally. Such remote sensing systems are non-invasive and provide minimal disruption and distress to animals both in captivity and in the wild. We present some of the veterinarian advantages of such all weather day and night systems to identify sickness and injuries at an early diagnostic stage, as well as age related effects and mammalian cancer. Animals have very different textured surfaces, reflective and emissive properties in the NIR and thermal bands than when compared with the visible spectrum. Some surface features may offer biomimetic materials design advantages.

  19. Current application of proteomics in biomarker discovery for inflammatory bowel disease

    PubMed Central

    Chan, Patrick PY; Wasinger, Valerie C; Leong, Rupert W

    2016-01-01

    Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD. PMID:26909226

  20. What Features of Smartphone Medication Applications Are Patients with Chronic Diseases and Caregivers Looking for?

    PubMed

    Liu, Yisi; Wang, Liuyu; Chang, Polun; Lamb, Karen V; Cui, Yanyan; Wu, Ying

    2016-01-01

    We explored the desired features of medication applications for patients with chronic disease and their caregivers with a questionnaire survey, 50 from patients and 50 from their caregivers. Although the majority of people (75%) are willing to use medication apps, the actual usage rate is quite low (11%). Worrying about privacy of personal information seems to be the main reason of not using applications. The overall score desired for use was 3.29 ± 1.02 (out of 5). Searching medications and diseases and assistance with making doctors' appointments are the most wanted categories. Online shopping for drugs and delivery were the least desired items. The main concerns for people who do not want certain features include: they are not useful, worrying about buying counterfeit drugs and reliability of content. Compared with patients, caregivers seems to be more concerned on nutrition tips for chronic illness, fall detection, and privacy protection (P < 0.05 for all). PMID:27332254

  1. Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives

    PubMed Central

    Precone, Vincenza; Del Monaco, Valentina; Esposito, Maria Valeria; De Palma, Fatima Domenica Elisa; Ruocco, Anna; D'Argenio, Valeria

    2015-01-01

    Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics. PMID:26665001

  2. Application of nanomaterials in the bioanalytical detection of disease-related genes.

    PubMed

    Zhu, Xiaoqian; Li, Jiao; He, Hanping; Huang, Min; Zhang, Xiuhua; Wang, Shengfu

    2015-12-15

    In the diagnosis of genetic diseases and disorders, nanomaterials-based gene detection systems have significant advantages over conventional diagnostic systems in terms of simplicity, sensitivity, specificity, and portability. In this review, we describe the application of nanomaterials for disease-related genes detection in different methods excluding PCR-related method, such as colorimetry, fluorescence-based methods, electrochemistry, microarray methods, surface-enhanced Raman spectroscopy (SERS), quartz crystal microbalance (QCM) methods, and dynamic light scattering (DLS). The most commonly used nanomaterials are gold, silver, carbon and semiconducting nanoparticles. Various nanomaterials-based gene detection methods are introduced, their respective advantages are discussed, and selected examples are provided to illustrate the properties of these nanomaterials and their emerging applications for the detection of specific nucleic acid sequences. PMID:26134290

  3. Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives.

    PubMed

    Precone, Vincenza; Del Monaco, Valentina; Esposito, Maria Valeria; De Palma, Fatima Domenica Elisa; Ruocco, Anna; Salvatore, Francesco; D'Argenio, Valeria

    2015-01-01

    Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics. PMID:26665001

  4. Current application of proteomics in biomarker discovery for inflammatory bowel disease.

    PubMed

    Chan, Patrick Py; Wasinger, Valerie C; Leong, Rupert W

    2016-02-15

    Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease (IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD. PMID:26909226

  5. Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases

    PubMed Central

    Lu, Yudong; Li, Zhong; Teng, Huan; Xu, Hongke; Qi, Songnan; He, Jian’an; Gu, Dayong; Chen, Qijun; Ma, Hongwei

    2015-01-01

    Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression. PMID:26293607

  6. Cell mechanics as a marker for diseases: Biomedical applications of AFM

    NASA Astrophysics Data System (ADS)

    Rianna, Carmela; Radmacher, Manfred

    2016-08-01

    Many diseases are related to changes in cell mechanics. Atomic Force Microscopy (AFM) is one of the most suitable techniques allowing the investigation of both topography and mechanical properties of adherent cells with high spatial resolution under physiological conditions. Over the years the use of this technique in medical and clinical applications has largely increased, resulting in the notion of cell mechanics as a biomarker to discriminate between different physiological and pathological states of cells. Cell mechanics has proven to be a biophysical fingerprint able discerning between cell phenotypes, unraveling processes in aging or diseases, or even detecting and diagnosing cellular pathologies. We will review in this report some of the works on cell mechanics investigated by AFM with clinical and medical relevance in order to clarify the state of research in this field and to highlight the role of cell mechanics in the study of pathologies, focusing on cancer, blood and cardiovascular diseases.

  7. What Can Biosignal Entropy Tell Us About Health and Disease? Applications in Some Clinical Fields.

    PubMed

    Vargas, Borja; Cuesta-Frau, David; Ruiz-Esteban, Raúl; Cirugeda, Eva; Varela, Manuel

    2015-10-01

    Many physiological systems are paradigmatic examples of complex networks, displaying behaviors best studied by means of tools derived from nonlinear dynamics and fractal geometry. Furthermore, while conventional wisdom considers health as an 'orderly' situation (and diseases are often called 'disorders'), truth is that health is characterized by a remarkable (pseudo)-randomness, and the loss of this pseudo-randomness (i.e., the 'decomplex-ification' of the system's output) is one of the earliest signs of the system's dysfunction. The potential clinical uses of this information are evident. However, the instruments used to assess complexity are still under debate, and these tools are just beginning to find their place at the bedside. We present a brief overview of the potential uses of complexity analysis in several areas of clinical medicine. We comment on the metrics most frequently used, and we review specifically their application on certain neurologic diseases, aging, diabetes, febrile diseases and the critically ill patient. PMID:26375934

  8. Chimeric peptide constructs comprising linear B-cell epitopes: application to the serodiagnosis of infectious diseases.

    PubMed

    Lu, Yudong; Li, Zhong; Teng, Huan; Xu, Hongke; Qi, Songnan; He, Jian'an; Gu, Dayong; Chen, Qijun; Ma, Hongwei

    2015-01-01

    Linear B-cell epitopes are ideal biomarkers for the serodiagnosis of infectious diseases. However, the long-predicted diagnostic value of epitopes has not been realized. Here, we demonstrated a method, diagnostic epitopes in four steps (DEIFS), that delivers a combination of epitopes for the serodiagnosis of infectious diseases with a high success rate. Using DEIFS for malaria, we identified 6 epitopes from 8 peptides and combined them into 3 chimeric peptide constructs. Along with 4 other peptides, we developed a rapid diagnostic test (RDT), which is able to differentiate Plasmodium falciparum (P. falciparum) from Plasmodium vivax (P. vivax) infections with 95.6% overall sensitivity and 99.1% overall specificity. In addition to applications in diagnosis, DEIFS could also be used in the diagnosis of virus and bacterium infections, discovery of vaccine candidates, evaluation of vaccine potency, and study of disease progression. PMID:26293607

  9. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  10. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  11. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  12. 10 CFR 20.1406 - Minimization of contamination.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Minimization of contamination. 20.1406 Section 20.1406... License Termination § 20.1406 Minimization of contamination. (a) Applicants for licenses, other than early... procedures for operation will minimize, to the extent practicable, contamination of the facility and...

  13. Untargeted UPLC-MS Profiling Pipeline to Expand Tissue Metabolome Coverage: Application to Cardiovascular Disease

    PubMed Central

    2015-01-01

    Metabolic profiling studies aim to achieve broad metabolome coverage in specific biological samples. However, wide metabolome coverage has proven difficult to achieve, mostly because of the diverse physicochemical properties of small molecules, obligating analysts to seek multiplatform and multimethod approaches. Challenges are even greater when it comes to applications to tissue samples, where tissue lysis and metabolite extraction can induce significant systematic variation in composition. We have developed a pipeline for obtaining the aqueous and organic compounds from diseased arterial tissue using two consecutive extractions, followed by a different untargeted UPLC-MS analysis method for each extract. Methods were rationally chosen and optimized to address the different physicochemical properties of each extract: hydrophilic interaction liquid chromatography (HILIC) for the aqueous extract and reversed-phase chromatography for the organic. This pipeline can be generic for tissue analysis as demonstrated by applications to different tissue types. The experimental setup and fast turnaround time of the two methods contributed toward obtaining highly reproducible features with exceptional chromatographic performance (CV % < 0.5%), making this pipeline suitable for metabolic profiling applications. We structurally assigned 226 metabolites from a range of chemical classes (e.g., carnitines, α-amino acids, purines, pyrimidines, phospholipids, sphingolipids, free fatty acids, and glycerolipids) which were mapped to their corresponding pathways, biological functions and known disease mechanisms. The combination of the two untargeted UPLC-MS methods showed high metabolite complementarity. We demonstrate the application of this pipeline to cardiovascular disease, where we show that the analyzed diseased groups (n = 120) of arterial tissue could be distinguished based on their metabolic profiles. PMID:25664760

  14. Recent advances in the application of metabolomics to Alzheimer’s Disease

    PubMed Central

    Trushina, Eugenia; Mielke, Michelle M.

    2013-01-01

    The pathophysiological changes associated with Alzheimer’s Disease (AD) begin decades before the emergence of clinical symptoms. Understanding the early mechanisms associated with AD pathology is, therefore, especially important for identifying disease-modifying therapeutic targets. While the majority of AD clinical trials to date have focused on anti-amyloid-beta (Aβ) treatments, other therapeutic approaches may be necessary. The ability to monitor changes in cellular networks that include both Aβ and non-Aβ pathways is essential to advance our understanding of the etiopathogenesis of AD and subsequent development of cognitive symptoms and dementia. Metabolomics is a powerful tool that detects perturbations in the metabolome, a pool of metabolites that reflects changes downstream of genomic, transcriptomic and proteomic fluctuations, and represents an accurate biochemical profile of the organism in health and disease. The application of metabolomics could help to identify biomarkers for early AD diagnosis, to discover novel therapeutic targets, and to monitor therapeutic response and disease progression. Moreover, given the considerable parallel between mouse and human metabolism, the use of metabolomics provides ready translation of animal research into human studies for accelerated drug design. In this review, we will summarize current progress in the application of metabolomics in both animal models and in humans to further understanding of the mechanisms involved in AD pathogenesis. PMID:23816564

  15. The simultaneous application of positive-end expiratory pressure with the Trendelenburg position minimizes respiratory fluctuations in internal jugular vein size

    PubMed Central

    Han, Sun Sook; Han, Woong Ki; Ko, Dong Chan

    2014-01-01

    Background The respiratory cycle alters the size of the right internal jugular vein (RIJV). We assessed the changes in RIJV size during the respiratory cycle in patients under positive pressure ventilation. Moreover, we examined the effects of positive-end expiratory pressure (PEEP) and the Trendelenburg position on respiratory fluctuations. Methods A prospective study of 24 patients undergoing general endotracheal anesthesia was performed. Images of the RIJV were obtained in the supine position with no PEEP (baseline, S0) and after applying three different maneuvers in random order: (1) a PEEP of 10 cmH2O (S10), (2) a 10° Trendelenburg tilt position (T0), and (3) a 10° Trendelenburg tilt position combined with a PEEP of 10 cmH2O (T10). Using the images when the area was smallest and largest, cross-sectional area (CSA), anteroposterior diameter, and transverse diameter were measured. Results All maneuvers minimized the fluctuation in RIJV size (all P = 0.0004). During the respiratory cycle, the smallest CSA compared to the largest CSA at S0, S10, T0, and T10 decreased by 28.3 8.5, 8.0, and 4.4%, respectively. Furthermore, compared to S0, a 10° Trendelenburg tilt position with a PEEP of 10 cmH2O significantly increased the CSA in the largest areas by 83.8% and in the smallest areas by 169.4%. Conclusions A 10° Trendelenburg tilt position combined with a PEEP of 10 cmH2O not only increases the size of the RIJV but also reduces fluctuation by the respiratory cycle. PMID:24910725

  16. An adaptive algorithm for detection of multiple-type, positively stained nuclei in IHC images with minimal prior information: application to OLIG2 staining gliomas

    NASA Astrophysics Data System (ADS)

    Akakin, Hatice C.; Gokozan, Hamza; Otero, Jose; Gurcan, Metin N.

    2015-03-01

    We propose a method to detect and segment the oligodendrocytes and gliomas in OLIG2 immunoperoxidase stained tissue sections. Segmentation of cell nuclei is essential for automatic, fast, accurate and consistent analysis of pathology images. In general, glioma cells and oligodendrocytes mostly differ in shape and size within the tissue slide. In OLIG2 stained tissue images, gliomas are represented with irregularly shaped nuclei with varying sizes and brown shades. On the other hand, oligodendrocytes have more regular round nuclei shapes and are smaller in size when compared to glioma cells found in oligodendroglioma, astrocytomas, or oligoastrocytomas. The first task is to detect the OLIG2 positive cell regions within a region of interest image selected from a whole slide. The second task is to segment each cell nucleus and count the number of cell nuclei. However, the cell nuclei belonging to glioma cases have particularly irregular nuclei shapes and form cell clusters by touching or overlapping with each other. In addition to this clustered structure, the shading of the brown stain and the texture of the nuclei differ slightly within a tissue image. The final step of the algorithm is to classify glioma cells versus oligodendrocytes. Our method starts with color segmentation to detect positively stained cells followed by the classification of single individual cells and cell clusters by K-means clustering. Detected cell clusters are segmented with the H-minima based watershed algorithm. The novel aspects of our work are: 1) the detection and segmentation of multiple-type, positively-stained nuclei by incorporating only minimal prior information; and 2) adaptively determining clustering parameters to adjust to the natural variation in staining as well as the underlying cellular structure while accommodating multiple cell types in the image. Performance of the algorithm to detect individual cells is evaluated by sensitivity and precision metrics. Promising

  17. A phosphorescent rhenium emitter with minimal fluorescent component induced by heavy atom: Synthetic procedure, molecular structure, photophysical feature and optoelectronic application

    NASA Astrophysics Data System (ADS)

    Cui, Xiao; Zhang, He Ming

    2014-01-01

    In this paper, a Br-containing diamine ligand of 2-(4-bromophenyl)-5-(pyridin-2-yl)-1,3,4-oxadiazole (referred to as BrPO) and its corresponding Re(I) complex of Re(CO)3(BrPO)Br are synthesized and studied in detail, including molecular structure, photophysical feature, thermal stability and electrochemical property. Experimental data suggest that Re(CO)3(BrPO)Br takes a octahedral coordination environment, and the π-π attraction between BrPO ligands makes complex molecules take a highly-ordered arrangement. Re(CO)3(BrPO)Br is found to be a yellow emitter peaking at 565 nm with emission yield of 0.11 and excited state lifetime of 4.21 μs. The emission comes from triplet excited state of ML&LLCT, where ML&LLCT means metal-to-ligand-charge-transfer and ligand-to-ligand-charge-transfer as suggested by theoretical calculation. The fluorescent component in the emissive center is minimized by the heavy-atom turbulence effect. Re(CO)3(BrPO)Br owns a high thermal decomposition of 280 °C, with HOMO of -5.45 eV and LUMO of -3.12 eV. The optimal electroluminescent device using Re(CO)3(BrPO)Br as the emitting dopant gives a maximum brightness of 5906 cd/m2 and a maximum current efficiency of 5.6 cd/A.

