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Sample records for detect potential adverse

  1. The Potential Return on Public Investment in Detecting Adverse Drug Effects.

    PubMed

    Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

    2017-06-01

    Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

  2. Erythropoietin as a performance-enhancing drug: Its mechanistic basis, detection, and potential adverse effects.

    PubMed

    Salamin, Olivier; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas

    2017-01-22

    Erythropoietin (EPO) is the main hormone regulating red blood cell (RBC) production. The large-scale production of a recombinant human erythropoietin (rHuEPO) by biotechnological methods has made possible its widespread therapeutic use as well as its misuse in sports. Since the marketing of the first epoetin in 1989, the development has progressed to the third-generation analogs. However, the production of rHuEPO is costly, and the frequent administration of an injectable formula is not optimal for compliance of therapeutic patients. Hence, pharmaceutical industries are currently developing alternative approaches to stimulate erythropoiesis, which might offer new candidates for doping purposes. The hypoxia inducible factors (HIF) pathway is of particular interest. The introduction of new erythropoiesis-stimulating agents (ESAs) for clinical use requires subsequent development of anti-doping methods for detecting the abuse of these substances. The detection of ESAs is based on two different approaches, namely, the direct detection of exogenous substances and the indirect detection, for which the effects of the substances on specific biomarkers are monitored. Omics technologies, such as ironomics or transcriptomics, are useful for the development of new promising biomarkers for the detection of ESAs. Finally, the illicit use of ESAs associates with multiple health risks that can be irreversible, and an essential facet of anti-doping work is to educate athletes of these risks. The aim of this review is to provide an overview of the evolution of ESAs, the research and implementation of the available detection methods, and the side effects associated with the misuse of ESAs. Copyright © 2017. Published by Elsevier B.V.

  3. Sequence Symmetry Analysis as a Signal Detection Tool for Potential Heart Failure Adverse Events in an Administrative Claims Database.

    PubMed

    Wahab, Izyan A; Pratt, Nicole L; Ellett, Lisa Kalisch; Roughead, Elizabeth E

    2016-04-01

    The potential for routine sequence symmetry analysis (SSA) signal detection in health claims databases to detect new safety signals of medicines is unknown. Our objective was to assess the potential utility of SSA as a signal detection tool in health claims data for detecting medicines with potential heart failure (HF) adverse event signals. We applied the SSA method to all subsidized single-ingredient medicines in Australia. The source of data was the Australian Government Department of Veterans' Affairs (DVA) administrative claims database using data collected between 2002 and 2011. We used first ever HF hospitalization and frusemide initiation as indicators for HF. A signal was considered to be present if the lower limit of the 95 % confidence interval for the adjusted sequence ratio was greater than one. To identify potential new signals of HF, we excluded medicines where HF or edema was listed in the product information (PI) of that medicine or for any other medicine in the same class. We also excluded medicines that were used in HF treatment and medicines indicated for diseases that may contribute to the development of HF. We tested 691 medicines. HF signals were detected for 12 % (80/691) using the hospitalization event and 22 % (153/691) using frusemide initiation. Among medicines that did not have HF listed in the PI, SSA found 11 % (44/397) associated with HF hospitalization and 15 % (60/397) associated with frusemide initiation. Of the medicines tested in which no other medicine in the same class had HF or edema in the PI, and where the medicine was not indicated for a disease that is a risk factor for HF, potential new signals were generated for 2-3 % of these medicines tested (12 of 397 medicines using HF hospitalization and 9 of 397 medicines using frusemide initiation). SSA generated potential new signals of HF for some anti-glaucoma and anti-dyspepsia medicines. For some of the potential signals, the event is biologically plausible and some have pre

  4. Potential utility of data-mining algorithms for early detection of potentially fatal/disabling adverse drug reactions: a retrospective evaluation.

    PubMed

    Hauben, Manfred; Reich, Lester

    2005-04-01

    The objective of this study was to apply 2 data-mining algorithms to a drug safety database to determine if these methods would have flagged potentially fatal/disabling adverse drug reactions that triggered black box warnings/drug withdrawals in advance of initial identification via "traditional" methods. Relevant drug-event combinations were identified from a journal publication. Data-mining algorithms using commonly cited disproportionality thresholds were then applied to the US Food and Drug Administration database. Seventy drug-event combinations were considered sufficiently specific for retrospective data mining. In a minority of instances, potential signals of disproportionate reporting were provided clearly in advance of initial identification via traditional pharmacovigilance methods. Data-mining algorithms have the potential to improve pharmacovigilance screening; however, for the majority of drug-event combinations, there was no substantial benefit of either over traditional methods. They should be considered as potential supplements to, and not substitutes for, traditional pharmacovigilance strategies. More research and experience will be needed to optimize deployment of data-mining algorithms in pharmacovigilance.

  5. Potential adverse effects of phytoestrogens.

    PubMed

    Whitten, P L; Lewis, C; Russell, E; Naftolin, F

    1995-03-01

    Evaluation of the potential benefits and risks offered by naturally occurring plant estrogens requires investigation of their potency and sites of action when consumed at natural dietary concentrations. Our investigations have examined the effects of a range of natural dietary concentrations of the most potent plant isoflavonoid, coumestrol, using a rat model and a variety of estrogen-dependent tissues and endpoints. Treatments of immature females demonstrated agonistic action in the reproductive tract, brain, and pituitary at natural dietary concentrations. Experiments designed to test for estrogen antagonism demonstrated that coumestrol did not conform to the picture of a classic antiestrogen. However, coumestrol did suppress estrous cycles in adult females. Developmental actions were examined by neonatal exposure of pups through milk of rat dams fed a coumestrol, control, or commercial soy-based diet during the critical period of the first 10 postnatal days or throughout the 21 days of lactation. The 10-day treatment did not significantly alter adult estrous cyclicity, but the 21-day treatment produced in a persistent estrus state in coumestrol-treated females by 132 days of age. In contrast, the 10-day coumestrol treatments produced significant deficits in the sexual behavior of male offspring. These findings illustrate the broad range of actions of these natural estrogens and the variability in potency across endpoints. This variability argues for the importance of fully characterizing each phytoestrogen in terms of its sites of action, balance of agonistic and antagonistic properties, natural potency, and short-term and long-term effects.

  6. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  7. Environmental perchlorate exposure: potential adverse thyroid effects.

    PubMed

    Leung, Angela M; Pearce, Elizabeth N; Braverman, Lewis E

    2014-10-01

    This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant intelligence quotient in groups who would be particularly susceptible to perchlorate effects. An update regarding the recently proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants.

  8. Lack of essential information in spontaneous reports of adverse drug reactions in Catalonia-a restraint to the potentiality for signal detection.

    PubMed

    Plessis, Lorraine; Gómez, Ainhoa; García, Núria; Cereza, Gloria; Figueras, Albert

    2017-06-01

    The aim of this study is to analyze the quality of the information contained in the adverse drug reactions (ADR) reports and to describe the magnitude and characteristics of the lacking information. All reports of serious ADR received by the Catalan Center of Pharmacovigilance in 2014 were analyzed using the VigiGrade and a more clinical and qualitative approach. Up to 824 reports describing serious ADR were included in the study; of them, 503 (61.0%) were sent by health care professionals (HPs) and the remaining 321 (39.0%) came from pharmaceutical companies (PhC). More than 80% of missing variables such as 'onset date' or 'time-to-onset' of the ADR were from PhCs reports. 'Onset of treatment date' was not filled in 28 (22.2%) of the reports including an 'additional monitoring' medicine, and 'end of treatment' date was not completed in 53 of those reports (42.1%). In summary, 39% of the reports involving a black triangle medicine sent by PhCs lacked some essential information such as the onset date of treatment. More than one third of the reports coming from manufacturers did not include information that is considered a limiting factor to evaluate any causal relationship, and can be an issue for the detection of safety signals. To take advantage of this huge amount of potentially important information that is almost useless at present, data mining tools and new algorithms should be developed and tested with the aim of finding formulas to deal with a huge amount of low quality data without losing it, nor generating a number of false associations.

  9. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  10. Diagnosis of potential stressors adversely affecting benthic ...

    EPA Pesticide Factsheets

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

  11. Prescription rate of medications potentially contributing to lower urinary tract symptoms and detection of adverse reactions by prescription sequence symmetry analysis.

    PubMed

    Hashimoto, Masako; Hashimoto, Kanako; Ando, Fumihiko; Kimura, Yoshiaki; Nagase, Keisuke; Arai, Kunizo

    2015-01-01

    The lower urinary tract symptoms (LUTS) increases with age and can have a significant effect on the quality of life of the patients. Elderly patients, who are often characterized by a decline in physiological functional and polypharmacy, are susceptible to adverse drug reactions to pharmacotherapy. LUTS can also be a side effect of medication. The purpose of this study was to investigate the possible association between the initiation of LUTS-causing drug therapy and the onset of LUTS. Drug dispensing data at the individual level were retrieved from the CISA (Platform for Clinical Information Statistical Analysis: http://www.cisa.jp) database. A retrospective study was conducted by reviewing patients with LUTS who were dispensed drugs that increased the risk of LUTS between April 2011 and March 2012. Prescription sequence symmetry analysis (PSSA) was employed to investigate the associations between the dispensing of medicines of LUTS and that of LUTS-causing drugs. LUTS-causing drugs were frequently dispensed to patients with LUTS. The use of medications potentially contributing to LUTS was associated with polypharmacy [number of prescription drugs:12.13 ± 6.78 (user) vs. 5.67 ± 5.24 (nonuser)] but not patient age [ age: (71.38 ± 13.28 (user) vs. 70.45 ± 14.80 (nonuser)]. Significant adverse drug events were observed the use of donepezil, cyclophosphamide, antiparkinson drugs, antidepressant, diazepam, antipsychotic drugs for peptic ulcer, tiotropium bromide, and opioids. The use of prescription LUTS-causing drugs was correlated with polypharmacy. The adverse drug events associated with LUTS-causing drugs were highly prevalent in elderly patients. To prevent of adverse drug events in patients with LUTS, pharmacists and physicians should regularly review medication lists and reduce the prescribed medicines.

  12. Data mining for signal detection of adverse event safety data.

    PubMed

    Chen, Hung-Chia; Tsong, Yi; Chen, James J

    2013-01-01

    The Adverse Event Reporting System (AERS) is the primary database designed to support the Food and Drug Administration (FDA) postmarketing safety surveillance program for all approved drugs and therapeutic biologic products. Most current disproportionality analysis focuses on the detection of potential adverse events (AE) involving a single drug and a single AE only. In this paper, we present a data mining biclustering technique based on the singular value decomposition to extract local regions of association for a safety study. The analysis consists of collection of biclusters, each representing an association between a set of drugs with the corresponding set of adverse events. Significance of each bicluster can be tested using disproportionality analysis. Individual drug-event combination can be further tested. A safety data set consisting of 193 drugs with 8453 adverse events is analyzed as an illustration.

  13. Automated adverse event detection collaborative: electronic adverse event identification, classification, and corrective actions across academic pediatric institutions.

    PubMed

    Stockwell, David C; Kirkendall, Eric; Muething, Stephen E; Kloppenborg, Elizabeth; Vinodrao, Hima; Jacobs, Brian R

    2013-12-01

    Historically, the gold standard for detecting medical errors has been the voluntary incident reporting system. Voluntary reporting rates significantly underestimate the number of actual adverse events in any given organization. The electronic health record (EHR) contains clinical and administrative data that may indicate the occurrence of an adverse event and can be used to detect adverse events that may otherwise remain unrecognized. Automated adverse event detection has been shown to be efficient and cost effective in the hospital setting. The Automated Adverse Event Detection Collaborative (AAEDC) is a group of academic pediatric organizations working to identify optimal electronic methods of adverse event detection. The Collaborative seeks to aggregate and analyze data around adverse events as well as identify and share specific intervention strategies to reduce the rate of such events, ultimately to deliver higher quality and safer care. The objective of this study is to describe the process of automated adverse event detection, report early results from the Collaborative, identify commonalities and notable differences between 2 organizations, and suggest future directions for the Collaborative. In this retrospective observational study, the implementation and use of an automated adverse event detection system was compared between 2 academic children's hospital participants in the AAEDC, Children's National Medical Center, and Cincinnati Children's Hospital Medical Center. Both organizations use the EHR to identify potential adverse events as designated by specific electronic data triggers. After gathering the electronic data, a clinical investigator at each hospital manually examined the patient record to determine whether an adverse event had occurred, whether the event was preventable, and the level of harm involved. The Automated Adverse Event Detection Collaborative data from the 2 organizations between July 2006 and October 2010 were analyzed. Adverse

  14. Potential adverse health effects of wood smoke

    SciTech Connect

    Pierson, W.E.; Koenig, J.Q.; Bardana, E.J. Jr.

    1989-09-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo(a)pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal.29 references.

  15. Data mining for potential adverse drug-drug interactions.

    PubMed

    Hammann, Felix; Drewe, Juergen

    2014-05-01

    Patients, in particular elderly ones, frequently receive more than one drug at a time. With each drug added to a regime, the number of potential drug-drug interactions (DDIs) increases by a power law. Early prediction of relevant interactions by computerized tools greatly aids clinicians and can guide their prescribing choices. In this article, we discuss different types of DDIs, on which levels they can arise and what efforts have been made in the past to detect and predict them. The emphasis is on data mining technology and network analysis, but overlaps with traditional pharmacovigilance are also discussed. Finally, we discuss strategies to focus and simplify mining efforts to get meaningful results with less effort. The necessary technology for detecting adverse DDIs exists and is quite refined, although it is more often implied in lower risk scenarios (such as syntactic analysis in web searches and online libraries). Data mining for DDIs, on the other hand, still requires a great deal of human intervention, not only to validate the results but also, more importantly, to separate the relevant from the spurious. The fields of network analysis and graph theory show great promise but have not yet shown much beyond descriptive analyses.

  16. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  17. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

    Soukavong, Mick; Kim, Jungmee; Park, Kyounghoon; Yang, Bo Ram; Lee, Joongyub; Jin, Xue Mei; Park, Byung Joo

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability.

  18. Adverse drug events and medication errors: detection and classification methods.

    PubMed

    Morimoto, T; Gandhi, T K; Seger, A C; Hsieh, T C; Bates, D W

    2004-08-01

    Investigating the incidence, type, and preventability of adverse drug events (ADEs) and medication errors is crucial to improving the quality of health care delivery. ADEs, potential ADEs, and medication errors can be collected by extraction from practice data, solicitation of incidents from health professionals, and patient surveys. Practice data include charts, laboratory, prescription data, and administrative databases, and can be reviewed manually or screened by computer systems to identify signals. Research nurses, pharmacists, or research assistants review these signals, and those that are likely to represent an ADE or medication error are presented to reviewers who independently categorize them into ADEs, potential ADEs, medication errors, or exclusions. These incidents are also classified according to preventability, ameliorability, disability, severity, stage, and responsible person. These classifications, as well as the initial selection of incidents, have been evaluated for agreement between reviewers and the level of agreement found ranged from satisfactory to excellent (kappa = 0.32-0.98). The method of ADE and medication error detection and classification described is feasible and has good reliability. It can be used in various clinical settings to measure and improve medication safety.

  19. 30-Day Potentially Avoidable Readmissions Due to Adverse Drug Events.

    PubMed

    Dalleur, Olivia; Beeler, Patrick E; Schnipper, Jeffrey L; Donzé, Jacques

    2017-03-17

    To analyze the patterns of potentially avoidable readmissions due to adverse drug events (ADEs) to identify the most appropriate risk reduction interventions. In this observational study, we analyzed a random sample of 534 potentially avoidable 30-day readmissions from 10,275 consecutive discharges from the medical department of an academic hospital. Readmissions due to ADEs were reviewed to identify the causative drugs and the severity and interventions to prevent them. Seventy cases (13.1%) of readmission were partially or predominantly due to ADEs, of which, 58 (82.9%) were serious ADEs. Overall, 65 (92.9%) of the ADEs have been confirmed to be preventable. Inappropriate prescribing was identified as the cause of ADE in 34 cases (48.6%) mainly involving diuretics, analgesics, or antithrombotics: misprescribing n = 19 (27.1%), underprescribing n = 8 (11.4%), and overprescribing n = 7 (10.0%). The remaining half of preventable ADEs (n = 36; 51.4%) were related to suboptimal patient monitoring/education, such as adherence issues (n = 6; 8.6%) or lack of monitoring (n = 31; 44.3%). In 64 cases (91.4%), the readmission could have been potentially prevented by better monitoring for drug efficacy/disease control, or for predictable side effect. Thirty-three (97.1%) of the 34 ADEs due to inappropriate prescribing could have also been prevented by better monitoring. Adverse drug events accounted for approximately 13% of 30-day preventable readmissions. A half were due to prescription errors involving mainly diuretics, analgesics, or antithrombotics, and the other half were due to suboptimal patient monitoring/education, most frequently with antineoplastics. Both these avoidable causes may represent opportunities to reduce the total drug-related adverse events.

  20. The potential adverse health effects of dental amalgam.

    PubMed

    Brownawell, Amy M; Berent, Stanley; Brent, Robert L; Bruckner, James V; Doull, John; Gershwin, Eric M; Hood, Ronald D; Matanoski, Genevieve M; Rubin, Raphael; Weiss, Bernard; Karol, Meryl H

    2005-01-01

    There is significant public concern about the potential health effects of exposure to mercury vapour (Hg(0)) released from dental amalgam restorations. The purpose of this article is to provide information about the toxicokinetics of Hg(0), evaluate the findings from the recent scientific and medical literature, and identify research gaps that when filled may definitively support or refute the hypothesis that dental amalgam causes adverse health effects. Dental amalgam is a widely used restorative dental material that was introduced over 150 years ago. Most standard dental amalgam formulations contain approximately 50% elemental mercury. Experimental evidence consistently demonstrates that Hg(0) is released from dental amalgam restorations and is absorbed by the human body. Numerous studies report positive correlations between the number of dental amalgam restorations or surfaces and urine mercury concentrations in non-occupationally exposed individuals. Although of public concern, it is currently unclear what adverse health effects are caused by the levels of Hg(0) released from this restoration material. Historically, studies of occupationally exposed individuals have provided consistent information about the relationship between exposure to Hg(0) and adverse effects reflecting both nervous system and renal dysfunction. Workers are usually exposed to substantially higher Hg(0) levels than individuals with dental amalgam restorations and are typically exposed 8 hours per day for 20-30 years, whereas persons with dental amalgam restorations are exposed 24 hours per day over some portion of a lifetime. This review has uncovered no convincing evidence pointing to any adverse health effects that are attributable to dental amalgam restorations besides hypersensitivity in some individuals.

  1. Herbal medication: potential for adverse interactions with analgesic drugs.

    PubMed

    Abebe, W

    2002-12-01

    The use of herbal supplements in the US has increased dramatically in recent years. These products are not regulated by the Food and Drug Administration (FDA) with the same scrutiny as conventional drugs. Patients who use herbal supplements often do so in conjunction with conventional drugs. This article is a review of potential adverse interactions between some of the commonly used herbal supplements and analgesic drugs. Non-steroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, have the potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (chamomile, motherworth, horse chestnut, fenugreek and red clover) and with tamarind, enhancing the risk of bleeding. Acetaminophen may also interact with ginkgo and possibly with at least some of the above herbs to increase the risk of bleeding. Further, the incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophen when concomitantly used with the potentially hepatotoxic herbs Echinacea and kava, and with herbs containing salicylate (willow, meadowsweet), respectively. The concomitant use of opioid analgesics with the sedative herbal supplements, valerian, kava and chamomile, may lead to increased central nervous system (CNS) depression. The analgesic effect of opioids may also be inhibited by ginseng. It is suggested that health-care professionals should be more aware of the potential adverse interactions between herbal supplements and analgesic drugs, and take appropriate precautionary measures to avoid their possible occurrences. However, as most of the interaction information available is based on individual case reports, animal studies and in vitro data, further research is needed to confirm and assess the clinical significance of these potential interactions.

  2. Toward automatic detection and prevention of adverse drug events.

    PubMed

    Leroy, Nicolas; Chazard, Emmanuel; Beuscart, Régis; Beuscart-Zephir, Marie Catherine

    2009-01-01

    Adverse Drug Events (ADE) due to medication errors and human factors are a major public health issue. They endanger patient safety and cause considerable extra healthcare costs. The European project PSIP (Patient Safety through Intelligent Procedures in medication) aims to identify and prevent ADE. Data mining of the structured hospital data bases will give a list of observed ADE with frequencies and probabilities, thereby giving a better understanding of potential risks. The main objective of the project is to develop innovative knowledge based on the mining results and to deliver to professionals and patients, in the form of alerts and decision support functions, a contextualized knowledge fitting the local risk parameters.

  3. Data mining to generate adverse drug events detection rules.

    PubMed

    Chazard, Emmanuel; Ficheur, Grégoire; Bernonville, Stéphanie; Luyckx, Michel; Beuscart, Régis

    2011-11-01

    Adverse drug events (ADEs) are a public health issue. Their detection usually relies on voluntary reporting or medical chart reviews. The objective of this paper is to automatically detect cases of ADEs by data mining. 115,447 complete past hospital stays are extracted from six French, Danish, and Bulgarian hospitals using a common data model including diagnoses, drug administrations, laboratory results, and free-text records. Different kinds of outcomes are traced, and supervised rule induction methods (decision trees and association rules) are used to discover ADE detection rules, with respect to time constraints. The rules are then filtered, validated, and reorganized by a committee of experts. The rules are described in a rule repository, and several statistics are automatically computed in every medical department, such as the confidence, relative risk, and median delay of outcome appearance. 236 validated ADE-detection rules are discovered; they enable to detect 27 different kinds of outcomes. The rules use a various number of conditions related to laboratory results, diseases, drug administration, and demographics. Some rules involve innovative conditions, such as drug discontinuations.

  4. Post-market surveillance to detect adverse events associated with Melody® valve implantation.

    PubMed

    Hill, Kevin D; Goldstein, Bryan H; Angtuaco, Michael J; Chu, Patricia Y; Fleming, Gregory A

    2017-08-01

    The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation. In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events. We reviewed the United States Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials. We identified 631 adverse events associated with "on-label" Melody® valve implants and 84 adverse events associated with "off-label" implants. The most frequent "on-label" adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5). Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with "on-label" Melody® valve implantation. Further study is needed to evaluate safety of "off-label" uses.

  5. Understanding pharmacist decision making for adverse drug event (ADE) detection.

    PubMed

    Phansalkar, Shobha; Hoffman, Jennifer M; Hurdle, John F; Patel, Vimla L

    2009-04-01

    Manual chart review is an effective but expensive method for adverse drug event (ADE) detection. Building an expert system capable of mimicking the human expert's decision pathway, to deduce the occurrence of an ADE, can improve efficiency and lower cost. As a first step to build such an expert system, this study explores pharmacist's decision-making processes for ADE detection. Think-aloud procedures were used to elicit verbalizations as pharmacists read through ADE case scenarios. Two types of information were extracted, firstly pharmacists' decision-making strategies regarding ADEs and secondly information regarding pharmacists' unmet information needs for ADE detection. Verbal protocols were recorded and analysed qualitatively to extract ADE information signals. Inter-reviewer agreement for classification of ADE information signals was calculated using Cohen's kappa. We extracted a total of 110 information signals, of which 73% consisted of information that was interpreted by the pharmacists from the case scenario and only about half (53%, n = 32) of the information signals were considered relevant for the detection of the ADEs. Excellent reliability was demonstrated between the reviewers for classifying signals. Fifty information signals regarding unmet information needs were extracted and grouped into themes based on the type of missing information. Pharmacists used a forward reasoning approach to make implicit deductions and validate hypotheses about possible ADEs. Verbal protocols also indicated that pharmacists' unmet information needs occurred frequently. Developing alerting systems that meet pharmacists' needs adequately will enhance their ability to reduce preventable ADEs, thus improving patient safety.

  6. Detecting Adverse Drug Events in Discharge Summaries Using Variations on the Simple Bayes Model

    PubMed Central

    Visweswaran, Shyam; Hanbury, Paul; Saul, Melissa; Cooper, Gregory F.

    2003-01-01

    Detection and prevention of adverse events and, in particular, adverse drug events (ADEs), is an important problem in health care today. We describe the implementation and evaluation of four variations on the simple Bayes model for identifying ADE-related discharge summaries. Our results show that these probabilistic techniques achieve an ROC curve area of up to 0.77 in correctly determining which patient cases should be assigned an ADE-related ICD-9-CM code. These results suggest a potential for these techniques to contribute to the development of an automated system that helps identify ADEs, as a step toward further understanding and preventing them. PMID:14728261

  7. Detecting adverse drug events in discharge summaries using variations on the simple Bayes model.

    PubMed

    Visweswaran, Shyam; Hanbury, Paul; Saul, Melissa; Cooper, Gregory F

    2003-01-01

    Detection and prevention of adverse events and, in particular, adverse drug events (ADEs), is an important problem in health care today. We describe the implementation and evaluation of four variations on the simple Bayes model for identifying ADE-related discharge summaries. Our results show that these probabilistic techniques achieve an ROC curve area of up to 0.77 in correctly determining which patient cases should be assigned an ADE-related ICD-9-CM code. These results suggest a potential for these techniques to contribute to the development of an automated system that helps identify ADEs, as a step toward further understanding and preventing them.

  8. Mining unexpected temporal associations: applications in detecting adverse drug reactions.

    PubMed

    Jin, Huidong Warren; Chen, Jie; He, Hongxing; Williams, Graham J; Kelman, Chris; O'Keefe, Christine M

    2008-07-01

    In various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. The MUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.

  9. Adverse reactions to oncologic drugs: spontaneous reporting and signal detection.

    PubMed

    Tuccori, Marco; Montagnani, Sabrina; Capogrosso-Sansone, Alice; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado

    2015-01-01

    Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting.

  10. Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

    PubMed

    Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

    2009-08-01

    Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

  11. Adverse drug reactions in older people: detection and prevention.

    PubMed

    Petrovic, Mirko; van der Cammen, Tischa; Onder, Graziano

    2012-06-01

    Adverse drug reactions (ADRs) in older adults are an important healthcare problem since they are frequently a cause of hospitalization, occur commonly during admission, and are an important cause of morbidity and mortality. Older adults are particularly susceptible to ADRs because they are usually on multiple drug regimens and because age is associated with changes in pharmacokinetics and pharmacodynamics. The presentation of an ADR in older adults is often atypical, which further complicates its recognition. One potential strategy for improving recognition of ADRs is to identify those patients who are at risk of an ADR. The recently developed GerontoNet ADR Risk Score is a practical tool for identification of older patients who are at increased risk for an ADR and who may represent a target for interventions aimed at reducing ADRs. Provision of adequate education in the domain of clinical geriatric pharmacology can improve recognition of ADRs. Besides formal surveillance systems, built-in computer programs with electronic prescribing databases and clinical pharmacist involvement in patient care within multidisciplinary geriatric teams might help to minimize the occurrence of ADRs. In addition, a number of actions can be taken in hospitals to stimulate appropriate prescribing and to assure adequate communication between primary and hospital care. In older adults with complex medical problems and needs, a global evaluation obtained through a comprehensive geriatric assessment may be helpful in simplifying drug prescription and prioritizing pharmacological and healthcare needs, resulting in an improvement in quality of prescribing.

  12. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear.

  13. Polybrominated diphenyl ether (PBDE) flame retardants: environmental contamination, human body burden and potential adverse health effects.

    PubMed

    Costa, Lucio G; Giordano, Gennaro; Tagliaferri, Sara; Caglieri, Andrea; Mutti, Antonio

    2008-12-01

    Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants, widely used in a variety of consumer products. In the past several years, PBDEs have become widespread environmental pollutants, and have been detected in water, soil, air, animals and human tissues. Exposure occurs in particular through the diet and the indoor environment. Infants and toddlers have the highest body burden, due to exposure via maternal milk and through house dust. Tetra-, penta- and hexa-BDEs are the congeners most commonly found in humans. Recent concerns on possible adverse health effects of PBDEs are focusing on their potential endocrine disrupting effects and on developmental neurotoxicity.

  14. Combing signals from spontaneous reports and electronic health records for detection of adverse drug reactions

    PubMed Central

    Harpaz, Rave; Vilar, Santiago; DuMouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol

    2013-01-01

    Objective Data-mining algorithms that can produce accurate signals of potentially novel adverse drug reactions (ADRs) are a central component of pharmacovigilance. We propose a signal-detection strategy that combines the adverse event reporting system (AERS) of the Food and Drug Administration and electronic health records (EHRs) by requiring signaling in both sources. We claim that this approach leads to improved accuracy of signal detection when the goal is to produce a highly selective ranked set of candidate ADRs. Materials and methods Our investigation was based on over 4 million AERS reports and information extracted from 1.2 million EHR narratives. Well-established methodologies were used to generate signals from each source. The study focused on ADRs related to three high-profile serious adverse reactions. A reference standard of over 600 established and plausible ADRs was created and used to evaluate the proposed approach against a comparator. Results The combined signaling system achieved a statistically significant large improvement over AERS (baseline) in the precision of top ranked signals. The average improvement ranged from 31% to almost threefold for different evaluation categories. Using this system, we identified a new association between the agent, rasburicase, and the adverse event, acute pancreatitis, which was supported by clinical review. Conclusions The results provide promising initial evidence that combining AERS with EHRs via the framework of replicated signaling can improve the accuracy of signal detection for certain operating scenarios. The use of additional EHR data is required to further evaluate the capacity and limits of this system and to extend the generalizability of these results. PMID:23118093

  15. Combing signals from spontaneous reports and electronic health records for detection of adverse drug reactions.

    PubMed

    Harpaz, Rave; Vilar, Santiago; Dumouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol

    2013-05-01

    Data-mining algorithms that can produce accurate signals of potentially novel adverse drug reactions (ADRs) are a central component of pharmacovigilance. We propose a signal-detection strategy that combines the adverse event reporting system (AERS) of the Food and Drug Administration and electronic health records (EHRs) by requiring signaling in both sources. We claim that this approach leads to improved accuracy of signal detection when the goal is to produce a highly selective ranked set of candidate ADRs. Our investigation was based on over 4 million AERS reports and information extracted from 1.2 million EHR narratives. Well-established methodologies were used to generate signals from each source. The study focused on ADRs related to three high-profile serious adverse reactions. A reference standard of over 600 established and plausible ADRs was created and used to evaluate the proposed approach against a comparator. The combined signaling system achieved a statistically significant large improvement over AERS (baseline) in the precision of top ranked signals. The average improvement ranged from 31% to almost threefold for different evaluation categories. Using this system, we identified a new association between the agent, rasburicase, and the adverse event, acute pancreatitis, which was supported by clinical review. The results provide promising initial evidence that combining AERS with EHRs via the framework of replicated signaling can improve the accuracy of signal detection for certain operating scenarios. The use of additional EHR data is required to further evaluate the capacity and limits of this system and to extend the generalizability of these results.

  16. Bayesian model selection in logistic regression for the detection of adverse drug reactions.

    PubMed

    Marbac, Matthieu; Tubert-Bitter, Pascale; Sedki, Mohammed

    2016-11-01

    Spontaneous adverse event reports have a high potential for detecting adverse drug reactions. However, due to their dimension, the analysis of such databases requires statistical methods. In this context, disproportionality measures can be used. Their main idea is to project the data onto contingency tables in order to measure the strength of associations between drugs and adverse events. However, due to the data projection, these methods are sensitive to the problem of coprescriptions and masking effects. Recently, logistic regressions have been used with a Lasso type penalty to perform the detection of associations between drugs and adverse events. On different examples, this approach limits the drawbacks of the disproportionality methods, but the choice of the penalty value is open to criticism while it strongly influences the results. In this paper, we propose to use a logistic regression whose sparsity is viewed as a model selection challenge. Since the model space is huge, a Metropolis-Hastings algorithm carries out the model selection by maximizing the BIC criterion. Thus, we avoid the calibration of penalty or threshold. During our application on the French pharmacovigilance database, the proposed method is compared to well-established approaches on a reference dataset, and obtains better rates of positive and negative controls. However, many signals (i.e., specific drug-event associations) are not detected by the proposed method. So, we conclude that this method should be used in parallel to existing measures in pharmacovigilance. Code implementing the proposed method is available at the following url: https://github.com/masedki/MHTrajectoryR.