  18. Automated cerebellar lobule segmentation with application to cerebellar structural analysis in cerebellar disease.

    PubMed

    Yang, Zhen; Ye, Chuyang; Bogovic, John A; Carass, Aaron; Jedynak, Bruno M; Ying, Sarah H; Prince, Jerry L

    2016-02-15

    The cerebellum plays an important role in both motor control and cognitive function. Cerebellar function is topographically organized and diseases that affect specific parts of the cerebellum are associated with specific patterns of symptoms. Accordingly, delineation and quantification of cerebellar sub-regions from magnetic resonance images are important in the study of cerebellar atrophy and associated functional losses. This paper describes an automated cerebellar lobule segmentation method based on a graph cut segmentation framework. Results from multi-atlas labeling and tissue classification contribute to the region terms in the graph cut energy function and boundary classification contributes to the boundary term in the energy function. A cerebellar parcellation is achieved by minimizing the energy function using the α-expansion technique. The proposed method was evaluated using a leave-one-out cross-validation on 15 subjects including both healthy controls and patients with cerebellar diseases. Based on reported Dice coefficients, the proposed method outperforms two state-of-the-art methods. The proposed method was then applied to 77 subjects to study the region-specific cerebellar structural differences in three spinocerebellar ataxia (SCA) genetic subtypes. Quantitative analysis of the lobule volumes shows distinct patterns of volume changes associated with different SCA subtypes consistent with known patterns of atrophy in these genetic subtypes. PMID:26408861

  19. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): applications in chest disease.

    PubMed

    Medford, Andrew R L; Bennett, Jonathan A; Free, Catherine M; Agrawal, Sanjay

    2010-01-01

    Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) offers a minimally invasive option for staging the mediastinum in suspect lung cancer but also in the diagnosis of mediastinal lesions accessible from the airway. This review is aimed at centres considering establishing an EBUS service that may not be so familiar with the technique. It focuses primarily on technical aspects of EBUS-TBNA, training issues, cost considerations, indications, advantages and disadvantages compared with other mediastinal sampling techniques as well as some reference to its performance in clinical studies. In summary, EBUS-TBNA is primarily used for staging non-small cell lung cancer, especially for bulky mediastinal disease and discrete N2 or N3 disease on CT, but also used for the diagnosis of unexplained mediastinal lymphadenopathy. For radical treatment staging, mediastinoscopy is still used at many centres and negative EBUS-TBNA results should be corroborated by mediastinoscopy. In the future, EBUS-TBNA may be used for staging the radiologically normal mediastinum and in re-staging. It is a procedure that can be taught with ease by an experienced operator, has numerous advantages over mediastinoscopy and is potentially cost saving by reducing the number of mediastinoscopies and associated peri-operative support required. PMID:19895387

  20. Advanced biomaterials and their potential applications in the treatment of periodontal disease.

    PubMed

    Chen, Xi; Wu, Guofeng; Feng, Zhihong; Dong, Yan; Zhou, Wei; Li, Bei; Bai, Shizhu; Zhao, Yimin

    2016-08-01

    Periodontal disease is considered as a widespread infectious disease and the most common cause of tooth loss in adults. Attempts for developing periodontal disease treatment strategies, including drug delivery and regeneration approaches, provide a useful experimental model for the evaluation of future periodontal therapies. Recently, emerging advanced biomaterials including hydrogels, films, micro/nanofibers and particles, hold great potential to be utilized as cell/drug carriers for local drug delivery and biomimetic scaffolds for future regeneration therapies. In this review, first, we describe the pathogenesis of periodontal disease, including plaque formation, immune response and inflammatory reactions caused by bacteria. Second, periodontal therapy and an overview of current biomaterials in periodontal regenerative medicine have been discussed. Third, the roles of state-of-the-art biomaterials, including hydrogels, films, micro/nanofibers and micro/nanoparticles, developed for periodontal disease treatment and periodontal tissue regeneration, and their fabrication methods, have been presented. Finally, biological properties, including biocompatibility, biodegradability and immunogenicity of the biomaterials, together with their current applications strategies are given. Conclusive remarks and future perspectives for such advanced biomaterials are discussed. PMID:26004052

  1. Postremission sequential monitoring of minimal residual disease by WT1 Q-PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk-adapted therapy in acute myeloid leukemia patients.

    PubMed

    Malagola, Michele; Skert, Cristina; Borlenghi, Erika; Chiarini, Marco; Cattaneo, Chiara; Morello, Enrico; Cancelli, Valeria; Cattina, Federica; Cerqui, Elisa; Pagani, Chiara; Passi, Angela; Ribolla, Rossella; Bernardi, Simona; Giustini, Viviana; Lamorgese, Cinzia; Ruggeri, Giuseppina; Imberti, Luisa; Caimi, Luigi; Russo, Domenico; Rossi, Giuseppe

    2016-02-01

    Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P < 0.0001] and 57% vs. 81%, respectively [P = 0.0003]) and PB-WT1 ≥ 16/10(4) ABL copies (P = 0.0001) (after 1st intensification) (RFS 43% vs. 95% [P < 0.0001]) Our data confirm the benefits of sequential MRD monitoring with both Q-PCR and MFC. If confirmed by further prospective trials, they may significantly improve the possibility of a risk-adapted, postinduction therapy of AML. PMID:26715369

  2. Minimizing the impact of the mosquito adulticide naled on honey bees, Apis mellifera (Hymenoptera: Apidae): aerial ultra-low-volume application using a high-pressure nozzle system.

    PubMed

    Zhong, He; Latham, Mark; Payne, Steve; Brock, Cate

    2004-02-01

    The impact of the mosquito adulticide naled on honey bees, Apis mellifera L., was evaluated by exposing test beehives to nighttime aerial ultra-low-volume (ULV) applications using a high-pressure nozzle system. The tests were conducted during routine mosquito control missions at Manatee County, Florida, in summer 2000. Two treatment sites were sprayed a total of four times over a 10-wk period. Honey bees, which clustered outside of the hive entrances, were subjected to naled exposure during these mosquito control sprays. The highest average naled ground deposition was 2,688 microg/m2 at the Port Manatee site, which resulted in statistically significant bee mortality (118) compared with the controls. At the Terra Ceia Road site, an intermediate level of naled deposition was found (1,435 microg/m2). For this spray mission, the range of dead bees per hive at Terra Ceia was 2 to 9 before spraying and 5 to 36 after naled application. Means of all other naled ground depositions were < 850 microl/m2. We concluded that substantial bee mortality (> 100 dead bees) resulted when naled residue levels were > 2,000 kg/m2 and honey bees were clustered outside of the hive entrances during mosquito adulticide applications. Compared with the flat-fan nozzle systems currently used by most of Florida's mosquito control programs, the high-pressure nozzle system used in this experiment substantially reduced environmental insecticide contamination and lead to decreased bee mortality. Statistical analysis also showed that average honey yield at the end of the season was not significantly reduced for those hives that were exposed to the insecticide. PMID:14998120

  3. Application of next generation sequencing to molecular diagnosis of inherited diseases.

    PubMed

    Zhang, Wei; Cui, Hong; Wong, Lee-Jun C

    2014-01-01

    Recent development of high throughput, massively parallel sequencing (MPS or next generation sequencing, NGS) technology has revolutionized the molecular diagnosis of human genetic disease. The ability to generate enormous amount of sequence data in a short time at an affordable cost makes this approach ideal for a wide range of applications from sequencing a group of candidate genes, all coding regions (known as exome sequencing) to the entire human genome. The technology brings about an unprecedented application to the identification of the molecular basis of hard-to-diagnose genetic disorders. This chapter reviews the up-to-date published application of next generation sequencing in clinical molecular diagnostic laboratories. We also emphasize the various target gene enrichment methods and their advantages and shortcomings. Obstacles to compliance with regulatory authorities like CLIA/CAP in clinical settings are also briefly discussed. PMID:22576358

  4. Minimizing travel claims cost with minimal-spanning tree model

    NASA Astrophysics Data System (ADS)

    Jamalluddin, Mohd Helmi; Jaafar, Mohd Azrul; Amran, Mohd Iskandar; Ainul, Mohd Sharizal; Hamid, Aqmar; Mansor, Zafirah Mohd; Nopiah, Zulkifli Mohd

    2014-06-01

    Travel demand necessitates a big expenditure in spending, as has been proven by the National Audit Department (NAD). Every year the auditing process is carried out throughout the country involving official travel claims. This study focuses on the use of the Spanning Tree model to determine the shortest path to minimize the cost of the NAD's official travel claims. The objective is to study the possibility of running a network based in the Kluang District Health Office to eight Rural Clinics in Johor state using the Spanning Tree model applications for optimizing travelling distances and make recommendations to the senior management of the Audit Department to analyze travelling details before an audit is conducted. Result of this study reveals that there were claims of savings of up to 47.4% of the original claims, over the course of the travel distance.

  5. Minimally refined biomass fuel

    DOEpatents

    Pearson, Richard K.; Hirschfeld, Tomas B.

    1984-01-01

    A minimally refined fluid composition, suitable as a fuel mixture and derived from biomass material, is comprised of one or more water-soluble carbohydrates such as sucrose, one or more alcohols having less than four carbons, and water. The carbohydrate provides the fuel source; water solubilizes the carbohydrates; and the alcohol aids in the combustion of the carbohydrate and reduces the vicosity of the carbohydrate/water solution. Because less energy is required to obtain the carbohydrate from the raw biomass than alcohol, an overall energy savings is realized compared to fuels employing alcohol as the primary fuel.

  6. Wake Vortex Minimization

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A status report is presented on research directed at reducing the vortex disturbances of aircraft wakes. The objective of such a reduction is to minimize the hazard to smaller aircraft that might encounter these wakes. Inviscid modeling was used to study trailing vortices and viscous effects were investigated. Laser velocimeters were utilized in the measurement of aircraft wakes. Flight and wind tunnel tests were performed on scale and full model scale aircraft of various design. Parameters investigated included the effect of wing span, wing flaps, spoilers, splines and engine thrust on vortex attenuation. Results indicate that vortives may be alleviated through aerodynamic means.

  7. Minimally Invasive Parathyroidectomy

    PubMed Central

    Starker, Lee F.; Fonseca, Annabelle L.; Carling, Tobias; Udelsman, Robert

    2011-01-01

    Minimally invasive parathyroidectomy (MIP) is an operative approach for the treatment of primary hyperparathyroidism (pHPT). Currently, routine use of improved preoperative localization studies, cervical block anesthesia in the conscious patient, and intraoperative parathyroid hormone analyses aid in guiding surgical therapy. MIP requires less surgical dissection causing decreased trauma to tissues, can be performed safely in the ambulatory setting, and is at least as effective as standard cervical exploration. This paper reviews advances in preoperative localization, anesthetic techniques, and intraoperative management of patients undergoing MIP for the treatment of pHPT. PMID:21747851

  8. Controlling molecular transport in minimal emulsions

    PubMed Central

    Gruner, Philipp; Riechers, Birte; Semin, Benoît; Lim, Jiseok; Johnston, Abigail; Short, Kathleen; Baret, Jean-Christophe

    2016-01-01

    Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of ‘minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions. PMID:26797564

  9. Genetic algorithms for minimal source reconstructions

    SciTech Connect

    Lewis, P.S.; Mosher, J.C.

    1993-12-01

    Under-determined linear inverse problems arise in applications in which signals must be estimated from insufficient data. In these problems the number of potentially active sources is greater than the number of observations. In many situations, it is desirable to find a minimal source solution. This can be accomplished by minimizing a cost function that accounts from both the compatibility of the solution with the observations and for its ``sparseness``. Minimizing functions of this form can be a difficult optimization problem. Genetic algorithms are a relatively new and robust approach to the solution of difficult optimization problems, providing a global framework that is not dependent on local continuity or on explicit starting values. In this paper, the authors describe the use of genetic algorithms to find minimal source solutions, using as an example a simulation inspired by the reconstruction of neural currents in the human brain from magnetoencephalographic (MEG) measurements.

  10. Controlling molecular transport in minimal emulsions

    NASA Astrophysics Data System (ADS)

    Gruner, Philipp; Riechers, Birte; Semin, Benoît; Lim, Jiseok; Johnston, Abigail; Short, Kathleen; Baret, Jean-Christophe

    2016-01-01

    Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of `minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions.

  11. Controlling molecular transport in minimal emulsions.

    PubMed

    Gruner, Philipp; Riechers, Birte; Semin, Benoît; Lim, Jiseok; Johnston, Abigail; Short, Kathleen; Baret, Jean-Christophe

    2016-01-01

    Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of 'minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions. PMID:26797564

  12. Land application of mine water causes minimal uranium loss offsite in the wet-dry tropics: Ranger Uranium Mine, Northern Territory, Australia.