  17. Evaluation of the Effects of Pharmacist Intervention for Adverse Drug Reaction Detection and Exacerbation Avoidance.

    PubMed

    Imaura, Masaharu; Yamaya, Takeshi; Uehara, Nozomi; Mano, Narutoshi; Nagase, Satoshi; Kimura, Koji; Kanno, Hiroshi; Yamada, Yasuhiko

    2017-01-01

     We evaluated the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, as well as the severity and outcome of reactions based on analyses of pharmacist involvement in a collaborative approach to medicine. Of 5436 cases with pharmacist involvement, adverse drug reaction prevention was seen in 440, accounting for 8.1%, and exacerbation avoidance in 213, accounting for 3.9%. We concluded that pharmacist involvement contributes to detect adverse drug reactions and avoid exacerbation, and improves pharmacotherapy safety. We also analyzed 131 cases in which the course after intervention was followed. When categorized by adverse drug reaction severity, Grade 1 and 2 were the same at 45.8%, Grade 3 at 8.4%, respectively. Those findings suggested that pharmacist intervention contributes to early detection of an adverse drug reaction. Also, the relationship between clues for detecting adverse drug reactions by a pharmacist and their severity showed that objective evaluations such as clinical laboratory test results, physical assessments and medication history were important for detecting reactions that became more serious. Patients recovered or recovering from an adverse reaction comprised 76.4%, indicating that pharmacist intervention contributed to exacerbation avoidance and improvement. Our findings revealed the effects of pharmacist intervention for adverse drug reaction detection and exacerbation avoidance, and for safety improvement of pharmacotherapy. Additionally, we considered it necessary for the future pharmacist intervention to improve skills of assessing an adverse drug reaction objectively.

  18. Using trigger phrases to detect adverse drug reactions in ambulatory care notes

    PubMed Central

    Cantor, Michael N; Feldman, Henry J; Triola, Marc M

    2007-01-01

    Background As medical care moves towards an outpatient focus, monitoring systems for ambulatory patients are increasingly important. Because adverse outcomes due to medications are an important problem in outpatients, the authors developed an automated monitoring system for detecting adverse drug reactions (ADRs) in ambulatory patients. Methods The authors obtained a set of approximately 110 000 ambulatory care notes from the medicine clinic at Bellevue Hospital Centre for 2003–4, and manually analysed a representative sample of 1250 notes to obtain a gold standard. To detect ADRs in the text of electronic ambulatory notes, the authors used a “trigger phrases” methodology, based on a simple grammar populated with a limited set of keywords. Results Under current functionality, this system detected 38 of 54 cases in the authors' gold standard set, of which 17 were true positives, for a sensitivity of 31%, a specificity of 98%, and a positive predictive value of 45%. Their proxy measure correlated with 70% of the ADRs in the gold standard. These values are comparable or superior to other systems described in the literature. Conclusions These results show that an automated system can detect ADRs with moderate sensitivity and high specificity, and has the potential to serve as the basis for a larger scale reporting system. PMID:17403760

  19. Data-mining-based detection of adverse drug events.

    PubMed

    Chazard, Emmanuel; Preda, Cristian; Merlin, Béatrice; Ficheur, Grégoire; Beuscart, Régis

    2009-01-01

    Every year adverse drug events (ADEs) are known to be responsible for 98,000 deaths in the USA. Classical methods rely on report statements, expert knowledge, and staff operated record review. One of our objectives, in the PSIP project framework, is to use data mining (e.g., decision trees) to electronically identify situations leading to risk of ADEs. 10,500 hospitalization records from Denmark and France were used. 500 rules were automatically obtained, which are currently being validated by experts. A decision support system to prevent ADEs is then to be developed. The article examines a decision tree and the rules in the field of vitamin K antagonists.

  20. Detecting adverse events for patient safety research: a review of current methodologies.

    PubMed

    Murff, Harvey J; Patel, Vimla L; Hripcsak, George; Bates, David W

    2003-01-01

    Promoting patient safety is a national priority. To evaluate interventions for reducing medical errors and adverse event, effective methods for detecting such events are required. This paper reviews the current methodologies for detection of adverse events and discusses their relative advantages and limitations. It also presents a cognitive framework for error monitoring and detection. While manual chart review has been considered the "gold-standard" for identifying adverse events in many patient safety studies, this methodology is expensive and imperfect. Investigators have developed or are currently evaluating, several electronic methods that can detect adverse events using coded data, free-text clinical narratives, or a combination of techniques. Advances in these systems will greatly facilitate our ability to monitor adverse events and promote patient safety research. But these systems will perform optimally only if we improve our understanding of the fundamental nature of errors and the ways in which the human mind can naturally, but erroneously, contribute to the problems that we observe.

  1. Lidar monitoring of infrared target detection ranges through adverse weather

    NASA Astrophysics Data System (ADS)

    Bissonnette, Luc R.; Roy, Gilles; Theriault, Jean-Marc

    1998-11-01

    Despite recent technical advances, adverse weather still constitutes an important decision factor in the efficient use of IR sensors. The presence of fog, clouds or precipitation affects both the IR transmission and background properties of the atmosphere. Taking these effects into account requires the knowledge of the optical parameters of fog, clouds or precipitation which, in general, fluctuate too much on a scale of a few kilometers to be predictable with acceptable accuracy. Therefore, systems performance calculations based on modeling alone cannot provide all the necessary information for real time, on-site decision making. A promising alternative is continuous monitoring of atmospheric aerosol properties with a lidar. The method use in this study is the multiple-field- of-view technique which takes advantage of the information contained in the multiple scattering contributions to solve for both the droplet concentration and effective diameter. We can then use these solutions to derive the atmospheric radiance and transmittance, and calculate from there the contrast-to-noise ratio of IR images of small targets. Using actual lidar probings, examples of performance curves of a generic surveillance sensor are obtained for two types of targets. Results show that performance can drastically change over an interval as short as one minute, which emphasizes the need for real time, on site monitoring in adverse weather.

  2. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  3. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  4. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  5. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who... potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for...

  6. Potential adverse health effects of genetically modified crops.

    PubMed

    Bakshi, Anita

    2003-01-01

    Genetically modified crops have the potential to eliminate hunger and starvation in millions of people, especially in developing countries because the genetic modification can produce large amounts of foods that are more nutritious. Large quantities are produced because genetically modified crops are more resistant to pests and drought. They also contain greater amounts of nutrients, such as proteins and vitamins. However, there are concerns about the safety of genetically modified crops. The concerns are that they may contain allergenic substances due to introduction of new genes into crops. Another concern is that genetic engineering often involves the use of antibiotic-resistance genes as "selectable markers" and this could lead to production of antibiotic-resistant bacterial strains that are resistant to available antibiotics. This would create a serious public health problem. The genetically modified crops might contain other toxic substances (such as enhanced amounts of heavy metals) and the crops might not be "substantially equivalent" in genome, proteome, and metabolome compared with unmodified crops. Another concern is that genetically modified crops may be less nutritious; for example, they might contain lower amounts of phytoestrogens, which protect against heart disease and cancer. The review of available literature indicates that the genetically modified crops available in the market that are intended for human consumption are generally safe; their consumption is not associated with serious health problems. However, because of potential for exposure of a large segment of human population to genetically modified foods, more research is needed to ensure that the genetically modified foods are safe for human consumption.

  7. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.

  8. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions

    PubMed Central

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2–10 months for known ADRs and 19–44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0–122.5 days and 185.5–306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  9. Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

    PubMed

    Mangoni, Arduino A

    2012-05-01

    Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

  10. Adverse event detection in drug development: recommendations and obligations beyond phase 3.

    PubMed

    Berlin, Jesse A; Glasser, Susan C; Ellenberg, Susan S

    2008-08-01

    Premarketing studies of drugs, although large enough to demonstrate efficacy and detect common adverse events, cannot reliably detect an increased incidence of rare adverse events or events with significant latency. For most drugs, only about 500 to 3000 participants are studied, for relatively short durations, before a drug is marketed. Systems for assessment of postmarketing adverse events include spontaneous reports, computerized claims or medical record databases, and formal postmarketing studies. We briefly review the strengths and limitations of each. Postmarketing surveillance is essential for developing a full understanding of the balance between benefits and adverse effects. More work is needed in analysis of data from spontaneous reports of adverse effects and automated databases, design of ad hoc studies, and design of economically feasible large randomized studies.

  11. Signal detection to identify serious adverse events (neuropsychiatric events) in travelers taking mefloquine for chemoprophylaxis of malaria

    PubMed Central

    Naing, Cho; Aung, Kyan; Ahmed, Syed Imran; Mak, Joon Wah

    2012-01-01

    Background For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies. Materials and methods We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2. Results Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review) were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2. Conclusion Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were not detected for mefloquine. Further studies are needed to substantiate this. PMID:22936859

  12. Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

    PubMed

    Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

    2013-11-01

    The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Advanced Clinical Decision Support for Vaccine Adverse Event Detection and Reporting.

    PubMed

    Baker, Meghan A; Kaelber, David C; Bar-Shain, David S; Moro, Pedro L; Zambarano, Bob; Mazza, Megan; Garcia, Crystal; Henry, Adam; Platt, Richard; Klompas, Michael

    2015-09-15

    Reporting of adverse events (AEs) following vaccination can help identify rare or unexpected complications of immunizations and aid in characterizing potential vaccine safety signals. We developed an open-source, generalizable clinical decision support system called Electronic Support for Public Health-Vaccine Adverse Event Reporting System (ESP-VAERS) to assist clinicians with AE detection and reporting. ESP-VAERS monitors patients' electronic health records for new diagnoses, changes in laboratory values, and new allergies following vaccinations. When suggestive events are found, ESP-VAERS sends the patient's clinician a secure electronic message with an invitation to affirm or refute the message, add comments, and submit an automated, prepopulated electronic report to VAERS. High-probability AEs are reported automatically if the clinician does not respond. We implemented ESP-VAERS in December 2012 throughout the MetroHealth System, an integrated healthcare system in Ohio. We queried the VAERS database to determine MetroHealth's baseline reporting rates from January 2009 to March 2012 and then assessed changes in reporting rates with ESP-VAERS. In the 8 months following implementation, 91 622 vaccinations were given. ESP-VAERS sent 1385 messages to responsible clinicians describing potential AEs. Clinicians opened 1304 (94.2%) messages, responded to 209 (15.1%), and confirmed 16 for transmission to VAERS. An additional 16 high-probability AEs were sent automatically. Reported events included seizure, pleural effusion, and lymphocytopenia. The odds of a VAERS report submission during the implementation period were 30.2 (95% confidence interval, 9.52-95.5) times greater than the odds during the comparable preimplementation period. An open-source, electronic health record-based clinical decision support system can increase AE detection and reporting rates in VAERS. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society

  14. The validity of sequence symmetry analysis (SSA) for adverse drug reaction signal detection.

    PubMed

    Wahab, Izyan A; Pratt, Nicole L; Wiese, Michael D; Kalisch, Lisa M; Roughead, Elizabeth E

    2013-05-01

    To determine the validity of sequence symmetry analysis (SSA) method to detect adverse drug reactions from an administrative claims database. Published randomised controlled trials (RCTs) of 19 medicines were identified through search databases, product information (PI) or the US Food and Drug Administration Web site. All adverse events (AEs) in the RCTs and the PI for the medicines were extracted. AEs were considered 'gold standard positive events' if they were reported as being statistically significant events in adequately powered RCTs. The remaining AEs were considered 'gold standard negative events' if the event was not listed as an AE in the PI for that medicine or any other medicine in its class. Indicators of AEs were identified by consensus from two clinical researchers. SSA was run for each medicine-indicator pair using four different time windows: 3, 6, 9 and 12 months. A total of 120 randomised placebo controlled trials were reviewed for the 19 tested medicines. A total of 165 medicine-indicator pairs (44 positive and 121 negative events) were identified and tested by SSA. At the 12-month time window, the sensitivity, specificity, positive and negative predictive values of SSA were 61% (95%CI 0.46-0.74), 93% (95%CI 0.87-0.96), 77% (95%CI 0.61-0.88) and 87% (95%CI 0.80-0.92), respectively. Using a 3-month time window, the SSA had a lower sensitivity (52%). The SSA technique was found to have moderate sensitivity and high specificity for detecting ADRs. These results suggest that SSA is a potential tool for detecting ADRs using administrative claims data that could complement existing pharmacosurveillance methods. Copyright © 2013 John Wiley & Sons, Ltd.

  15. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  16. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  17. 40 CFR 161.34 - Flagging of studies for potential adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Flagging of studies for potential... Provisions § 161.34 Flagging of studies for potential adverse effects. (a) Any person who submits a study of... registration, or to satisfy a requirement imposed under FIFRA sec. 3(c)(2)(B), must submit with the study...

  18. A potential causal association mining algorithm for screening adverse drug reactions in postmarketing surveillance.

    PubMed

    Ji, Yanqing; Ying, Hao; Dews, Peter; Mansour, Ayman; Tran, John; Miller, Richard E; Massanari, R Michael

    2011-05-01

    Early detection of unknown adverse drug reactions (ADRs) in postmarketing surveillance saves lives and prevents harmful consequences. We propose a novel data mining approach to signaling potential ADRs from electronic health databases. More specifically, we introduce potential causal association rules (PCARs) to represent the potential causal relationship between a drug and ICD-9 (CDC. (2010). International Classification of Diseases, Ninth Revision (ICD-9). [Online]. Available: http://www.cdc.gov/nchs/icd/icd9.html) coded signs or symptoms representing potential ADRs. Due to the infrequent nature of ADRs, the existing frequency-based data mining methods cannot effectively discover PCARs. We introduce a new interestingness measure, potential causal leverage, to quantify the degree of association of a PCAR. This measure is based on the computational, experience-based fuzzy recognition-primed decision (RPD) model that we developed previously (Y. Ji, R. M. Massanari, J. Ager, J. Yen, R. E. Miller, and H. Ying, "A fuzzy logic-based computational recognition-primed decision model," Inf. Sci., vol. 177, pp. 4338-4353, 2007) on the basis of the well-known, psychology-originated qualitative RPD model (G. A. Klein, "A recognition-primed decision making model of rapid decision making," in Decision Making in Action: Models and Methods, 1993, pp. 138-147). The potential causal leverage assesses the strength of the association of a drug-symptom pair given a collection of patient cases. To test our data mining approach, we retrieved electronic medical data for 16,206 patients treated by one or more than eight drugs of our interest at the Veterans Affairs Medical Center in Detroit between 2007 and 2009. We selected enalapril as the target drug for this ADR signal generation study. We used our algorithm to preliminarily evaluate the associations between enalapril and all the ICD-9 codes associated with it. The experimental results indicate that our approach has a potential to

  19. Generalized enrichment analysis improves the detection of adverse drug events from the biomedical literature.

    PubMed

    Winnenburg, Rainer; Shah, Nigam H

    2016-06-23

    Identification of associations between marketed drugs and adverse events from the biomedical literature assists drug safety monitoring efforts. Assessing the significance of such literature-derived associations and determining the granularity at which they should be captured remains a challenge. Here, we assess how defining a selection of adverse event terms from MeSH, based on information content, can improve the detection of adverse events for drugs and drug classes. We analyze a set of 105,354 candidate drug adverse event pairs extracted from article indexes in MEDLINE. First, we harmonize extracted adverse event terms by aggregating them into higher-level MeSH terms based on the terms' information content. Then, we determine statistical enrichment of adverse events associated with drug and drug classes using a conditional hypergeometric test that adjusts for dependencies among associated terms. We compare our results with methods based on disproportionality analysis (proportional reporting ratio, PRR) and quantify the improvement in signal detection with our generalized enrichment analysis (GEA) approach using a gold standard of drug-adverse event associations spanning 174 drugs and four events. For single drugs, the best GEA method (Precision: .92/Recall: .71/F1-measure: .80) outperforms the best PRR based method (.69/.69/.69) on all four adverse event outcomes in our gold standard. For drug classes, our GEA performs similarly (.85/.69/.74) when increasing the level of abstraction for adverse event terms. Finally, on examining the 1609 individual drugs in our MEDLINE set, which map to chemical substances in ATC, we find signals for 1379 drugs (10,122 unique adverse event associations) on applying GEA with p < 0.005. We present an approach based on generalized enrichment analysis that can be used to detect associations between drugs, drug classes and adverse events at a given level of granularity, at the same time correcting for known dependencies among

  20. A systematic review to evaluate the accuracy of electronic adverse drug event detection.

    PubMed

    Forster, Alan J; Jennings, Alison; Chow, Claire; Leeder, Ciera; van Walraven, Carl

    2012-01-01

    Adverse drug events (ADEs), defined as adverse patient outcomes caused by medications, are common and difficult to detect. Electronic detection of ADEs is a promising method to identify ADEs. We performed this systematic review to characterize established electronic detection systems and their accuracy. We identified studies evaluating electronic ADE detection from the MEDLINE and EMBASE databases. We included studies if they contained original data and involved detection of electronic triggers using information systems. We abstracted data regarding rule characteristics including type, accuracy, and rationale. Forty-eight studies met our inclusion criteria. Twenty-four (50%) studies reported rule accuracy but only 9 (18.8%) utilized a proper gold standard (chart review in all patients). Rule accuracy was variable and often poor (range of sensitivity: 40%-94%; specificity: 1.4%-89.8%; positive predictive value: 0.9%-64%). 5 (10.4%) studies derived or used detection rules that were defined by clinical need or the underlying ADE prevalence. Detection rules in 8 (16.7%) studies detected specific types of ADEs. Several factors led to inaccurate ADE detection algorithms, including immature underlying information systems, non-standard event definitions, and variable methods for detection rule validation. Few ADE detection algorithms considered clinical priorities. To enhance the utility of electronic detection systems, there is a need to systematically address these factors.

  1. 40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for Certain Genetically Modified Microbial Pesticides § 172.57 Submission of information regarding potential unreasonable adverse effects. Any person using a microbial pesticide in small-scale testing covered by this subpart who...

  2. Australian pharmacies prevent potential adverse reactions in patients taking warfarin requesting over-the-counter analgesia.

    PubMed

    MacFarlane, Brett V; Bergin, Jenny K; Reeves, Peter; Matthews, Andrew

    2015-06-01

    The objective of this article was to assess if Australian pharmacy staff prevent potential adverse reactions in warfarin patients requesting over-the-counter (OTC) analgesia. Mystery shoppers entered 170 pharmacies across Australia to request OTC analgesia for a hypothetical patient with a wrist injury who currently takes warfarin following a heart valve replacement. The request was made to the first pharmacist or non-pharmacist staff member to approach the mystery shopper. The interaction was audio-taped and assessed by a pharmacist. The OTC analgesic recommended was assessed for the potential to cause an adverse bleeding event. The quality of advice given with the OTC analgesic was assessed against determined criteria. Results were compared with scenarios of similar request type where the hypothetical patient was not taking warfarin. Mystery shoppers enquiring about taking OTC analgesics concomitantly with warfarin had access to the pharmacist in 97.0% of cases. All 170 pharmacies recommended OTC analgesics that were less likely to cause adverse events when taken with warfarin. The advice given and the communication between pharmacy staff and mystery shoppers were of high quality. Australian pharmacies support the quality use of medicines by patients taking warfarin by providing expeditious access to the pharmacist, appropriate recommendations of OTC analgesics, high standards of quality of advice and they communicate in a way to ensure ease of understanding by the consumer. The protocols used by pharmacy staff help prevent potentially serious adverse drug events. © 2014 Royal Pharmaceutical Society.

  3. Luteinizing hormone--releasing hormone agonists: a quick reference for prevalence rates of potential adverse effects.

    PubMed

    Walker, Lauren M; Tran, Susan; Robinson, John W

    2013-12-01

    Men with prostate cancer (PCa) frequently undergo androgen deprivation therapy (ADT), typically in the form of a depot injection of luteinizing hormone-releasing hormone agonists (LHRHa). LHRHa are associated with many adverse effects (eg, hot flashes, sexual dysfunction, loss of muscle mass, osteopenia, metabolic syndrome), which drastically impact patient quality of life. This literature review, which includes a comprehensive table documenting prevalence rates, provides a quick reference for health care professionals involved in the care of men undergoing ADT with LHRHa. Primary sources were acquired from PubMed using the search terms "androgen deprivation therapy" and each potentially adverse effect (eg, "androgen deprivation therapy and hot flashes"). Commonly cited review articles were also examined for citations of original studies containing prevalence rates. More than 270 articles were reviewed. In contrast to many existing reviews, rates are cited exclusively from original sources. The prevalence rates, obtained from original sources, suggest that more than half of documented adverse effects are experienced by as many as 40% or more of patients. A critique of the literature is also provided. Although there is a vast literature of both original and review articles on specific adverse effects of LHRHa, the quality of research on prevalence rates for some adverse effects is subpar. Many review articles contain inaccuracies and do not cite original sources. The table of prevalence rates will serve as a quick reference for health care providers when counseling patients and will aid in the development of evidence-based patient education materials.

  4. Using the AHRQ PSIs to Detect Post-Discharge Adverse Events in the Veterans Health Administration

    PubMed Central

    Mull, Hillary J.; Borzecki, Ann M.; Chen, Qi; Shin, Marlena H.; Rosen, Amy K.

    2015-01-01

    Background PSIs use inpatient administrative data to flag cases with potentially preventable adverse events (AEs) attributable to hospital care. We explored how many AEs the PSIs identified in the 30 days post-discharge. Methods We ran the PSI software (version 3.1a) on VA 2003–2007 administrative data for ten recently validated PSIs. Among PSI-eligible index hospitalizations not flagged with an AE, we evaluated how many AEs occurred within 1–14 and 15–30 days post-discharge using inpatient and outpatient administrative data. Results Considering all PSI-eligible index hospitalizations, we identified 11,141 post-discharge AEs, compared to 40,578 inpatient-flagged AEs. More than 60% of post-discharge AEs were detected within 14 days of discharge. The majority of post-discharge AEs were decubitus ulcers and postoperative pulmonary embolisms or deep vein thromboses. Conclusions Extending PSI algorithms to the post-discharge period may provide a more complete picture of hospital quality. Future work should use chart review to validate post-discharge PSI events. PMID:23939485

  5. Adverse drug reactions – examples of detection of rare events using databases

    PubMed Central

    Chan, Esther W; Liu, Kirin Q L; Chui, Celine S L; Sing, Chor-Wing; Wong, Lisa Y L; Wong, Ian C K

    2015-01-01

    It is recognised that randomised controlled trials are not feasible for capturing rare adverse events. There is an increasing trend towards observational research methodologies using large population-based health databases. These databases offer more scope for adequate sample sizes, allowing for comprehensive patient characterisation and assessment of the associated factors. While direct causality cannot be established and confounders cannot be ignored, databases present an opportunity to explore and quantify rare events. The use of databases for the detection of rare adverse events in the following conditions, sudden death associated with attention deficit hyperactivity disorder (ADHD) treatment, retinal detachment associated with the use of fluoroquinolones and toxic epidermal necrolysis associated with drug exposure, are discussed as examples. In general, rare adverse events tend to have immediate and important clinical implications and may be life-threatening. An understanding of the causative factors is therefore important, in addition to the research methodologies and database platforms that enable the undertaking of the research. PMID:25060360

  6. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA's Spontaneous Reporting System.

    PubMed

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S; Friedman, Carol

    2010-11-13

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS.

  7. Photoscreening to detect potential amblyopia.

    PubMed

    Maslin, K; Hope, C

    1990-08-01

    Photoscreening to detect amblyopiogenic conditions is particularly applicable for the child under three years of age because conventional testing is difficult. We have designed an eccentric photoscreener that is inexpensive, easily used and requires only one diagnostic photograph. Some 231 infants and children were refracted and photoscreened and results compared in a blind study. Compliance was good and all cases of strabismus, amblyopia, and amblyopiogenic conditions were diagnosed.

  8. Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

    PubMed

    Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

    2017-05-01

    To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals.

  9. Adverse effects of weight loss: Are persistent organic pollutants a potential culprit?

    PubMed

    Cheikh Rouhou, M; Karelis, A D; St-Pierre, D H; Lamontagne, L

    2016-09-01

    Health professionals commonly recommend weight loss to individuals with obesity. However, unexpected adverse health effects after a weight-loss program have been reported in several studies. The factors that could explain this phenomenon are currently poorly understood. However, one potential factor that has emerged is persistent organic pollutants (POPs). Due to their lipophilic nature, POPs are known to accumulate in the adipose tissue and their concentrations are found to be higher in obese individuals than lean subjects. There is evidence to suggest that weight loss induces a significant increase in POPs levels in the bloodstream. Furthermore, the increases in plasma POPs levels after weight loss are even greater with an intensive weight loss. Thus, a critical question that remains unresolved is whether POPs released from the adipose tissue to the bloodstream during intensive weight loss could increase the risk of cardiometabolic disturbances. In turn, the accumulation of POPs released in response to an intensive weight loss may impair energy metabolism and stimulate a subsequent weight regain. Thus, the purpose of this review is to provide insights about the role of POPs on cardiometabolic risk factors during weight loss and weight regain that could potentially explain, at least in part, the adverse effects observed in certain weight-loss studies. We will also discuss the potential synergistic or antagonistic POPs-dependent risks following weight-loss programs. Ultimately, this may lead in establishing new therapeutic boundaries to minimize potential health hazards related to weight loss. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Adverse surgical outcomes in screen-detected ductal carcinoma in situ of the breast.

    PubMed

    Thomas, Jeremy; Hanby, Andrew; Pinder, Sarah E; Ball, Graham; Lawrence, Gill; Maxwell, Anthony; Wallis, Matthew; Evans, Andrew; Dobson, Hilary; Clements, Karen; Thompson, Alastair

    2014-07-01

    The Sloane Project is the largest prospective audit of ductal carcinoma in situ (DCIS) worldwide, with over 12,000 patients registered between 2003 and 2012, accounting for 50% of screen-detected DCIS diagnosed in the United Kingdom (UK) over the period of accrual. Complete multidisciplinary data from 8313 patients with screen-detected DCIS were analysed for surgical outcome in relation to key radiological and pathological parameters for the cohort and also by hospital of treatment. Adverse surgical outcomes were defined as either failed breast conservation surgery (BCS) or mastectomy for small lesions (<20mm) (MFSL). Inter-hospital variation was analysed by grouping hospitals into high, medium and low frequency subgroups for these two adverse outcomes. Patients with failed BCS or MFSL together accounted for 49% of all mastectomies. Of 6633 patients embarking on BCS, 799 (12.0%) required mastectomy. MFSL accounted for 510 (21%) of 2479 mastectomy patients. Failed BCS was associated with significant radiological under-estimation of disease extent and MFSL significant radiological over-estimation of disease extent. There was considerable and significant inter-hospital variation in failed BCS (range 3-32%) and MFSL (0-60%) of a hospital's BCS/mastectomy workload respectively. Conversely, there were no differences between the key radiological and pathological parameters in high, medium and low frequency adverse-outcome hospitals. This evidence suggests significant practice variation, not patient factors, is responsible for these adverse surgical outcomes in screen-detected DCIS. The Sloane Project provides an evidence base for future practice benchmarking. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Using Structured Telephone Follow-up Assessments to Improve Suicide-related Adverse Event Detection

    PubMed Central

    Arias, Sarah A.; Zhang, Zi; Hillerns, Carla; Sullivan, Ashley F.; Boudreaux, Edwin D.; Miller, Ivan; Camargo, Carlos A.

    2014-01-01

    Adverse event (AE) detection and reporting practices were compared during the first phase of the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE), a suicide intervention study. Data were collected using a combination of chart reviews and structured telephone follow-up assessments post-enrollment. Beyond chart reviews, structured telephone follow-up assessments identified 45% of the total AEs in our study. Notably, detection of suicide attempts significantly varied by approach with 53 (18%) detected by chart review, 173 (59%) by structured telephone follow-up assessments, and 69 (23%) marked as duplicates. Findings provide support for utilizing multiple methods for more robust AE detection in suicide research. PMID:24588679

  12. Identifying causes of adverse events detected by an automated trigger tool through in-depth analysis.

    PubMed

    Muething, S E; Conway, P H; Kloppenborg, E; Lesko, A; Schoettker, P J; Seid, M; Kotagal, U

    2010-10-01

    To describe how in-depth analysis of adverse events can reveal underlying causes. Triggers for adverse events were developed using the hospital's computerised medical record (naloxone for opiate-related oversedation and administration of a glucose bolus while on insulin for insulin-related hypoglycaemia). Triggers were identified daily. Based on information from the medical record and interviews, a subject expert determined if an adverse drug event had occurred and then conducted a real-time analysis to identify event characteristics. Expert groups, consisting of frontline staff and specialist physicians, examined event characteristics and determined the apparent cause. 30 insulin-related hypoglycaemia events and 34 opiate-related oversedation events were identified by the triggers over 16 and 21 months, respectively. In the opinion of the experts, patients receiving continuous-infusion insulin and those receiving dextrose only via parenteral nutrition were at increased risk for insulin-related hypoglycaemia. Lack of standardisation in insulin-dosing decisions and variation regarding when and how much to adjust insulin doses in response to changing glucose levels were identified as common causes of the adverse events. Opiate-related oversedation events often occurred within 48 h of surgery. Variation in pain management in the operating room and post-anaesthesia care unit was identified by the experts as potential causes. Variations in practice, multiple services writing orders, multidrug regimens and variations in interpretation of patient assessments were also noted as potential contributing causes. Identification of adverse drug events through an automated trigger system, supplemented by in-depth analysis, can help identify targets for intervention and improvement.

  13. Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

    PubMed

    El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

  14. Potential adverse effects of amphetamine treatment on brain and behavior: a review.

    PubMed

    Berman, S M; Kuczenski, R; McCracken, J T; London, E D

    2009-02-01

    Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central toxicity and adverse

  15. Potential cardiovascular adverse events when phenylephrine is combined with paracetamol: simulation and narrative review.

    PubMed

    Atkinson, Hartley C; Potts, Amanda L; Anderson, Brian J

    2015-08-01

    Increased bioavailability of phenylephrine is reported when combined with paracetamol in over-the-counter formulations for the symptomatic treatment of the common cold and influenza. Such formulations could increase phenylephrine-related cardiovascular adverse events particularly in susceptible individuals. Quantification of the effect of phenylephrine concentration on blood pressure allows simulation of potential adverse combination therapy effects. MEDLINE and EMBASE databases were searched for papers discussing or describing any adverse effect, hypersensitivity or safety concerns related to phenylephrine alone or in combination with other drugs. The pharmacodynamic relationship between plasma phenylephrine concentration and mean arterial blood pressure was characterized using published observations of blood pressure changes after ophthalmic eye drops. The resulting pharmacokinetic and pharmacodynamic parameters were then used to predict mean arterial blood pressure (MAP) changes in that population if given an oral combination of phenylephrine and paracetamol. There were 1172 papers identified for examination. Forty-seven reports fulfilled the inclusion criteria. Increases in blood pressure and decreases in heart rate have been reported with doses over 15 mg. It has been estimated that a 20-mmHg increase in systolic blood pressure would occur with an oral dose of 45 mg phenylephrine in normotensive healthy people. Those taking monoamine oxidase inhibitors report increased systolic blood pressure of greater than 60 mmHg. Blood pressure and heart rate changes are potentiated in patients with underlying hypertension. Simulation showed a modest increase in MAP when phenylephrine 10 mg was co-administered with paracetamol 1 g (4.2 vs 12.3 mmHg). Combination paracetamol phenylephrine oral therapy has potential to increase blood pressure more than phenylephrine alone in those with cardiovascular compromise.

  16. The ability of animal studies to detect serious post marketing adverse events is limited.

    PubMed

    van Meer, Peter J K; Kooijman, Marlous; Gispen-de Wied, Christine C; Moors, Ellen H M; Schellekens, Huub

    2012-12-01

    The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Portable Automatic Text Classification for Adverse Drug Reaction Detection via Multi-corpus Training

    PubMed Central

    Gonzalez, Graciela

    2014-01-01

    Objective Automatic detection of Adverse Drug Reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media — where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. Methods One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Results Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Conclusions Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing

  18. High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

    PubMed

    Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

    2010-11-13

    Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

  19. Diagnosis of potential stressors adversely affecting benthic invertebrate communities in Greenwich Bay, Rhode Island, USA.

    PubMed

    Pelletier, Marguerite; Ho, Kay; Cantwell, Mark; Perron, Monique; Rocha, Kenneth; Burgess, Robert M; Johnson, Roxanne; Perez, Kenneth; Cardin, John; Charpentier, Michael A

    2017-02-01

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being of Greenwich Bay. This diagnostic procedure is useful for management of waterbodies impacted by multiple stressors. Environ Toxicol Chem 2017;36:449-462. © 2016 SETAC. © 2016 SETAC.

  20. Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

    PubMed

    Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

    2016-04-01

    Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

  1. Application of quantitative signal detection in the Dutch spontaneous reporting system for adverse drug reactions.

    PubMed

    van Puijenbroek, Eugène; Diemont, Willem; van Grootheest, Kees

    2003-01-01

    The primary aim of spontaneous reporting systems (SRSs) is the timely detection of unknown adverse drug reactions (ADRs), or signal detection. Generally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative signal detection, can provide additional information concerning a possible relationship between a drug and an ADR. We describe the role of quantitative signal detection and the way it is applied at the Netherlands Pharmacovigilance Centre Lareb. Results of the statistical analysis are implemented in the traditional case-by-case analysis. In addition, for data-mining purposes, a list of associations of ADRs and suspected drugs that are disproportionally present in the database is periodically generated. Finally, quantitative signal generation can be used to study more complex relationships, such as drug-drug interactions and syndromes. The results of quantitative signal detection should be considered as an additional source of information, complementary to the traditional analysis. Techniques for the detection of drug interactions and syndromes offer a new challenge for pharmacovigilance in the near future.

  2. Potentially inappropriate prescribing andthe risk of adverse drug reactions in critically ill older adults

    PubMed Central

    Galli, Thamires B.; Reis, Wálleri C.; Andrzejevski, Vânia M.

    2016-01-01

    Background: Potentially inappropriate medication (PIM) use in the elderly is associated with increased risk of adverse drug reactions (ADRs), but there is limited information regarding PIM use in the intensive care unit (ICU) setting. Objective: The aim of the study is to describe the prevalence and factors associated with the use of PIM and the occurrence of PIM-related adverse reactions in the critically ill elderly. Methods: This study enrolled all critically ill older adults (60 years or more) admitted to medical or cardiovascular ICUs between January and December 2013, in a large tertiary teaching hospital. For all patients, clinical pharmacists listed the medications given during the ICU stay and data on drugs were analyzed using 2012 Beers Criteria, to identify the prevalence of PIM. For each identified PIM the medical records were analyzed to evaluate factors associated with its use. The frequency of ADRs and, the causal relationship between PIM and the ADRs identified were also evaluated through review of medical records. Results: According to 2012 Beers Criteria, 98.2% of elderly patients used at least one PIM (n=599), of which 24.8% were newly started in the ICUs. In 29.6% of PIMs, there was a clinical circumstance that justified their prescription. The number of PIMs was associated with ICU length of stay and total number of medications. There was at least one ADR identified in 17.8% of patients; more than 40% were attributed to PIM, but there was no statistical association. Conclusions: There is a high prevalence of PIM used in acutely ill older people, but they do not seem to be the major cause of adverse drug reactions in this population. Although many PIMs had a clinical circumstance that led to their prescription during the course of ICU hospitalization, many were still present upon hospital discharge. Therefore, prescription of PIMs should be minimized to improve the safety of elderly patients. PMID:28042352

  3. Identifying High-Risk Patients without Labeled Training Data: Anomaly Detection Methodologies to Predict Adverse Outcomes

    PubMed Central

    Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan

    2010-01-01

    For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures. PMID:21347083

  4. Identifying High-Risk Patients without Labeled Training Data: Anomaly Detection Methodologies to Predict Adverse Outcomes.

    PubMed

    Syed, Zeeshan; Saeed, Mohammed; Rubinfeld, Ilan

    2010-11-13

    For many clinical conditions, only a small number of patients experience adverse outcomes. Developing risk stratification algorithms for these conditions typically requires collecting large volumes of data to capture enough positive and negative for training. This process is slow, expensive, and may not be appropriate for new phenomena. In this paper, we explore different anomaly detection approaches to identify high-risk patients as cases that lie in sparse regions of the feature space. We study three broad categories of anomaly detection methods: classification-based, nearest neighbor-based, and clustering-based techniques. When evaluated on data from the National Surgical Quality Improvement Program (NSQIP), these methods were able to successfully identify patients at an elevated risk of mortality and rare morbidities following inpatient surgical procedures.

  5. Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

    PubMed Central

    Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

    2009-01-01

    Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

  6. A web-based quantitative signal detection system on adverse drug reaction in China.

    PubMed

    Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan

    2009-07-01

    To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.

  7. Patient-specific risk factors of adverse drug events in adult inpatients - evidence detected using the Global Trigger Tool method.

    PubMed

    Härkänen, Marja; Kervinen, Marjo; Ahonen, Jouni; Voutilainen, Ari; Turunen, Hannele; Vehviläinen-Julkunen, Katri

    2015-02-01

    To identify the prevalence, preventability, and severity of adverse drug events in randomly selected adult hospital inpatients, and to study the association between adverse drug events and patient-specific factors. Adverse drug events represent one of the major concerns in patient safety. A retrospective record review. The study was conducted in an 800-bed university hospital in Finland within a 12-month period. Retrospective reviews of randomly selected discharged patients' (n = 463) records using the Global Trigger Tool method were undertaken. The prevalence, preventability, and severity of adverse drug events were studied, and the association between patient-specific factors and adverse drug events were examined using a binary logistic regression model and Pearson's chi-squared tests. A total of 180 adverse drug events were detected in 125 (27%) patients, of which 74 (41·1%) were preventable, and 94·4% caused temporary harm. An abnormal level of potassium in the blood was the most frequent adverse drug event (n = 37). The risk of adverse drug events increased with the length of hospital stay and the increased number of drugs patients used. The patients with coronary diseases (n = 130) had a 2·5 times higher risk of experiencing adverse drug events. In addition, the risk of adverse drug events during hospitalisation increased together with the co-morbidity of patients. Adverse drug events were experienced by a quarter of inpatients, while severe adverse drug events were rare. The risk of adverse drug events increased with patients' prolonged hospital stay, polypharmacy, and morbidity. In addition, information of the usefulness of the Global Trigger tool can be used for future development of the method. Patient-specific risk factors were identified using the Global Trigger Tool method revealing that more efficient monitoring of inpatients with these risk factors may be profitable for decreasing adverse drug events. © 2014 John Wiley & Sons Ltd.

  8. Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events

    PubMed Central

    Wang, Kejian; Wan, Mei; Wang, Rui-Sheng

    2016-01-01

    Background Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. Objective We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. Methods We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Results Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. Conclusions We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning. PMID:27036325

  9. The Evaluation of a Pulmonary Display to Detect Adverse Respiratory Events Using High Resolution Human Simulator

    PubMed Central

    Wachter, S. Blake; Johnson, Ken; Albert, Robert; Syroid, Noah; Drews, Frank; Westenskow, Dwayne

    2006-01-01

    Objective Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. Design To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. Measurements Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. Results Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). Conclusion Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events. PMID:16929038

  10. Information Systems Developments to Detect and Analyze Chemotherapy-associated Adverse Drug Events

    PubMed Central

    Weiner, Mark G.; Livshits, Alice; Carozzoni, Carol; McMenamin, Erin; Gibson, Gene; Loren, Alison W.; Hennessy, Sean

    2002-01-01

    A difficult balance exists in the use of cancer chemotherapy in which the cytotoxic medicine must act on the cancer without causing neutropenic fever, a condition that is caused by over-suppression of the immune system. An improved understanding of dosing strategies as well as the use of medications to support the immune system has helped to reduce the likelihood of an admission for neutropenic fever following cancer chemotherapy. Therefore, as with any drug therapy, chemotherapy administration that is temporally associated with an unexpected hospitalization for neutropenia is an adverse drug event (ADE). Analogous to other informatics research to monitor and address the occurrence of ADEs, this work develops and validates the information systems infrastructure necessary to detect the occurrence of and analyze the factors contributing to chemotherapy associated ADEs.

  11. Adverse event detection (AED) system for continuously monitoring and evaluating structural health status

    NASA Astrophysics Data System (ADS)

    Yun, Jinsik; Ha, Dong Sam; Inman, Daniel J.; Owen, Robert B.

    2011-03-01

    Structural damage for spacecraft is mainly due to impacts such as collision of meteorites or space debris. We present a structural health monitoring (SHM) system for space applications, named Adverse Event Detection (AED), which integrates an acoustic sensor, an impedance-based SHM system, and a Lamb wave SHM system. With these three health-monitoring methods in place, we can determine the presence, location, and severity of damage. An acoustic sensor continuously monitors acoustic events, while the impedance-based and Lamb wave SHM systems are in sleep mode. If an acoustic sensor detects an impact, it activates the impedance-based SHM. The impedance-based system determines if the impact incurred damage. When damage is detected, it activates the Lamb wave SHM system to determine the severity and location of the damage. Further, since an acoustic sensor dissipates much less power than the two SHM systems and the two systems are activated only when there is an acoustic event, our system reduces overall power dissipation significantly. Our prototype system demonstrates the feasibility of the proposed concept.

  12. Is detection of adverse events affected by record review methodology? an evaluation of the "Harvard Medical Practice Study" method and the "Global Trigger Tool".

    PubMed

    Unbeck, Maria; Schildmeijer, Kristina; Henriksson, Peter; Jürgensen, Urban; Muren, Olav; Nilsson, Lena; Pukk Härenstam, Karin

    2013-04-15

    There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the "Harvard Medical Practice Study" method and the "Global Trigger Tool" in detecting adverse events in adult orthopaedic inpatients. We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The "Harvard Medical Practice Study" method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the "Global Trigger Tool". Adverse events "causing harm without permanent disability" accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the "Harvard Medical Practice Study" method and the "Global Trigger Tool" was 40.3% and 30.4%, respectively. More adverse events were identified using the "Harvard Medical Practice Study

  13. Is detection of adverse events affected by record review methodology? an evaluation of the “Harvard Medical Practice Study” method and the “Global Trigger Tool”

    PubMed Central

    2013-01-01

    Background There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the “Harvard Medical Practice Study” method and the “Global Trigger Tool” in detecting adverse events in adult orthopaedic inpatients. Methods We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Results Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The “Harvard Medical Practice Study” method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the “Global Trigger Tool”. Adverse events “causing harm without permanent disability” accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the “Harvard Medical Practice Study” method and the “Global Trigger Tool” was 40.3% and 30.4%, respectively. Conclusions More adverse

  14. Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer.

    PubMed

    Knijnenburg, Sebastiaan L; Mulder, Renée L; Schouten-Van Meeteren, Antoinette Y N; Bökenkamp, Arend; Blufpand, Hester; van Dulmen-den Broeder, Eline; Veening, Margreet A; Kremer, Leontien C M; Jaspers, Monique W M

    2013-10-08

    Great improvements in diagnostics and treatment for malignant disease in childhood have led to a major increase in survival. However, childhood cancer survivors (CCS) are at great risk for developing adverse effects caused by multimodal treatment for their malignancy. Nephrotoxicity is one of these known (acute) side effects of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate impairment, proteinuria, tubulopathy and hypertension. However, evidence about the long-term effects of these treatments on renal function remains inconclusive. To reduce the number of (long-term) nephrotoxic events in CCS, it is important to know the risk of, and risk factors for, early and late renal adverse effects, so that ultimately treatment and screening protocols can be adjusted. To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of and associated risk factors for renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with healthy controls or CCS treated without potentially nephrotoxic treatment. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2011), MEDLINE/PubMed (from 1945 to December 2011) and EMBASE/Ovid (from 1980 to December 2011). With the exception of case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment) in children and adults who were treated for a paediatric malignancy (aged 18 years or younger at diagnosis) with cisplatin, carboplatin, ifosfamide, radiation including the kidney region and/or a nephrectomy. Two review authors independently performed study selection, risk of bias

  15. Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review

    PubMed Central

    Hanskamp-Sebregts, Mirelle; Zegers, Marieke; Vincent, Charles; van Gurp, Petra J; de Vet, Henrica C W; Wollersheim, Hub

    2016-01-01

    Objectives Record review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review. Design A systematic review of the literature. Methods We searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled κ values (κ) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events. Results In 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-rater reliability of the GTT and HMPS showed a pooled κ of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS. Conclusions The reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are potential reference methods that can be used to test concurrent validity. PMID:27550650

  16. Detecting associations between behavioral addictions and dopamine agonists in the Food & Drug Administration’s Adverse Event database

    PubMed Central

    Gendreau, Katherine E.; Potenza, Marc N.

    2014-01-01

    Background/Aims: Studies have reported higher prevalences of four behavioral addictions (binge eating, compulsive shopping, hypersexuality, and pathological gambling) in dopamine agonist-treated Parkinson’s disease relative to non-dopamine agonist-treated Parkinson’s. However, recent case-control and epidemiological studies suggest that prevalences of behavioral addictions in dopamine agonist-treated Parkinson’s may be similar to background population rates. This study tests that hypothesis by examining the FDA Adverse Event Reporting System (FAERS) for evidence of these associations, taking into account the potential impact of publicity on reporting rates. Methods: FAERS reports in 2004 (pre-publicity for all but pathological gambling) and 2007 (post-publicity for all four behaviors) were analyzed. A threshold consisting of ≥3 cases, proportional reporting ratio ≥2, and χ2 with Yates’ correction ≥4 was used to detect signals (drug-associated adverse reactions) involving any of five dopamine agonists and any of four behavioral addictions. Results: No reports containing compulsive shopping and no signal for binge eating and dopamine agonists were found in either year. A weak signal was found for hypersexuality in 2004, with a stronger signal in 2007. A robust signal was found for pathological gambling in 2004, with a more robust signal in 2007. Discussion/Conclusions: These results suggest that publicity may increase reporting rates in the FAERS. Findings for binge eating, compulsive shopping, and hypersexuality suggest that prevalences of these behaviors among those treated with dopamine agonists may be similar to background population rates and thus may not reflect an adverse safety signal. Further investigation of the relationship between dopamine agonists and behavioral addictions is warranted. PMID:25215211

  17. [Detection of adverse events in hospitalized adult patients by using the Global Trigger Tool method].

    PubMed

    Guzmán-Ruiz, O; Ruiz-López, P; Gómez-Cámara, A; Ramírez-Martín, M

    2015-01-01

    To identify and characterize adverse events (AE) in an Internal Medicine Department of a district hospital using an extension of the Global Trigger Tool (GTT), analyzing the diagnostic validity of the tool. An observational, analytical, descriptive and retrospective study was conducted on 2013 clinical charts from an Internal Medicine Department in order to detect EA through the identification of 'triggers' (an event often related to an AE). The 'triggers' and AE were located by systematic review of clinical documentation. The AE were characterized after they were identified. A total of 149 AE were detected in 291 clinical charts during 2013, of which 75.3% were detected directly by the tool, while the rest were not associated with a trigger. The percentage of charts that had at least one AE was 35.4%. The most frequent AE found was pressure ulcer (12%), followed by delirium, constipation, nosocomial respiratory infection and altered level of consciousness by drugs. Almost half (47.6%) of the AE were related to drug use, and 32.2% of all AE were considered preventable. The tool demonstrated a sensitivity of 91.3% (95%CI: 88.9-93.2) and a specificity of 32.5% (95%CI: 29.9-35.1). It had a positive predictive value of 42.5% (95%CI: 40.1-45.1) and a negative predictive value of 87.1% (95%CI: 83.8-89.9). The tool used in this study is valid, useful and reproducible for the detection of AE. It also serves to determine rates of injury and to observe their progression over time. A high frequency of both AE and preventable events were observed in this study. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

  18. Relational resilience as a potential mediator between adverse childhood experiences and prenatal depression.

    PubMed

    Howell, Kathryn H; Miller-Graff, Laura E; Schaefer, Lauren M; Scrafford, Kathryn E

    2017-08-01

    This study examined the indirect effects of individual, relational, and contextual resilience in the relationship between adverse childhood experiences and prenatal depression. Participants included 101 pregnant women. Adverse childhood experiences had a direct effect on depression, B = 1.11, standard error = .44, p = .01, and relational resilience, B = -1.15, standard error = .19, p < .001, but not individual or contextual resilience. With resilience as a mediator, the effect of adverse childhood experiences on depression was no longer significant. Specifically, relational resilience had a significant indirect effect (IE) on the association between adverse childhood experiences and depression, IE = 1.04, boot standard error  = .28 (95% confidence interval  = .58, 1.68). Results emphasize the associated role of relational qualities, such as sense of security and belongingness, with childhood adversity and mental health.

  19. Childhood adversities and adult use of potentially injurious physical discipline in Japan

    PubMed Central

    Umeda, Maki; Kawakami, Norito; Kessler, Ronald C.; Miller, Elizabeth

    2015-01-01

    Using data derived from the World Mental Health Japan Survey (n = 1,186), this study examined the intergenerational continuity of potentially injurious physical discipline of children in a community sample from Japan with a special focus on the confounding effects of 11 other types of childhood adversities (CAs) and the intervening effects of mental disorders and socioeconomic status. Bivariate analyses revealed that having experienced physical discipline as children and five other CAs was significantly associated with the use of physical discipline as parents in the Japanese community examined. However, childhood physical discipline was the only CA that remained significant after adjusting for the other CAs. The association of childhood physical discipline with adult perpetration was independent of the respondents’ mental disorders and household income. No significant gender differences were found in the associations between childhood physical discipline and adult perpetration. The current study on Japan provided empirical support consistent with results found in other countries regarding the intergenerational transmission of child physical abuse. PMID:26478655

  20. Childhood adversities and adult use of potentially injurious physical discipline in Japan.

    PubMed

    Umeda, Maki; Kawakami, Norito; Kessler, Ronald C; Miller, Elizabeth

    2015-05-01

    Using data derived from the World Mental Health Japan Survey (n = 1,186), this study examined the intergenerational continuity of potentially injurious physical discipline of children in a community sample from Japan with a special focus on the confounding effects of 11 other types of childhood adversities (CAs) and the intervening effects of mental disorders and socioeconomic status. Bivariate analyses revealed that having experienced physical discipline as children and five other CAs was significantly associated with the use of physical discipline as parents in the Japanese community examined. However, childhood physical discipline was the only CA that remained significant after adjusting for the other CAs. The association of childhood physical discipline with adult perpetration was independent of the respondents' mental disorders and household income. No significant gender differences were found in the associations between childhood physical discipline and adult perpetration. The current study on Japan provided empirical support consistent with results found in other countries regarding the intergenerational transmission of child physical abuse.

  1. The immune system of the gut and potential adverse effects of oral nanocarriers on its function.

    PubMed

    Őrfi, Erik; Szebeni, János

    2016-11-15

    There is substantial effort in modern pharmacotherapy to use nanoparticle-based drug delivery systems (nDDS) for improving the oral absorption of drugs. An often neglected circumstance regarding this approach is that the gut is a major part of the immune system that may be vulnerable for immune-cell toxicity, or mediate humoral immune response against various components of nDDS, recognized as foreign. This review recapitulates the structure and function of gut-associated lymphoid tissue (GALT), i.e., the enteral section of mucosa-associated lymphoid tissue (MALT) and reminds how virus-like nDDS may potentially induce immunogenicity just as attenuated or killed viruses do in oral vaccines. Furthermore, we present examples for immune toxicities of emulsifiers and polymer-containing micelles, manifested in complement activation-related pseudoallergy (CARPA). A major message of the review is that early testing of immunogenicity or other adverse immune effects of nDDS in appropriate test systems or models may be prudent to recognize the risk of rare immune problems that may surface in late-stage clinical trials or after marketing of nDDS. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. How Usability of a Web-Based Clinical Decision Support System Has the Potential to Contribute to Adverse Medical Events

    PubMed Central

    Graham, Timothy A.D.; Kushniruk, Andre W.; Bullard, Michael J.; Holroyd, Brian R.; Meurer, David P.; Rowe, Brian H.

    2008-01-01

    Introduction Clinical decision support systems (CDSS) have the potential to reduce adverse medical events, but improper design can introduce new forms of error. CDSS pertaining to community acquired pneumonia and neutropenic fever were studied to determine whether usability of the graphical user interface might contribute to potential adverse medical events. Methods Automated screen capture of 4 CDSS being used by volunteer emergency physicians was analyzed using structured methods. Results 422 events were recorded over 56 sessions. In total, 169 negative comments, 55 positive comments, 130 neutral comments, 21 application events, 34 problems, 6 slips, and 5 mistakes were identified. Three mistakes could have had life-threatening consequences. Conclusion Evaluation of CDSS will be of utmost importance in the future with increasing use of electronic health records. Usability engineering principles can identify interface problems that may lead to potential medical adverse events, and should be incorporated early in the software design phase. PMID:18998968

  3. Detection of adverse events in general surgery using the " Trigger Tool" methodology.

    PubMed

    Pérez Zapata, Ana Isabel; Gutiérrez Samaniego, María; Rodríguez Cuéllar, Elías; Andrés Esteban, Eva María; Gómez de la Cámara, Agustín; Ruiz López, Pedro

    2015-02-01

    Surgery is one of the high-risk areas for the occurrence of adverse events (AE). The purpose of this study is to know the percentage of hospitalisation-related AE that are detected by the «Global Trigger Tool» methodology in surgical patients, their characteristics and the tool validity. Retrospective, observational study on patients admitted to a general surgery department, who underwent a surgical operation in a third level hospital during the year 2012. The identification of AE was carried out by patient record review using an adaptation of «Global Trigger Tool» methodology. Once an AE was identified, a harm category was assigned, including the grade in which the AE could have been avoided and its relation with the surgical procedure. The prevalence of AE was 36,8%. There were 0,5 AE per patient. 56,2% were deemed preventable. 69,3% were directly related to the surgical procedure. The tool had a sensitivity of 86% and a specificity of 93,6%. The positive predictive value was 89% and the negative predictive value 92%. Prevalence of AE is greater than the estimate of other studies. In most cases the AE detected were related to the surgical procedure and more than half were also preventable. The adapted «Global Trigger Tool» methodology has demonstrated to be highly effective and efficient for detecting AE in surgical patients, identifying all the serious AE with few false negative results. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Can social media data lead to earlier detection of drug‐related adverse events?

    PubMed Central

    Cremieux, Pierre; Audenrode, Marc Van; Vekeman, Francis; Karner, Paul; Zhang, Haimin; Greenberg, Paul

    2016-01-01

    Abstract Purpose To compare the patient characteristics and the inter‐temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor®) and sibutramine (Meridia®) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). Methods We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. Results We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. Conclusions Social media AE reporters were younger and focused on less‐serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. PMID:27601271

  5. Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review

    PubMed Central

    Black, Corri; Tagiyeva-Milne, Nara; Helms, Peter; Moir, Dorothy

    2015-01-01

    Aims A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children. Methods MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed. Results From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants. Conclusions Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base. PMID:25819310

  6. Chemical-Sensing Cables Detect Potential Threats

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Intelligent Optical Systems Inc. (IOS) completed Phase I and II Small Business Innovation Research (SBIR) contracts with NASA's Langley Research Center to develop moisture- and pH-sensitive sensors to detect corrosion or pre-corrosive conditions, warning of potentially dangerous conditions before significant structural damage occurs. This new type of sensor uses a specially manufactured optical fiber whose entire length is chemically sensitive, changing color in response to contact with its target, and demonstrated to detect potentially corrosive moisture incursions to within 2 cm. After completing the work with NASA, the company received a Defense Advanced Research Projects Agency (DARPA) Phase III SBIR to develop the sensors further for detecting chemical warfare agents, for which they proved just as successful. The company then worked with the U.S. Department of Defense (DoD) to fine tune the sensors for detecting potential threats, such as toxic industrial compounds and nerve agents. In addition to the work with government agencies, Intelligent Optical Systems has sold the chemically sensitive fiber optic cables to major automotive and aerospace companies, who are finding a variety of uses for the devices. Marketed under the brand name Distributed Intrinsic Chemical Agent Sensing and Transmission (DICAST), these unique continuous-cable fiber optic chemical sensors can serve in a variety of applications: Corrosive-condition monitoring, aiding experimentation with nontraditional power sources, as an economical means of detecting chemical release in large facilities, as an inexpensive "alarm" systems to alert the user to a change in the chemical environment anywhere along the cable, or in distance-resolved optical time domain reflectometry systems to provide detailed profiles of chemical concentration versus length.

  7. Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo.

    PubMed

    Hynynen, K; Chung, A H; Colucci, V; Jolesz, F A

    1996-01-01

    The aim of the study was to evaluate the potential adverse effects of high intensity ultrasound exposure on blood vessels during noninvasive focused ultrasound surgery. A hydraulic MR-compatible positioning device was used to manipulate a focused ultrasound transducer (frequency 1.49 MHz, f-number = 0.8) in an MRI scanner. The system was used to sonicate a branch of the femoral artery and vein of 19 rabbits (26 thighs) in vivo at intensity levels above the threshold for transient cavitation; i.e., between 4400 and 8800 W cm-2 with multiple 1 s pulses stepped across the vessels (step size = 0.7 mm). The vessels were located and followed by MR angiography. In 13 rabbits, x-ray angiograms were also performed after the animals were euthanized. The results demonstrated that the 1 s high-intensity exposures caused the arteries to constrict at all exposure levels tested. At the intensity of 5800 W cm-2 and above, the MRI angiogram immediately after the sonications showed no flow. The x-ray angiograms (1-2 h later) showed that the blood vessels were open, but constricted to about 50% or less of their diameter. Both the MR and x-ray angiograms showed that the vessel diameters relaxed toward their initial diameter during the first week after sonication. In five cases, hemorrhage or vessel rupture was caused by the sonication. This study demonstrates that short, high-intensity focused ultrasound exposure can cause vessel spasm and hemorrhage when transient cavitation is present. This condition should be avoided during noninvasive focused ultrasound surgery.

  8. Flagging clinical adverse experiences: reducing false discoveries without materially compromising power for detecting true signals.

    PubMed

    Mehrotra, Devan V; Adewale, Adeniyi J

    2012-08-15

    Comparative analyses of safety/tolerability data from a typical phase III randomized clinical trial generate multiple p-values associated with adverse experiences (AEs) across several body systems. A common approach is to 'flag' any AE with a p-value less than or equal to 0.05, ignoring the multiplicity problem. Despite the fact that this approach can result in excessive false discoveries (false positives), many researchers avoid a multiplicity adjustment to curtail the risk of missing true safety signals. We propose a new flagging mechanism that significantly lowers the false discovery rate (FDR) without materially compromising the power for detecting true signals, relative to the common no-adjustment approach. Our simple two-step procedure is an enhancement of the Mehrotra-Heyse-Tukey approach that leverages the natural grouping of AEs by body systems. We use simulations to show that, on the basis of FDR and power, our procedure is an attractive alternative to the following: (i) the no-adjustment approach; (ii) a one-step FDR approach that ignores the grouping of AEs by body systems; and (iii) a recently proposed two-step FDR approach for much larger-scale settings such as genome-wide association studies. We use three clinical trial examples for illustration. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Comparative analysis of pharmacovigilance methods in the detection of adverse drug reactions using electronic medical records

    PubMed Central

    Liu, Mei; McPeek Hinz, Eugenia Renne; Matheny, Michael Edwin; Denny, Joshua C; Schildcrout, Jonathan Scott; Miller, Randolph A; Xu, Hua

    2013-01-01

    Objective Medication  safety requires that each drug be monitored throughout its market life as early detection of adverse drug reactions (ADRs) can lead to alerts that prevent patient harm. Recently, electronic medical records (EMRs) have emerged as a valuable resource for pharmacovigilance. This study examines the use of retrospective medication orders and inpatient laboratory results documented in the EMR to identify ADRs. Methods Using 12 years of EMR data from Vanderbilt University Medical Center (VUMC), we designed a study to correlate abnormal laboratory results with specific drug administrations by comparing the outcomes of a drug-exposed group and a matched unexposed group. We assessed the relative merits of six pharmacovigilance measures used in spontaneous reporting systems (SRSs): proportional reporting ratio (PRR), reporting OR (ROR), Yule's Q (YULE), the χ2 test (CHI), Bayesian confidence propagation neural networks (BCPNN), and a gamma Poisson shrinker (GPS). Results We systematically evaluated the methods on two independently constructed reference standard datasets of drug–event pairs. The dataset of Yoon et al contained 470 drug–event pairs (10 drugs and 47 laboratory abnormalities). Using VUMC's EMR, we created another dataset of 378 drug–event pairs (nine drugs and 42 laboratory abnormalities). Evaluation on our reference standard showed that CHI, ROR, PRR, and YULE all had the same F score (62%). When the reference standard of Yoon et al was used, ROR had the best F score of 68%, with 77% precision and 61% recall. Conclusions Results suggest that EMR-derived laboratory measurements and medication orders can help to validate previously reported ADRs, and detect new ADRs. PMID:23161894

  10. Optimization of a quantitative signal detection algorithm for spontaneous reports of adverse events post immunization.

    PubMed

    Van Holle, Lionel; Bauchau, Vincent

    2013-05-01

    To optimize the efficiency of signal detection by maximizing the proportion of true positive (TP) signals among signals detected by a disproportionality algorithm. We compared 176 different combinations of stratification factors, sex (S), age (A), region (R) and year of report (Y), and cut-off values of a Multi-Item Gamma Poisson Schrinker (MGPS) algorithm. Spontaneous adverse event reports of eight vaccines from the GlaxoSmithKline Biologicals safety database were used. Defining events listed in the Product Information as proxy of true safety signals, we compared each algorithm performance in terms of positive predictive value (PPV). For each vaccine, each algorithm was ranked according to PPV. Median rank and overall PPV were computed across vaccines. For a standard cut-off of 2, the optimal stratification factors differed by vaccine and led to a set of algorithms with a median rank of 34.5 (PPV = 0.22; 34 TP). Keeping the original SARY stratification led to optimal cut-offs that differed by vaccine and a set of algorithms with a median rank of 1.75 (PPV = 0.20; 142 TP). The optimal combination of cut-off and stratification led to different algorithms by vaccine with a median rank of 1 (PPV = 0.19; 139 TP). The best unique algorithm parameterization across vaccines was 0.8-SARY (cut-off-stratification), with a median rank of 3 (PPV = 0.20; 195 TP). The original 2-SARY was one of the worst algorithms, with a median rank of 150.75 (PPV = 0.13; 8 TP). Within the scope of this study, a unique MGPS algorithm across vaccines with the original full stratification but a lowered cut-off provided major performance improvement. Copyright © 2012 John Wiley & Sons, Ltd.

  11. Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions.

    PubMed

    Grosso, Anthony; Douglas, Ian; Hingorani, Aroon; MacAllister, Raymond; Smeeth, Liam

    2008-11-01

    Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs.

  12. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    PubMed

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered plants on non-target organisms

    USDA-ARS?s Scientific Manuscript database

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs...

  14. Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

    PubMed

    Oshima, Shinji; Enjuji, Takako; Negishi, Akio; Akimoto, Hayato; Ohara, Kousuke; Okita, Mitsuyoshi; Numajiri, Sachihiko; Inoue, Naoko; Ohshima, Shigeru; Terao, Akira; Kobayashi, Daisuke

    2017-09-01

    In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

  15. Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review.

    PubMed

    Hanskamp-Sebregts, Mirelle; Zegers, Marieke; Vincent, Charles; van Gurp, Petra J; de Vet, Henrica C W; Wollersheim, Hub

    2016-08-22

    Record review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review. A systematic review of the literature. We searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled κ values (κ) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events. In 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-rater reliability of the GTT and HMPS showed a pooled κ of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS. The reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are potential reference methods that can be used to test concurrent validity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Can social media data lead to earlier detection of drug-related adverse events?

    PubMed

    Duh, Mei Sheng; Cremieux, Pierre; Audenrode, Marc Van; Vekeman, Francis; Karner, Paul; Zhang, Haimin; Greenberg, Paul

    2016-12-01

    To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor(®) ) and sibutramine (Meridia(®) ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. Social media AE reporters were younger and focused on less-serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

  17. The Noise from Wind Turbines: Potential Adverse Impacts on Children's Well-Being

    ERIC Educational Resources Information Center

    Bronzaft, Arline L.

    2011-01-01

    Research linking loud sounds to hearing loss in youngsters is now widespread, resulting in the issuance of warnings to protect children's hearing. However, studies attesting to the adverse effects of intrusive sounds and noise on children's overall mental and physical health and well-being have not received similar attention. This, despite the…

  18. The Noise from Wind Turbines: Potential Adverse Impacts on Children's Well-Being

    ERIC Educational Resources Information Center

    Bronzaft, Arline L.