    PubMed

    Mumtaz, Saqib; Streten, Claire; Parry, David L; McGuinness, Keith A; Lu, Ping; Gibb, Karen S

    2015-11-01

    Ranger Uranium Mine (RUM) is situated in the wet-dry tropics of Northern Australia. Land application (irrigation) of stockpile (ore and waste) runoff water to natural woodland on the mine lease is a key part of water management at the mine. Consequently, the soil in these Land Application Areas (LAAs) presents a range of uranium (U) and other metals concentrations. Knowledge of seasonal and temporal changes in soil U and physicochemical parameters at RUM LAAs is important to develop suitable management and rehabilitation strategies. Therefore, soil samples were collected from low, medium, high and very high U sites at RUM LAAs for two consecutive years and the effect of time and season on soil physicochemical parameters particularly U and other major solutes applied in irrigation water was measured. Concentrations of some of the solutes applied in the irrigation water such as sulphur (S), iron (Fe) and calcium (Ca) showed significant seasonal and temporal changes. Soil S, Fe and Ca concentration decreased from year 1 to year 2 and from dry to wet seasons during both years. Soil U followed the same pattern except that we recorded an increase in soil U concentrations at most of the RUM LAAs after year 2 wet season compared to year 2 dry season. Thus, these sites did not show a considerable decrease in soil U concentration from year 1 to year 2. Sites which contained elevated U after wet season 2 also had higher moisture content which suggests that pooling of U containing rainwater at these sites may be responsible for elevated U. Thus, U may be redistributed within RUM LAAs due to surface water movement. The study also suggested that a decrease in U concentrations in LAA soils at very high U (>900 mg kg(-1)) sites is most likely due to transport of particulate matter bound U by surface runoff and U may not be lost from the surface soil due to vertical movement through the soil profile. Uranium attached to particulate matter may reduce its potential for environmental

  13. Esophageal surgery in minimally invasive era.

    PubMed

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-27

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  14. Esophageal surgery in minimally invasive era

    PubMed Central

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-01

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  15. Practical Application of Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) Imaging in Minimizing Metallic Artifacts

    PubMed Central

    Hong, Hyun Sook; Park, Jai Soung; Paik, Sang Hyun; Lee, Hae Kyung

    2012-01-01

    Iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) is a recently developed method for robust separation of fat and water with very high signal-to-noise-ratio (SNR) efficiency. In contrast to conventional fat-saturation methods, IDEAL is insensitive to magnetic field (B0 and B1) inhomogeneity. The aim of this study was to illustrate the practical application of the IDEAL technique in reducing metallic artifacts in postoperative patients with metallic hardware. The IDEAL technique can help musculoskeletal radiologists make an accurate diagnosis particularly in musculoskeletal imaging by reducing metallic artifacts, enabling the use of contrast enhancement, improving SNR performance, and providing various modes of MR images with one scan parameter. PMID:22563271

  16. Metabolomic Applications to Decipher Gut Microbial Metabolic Influence in Health and Disease

    PubMed Central

    Martin, François-Pierre J.; Collino, Sebastiano; Rezzi, Serge; Kochhar, Sunil

    2012-01-01

    Dietary preferences and nutrients composition have been shown to influence human and gut microbial metabolism, which ultimately has specific effects on health and diseases’ risk. Increasingly, results from molecular biology and microbiology demonstrate the key role of the gut microbiota metabolic interface to the overall mammalian host’s health status. There is therefore raising interest in nutrition research to characterize the molecular foundations of the gut microbial–mammalian cross talk at both physiological and biochemical pathway levels. Tackling these challenges can be achieved through systems biology approaches, such as metabolomics, to underpin the highly complex metabolic exchanges between diverse biological compartments, including organs, systemic biofluids, and microbial symbionts. By the development of specific biomarkers for prediction of health and disease, metabolomics is increasingly used in clinical applications as regard to disease etiology, diagnostic stratification, and potentially mechanism of action of therapeutical and nutraceutical solutions. Surprisingly, an increasing number of metabolomics investigations in pre-clinical and clinical studies based on proton nuclear magnetic resonance (1H NMR) spectroscopy and mass spectrometry provided compelling evidence that system wide and organ-specific biochemical processes are under the influence of gut microbial metabolism. This review aims at describing recent applications of metabolomics in clinical fields where main objective is to discern the biochemical mechanisms under the influence of the gut microbiota, with insight into gastrointestinal health and diseases diagnostics and improvement of homeostasis metabolic regulation. PMID:22557976

  17. Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare.

    PubMed

    Jorge, Carla D; Borges, Nuno; Bagyan, Irina; Bilstein, Andreas; Santos, Helena

    2016-05-01

    Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer's, Parkinson's and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer's Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed. PMID:27071404

  18. Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications

    PubMed Central

    Kim, Jong-Hoon

    2012-01-01

    Ginseng is one of the most widely used herbal medicines and is reported to have a wide range of therapeutic and pharmacological applications. Ginseng may also be potentially valuable in treating cardiovascular diseases. Research concerning cardiovascular disease is focusing on purified individual ginsenoside constituents of ginseng to reveal specific mechanisms instead of using whole ginseng extracts. The most commonly studied ginsenosides are Rb1, Rg1, Rg3, Rh1, Re, and Rd. The molecular mechanisms and medical applications of ginsenosides in the treatment of cardiovascular disease have attracted much attention and been the subject of numerous publications. Here, we review the current literature on the myriad pharmacological functions and the potential benefits of ginseng in this area. In vitro investigations using cell cultures and in vivo animal models have indicated ginseng’s potential cardiovascular benefits through diverse mechanisms that include antioxidation, modifying vasomotor function, reducing platelet adhesion, influencing ion channels, altering autonomic neurotransmitters release, and improving lipid profiles. Some 40 ginsenosides have been identified. Each may have different effects in pharmacology and mechanisms due to their different chemical structures. This review also summarizes results of relevant clinical trials regarding the cardiovascular effects of ginseng, particularly in the management of hypertension and improving cardiovascular function. PMID:23717100

  19. Deformation-based atrophy computation by surface propagation and its application to Alzheimer's disease.

    PubMed

    Pai, Akshay; Sporring, Jon; Darkner, Sune; Dam, Erik B; Lillholm, Martin; Jørgensen, Dan; Oh, Joonmi; Chen, Gennan; Suhy, Joyce; Sørensen, Lauge; Nielsen, Mads

    2016-01-01

    Obtaining regional volume changes from a deformation field is more precise when using simplex counting (SC) compared with Jacobian integration (JI) due to the numerics involved in the latter. Although SC has been proposed before, numerical properties underpinning the method and a thorough evaluation of the method against JI is missing in the literature. The contributions of this paper are: (a) we propose surface propagation (SP)-a simplification to SC that significantly reduces its computational complexity; (b) we will derive the orders of approximation of SP which can also be extended to SC. In the experiments, we will begin by empirically showing that SP is indeed nearly identical to SC, and that both methods are more stable than JI in presence of moderate to large deformation noise. Since SC and SP are identical, we consider SP as a representative of both the methods for a practical evaluation against JI. In a real application on Alzheimer's disease neuroimaging initiative data, we show the following: (a) SP produces whole brain and medial temporal lobe atrophy numbers that are significantly better than JI at separating between normal controls and Alzheimer's disease patients; (b) SP produces disease group atrophy differences comparable to or better than those obtained using FreeSurfer, demonstrating the validity of the obtained clinical results. Finally, in a reproducibility study, we show that the voxel-wise application of SP yields significantly lower variance when compared to JI. PMID:27014717

  20. Minimizing hazardous waste

    SciTech Connect

    DeClue, S.C.

    1996-06-01

    Hazardous waste minimization is a broad term often associated with pollution prevention, saving the environment or protecting Mother Earth. Some associate hazardous waste minimization with saving money. Thousands of hazardous materials are used in processes every day, but when these hazardous materials become hazardous wastes, dollars must be spent for disposal. When hazardous waste is reduced, an organization will spend less money on hazardous waste disposal. In 1993, Fort Bragg reduced its hazardous waste generation by over 100,000 pounds and spent nearly $90,000 less on hazardous waste disposal costs than in 1992. Fort Bragg generates a variety of wastes: Vehicle maintenance wastes such as antifreeze, oil, grease and solvents; helicopter maintenance wastes, including solvents, adhesives, lubricants and paints; communication operation wastes such as lithium, magnesium, mercury and nickel-cadmium batteries; chemical defense wastes detection, decontamination, and protective mask filters. The Hazardous Waste Office has the responsibility to properly identify, characterize, classify and dispose of these waste items in accordance with US Environmental Protection Agency (EPA) and US Department of Transportation (DOT) regulations.

  1. PET/CT in nononcological lung diseases: current applications and future perspectives.

    PubMed

    Capitanio, Selene; Nordin, Abdul Jalil; Noraini, Abdul Rahim; Rossetti, Claudio

    2016-09-01

    Positron emission tomography (PET) combined with computed tomography (CT) is an established diagnostic modality that has become an essential imaging tool in oncological practice. However, thanks to its noninvasive nature and its capability to provide physiological information, the main applications of this technique have significantly expanded.(18)F-labelled fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical for PET scanning and demonstrates metabolic activity in various tissues. Since activated inflammatory cells, like malignant cells, predominantly metabolise glucose as a source of energy and increase expression of glucose transporters when activated, FDG-PET/CT can be successfully used to detect and monitor a variety of lung diseases, such as infections and several inflammatory conditions.The added value of FDG-PET/CT as a molecular imaging technique relies on its capability to identify disease in very early stages, long before the appearance of structural changes detectable by conventional imaging. Furthermore, by detecting the active phase of infectious or inflammatory processes, disease progression and treatment efficacy can be monitored.This review will focus on the clinical use of FDG-PET/CT in nonmalignant pulmonary diseases. PMID:27581824

  2. Towards a European Framework to Monitor Infectious Diseases among Migrant Populations: Design and Applicability

    PubMed Central

    Riccardo, Flavia; Dente, Maria Grazia; Kärki, Tommi; Fabiani, Massimo; Napoli, Christian; Chiarenza, Antonio; Giorgi Rossi, Paolo; Velasco Munoz, Cesar; Noori, Teymur; Declich, Silvia

    2015-01-01

    There are limitations in our capacity to interpret point estimates and trends of infectious diseases occurring among diverse migrant populations living in the European Union/European Economic Area (EU/EEA). The aim of this study was to design a data collection framework that could capture information on factors associated with increased risk to infectious diseases in migrant populations in the EU/EEA. The authors defined factors associated with increased risk according to a multi-dimensional framework and performed a systematic literature review in order to identify whether those factors well reflected the reported risk factors for infectious disease in these populations. Following this, the feasibility of applying this framework to relevant available EU/EEA data sources was assessed. The proposed multidimensional framework is well suited to capture the complexity and concurrence of these risk factors and in principle applicable in the EU/EEA. The authors conclude that adopting a multi-dimensional framework to monitor infectious diseases could favor the disaggregated collection and analysis of migrant health data. PMID:26393623

  3. Recent Clinical Applications of Laser Speckle Flowgraphy in Eyes with Retinal Disease.

    PubMed

    Kunikata, Hiroshi; Nakazawa, Toru

    2016-01-01

    Retinal diseases related to ischemia, such as diabetic retinopathy, are the main cause of blindness worldwide. However, the pathogenesis of these diseases remains unclear, as does the time course of associated changes in ocular blood flow. Laser speckle flowgraphy (LSFG), which uses the laser speckle phenomenon to detect and quantify ocular circulation, is a promising candidate for a noninvasive method to measure ocular blood flow in living eyes. A recently developed LSFG measurement parameter, mean blur rate (MBR), can serve as a quantitative and reproducible index of retinal blood cell velocity. Mean blur rate can be used in the study of retinal diseases to evaluate microcirculation in the retinal vessels, choroid, and optic nerve head. In addition to overall MBR (MA), LSFG measurements of optic nerve head microcirculation can be divided into vessel-area MBR (MV) and tissue-area MBR (MT). Absolute values for MT have been shown to be linearly correlated with capillary blood flow, regardless of fundus pigmentation. Recently, there has been an increasing number of reports on the clinical applications of LSFG in retinal disease. PMID:26649761

  4. The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside

    PubMed Central

    Xie, Nina; Tang, Beisha

    2016-01-01

    In principle, induced pluripotent stem cells (iPSCs) are generated from somatic cells by reprogramming and gaining the capacity to self-renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs) and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases. PMID:26880979

  5. Applicability of a field-portable toxic heavy metal detector, using a radioisotope-tagged metalloprotein, to DOE environmental remediation and waste minimization initiatives

    SciTech Connect

    Randles, K.E.; Bragg, D.J.; Bodette, D.E.; Lipinski, R.J.; Luera, T.F.

    1998-08-01

    A system based on the metal-binding kidney protein, metallothionein, bound with a trace quantity of radioactive metal, has been shown to be capable of detecting parts-per-million (ppm) to parts-per-billion (ppb) concentrations of some heavy metals in liquid solution. The main objective of this study was to determine if this type of system has adequate sensitivity and selectivity for application in detecting a number of metallic species of concern to DOE, such as mercury, lead, and chromium. An affinity-displacement study is reported here using the heavy metal radiotracers {sup 65}Zn and {sup 109}Cd bound to metallothionein immobilized on an Affi-Gel 10 filter support. When a heavy metal solution with a greater affinity than the tracer for the protein is poured through the filter the radiotracer is displaced by a mechanism similar to ion exchange. The main objective of this study was to verify previous internal experimental parameters and results, and to determine the specific affinities of metallothionein for the metallic species of most concern to DOE.