    2011-01-01

    Research linking loud sounds to hearing loss in youngsters is now widespread, resulting in the issuance of warnings to protect children's hearing. However, studies attesting to the adverse effects of intrusive sounds and noise on children's overall mental and physical health and well-being have not received similar attention. This, despite the…

  19. Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

    EPA Science Inventory

    The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

  20. Potential roles of omics data in the use of adverse outcome pathways for environmental risk assessment

    EPA Science Inventory

    The current approach to assessing adverse effects of chemicals in the environment is largely based on a battery of in-vivo study methods and a limited number of accepted in-silico approaches. For most substances the pool of data from which to predict ecosystem effects is limited ...

  1. A secure distributed logistic regression protocol for the detection of rare adverse drug events

    PubMed Central

    El Emam, Khaled; Samet, Saeed; Arbuckle, Luk; Tamblyn, Robyn; Earle, Craig; Kantarcioglu, Murat

    2013-01-01

    Background There is limited capacity to assess the comparative risks of medications after they enter the market. For rare adverse events, the pooling of data from multiple sources is necessary to have the power and sufficient population heterogeneity to detect differences in safety and effectiveness in genetic, ethnic and clinically defined subpopulations. However, combining datasets from different data custodians or jurisdictions to perform an analysis on the pooled data creates significant privacy concerns that would need to be addressed. Existing protocols for addressing these concerns can result in reduced analysis accuracy and can allow sensitive information to leak. Objective To develop a secure distributed multi-party computation protocol for logistic regression that provides strong privacy guarantees. Methods We developed a secure distributed logistic regression protocol using a single analysis center with multiple sites providing data. A theoretical security analysis demonstrates that the protocol is robust to plausible collusion attacks and does not allow the parties to gain new information from the data that are exchanged among them. The computational performance and accuracy of the protocol were evaluated on simulated datasets. Results The computational performance scales linearly as the dataset sizes increase. The addition of sites results in an exponential growth in computation time. However, for up to five sites, the time is still short and would not affect practical applications. The model parameters are the same as the results on pooled raw data analyzed in SAS, demonstrating high model accuracy. Conclusion The proposed protocol and prototype system would allow the development of logistic regression models in a secure manner without requiring the sharing of personal health information. This can alleviate one of the key barriers to the establishment of large-scale post-marketing surveillance programs. We extended the secure protocol to account for

  2. Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous Adverse Event Reporting System: An Application of the Sequential Probability Ratio Test.

    PubMed

    Chan, Cheng Leng; Rudrappa, Sowmya; Ang, Pei San; Li, Shu Chuen; Evans, Stephen J W

    2017-08-01

    The ability to detect safety concerns from spontaneous adverse drug reaction reports in a timely and efficient manner remains important in public health. This paper explores the behaviour of the Sequential Probability Ratio Test (SPRT) and ability to detect signals of disproportionate reporting (SDRs) in the Singapore context. We used SPRT with a combination of two hypothesised relative risks (hRRs) of 2 and 4.1 to detect signals of both common and rare adverse events in our small database. We compared SPRT with other methods in terms of number of signals detected and whether labelled adverse drug reactions were detected or the reaction terms were considered serious. The other methods used were reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS). The SPRT produced 2187 signals in common with all methods, 268 unique signals, and 70 signals in common with at least one other method, and did not produce signals in 178 cases where two other methods detected them, and there were 403 signals unique to one of the other methods. In terms of sensitivity, ROR performed better than other methods, but the SPRT method found more new signals. The performances of the methods were similar for negative predictive value and specificity. Using a combination of hRRs for SPRT could be a useful screening tool for regulatory agencies, and more detailed investigation of the medical utility of the system is merited.

  3. Disrupted Executive Function and Aggression in Individuals With a History of Adverse Childhood Experiences: An Event-Related Potential Study.

    PubMed

    Xue, Jiao-Mei; Lin, Ping-Zhen; Sun, Ji-Wei; Cao, Feng-Lin

    2017-10-02

    Here, we explored the functional and neural mechanisms underlying aggression related to adverse childhood experiences. We assessed behavioral performance and event-related potentials during a go/no-go and N-back paradigm. The participants were 15 individuals with adverse childhood experiences and high aggression (ACE + HA), 13 individuals with high aggression (HA), and 14 individuals with low aggression and no adverse childhood experiences (control group). The P2 latency (initial perceptual processing) was longer in the ACE + HA group for the go trials. The HA group had a larger N2 (response inhibition) than controls for the no-go trials. Error-related negativity (error processing) in the ACE + HA and HA groups was smaller than that of controls for false alarm go trials. Lastly, the ACE + HA group had shorter error-related negativity latencies than controls for false alarm trials. Overall, our results reveal the neural correlates of executive function in aggressive individuals with ACEs.

  4. Detection of adverse events of transfusion in a teaching hospital in Ghana.

    PubMed

    Owusu-Ofori, A K; Owusu-Ofori, S P; Bates, I

    2017-06-01

    Monitoring the whole chain of events from the blood donors to recipients, documenting any undesirable or untoward effects and introducing measures to prevent their recurrence if possible are components of haemovigilance systems. Only few sub-Saharan African countries have haemovigilance systems, and there are very little data on adverse events of transfusion. Adverse events monitoring is an integral part of a haemovigilance system. Our study aimed to establish the incidence and types of adverse events of transfusions in Ghana and to identify interventions to improve effectiveness. This prospective observational 1-year study enrolled 372 recipients of 432 transfusions in a Ghanaian teaching hospital. Vital signs were monitored at 15, 30 and 60 min intervals during the transfusion, then 8 h until 24 h post-transfusion. Three investigators independently classified any new signs and symptoms according to Serious Hazards of Transfusion definitions. The adverse events incidence was 21·3% (92/432), predominantly mild acute transfusion reactions (84%). A total of 20 transfusions (4·6%) were stopped before completion, 60% of them for mild febrile reactions, which could have been managed with transfusion in situ. This prospective study indicates a high incidence of adverse events of transfusion in Kumasi, Ghana. The significant numbers of discontinued transfusions suggest that guidelines on how to manage transfusion reactions would help preserve scarce blood stocks. Gradual implementation of a haemovigilance system, starting with monitoring adverse transfusion events, is a pragmatic approach in resource-limited settings. © 2017 British Blood Transfusion Society.

  5. From adverse drug event detection to prevention. A novel clinical decision support framework for medication safety.

    PubMed

    Koutkias, V G; McNair, P; Kilintzis, V; Skovhus Andersen, K; Niès, J; Sarfati, J-C; Ammenwerth, E; Chazard, E; Jensen, S; Beuscart, R; Maglaveras, N

    2014-01-01

    Errors related to medication seriously affect patient safety and the quality of healthcare. It has been widely argued that various types of such errors may be prevented by introducing Clinical Decision Support Systems (CDSSs) at the point of care. Although significant research has been conducted in the field, still medication safety is a crucial issue, while few research outcomes are mature enough to be considered for use in actual clinical settings. In this paper, we present a clinical decision support framework targeting medication safety with major focus on adverse drug event (ADE) prevention. The novelty of the framework lies in its design that approaches the problem holistically, i.e., starting from knowledge discovery to provide reliable numbers about ADEs per hospital or medical unit to describe their consequences and probable causes, and next employing the acquired knowledge for decision support services development and deployment. Major design features of the framework's services are: a) their adaptation to the context of care (i.e. patient characteristics, place of care, and significance of ADEs), and b) their straightforward integration in the healthcare information technologies (IT) infrastructure thanks to the adoption of a service-oriented architecture (SOA) and relevant standards. Our results illustrate the successful interoperability of the framework with two commercially available IT products, i.e., a Computerized Physician Order Entry (CPOE) and an Electronic Health Record (EHR) system, respectively, along with a Web prototype that is independent of existing healthcare IT products. The conducted clinical validation with domain experts and test cases illustrates that the impact of the framework is expected to be major, with respect to patient safety, and towards introducing the CDSS functionality in practical use. This study illustrates an important potential for the applicability of the presented framework in delivering contextualized decision

  6. [Comparison of the "Trigger" tool with the minimum basic data set for detecting adverse events in general surgery].

    PubMed

    Pérez Zapata, A I; Gutiérrez Samaniego, M; Rodríguez Cuéllar, E; Gómez de la Cámara, A; Ruiz López, P

    Surgery is a high risk for the occurrence of adverse events (AE). The main objective of this study is to compare the effectiveness of the Trigger tool with the Hospital National Health System registration of Discharges, the minimum basic data set (MBDS), in detecting adverse events in patients admitted to General Surgery and undergoing surgery. Observational and descriptive retrospective study of patients admitted to general surgery of a tertiary hospital, and undergoing surgery in 2012. The identification of adverse events was made by reviewing the medical records, using an adaptation of "Global Trigger Tool" methodology, as well as the (MBDS) registered on the same patients. Once the AE were identified, they were classified according to damage and to the extent to which these could have been avoided. The area under the curve (ROC) were used to determine the discriminatory power of the tools. The Hanley and Mcneil test was used to compare both tools. AE prevalence was 36.8%. The TT detected 89.9% of all AE, while the MBDS detected 28.48%. The TT provides more information on the nature and characteristics of the AE. The area under the curve was 0.89 for the TT and 0.66 for the MBDS. These differences were statistically significant (P<.001). The Trigger tool detects three times more adverse events than the MBDS registry. The prevalence of adverse events in General Surgery is higher than that estimated in other studies. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Ivermectin detection in serum of onchocerciasis patients: relationship to adverse reactions.

    PubMed

    Njoo, F L; Beek, W M; Keukens, H J; van Wilgenburg, H; Oosting, J; Stilma, J S; Kijlstra, A

    1995-01-01

    Ivermectin treatment of onchocerciasis patients can be accompanied by adverse reactions. Not much is known concerning the pathogenesis of these reactions. Previous studies have demonstrated that the occurrence and extent of adverse reactions are related to infection intensity. However, some severely infected patients experience relatively few adverse effects. The aim of the present study was to investigate whether this seeming discrepancy could be due to diminished ivermectin absorption. Ivermectin concentrations one and two days after treatment were measured by high-performance liquid chromatography in sera of 71 skin snip-positive onchocerciasis patients (21 without reactions, 25 with mild reactions, 14 with moderate reactions, and 11 with severe reactions). The overall mean +/- SD ivermectin concentrations one and two days after a single oral dose (150 micrograms/kg) were 16.4 +/- 6.4 and 6.6 +/- 3.1 ng/ml, respectively. The overall mean +/- SD half-life was estimated to be 19.9 +/- 8.6 hr. The data presented did not show a relationship between ivermectin concentrations and the grade of adverse reactions.

  8. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  9. Data mining in the US Vaccine Adverse Event Reporting System (VAERS): early detection of intussusception and other events after rotavirus vaccination.

    PubMed

    Niu, M T; Erwin, D E; Braun, M M

    2001-09-14

    The Vaccine Adverse Event Reporting System (VAERS) is the US passive surveillance system monitoring vaccine safety. A major limitation of VAERS is the lack of denominator data (number of doses of administered vaccine), an element necessary for calculating reporting rates. Empirical Bayesian data mining, a data analysis method, utilizes the number of events reported for each vaccine and statistically screens the database for higher than expected vaccine-event combinations signaling a potential vaccine-associated event. This is the first study of data mining in VAERS designed to test the utility of this method to detect retrospectively a known side effect of vaccination-intussusception following rotavirus (RV) vaccine. From October 1998 to December 1999, 112 cases of intussusception were reported. The data mining method was able to detect a signal for RV-intussusception in February 1999 when only four cases were reported. These results demonstrate the utility of data mining to detect significant vaccine-associated events at early date. Data mining appears to be an efficient and effective computer-based program that may enhance early detection of adverse events in passive surveillance systems.

  10. Adverse drug events with hyperkalaemia during inpatient stays: evaluation of an automated method for retrospective detection in hospital databases.

    PubMed

    Ficheur, Grégoire; Chazard, Emmanuel; Beuscart, Jean-Baptiste; Merlin, Béatrice; Luyckx, Michel; Beuscart, Régis

    2014-09-12

    Adverse drug reactions and adverse drug events (ADEs) are major public health issues. Many different prospective tools for the automated detection of ADEs in hospital databases have been developed and evaluated. The objective of the present study was to evaluate an automated method for the retrospective detection of ADEs with hyperkalaemia during inpatient stays. We used a set of complex detection rules to take account of the patient's clinical and biological context and the chronological relationship between the causes and the expected outcome. The dataset consisted of 3,444 inpatient stays in a French general hospital. An automated review was performed for all data and the results were compared with those of an expert chart review. The complex detection rules' analytical quality was evaluated for ADEs. In terms of recall, 89.5% of ADEs with hyperkalaemia "with or without an abnormal symptom" were automatically identified (including all three serious ADEs). In terms of precision, 63.7% of the automatically identified ADEs with hyperkalaemia were true ADEs. The use of context-sensitive rules appears to improve the automated detection of ADEs with hyperkalaemia. This type of tool may have an important role in pharmacoepidemiology via the routine analysis of large inter-hospital databases.

  11. Adverse drug events with hyperkalaemia during inpatient stays: evaluation of an automated method for retrospective detection in hospital databases

    PubMed Central

    2014-01-01

    Background Adverse drug reactions and adverse drug events (ADEs) are major public health issues. Many different prospective tools for the automated detection of ADEs in hospital databases have been developed and evaluated. The objective of the present study was to evaluate an automated method for the retrospective detection of ADEs with hyperkalaemia during inpatient stays. Methods We used a set of complex detection rules to take account of the patient’s clinical and biological context and the chronological relationship between the causes and the expected outcome. The dataset consisted of 3,444 inpatient stays in a French general hospital. An automated review was performed for all data and the results were compared with those of an expert chart review. The complex detection rules’ analytical quality was evaluated for ADEs. Results In terms of recall, 89.5% of ADEs with hyperkalaemia “with or without an abnormal symptom” were automatically identified (including all three serious ADEs). In terms of precision, 63.7% of the automatically identified ADEs with hyperkalaemia were true ADEs. Conclusions The use of context-sensitive rules appears to improve the automated detection of ADEs with hyperkalaemia. This type of tool may have an important role in pharmacoepidemiology via the routine analysis of large inter-hospital databases. PMID:25212108

  12. The potential benefits and adverse effects of phytic Acid supplement in streptozotocin-induced diabetic rats.

    PubMed

    Omoruyi, F O; Budiaman, A; Eng, Y; Olumese, F E; Hoesel, J L; Ejilemele, A; Okorodudu, A O

    2013-01-01

    In this study, the effect of phytic acid supplement on streptozotocin-induced diabetic rats was investigated. Diabetic rats were fed rodent chow with or without phytic acid supplementation for thirty days. Blood and organ samples were collected for assays. The average food intake was the highest and the body weight gain was the lowest in the group fed phytic acid supplement compared to the diabetic and normal control groups. There was a downward trend in intestinal amylase activity in the group fed phytic acid supplement compared to the other groups. The spike in random blood glucose was the lowest in the same group. We noted reduced serum triglycerides and increased total cholesterol and HDL cholesterol levels in the group fed phytic acid supplement. Serum alkaline phosphatase and alanine amino transferase activities were significantly (P < 0.05) increased by phytic acid supplementation. Systemic IL-1 β level was significantly (P < 0.05) elevated in the diabetic control and supplement treated groups. The liver lipogenic enzyme activities were not significantly altered among the groups. These results suggest that phytic acid supplementation may be beneficial in the management of diabetes mellitus. The observed adverse effect on the liver may be due to the combined effect of streptozotocin-induced diabetes and phytic acid supplementation.

  13. Potential adverse effects of applying phosphate amendments to immobilize soil contaminants.

    PubMed

    Majs, Frantisek

    2011-01-01

    Seven-day batch equilibrium experiments were conducted to measure the efficacy of four phosphate amendments (trisodium trimetaphosphate [TP3], dodecasodium phytate [Na-IP6], precipitated calcium phytate [Ca-IP6], and hydroxyapatite [HA]) for immobilizing Ni and U in organic-rich sediment. Using the eight-step modified Miller's sequential extraction procedure and the USEPA's Toxicity Characteristic Leaching Procedure, the effect of these amendments on the distribution of Ni and U was assessed. Relative to unamended controls, equilibrium aqueous-phase U concentrations were lower following HA and Ca-IP6 additions but higher following TP3 and Na-IP6 amendments, whereas aqueous Ni concentrations were not decreased only in the Na-IP6 amended treatment relative to the control. The poor rates of contaminant immobilization following TP3 and Na-IP6 amendments correlate with the dispersion of organic matter and organo-mineral colloids, which probably contain sorbed U and Ni. While all amendments shifted the U distribution toward more recalcitrant soil fractions, Ni was redistributed to more labile soil fractions. This study cautions that the addition of orthophosphates and organophosphates as contaminant immobilizing amendments may in fact have adverse effects, especially in high-organic soils. Particular attention is warranted at sites with mixed contaminants with varying geochemical behaviors. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  14. Diagnosis of potential stressors adversely affecting benthic invertebrate communities in Greenwich Bay, Rhode Island, USA

    EPA Science Inventory

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was imp...

  15. Diagnosis of potential stressors adversely affecting benthic invertebrate communities in Greenwich Bay, Rhode Island, USA

    EPA Science Inventory

    Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was imp...

  16. The CTIS Womb to Classroom Screening Program for the detection of agents with adverse effects on neuropsychological development.

    PubMed

    Adams, Jane; Janulewicz, Patricia A; Kao, Kelly; Jones, Kenneth Lyons; Chambers, Christina

    2012-06-01

    Over the last several decades, federal agencies engaged in the screening of environmental or pharmaceutical agents have recognized the need to conduct research in animal models to identify agents that have classic teratogenic effects as well as effects on neural and behavioral development. Many questions typically addressed in rodent models can be further addressed using real-world, everyday human exposures. Although some postmarketing surveillance programs have been put in place to examine the influences on birth characteristics, it is now urgent that programs be launched to examine the long-term risks associated with exposure to the many medications, drugs, and environmental chemicals for which data are currently unavailable and unexplored. The California Teratogen Information Service (CTIS), established in 1983, and its corresponding Clinical Research Program represent the oldest national program directed at identifying pregnancy risk factors and exposures associated with adverse pregnancy outcome, including behavioral dysfunction. In recognition of the rising rates of developmental disorders involving compromised mental ability, in 2007, CTIS committed to the development of a more comprehensive screening program designed to detect relationships between adverse prenatal exposures and compromised human neurobehavioral development. The "CTIS Womb to Classroom Screening Program for the Detection of Agents with Adverse Effects on Neuropsychological Development" is the first program designed to identify agents not yet known to be of concern.

  17. Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development.

    PubMed

    Balmer, Nina V; Leist, Marcel

    2014-07-01

    Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life.

  18. Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

    PubMed

    Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

    2016-06-01

    Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

  19. Exposures of children to organophosphate pesticides and their potential adverse health effects.

    PubMed Central

    Eskenazi, B; Bradman, A; Castorina, R

    1999-01-01

    Recent studies show that young children can be exposed to pesticides during normal oral exploration of their environment and their level of dermal contact with floors and other surfaces. Children living in agricultural areas may be exposed to higher pesticide levels than other children because of pesticides tracked into their homes by household members, by pesticide drift, by breast milk from their farmworker mother, or by playing in nearby fields. Nevertheless, few studies have assessed the extent of children's pesticide exposure, and no studies have examined whether there are adverse health effects of chronic exposure. There is substantial toxicologic evidence that repeated low-level exposure to organophosphate (OP) pesticides may affect neurodevelopment and growth in developing animals. For example, animal studies have reported neurobehavorial effects such as impairment on maze performance, locomotion, and balance in neonates exposed (italic)in utero(/italic) and during early postnatal life. Possible mechanisms for these effects include inhibition of brain acetylcholinesterase, downregulation of muscarinic receptors, decreased brain DNA synthesis, and reduced brain weight in offspring. Research findings also suggest that it is biologically plausible that OP exposure may be related to respiratory disease in children through dysregulation of the autonomic nervous system. The University of California Berkeley Center for Children's Environmental Health Research is working to build a community-university partnership to study the environmental health of rural children. This Center for the Health Assessment of Mothers and Children of Salinas, or CHAMACOS in Monterey County, California, will assess (italic)in utero(/italic) and postnatal OP pesticide exposure and the relationship of exposure to neurodevelopment, growth, and symptoms of respiratory illness in children. The ultimate goal of the center is to translate research findings into a reduction of children

  20. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels.

    PubMed

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P; Chambliss, C Kevin; Brooks, Bryan W; Fabbri, Elena

    2014-06-01

    The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03-300ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress effects of FX were investigated using a battery of biomarkers for mussel health status that included lysosomal parameters, antioxidant enzyme activities, lipid peroxidation, and acetylcholinesterase activity. FX reduced the health status of mussels and induced lysosomal alterations, as suggested by reduction of lysosomal membrane stability in haemocytes and by lysosomal accumulation of neutral lipids in digestive gland. No clear antioxidant responses to FX were detected in digestive gland, while gills displayed significant increases of catalase and glutathione-s-transferase activities and a

  1. The potential of wetlands for mitigating adverse effects of agricultural drainage

    SciTech Connect

    Silverman, G.S.

    1995-12-01

    Agricultural runoff has been clearly identified as a major contributor to the failure of much of the surface water in the United States to meet designated use objectives. Control of agricultural drainage is very problematic. The agriculture industry strongly resists mandated controls, and warns of potential catastrophic consequences in food shortages should production methods be altered. Yet concern grows over the long and short term impact of a variety of contaminants - particularly sediments, nutrients, and pesticides - released to our waters as part of normal agricultural practices. For quite some time, wetlands have been explored for their potential in treating sewage (from both municipal and private systems) and acid mine drainage. Much less work has been done looking at the potential for wetlands to treat agricultural drainage. yet, wetlands may offer tremendous potential for mitigating problems of agricultural runoff while offering farmers desirable (or at least acceptable) uses of marginal land. This paper has two objectives. First, the opportunities for wetlands to be used as agricultural drainage treatment facilities are described. Processes are identified which trap or degrade pollutants, with particular attention given to long-term environmental fate. Second, an experimental wetlands system recently developed in Northwest Ohio is used as an example of system implementation. Emphasis will be given to how the system was developed to optimize pollutant removal within the physical constraints of the site. Preliminary performance data with respect to water quality changes will also be presented.

  2. Pediatric psychopharmacology and local anesthesia: potential adverse drug reactions with vasoconstrictor use in dental practice.

    PubMed

    Waits, Joe; Cretton-Scott, Erika; Childers, Noel K; Sims, Pamela J

    2014-01-01

    Pain management is important when dealing with pediatric dental patients. The use of local anesthetics can be especially challenging for children taking psychotropic medications. The purpose of this paper was to identify pertinent information regarding drug interactions between vasoconstrictor/local anesthetic combinations and medications for the management of psychiatric or behavior disorders in children. Many of the reported interactions are controversial, largely theoretical with very limited clinical evidence, and not well defined. However, when considering the potential for significant increased blood pressure when local anesthesia containing a vasoconstrictor is used, a thorough under standing of the pharmacological actions of medications used to treat psychiatric or behavioral disorders and vasoconstrictors can help dental professionals minimize the potential risk of drug interactions in their practice.

  3. Combined approaches using adverse outcome pathways and big data to find potential diseases associated with humidifier disinfectant

    PubMed Central

    2017-01-01

    According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD. PMID:28111421

  4. Using patient safety indicators to estimate the impact of potential adverse events on outcomes.

    PubMed

    Rivard, Peter E; Luther, Stephen L; Christiansen, Cindy L; Shibei Zhao; Loveland, Susan; Elixhauser, Anne; Romano, Patrick S; Rosen, Amy K

    2008-02-01

    The authors estimated the impact of potentially preventable patient safety events, identified by Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSIs), on patient outcomes: mortality, length of stay (LOS), and cost. The PSIs were applied to all acute inpatient hospitalizations at Veterans Health Administration (VA) facilities in fiscal 2001. Two methods-regression analysis and multivariable case matching- were used independently to control for patient and facility characteristics while predicting the effect of the PSI on each outcome. The authors found statistically significant (p < .0001) excess mortality, LOS, and cost in all groups with PSIs. The magnitude of the excess varied considerably across the PSIs. These VA findings are similar to those from a previously published study of nonfederal hospitals, despite differences between VA and non-VA systems. This study contributes to the literature measuring outcomes of medical errors and provides evidence that AHRQ PSIs may be useful indicators for comparison across delivery systems.

  5. Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

    PubMed

    Ostadhadi, Sattar; Rahmatollahi, Mahdieh; Dehpour, Ahmad-Reza; Rahimian, Reza

    2015-03-01

    Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.

  6. An algorithm to detect adverse drug reactions in the neonatal intensive care unit.

    PubMed

    Du, Wei; Lehr, Victoria Tutag; Lieh-Lai, Mary; Koo, Winston; Ward, Robert M; Rieder, Michael J; Van Den Anker, John N; Reeves, Jaxk H; Mathew, Merene; Lulic-Botica, Mirjana; Aranda, Jacob V

    2013-01-01

    Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus "gold standard" was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.

  7. [Performance and optimisation of a trigger tool for the detection of adverse events in hospitalised adult patients].

    PubMed

    Guzmán Ruiz, Óscar; Pérez Lázaro, Juan José; Ruiz López, Pedro

    2017-05-22

    To characterise the performance of the triggers used in the detection of adverse events (AE) of hospitalised adult patients and to define a simplified panel of triggers to facilitate the detection of AE. Cross-sectional study of charts of patients from a service of internal medicine to detect EA through systematic review of the charts and identification of triggers (clinical event often related to AE), determining if there was AE as the context in which it appeared the trigger. Once the EA was detected, we proceeded to the characterization of the triggers that detected it. Logistic regression was applied to select the triggers with greater AE detection capability. A total of 291 charts were reviewed, with a total of 562 triggers in 103 patients, of which 163 were involved in detecting an AE. The triggers that detected the most AE were "A.1. Pressure ulcer" (9.82%), "B.5. Laxative or enema" (8.59%), "A.8. Agitation" (8.59%), "A.9. Over-sedation" (7.98%), "A.7. Haemorrhage" (6.75%) and "B.4. Antipsychotic" (6.75%). A simplified model was obtained using logistic regression, and included the variable "Number of drugs" and the triggers "Over-sedation", "Urinary catheterisation", "Readmission in 30 days", "Laxative or enema" and "Abrupt medication stop". This model showed a probability of 81% to correctly classify charts with EA or without EA (p <0.001; 95% confidence interval: 0.763-0.871). A high number of triggers were associated with AE. The summary model is capable of detecting a large amount of AE, with a minimum of elements. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Monitoring for potential adverse effects of prenatal gene therapy: use of large animal models with relevance to human application.

    PubMed

    Mehta, Vedanta; Abi-Nader, Khalil N; Carr, David; Wallace, Jacqueline; Coutelle, Charles; Waddington, Simon N; Peebles, Donald; David, Anna L

    2012-01-01

    Safety is an absolute prerequisite for introducing any new therapy, and the need to monitor the consequences of administration of both vector and transgene to the fetus is particularly important. The unique features of fetal development that make it an attractive target for gene therapy, such as its immature immune system and rapidly dividing populations of stem cells, also mean that small perturbations in pregnancy can have significant short- and long-term consequences. Certain features of the viral vectors used, the product of the delivered gene, and sometimes the invasive techniques necessary to deliver the construct to the fetus in utero have the potential to do harm. An important goal of prenatal gene therapy research is to develop clinically relevant techniques that could be applied to cure or ameliorate human disease in utero on large animal models such as sheep or nonhuman primates. Equally important is the use of these models to monitor for potential adverse effects of such interventions. These large animal models provide good representation of individual patient-based investigations. However, analyses that require defined genetic backgrounds, high throughput, defined variability and statistical analyses, e.g. for initial studies on teratogenic and oncogenic effects, are best performed on larger groups of small animals, in particular mice. This chapter gives an overview of the potential adverse effects in relation to prenatal gene therapy and describes the techniques that can be used experimentally in a large animal model to monitor the potential adverse consequences of prenatal gene therapy, with relevance to clinical application. The sheep model is particularly useful to allow serial monitoring of fetal growth and well-being after delivery of prenatal gene therapy. It is also amenable to serially sampling using minimally invasive and clinically relevant techniques such as ultrasound-guided blood sampling. For more invasive long-term monitoring, we

  9. Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos?

    PubMed Central

    Sanchez, Vanesa C.; Pietruska, Jodie R.; Miselis, Nathan R.; Hurt, Robert H.; Kane, Agnes B.

    2010-01-01

    Human diseases associated with exposure to asbestos fibers include pleural fibrosis and plaques, pulmonary fibrosis (asbestosis), lung cancer, and diffuse malignant mesothelioma. The critical determinants of fiber bioactivity and toxicity include not only fiber dimensions, but also shape, surface reactivity, crystallinity, chemical composition, and presence of transition metals. Depending on their size and dimensions, inhaled fibers can penetrate the respiratory tract to the distal airways and into the alveolar spaces. Fibers can be cleared by several mechanisms, including the mucociliary escalator, engulfment, and removal by macrophages, or through splitting and chemical modification. Biopersistence of long asbestos fibers can lead to inflammation, granuloma formation, fibrosis, and cancer. Exposure to synthetic carbon nanomaterials, including carbon nanofibers and carbon nanotubes (CNTs), is considered a potential health hazard because of their physical similarities with asbestos fibers. Respiratory exposure to CNTs can produce an inflammatory response, diffuse interstitial fibrosis, and formation of fibrotic granulomas similar to that observed in asbestos-exposed animals and humans. Given the known cytotoxic and carcinogenic properties of asbestos fibers, toxicity of fibrous nanomaterials is a topic of intense study. The mechanisms of nanomaterial toxicity remain to be fully elucidated, but recent evidence suggests points of similarity with asbestos fibers, including a role for generation of reactive oxygen species, oxidative stress, and genotoxicity. Considering the rapid increase in production and use of fibrous nanomaterials, it is imperative to gain a thorough understanding of their biologic activity to avoid the human health catastrophe that has resulted from widespread use of asbestos fibers. PMID:20049814

  10. Empirical Examination of the Potential Adverse Psychological Effects Associated with Pediatric fMRI Scanning

    PubMed Central

    Wakschlag, Naomi; Britton, Jennifer C.; Jarcho, Johanna; Ernst, Monique; Pine, Daniel S.

    2013-01-01

    Abstract Background Over the past decade, the number of functional magnetic resonance imaging (fMRI) studies has increased dramatically. As MRI scans may be anxiety provoking, performing them in a research setting, particularly with children already prone to anxiety, raises questions about ethics as well as methodological feasibility. It is essential to address these questions before expanding the use of this technique to clinical settings, or more widely in the context of pediatric psychopharmacology and biological psychiatry research. The current study investigates the psychological reactions of anxious and non-anxious children and non-anxious adults to an fMRI scan. Methods Eighty-seven anxious children, 140 non-anxious children, and 98 non-anxious adults rated their emotional reactions to an fMRI scan. Results Results indicated that anxious and non-anxious children reported no greater anxiety after fMRI scanning than did adults. In addition, no age-related differences in distress were observed. These data demonstrate that anxious children, healthy children, and healthy adults have similar emotional reactions to fMRI scanning. Conclusions The observed findings suggest that the potential for fMRI to produce anxiety should not impede its widespread use in clinical research, psychopharmacology, and biological psychiatry. PMID:23738869

  11. Biopersistence and potential adverse health impacts of fibrous nanomaterials: what have we learned from asbestos?

    PubMed

    Sanchez, Vanesa C; Pietruska, Jodie R; Miselis, Nathan R; Hurt, Robert H; Kane, Agnes B

    2009-01-01

    Human diseases associated with exposure to asbestos fibers include pleural fibrosis and plaques, pulmonary fibrosis (asbestosis), lung cancer, and diffuse malignant mesothelioma. The critical determinants of fiber bioactivity and toxicity include not only fiber dimensions, but also shape, surface reactivity, crystallinity, chemical composition, and presence of transition metals. Depending on their size and dimensions, inhaled fibers can penetrate the respiratory tract to the distal airways and into the alveolar spaces. Fibers can be cleared by several mechanisms, including the mucociliary escalator, engulfment, and removal by macrophages, or through splitting and chemical modification. Biopersistence of long asbestos fibers can lead to inflammation, granuloma formation, fibrosis, and cancer. Exposure to synthetic carbon nanomaterials, including carbon nanofibers and carbon nanotubes (CNTs), is considered a potential health hazard because of their physical similarities with asbestos fibers. Respiratory exposure to CNTs can produce an inflammatory response, diffuse interstitial fibrosis, and formation of fibrotic granulomas similar to that observed in asbestos-exposed animals and humans. Given the known cytotoxic and carcinogenic properties of asbestos fibers, toxicity of fibrous nanomaterials is a topic of intense study. The mechanisms of nanomaterial toxicity remain to be fully elucidated, but recent evidence suggests points of similarity with asbestos fibers, including a role for generation of reactive oxygen species, oxidative stress, and genotoxicity. Considering the rapid increase in production and use of fibrous nanomaterials, it is imperative to gain a thorough understanding of their biologic activity to avoid the human health catastrophe that has resulted from widespread use of asbestos fibers.

  12. Empirical examination of the potential adverse psychological effects associated with pediatric FMRI scanning.

    PubMed

    Shechner, Tomer; Wakschlag, Naomi; Britton, Jennifer C; Jarcho, Johanna; Ernst, Monique; Pine, Daniel S

    2013-06-01

    Over the past decade, the number of functional magnetic resonance imaging (fMRI) studies has increased dramatically. As MRI scans may be anxiety provoking, performing them in a research setting, particularly with children already prone to anxiety, raises questions about ethics as well as methodological feasibility. It is essential to address these questions before expanding the use of this technique to clinical settings, or more widely in the context of pediatric psychopharmacology and biological psychiatry research. The current study investigates the psychological reactions of anxious and non-anxious children and non-anxious adults to an fMRI scan. Eighty-seven anxious children, 140 non-anxious children, and 98 non-anxious adults rated their emotional reactions to an fMRI scan. Results indicated that anxious and non-anxious children reported no greater anxiety after fMRI scanning than did adults. In addition, no age-related differences in distress were observed. These data demonstrate that anxious children, healthy children, and healthy adults have similar emotional reactions to fMRI scanning. The observed findings suggest that the potential for fMRI to produce anxiety should not impede its widespread use in clinical research, psychopharmacology, and biological psychiatry.

  13. Cumulative adversity and depressive symptoms among older adults in Israel: the differential roles of self-oriented versus other-oriented events of potential trauma

    PubMed Central

    Shmotkin, Dov; Litwin, Howard

    2013-01-01

    Background The study examined the association between cumulative adversity and current depressive symptoms in a national sample of Israelis aged 50+. Referring to cumulative adversity as exposure to potentially traumatic events along life, the study distinguished between events primarily inflicted upon the self (self-oriented adversity) versus upon another person (other-oriented adversity). Method Data were drawn from the Israeli component of the Survey of Health, Aging and Retirement in Europe (SHARE). During 2005–2006, 1710 Jews and Arabs completed an inventory of potentially traumatic events and two measures of depressive symptoms: the European Depression scale (Euro-D) and the Adapted Center for Epidemiological Studies—Depression scale (ACES-D). The Euro-D is more detailed in querying cognitions and motivations while the ACES-D is more detailed in querying feelings and social alienation. Results In line with the hypothesis, self-oriented adversity had a positive association with depressive symptoms whereas other-oriented adversity had either no association or an inverse association with depressive symptoms. Sociodemographic characteristics and perceived health were controlled in the multivariate regressions. Conclusions The differential association of self- versus other-oriented adversity with depressive symptoms may be explained in terms of social commitments that are inherent in other-oriented adversity and incompatible with depressive symptoms. The study points to the variations in the symptom compositions represented by the Euro-D and ACES-D, with the latter better capturing the difference between self- and other-oriented adversities. PMID:19288036

  14. Assessment of the potential of polyphenols as a CYP17 inhibitor free of adverse corticosteroid elevation.

    PubMed

    Lin, Chun-Ju; Cheng, Li-Chuan; Lin, Tsu-Chun Emma; Wang, Chien-Jen; Li, Lih-Ann

    2014-08-01

    Inhibition of 17α-hydroxylase/17,20-lyase (CYP17), which dictates the proceeding of androgen biosynthesis, is recommended as an effective treatment for androgen-dependent diseases. However, androgen depletion by selective CYP17 inhibition is accompanied with corticosteroid elevation, which increases risk of cardiovascular diseases. In this study, we evaluated the likelihood of polyphenols as a CYP17 inhibitor without cardiovascular complications. All examined polyphenols significantly inhibited CYP17 in human adrenocortical H295R cells, but their effects on androgen and cortisol biosynthesis were diverse. Resveratrol was the most potent CYP17 inhibitor with an approximate IC50 of 4 μM, and the inhibition might weigh on the 17α-hydroxylase activity more than the 17,20-lyase activity. Resveratrol also inhibited 21α-hydroxylase (CYP21) essential for corticosteroid biosynthesis but to a lesser extent, thus preventing the occurrence of cortisol elevation following CYP17 blockade. Although transcriptional down-regulation was important for α-naphthoflavone-mediated CYP17 inhibition, resveratrol inhibited CYP17 and CYP21 mainly at the level of enzyme activity rather than enzyme abundance and cytochrome P450 electron transfer. Daidzein also inhibited CYP17 and CYP21 although less potent than resveratrol. Daidzein was the only polyphenol showing inhibition of 3β-hydroxysteroid dehydrogenase type II (3βHSD2). The exceptional 3βHSD2 inhibition led to dehydroepiandrosterone accumulation alongside daidzein-caused androgen biosynthetic impairment. In contrast, androgen and cortisol secretion was increased or remained normal under α-naphthoflavone and β-naphthoflavone treatments, suggesting that CYP17 inhibition was counteracted by increased substrate generation. α-naphthoflavone and β-naphthoflavone also enhanced the formation of cortisol from 17-hydroxyprogesterone and testosterone from androstenedione. Our findings suggest a potential application of resveratrol in

  15. [Potentially inappropriate medications in geriatrics: Which tools to detect them?

    PubMed

    Desnoyer, Aude; Guignard, Bertrand; Lang, Pierre-Olivier; Desmeules, Jules; Vogt-Ferrier, Nicole; Bonnabry, Pascal

    2016-11-01

    Potentially inappropriate prescriptions include over-prescription, which refers to prescription of more drugs than clinically needed, mis-prescription which refers to incorrect prescription of a drug that is needed (as per drug, dose, drug interactions, duration of therapy, duplication, follow-up, etc.) and under-prescription which stands for failure to prescribe drugs that are needed. They are associated with adverse drug events, increased use of health-care services, morbimortality and health-care costs, and poorer quality of life. Due to polymorbidity and polypharmacy, potentially inappropriate prescription is common among the elderly. In the last 2 decades, explicit indicators to detect inappropriate prescriptions were developed in geriatrics. The aim of this review is to summarize, compare and critically review existing explicit criteria. We conducted a systematic literature search in PubMed, Embase, Cochrane Library and Google Scholar, from January 1991 to November 2015. The following keywords were used: "("inappropriate prescribing" [MeSH Terms] OR "medication errors" [MeSH Terms] AND "potentially inappropriate medications" [MeSH Terms] AND "elderly" [MeSH All field] AND "explicit criteria" [MeSH Terms])". Articles describing the development of new list of explicit indicators dedicated to geriatrics, in English and in French, were included in this review. Their characteristics, organization, content, and assessments of their validity and of the optimal tool for geriatrics are presented. Fourteen lists of explicit indicators were included in the review. An organization based on physiological systems and pathologies, as observed in ACOVE, 5th version of Beers criteria and STOPP/START enables quick application in general practice. A low overlap among criteria was observed between tools. This may be due to a lack of completeness for some tools. Mimica, ACOVE, PIEA, and STOPP/START are the most exhaustive ones, only the last three addressing the under

  16. Potential adverse effects of inorganic pollutants on clinical parameters of loggerhead sea turtles (Caretta caretta): results from a nesting colony from Cape Verde, West Africa.

    PubMed

    Camacho, M; Orós, J; Boada, L D; Zaccaroni, A; Silvi, M; Formigaro, C; López, P; Zumbado, M; Luzardo, O P

    2013-12-01

    A large number of nesting loggerhead sea turtles (n = 201) were sampled to establish the blood levels of 11 elements (Cu, Mn, Pb, Zn, Cd, Ni, Cr, As, Al, Hg, and Se). Almost all of the samples showed detectable levels of these 11 elements, and Zn and Se exhibited the highest concentrations (median values as high as 6.05 and 2.28 μg/g, respectively). The median concentrations of the most toxic compounds, As, Cd, Pb, and Hg, were relatively low (0.38, 0.24, 0.06, and 0.03 μg/g, respectively). We also determined the haematological and biochemical parameters in a subsample of 50 turtles to evaluate the potential effects of these contaminants on clinical parameters and found several associations. Our study reinforces the usefulness of blood for the monitoring of the levels of contaminating elements and their adverse effects on blood parameters in sea turtles.

  17. STROBE-based methodology for detection of adverse events across multiple communities.

    PubMed

    Sordo, Margarita; Colecchi, Judith; Dubey, Anil; Dubey, Anil Kumar; Gainer, Vivian; Murphy, Shawn N

    2008-11-06

    Partners Healthcare is one of five institutions in conjunction with eHealth Initiative (eHI) and the FDA that is collaborating in a nation-wide effort to develop novel health information technology tools to create an active drug safety surveillance system across the U.S. The STROBE statement serves as the standard for the definition of a structured, systematic, reproducible approach for detecting both the risks and benefits of drug treatments in multiple settings.

  18. Investigation of landslide potential parameters on Zonguldak-Ereğli Highway and adverse effects of landslides in the region.

    PubMed

    Can, Eray

    2014-04-01

    Landslides are natural phenomena in the same class of natural disasters as earthquakes, floods, hurricanes, erosion, and volcanic eruptions that adversely affect human lives and property. Owing to their widespread occurrence, landslides are easily visible and able to be partially understood by people witnessing them. Nevertheless, to comprehend the detail of their formation and determine their potential, it is necessary to undertake geodetic, geological, and geophysical measurements in regions prone to landslides. By analyzing these measurements, it is possible to better ascertain those regions predisposed to landslides and thus provide the means to prevent loss of life and property. The city of Zonguldak, situated in the Western Black Sea region of Turkey, has a high occurrence of landslides owing to its harsh topography with rugged and steep slopes and rainfall in almost every season. Furthermore, the diurnal temperature ranging up to 10 °C in all seasons, especially in winter, plays a crucial role in rock disintegration in this region. Other factors damage ground composition and trigger landslides, such as underground mining operations, road construction that collapses rocky hills using explosives, and excavation works in steep terrain for building construction. This study gives a detailed account of the causes and adverse effects of landslides and their parameters through examples of landslide occurrences in the region, together with the results and analyses of two periods of geodetic measurements conducted on the Zonguldak-Ereğli Highway in Ilıksu district.

  19. Epoxy Thermosets: The Detection of Adverse Stoichiometry Using Ultrasonic, Dielectric and NMR Techniques

    NASA Astrophysics Data System (ADS)

    Unwin, M. E.; Challis, R. E.

    2004-02-01

    The relative proportions of hardener and resin (the stoichiometric ratio, SR) in a curing epoxy thermoset strongly influence the engineering properties of the material. We investigate how NMR, dielectric and ultrasonic techniques can be used to track cure and estimate SR in the material. We show that all three methods are sensitive to SR and can give clear and quantitative indications of excess resin. Detection of excess hardener in the finally cured material is more difficult but can be achieved by combined measures of elastic modulus, from the ultrasonic velocity, and loss angle, from ultrasonic attenuation.

  20. Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature

    PubMed Central

    2013-01-01

    Background Omega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults. Methods A comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs. Results Of the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p = 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p = 0.18). Conclusions The potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well

  1. Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

    PubMed

    Swank, Kimberley A; Wu, Eileen; Kortepeter, Cindy; McAninch, Jana; Levin, Robert L

    The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to

  2. Decision support methods for the detection of adverse events in post-marketing data.

    PubMed

    Hauben, M; Bate, A

    2009-04-01

    Spontaneous reporting is a crucial component of post-marketing drug safety surveillance despite its significant limitations. The size and complexity of some spontaneous reporting system databases represent a challenge for drug safety professionals who traditionally have relied heavily on the scientific and clinical acumen of the prepared mind. Computer algorithms that calculate statistical measures of reporting frequency for huge numbers of drug-event combinations are increasingly used to support pharamcovigilance analysts screening large spontaneous reporting system databases. After an overview of pharmacovigilance and spontaneous reporting systems, we discuss the theory and application of contemporary computer algorithms in regular use, those under development, and the practical considerations involved in the implementation of computer algorithms within a comprehensive and holistic drug safety signal detection program.

  3. [Measurement of patient safety: a systematic review of the reliability and validity of adverse event detection with record review].

    PubMed

    Hanskamp-Sebregts, M; Zegers, M; van Gurp, P J; de Vet, H C W; Wollersheim, H

    2017-01-01

    Record review is the most used method to quantify patient safety. We systematically reviewed the reliability and validity of adverse event detection with record review. A systematic review of the literature. We searched PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Library and from their inception through February 2015. We included all studies that aimed to describe the reliability and/or validity of record review. Two reviewers conducted data extraction. We pooled κ values (κ) and analysed the differences in subgroups according to number of reviewers, reviewer experience and training level, adjusted for the prevalence of adverse events. In 25 studies, the psychometric data of the Global Trigger Tool (GTT) and the Harvard Medical Practice Study (HMPS) were reported and 24 studies were included for statistical pooling. The inter-raterreliability of the GTT and HMPS showed a pooled κ of 0.65 and 0.55, respectively. The inter-rater agreement was statistically significantly higher when the group of reviewers within a study consisted of a maximum five reviewers. We found no studies reporting on the validity of the GTT and HMPS. The reliability of record review is moderate to substantial and improved when a small group of reviewers carried out record review. The validity of the record review method has never been evaluated, while clinical data registries, autopsy or direct observations of patient care are methods that can be used to test concurrent validity.

  4. Association of caffeine to MDMA does not increase antinociception but potentiates adverse effects of this recreational drug.

    PubMed

    Camarasa, Jordi; Pubill, David; Escubedo, Elena

    2006-09-21

    Ecstasy (MDMA) street tablets often contain several other compounds in addition to MDMA, particularly caffeine. Then, it becomes necessary to study the consequences of caffeine plus MDMA combination. MDMA (1 mg/kg) elicited an analgesic response both at the spinal and supraspinal levels. However, when associated, MDMA and caffeine did not show any synergistic interaction. When caffeine was administered prior to MDMA, a potentiation of locomotor activity was observed, which consisted in an increase in maximal values and in a prolonged time of activity. In the neurotoxicity studies, a hyperthermic effect of MDMA was observed. Although caffeine alone failed to alter body temperature, it potentiated MDMA-induced hyperthermia. This association also significantly increased MDMA lethality (from 22% to 34%). Following administration of MDMA to rats, there was a persistent decrease in the number of serotonin transporter sites in the cortex, striatum and hippocampus, which was potentiated by caffeine co-treatment. This MDMA toxicity in rats was accompanied by a transient dopaminergic impairment in the striatum, measured as decreased [(3)H]WIN35428 binding sites, by 31% 3 days after treatment, which was not modified by caffeine. A transient down-regulation of 5-HT(2) receptors occurred in the cortex of MDMA-treated rats, whose recovery was slowed by co-treatment with caffeine. In conclusion, the association of MDMA with caffeine does not generate any beneficial effects at the antinociceptive level. The acute effects stemming from this association, in tandem with the final potentiation of serotonergic terminals injury, provide evidence of the potentially greater long-term adverse effects of this particular recreational drug combination.

  5. Plasma neutrophil gelatinase-associated lipocalin as a potential predictor of adverse renal outcomes in immunoglobulin A nephropathy

    PubMed Central

    Park, Ga-Young; Yu, Chung-Hoon; Kim, Jun-Seop; Kang, Yun-Jeong; Kwon, Owen; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim

    2015-01-01

    Background/Aims Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). Methods In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. Results The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. Conclusions pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value. PMID:25995665

  6. Benzodiazepine Use During Hospitalization: Automated Identification of Potential Medication Errors and Systematic Assessment of Preventable Adverse Events

    PubMed Central

    Niedrig, David Franklin; Hoppe, Liesa; Mächler, Sarah; Russmann, Heike; Russmann, Stefan

    2016-01-01

    Objective Benzodiazepines and “Z-drug” GABA-receptor modulators (BDZ) are among the most frequently used drugs in hospitals. Adverse drug events (ADE) associated with BDZ can be the result of preventable medication errors (ME) related to dosing, drug interactions and comorbidities. The present study evaluated inpatient use of BDZ and related ME and ADE. Methods We conducted an observational study within a pharmacoepidemiological database derived from the clinical information system of a tertiary care hospital. We developed algorithms that identified dosing errors and interacting comedication for all administered BDZ. Associated ADE and risk factors were validated in medical records. Results Among 53,081 patients contributing 495,813 patient-days BDZ were administered to 25,626 patients (48.3%) on 115,150 patient-days (23.2%). We identified 3,372 patient-days (2.9%) with comedication that inhibits BDZ metabolism, and 1,197 (1.0%) with lorazepam administration in severe renal impairment. After validation we classified 134, 56, 12, and 3 cases involving lorazepam, zolpidem, midazolam and triazolam, respectively, as clinically relevant ME. Among those there were 23 cases with associated adverse drug events, including severe CNS-depression, falls with subsequent injuries and severe dyspnea. Causality for BDZ was formally assessed as ‘possible’ or ‘probable’ in 20 of those cases. Four cases with ME and associated severe ADE required administration of the BDZ antagonist flumazenil. Conclusions BDZ use was remarkably high in the studied setting, frequently involved potential ME related to dosing, co-medication and comorbidities, and rarely cases with associated ADE. We propose the implementation of automated ME screening and validation for the prevention of BDZ-related ADE. PMID:27711224

  7. ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions

    PubMed Central

    2012-01-01

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  8. Extramural venous invasion detected by MDCT as an adverse imaging feature for predicting synchronous metastases in T4 gastric cancer.

    PubMed

    Cheng, Jin; Wu, Jing; Ye, Yingjiang; Zhang, Chunfang; Zhang, Yinli; Wang, Yi

    2017-04-01

    Background Extramural venous invasion (EMVI) is defined histologically as the active invasion of tumor cells to the lumens of mesenteric vessels beyond the muscularis propria in advanced gastrointestinal cancer, resulting in distant metastases. Purpose To determine the association between synchronous metastatic disease in patients with T4 gastric cancer and EMVI detected on contrast-enhanced multiple-row detector computed tomography (MDCT). Material and Methods A total of 152 patients with T4 gastric carcinoma were retrospectively reviewed and divided into EMVI-positive and EMVI-negative groups where EMVI, as detected on MDCT, was defined as a tubular or nodular soft tissue thickening extending from the tumor along the vessels of the mesentery. Synchronous metastases were detected by MDCT and/or confirmed by postoperative diagnosis. Logistic regression analyses were performed to analyze the predictive factors of synchronous metastases in gastric cancer. Results Synchronous metastases were found in 47 of 152 (30.9%) patients with T4 gastric cancer. Thirty-one of 77 (40.3%) patients in the EMVI-positive group had evidence of metastases compared to 16 (21.3%) of 75 patients in the EMVI-negative group ( P = 0.019). Synchronous metastases were significantly associated with EMVI with an odds ratio (OR) of 2.250 (95% CI, 1.072-4.724). Conclusion EMVI-positive tumors, as an adverse imaging feature, were significantly associated with synchronous metastases in patients with T4 gastric cancer.

  9. Standard-based comprehensive detection of adverse drug reaction signals from nursing statements and laboratory results in electronic health records.

    PubMed

    Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han

    2017-07-01

    We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n   = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation.

  10. Neuropsychological assessment for detecting adverse effects of volatile organic compounds on the central nervous system

    SciTech Connect

    Bolla, K.I. )

    1991-11-01

    Because there are no direct biological markers for the substances implicated in indoor air exposure, it is impossible to directly measure if an individual or group of individuals has been exposed to a potentially neurotoxic substance in the workplace. Behavioral changes may be the earliest and only manifestation of central nervous system (CNS) effects and are often too subtle to be revealed by routine physical or neurological examination. Neuropsychological techniques are sensitive to subtle behavioral/cognitive changes that can results from exposure to neurotoxins. These techniques consist of oral and written tests that are administered by a trained examiner on a on-to-one basis. In general, a wide variety of cognitive domains are evaluated. The typical battery generally includes assessing orientation, attention, intelligence, language, visual memory, verbal memory, perception, visuoconstruction, simple motor speed, psychomotor speed, and mood. As with most assessment techniques, the neuropsychological methods have limitations. One major drawback is the availability of appropriate norms that are used to compare the results of a specific individual. Although neuropsychological tests are sensitive to the presence of CNS involvement, they are not specific. Patterns of performance seen with specific instances of neurotoxic exposure may also be seen with a number of other diseases of the CNS such as dementia, cerebrovascular disease, hydrocephalus, or normal aging. Some of the more sensitive neuropsychological tests are presented. Interpretations of test performance as they relate to toxic effects on the CNS are discussed.

  11. Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care

    PubMed Central

    Novak, Philipp H; Ekins-Daukes, Suzie; Simpson, Colin R; Milne, Robert M; Helms, Peter; McLay, James S

    2005-01-01

    Aims To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions. Design Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Setting One hundred and sixty-one general practices throughout Scotland. Results During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning. Conclusions In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could

  12. DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical–protein interactome

    PubMed Central

    Luo, Heng; Chen, Jian; Shi, Leming; Mikailov, Mike; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun

    2011-01-01

    Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical–protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical–protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user’s molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug–drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. PMID:21558322

  13. Adverse Events in Healthy Individuals and MDR-TB Contacts Treated with Anti-Tuberculosis Drugs Potentially Effective for Preventing Development of MDR-TB: A Systematic Review

    PubMed Central

    Langendam, Miranda W.; Tiemersma, Edine W.; van der Werf, Marieke J.; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58–100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption. PMID:23326464

  14. Adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB: a systematic review.

    PubMed

    Langendam, Miranda W; Tiemersma, Edine W; van der Werf, Marieke J; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58-100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption.

  15. The effect of childhood adversity on 4-year outcome in individuals at ultra high risk for psychosis in the Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

    PubMed

    Kraan, Tamar C; Ising, Helga K; Fokkema, Marjolein; Velthorst, Eva; van den Berg, David P G; Kerkhoven, Margot; Veling, Wim; Smit, Filip; Linszen, Don H; Nieman, Dorien H; Wunderink, Lex; Boonstra, Nynke; Klaassen, Rianne M C; Dragt, Sara; Rietdijk, Judith; de Haan, Lieuwe; van der Gaag, Mark

    2017-01-01

    Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients.

  16. Computational identification of potential multitarget treatments for ameliorating the adverse effects of amyloid-β on synaptic plasticity

    PubMed Central

    Anastasio, Thomas J.

    2014-01-01

    The leading hypothesis on Alzheimer Disease (AD) is that it is caused by buildup of the peptide amyloid-β (Aβ), which initially causes dysregulation of synaptic plasticity and eventually causes destruction of synapses and neurons. Pharmacological efforts to limit Aβ buildup have proven ineffective, and this raises the twin challenges of understanding the adverse effects of Aβ on synapses and of suggesting pharmacological means to prevent them. The purpose of this paper is to initiate a computational approach to understanding the dysregulation by Aβ of synaptic plasticity and to offer suggestions whereby combinations of various chemical compounds could be arrayed against it. This data-driven approach confronts the complexity of synaptic plasticity by representing findings from the literature in a course-grained manner, and focuses on understanding the aggregate behavior of many molecular interactions. The same set of interactions is modeled by two different computer programs, each written using a different programming modality: one imperative, the other declarative. Both programs compute the same results over an extensive test battery, providing an essential crosscheck. Then the imperative program is used for the computationally intensive purpose of determining the effects on the model of every combination of ten different compounds, while the declarative program is used to analyze model behavior using temporal logic. Together these two model implementations offer new insights into the mechanisms by which Aβ dysregulates synaptic plasticity and suggest many drug combinations that potentially may reduce or prevent it. PMID:24847263

  17. Safety of infliximab for the treatment of inflammatory bowel disease: current understanding of the potential for serious adverse events.

    PubMed

    Khanna, Reena; Feagan, Brian G

    2015-06-01

    Infliximab , a chimeric monoclonal antibody directed towards TNF-α, has revolutionized the treatment of inflammatory bowel disease (IBD). Since this therapy suppresses the immune system by neutralizing the immunological activity of TNF, concerns exist regarding the potential for infection, malignancy and immune disorders. Comprehensive data from randomized controlled trials, meta-analyses and cohort studies have defined the risk of infection and malignancy with infliximab. Additional data regarding associations with immune disorders, such as drug-induced lupus, demyelinating syndromes and psoriaform skin disease have emerged, primarily from case reports. We report evidence from the most robust data sources that have examined these adverse events. A modest increase in the incidence of serious infection with infliximab and TNF-antagonists has been observed in methodologically rigorous studies. Combination therapy with an immunosuppressant does not confer a higher risk of serious infection than infliximab monotherapy. TNF-antagonist therapy alone with an immunosuppressant is not associated with higher rates of malignancy. Additional data are required to define causality, the magnitude and determinants of risk for other immune-related complications. Available data suggest the therapeutic index of infliximab is favorable for treatment of moderate-to-severe IBD.

  18. Characterisations of adverse events detected in a university hospital: a 4-year study using the Global Trigger Tool method.

    PubMed

    Rutberg, Hans; Borgstedt Risberg, Madeleine; Sjödahl, Rune; Nordqvist, Pernilla; Valter, Lars; Nilsson, Lena

    2014-05-28

    To describe the level, preventability and categories of adverse events (AEs) identified by medical record review using the Global Trigger Tool (GTT). To estimate when the AE occurred in the course of the hospital stay and to compare voluntary AE reporting with medical record reviewing. Two-stage retrospective record review. 650-bed university hospital. 20 randomly selected medical records were reviewed every month from 2009 to 2012. AE/1000 patient-days. Proportion of AEs found by GTT found also in the voluntary reporting system. AE categorisation. Description of when during hospital stay AEs occur. A total of 271 AEs were detected in the 960 medical records reviewed, corresponding to 33.2 AEs/1000 patient-days or 20.5% of the patients. Of the AEs, 6.3% were reported in the voluntary AE reporting system. Hospital-acquired infections were the most common AE category. The AEs occurred and were detected during the hospital stay in 65.5% of cases; the rest occurred or were detected within 30 days before or after the hospital stay. The AE usually occurred early during the hospital stay, and the hospital stay was 5 days longer on average for patients with an AE. Record reviewing identified AEs to a much larger extent than voluntary AE reporting. Healthcare organisations should consider using a portfolio of tools to gain a comprehensive picture of AEs. Substantial costs could be saved if AEs were prevented. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage.

    PubMed

    Liu, Fang; Rainosek, Shuo W; Frisch-Daiello, Jessica L; Patterson, Tucker A; Paule, Merle G; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-10-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage.

  20. Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey Brain: From Abnormal Lipid Metabolism to Neuronal Damage

    PubMed Central

    Liu, Fang; Rainosek, Shuo W.; Frisch-Daiello, Jessica L.; Patterson, Tucker A.; Paule, Merle G.; Slikker, William; Wang, Cheng; Han, Xianlin

    2015-01-01

    Sevoflurane is a volatile anesthetic that has been widely used in general anesthesia, yet its safety in pediatric use is a public concern. This study sought to evaluate whether prolonged exposure of infant monkeys to a clinically relevant concentration of sevoflurane is associated with any adverse effects on the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h, and frontal cortical tissues were harvested for DNA microarray, lipidomics, Luminex protein, and histological assays. DNA microarray analysis showed that sevoflurane exposure resulted in a broad identification of differentially expressed genes (DEGs) in the monkey brain. In general, these genes were associated with nervous system development, function, and neural cell viability. Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic analysis demonstrated that critical lipid components, (eg, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were significantly downregulated by prolonged exposure of sevoflurane. Luminex protein analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains. Consistently, Fluoro-Jade C staining revealed more degenerating neurons after sevoflurane exposure. These data demonstrate that a clinically relevant concentration of sevoflurane (2.5%) is capable of inducing and maintaining an effective surgical plane of anesthesia in the developing nonhuman primate and that a prolonged exposure of 9 h resulted in profound changes in gene expression, cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally, sevoflurane-induced neuronal damage was also associated with changes in lipid content, composition, or both; and specific lipid changes could provide insights into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and may be sensitive biomarkers for the early detection of anesthetic-induced neuronal damage. PMID:26206149

  1. Properties and Therapeutic Potential of Transient Receptor Potential Channels with Putative Roles in Adversity: Focus on TRPC5, TRPM2 and TRPA1

    PubMed Central

    Jiang, L.H; Gamper, N; Beech, D.J

    2011-01-01

    Mammals contain 28 genes encoding Transient Receptor Potential (TRP) proteins. The proteins assemble into cationic channels, often with calcium permeability. Important roles in physiology and disease have emerged and so there is interest in whether the channels might be suitable therapeutic drug targets. Here we review selected members of three subfamilies of mammalian TRP channel (TRPC5, TRPM2 and TRPA1) that show relevance to sensing of adversity by cells and biological systems. Summarized are the cellular and tissue distributions, general properties, endogenous modulators, protein partners, cellular and tissue functions, therapeutic potential, and pharmacology. TRPC5 is stimulated by receptor agonists and other factors that include lipids and metal ions; it heteromultimerises with other TRPC proteins and is involved in cell movement and anxiety control. TRPM2 is activated by hydrogen peroxide; it is implicated in stress-related inflammatory, vascular and neurodegenerative conditions. TRPA1 is stimulated by a wide range of irritants including mustard oil and nicotine but also, controversially, noxious cold and mechanical pressure; it is implicated in pain and inflammatory responses, including in the airways. The channels have in common that they show polymodal stimulation, have activities that are enhanced by redox factors, are permeable to calcium, and are facilitated by elevations of intracellular calcium. Developing inhibitors of the channels could lead to new agents for a variety of conditions: for example, suppressing unwanted tissue remodeling, inflammation, pain and anxiety, and addressing problems relating to asthma and stroke. PMID:21291387

  2. Multidimensional Approach to Detecting Creative Potential in Managers

    ERIC Educational Resources Information Center

    Caroff, Xavier; Lubart, Todd

    2012-01-01

    Creativity is increasingly recognized as a key component to success in the workplace. This article explores the detection of creative potential in managers. In a first part, creative potential is defined and a multivariate approach concerning the psychological resources for creativity is presented. Then, in a second part, an application of this…

  3. Multidimensional Approach to Detecting Creative Potential in Managers

    ERIC Educational Resources Information Center

    Caroff, Xavier; Lubart, Todd

    2012-01-01

    Creativity is increasingly recognized as a key component to success in the workplace. This article explores the detection of creative potential in managers. In a first part, creative potential is defined and a multivariate approach concerning the psychological resources for creativity is presented. Then, in a second part, an application of this…

  4. The Feasibility of Using Large-Scale Text Mining to Detect Adverse Childhood Experiences in a VA-Treated Population.

    PubMed

    Hammond, Kenric W; Ben-Ari, Alon Y; Laundry, Ryan J; Boyko, Edward J; Samore, Matthew H

    2015-12-01

    Free text in electronic health records resists large-scale analysis. Text records facts of interest not found in encoded data, and text mining enables their retrieval and quantification. The U.S. Department of Veterans Affairs (VA) clinical data repository affords an opportunity to apply text-mining methodology to study clinical questions in large populations. To assess the feasibility of text mining, investigation of the relationship between exposure to adverse childhood experiences (ACEs) and recorded diagnoses was conducted among all VA-treated Gulf war veterans, utilizing all progress notes recorded from 2000-2011. Text processing extracted ACE exposures recorded among 44.7 million clinical notes belonging to 243,973 veterans. The relationship of ACE exposure to adult illnesses was analyzed using logistic regression. Bias considerations were assessed. ACE score was strongly associated with suicide attempts and serious mental disorders (ORs = 1.84 to 1.97), and less so with behaviorally mediated and somatic conditions (ORs = 1.02 to 1.36) per unit. Bias adjustments did not remove persistent associations between ACE score and most illnesses. Text mining to detect ACE exposure in a large population was feasible. Analysis of the relationship between ACE score and adult health conditions yielded patterns of association consistent with prior research. Copyright © 2015 International Society for Traumatic Stress Studies.