  6. Chronic cough in subjects with upper airway diseases - analysis of mechanisms and clinical applications

    PubMed Central

    Song, Woo-Jung

    2013-01-01

    Cough is the commonest respiratory symptom leading to a medical consultation. Although acute cough which is usually associated with respiratory viral infection is not a problem to manage, chronic cough is frequently a diagnostic and therapeutic challenge as it does not respond to usual treatments. Specific group of chronic coughers are considered to have upper airway diseases, lately categorized as having upper airway cough syndrome. There is an increasing pool of evidence that upper airway diseases have significant involvements in the regulation of cough reflex, indicating that they must be taken into considerations as major triggers of coughing in the patients. Here we summarize current literature and experiences on the pathogenesis of upper airway cough syndrome, and discuss further clinical applications. PMID:23667837

  7. A regression approach to ROC surface, with applications to Alzheimer's disease.

    PubMed

    Li, Jialiang; Zhou, Andrew Xiaohua; Fine, Jason P

    2012-08-01

    We consider the estimation of three-dimensional ROC surfaces for continuous tests given covariates. Three way ROC analysis is important in our motivating example where patients with Alzheimer's disease are usually classified into three categories and should receive different category-specific medical treatment. There has been no discussion on how covariates affect the three way ROC analysis. We propose a regression framework induced from the relationship between test results and covariates. We consider several practical cases and the corresponding inference procedures. Simulations are conducted to validate our methodology. The application on the motivating example illustrates clearly the age and sex effects on the accuracy for Mini-Mental State Examination of Alzheimer's disease. PMID:24459466

  8. Applications of Nanoparticles in the Detection and Treatment of Kidney Diseases

    PubMed Central

    Brede, Chris; Labhasetwar, Vinod

    2013-01-01

    Nanoparticles have emerged in the medical field as a technology well-suited for the diagnosis and treatment of a variety of disease states. They have been heralded as efficacious owing to both in terms of improved therapeutic efficacy as well as reduction of treatment side effects in some cases. Various nanomaterials have been developed which can be tagged with targeting moieties, and with drug delivery and imaging capability or combination of both as theranostic agent. These nanomaterials have been investigated for treatment and detection of various pathological conditions. The emphasis of this review is to demonstrate current research and clinical applications for nanoparticles in the diagnosis and treatment of renal diseases. PMID:24206598

  9. Minimal noise subsystems

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoting; Byrd, Mark; Jacobs, Kurt

    2016-03-01

    A system subjected to noise contains a decoherence-free subspace or subsystem (DFS) only if the noise possesses an exact symmetry. Here we consider noise models in which a perturbation breaks a symmetry of the noise, so that if S is a DFS under a given noise process it is no longer so under the new perturbed noise process. We ask whether there is a subspace or subsystem that is more robust to the perturbed noise than S . To answer this question we develop a numerical method that allows us to search for subspaces or subsystems that are maximally robust to arbitrary noise processes. We apply this method to a number of examples, and find that a subsystem that is a DFS is often not the subsystem that experiences minimal noise when the symmetry of the noise is broken by a perturbation. We discuss which classes of noise have this property.

  10. Minimal quiver standard model

    SciTech Connect

    Berenstein, David; Pinansky, Samuel

    2007-05-01

    This paper discusses the minimal quiver gauge theory embedding of the standard model that could arise from brane world type string theory constructions. It is based on the low energy effective field theory of D branes in the perturbative regime. The model differs from the standard model by the addition of one extra massive gauge boson, and contains only one additional parameter to the standard model: the mass of this new particle. The coupling of this new particle to the standard model is uniquely determined by input from the standard model and consistency conditions of perturbative string theory. We also study some aspects of the phenomenology of this model and bounds on its possible observation at the Large Hadron Collider.

  11. Minimally invasive parathyroid surgery

    PubMed Central

    Noureldine, Salem I.; Gooi, Zhen

    2015-01-01

    Traditionally, bilateral cervical exploration for localization of all four parathyroid glands and removal of any that are grossly enlarged has been the standard surgical treatment for primary hyperparathyroidism (PHPT). With the advances in preoperative localization studies and greater public demand for less invasive procedures, novel targeted, minimally invasive techniques to the parathyroid glands have been described and practiced over the past 2 decades. Minimally invasive parathyroidectomy (MIP) can be done either through the standard Kocher incision, a smaller midline incision, with video assistance (purely endoscopic and video-assisted techniques), or through an ectopically placed, extracervical, incision. In current practice, once PHPT is diagnosed, preoperative evaluation using high-resolution radiographic imaging to localize the offending parathyroid gland is essential if MIP is to be considered. The imaging study results suggest where the surgeon should begin the focused procedure and serve as a road map to allow tailoring of an efficient, imaging-guided dissection while eliminating the unnecessary dissection of multiple glands or a bilateral exploration. Intraoperative parathyroid hormone (IOPTH) levels may be measured during the procedure, or a gamma probe used during radioguided parathyroidectomy, to ascertain that the correct gland has been excised and that no other hyperfunctional tissue is present. MIP has many advantages over the traditional bilateral, four-gland exploration. MIP can be performed using local anesthesia, requires less operative time, results in fewer complications, and offers an improved cosmetic result and greater patient satisfaction. Additional advantages of MIP are earlier hospital discharge and decreased overall associated costs. This article aims to address the considerations for accomplishing MIP, including the role of preoperative imaging studies, intraoperative adjuncts, and surgical techniques. PMID:26425454

  12. Limited fungicide applications affect foliar and fruit disease severity and phytochemical content of muscadine grape (Vitis rotundifolia Michx.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Berry rot diseases cause significant reductions in yield and quality of muscadine grapes, but these losses may be reduced significantly by fungicide applications. Four studies were conducted to explore the relationship between yield, disease control, berry quality, and phytochemical content followin...

  13. Contrast enhancement and elastography in endoscopic ultrasound: an update of clinical applications in pancreatic diseases.

    PubMed

    Serrani, Marta; Lisotti, Andrea; Caletti, Giancarlo; Fusaroli, Pietro

    2016-08-01

    It is well established that endoscopic ultrasound (EUS) is fundamental in the characterization of many diseases concerning different organs, i.e. pancreaticobiliary diseases, gastrointestinal pathologic conditions, and lymph nodes of unknown origin. It is also well known that many factors can hamper the accuracy of EUS, i.e. biliary stents, chronic pancreatitis, poor operator's expertise. These factors can also lead to suboptimal accuracy when cytological confirmation through EUS-fine needle aspiration (EUS-FNA) is indicated. In recent years, new technological tools have rapidly increased their clinical impact improving the diagnostic power of EUS and EUS-FNA. Among these new tools, the most investigated and useful ones are represented by contrast harmonic-EUS (CH-EUS) and EUS-elastography (EUS-E). The purpose of this paper is to provide, through a review of the literature, an update of the applications of CH-EUS and EUS-E in the routine clinical practice in pancreatic diseases. We discussed the first reports and applications of these techniques in our previous review published in Minerva Medica. The applications of CH-EUS and EUS-E to the study of pancreatic diseases appear feasible and safe. The use of both techniques is very simple and does not require any relevant additional workload for the endoscopic personnel. CH-EUS is now considered an important and accurate tool in the diagnosis of solid pancreatic masses and in the differential diagnosis of pancreatic cystic lesions. CH-EUS targeted FNA is an active field of research. However the available studies show that CH-EUS increases FNA accuracy by a little extent, without statistical significance; moreover, CH-EUS FNA showed a trend toward being more efficient vs. simple EUS FNA (less needle passes and more abundance in cytological material) but this trend did not reach statistical significance. On the other hand, the clinical impact of EUS-E in terms of differential diagnosis of pancreatic masses is still under

  14. The Application of Biomedical Engineering Techniques to the Diagnosis and Management of Tropical Diseases: A Review

    PubMed Central

    Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Faisal, Tarig; Neuman, Michael

    2015-01-01

    This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications. PMID:25806872

  15. The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review.

    PubMed

    Ibrahim, Fatimah; Thio, Tzer Hwai Gilbert; Faisal, Tarig; Neuman, Michael

    2015-01-01

    This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications. PMID:25806872

  16. Personalized medicine in the care of the child with congenital heart disease: discovery to application.

    PubMed

    Binesh Marvasti, Tina; D'Alessandro, Lisa C A; Manase, Dorin; Papaz, Tanya; Mital, Seema

    2013-01-01

    On October 27-28, 2012, the SickKids Labatt Family Heart Centre and the Heart Centre Biobank Registry hosted the second international GenomeHeart symposium in Toronto, Ontario. The symposium featured experts in cardiology, developmental biology, pharmacology, genomics, bioinformatics, stem cell biology, biobanking, and ethics. The theme of this year's symposium was the application of emerging technologies in genomics, proteomics, transcriptomics, and bioinformatics to diagnostics and therapeutics of the child with heart disease. Social, ethical, and economic issues were also discussed in the context of clinical translation. We highlight some of the themes that emerged from this exciting 2-day event. PMID:23601919

  17. Patients welcome the Sickle Cell Disease Mobile Application to Record Symptoms via Technology (SMART).

    PubMed

    Shah, Nirmish; Jonassaint, Jude; De Castro, Laura

    2014-01-01

    The widespread use of mobile phones among patients provides a unique opportunity for the development of mobile health intervention designed specifically for sickle cell disease, which will improve self-management as well as health care delivery. Our objective was to determine the receptiveness of patients with sickle cell disease to technology and a mobile application (app) designed for sickle cell disease. Phase I included 100 patients who completed a survey inquiring about receptiveness to technology and use of mobile devices to self-manage and communicate with providers. Phase II surveyed 17 additional patients who tested a newly developed sickle cell disease app, to report its usability and utility. In Phase I, on a 0-10 Likert scale where 0 is not comfortable, and 10 is extremely comfortable, 87.0% of participants reported >5 comfort level using a mobile device for health care management. Participants were comfortable with texting (81.0%) and emailing (77.0%) but not with social media (40.0%). Most participants (84.0%) owned computer devices (desktops, laptops, tablets, or iPads), and 92.0% owned mobile devices. In Phase II, participants reported that the app tested was useful to track pain (88.0%), and 94.0% reported that it was easy to use, practical, and useful for health self-management. All reported that the app was useful to help one communicate with providers. Following the use of our app, patients found it an extremely valuable tool for tracking pain, health management, and communicating with providers. We conclude that mobile technology might provide an appropriate venue for sickle cell disease healthcare management. PMID:24512633

  18. The Application of Microencapsulation Techniques in the Treatment of Endodontic and Periodontal Disease

    PubMed Central

    Álvarez, Asteria Luzardo; Espinar, Francisco Otero; Méndez, José Blanco

    2011-01-01

    In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained drug release, high antimicrobial activity and low systemic side effects. Microparticles made from biodegradable polymers have been reported to be an effective means of delivering antibacterial drugs in endodontic and periodontal therapy. The aim of this review article is to assess recent therapeutic strategies in which biocompatible microparticles are used for effective management of periodontal and endodontic diseases. In vitro and in vivo studies that have investigated the biocompatibility or efficacy of certain microparticle formulations and devices are presented. Future directions in the application of microencapsulation techniques in endodontic and periodontal therapies are discussed. PMID:24310596

  19. Multifunction minimization for programmable logic arrays

    SciTech Connect

    Campbell, J.A.

    1984-01-01

    The problem of minimizing two-level AND/OR Boolean algebraic functions of n inputs and m outputs for implementation on programmable logic arrays (PLA) is examined. The theory of multiple-output functions as well as the historically alternative approaches to reckoning the cost of an equation implementation are reviewed. The PLA is shown to be a realization of the least product gate equation cost criterion. The multi-function minimization is dealt with in the context of a directed tree search algorithm developed in previous research. The PLA oriented minimization is shown to alter the nature of each of the basic tenets of multiple-output minimization used in earlier work. The concept of a non-prime but selectable implicant is introduced. A new cost criterion, the quantum cost, is discussed, and an approximation algorithm utilizing this criterion is developed. A timing analysis of a cyclic resolution algorithm for PLA based functions is presented. Lastly, the question of efficiency in automated minimization algorithms is examined. The application of the PLA cost criterion is shown to exhibit intrinsic increases in computational efficiency. A minterm classification algorithm is suggested and a PLA minimization algorithm is implemented in the FORTRAN language.

  20. Minimal Marking: A Success Story

    ERIC Educational Resources Information Center

    McNeilly, Anne

    2014-01-01

    The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

  1. A game plan: Gamification design principles in mHealth applications for chronic disease management.

    PubMed

    Miller, Aaron S; Cafazzo, Joseph A; Seto, Emily

    2016-06-01

    Effective chronic disease management is essential to improve positive health outcomes, and incentive strategies are useful in promoting self-care with longevity. Gamification, applied with mHealth (mobile health) applications, has the potential to better facilitate patient self-management. This review article addresses a knowledge gap around the effective use of gamification design principles, or mechanics, in developing mHealth applications. Badges, leaderboards, points and levels, challenges and quests, social engagement loops, and onboarding are mechanics that comprise gamification. These mechanics are defined and explained from a design and development perspective. Health and fitness applications with gamification mechanics include: bant which uses points, levels, and social engagement, mySugr which uses challenges and quests, RunKeeper which uses leaderboards as well as social engagement loops and onboarding, Fitocracy which uses badges, and Mango Health, which uses points and levels. Specific design considerations are explored, an example of the efficacy of a gamified mHealth implementation in facilitating improved self-management is provided, limitations to this work are discussed, a link between the principles of gaming and gamification in health and wellness technologies is provided, and suggestions for future work are made. We conclude that gamification could be leveraged in developing applications with the potential to better facilitate self-management in persons with chronic conditions. PMID:24986104

  2. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery

    PubMed Central

    Singh, Vimal K.; Kalsan, Manisha; Kumar, Neeraj; Saini, Abhishek; Chandra, Ramesh

    2015-01-01

    such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. Thus, the applications of iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner. PMID:25699255

  3. A method for detecting IBD regions simultaneously in multiple individuals--with applications to disease genetics.

    PubMed

    Moltke, Ida; Albrechtsen, Anders; Hansen, Thomas V O; Nielsen, Finn C; Nielsen, Rasmus

    2011-07-01

    All individuals in a finite population are related if traced back long enough and will, therefore, share regions of their genomes identical by descent (IBD). Detection of such regions has several important applications-from answering questions about human evolution to locating regions in the human genome containing disease-causing variants. However, IBD regions can be difficult to detect, especially in the common case where no pedigree information is available. In particular, all existing non-pedigree based methods can only infer IBD sharing between two individuals. Here, we present a new Markov Chain Monte Carlo method for detection of IBD regions, which does not rely on any pedigree information. It is based on a probabilistic model applicable to unphased SNP data. It can take inbreeding, allele frequencies, genotyping errors, and genomic distances into account. And most importantly, it can simultaneously infer IBD sharing among multiple individuals. Through simulations, we show that the simultaneous modeling of multiple individuals makes the method more powerful and accurate than several other non-pedigree based methods. We illustrate the potential of the method by applying it to data from individuals with breast and/or ovarian cancer, and show that a known disease-causing mutation can be mapped to a 2.2-Mb region using SNP data from only five seemingly unrelated affected individuals. This would not be possible using classical linkage mapping or association mapping. PMID:21493780

  4. Principles and Clinical Application of Dual-energy Computed Tomography in the Evaluation of Cerebrovascular Disease.

    PubMed

    Hsu, Charlie Chia-Tsong; Kwan, Gigi Nga Chi; Singh, Dalveer; Pratap, Jit; Watkins, Trevor William

    2016-01-01

    Dual-energy computed tomography (DECT) simultaneously acquires images at two X-ray energy levels, at both high- and low-peak voltages (kVp). The material attenuation difference obtained from the two X-ray energies can be processed by software to analyze material decomposition and to create additional image datasets, namely, virtual noncontrast, virtual contrast also known as iodine overlay, and bone/calcium subtraction images. DECT has a vast array of clinical applications in imaging cerebrovascular diseases, which includes: (1) Identification of active extravasation of iodinated contrast in various types of intracranial hemorrhage; (2) differentiation between hemorrhagic transformation and iodine staining in acute ischemic stroke following diagnostic and/or therapeutic catheter angiography; (3) identification of culprit lesions in intra-axial hemorrhage; (4) calcium subtraction from atheromatous plaque for the assessment of plaque morphology and improved quantification of luminal stenosis; (5) bone subtraction to improve the depiction of vascular anatomy with more clarity, especially at the skull base; (6) metal artifact reduction utilizing virtual monoenergetic reconstructions for improved luminal assessment postaneurysm coiling or clipping. We discuss the physical principles of DECT and review the clinical applications of DECT for the evaluation of cerebrovascular diseases. PMID:27512615

  5. Cardiovascular Biomarkers in Chronic Kidney Disease: State of Current Research and Clinical Applicability

    PubMed Central

    D'Marco, Luis; Bellasi, Antonio; Raggi, Paolo

    2015-01-01

    The high incidence of cardiovascular events in chronic kidney disease (CKD) warrants an accurate evaluation of risk aimed at reducing the burden of disease and its consequences. The use of biomarkers to identify patients at high risk has been in use in the general population for several decades and has received mixed reactions in the medical community. Some practitioners have become staunch supporters and users while others doubt the utility of biomarkers and rarely measure them. In CKD patients numerous markers similar to those used in the general population and others more specific to the uremic population have emerged; however their utility for routine clinical application remains to be fully elucidated. The reproducibility and standardization of the serum assays are serious limitations to the broad implementation of these tests. The lack of focused research and validation in randomized trials rather than ad hoc measurement of multiple serum markers in observational studies is also cause for concern related to the clinical applicability of these markers. We review the current literature on biomarkers that may have a relevant role in field of nephrology. PMID:25944976

  6. Principles and Clinical Application of Dual-energy Computed Tomography in the Evaluation of Cerebrovascular Disease

    PubMed Central

    Hsu, Charlie Chia-Tsong; Kwan, Gigi Nga Chi; Singh, Dalveer; Pratap, Jit; Watkins, Trevor William

    2016-01-01

    Dual-energy computed tomography (DECT) simultaneously acquires images at two X-ray energy levels, at both high- and low-peak voltages (kVp). The material attenuation difference obtained from the two X-ray energies can be processed by software to analyze material decomposition and to create additional image datasets, namely, virtual noncontrast, virtual contrast also known as iodine overlay, and bone/calcium subtraction images. DECT has a vast array of clinical applications in imaging cerebrovascular diseases, which includes: (1) Identification of active extravasation of iodinated contrast in various types of intracranial hemorrhage; (2) differentiation between hemorrhagic transformation and iodine staining in acute ischemic stroke following diagnostic and/or therapeutic catheter angiography; (3) identification of culprit lesions in intra-axial hemorrhage; (4) calcium subtraction from atheromatous plaque for the assessment of plaque morphology and improved quantification of luminal stenosis; (5) bone subtraction to improve the depiction of vascular anatomy with more clarity, especially at the skull base; (6) metal artifact reduction utilizing virtual monoenergetic reconstructions for improved luminal assessment postaneurysm coiling or clipping. We discuss the physical principles of DECT and review the clinical applications of DECT for the evaluation of cerebrovascular diseases. PMID:27512615

  7. Fibrosis assessment: impact on current management of chronic liver disease and application of quantitative invasive tools.

    PubMed

    Wang, Yan; Hou, Jin-Lin

    2016-05-01

    Fibrosis, a common pathogenic pathway of chronic liver disease (CLD), has long been indicated to be significantly and most importantly associated with severe prognosis. Nowadays, with remarkable advances in understanding and/or treatment of major CLDs such as hepatitis C, B, and nonalcoholic fatty liver disease, there is an unprecedented requirement for the diagnosis and assessment of liver fibrosis or cirrhosis in various clinical settings. Among the available approaches, liver biopsy remains the one which possibly provides the most direct and reliable information regarding fibrosis patterns and changes in the parenchyma at different clinical stages and with different etiologies. Thus, many endeavors have been undertaken for developing methodologies based on the strategy of quantitation for the invasive assessment. Here, we analyze the impact of fibrosis assessment on the CLD patient care based on the data of recent clinical studies. We discuss and update the current invasive tools regarding their technological features and potentials for the particular clinical applications. Furthermore, we propose the potential resolutions with application of quantitative invasive tools for some major issues in fibrosis assessment, which appear to be obstacles against the nowadays rapid progress in CLD medicine. PMID:26742762

  8. Functional Principal Component Analysis of Spatio-Temporal Point Processes with Applications in Disease Surveillance

    PubMed Central

    Li, Yehua; Guan, Yongtao

    2014-01-01

    In disease surveillance applications, the disease events are modeled by spatio-temporal point processes. We propose a new class of semiparametric generalized linear mixed model for such data, where the event rate is related to some known risk factors and some unknown latent random effects. We model the latent spatio-temporal process as spatially correlated functional data, and propose Poisson maximum likelihood and composite likelihood methods based on spline approximations to estimate the mean and covariance functions of the latent process. By performing functional principal component analysis to the latent process, we can better understand the correlation structure in the point process. We also propose an empirical Bayes method to predict the latent spatial random effects, which can help highlight hot areas with unusually high event rates. Under an increasing domain and increasing knots asymptotic framework, we establish the asymptotic distribution for the parametric components in the model and the asymptotic convergence rates for the functional principal component estimators. We illustrate the methodology through a simulation study and an application to the Connecticut Tumor Registry data. PMID:25368436

  9. Genome engineering in ophthalmology: Application of CRISPR/Cas to the treatment of eye disease.

    PubMed

    Hung, Sandy S C; McCaughey, Tristan; Swann, Olivia; Pébay, Alice; Hewitt, Alex W

    2016-07-01

    The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) and CRISPR-associated protein (Cas) system has enabled an accurate and efficient means to edit the human genome. Rapid advances in this technology could results in imminent clinical application, and with favourable anatomical and immunological profiles, ophthalmic disease will be at the forefront of such work. There have been a number of breakthroughs improving the specificity and efficacy of CRISPR/Cas-mediated genome editing. Similarly, better methods to identify off-target cleavage sites have also been developed. With the impending clinical utility of CRISPR/Cas technology, complex ethical issues related to the regulation and management of the precise applications of human gene editing must be considered. This review discusses the current progress and recent breakthroughs in CRISPR/Cas-based gene engineering, and outlines some of the technical issues that must be addressed before gene correction, be it in vivo or in vitro, is integrated into ophthalmic care. We outline a clinical pipeline for CRISPR-based treatments of inherited eye diseases and provide an overview of the important ethical implications of gene editing and how these may influence the future of this technology. PMID:27181583

  10. Nanomedicine for Infectious Disease Applications: Innovation towards Broad-Spectrum Treatment of Viral Infections.

    PubMed

    Jackman, Joshua A; Lee, Jaywon; Cho, Nam-Joon

    2016-03-01

    Nanomedicine enables unique diagnostic and therapeutic capabilities to tackle problems in clinical medicine. As multifunctional agents with programmable properties, nanomedicines are poised to revolutionize treatment strategies. This promise is especially evident for infectious disease applications, for which the continual emergence, re-emergence, and evolution of pathogens has proven difficult to counter by conventional approaches. Herein, a conceptual framework is presented that envisions possible routes for the development of nanomedicines as superior broad-spectrum antiviral agents against enveloped viruses. With lipid membranes playing a critical role in the life cycle of medically important enveloped viruses including HIV, influenza, and Ebola, cellular and viral membrane interfaces are ideal elements to incorporate into broad-spectrum antiviral strategies. Examples are presented that demonstrate how nanomedicine strategies inspired by lipid membranes enable a wide range of targeting opportunities to gain control of critical stages in the virus life cycle through either direct or indirect approaches involving membrane interfaces. The capabilities can be realized by enabling new inhibitory functions or improving the function of existing drugs through nanotechnology-enabled solutions. With these exciting opportunities, due attention is also given to the clinical translation of nanomedicines for infectious disease applications, especially as pharmaceutical drug-discovery pipelines demand new routes of innovation. PMID:26551316

  11. Application of computational methods in genetic study of inflammatory bowel disease

    PubMed Central

    Li, Jin; Wei, Zhi; Hakonarson, Hakon

    2016-01-01

    Genetic factors play an important role in the etiology of inflammatory bowel disease (IBD). The launch of genome-wide association study (GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods. PMID:26811639

  12. Bioavailability of dietary polyphenols: Factors contributing to their clinical application in CNS diseases.

    PubMed

    Pandareesh, M D; Mythri, R B; Srinivas Bharath, M M

    2015-10-01

    The anatomical location of the central nervous system (CNS) renders it immunologically and pharmacologically privileged due to the blood brain barrier (BBB). Although this limits the transport of unfavorable molecules to the CNS, the ensuing privilege could be disadvantageous for therapeutic compounds. Hence, the greatest challenge in the pharmacotherapy of CNS diseases is to ensure efficient brain targeting and drug delivery. Research evidences indicate that dietary polyphenols have neuroprotective potential against CNS diseases. However, their selective permeability across BBB, poor absorption, rapid metabolism and systemic elimination limit their bioavailability and therapeutic efficacy. Consequently, the beneficial effects of these orally administered agents in the CNS still remain a subject of debate. This has also limited its clinical application either as independent or adjunctive therapy. Improving the in vivo bioavailability by novel methods could improve the therapeutic feasibility of polyphenols and assist in evolving novel drugs and their derivatives with improved efficacy in vivo. Here we review the mechanistic and pharmacological issues related to the bioavailability of polyphenols with therapeutic implications for CNS diseases. We surmise that improving the bioavailability of polyphenols entails efficient in vivo transport across BBB, biochemical stability, improved half-life and persistent neuroprotection in the CNS. PMID:26163045

  13. [Towards the Clinical Application of iPS Cell Technology for the Treatment of Kidney Diseases].

    PubMed

    Osafune, Kenji

    2015-02-01

    In Japan, around 13 million adults have been estimated to suffer from chronic kidney disease (CKD), and more than 300 thousand patients with end-stage renal failure are receiving dialysis therapy, causing both medical and medicoeconomic problems. Regenerative medicine strategies using induced pluripotent stem (iPS) cells are among the candidate approaches to solve the problems. The mechanisms of kidney development and cell fate in the development of renal lineage cells have been elucidated using experimental animal models. Based on the knowledge of kidney development, intensive research has already been conducted to generate renal lineage cells from mouse embryonic stem (ES) cells, while few reports have been on studies using human iPS/ES cells. Recently, several research groups, including ours, have established methods to differentiate human iPS/ES cells into the intermediate mesoderm, an embryonic germ layer that gives rise to the kidney, and embryonic renal progenitors. Some reports also described the formation of three-dimensional renal tissues, such as renal tubules and glomeruli. Continued efforts are required to elucidate the mechanisms of kidney development and generate renal cells or tissues from human iPS cells, which could open up the new research avenues towards clinical application and practical use to overcome problems associated with kidney disease, such as human embryology, cell therapy, toxicology, drug discovery, and disease modeling. PMID:26529981

  14. Clinical applications, limitations and future role of transient elastography in the management of liver disease

    PubMed Central

    Chang, Pik Eu; Goh, George Boon-Bee; Ngu, Jing Hieng; Tan, Hiang Keat; Tan, Chee Kiat

    2016-01-01

    Transient elastography (TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate non-invasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in-time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease. PMID:26855815

  15. Potential applications of magnetic particles to detect and treat Alzheimer's disease

    PubMed Central

    2014-01-01

    Nanotechnology is an exciting and promising scientific discipline. At the nanoscale, a material displays novel physical properties that offer many new and beneficial products and applications. In particular, magnetic nanoparticles - a core/shell nanoparticle - present considerable diagnostic and therapeutic potentials, and superparamagnetic iron oxide nanoparticles (SPIONs) are considered promising theranostic tools. Alzheimer's disease (AD) is a neurodegenerative disorder that predominantly affects people over 65 years of age. The disease is characterized by the presence of extracellular plaques in the brain which are formed by interwoven fibrils composed of variants of the β-amyloid peptide. Medication can temporarily retard worsening of symptoms, but only in the first stages of the disease; early detection is thus of crucial importance. This minireview covers the progress made in research on the use of magnetic nanoparticles for ex vivo and/or in vivo detection and diagnosis of AD by means of magnetic resonance imaging (MRI), or to label peptides and fibrils. Of particular importance is the use of these nanoparticles to detect AD biomarkers in biological fluids. A description is given of the bio-barcode amplification assay using functionalized magnetic particles, as well as the use of such nanoparticles as a system for inhibiting or delaying the assembly of peptide monomers into oligomers and fibrils. Lastly, a brief overview is given of possible future lines of research in this. PMID:25288921

  16. 10 CFR 850.25 - Exposure reduction and minimization.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Exposure reduction and minimization. 850.25 Section 850.25 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker...

  17. 10 CFR 850.25 - Exposure reduction and minimization.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Exposure reduction and minimization. 850.25 Section 850.25 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker...

  18. 10 CFR 850.25 - Exposure reduction and minimization.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Exposure reduction and minimization. 850.25 Section 850.25 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker...

  19. 10 CFR 850.25 - Exposure reduction and minimization.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Exposure reduction and minimization. 850.25 Section 850.25 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker...

  20. 10 CFR 850.25 - Exposure reduction and minimization.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Exposure reduction and minimization. 850.25 Section 850.25 Energy DEPARTMENT OF ENERGY CHRONIC BERYLLIUM DISEASE PREVENTION PROGRAM Specific Program Requirements § 850.25 Exposure reduction and minimization. (a) The responsible employer must ensure that no worker...