  5. Adverse Events Associated with Hospitalization or Detected through the RAI-HC Assessment among Canadian Home Care Clients

    PubMed Central

    Doran, Diane; Hirdes, John P.; Blais, Régis; Baker, G. Ross; Poss, Jeff W.; Li, Xiaoqiang; Dill, Donna; Gruneir, Andrea; Heckman, George; Lacroix, Hélène; Mitchell, Lori; O'Beirne, Maeve; Foebel, Andrea; White, Nancy; Qian, Gan; Nahm, Sang-Myong; Yim, Odilia; Droppo, Lisa; McIsaac, Corrine

    2013-01-01

    Background: The occurrence of adverse events (AEs) in care settings is a patient safety concern that has significant consequences across healthcare systems. Patient safety problems have been well documented in acute care settings; however, similar data for clients in home care (HC) settings in Canada are limited. The purpose of this Canadian study was to investigate AEs in HC, specifically those associated with hospitalization or detected through the Resident Assessment Instrument for Home Care (RAI-HC). Method: A retrospective cohort design was used. The cohort consisted of HC clients from the provinces of Nova Scotia, Ontario, British Columbia and the Winnipeg Regional Health Authority. Results: The overall incidence rate of AEs associated with hospitalization ranged from 6% to 9%. The incidence rate of AEs determined from the RAI-HC was 4%. Injurious falls, injuries from other than fall and medication-related events were the most frequent AEs associated with hospitalization, whereas new caregiver distress was the most frequent AE identified through the RAI-HC. Conclusion: The incidence of AEs from all sources of data ranged from 4% to 9%. More resources are needed to target strategies for addressing safety risks in HC in a broader context. Tools such as the RAI-HC and its Clinical Assessment Protocols, already available in Canada, could be very useful in the assessment and management of HC clients who are at safety risk. PMID:23968676

  6. Antidepressant/anxiolytic potential and adverse effect liabilities of melanin-concentrating hormone receptor 1 antagonists in animal models.

    PubMed

    Chaki, Shigeyuki; Shimazaki, Toshiharu; Nishiguchi, Mariko; Funakoshi, Takeo; Iijima, Michihiko; Ito, Akie; Kanuma, Kosuke; Sekiguchi, Yoshinori

    2015-08-01

    Melanin-concentrating hormone receptor 1 (MCH1 receptor) is known to be involved in the control of mood and stress, in addition to the regulation of feeding. Here, we report further evidence that the blockade of the MCH1 receptor exhibits antidepressant and anxiolytic-like effects in a variety of animal models using TASP0382650 and TASP0489838, newly synthesized MCH1 receptor antagonists, with different scaffolds. Both TASP0382650 and TASP0489838 exhibited high affinities for human MCH1 receptor with IC50 values of 7.13 and 3.80nM, respectively. Both compounds showed potent antagonist activities at the MCH1 receptor, as assessed using MCH-increased [(35)S]GTPγS binding to human MCH1 receptor and an MCH-induced [Ca(2+)]i assay in rat MCH1 receptor expressing cells. In contrast, neither TASP0382650 nor TASP0489838 showed an affinity for the MCH2 receptor, another MCH receptor subtype. The oral administration of TASP0382650 or TASP0489838 significantly reduced the immobility time during the forced swimming test in rats, and reduced hyperemotionality induced by an olfactory bulbectomy, both of which are indicative of an antidepressant-like potential. In the olfactory bulbectomy model, the antidepressant effect of TASP0382650 appeared following a single administration, suggesting a faster onset of action, compared with current medications. Moreover, both TASP0382650 and TASP0489838 exhibited anxiolytic effects in several animal models of anxiety. In contrast, both TASP0382650 and TASP0489838 did not affect spontaneous locomotor activity, motor function, spatial memory during the Morris water maze task, or the convulsion threshold to pentylenetetrazole. These findings provide additional evidence that the blockade of the MCH1 receptor exhibits antidepressant- and anxiolytic activities with no adverse effects in experimental animal models.

  7. Serratia marcescens strains implicated in adverse transfusion reactions form biofilms in platelet concentrates and demonstrate reduced detection by automated culture.

    PubMed

    Greco-Stewart, V S; Brown, E E; Parr, C; Kalab, M; Jacobs, M R; Yomtovian, R A; Ramírez-Arcos, S M

    2012-04-01

    Serratia marcescens is a gram-negative bacterium that has been implicated in adverse transfusion reactions associated with contaminated platelet concentrates. The aim of this study was to investigate whether the ability of S. marcescens to form surface-attached aggregates (biofilms) could account for contaminated platelet units being missed during screening by the BacT/ALERT automated culture system. Seven S. marcescens strains, including biofilm-positive and biofilm-negative control strains and five isolates recovered from contaminated platelet concentrates, were grown in enriched Luria-Bertani medium and in platelets. Biofilm formation was examined by staining assay, dislodging experiments and scanning electron microscopy. Clinical strains were also analysed for their ability to evade detection by the BacT/ALERT system. All strains exhibited similar growth in medium and platelets. While only the biofilm-positive control strain formed biofilms in medium, this strain and three clinical isolates associated with transfusion reactions formed biofilms in platelet concentrates. The other two clinical strains, which had been captured during platelet screening by BacT/ALERT, failed to form biofilms in platelets. Biofilm-forming clinical isolates were approximately three times (P<0·05) more likely to be missed by BacT/ALERT screening than biofilm-negative strains. S. marcescens strains associated with transfusion reactions form biofilms under platelet storage conditions, and initial biofilm formation correlates with missed detection of contaminated platelet concentrates by the BacT/ALERT system. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

  8. The incidence, root-causes, and outcomes of adverse events in surgical units: implication for potential prevention strategies

    PubMed Central

    2011-01-01

    Background We need to know the scale and underlying causes of surgical adverse events (AEs) in order to improve the safety of care in surgical units. However, there is little recent data. Previous record review studies that reported on surgical AEs in detail are now more than ten years old. Since then surgical technology and quality assurance have changed rapidly. The objective of this study was to provide more recent data on the incidence, consequences, preventability, causes and potential strategies to prevent AEs among hospitalized patients in surgical units. Methods A structured record review study of 7,926 patient records was carried out by trained nurses and medical specialist reviewers in 21 Dutch hospitals. The aim was to determine the presence of AEs during hospitalizations in 2004 and to consider how far they could be prevented. Of all AEs, the consequences, responsible medical specialty, causes and potential prevention strategies were identified. Surgical AEs were defined as AEs attributable to surgical treatment and care processes and were selected for analysis in detail. Results Surgical AEs occurred in 3.6% of hospital admissions and represented 65% of all AEs. Forty-one percent of the surgical AEs was considered to be preventable. The consequences of surgical AEs were more severe than for other types of AEs, resulting in more permanent disability, extra treatment, prolonged hospital stay, unplanned readmissions and extra outpatient visits. Almost 40% of the surgical AEs were infections, 23% bleeding, and 22% injury by mechanical, physical or chemical cause. Human factors were involved in the causation of 65% of surgical AEs and were considered to be preventable through quality assurance and training. Conclusions Surgical AEs occur more often than other types of AEs, are more often preventable and their consequences are more severe. Therefore, surgical AEs have a major impact on the burden of AEs during hospitalizations. These findings concur with the

  9. Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Poluzzi, Elisabetta; Raschi, Emanuel; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2015-01-01

    Background There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by

  10. Abnormality degree detection method using negative potential field group detectors

    NASA Astrophysics Data System (ADS)

    Zhang, Hongli; Liu, Shulin; Li, Dong; Shi, Kunju; Wang, Bo; Cui, Jiqiang

    2015-09-01

    Online monitoring methods have been widely used in many major devices, however the normal and abnormal states of equipment are estimated mainly based on the monitoring results whether monitored parameters exceed the setting thresholds. Using these monitoring methods may cause serious false positive or false negative results. In order to precisely monitor the state of equipment, the problem of abnormality degree detection without fault sample is studied with a new detection method called negative potential field group detectors(NPFG-detectors). This method achieves the quantitative expression of abnormality degree and provides the better detection results compared with other methods. In the process of Iris data set simulation, the new algorithm obtains the successful results in abnormal detection. The detection rates for 3 types of Iris data set respectively reach 100%, 91.6%, and 95.24% with 50% training samples. The problem of Bearing abnormality degree detection via an abnormality degree curve is successfully solved.

  11. Extended likelihood ratio test-based methods for signal detection in a drug class with application to FDA's adverse event reporting system database.

    PubMed

    Zhao, Yueqin; Yi, Min; Tiwari, Ram C

    2016-05-02

    A likelihood ratio test, recently developed for the detection of signals of adverse events for a drug of interest in the FDA Adverse Events Reporting System database, is extended to detect signals of adverse events simultaneously for all the drugs in a drug class. The extended likelihood ratio test methods, based on Poisson model (Ext-LRT) and zero-inflated Poisson model (Ext-ZIP-LRT), are discussed and are analytically shown, like the likelihood ratio test method, to control the type-I error and false discovery rate. Simulation studies are performed to evaluate the performance characteristics of Ext-LRT and Ext-ZIP-LRT. The proposed methods are applied to the Gadolinium drug class in FAERS database. An in-house likelihood ratio test tool, incorporating the Ext-LRT methodology, is being developed in the Food and Drug Administration.

  12. Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.

    PubMed

    Ebile, Akoh Walter; Ateudjieu, Jerome; Yakum, Martin Ndinakie; Djuidje, Marceline Ngounoue; Watcho, Pierre

    2015-09-29

    International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan

  13. Detecting adverse events in surgery: comparing events detected by the Veterans Health Administration Surgical Quality Improvement Program and the Patient Safety Indicators.

    PubMed

    Mull, Hillary J; Borzecki, Ann M; Loveland, Susan; Hickson, Kathleen; Chen, Qi; MacDonald, Sally; Shin, Marlena H; Cevasco, Marisa; Itani, Kamal M F; Rosen, Amy K

    2014-04-01

    The Patient Safety Indicators (PSIs) use administrative data to screen for select adverse events (AEs). In this study, VA Surgical Quality Improvement Program (VASQIP) chart review data were used as the gold standard to measure the criterion validity of 5 surgical PSIs. Independent chart review was also used to determine reasons for PSI errors. The sensitivity, specificity, and positive predictive value of PSI software version 4.1a were calculated among Veterans Health Administration hospitalizations (2003-2007) reviewed by VASQIP (n = 268,771). Nurses re-reviewed a sample of hospitalizations for which PSI and VASQIP AE detection disagreed. Sensitivities ranged from 31% to 68%, specificities from 99.1% to 99.8%, and positive predictive values from 31% to 72%. Reviewers found that coding errors accounted for some PSI-VASQIP disagreement; some disagreement was also the result of differences in AE definitions. These results suggest that the PSIs have moderate criterion validity; however, some surgical PSIs detect different AEs than VASQIP. Future research should explore using both methods to evaluate surgical quality. Published by Elsevier Inc.

  14. Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events

    PubMed Central

    2013-01-01

    Background To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. Methods Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. Results Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p’s < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. Conclusions The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation. PMID:23570306

  15. Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events.

    PubMed

    Davison, Karen M; Kaplan, Bonnie J

    2013-04-09

    To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p's < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation.

  16. Detection of adverse events in an acute geriatric hospital over a 6-year period using the Global Trigger Tool.

    PubMed

    Suarez, Cristina; Menendez, María Dolores; Alonso, Josefina; Castaño, Nieves; Alonso, Marta; Vazquez, Fernando

    2014-05-01

    To assess the frequency, severity, and preventability of adverse events (AEs) detected using the Global Trigger Tool (GTT) in an acute geriatric hospital. A 6-year retrospective study. An urban Spanish acute geriatric teaching hospital of 200 beds. Ten randomly selected clinical records were chosen every fortnight from January 2007 to December 2012 (1,440 records, 240 per year). Triggers, AEs, Index of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) categories of severity, and Likert scale to evaluate the preventability of AEs. Four hundred twenty-four AEs (categories E to I of the NCC MERP Index) were identified in 335 of the 1,440 individuals scrutinized, which corresponded to 29.4 physical injuries per 100 admissions (95% confidence interval (CI) = 25.7-34.7). Of these, 351 (91.7%) occurred 3 or more days after admission; 279 harms (65.8%) were preventable. Significant decreases in the rate of harms per 1,000 patient-days (21.8 vs 27.1, relative risk (RR) = 0.77, 95% CI 0.66-0.91, P = .02) and in high-severity events (categories F to I) (11/720 clinical records in 2011-2012 vs 23/720 clinical records in 2007-2009) (RR = 0.48, 95% CI = 0.24-0.96, P = .04) were observed during the second half of the study from the first. The number needed to alert was 7.8. The frequency and severity of AEs decreased during the period of study. Factors possibly contributing to the decrease in AEs include new beds with variable height, pressure ulcer prevention, introduction of clinical electronic records, staff training on hand washing, surgical check list, correct patient identification, and Agency for Healthcare Research and Quality surveys on patient safety culture. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  17. Determining potential adverse effects in marine fish exposed to pharmaceuticals and personal care products with the fish plasma model and whole-body tissue concentrations.

    PubMed

    Meador, James P; Yeh, Andrew; Gallagher, Evan P

    2017-11-01

    The Fish Plasma Model (FPM) was applied to water exposure and tissue concentrations in fish collected from two wastewater treatment plant impacted estuarine sites. In this study we compared predicted fish plasma concentrations to Cmax values for humans, which represents the maximum plasma concentration for the minimum therapeutic dose. The results of this study show that predictions of plasma concentrations for a variety of pharmaceutical and personal care products (PPCPs) from effluent concentrations resulted in 37 compounds (54%) exceeding the response ratio (RR = Fish [Plasma]/1%Cmaxtotal) of 1 compared to 3 compounds (14%) detected with values generated with estuarine receiving water concentrations. When plasma concentrations were modeled from observed whole-body tissue residues, 16 compounds out of 24 detected for Chinook (67%) and 7 of 14 (50%) for sculpin resulted in an RRtissue value greater than 1, which highlights the importance of this dose metric over that using estuarine water. Because the tissue residue approach resulted in a high percentage of compounds with calculated response ratios exceeding a value of unity, we believe this is a more accurate representation for exposure in the field. Predicting plasma concentrations from tissue residues improves our ability to assess the potential for adverse effects in fish because exposure from all sources is captured. Tissue residues are also more likely to represent steady-state conditions compared to those from water exposure because of the inherent reduction in variability usually observed for field data and the time course for bioaccumulation. We also examined the RR in a toxic unit approach to highlight the importance of considering multiple compounds exhibiting a similar mechanism of action. Published by Elsevier Ltd.

  18. Potentials for change detection using Seasat synthetic aperture radar data

    NASA Technical Reports Server (NTRS)

    Bryan, M. L.

    1981-01-01

    Synthetic aperture radars (SAR) image from a non-nadir position. Thus the orientation of the target and sensor to one another is of paramount importance. This has posed problems for data interpretation and with the potentials of radar data for change detection studies. It is possible to use Seasat radar data for change detection even though the look directions are fixed for each location. Especially in areas with repeated coverage on descending or ascending orbits or where the terrain is flat and the targets nonoriented, coverage may be sufficient to provide data for change detection. Examples of Los Angeles and the Everglades of Florida help develop and support the argument.

  19. Subclinical and Overt Adverse Cardiac Effects with Ozone Inhalation in Rats: Potentially Dire Implications of Low Exposures

    EPA Science Inventory

    Ozone is a ubiquitous smog-associated photochemical oxidant with deleterious health effects. While most of the adverse effects described to date involve the respiratory system (i.e, decrements in lung function, airway injury and inflammation, exacerbation of asthma, and compromis...

  20. Subclinical and Overt Adverse Cardiac Effects with Ozone Inhalation in Rats: Potentially Dire Implications of Low Exposures

    EPA Science Inventory

    Ozone is a ubiquitous smog-associated photochemical oxidant with deleterious health effects. While most of the adverse effects described to date involve the respiratory system (i.e, decrements in lung function, airway injury and inflammation, exacerbation of asthma, and compromis...

  1. Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

    PubMed

    Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

    2017-03-01

    Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1

  2. Potential Mechanisms of Hematological Adverse Drug Reactions in Patients Receiving Clozapine in Combination With Proton Pump Inhibitors.

    PubMed

    Wiciński, Michał; Węclewicz, Mateusz M; Miętkiewicz, Mateusz; Malinowski, Bartosz; Grześk, Elżbieta; Klonowska, Joanna

    2017-03-01

    Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis. The mechanism in idiosyncratic agranulocytosis is not dose related and involves either a direct toxic or an immune-allergic effect. It is suspected that the clozapine metabolites nitrenium ion and N-desmethylclozapine may cause apoptosis or impair growth of granulocytes. Formation of N-desmethylclozapine is correlated with activity of the cytochrome P450 enzymes 1A2 and 3A4 (CYP1A2 and CYP3A4). Nitrenium ion is produced by the flavin-containing monooxygenase system of leukocytes. A drug interaction between clozapine and a PPI is a consequence of the induction of common metabolic pathways either by the PPI or clozapine. Findings to date suggest that indirect induction of flavin-containing monooxygenase by omeprazole through the aryl hydrocarbon receptor increases the expression of the enzyme mRNA and in the long term may cause the increase in activity. Moreover, induction of CYP1A2, especially by omeprazole and lansoprazole, may increase the serum concentration of N-desmethylclozapine, which can accumulate in lymphocytes and may achieve toxic levels. Another hypothesis that may explain hematological adverse drug reactions is competitive inhibition of CYP2C19, which may contribute to increased serum concentrations of toxic metabolites.

  3. Potential Climate Change Health Risks from Increases in Heat Waves: Abnormal Birth Outcomes and Adverse Maternal Health Conditions.

    PubMed

    Cil, Gulcan; Cameron, Trudy Ann

    2017-02-23

    We investigate the risks presented by heat waves for adverse health conditions for babies and expectant mothers when these mothers have been exposed to heat waves during gestation or during the period just prior to conception. Rather than just birth weight and gestational age, we focus on less common metrics such as abnormal conditions in the newborn (fetal distress, reliance on a ventilator, and meconium aspiration) and adverse health conditions in the mother (pregnancy-related hypertension, uterine bleeding during pregnancy, eclampsia, and incompetent cervix). We use monthly panel data for over 3,000 U.S. counties, constructed from the confidential version of the U.S. Natality Files for 1989-2008. Our models control for sociodemographic factors and include county, month, and state-by-year fixed effects to control for unobserved spatial and timewise heterogeneity in the data. Even within the United States, where there is widespread access to air conditioning, heat waves increase the fraction of babies with abnormal conditions related to maternal stress, as well as the fraction of mothers who experience pregnancy-related adverse health conditions. The scope for these risks in developing countries is likely to be even greater.

  4. Potential therapeutic competition in community-living older adults in the U.S.: use of medications that may adversely affect a coexisting condition.

    PubMed

    Lorgunpai, Songprod Jonathan; Grammas, Marianthe; Lee, David S H; McAvay, Gail; Charpentier, Peter; Tinetti, Mary E

    2014-01-01

    The 75% of older adults with multiple chronic conditions are at risk of therapeutic competition (i.e. treatment for one condition may adversely affect a coexisting condition). The objective was to determine the prevalence of potential therapeutic competition in community-living older adults. Cross-sectional descriptive study of a representative sample of 5,815 community-living adults 65 and older in the U.S, enrolled 2007-2009. The 14 most common chronic conditions treated with at least one medication were ascertained from Medicare claims. Medication classes recommended in national disease guidelines for these conditions and used by ≥ 2% of participants were identified from in-person interviews conducted 2008-2010. Criteria for potential therapeutic competition included: 1), well-acknowledged adverse medication effect; 2) mention in disease guidelines; or 3) report in a systematic review or two studies published since 2000. Outcomes included prevalence of situations of potential therapeutic competition and frequency of use of the medication in individuals with and without the competing condition. Of 27 medication classes, 15 (55.5%) recommended for one study condition may adversely affect other study conditions. Among 91 possible pairs of study chronic conditions, 25 (27.5%) have at least one potential therapeutic competition. Among participants, 1,313 (22.6%) received at least one medication that may worsen a coexisting condition; 753 (13%) had multiple pairs of such competing conditions. For example, among 846 participants with hypertension and COPD, 16.2% used a nonselective beta-blocker. In only 6 of 37 cases (16.2%) of potential therapeutic competition were those with the competing condition less likely to receive the medication than those without the competing condition. One fifth of older Americans receive medications that may adversely affect coexisting conditions. Determining clinical outcomes in these situations is a research and clinical priority

  5. Potential Therapeutic Competition in Community-Living Older Adults in the U.S.: Use of Medications That May Adversely Affect a Coexisting Condition

    PubMed Central

    Lorgunpai, Songprod Jonathan; Grammas, Marianthe; Lee, David S. H.; McAvay, Gail; Charpentier, Peter; Tinetti, Mary E.

    2014-01-01

    Objective The 75% of older adults with multiple chronic conditions are at risk of therapeutic competition (i.e. treatment for one condition may adversely affect a coexisting condition). The objective was to determine the prevalence of potential therapeutic competition in community-living older adults. Methods Cross-sectional descriptive study of a representative sample of 5,815 community-living adults 65 and older in the U.S, enrolled 2007–2009. The 14 most common chronic conditions treated with at least one medication were ascertained from Medicare claims. Medication classes recommended in national disease guidelines for these conditions and used by ≥2% of participants were identified from in-person interviews conducted 2008–2010. Criteria for potential therapeutic competition included: 1), well-acknowledged adverse medication effect; 2) mention in disease guidelines; or 3) report in a systematic review or two studies published since 2000. Outcomes included prevalence of situations of potential therapeutic competition and frequency of use of the medication in individuals with and without the competing condition. Results Of 27 medication classes, 15 (55.5%) recommended for one study condition may adversely affect other study conditions. Among 91 possible pairs of study chronic conditions, 25 (27.5%) have at least one potential therapeutic competition. Among participants, 1,313 (22.6%) received at least one medication that may worsen a coexisting condition; 753 (13%) had multiple pairs of such competing conditions. For example, among 846 participants with hypertension and COPD, 16.2% used a nonselective beta-blocker. In only 6 of 37 cases (16.2%) of potential therapeutic competition were those with the competing condition less likely to receive the medication than those without the competing condition. Conclusions One fifth of older Americans receive medications that may adversely affect coexisting conditions. Determining clinical outcomes in these situations

  6. Assessing the Potential Adoption and Usefulness of Concurrent, Action-Oriented, Electronic Adverse Drug Event Triggers Designed for the Outpatient Setting

    PubMed Central

    Mull, Hillary J.; Rosen, Amy K.; Shimada, Stephanie L.; Rivard, Peter E.; Nordberg, Brian; Long, Brenna; Hoffman, Jennifer M.; Leecaster, Molly; Savitz, Lucy A.; Shanahan, Christopher W.; Helwig, Amy; Nebeker, Jonathan R.

    2015-01-01

    Background: Adverse drug event (ADE) detection is an important priority for patient safety research. Trigger tools have been developed to help identify ADEs. In previous work we developed seven concurrent, action-oriented, electronic trigger algorithms designed to prompt clinicians to address ADEs in outpatient care. Objectives: We assessed the potential adoption and usefulness of the seven triggers by testing the positive predictive validity and obtaining stakeholder input. Methods: We adapted ADE triggers, “bone marrow toxin—white blood cell count (BMT-WBC),” “bone marrow toxin - platelet (BMT-platelet),” “potassium raisers,” “potassium reducers,” “creatinine,” “warfarin,” and “sedative hypnotics,” with logic to suppress flagging events with evidence of clinical intervention and applied the triggers to 50,145 patients from three large health care systems. Four pharmacists assessed trigger positive predictive value (PPV) with respect to ADE detection (conservatively excluding ADEs occurring during clinically appropriate care) and clinical usefulness (i.e., whether the trigger alert could change care to prevent harm). We measured agreement between raters using the free kappa and assessed positive PPV for the trigger’s detection of harm, clinical usefulness, and both. Stakeholders from the participating health care systems rated the likelihood of trigger adoption and the perceived ease of implementation. Findings: Agreement between pharmacist raters was moderately high for each ADE trigger (kappa free > 0.60). Trigger PPVs for harm ranged from 0 (Creatinine, BMT-WBC) to 17 percent (potassium raisers), while PPV for care change ranged from 0 (WBC) to 60 percent (Creatinine). Fifteen stakeholders rated the triggers. Our assessment identified five of the seven triggers as good candidates for implementation: Creatinine, BMT-Platelet, Potassium Raisers, Potassium Reducers, and Warfarin. Conclusions: At least five outpatient ADE triggers

  7. Characterization of adverse events detected in a large health care delivery system using an enhanced global trigger tool over a five-year interval.

    PubMed

    Kennerly, Donald A; Kudyakov, Rustam; da Graca, Briget; Saldaña, Margaret; Compton, Jan; Nicewander, David; Gilder, Richard

    2014-10-01

    To report 5 years of adverse events (AEs) identified using an enhanced Global Trigger Tool (GTT) in a large health care system. Records from monthly random samples of adults admitted to eight acute care hospitals from 2007 to 2011 with lengths of stay ≥3 days were reviewed. We examined AE incidence overall and by presence on admission, severity, stemming from care provided versus omitted, preventability, and category; and the overlap with commonly used AE-detection systems. Professional nurse reviewers abstracted 9,017 records using the enhanced GTT, recording triggers and AEs. Medical record/account numbers were matched to identify overlapping voluntary reports or AHRQ Patient Safety Indicators (PSIs). Estimated AE rates were as follows: 61.4 AEs/1,000 patient-days, 38.1 AEs/100 discharges, and 32.1 percent of patients with ≥1 AE. Of 1,300 present-on-admission AEs (37.9 percent of total), 78.5 percent showed NCC-MERP level F harm and 87.6 percent were "preventable/possibly preventable." Of 2,129 hospital-acquired AEs, 63.3 percent had level E harm, 70.8 percent were "preventable/possibly preventable"; the most common category was "surgical/procedural" (40.5 percent). Voluntary reports and PSIs captured <5 percent of encounters with hospital-acquired AEs. AEs are common and potentially amenable to prevention. GTT-identified AEs are seldom caught by commonly used AE-detection systems. © Health Research and Educational Trust.

  8. Characterization of Adverse Events Detected in a Large Health Care Delivery System Using an Enhanced Global Trigger Tool over a Five-Year Interval

    PubMed Central

    Kennerly, Donald A; Kudyakov, Rustam; da Graca, Briget; Saldaña, Margaret; Compton, Jan; Nicewander, David; Gilder, Richard

    2014-01-01

    Objective To report 5 years of adverse events (AEs) identified using an enhanced Global Trigger Tool (GTT) in a large health care system. Study Setting Records from monthly random samples of adults admitted to eight acute care hospitals from 2007 to 2011 with lengths of stay ≥3 days were reviewed. Study Design We examined AE incidence overall and by presence on admission, severity, stemming from care provided versus omitted, preventability, and category; and the overlap with commonly used AE-detection systems. Data Collection Professional nurse reviewers abstracted 9,017 records using the enhanced GTT, recording triggers and AEs. Medical record/account numbers were matched to identify overlapping voluntary reports or AHRQ Patient Safety Indicators (PSIs). Principal Findings Estimated AE rates were as follows: 61.4 AEs/1,000 patient-days, 38.1 AEs/100 discharges, and 32.1 percent of patients with ≥1 AE. Of 1,300 present-on-admission AEs (37.9 percent of total), 78.5 percent showed NCC-MERP level F harm and 87.6 percent were “preventable/possibly preventable.” Of 2,129 hospital-acquired AEs, 63.3 percent had level E harm, 70.8 percent were “preventable/possibly preventable”; the most common category was “surgical/procedural” (40.5 percent). Voluntary reports and PSIs captured <5 percent of encounters with hospital-acquired AEs. Conclusions AEs are common and potentially amenable to prevention. GTT-identified AEs are seldom caught by commonly used AE-detection systems. PMID:24628436

  9. Deformation Detection of Potential Landslide with InSAR Observation

    NASA Astrophysics Data System (ADS)

    Liu, Yuzhou; Liao, Mingsheng; Shi, Xuguo; Zhang, Lu

    2016-08-01

    Influenced by geological and climate conditions, Guide County has been identified as a landslide prone area. Multi-temporal InSAR technique can implement continuous earth surface deformation detection with long time scale and wide geography coverage. In this research, we employ the SBAS method to survey potential landslide in Guide County. Two anomalous deformation regions have been detected by L-band PALSAR stacks. Preliminary correlation between the time series deformation and triggering factors is analyzed to explore the driving mechanism for landslide movement. As a consequence, L-band SAR has a good application potential in landslide monitoring and the results can be the basis for landslide recognizing and early warning.

  10. Potential detection systems for monitoring UF{sub 6} releases

    SciTech Connect

    Beck, D.E.; Bostick, W.D.; Armstrong, D.P.; McNeely, J.R.; Stockdale, J.A.D.

    1994-09-01

    In the near future, the Nuclear Regulatory Commission (NRC) will begin to regulate the gaseous diffusion plants. Them is a concern that the smoke detectors currently used for uranium hexafluoride (UF{sub 6}) release detection will not meet NRC safety system requirements such as high reliability and rapid response. The NRC`s position is that licensees should utilize state-of-the-art equipment such as hydrogen fluoride (HF) detectors that would provide more dependable detection of a UF{sub 6} release. A survey of the literature and current vendor information was undertaken to define the state-of-the-art and commercial availability of HF (or other appropriate) detection systems. For the purpose of this report, classification of the available HF detection systems is made on the basis of detection principle (e.g., calorimetric, electrochemical, separational, or optical). Emphasis is also placed on whether the device is primarily sensitive to response from a point source (e.g., outleakage in the immediate vicinity of a specific set of components), or whether the device is potentially applicable to remote sensing over a larger area. Traditional HF point source monitoring typically uses gas sampling tubes or coated paper tapes with color developing indicator, portable and small area HF monitors are often based upon electrochemical or extractive/separational systems; and remote sensing by optical systems holds promise for indoor and outdoor large area monitoring (including plant boundary/ambient air monitoring).

  11. Anxiolytic activity and evaluation of potentially adverse effects of a bradykinin-related peptide isolated from a social wasp venom.

    PubMed

    dos Anjos, Lilian Carneiro; Gomes, Flávia Maria Medeiros; do Couto, Lucianna Lopes; Mourão, Cecília Alves; Moreira, Karla Graziela; Silva, Luciano Paulino; Mortari, Márcia Renata

    2016-03-15

    Anxiety disorders are major health problems in terms of costs stemming from sick leave, disabilities, healthcare and premature mortality. Despite the availability of classic anxiolytics, some anxiety disorders are still resistant to treatment, with higher rates of adverse effects. In this respect, several toxins isolated from arthropod venoms are useful in identifying new compounds to treat neurological disorders, particularly pathological anxiety. Thus, the aims of this study were to identify and characterize an anxiolytic peptide isolated from the venom of the social wasp Polybia paulista. The peptide was identified as Polisteskinin R, with nominal molecular mass [M+H](+)=1301Da and primary structure consisting of Ala-Arg-Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH. The anxiolytic effect was tested using the elevated plus maze test. Moreover, adverse effects on the spontaneous behavior and motor coordination of animals were assessed using the open field and rotarod tests. Polisteskinin R induced a dose-dependent anxiolytic effect. Animals treated with the peptide and diazepam spent significantly more time into the open arms when compared to the groups treated with the vehicle and pentylenetetrazole. No significant differences in spontaneous behavior or motor coordination were observed between the groups, showing that the peptide was well tolerated. The interaction by agonists in both known BK receptors induces a variability of physiological effects; Polisteskinin R can act on these receptors, inducing modulatory activity and thus, attenuating anxiety behaviors. The results of this study demonstrated that the compound Polisteskinin R exerted potent anxiolytic effects and its analogues are promising candidates for experimental pharmacology.