  1. Minimal distances between SCFTs

    NASA Astrophysics Data System (ADS)

    Buican, Matthew

    2014-01-01

    We study lower bounds on the minimal distance in theory space between four-dimensional superconformal field theories (SCFTs) connected via broad classes of renormalization group (RG) flows preserving various amounts of supersymmetry (SUSY). For = 1 RG flows, the ultraviolet (UV) and infrared (IR) endpoints of the flow can be parametrically close. On the other hand, for RG flows emanating from a maximally supersymmetric SCFT, the distance to the IR theory cannot be arbitrarily small regardless of the amount of (non-trivial) SUSY preserved along the flow. The case of RG flows from =2 UV SCFTs is more subtle. We argue that for RG flows preserving the full =2 SUSY, there are various obstructions to finding examples with parametrically close UV and IR endpoints. Under reasonable assumptions, these obstructions include: unitarity, known bounds on the c central charge derived from associativity of the operator product expansion, and the central charge bounds of Hofman and Maldacena. On the other hand, for RG flows that break = 2 → = 1, it is possible to find IR fixed points that are parametrically close to the UV ones. In this case, we argue that if the UV SCFT possesses a single stress tensor, then such RG flows excite of order all the degrees of freedom of the UV theory. Furthermore, if the UV theory has some flavor symmetry, we argue that the UV central charges should not be too large relative to certain parameters in the theory.

  2. Swarm robotics and minimalism

    NASA Astrophysics Data System (ADS)

    Sharkey, Amanda J. C.

    2007-09-01

    Swarm Robotics (SR) is closely related to Swarm Intelligence, and both were initially inspired by studies of social insects. Their guiding principles are based on their biological inspiration and take the form of an emphasis on decentralized local control and communication. Earlier studies went a step further in emphasizing the use of simple reactive robots that only communicate indirectly through the environment. More recently SR studies have moved beyond these constraints to explore the use of non-reactive robots that communicate directly, and that can learn and represent their environment. There is no clear agreement in the literature about how far such extensions of the original principles could go. Should there be any limitations on the individual abilities of the robots used in SR studies? Should knowledge of the capabilities of social insects lead to constraints on the capabilities of individual robots in SR studies? There is a lack of explicit discussion of such questions, and researchers have adopted a variety of constraints for a variety of reasons. A simple taxonomy of swarm robotics is presented here with the aim of addressing and clarifying these questions. The taxonomy distinguishes subareas of SR based on the emphases and justifications for minimalism and individual simplicity.

  3. Research toward integrate management of the emerging viroid disease on tomato through seed health test, disinfectant application and disease resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the last few years, several devastating viroid disease outbreaks were identified on greenhouse tomatoes in North America. These emerging diseases have caused serious concerns to the tomato industry and seed suppliers. Several closely related viroid species, including Potato spindle tuber viroid...

  4. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

    PubMed

    Chen, L W; Kuang, F; Wei, L C; Ding, Y X; Yung, K K L; Chan, Y S

    2011-06-01

    Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for

  5. Minimal Higgs inflation

    NASA Astrophysics Data System (ADS)

    Hamada, Yuta; Kawai, Hikaru; Oda, Kin-ya

    2014-02-01

    We consider a possibility that the Higgs field in the Standard Model (SM) serves as an inflaton when its value is around the Planck scale. We assume that the SM is valid up to an ultraviolet cutoff scale Λ , which is slightly below the Planck scale, and that the Higgs potential becomes almost flat above Λ . Contrary to the ordinary Higgs inflation scenario, we do not assume the huge non-minimal coupling, of O(10^4), of the Higgs field to the Ricci scalar. We find that Λ must be less than 5× 10^{17} {GeV} in order to explain the observed fluctuation of the cosmic microwave background, no matter how we extrapolate the Higgs potential above Λ . The scale 10^{17} {GeV} coincides with the perturbative string scale, which suggests that the SM is directly connected with string theory. For this to be true, the top quark mass is restricted to around 171 GeV, with which Λ can exceed 10^{17} {GeV}. As a concrete example of the potential above Λ , we propose a simple log-type potential. The predictions of this specific model for the e-foldings N_*=50-60 are consistent with the current observation, namely, the scalar spectral index is n_s=0.977hbox {-}0.983 and the tensor to scalar ratio 0

  6. Minimally invasive thyroidectomy: a ten years experience

    PubMed Central

    Viani, Lorenzo; Montana, Chiara Montana; Cozzani, Federico; Sianesi, Mario

    2016-01-01

    Background The conventional thyroidectomy is the most frequent surgical procedure for thyroidal surgical disease. From several years were introduced minimally invasive approaches to thyroid surgery. These new procedures improved the incidence of postoperative pain, cosmetic results, patient’s quality of life, postoperative morbidity. The mini invasive video-assisted thyroidectomy (MIVAT) is a minimally invasive procedure that uses a minicervicotomy to treat thyroidal diseases. Methods We present our experience on 497 consecutively treated patients with MIVAT technique. We analyzed the mean age, sex, mean operative time, rate of bleeding, hypocalcemia, transitory and definitive nerve palsy (6 months after the procedure), postoperative pain scale from 0 to 10 at 1 hour and 24 hours after surgery, mean hospital stay. Results The indications to treat were related to preoperative diagnosis: 182 THYR 6, 184 THYR 3–4, 27 plummer, 24 basedow, 28 toxic goiter, 52 goiter. On 497 cases we have reported 1 case of bleeding (0,2%), 12 (2,4%) cases of transitory nerve palsy and 4 (0,8%) definitive nerve palsy. The rate of serologic hypocalcemia was 24.9% (124 cases) and clinical in 7.2% (36 cases); 1 case of hypoparathyroidism (0.2%). Conclusions The MIVAT is a safe approach to surgical thyroid disease, the cost are similar to CT as the adverse events. The minicervicotomy is really a minimally invasive tissue dissection. PMID:27294036

  7. Minimal invasive treatments for liver malignancies.

    PubMed

    Orsi, Franco; Varano, Gianluca

    2015-11-01

    Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis. PMID:26050603

  8. Applications of mathematical modeling in managing the spread of chronic wasting disease (CWD) in wild deer under alternative harvesting scenarios.

    PubMed

    Al-Arydah, M; Croteau, M C; Oraby, T; Smith, R J; Krewski, D

    2016-01-01

    The application of a recently developed mathematical model for predicting the spread of chronic wasting disease (CWD) in wild deer was assessed under different scenarios where harvesting is employed in disease management. A process-based mathematical model for CWD transmission in wild deer populations was recently developed and parameterized by Al-arydah et al. (2011) to provide a scientific basis for understanding the factors that affect spread of CWD and evaluate concomitant disease-control strategies. The impact of gender on CWD transmission was shown to have a significant influence on the spread of the disease in the wild. Our model demonstrates a range of harvesting rates in which CWD is controlled and deer populations survive. However, if harvesting rates are too low, the disease remains endemic for decades. Conversely, the Canadian deer population is eradicated if harvesting rates are excessive. Future investigation includes building the model to assess the spread of CWD under different disease-management scenarios. PMID:27556563

  9. Application of Cavity Enhanced Absorption Spectroscopy to the Detection of Nitric Oxide, Carbonyl Sulphide, and Ethane--Breath Biomarkers of Serious Diseases.

    PubMed

    Wojtas, Jacek

    2015-01-01

    The paper presents one of the laser absorption spectroscopy techniques as an effective tool for sensitive analysis of trace gas species in human breath. Characterization of nitric oxide, carbonyl sulphide and ethane, and the selection of their absorption lines are described. Experiments with some biomarkers showed that detection of pathogenic changes at the molecular level is possible using this technique. Thanks to cavity enhanced spectroscopy application, detection limits at the ppb-level and short measurements time (<3 s) were achieved. Absorption lines of reference samples of the selected volatile biomarkers were probed using a distributed feedback quantum cascade laser and a tunable laser system consisting of an optical parametric oscillator and difference frequency generator. Setup using the first source provided a detection limit of 30 ppb for nitric oxide and 250 ppb for carbonyl sulphide. During experiments employing a second laser, detection limits of 0.9 ppb and 0.3 ppb were obtained for carbonyl sulphide and ethane, respectively. The conducted experiments show that this type of diagnosis would significantly increase chances for effective therapy of some diseases. Additionally, it offers non-invasive and real time measurements, high sensitivity and selectivity as well as minimizing discomfort for patients. For that reason, such sensors can be used in screening for early detection of serious diseases. PMID:26091398

  10. Application of Cavity Enhanced Absorption Spectroscopy to the Detection of Nitric Oxide, Carbonyl Sulphide, and Ethane—Breath Biomarkers of Serious Diseases

    PubMed Central

    Wojtas, Jacek

    2015-01-01

    The paper presents one of the laser absorption spectroscopy techniques as an effective tool for sensitive analysis of trace gas species in human breath. Characterization of nitric oxide, carbonyl sulphide and ethane, and the selection of their absorption lines are described. Experiments with some biomarkers showed that detection of pathogenic changes at the molecular level is possible using this technique. Thanks to cavity enhanced spectroscopy application, detection limits at the ppb-level and short measurements time (<3 s) were achieved. Absorption lines of reference samples of the selected volatile biomarkers were probed using a distributed feedback quantum cascade laser and a tunable laser system consisting of an optical parametric oscillator and difference frequency generator. Setup using the first source provided a detection limit of 30 ppb for nitric oxide and 250 ppb for carbonyl sulphide. During experiments employing a second laser, detection limits of 0.9 ppb and 0.3 ppb were obtained for carbonyl sulphide and ethane, respectively. The conducted experiments show that this type of diagnosis would significantly increase chances for effective therapy of some diseases. Additionally, it offers non-invasive and real time measurements, high sensitivity and selectivity as well as minimizing discomfort for patients. For that reason, such sensors can be used in screening for early detection of serious diseases. PMID:26091398

  11. Voxelwise spectral diffusional connectivity and its applications to Alzheimer's disease and intelligence prediction.

    PubMed

    Li, Junning; Jin, Yan; Shi, Yonggang; Dinov, Ivo D; Wang, Danny J; Toga, Arthur W; Thompson, Paul M

    2013-01-01

    Human brain connectivity can be studied using graph theory. Many connectivity studies parcellate the brain into regions and count fibres extracted between them. The resulting network analyses require validation of the tractography, as well as region and parameter selection. Here we investigate whole brain connectivity from a different perspective. We propose a mathematical formulation based on studying the eigenvalues of the Laplacian matrix of the diffusion tensor field at the voxel level. This voxelwise matrix has over a million parameters, but we derive the Kirchhoff complexity and eigen-spectrum through elegant mathematical theorems, without heavy computation. We use these novel measures to accurately estimate the voxelwise connectivity in multiple biomedical applications such as Alzheimer's disease and intelligence prediction. PMID:24505723

  12. Alzheimer’s Disease: Pathophysiology and Applications of Magnetic Nanoparticles as MRI Theranostic Agents

    PubMed Central

    2013-01-01

    Alzheimer’s disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis. Then magnetic nanoparticles (MNPs) and recent works on their applications in AD, focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are reviewed. Furthermore, the amyloid–nanoparticle interaction is highlighted, with the scope to be highly considered by the scientists aiming for diagnostics and/or treatment of AD employing nanoparticles. Furthermore, recent findings on the “ignored” parameters (e.g., effect of protein “corona” at the surface of nanoparticles on amyloid-β (Aβ) fibrillation process) are discussed. PMID:24024702

  13. A compact microscope setup for multimodal nonlinear imaging in clinics and its application to disease diagnostics.

    PubMed

    Meyer, Tobias; Baumgartl, Martin; Gottschall, Thomas; Pascher, Torbjörn; Wuttig, Andreas; Matthäus, Christian; Romeike, Bernd F M; Brehm, Bernhard R; Limpert, Jens; Tünnermann, Andreas; Guntinas-Lichius, Orlando; Dietzek, Benjamin; Schmitt, Michael; Popp, Jürgen

    2013-07-21

    The past years have seen increasing interest in nonlinear optical microscopic imaging approaches for the investigation of diseases due to the method's unique capabilities of deep tissue penetration, 3D sectioning and molecular contrast. Its application in clinical routine diagnostics, however, is hampered by large and costly equipment requiring trained staff and regular maintenance, hence it has not yet matured to a reliable tool for application in clinics. In this contribution implementing a novel compact fiber laser system into a tailored designed laser scanning microscope results in a small footprint easy to use multimodal imaging platform enabling simultaneously highly efficient generation and acquisition of second harmonic generation (SHG), two-photon excited fluorescence (TPEF) as well as coherent anti-Stokes Raman scattering (CARS) signals with optimized CARS contrast for lipid imaging for label-free investigation of tissue samples. The instrument combining a laser source and a microscope features a unique combination of the highest NIR transmission and a fourfold enlarged field of view suited for investigating large tissue specimens. Despite its small size and turnkey operation rendering daily alignment dispensable the system provides the highest flexibility, an imaging speed of 1 megapixel per second and diffraction limited spatial resolution. This is illustrated by imaging samples of squamous cell carcinoma of the head and neck (HNSCC) and an animal model of atherosclerosis allowing for a complete characterization of the tissue composition and morphology, i.e. the tissue's morphochemistry. Highly valuable information for clinical diagnostics, e.g. monitoring the disease progression at the cellular level with molecular specificity, can be retrieved. Future combination with microscopic probes for in vivo imaging or even implementation in endoscopes will allow for in vivo grading of HNSCC and characterization of plaque deposits towards the detection of high

  14. Application of Radar Altimetry Methods to Monitoring of Parasitic Disease Transmission: Schistosomiasis in Poyang Lake, China

    NASA Astrophysics Data System (ADS)

    McCandless, M.; Ibaraki, M.; Shum, C.; Lee, H.; Liang, S.