  12. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    PubMed

    Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

    2014-01-01

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

  13. Molecular detection of a potentially toxic diatom species.

    PubMed

    Dhar, Bidhan Chandra; Cimarelli, Lucia; Singh, Kumar Saurabh; Brandi, Letizia; Brandi, Anna; Puccinelli, Camilla; Marcheggiani, Stefania; Spurio, Roberto

    2015-05-06

    A few diatom species produce toxins that affect human and animal health. Among these, members of the Pseudo-nitzschia genus were the first diatoms unambiguously identified as producer of domoic acid, a neurotoxin affecting molluscan shell-fish, birds, marine mammals, and humans. Evidence exists indicating the involvement of another diatom genus, Amphora, as a potential producer of domoic acid. We present a strategy for the detection of the diatom species Amphora coffeaeformis based on the development of species-specific oligonucleotide probes and their application in microarray hybridization experiments. This approach is based on the use of two marker genes highly conserved in all diatoms, but endowed with sufficient genetic divergence to discriminate diatoms at the species level. A region of approximately 450 bp of these previously unexplored marker genes, coding for elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), was used to design oligonucleotide probes that were tested for specificity in combination with the corresponding fluorescently labeled DNA targets. The results presented in this work suggest a possible use of this DNA chip technology for the selective detection of A. coffeaeformis in environmental settings where the presence of this potential toxin producer may represent a threat to human and animal health. In addition, the same basic approach can be adapted to a wider range of diatoms for the simultaneous detection of microorganisms used as biomarkers of different water quality levels.

  14. Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

    PubMed

    Chen, Chun-An; Lu, Meng-Yao; Peng, Shinn-Forng; Lin, Kai-Hsin; Chang, Hsiu-Hao; Yang, Yung-Li; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Liu, Yen-Bin; Horng, Herng-Er; Yang, Hong-Chang; Wang, Jou-Kou; Wu, Mei-Hwan; Wu, Chau-Chung

    2014-01-01

    Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = -0.609, p<0.001), SD-QTc (r = -0.572, p<0.001), and QTc dispersion (r = -0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.

  15. Alleviation of adverse effects of drought stress on growth and some potential physiological attributes in maize (Zea mays L.) by seed electromagnetic treatment.

    PubMed

    Javed, Namra; Ashraf, Muhammad; Akram, Nudrat Aisha; Al-Qurainy, Fahad

    2011-01-01

    Effects of varying preseed magnetic treatments on growth, chlorophyll pigments, photosynthesis, water relation attributes, fluorescence and levels of osmoprotectants in maize plants were tested under normal and drought stress conditions. Seeds of two maize cultivars were treated with different (T0 [0 mT], T1 [100 mT for 5 min], T2 [100 mT for 10 min], T3 [150 mT for 5 min] and T4 [150 mT for 10 min]) electromagnetic treatments. Drought stress considerably suppressed growth, chlorophyll a and b pigments, leaf water potential, photosynthetic rate (A), stomatal conductance (g(s)) and substomatal CO(2) concentration (C(i)), while it increased leaf glycinebetaine and proline accumulation in both maize cultivars. However, pretreated seeds with different magnetic treatments significantly alleviated the drought-induced adverse effects on growth by improving chlorophyll a, A, E, g(s), C(i) and photochemical quenching and nonphotochemical quenching, while it had no significant effect on other attributes. However, different magnetic treatments negatively affected the g(s) and C(i) particularly in cv. Agaiti-2002 under drought stress conditions. Of all magnetic treatments, 100 and 150 mT for 10 min were most effective in alleviating the drought-induced adverse effects. Overall, preseed electromagnetic treatments could be used to minimize the drought-induced adverse effects on different crop plants.

  16. 5-HTTLPR as a potential moderator of the effects of adverse childhood experiences on risk of antisocial personality disorder.

    PubMed

    Douglas, Kara; Chan, Grace; Gelernter, Joel; Arias, Albert J; Anton, Raymond F; Poling, James; Farrer, Lindsay; Kranzler, Henry R

    2011-10-01

    Antisocial personality disorder (ASPD) frequently co-occurs with substance dependence (SD). A functional polymorphism (5-HTTLPR) in the serotonin transporter gene has been widely studied as a risk factor for a variety of psychopathologic conditions including aggressive/violent behavior. Childhood abuse is an important predictor of ASPD. We examined 5-HTTLPR genotype and adverse childhood events (ACEs) as risk factors for ASPD in a SD sample. Study participants [602 European-Americans (EAs) and 779 African-Americans (AAs)] were interviewed to obtain lifetime diagnoses of ASPD and SD and information on ACEs. Triallelic genotypes for 5-HTTLPR were obtained using standard methods. We used logistic generalized estimating equations regression to examine ACEs and 5-HTTLPR genotype and their interaction as predictors of ASPD, separately by population group. There were 203 (14.7%) participants diagnosed with ASPD. The frequency of the low-activity 5-HTTLPR S' allele did not differ by ASPD diagnosis, and there was no overall 5-HTTLPR×ACE interaction. However, among European-Americans, male sex (odds ratio=3.36; P<0.001) and ACE history (odds ratio=1.47; P=0.002) were significant predictors of ASPD. Among AAs, there was a significant interaction of sex×5-HTTLPR genotype×ACEs (χ=13.92, P<0.001). Among AA men, each additional ACE significantly increased the odds of ASPD irrespective of genotype, whereas among AA women, the effect of ACEs on ASPD was significant only among S' homozygotes. However, these results are limited by the small sample size in each subgroup, (particularly AA women with S'S' genotype; N=7) and require replication. Childhood maltreatment contributes to the risk of ASPD, an effect for which there is preliminary evidence of moderation by 5-HTTLPR genotype in AA women.

  17. 5-HTTLPR as a Potential Moderator of the Effects of Adverse Childhood Experiences on Risk of Antisocial Personality Disorder

    PubMed Central

    Douglas, Kara; Chan, Grace; Gelernter, Joel; Arias, Albert J.; Anton, Raymond F.; Poling, James; Farrer, Lindsay; Kranzler, Henry R.

    2011-01-01

    INTRODUCTION Antisocial personality disorder (ASPD) frequently co-occurs with substance dependence (SD). A functional polymorphism (5-HTTLPR) in the serotonin transporter gene has been widely studied as a risk factor for a variety of psychopathologic conditions, including aggressive/violent behavior. Childhood abuse is an important predictor of ASPD. We examined 5-HTTLPR genotype and adverse childhood events (ACEs) as risk factors for ASPD in a SD sample. METHOD Study participants [602 European Americans (EAs) and 779 African Americans (AAs)] were interviewed to obtain lifetime diagnoses of ASPD and SD and information on ACEs. Tri-allelic genotypes for 5-HTTLPR were obtained using standard methods. We used logistic generalized estimating equations (GEE) regression to examine ACEs and 5-HTTLPR genotype and their interaction as predictors of ASPD, separately by population group. RESULTS There were 203 (14.7%) participants diagnosed with ASPD. The frequency of the low-activity 5-HTTLPR S’ allele did not differ by ASPD diagnosis, and there was no overall 5-HTTLPR × ACE interaction. However, among EAs, male sex (OR=3.36; p<0.001) and ACE history (OR=1.47; p=0.002) were significant predictors of ASPD. Among AAs, there was a significant interaction of sex × 5-HTTLPR genotype × ACEs (χ2=13.92, p<0.001). Among AA men, each additional ACE significantly increased the odds of ASPD irrespective of genotype, while among AA women, the effect of ACEs on ASPD was significant only among S’ homozygotes. However, these results are limited by the small sample size in each subgroup, (particularly AA women with S’S’ genotype; N=7) and require replication. CONCLUSIONS Childhood maltreatment contributes to the risk of antisocial personality disorder, an effect for which there is preliminary evidence of moderation by 5-HTTLPR genotype in AA women. PMID:21399568

  18. Acoustic Detection of Neutrinos: Review and Future Potential

    NASA Astrophysics Data System (ADS)

    Lahmann, Robert

    2016-04-01

    The acoustic neutrino detection technique is a promising approach for future large-scale detectors with the aim of measuring the small expected flux of cosmogenic neutrinos at energies exceeding 100 PeV. The technique is based on the thermo-acoustic model, which implies that the energy deposition by a particle cascade-resulting from a neutrino interaction in a medium with suitable thermal and acoustic properties-leads to a local heating and a subsequent characteristic pressure pulse that propagates in the surrounding medium. The main advantage of using sound for the detection of neutrino interactions, as opposed to Cherenkov light, lies in the much longer attenuation length of the former type of radiation: several kilometres for sound compared to several ten metres for light in the respective frequency ranges of interest in sea water. As detection media for future detectors, water, ice, salt domes and permafrost have been discussed, but it is the first two which have been investigated most thoroughly by using existing arrays of acoustic receivers-mainly military arrays in various bodies of water-or by implementing dedicated acoustic arrays in Cherenkov neutrino telescopes. Such arrays have been installed in IceCube at the South Pole, in the Lake Baikal experiment in Siberia and in ANTARES and the former NEMO experiment in the Mediterranean Sea. The future KM3NeT neutrino telescope to be installed in the Mediterranean Sea will be equipped with acoustic sensors for position calibration that are suited to also serve acoustic detection purposes. Ongoing experiments in water and ice have established the feasibility of the acoustic neutrino detection technique and allowed for the investigation of prevailing background conditions. Methods to improve the signal detection efficiency and to reduce the rate of misidentified neutrinos have been devised and potential future large-scale detector designs are investigated using detailed simulations in combination with the wealth

  19. Communication of ALS Patients by Detecting Event-Related Potential

    NASA Astrophysics Data System (ADS)

    Kanou, Naoyuki; Sakuma, Kenji; Nakashima, Kenji

    Amyotrophic Lateral Sclerosis(ALS) patients are unable to successfully communicate their desires, although their mental capacity is the same as non-affected persons. Therefore, the authors put emphasis on Event-Related Potential(ERP) which elicits the highest outcome for the target visual and hearing stimuli. P300 is one component of ERP. It is positive potential that is elicited when the subject focuses attention on stimuli that appears infrequently. In this paper, the authors focused on P200 and N200 components, in addition to P300, for their great improvement in the rate of correct judgment in the target word-specific experiment. Hence the authors propose the algorithm that specifies target words by detecting these three components. Ten healthy subjects and ALS patient underwent the experiment in which a target word out of five words, was specified by this algorithm. The rates of correct judgment in nine of ten healthy subjects were more than 90.0%. The highest rate was 99.7%. The highest rate of ALS patient was 100.0%. Through these results, the authors found the possibility that ALS patients could communicate with surrounding persons by detecting ERP(P200, N200 and P300) as their desire.

  20. Spatial Repolarization Heterogeneity Detected by Magnetocardiography Correlates with Cardiac Iron Overload and Adverse Cardiac Events in Beta-Thalassemia Major

    PubMed Central

    Chen, Chun-An; Lu, Meng-Yao; Peng, Shinn-Forng; Lin, Kai-Hsin; Chang, Hsiu-Hao; Yang, Yung-Li; Jou, Shiann-Tarng; Lin, Dong-Tsamn; Liu, Yen-Bin; Horng, Herng-Er; Yang, Hong-Chang; Wang, Jou-Kou; Wu, Mei-Hwan; Wu, Chau-Chung

    2014-01-01

    Background Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. Methods and Results Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = −0.609, p<0.001), SD-QTc (r = −0.572, p<0.001), and QTc dispersion (r = −0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. Conclusions Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events. PMID:24475137

  1. Adverse influence on reproduction and potential fitness cost in survivors of orthene-treated tarnished plant bug, Lygus lineolaris

    USDA-ARS?s Scientific Manuscript database

    By using dose response to Orthene at 80 mg/L (LC50 of the laboratory susceptible colony), a relative resistant population (71% survival rate) of the tarnished plant bug, Lygus lineolaris, was located near Tillar, Arkansas. This population was used in this study to evaluate potential fitness cost in ...

  2. Modern maize hybrids in Northeast China exhibit increased yield potential and resource use efficiency despite adverse climate change.

    PubMed

    Chen, Xiaochao; Chen, Fanjun; Chen, Yanling; Gao, Qiang; Yang, Xiaoli; Yuan, Lixing; Zhang, Fusuo; Mi, Guohua

    2013-03-01

    The impact of global changes on food security is of serious concern. Breeding novel crop cultivars adaptable to climate change is one potential solution, but this approach requires an understanding of complex adaptive traits for climate-change conditions. In this study, plant growth, nitrogen (N) uptake, and yield in relation to climatic resource use efficiency of nine representative maize cultivars released between 1973 and 2000 in China were investigated in a 2-year field experiment under three N applications. The Hybrid-Maize model was used to simulate maize yield potential in the period from 1973 to 2011. During the past four decades, the total thermal time (growing degree days) increased whereas the total precipitation and sunshine hours decreased. This climate change led to a reduction of maize potential yield by an average of 12.9% across different hybrids. However, the potential yield of individual hybrids increased by 118.5 kg ha(-1)  yr(-1) with increasing year of release. From 1973 to 2000, the use efficiency of sunshine hours, thermal time, and precipitation resources increased by 37%, 40%, and 41%, respectively. The late developed hybrids showed less reduction in yield potential in current climate conditions than old cultivars, indicating some adaptation to new conditions. Since the mid-1990s, however, the yield impact of climate change exhibited little change, and even a slight worsening for new cultivars. Modern breeding increased ear fertility and grain-filling rate, and delayed leaf senescence without modification in net photosynthetic rate. The trade-off associated with delayed leaf senescence was decreased grain N concentration rather than increased plant N uptake, therefore N agronomic efficiency increased simultaneously. It is concluded that modern maize hybrids tolerate the climatic changes mainly by constitutively optimizing plant productivity. Maize breeding programs in the future should pay more attention to cope with the limiting

  3. Adverse childhood experiences (ACEs) and later-life depression: perceived social support as a potential protective factor.

    PubMed

    Cheong, E Von; Sinnott, Carol; Dahly, Darren; Kearney, Patricia M

    2017-09-01

    To investigate associations between adverse childhood experiences (ACEs) and later-life depressive symptoms; and to explore whether perceived social support (PSS) moderates these. We analysed baseline data from the Mitchelstown (Ireland) 2010-2011 cohort of 2047 men and women aged 50-69 years. Self-reported measures included ACEs (Centre for Disease Control ACE questionnaire), PSS (Oslo Social Support Scale) and depressive symptoms (CES-D). The primary exposure was self-report of at least one ACE. We also investigated the effects of ACE exposure by ACE scores and ACE subtypes abuse, neglect and household dysfunction. Associations between each of these exposures and depressive symptoms were estimated using logistic regression, adjusted for socio-demographic factors. We tested whether the estimated associations varied across levels of PSS (poor, moderate and strong). 23.7% of participants reported at least one ACE (95% CI 21.9% to 25.6%). ACE exposures (overall, subtype or ACE scores) were associated with a higher odds of depressive symptoms, but only among individuals with poor PSS. Exposure to any ACE (vs none) was associated with almost three times the odds of depressive symptoms (adjusted OR 2.85; 95% CI 1.64 to 4.95) among individuals reporting poor PSS, while among those reporting moderate and strong PSS, the adjusted ORs were 2.21 (95% CI 1.52 to 3.22) and 1.39 (95% CI 0.85 to 2.29), respectively. This pattern of results was similar when exposures were based on ACE subtype and ACE scores, though the interaction was clearly strongest among those reporting abuse. ACEs are common among older adults in Ireland and are associated with higher odds of later-life depressive symptoms, particularly among those with poor PSS. Interventions that enhance social support, or possibly perceptions of social support, may help reduce the burden of depression in older populations with ACE exposure, particularly in those reporting abuse. © Article author(s) (or their employer

  4. Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital

    PubMed Central

    Alvim, Mariana Macedo; da Silva, Lidiane Ayres; Leite, Isabel Cristina Gonçalves; Silvério, Marcelo Silva

    2015-01-01

    Objective To evaluate the incidence of potential drug-drug interactions in an intensive care unit of a hospital, focusing on antimicrobial drugs. Methods This cross-sectional study analyzed electronic prescriptions of patients admitted to the intensive care unit of a teaching hospital between January 1 and March 31, 2014 and assessed potential drug-drug interactions associated with antimicrobial drugs. Antimicrobial drug consumption levels were expressed in daily doses per 100 patient-days. The search and classification of the interactions were based on the Micromedex® system. Results The daily prescriptions of 82 patients were analyzed, totaling 656 prescriptions. Antimicrobial drugs represented 25% of all prescription drugs, with meropenem, vancomycin and ceftriaxone being the most prescribed medications. According to the approach of daily dose per 100 patient-days, the most commonly used antimicrobial drugs were cefepime, meropenem, sulfamethoxazole + trimethoprim and ciprofloxacin. The mean number of interactions per patient was 2.6. Among the interactions, 51% were classified as contraindicated or significantly severe. Highly significant interactions (clinical value 1 and 2) were observed with a prevalence of 98%. Conclusion The current study demonstrated that antimicrobial drugs are frequently prescribed in intensive care units and present a very high number of potential drug-drug interactions, with most of them being considered highly significant. PMID:26761473

  5. Earliest detection of magma movements by measuring transient streaming potential

    NASA Astrophysics Data System (ADS)

    Fujinawa, Yukio; Matsumoto, Takumi; Iitaka, Hiroshi; Takahashi, Kozo; Nakano, Hiroshi; Doi, Takuya; Saito, Toshiyuki; Kasai, Naoko; Sato, Sohjun

    Volcanic eruptions are generally preceded by magma intrusion. Volcanic forecasting is sure to make considerable progress if we have a practical means to detect magma movements. Electric potential variations have been observed since April 1999 at Miyake Island, a volcanic island in Japan. Measurements have been conducted by a special long vertical antenna using a steel casing pipe and a short horizontal dipole. Beginning about half a day before as well as at the time period of the largest eruption in 2000 of Miyake-jima volcano on August 18, 2000, conspicuous electric field variations were observed on the horizontal and vertical components in the frequency bands of DC, ULF and ELF/VLF. And several types of anomalies were found to occur in association with different stage of volcanic activities. We suggest that transient self-potential variations are induced by confined ground water pressure fluctuations through interaction between intruding magma and hydrothermal circulation through electro-kinetic effect. Subsurface transient self-potential measurement has been suggested to be useful means for monitoring volcanic eruption and to provide an efficient window for looking into modification of hydrothermal circulation induced by the volcanic activity.

  6. First Indian study evaluating role of biochemical investigations and diagnostic tools in detection of adverse drug reactions.

    PubMed

    Tandon, Vishal R; Khajuria, Vijay; Raina, Kapila; Mahajan, Vivek; Sharma, Aman; Gillani, Zahid

    2014-09-01

    To evaluate the role of biochemical investigations (BI) and diagnostic tools (DT) in ADR detection. An observational prospective cross-sectional study was done using suspected ADR data collection form. A total of 2381 ADR related events were recorded in two years. Total number/percentage of biochemical abnormalities (BA) related ADR detection rate was 14.57% and of DT was 1.091% in contrast to 84.33% recorded with clinical presentation. Maximum cases were inward patients (87.13%), 67.02% were recorded by active surveillance. ADR detection rate at one point & detection on follow up was 56.31% Vs 46.38%. ADR detection rate of ECG, endoscopy, X-ray were 0.57%, 0.22%, 0.22% and of CT scan, MRI, DEXA scan, USG and biopsy was 0.04% each. Maximum ADRs were severe/serious, latent and Type-A in nature. Anemia (4.6%), followed by liver dysfunction (2.8%), renal dysfunction, electrolyte imbalance, hyperglycemia (1.1% each), abnormal coagulation profile (1%), decrease platelet count (0.8%), hypoglycemia (0.7%) were the most common BAs. Anti retroviral drugs (ART), tirofiban and methotrexate accounted for anemia, ART and anti tubercular drugs for liver & renal dysfunction, insulin for hypoglycemia, tirofiban, paclitaxel, capecipabine and ifosfamide for thrombocytopenia, hematuria by enoxaparin & dyslipidemia with ART were common ADRs. BI and DT can play very important role in ADR detection.

  7. Monitoring for potential adverse effects of prenatal gene therapy: mouse models for developmental aberrations and inadvertent germ line transmission.

    PubMed

    Coutelle, Charles; Waddington, Simon N; Themis, Michael

    2012-01-01

    So far no systematic studies have been conducted to investigate developmental aberrations after prenatal gene transfer in mice. Here, we suggest procedures for such observations to be applied, tested and improved in further in utero gene therapy experiments. They are based on our own experience in husbandry for transgenic human diseases mouse models and breading, rearing, and observing mice after fetal gene transfer as well as on the systematic screens for monitoring of knock-out mutant mouse phenotypes established in international mutagenesis projects (EUMORPHIA and EUMODIC and subsequently the International Mouse Phenotyping Consortium). We also describe here the analysis procedures for detection of germ line mutations based on quantitative PCR (qPCR) by sperm-DNA analysis and breeding studies.

  8. Non-toxic fluorescent phosphonium probes to detect mitochondrial potential

    NASA Astrophysics Data System (ADS)

    Šarić, Ana; Crnolatac, Ivo; Bouillaud, Frédéric; Sobočanec, Sandra; Mikecin, Ana-Matea; Mačak Šafranko, Željka; Delgeorgiev, Todor; Piantanida, Ivo; Balog, Tihomir; Petit, Patrice X.

    2017-03-01

    We evaluated our phosphonium-based fluorescent probes for selective staining of mitochondria. Currently used probes for monitoring mitochondrial membrane potential show varying degrees of interference with cell metabolism, photo-induced damage and probe binding. Here presented probes are characterised by highly efficient cellular uptake and specific accumulation in mitochondria. Fluorescent detection of the probes was accomplished using flow cytometry and confocal microscopy imaging of yeast and mammalian cells. Toxicity analysis (impedimetry—xCELLigence for the cellular proliferation and Seahorse technology for respiratory properties) confirms that these dyes exhibit no-toxicity on mitochondrial or cellular functioning even for long time incubation. The excellent chemical and photophysical stability of the dyes makes them promising leads toward improved fluorescent probes. Therefore, the probes described here offer to circumvent the problems associated with existing-probe’s limitations.

  9. Detecting Drug Interactions From Adverse-Event Reports: Interaction Between Paroxetine and Pravastatin Increases Blood Glucose Levels

    PubMed Central

    Tatonetti, NP; Denny, JC; Murphy, SN; Fernald, GH; Krishnan, G; Castro, V; Yue, P; Tsau, PS; Kohane, I; Roden, DM; Altman, RB

    2011-01-01

    The lipid-lowering agent pravastatin and the antidepressant paroxetine are among the most widely prescribed drugs in the world. Unexpected interactions between them could have important public health implications. We mined the US Food and Drug Administration’s (FDA’s) Adverse Event Reporting System (AERS) for side-effect profiles involving glucose homeostasis and found a surprisingly strong signal for comedication with pravastatin and paroxetine. We retrospectively evaluated changes in blood glucose in 104 patients with diabetes and 135 without diabetes who had received comedication with these two drugs, using data in electronic medical record (EMR) systems of three geographically distinct sites. We assessed the mean random blood glucose levels before and after treatment with the drugs. We found that pravastatin and paroxetine, when administered together, had a synergistic effect on blood glucose. The average increase was 19 mg/dl (1.0 mmol/l) overall, and in those with diabetes it was 48 mg/dl (2.7 mmol/l). In contrast, neither drug administered singly was associated with such changes in glucose levels. An increase in glucose levels is not a general effect of combined therapy with selective serotonin reuptake inhibitors (SSRIs) and statins. PMID:21613990

  10. Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

    PubMed Central

    Brown, Jeffrey S.; Petronis, Kenneth R.; Bate, Andrew; Zhang, Fang; Dashevsky, Inna; Kulldorff, Martin; Avery, Taliser R.; Davis, Robert L.; Chan, K. Arnold; Andrade, Susan E.; Boudreau, Denise; Gunter, Margaret J.; Herrinton, Lisa; Pawloski, Pamala A.; Raebel, Marsha A.; Roblin, Douglas; Smith, David; Reynolds, Robert

    2013-01-01

    Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds. PMID:24300404

  11. Laser photoacoustic trace detection of C2H4 revealing adverse environmental effects of atmospheric pollution on plant material

    NASA Astrophysics Data System (ADS)

    Harren, Frans J. M.; Petruzzelli, Luciana

    1993-03-01

    The photoacoustic detection method for trace gases in the atmosphere is well developed towards very low limits of detection, in the last years. Due to the combination of a sensitive photoacoustic cell placed intracavity in an infrared CO2 laser we were able to detect C2H4 at ultralow (< 1:1011) concentrations within 10 seconds, C2H4 in a plant hormone which seems to play an important role throughout all the life stages of a plant, including seed germination. In addition, various types of stress have been reported to promote ethylene production from different plant tissues. As part of our ongoing research on the role of ethylene in seed germination, we have compared our laser photoacoustic set-up to a gaschromatograph for measuring C2H4 produced by germinating Pisum sativum L. seeds within the first days of imbibition. C2H4 evolution by intact seeds shows a maximum at about 25 hours of germination. Thereafter, the rate of ethylene measured by gaschromatograph continues to decrease while that measured by the laser-driven photoacoustic system shows further increases. Most of the ethylene produced by seeds is found in isolated embryonic axes. The fumigation with ozone affects the growth of seedlings and their ethylene evolution.

  12. Distinguishing hazards and harms, adverse drug effects and adverse drug reactions : implications for drug development, clinical trials, pharmacovigilance, biomarkers, and monitoring.

    PubMed

    Aronson, Jeffrey K

    2013-03-01

    The terms 'adverse drug effects' and 'adverse drug reactions' are commonly used interchangeably, but they have different implications. Adverse drug reactions arise when a compound (e.g. a drug or metabolite, a contaminant or adulterant) is distributed in the same place as a body tissue (e.g. a receptor, enzyme, or ion channel), and the encounter results in an adverse effect (a physiological or pathological change), which results in a clinically appreciable adverse reaction. Both the adverse effect and the adverse reaction have manifestations by which they can be recognized: adverse effects are usually detected by laboratory tests (e.g. biochemical, haematological, immunological, radiological, pathological) or by clinical investigations (e.g. endoscopy, cardiac catheterization), and adverse reactions by their clinical manifestations (symptoms and/or signs). This distinction suggests five scenarios: (i) adverse reactions can result directly from adverse effects; (ii) adverse effects may not lead to appreciable adverse reactions; (iii) adverse reactions can occur without preceding adverse effects; (iv) adverse effects and reactions may be dissociated; and (v) adverse effects and reactions can together constitute syndromes. Defining an adverse drug reaction as "an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product" suggests a definition of an adverse drug effect: "a potentially harmful effect resulting from an intervention related to the use of a medicinal product, which constitutes a hazard and may or may not be associated with a clinically appreciable adverse reaction and/or an abnormal laboratory test or clinical investigation, as a marker of an adverse reaction."

  13. Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

    PubMed

    Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

    2017-06-06

    Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

  14. Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

    PubMed

    Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

    2017-06-15

    The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems

  15. A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions

    PubMed Central

    Rosenberg, Yvonne J.; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

    2015-01-01

    Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1–2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product. PMID:26268538

  16. A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

    PubMed

    Rosenberg, Yvonne J; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

    2015-08-13

    Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.

  17. "Prepandemic" immunization for novel influenza viruses, "swine flu" vaccine, Guillain-Barré syndrome, and the detection of rare severe adverse events.

    PubMed

    Evans, David; Cauchemez, Simon; Hayden, Frederick G

    2009-08-01

    The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against "swine" influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or "priming" of populations in the so-called "prepandemic" (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against "swine flu" and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.

  18. Public health intelligence and the detection of potential pandemics.

    PubMed

    French, Martin; Mykhalovskiy, Eric

    2013-02-01

    This article considers contemporary developments in public health intelligence (PHI), especially their focus on health events of pandemic potential. It argues that the sociological study of PHI can yield important insights for the sociology of pandemics. PHI aims to detect health events as (or even before) they unfold. Whilst its apparatuses envelope traditional public health activities, such as epidemiological surveillance, they increasingly extend to non-traditional public health activities such as data-mining in electronically mediated social networks. With a focus on non-traditional PHI activities, the article first situates the study of PHI in relation to the sociology of public health. It then discusses the conceptualisation and actualisation of pandemics, reflecting on how public health professionals and organisations must equip themselves with diverse allies in order to realise the claims they make about pandemic phenomena. Finally, using the analytic tools of actor-network theory, sites for future empirical research that can contribute to the sociology of pandemics are suggested. © 2012 The Authors. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

  19. Imaging atlas for eligibility and on-study safety of potential shoulder adverse events in anti-NGF studies (Part 3).

    PubMed

    Roemer, F W; Hayes, C W; Miller, C G; Hoover, K; Guermazi, A

    2015-01-01

    Despite promising results, the U.S. Food and Drug Administration (FDA) put on hold trials assessing anti-nerve growth factor (a-NGF) compounds due to concerns over accelerated rates of OA progression. The mechanism of these events is unclear but joint adverse events were observed particularly in patients using a-NGFs in combination with non-steroidal anti-inflammatory drugs (NSAIDs), suggesting that the significantly greater analgesic effect of these separate classes of drugs prompted patients to permit increased joint load without experiencing the usual pain that would limit joint stress. Development of a-NGF drugs is continuing with stringent safety criteria included in future trials as a-NGF therapies offer potential as the first new class of analgesics in many years. Potential imaging joint safety findings and exclusionary criteria for eligibility for the large weight bearing joints were presented in parts I and II of this atlas. The shoulder as a non-weight bearing joint is likely to be less affected by increased loading due to efficacious pain reduction. However, it remains prone to degeneration especially due to concomitant rotator cuff pathology and previous trauma and inflammatory disorders. This third part of the atlas illustrates imaging findings relevant for eligibility and potential joint safety findings such as osteonecrosis, incidental findings such as large cystic lesions, inflammatory disorders, bone marrow disorders and metastases.

  20. Vestibular Evoked Myogenic Potentials (VEMP) Can Detect Asymptomatic Saccular Hydrops

    PubMed Central

    Lin, Ming-Yee; Timmer, Ferdinand C. A.; Oriel, Brad S.; Zhou, Guangwei; Guinan, John J.; Kujawa, Sharon G.; Herrmann, Barbara S.; Merchant, Saumil N.; Rauch, Steven D.

    2009-01-01

    Objective The objective of this study was to explore the useful of vestibular evoked myogenic potential (VEMP) testing for detecting endolymphatic hydrops, especially in the second ear of patients with unilateral Ménière disease (MD). Methods This study was performed at a tertiary care academic medical center. Part I consisted of postmortem temporal bone specimens from the temporal bone collection of the Massachusetts Eye & Ear Infirmary; part II consisted of consecutive consenting adult patients (n = 82) with unilateral MD by American Academy of Otolaryngology–Head and Neck Surgery criteria case histories. Out-come measures consisted of VEMP thresholds in patients and histologic saccular endolymphatic hydrops in postmortem temporal bones. Results Saccular hydrops was observed in the asymptomatic ear in six of 17 (35%) of temporal bones from donors with unilateral MD. Clinic patients with unilateral MD showed elevated mean VEMP thresholds and altered VEMP tuning in their symptomatic ears and, to a lesser degree, in their asymptomatic ears. Specific VEMP frequency and tuning criteria were used to define a “Ménière-like” response. This “Ménière-like” response was seen in 27% of asymptomatic ears of our patients with unilateral MD. Conclusions Bilateral involvement is seen in approximately one third of MD cases. Saccular hydrops appears to precede symptoms in bilateral MD. Changes in VEMP threshold and tuning appear to be sensitive to these structural changes in the saccule. If so, then VEMP may be useful as a detector of asymptomatic saccular hydrops and as a predictor of evolving bilateral MD. PMID:16735912

  1. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey.

    PubMed

    Bush, Thomas M; Rayburn, Keith S; Holloway, Sandra W; Sanchez-Yamamoto, Deanna S; Allen, Blaine L; Lam, Tiffany; So, Brian K; Tran, De H; Greyber, Elizabeth R; Kantor, Sophia; Roth, Larry W

    2007-01-01

    Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. The rate of potential and observed adverse herb-drug interactions. Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications.