    2008-12-01

    Schistosomiasis is the second-most prevalent tropical disease after malaria affecting two-hundred million people annually world-wide; it shortens lifespan on average by ten years in endemic areas and no vaccine exists. The current control methods of human host chemotherapy and application of molluscicides to the environment do not break the disease transmission cycle. Schistosomiasis transmission in southern China involves an amphibious intermediate host snail for which hydrology is a key factor because the adults need moist vegetation while the juveniles are fully aquatic. Thus, hydrology is a key factor in schistosomiasis transmission and understanding its role can inform control measures. Our objective is to integrate hydrologic, ecologic, and other environmental factors to determine the changes in available snail habitat through space and time. We use radar altimetry measurements to determine water level every 35 days when the Envisat (Environmental Satellite) passes over the lake. The radar altimetry readings have been calibrated to levels from in-situ gauging stations and will support remote analysis of disease transmission potential without the need for gauging station data. A geographic information system was used to combine key factors including water level, topography, and air temperature data to identify areas of available snail habitat. In order to accomplish this, we conducted three steps including: delineating the watershed, specifying potential snail habitat areas through topography and air temperature classification, and calculating the intersection between potential snail habitat and non-flooded areas in the watershed. Statistical analyses of total available habitat area are also conducted. These maps and statistics analyses can be used by public health agencies to monitor snail habitat trends over time. Coupling remote sensing of water levels with a geographic information system model will continue to be important as the hydrology of the lake

  15. Syndromic Surveillance of Infectious Diseases meets Molecular Epidemiology in a Workflow and Phylogeographic Application.

    PubMed

    Janies, Daniel; Witter, Zachary; Gibson, Christian; Kraft, Thomas; Senturk, Izzet F; Çatalyürek, Ümit

    2015-01-01

    Traditionally, epidemiologists have counted cases and groups of symptoms. Modeling on these data consists of predicting expansion or contraction in the number of cases over time in epidemic curves or compartment models. Geography is considered a variable when these data are presented in choropleth maps. These approaches have significant drawbacks if the cases counted are not accurately diagnosed. For example, most regional public health authorities count influenza like illnesses (ILI). Cases of these diseases are designated as ILI if the patient exhibits fever, respiratory symptoms, and perhaps gastrointestinal symptoms. Several molecular epidemiological studies have shown that there are many pathogens that cause these symptoms and the relative proportions of these pathogens change over time and space. One way to bridge the gap between syndromic and genetic surveillance of infectious diseases is to compare signals of symptoms to pathogens recorded in molecular databases. We present a web-based workflow application that uses chief complaints found in the public Twitter feed as a syndromic surveillance tool and connects outbreak signals in these data to pathogens historically known to circulate in the same area. For the pathogen(s) of interest, we provide Genbank links to metadata and sequences in a workflow for phylogeographic analysis and visualization. The visualizations provide information on the geographic traffic of the spread of the pathogens and places that are hubs for their transport. PMID:26262155

  16. REACTIN: Regulatory activity inference of transcription factors underlying human diseases with application to breast cancer

    PubMed Central

    2013-01-01

    Background Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Results Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients. Conclusions REACTIN provides a useful tool to investigate regulatory programs underlying a biological process providing the related case and control gene expression data. Considering the enormous amount of cancer gene expression data and the increasingly accumulating ChIP-seq data, we expect wide application of REACTIN for revealing the regulatory mechanisms of various diseases. PMID:23885756

  17. Application of aqueous dispersions of silver nanostructures for treatment of pyoinflammatory diseases with a chronic component

    NASA Astrophysics Data System (ADS)

    Rutberg, Ph; Kolikov, V.; Snetov, V.; Stogov, A.; Moshkin, A.; Khalilov, M.

    2011-01-01

    Bactericidal properties of aqueous dispersions of oxide silver nanostructures (ADSN) produced by means of pulsed electric discharges (PED) in water can use in surgery for treatment of upper purulent wounds with a chronic component. The patients with such wounds are of large number and differ on etiology of diseases but their mutual feature is long treatment without marked positive changes. Thus long application of antibiotics leads to abnormality of immune processes and antibacterial resistance of microbial flora. Moreover, local antiseptics are frequently toxic and one can oppress processes of reparation in a wound. The investigation is addressed to finding out the opportunity of usage of an ADSN for treatment of purulent wounds with a chronic component and comparison of its efficiency with the sodium hypochlorite. At investigation, the ADSN formed at PED of 5 - 10 μs duration, with highest share of "small" (hydrodynamic diameter <= 100 nm) nanostructures and greatest surface electric charge we used. It was found that the usage of ADSN during the first 5 days characterized by high active reparative processes with their maximum at 3rd - 4th days and subsequent moderate further healing. At local use of ADSN, there were no cellular atypia and preternatural representations about inflammatory reactions. It is possible to assume that usage of ADSN will allow in prospect to correct the practice of out-patient therapy of chronic and slow pyoinflammatory diseases.

  18. Application of genome-wide expression analysis to human health and disease

    PubMed Central

    Cobb, J. Perren; Mindrinos, Michael N.; Miller-Graziano, Carol; Calvano, Steve E.; Baker, Henry V.; Xiao, Wenzhong; Laudanski, Krzysztof; Brownstein, Bernard H.; Elson, Constance M.; Hayden, Douglas L.; Herndon, David N.; Lowry, Stephen F.; Maier, Ronald V.; Schoenfeld, David A.; Moldawer, Lyle L.; Davis, Ronald W.; Tompkins, Ronald G.

    2005-01-01

    The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease. PMID:15781863

  19. Applications of Surface Plasmon Resonance for Characterization of Molecules Important in the Pathogenesis and Treatment of Neurodegenerative Diseases

    PubMed Central

    Wittenberg, Nathan J.; Wootla, Bharath; Jordan, Luke R.; Denic, Aleksandar; Warrington, Arthur E.; Oh, Sang-Hyun; Rodriguez, Moses

    2014-01-01

    Characterization of binding kinetics and affinity between a potential new drug and its receptor are key steps in the development of new drugs. Among the techniques available to determine binding affinities, surface plasmon resonance has emerged as the gold standard because it can measure binding and dissociation rates in real-time in a label-free fashion. Surface plasmon resonance is now finding applications in the characterization of molecules for treatment of neurodegenerative diseases, characterization of molecules associated with pathogenesis of neurodegenerative diseases and detection of neurodegenerative disease biomarkers. In addition it has been used in the characterization of a new class of natural autoantibodies that have therapeutic potential in a number of neurologic diseases. In this review we will introduce surface plasmon resonance and describe some applications of the technique that pertain to neurodegenerative disorders and their treatment. PMID:24625008

  20. Applications of SPR for the characterization of molecules important in the pathogenesis and treatment of neurodegenerative diseases.

    PubMed

    Wittenberg, Nathan J; Wootla, Bharath; Jordan, Luke R; Denic, Aleksandar; Warrington, Arthur E; Oh, Sang-Hyun; Rodriguez, Moses

    2014-04-01

    Characterization of binding kinetics and affinity between a potential drug and its receptor are key steps in the development of new drugs. Among the techniques available to determine binding affinities, surface plasmon resonance has emerged as the gold standard because it can measure binding and dissociation rates in real-time in a label-free fashion. Surface plasmon resonance is now finding applications in the characterization of molecules for treatment of neurodegenerative diseases, characterization of molecules associated with pathogenesis of neurodegenerative diseases and detection of neurodegenerative disease biomarkers. In addition it has been used in the characterization of a new class of natural autoantibodies that have therapeutic potential in a number of neurologic diseases. In this review we will introduce surface plasmon resonance and describe some applications of the technique that pertain to neurodegenerative disorders and their treatment. PMID:24625008

  1. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  2. Application of odor identification test in Parkinson's disease in China: a matched case-control study.

    PubMed

    Chen, Wei; Chen, Shuai; Kang, Wen-Yan; Li, Bo; Xu, Zhi-Min; Xiao, Qin; Liu, Jun; Wang, Ying; Wang, Gang; Chen, Sheng-Di

    2012-05-15

    As one of the most common non-motor symptoms in Parkinson's disease (PD), hyposmia is of great importance in establishing the early diagnosis of PD. To date, there are still no studies on the application of the 16-item odor identification test from Sniffin' Sticks (SS-16) in Chinese patients with PD. The aim of this study was to investigate the validity of SS-16 in Chinese PD patients (n=110) compared with age and gender matched controls (n=110), and to explore the associated factors with olfactory function in PD patients. The 16 odors in the original odor identification test were retained but some alternative descriptions were developed before applications. Mean identification scores in patients were significantly lower than in controls (7.3 ± 2.8 VS. 11.6 ± 2.0 P<0.01), with 66.4% of patients had an impairment of odor identification as evaluated by 95% confidential interval of the identification score of the control group. Receiver operating characteristic curves revealed 86% sensitivity and 81% specificity in separating PD and healthy controls with a cut-off value of 9.5. Multiple linear regression analysis revealed that autonomic dysfunction was a significant influential factor of odor identification scores in patients with PD. In conclusion, SS-16 provides a valid instrument for olfactory assessment in Chinese PD patients, and hyposmia may correlate with autonomic dysfunction in patients with PD. PMID:22364958

  3. Guidelines for mixed waste minimization

    SciTech Connect

    Owens, C.

    1992-02-01

    Currently, there is no commercial mixed waste disposal available in the United States. Storage and treatment for commercial mixed waste is limited. Host States and compacts region officials are encouraging their mixed waste generators to minimize their mixed wastes because of management limitations. This document provides a guide to mixed waste minimization.

  4. A generic model of contagious disease and its application to human-to-human transmission of avian influenza.

    SciTech Connect

    Hirsch, Gary B.

    2007-03-01

    Modeling contagious diseases has taken on greater importance over the past several years as diseases such as SARS and avian influenza have raised concern about worldwide pandemics. Most models developed to consider projected outbreaks have been specific to a single disease. This paper describes a generic System Dynamics contagious disease model and its application to human-to-human transmission of a mutant version of avian influenza. The model offers the option of calculating rates of new infections over time based either on a fixed ''reproductive number'' that is traditional in contagious disease models or on contact rates for different sub-populations and likelihood of transmission per contact. The paper reports on results with various types of interventions. These results suggest the potential importance of contact tracing, limited quarantine, and targeted vaccination strategies as methods for controlling outbreaks, especially when vaccine supplies may initially be limited and the efficacy of anti-viral drugs uncertain.

  5. Integration of selective breeding and vaccination to improve disease resistance in aquaculture: Application to control bacterial cold water disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bacterial cold water disease (BCWD) is a frequent cause of elevated mortality in rainbow trout and the development of effective control strategies is a priority within the U.S. A goal of the NCCCWA breeding program is to produce germplasm with superior growth and survival following exposure to infe...

  6. Emerging Techniques in Minimally Invasive Surgery. Pros and Cons.

    PubMed

    Fisichella, P Marco; DeMeester, Steven R; Hungness, Eric; Perretta, Silvana; Soper, Nathaniel J; Rosemurgy, Alexander; Torquati, Alfonso; Sachdeva, Ajit K; Patti, Marco G

    2015-07-01

    New trends have emerged regarding the best minimally invasive access approaches to perform gastrointestinal surgery. However, these newer approaches are seen critically by those who demand a more strict assessment of outcomes and safety. An international panel of expert gathered at the 2014 American College of Surgeons Meeting with the goal of providing an evidence-based understanding of the real value of these approaches in gastrointestinal surgery. The panel has compared the efficacy and safety of most established approaches to gastrointestinal diseases to those of new treatment modalities: peroral esophageal myotomy vs. laparoscopic myotomy for achalasia, transgastric vs. transvaginal approach, and single-incision vs. multi-port access minimally invasive surgery. The panel found that (1) the outcome of these new approaches was not superior to that of established surgical procedures; (2) the new approaches are generally performed in few highly specialized centers; and (3) transgastric and transvaginal approaches might be safe and feasible in very experienced hands, but cost, training, operative time, and tools seem to limit their application for the treatment of common procedures such as cholecystectomy and appendectomy. Because the expected advantages of new approaches have yet to be proven in controlled trials, new approaches should be considered for adoption into practice only after thorough analyses of their efficacy and effectiveness and appropriate training. PMID:25678255

  7. Inverse Modeling Via Linearized Functional Minimization

    NASA Astrophysics Data System (ADS)

    Barajas-Solano, D. A.; Wohlberg, B.; Vesselinov, V. V.; Tartakovsky, D. M.

    2014-12-01

    We present a novel parameter estimation methodology for transient models of geophysical systems with uncertain, spatially distributed, heterogeneous and piece-wise continuous parameters.The methodology employs a bayesian approach to propose an inverse modeling problem for the spatial configuration of the model parameters.The likelihood of the configuration is formulated using sparse measurements of both model parameters and transient states.We propose using total variation regularization (TV) as the prior reflecting the heterogeneous, piece-wise continuity assumption on the parameter distribution.The maximum a posteriori (MAP) estimator of the parameter configuration is then computed by minimizing the negative bayesian log-posterior using a linearized functional minimization approach. The computation of the MAP estimator is a large-dimensional nonlinear minimization problem with two sources of nonlinearity: (1) the TV operator, and (2) the nonlinear relation between states and parameters provided by the model's governing equations.We propose a a hybrid linearized functional minimization (LFM) algorithm in two stages to efficiently treat both sources of nonlinearity.The relation between states and parameters is linearized, resulting in a linear minimization sub-problem equipped with the TV operator; this sub-problem is then minimized using the Alternating Direction Method of Multipliers (ADMM). The methodology is illustrated with a transient saturated groundwater flow application in a synthetic domain, stimulated by external point-wise loadings representing aquifer pumping, together with an array of discrete measurements of hydraulic conductivity and transient measurements of hydraulic head.We show that our inversion strategy is able to recover the overall large-scale features of the parameter configuration, and that the reconstruction is improved by the addition of transient information of the state variable.

  8. Characterization of a minimal pKW2124 replicon from Weissella cibaria KLC140 and its application for the construction of the Weissella expression vector pKUCm1.

    PubMed

    Ku, Hye-Jin; Park, Myeong Soo; Lee, Ju-Hoon

    2015-01-01

    A 2.1-kb plasmid was previously isolated from Weissella cibaria KLC140 in kimchi and cloned into pUC19 along with the slpA and gfp genes, resulting in an 8.6-kb pKWCSLGFP construct for use as a novel surface display vector. To reduce the size of the vector, the minimal replicon of pKW2124 was determined. The pKW2124 plasmid contains a putative origin of replication (ori), a potential ribosomal binding site (RBS), and the repA gene encoding a plasmid replication protein. To conduct the minimal replicon experiment, four different PCR products (MR1, ori+RBS+repA; MR2, RBS+repA; MR2', repA; MR3, fragment of repA) were obtained and cloned into pUC19 (pKUCm1, pKUCm2, pKUCm2', and pKUCm3, respectively) containing the chloramphenicol acetyltransferase (CAT) gene. These constructed vectors were electroporated into W. confusa ATCC 10881 with different transformation efficiencies of 1.5 × 10(5) CFU/μg, 1.3 × 10(1) CFU/μg, and no transformation, respectively, suggesting that the putative ori, RBS, and repA gene are essential for optimum plasmid replication. Subsequent segregational plasmid stability testing of pKUCm1 and pKUCm2 showed that the vector pKUCm1 is highly stable up to 100 generations but pKUCm2 was completely lost after 60 generations, suggesting that the putative ori may be important for plasmid stability in the host strain. In addition, a host range test of pKUCm1 revealed that it has a broad host range spectrum including Weissella, Lactococcus, Leuconostoc, and even Lactobacillus. To verify the application of pKUCm1, the β-galactosidase gene and its promoter region from W. cibaria KSD1 were cloned in the vector, resulting in pKUGal. Expression of the β-galactosidase gene was confirmed using blue-white screening after IPTG induction. The small and stable pKUGal vector will be useful for gene transfer, expression, and manipulation in the Weissella genome and in other lactic acid bacteria. PMID:25691882

  9. Characterization of a minimal pKW2124 replicon from Weissella cibaria KLC140 and its application for the construction of the Weissella expression vector pKUCm1

    PubMed Central

    Ku, Hye-Jin; Park, Myeong Soo; Lee, Ju-Hoon

    2015-01-01

    A 2.1-kb plasmid was previously isolated from Weissella cibaria KLC140 in kimchi and cloned into pUC19 along with the slpA and gfp genes, resulting in an 8.6-kb pKWCSLGFP construct for use as a novel surface display vector. To reduce the size of the vector, the minimal replicon of pKW2124 was determined. The pKW2124 plasmid contains a putative origin of replication (ori), a potential ribosomal binding site (RBS), and the repA gene encoding a plasmid replication protein. To conduct the minimal replicon experiment, four different PCR products (MR1, ori+RBS+repA; MR2, RBS+repA; MR2’, repA; MR3, fragment of repA) were obtained and cloned into pUC19 (pKUCm1, pKUCm2, pKUCm2’, and pKUCm3, respectively) containing the chloramphenicol acetyltransferase (CAT) gene. These constructed vectors were electroporated into W. confusa ATCC 10881 with different transformation efficiencies of 1.5 × 105 CFU/μg, 1.3 × 101 CFU/μg, and no transformation, respectively, suggesting that the putative ori, RBS, and repA gene are essential for optimum plasmid replication. Subsequent segregational plasmid stability testing of pKUCm1 and pKUCm2 showed that the vector pKUCm1 is highly stable up to 100 generations but pKUCm2 was completely lost after 60 generations, suggesting that the putative ori may be important for plasmid stability in the host strain. In addition, a host range test of pKUCm1 revealed that it has a broad host range spectrum including Weissella, Lactococcus, Leuconostoc, and even Lactobacillus. To verify the application of pKUCm1, the β-galactosidase gene and its promoter region from W. cibaria KSD1 were cloned in the vector, resulting in pKUGal. Expression of the β-galactosidase gene was confirmed using blue-white screening after IPTG induction. The small and stable pKUGal vector will be useful for gene transfer, expression, and manipulation in the Weissella genome and in other lactic acid bacteria. PMID:25691882

  10. Differentiation between diseases using a programmable hand-held calculator and Bayes' theorem: application to lower gastrointestinal tract disorders.

    PubMed

    van de Merwe, J P

    1984-01-01

    A program is presented for the Hewlett-Packard HP-41C programmable pocket calculator that computes posterior probabilities of more than 200 diseases on the basis of Bayes' theorem. Data for specific applications are stored in ASCII files. The program and data are retained in the non-volatile memory of the calculator. An example of the application of the program to six lower gastrointestinal tract disorders is given using data from the literature. PMID:6391801

  11. Constrained \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm T}p{\\rm V}$\\end{document} Minimization for Enhanced Exploitation of Gradient Sparsity: Application to CT Image Reconstruction

    PubMed Central

    Chartrand, Rick; Boone, John M.; Pan, Xiaochuan

    2014-01-01

    Exploiting sparsity in the image gradient magnitude has proved to be an effective means for reducing the sampling rate in the projection view angle in computed tomography (CT). Most of the image reconstruction algorithms, developed for this purpose, solve a nonsmooth convex optimization problem involving the image total variation (TV). The TV seminorm is the \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\ell_{1}$\\end{document} norm of the image gradient magnitude, and reducing the \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\ell_{1}$\\end{document} norm is known to encourage sparsity in its argument. Recently, there has been interest in employing nonconvex \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\ell_{p}$\\end{document} quasinorms with \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$0minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\ell_{1}$\\end{document} because nonconvex

  12. [Problems occurring in the application of cytogenetic biomarkers for alcoholics with and without malignant diseases].

    PubMed

    Gundy, Sarolta; Székely, Gábor; Farkas, Gyöngyi; Pulay, Attila; Remenár, Eva

    2008-06-01

    Applicability of alcohol- and smoking-related cancer-risk biomarkers might be modified by several factors. Among those, reality of self-reports on alcohol consumption of alcoholic patients with different diseases and extreme high mutagen hypersensitivity of Hungarians, as well as the immunologic role of peripheral lymphocytes as experimental objects of cytogenetic biomarkers seem to be new viewpoints of interest. To clarify these problems, 432 head and neck cancer patients (HNCP), 62 alcoholics with alcoholic hepatitis (ALCL), and 101 disease-free chronic alcoholics (ALC) were examined. Despite clinically confirmed alcohol-related diagnoses (and GGT and MCV values) only about half of HNCPs and ALCLs reported about any alcohol consumption, in contrast to the realistic self-reports of ALCs. In cytogenetic case control investigations no difference between the spontaneous rate of chromosomal aberrations (CAs) of healthy controls and ALCs was found, however, genetic instability expressed as a 40-50% elevation rate of CAs in HNCPs and ALCLs might be associated with systemic inflammatory reaction of lymphocytes. Bleomycin sensitivity assay showed the highest break/cell (b/c) values not in HNCPs (1.06 b/c) as it was reported earlier, but in "healthy" ALCs (1.52 b/c). This phenomenon can be related to the local effect of genotoxins (alcohol, smoking, and in particular the diet), which probably reflects merely a reaction of mucosal immune system. Nearly 50% of mutagen-hypersensitive Hungarian controls, in contrary to the expected 10-20% ones, might also be explained by this. Similarly, HNCPs with oral cancer, where the local mutagen effect was the most intensive, had the highest b/c values. In conclusion, when cytogenetic biomarkers of alcoholism are examined, the subjective character of self-reports at epidemiologic level and immunologic role of lymphocyte subpopulations as genetic confounders must also be taken into consideration. PMID:18640891

  13. Clinical Therapeutic Effects of the Application of Doxycycline in the Treatment of Periodontal Disease

    PubMed Central

    Spasovski, Spiro; Belazelkoska, Zlatanka; Popovska, Mirjana; Atanasovska-Stojanovska, Aneta; Radojkova-Nikolovska, Vera; Muratovska, Ilijana; Toseska-Spasova, Natasa; Dzipunova, Biljana; Nikolovski, Bruno

    2016-01-01

    OBJECTIVE: To compare the therapeutic effects of the application of doxycycline-full dose (100 mg) and sub-dose (20 mg) in the treatment of periodontal disease. MATERIAL AND METHODS: A total of 60 patients with periodontal disease were examined. Patients are divided into two groups: A) treated with antimicrobial dose of 100 mg doxycycline once daily for 30 days, and B) treated with 2 x 20 mg/day. doxycycline, during 75 days. Among all patients a conservative treatment was carried out and ordinated the proper dose doxycycline in total dose during treatment from 3 gr. Index of dental plaque by Löe-Sillness, index of gingival inflammation and gingival bleeding by Cowell were followed. RESULTS: Values of dental plaque in relation first examination, 10th, 20th day, 1 month and 2.5 months, showed that after 2.5 months, average value (x = 0.83) of dental plaque in second group is slightly less than the value (x = 0.93) of dental plaque in the first group. The average value (x = 0.17) of gingival inflammation in second group is significantly less than the value (x = 0.50) of gingival inflammation in the first group. The average value (x = 0.97) of gingival bleeding in patients from the first group was significantly higher than value(x = 0.37) of gingival bleeding in the second group. CONCLUSION: Patients whose therapy was helped by a sub-dose doxycycline demonstrated positive therapeutic effects on gingival inflammation and bleeding. PMID:27275351

  14. Minimizing waste in environmental restoration

    SciTech Connect

    Moos, L.; Thuot, J.R.

    1996-07-01

    Environmental restoration, decontamination and decommissioning and facility dismantelment projects are not typically known for their waste minimization and pollution prevention efforts. Typical projects are driven by schedules and milestones with little attention given to cost or waste minimization. Conventional wisdom in these projects is that the waste already exists and cannot be reduced or minimized. In fact, however, there are three significant areas where waste and cost can be reduced. Waste reduction can occur in three ways: beneficial reuse or recycling; segregation of waste types; and reducing generation of secondary waste. This paper will discuss several examples of reuse, recycle, segregation, and secondary waste reduction at ANL restoration programs.

  15. Overview of USDA-SCRI Project: Cucumber applied genomics: tool development and applications for recessive disease resistance genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A cucumber project was recently funded by the USDA NIFA-SCRI program which is titled “Translational genomics in cucumber - tool development and application for recessive disease resistances”. This grant was the result of a joint effort of the UW public cucumber research community with strong support...

  16. The Application of an Anatomical Database for Fetal Congenital Heart Disease

    PubMed Central

    Yang, Li; Pei, Qiu-Yan; Li, Yun-Tao; Yang, Zhen-Juan

    2015-01-01

    Background: Fetal congenital heart anomalies are the most common congenital anomalies in live births. Fetal echocardiography (FECG) is the only prenatal diagnostic approach used to detect fetal congenital heart disease (CHD). FECG is not widely used, and the antenatal diagnosis rate of CHD varies considerably. Thus, mastering the anatomical characteristics of different kinds of CHD is critical for ultrasound physicians to improve FECG technology. The aim of this study is to investigate the applications of a fetal CHD anatomic database in FECG teaching and training program. Methods: We evaluated 60 transverse section databases including 27 types of fetal CHD built in the Prenatal Diagnosis Center in Peking University People's Hospital. Each original database contained 400–700 cross-sectional digital images with a resolution of 3744 pixels × 5616 pixels. We imported the database into Amira 5.3.1 (Australia Visage Imaging Company, Australia) three-dimensional (3D) software. The database functions use a series of 3D software visual operations. The features of the fetal CHD anatomical database were analyzed to determine its applications in FECG continuing education and training. Results: The database was rebuilt using the 3D software. The original and rebuilt databases can be displayed dynamically, continuously, and synchronically and can be rotated at arbitrary angles. The sections from the dynamic displays and rotating angles are consistent with the sections in FECG. The database successfully reproduced the anatomic structures and spatial relationship features of different fetal CHDs. We established a fetal CHD anatomy training database and a standardized training database for FECG. Ultrasound physicians and students can learn the anatomical features of fetal CHD and FECG through either centralized training or distance education. Conclusions: The database of fetal CHD successfully reproduced the anatomic structures and spatial relationship of different kinds of

  17. Topology based Kernels with Application to Inference Problems in Alzheimer’s disease

    PubMed Central

    Pachauri, Deepti; Hinrichs, Chris; Chung, Moo K.; Johnson, Sterling C.; Singh, Vikas

    2011-01-01

    Alzheimer’s disease (AD) research has recently witnessed a great deal of activity focused on developing new statistical learning tools for automated inference using imaging data. The workhorse for many of these techniques is the Support Vector Machine (SVM) framework (or more generally kernel based methods). Most of these require, as a first step, specification of a kernel matrix between input examples (i.e., images). The inner product between images Ii and Ij in a feature space can generally be written in closed form, and so it is convenient to treat as “given”. However, in certain neuroimaging applications such an assumption becomes problematic. As an example, it is rather challenging to provide a scalar measure of similarity between two instances of highly attributed data such as cortical thickness measures on cortical surfaces. Note that cortical thickness is known to be discriminative for neurological disorders, so leveraging such information in an inference framework, especially within a multi-modal method, is potentially advantageous. But despite being clinically meaningful, relatively few works have successfully exploited this measure for classification or regression. Motivated by these applications, our paper presents novel techniques to compute similarity matrices for such topologically-based attributed data. Our ideas leverage recent developments to characterize signals (e.g., cortical thickness) motivated by the persistence of their topological features, leading to a scheme for simple constructions of kernel matrices. As a proof of principle, on a dataset of 356 subjects from the ADNI study, we report good performance on several statistical inference tasks without any feature selection, dimensionality reduction, or parameter tuning. PMID:21536520

  18. Mitral valve surgery - minimally invasive

    MedlinePlus

    ... that does many of these procedures. Minimally invasive heart valve surgery has improved greatly in recent years. These ... WT, Mack MJ. Transcatheter cardiac valve interventions. Surg Clin North Am . 2009;89:951-66. ...

  19. Heart bypass surgery - minimally invasive

    MedlinePlus

    ... in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass ... Thiele H, Neumann-Schniedewind P, Jacobs S, et al. Randomized comparison of minimally invasive direct coronary artery bypass ...

  20. Transactional Database Transformation and Its Application in Prioritizing Human Disease Genes

    PubMed Central

    Xiang, Yang; Payne, Philip R.O.; Huang, Kun

    2013-01-01

    Binary (0,1) matrices, commonly known as transactional databases, can represent many application data, including gene-phenotype data where “1” represents a confirmed gene-phenotype relation and “0” represents an unknown relation. It is natural to ask what information is hidden behind these “0”s and “1”s. Unfortunately, recent matrix completion methods, though very effective in many cases, are less likely to infer something interesting from these (0,1)-matrices. To answer this challenge, we propose IndEvi, a very succinct and effective algorithm to perform independent-evidence-based transactional database transformation. Each entry of a (0,1)-matrix is evaluated by “independent evidence” (maximal supporting patterns) extracted from the whole matrix for this entry. The value of an entry, regardless of its value as 0 or 1, has completely no effect for its independent evidence. The experiment on a gene-phenotype database shows that our method is highly promising in ranking candidate genes and predicting unknown disease genes. PMID:21422495