  2. Identification and prevalence of adverse drug events caused by potentially inappropriate medication in homebound elderly patients: a retrospective study using a nationwide survey in Japan

    PubMed Central

    Onda, Mitsuko; Imai, Hirohisa; Takada, Yurina; Fujii, Shingo; Shono, Takako; Nanaumi, Yoko

    2015-01-01

    Objectives A nationwide large-scale survey was conducted to identify the prevalence and causal medications of adverse drug events (ADEs) that are caused by potentially inappropriate medications (PIMs) given to homebound elderly patients, factors associated with ADEs, and measures taken by pharmacists to manage ADEs and their effects on ADEs. Settings A questionnaire was mailed to 3321 pharmacies nationwide. It asked about the details of PIMs and ADEs of up to 5 patients for whom home visits were provided by a pharmacist. Questionnaire forms were filled in by pharmacists who visited the patients. Design and participants Between 23 January and 13 February 2013, comprehensive assessment forms were sent to 3321 pharmacies. Data collected from 1890 pharmacies including data of 4815 patients were analysed and 28 patients of unknown sex were excluded. Their average age was 82.7 years. PIMs were identified based on the 2003 Beers Criteria Japan. Results There were 600 patients who did not provide valid answers regarding the medications. In the remaining 4243 patients, one or more medications that were considered to be PIMs had been prescribed to 48.4% of patients. PIM-induced ADEs were found in 8% of these patients by pharmacists during home visits. The top ADE-inducing medications were strong anticholinergic antihistamines, benzodiazepines, sulpiride and digoxin. The most common ADEs associated with benzodiazepines were frequent lightheadedness, somnolence and sleepiness, which increase the risk of falls and subsequent fractures in elderly patients. The following factors associated with ADEs were identified: sex, pharmacist awareness of prescription issues, frequency of visits and time spent at patients’ homes, and the frequency of detailed checks for patient adverse reactions by pharmacists. Conclusions The PIM prevalence associated with home healthcare in Japan was relatively high, as reported in previous studies. The present study suggests that pharmacists could

  3. Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality.

    PubMed

    Necyk, Candace; Tsuyuki, Ross T; Boon, Heather; Foster, Brian C; Legatt, Don; Cembrowski, George; Murty, Mano; Barnes, Joanne; Charrois, Theresa L; Arnason, John T; Ware, Mark A; Rosychuk, Rhonda J; Vohra, Sunita

    2014-03-28

    To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Cross-sectional study of screened patients. 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011. The participating pharmacy staff screened consecutive patients, or agents of patients, who were dropping or picking up prescription medications. Patients were screened to determine the proportions of them using prescription drugs and/or NHPs, as well as their respective AE rates. All AEs reported by the screened patients who took a NHP, consented to, and were available for, a detailed telephone interview (14%) were adjudicated fully to assess for causality. Over a total of 105 pharmacy weeks and 1118 patients screened, 410 patients reported taking prescription drugs only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI 2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE, representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3% (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients who reported using prescription drugs, the patients who reported using prescription drugs and NHPs concurrently were 6.4 times more likely to experience an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario, Canada, a national proportion was calculated, which found that 45.4% (95% CI 43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report an AE. A substantial proportion of community pharmacy patients use prescription drugs and NHPs concurrently; these patients are at a greater risk of experiencing an AE. Active surveillance provides a means of

  4. Pharmacy study of natural health product adverse reactions (SONAR): a cross-sectional study using active surveillance in community pharmacies to detect adverse events associated with natural health products and assess causality

    PubMed Central

    Necyk, Candace; Tsuyuki, Ross T; Boon, Heather; Foster, Brian C; LeGatt, Don; Cembrowski, George; Murty, Mano; Barnes, Joanne; Charrois, Theresa L; Arnason, John T; Ware, Mark A; Rosychuk, Rhonda J; Vohra, Sunita

    2014-01-01

    Objectives To investigate the rates and causality of adverse event(s) (AE) associated with natural health product (NHP) use, prescription drug use and concurrent NHP-drug use through active surveillance in community pharmacies. Design Cross-sectional study of screened patients. Setting 10 community pharmacies across Alberta and British Columbia, Canada from 14 January to 30 July 2011. Participants The participating pharmacy staff screened consecutive patients, or agents of patients, who were dropping or picking up prescription medications. Primary outcome measures Patients were screened to determine the proportions of them using prescription drugs and/or NHPs, as well as their respective AE rates. All AEs reported by the screened patients who took a NHP, consented to, and were available for, a detailed telephone interview (14%) were adjudicated fully to assess for causality. Results Over a total of 105 pharmacy weeks and 1118 patients screened, 410 patients reported taking prescription drugs only (36.7%; 95% CI 33.9% to 39.5%), 37 reported taking NHPs only (3.3%; 95% CI 2.4% to 4.5%) and 657 reported taking prescription drugs and NHPs concurrently (58.8%; 95% CI 55.9% to 61.6%). In total, 54 patients reported an AE, representing 1.2% (95% CI 0.51% to 2.9%), 2.7% (95% CI 0.4% to 16.9%) and 7.3% (95% CI 5.6% to 9.6%) of each population, respectively. Compared with patients who reported using prescription drugs, the patients who reported using prescription drugs and NHPs concurrently were 6.4 times more likely to experience an AE (OR; 95% CI 2.52 to 16.17; p<0.001). Combined with data from Ontario, Canada, a national proportion was calculated, which found that 45.4% (95% CI 43.8% to 47.0%) of Canadians who visit community pharmacies take NHPs and prescription drugs concurrently, and of those, 7.4% (95% CI 6.3% to 8.8%) report an AE. Conclusions A substantial proportion of community pharmacy patients use prescription drugs and NHPs concurrently; these patients are at a

  5. Potential adverse health effects of persistent organic pollutants on sea turtles: evidences from a cross-sectional study on Cape Verde loggerhead sea turtles.

    PubMed

    Camacho, María; Luzardo, Octavio P; Boada, Luis D; López Jurado, Luis F; Medina, María; Zumbado, Manuel; Orós, Jorge

    2013-08-01

    The Cape Verde nesting population of loggerhead sea turtles (Caretta caretta) is the third largest population of this species in the world. For conservation purposes, it is essential to determine how these reptiles respond to different types of anthropogenic contaminants. We evaluated the presence of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) in the plasma of adult nesting loggerheads from Boa Vista Island, Cape Verde, and studied the effects of the contaminants on the health status of the turtles using hematological and biochemical parameters. All turtles had detectable levels of non-dioxin like PCBs, whereas dioxin-like congeners (DL-PCBs) were detected in only 30% of the turtles. Packed cell volume decreased with higher concentrations of PCBs, which suggests that PCB exposure could result in anemia in sea turtles. In addition, a negative association between some OCPs and white blood cells (WBC) and thrombocyte estimate was noted. The DDT-metabolite, p,p'-DDE was negatively correlated with the Na/K ratio and, additionally, a number of correlations between certain PAHs and electrolyte balances were found, which suggest that exposure to these environmental contaminants could affect the kidneys and salt glands in sea turtles. Additionally, several correlations were observed between these environmental pollutants (OCPs and PAHs) and enzyme activity (GGT, ALT, ALP and amylase) and serum protein levels, pointing to the possibility that these contaminants could induce adverse metabolic effects in sea turtles. Our results indicate that anthropogenic pollutants are present in the Cape Verde loggerhead turtle nesting population and could exert negative effects on several health parameters. Because of the importance of this loggerhead nesting population, protective regulations at national and international levels as well as international action are necessary for assuring the conservation of this population.

  6. Detectability of Potentially Entrained Microorganisms at the Surface of Europa

    NASA Technical Reports Server (NTRS)

    Dalton, J. B.

    2002-01-01

    New spectral measurements of bacteria taken at cryogenic temperatures provide insights on the surface composition of Europa as well as the detectability of microbes on the surface. Additional information is contained in the original extended abstract.

  7. Detectability of Potentially Entrained Microorganisms at the Surface of Europa

    NASA Technical Reports Server (NTRS)

    Dalton, J. B.

    2002-01-01

    New spectral measurements of bacteria taken at cryogenic temperatures provide insights on the surface composition of Europa as well as the detectability of microbes on the surface. Additional information is contained in the original extended abstract.

  8. Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions

    PubMed Central

    Chase, Herbert

    2016-01-01

    Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs. PMID:27716785

  9. Adverse Events Detection Through Global Trigger Tool Methodology: Results From a 5-Year Study in an Italian Hospital and Opportunities to Improve Interrater Reliability.

    PubMed

    Mortaro, Alberto; Moretti, Francesca; Pascu, Diana; Tessari, Lorella; Tardivo, Stefano; Pancheri, Serena; Marta, Garon; Romano, Gabriele; Mazzi, Mariangela; Montresor, Paolo; Naessens, James M

    2017-06-09

    Global Trigger Tool (GTT) has been proposed as a low-cost method to detect adverse events (AEs). The validity of the methodology has been questioned because of moderate interrater agreement. Continuous training has been suggested as a means to improve consistency over time. We present the main findings of the implementation of the Italian version of the GTT and evaluate efforts to improve the interrater reliability over time. The Italian version of the GTT was developed and implemented at the San Bonifacio Hospital, a 270-bed secondary care acute hospital in Verona, Italy. Ten clinical records randomly selected every 2 weeks were reviewed from 2009 to 2014. Two-stage interrater reliability assessment between team members was conducted on 2 subsamples of 50 clinical records before and after the implementation of specific review rules and staff training. Among 1320 medical records reviewed, a total of 366 AEs were found with at least 1 AE on 20.2% of all discharges, 27.7 AEs/100 admissions, and 30.6 AEs/1000 patient-days. Adverse events with harm score E and F were respectively 58.2% (n = 213) and 38.8% (n = 142). First round interrater reliability was comparable with other international studies. The interrater agreement improved significantly after intervention (κ interrater I = 0.52, κ interrater II = 0.80, P < 0.001). Despite the improvements in the interrater consistency, overall results did not show any significant trend in AEs over time. Future studies may be directed to apply and adapt the GTT methodology to more specific settings to explore how to improve its sensitivity.

  10. Potential for portal detection of human chemical and biological contamination

    NASA Astrophysics Data System (ADS)

    Settles, Gary S.; McGann, William J.

    2001-08-01

    The walk-through metal-detection portal is a paradigm of non-intrusive passenger screening in aviation security. Modern explosive detection portals based on this paradigm will soon appear in airports. This paper suggests that the airborne trace detection technology developed for that purpose can also be adapted to human chemical and biological contamination. The waste heat of the human body produces a rising warm-air sheath of 50-80 liters/sec known as the human thermal plume. Contained within this plume are hundreds of bioeffluents from perspiration and breath, and millions of skin flakes. Since early medicine, the airborne human scent was used in the diagnosis of disease. Recent examples also include toxicity and substance abuse, but this approach has never been quantified. The appearance of new bioeffluents or subtle changes in the steady-state may signal the onset of a chemical/biological attack. Portal sampling of the human thermal plume is suggested, followed by a pre-concentration step and the detection of the attacking agent or the early human response. The ability to detect nanogram levels of explosive trace contamination this way was already demonstrated. Key advantages of the portal approach are its rapidity and non-intrusiveness, and the advantage that it does not require the traditional bodily fluid or tissue sampling.

  11. Mycobacterium bovis DNA detection in colostrum as a potential indicator of vaccination effectiveness against bovine tuberculosis.

    PubMed

    Herrera-Rodríguez, Sara E; Gordiano-Hidalgo, María Alejandra; López-Rincón, Gonzálo; Bojorquez-Narváez, Luis; Padilla-Ramírez, Francisco Javier; Pereira-Suárez, Ana Laura; Flores-Valdez, Mario Alberto; Estrada-Chávez, Ciro

    2013-04-01

    Bovine tuberculosis (bTB) remains a problem on many dairy farms in Mexico, as well as a public health risk. We previously found a high frequency of Mycobacterium bovis DNA in colostrum from dairy cows using a nested PCR to detect mpb70. Since there are no reliable in vivo tests to determine the effectiveness of booster Mycobacterium bovis BCG vaccination against bTB, in this work we monitored M. bovis DNA in colostrum by using this nested PCR. In order to decrease the risk of adverse reactions in animals likely containing viable M. bovis, a single application of BCG and a subunit vaccine (EEP-1) formulated with M. bovis culture filtrate proteins (CFP) and a copolymer as the adjuvant was performed in tuberculin skin test-negative cattle (TST(-)), while TST reactor animals (TST(+)) received EEP-1 only. Booster immunization using EEP-1 was applied to both groups, 2 months after primary vaccination to whole herds and 12 months later to lactating cows. Colostrum samples were collected from 6 farms where the cows were vaccinated over a 12-month period postvaccination and, for comparison, from one control farm where the cows were not vaccinated with comparable bTB prevalence. We observed an inverse relationship between the frequency of M. bovis DNA detection and time postvaccination at the first (P < 0.001) and second (P < 0.0001) 6-month periods. Additionally, the concentration of gamma interferon (IFN-γ) was higher in mpb70 PCR-positive colostrum samples (P = 0.0003). These results suggest that M. bovis DNA frequency in colostrum could be a potentially useful biomarker for bTB vaccine efficacy on commercial dairy farms.

  12. Mycobacterium bovis DNA Detection in Colostrum as a Potential Indicator of Vaccination Effectiveness against Bovine Tuberculosis

    PubMed Central

    Herrera-Rodríguez, Sara E.; Gordiano-Hidalgo, María Alejandra; López-Rincón, Gonzálo; Bojorquez-Narváez, Luis; Padilla-Ramírez, Francisco Javier; Pereira-Suárez, Ana Laura; Flores-Valdez, Mario Alberto

    2013-01-01

    Bovine tuberculosis (bTB) remains a problem on many dairy farms in Mexico, as well as a public health risk. We previously found a high frequency of Mycobacterium bovis DNA in colostrum from dairy cows using a nested PCR to detect mpb70. Since there are no reliable in vivo tests to determine the effectiveness of booster Mycobacterium bovis BCG vaccination against bTB, in this work we monitored M. bovis DNA in colostrum by using this nested PCR. In order to decrease the risk of adverse reactions in animals likely containing viable M. bovis, a single application of BCG and a subunit vaccine (EEP-1) formulated with M. bovis culture filtrate proteins (CFP) and a copolymer as the adjuvant was performed in tuberculin skin test-negative cattle (TST−), while TST reactor animals (TST+) received EEP-1 only. Booster immunization using EEP-1 was applied to both groups, 2 months after primary vaccination to whole herds and 12 months later to lactating cows. Colostrum samples were collected from 6 farms where the cows were vaccinated over a 12-month period postvaccination and, for comparison, from one control farm where the cows were not vaccinated with comparable bTB prevalence. We observed an inverse relationship between the frequency of M. bovis DNA detection and time postvaccination at the first (P < 0.001) and second (P < 0.0001) 6-month periods. Additionally, the concentration of gamma interferon (IFN-γ) was higher in mpb70 PCR-positive colostrum samples (P = 0.0003). These results suggest that M. bovis DNA frequency in colostrum could be a potentially useful biomarker for bTB vaccine efficacy on commercial dairy farms. PMID:23425597

  13. Adverse prognostic impact of abnormal lesions detected by genome-wide single nucleotide polymorphism array-based karyotyping analysis in acute myeloid leukemia with normal karyotype.

    PubMed

    Yi, Jun Ho; Huh, Jungwon; Kim, Hee-Jin; Kim, Sun-Hee; Kim, Hyeoung-Joon; Kim, Yeo-Kyeoung; Sohn, Sang Kyun; Moon, Joon Ho; Kim, Sung Hyun; Kim, Kyoung Ha; Won, Jong Ho; Mun, Yeung Chul; Kim, Hawk; Park, Jinny; Jung, Chul Won; Kim, Dong Hwan

    2011-12-10

    This study attempted to analyze the prognostic role of single nucleotide polymorphism array (SNP-A) -based karyotying in 133 patients with acute myeloid leukemia with normal karyotype (AML-NK), which presents with diverse clinical outcomes, thus requiring further stratification of patient subgroups according to their prognoses. A total of 133 patients with AML-NK confirmed by metaphase cytogenetics (MC) and fluorescent in situ hybridization analysis were included in this study. Analysis by Genome-Wide Human SNP 6.0 Array was performed by using DNAs derived from marrow samples at diagnosis. Forty-three patients (32.3%) had at least one abnormal SNP lesion that was not detected by MC. One hundred thirteen abnormal SNP lesions included 55 losses, 23 gains, and 35 copy-neutral losses of heterozygosity. Multivariate analyses showed that detection of abnormal SNP lesions by SNP-A karyotyping results in an unfavorable prognostic value for overall survival (hazard ratio [HR], 2.69; 95% CI, 1.50 to 4.82; P = .001); other significant prognostic factors included secondary AML (HR, 5.55; 95% CI, 1.80 to 17.14; P = .003), presence of the FLT3 mutation (HR, 3.17; 95% CI, 1.71 to 5.87; P < .001), and age (HR, 1.03; 95% CI, 1.01 to 1.05; P = .020). Our data demonstrated that abnormal SNP lesions detected by SNP-A karyotyping might indicate an adverse prognosis in patients with AML-NK, thus requiring a more sophisticated treatment strategy for improvement of treatment outcomes.

  14. Geographical distribution and potential for adverse biological effects of selected trace elements and organic compounds in streambed sediment in the Connecticut, Housatonic, and Thames River basins, 1992-94

    USGS Publications Warehouse

    Breault, Robert F.; Harris, Sandra L.

    1997-01-01

    Streambed-sediment samples were collected in 1992-94 at selected sites in the Connecticut, Housatonic, and Thames River Basins to determine the geographical distribution of trace elements and organic compounds and their potential for adverse biological effects on aquatic organisms. Chromium, copper, lead, mercury, nickel, zinc, chlordane, DDT, PAHs, and PCBs were detected in samples from throughout the basins, but concentrations of these constituents generally were lowest in the northern forested drainage basins and highest in the southern urbanized drainage basins of Springfield, Massachusetts, and Hartford, New Haven and Bridgeport, Connecticut. Possible anthropogenic sources of these contaminants include industrial effluent; municipal wastewater; runoff from agricultural, urban and forested areas; and atmospheric deposition. Some organic compounds pose the greatest threat to biological organisms in terms of exceedances of sediment-quality guidelines; those compounds are present at sufficiently high concentrations to potentially cause severe effects at several locations in the basins.Some trace elements represent the most geographically widespread threat to living organisms. These exceed sediment-quality guidelines over a wider geographical area, although usually by lower ratios of contaminant concentration to sediment-quality guideline than the organic compounds.

  15. Detecting rapid mass movements using electrical self-potential measurements

    NASA Astrophysics Data System (ADS)

    Heinze, Thomas; Limbrock, Jonas; Pudasaini, Shiva P.; Kemna, Andreas

    2017-04-01

    Rapid mass movements are a latent danger for lives and infrastructure in almost any part of the world. Often such mass movements are caused by increasing pore pressure, for example, landslides after heavy rainfall or dam breaking after intrusion of water in the dam. Among several other geophysical methods used to observe water movement, the electrical self-potential method has been applied to a broad range of monitoring studies, especially focusing on volcanism and dam leakage but also during hydraulic fracturing and for earthquake prediction. Electrical self-potential signals may be caused by various mechanisms. Though, the most relevant source of the self-potential field in the given context is the streaming potential, caused by a flowing electrolyte through porous media with electrically charged internal surfaces. So far, existing models focus on monitoring water flow in non-deformable porous media. However, as the self-potential is sensitive to hydraulic parameters of the soil, any change in these parameters will cause an alteration of the electric signal. Mass movement will significantly influence the hydraulic parameters of the solid as well as the pressure field, assuming that fluid movement is faster than the pressure diffusion. We will present results of laboratory experiments under drained and undrained conditions with fluid triggered as well as manually triggered mass movements, monitored with self-potential measurements. For the undrained scenarios, we observe a clear correlation between the mass movements and signals in the electric potential, which clearly differ from the underlying potential variations due to increased saturation and fluid flow. In the drained experiments, we do not observe any measurable change in the electric potential. We therefore assume that change in fluid properties and release of the load causes disturbances in flow and streaming potential. We will discuss results of numerical simulations reproducing the observed effect. Our

  16. Transiting planets with LSST. I. Potential for LSST exoplanet detection

    SciTech Connect

    Lund, Michael B.; Pepper, Joshua; Stassun, Keivan G.

    2015-01-01

    The Large Synoptic Survey Telescope (LSST) is designed to meet several scientific objectives over a 10 year synoptic sky survey. Beyond its primary goals, the large amount of LSST data can be exploited for additional scientific purposes. We show that LSST data are sufficient to detect the transits of exoplanets, including planets orbiting stars that are members of stellar populations that have so far been largely unexplored. Using simulated LSST light curves, we find that existing transit detection algorithms can identify the signatures of Hot Jupiters around solar-type stars, Hot Neptunes around K-dwarfs, and (in favorable cases) Super-Earths in habitable-zone orbits of M-dwarfs. We also find that LSST may identify Hot Jupiters orbiting stars in the Large Magellanic Cloud—a remarkable possibility that would advance exoplanet science into the extragalactic regime.

  17. Detection, Estimation, and Multidimensional Processing of Single Evoked Potentials.

    DTIC Science & Technology

    1985-09-01

    ind,,". 1i Is alo (lsia)c !o odmd nk, the dat a containing thle signal ill the traniisf(:ried (iat ai so that the transform wil - r~iet (livthaIt...vement. ’The b. a vera ged accu racv result.s for detection of the non-target L’s are I) f)7.8(., 18’ X =15 Ilz, Nkit hout frequency transforniat ion, 2

  18. ALMA detection and astrobiological potential of vinyl cyanide on Titan

    PubMed Central

    Palmer, Maureen Y.; Cordiner, Martin A.; Nixon, Conor A.; Charnley, Steven B.; Teanby, Nicholas A.; Kisiel, Zbigniew; Irwin, Patrick G. J.; Mumma, Michael J.

    2017-01-01

    Recent simulations have indicated that vinyl cyanide is the best candidate molecule for the formation of cell membranes/vesicle structures in Titan’s hydrocarbon-rich lakes and seas. Although the existence of vinyl cyanide (C2H3CN) on Titan was previously inferred using Cassini mass spectrometry, a definitive detection has been lacking until now. We report the first spectroscopic detection of vinyl cyanide in Titan’s atmosphere, obtained using archival data from the Atacama Large Millimeter/submillimeter Array (ALMA), collected from February to May 2014. We detect the three strongest rotational lines of C2H3CN in the frequency range of 230 to 232 GHz, each with >4σ confidence. Radiative transfer modeling suggests that most of the C2H3CN emission originates at altitudes of ≳200 km, in agreement with recent photochemical models. The vertical column densities implied by our best-fitting models lie in the range of 3.7 × 1013 to 1.4 × 1014 cm−2. The corresponding production rate of vinyl cyanide and its saturation mole fraction imply the availability of sufficient dissolved material to form ~107 cell membranes/cm3 in Titan’s sea Ligeia Mare. PMID:28782019

  19. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection

    PubMed Central

    2014-01-01

    Background Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. Results The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. Conclusions We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance. PMID:24428898

  20. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    PubMed

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  1. Listeria Occurrence in Poultry Flocks: Detection and Potential Implications

    USDA-ARS?s Scientific Manuscript database

    Foodborne pathogens such as Salmonella, Campylobacter, Escherichia coli, and Listeria are a major concern within the food industry due to their pathogenic potential to cause infection. Of these, Listeria monocytogenes, possesses a high mortality rate (approximately20%) and is considered one of the m...

  2. Mechanisms, detection, and potential management of microcirculatory disturbances in sepsis.

    PubMed

    Mohammed, Imran; Nonas, Stephanie A

    2010-04-01

    Despite improvements in resuscitation and treatment of sepsis, the morbidity and mortality remain unacceptably high. Microvascular dysfunction has been shown to play a significant role in the pathogenesis of sepsis and is a potential new target in the management of sepsis. Clinical studies, aided by new techniques that allow for real-time assessment of the microcirculation, have shown that disturbances in microcirculatory flow are common in sepsis and correlate with worse outcomes. Bedside measurement of microcirculatory perfusion has become simpler and more accessible, and may provide key insights into prognosis in sepsis and guide future therapeutics, much like mean arterial pressure (MAP), lactate, and mixed central oxygen saturation (SvO(2)) do now. The authors review here the role of microcirculatory dysfunction in sepsis and its potential role as a therapeutic target in sepsis.

  3. Thunderstorm detection and warning system atmospheric potential monitor

    NASA Technical Reports Server (NTRS)

    1991-01-01

    An new type of electric field instrumentation was developed for lighting prediction at KSC. Currently, it is being installed at several government laboratories and is being made available to the public. It has important advantages over the previous method for measuring electric fields with motor driven field mills: (1) it has no moving parts and requires little maintenance compared to rotating machinery; (2) it is unaffected by rain, snow, sand, or insects, all of which can influence field mills; and (3) the lightweight sensor can be mounted easily on a tall mast. By mounting the instrumentation on a tall mast the instrumentation is placed above much of the blanket of point discharge ions that are emitted from objects on the ground during thunderstorms. This space charge limits the ability of any ground based electric field sensor to accurately measure cloud electric fields which produce lightning. The elevated mounting was demonstrated to significantly improve monitoring of thunderstorm electric fields. This instrumentation measures the atmospheric potential relative to earth at a corona needle sensor on top of a mast which normally is mounted on a tower or roof. The needle is kept in corona at all times by a low power high voltage power supply. This produces a small cloud of ions around the needle allowing a current to flow. Measurement of the current provides the atmospheric potential. The potential divided by the height of the needle above the ground is proportional to the average electric field between the needle and earth. The potential on top of a tall pole or above a rooftop is more representative of the intensity of cloud electrification than electric field measurements made at ground level. Photographs that depict the computer terminal, video display of a two sensor system, and the individual components installed on a tower are presented.

  4. The potential for very high-frequency gravitational wave detection

    NASA Astrophysics Data System (ADS)

    Cruise, A. M.

    2012-05-01

    The science case for observing gravitational waves at frequencies in the millihertz-kilohertz range using LIGO, VIRGO, GEO600 or LISA is very strong and the first results are expected at these frequencies. However, as gravitational wave astronomy progresses beyond the first detections, other frequency bands may be worth exploring. Early predictions of gravitational wave emission from discrete sources at very much higher frequencies (megahertz and above) have been published and more recent studies of cosmological signals from inflation, Kaluza-Klein modes from gravitational interactions in brane worlds and plasma instabilities surrounding violent astrophysical events, are all possible sources. This communication examines current observational possibilities and the detector technology required to make meaningful observations at these frequencies.

  5. Potential Deaths Averted and Serious Adverse Events Incurred from Adoption of the SPRINT Intensive Blood Pressure Regimen in the U.S.: Projections from NHANES.

    PubMed

    Bress, Adam P; Kramer, Holly; Khatib, Rasha; Beddhu, Srinivasan; Cheung, Alfred K; Hess, Rachel; Bansal, Vinod K; Cao, Guichan; Yee, Jerry; Moran, Andrew E; Durazo-Arvizu, Ramon A; Muntner, Paul; Cooper, Richard S

    2017-02-13

    Background -The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause mortality with a systolic blood-pressure (SBP) goal of <120 mmHg versus <140 mmHg among U.S. adults at high cardiovascular disease (CVD) risk but without diabetes, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events (SAEs) incurred if the SPRINT intensive SBP treatment goal was implemented in all eligible U.S. adults. Methods -SPRINT eligibility criteria were applied to the 1999-2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥ 50 years, SBP of 130-180 mmHg (depending on the number of antihypertensive medications being taken), and high CVD risk. Exclusion criteria were diabetes, history of stroke, >1 gram of proteinuria, heart failure, estimated glomerular filtration rate < 20 ml/min/1.73m(2), or dialysis. Annual mortality rates were calculated by dividing the Kaplan-Meier 5-year mortality by 5. Hazard ratios for all-cause mortality and heart failure and absolute risks for SAEs in SPRINT were used to estimate the number of potential deaths and heart failure cases prevented and SAEs incurred with intensive SBP treatment. Results -The mean age was 68.6 years and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95%CI 1.91%-2.48%) and intensive SBP treatment was projected to prevent about 107,500 deaths per year (95%CI 93,300-121,200) and give rise to 56,100 (95%CI 50,800-61,400) episodes of hypotension, 34,400 (95%CI 31,200-37,600) episodes of syncope, 43,400 (95%CI 39,400-47,500) serious electrolyte disorders, and 88,700 (95%CI 80,400-97,000) cases of acute kidney injury per year. The analysis of extremes approach indicated that the range of estimated lower and upper

  6. Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets- An Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

    PubMed Central

    Ilekis, John V.; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M.; Soares, Michael J.; Cross, James C.; Zamudio, Stacy; Illsley, Nicholas P.; Myatt, Leslie; Colvis, Christine; Costantine, Maged M.; Haas, David M.; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-01-01

    Although much progress is being made in understanding the molecular pathways in the placenta involved in the pathophysiology of pregnancy related disorders, a significant gap exists in utilizing this information for developing new drug therapies to improve pregnancy outcome. On March 5–6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a two day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given in the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of this workshop. A broad number of topics were covered ranging from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and non-infectious agents. Research findings in these areas will be critical for formulating developing future treatments and developing therapies for the prevention of a number of pregnancy disorders of placental origin including preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented summarizing ongoing clinical efforts in the U.S. and in Europe testing novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy using virally-delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by enhancing nutrient transport to the fetus by modulating their placental transporters, as well as targeting placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles

  7. S100B as a potential biomarker for the detection of cytotoxicity of melanocytes.

    PubMed

    Cheong, Kyung Ah; Noh, Minsoo; Kim, Chang-Hyun; Lee, Ai-Young

    2014-03-01

    Skin irritation is one of the most common adverse reactions in hydroquinone (HQ) and retinoic acid (RA). Although melanocytes have rarely been considered to be involved in skin irritation, RA and particularly HQ could induce melanocyte toxicity, resulting in depigmentation. We chose S100B as a candidate gene for melanocytotoxicity from a genome-wide transcriptional profiling analysis after applying irritant doses of HQ, RA and sodium lauryl sulphate (SLS) to cultures of keratinocytes and/or melanocytes. In this study, the role of S100B on melanocyte viability and cytotoxicity was examined. S100B was detected in melanocytes, but not in keratinocytes or fibroblasts. Melanocytes after treatment with increasing concentrations of HQ, RA, SLS and urushiol showed significant increases in intracellular and extracellular S100B expression with reduced viable cell number and increased release of lactate dehydrogenase. No RAGE expression and no significant function of CD166/ALCAM in melanocyte survival and cytotoxicity favoured the role of intracellular S100B in chemically irritated melanocytes. S100B knock-down increased apoptosis through inhibition of PI3K/AKT, NF-κB and ERK activation, suggesting the increased intracellular S100B expression by chemical irritation as a compensatory reaction to reduce cytotoxicity. The numerical decrease in S100B/c-kit-double-positive melanocytes was also examined in human skin epidermis irritated by HQ or RA with stronger staining intensities of S100B. Collectively, the decrease in viable cell number by reduced intracellular S100B levels in vitro and by chemical irritation in vivo suggests that S100B could be a potential biomarker for melanocytes cytotoxicity.

  8. IDMap: facilitating the detection of potential leads with therapeutic targets.

    PubMed

    Ha, Soyang; Seo, Young-Ju; Kwon, Min-Seok; Chang, Byung-Ha; Han, Cheol-Kyu; Yoon, Jeong-Hyeok

    2008-06-01

    Pharmaceutical industry has been striving to reduce the costs of drug development and increase productivity. Among the many different attempts, drug repositioning (retargeting existing drugs) comes into the spotlight because of its financial efficiency. We introduce IDMap which predicts novel relationships between targets and chemicals and thus is capable of repositioning the marketed drugs by using text mining and chemical structure information. Also capable of mapping commercial chemicals to possible drug targets and vice versa, IDMap creates convenient environments for identifying the potential lead and its targets, especially in the field of drug repositioning. IDMap executable and its user manual including color images are freely available to non-commercial users at http://www.equispharm.com/idmap

  9. Single-trial detection for intraoperative somatosensory evoked potentials monitoring.

    PubMed

    Hu, L; Zhang, Z G; Liu, H T; Luk, K D K; Hu, Y

    2015-12-01

    Abnormalities of somatosensory evoked potentials (SEPs) provide effective evidence for impairment of the somatosensory system, so that SEPs have been widely used in both clinical diagnosis and intraoperative neurophysiological monitoring. However, due to their low signal-to-noise ratio (SNR), SEPs are generally measured using ensemble averaging across hundreds of trials, thus unavoidably producing a tardiness of SEPs to the potential damages caused by surgical maneuvers and a loss of dynamical information of cortical processing related to somatosensory inputs. Here, we aimed to enhance the SNR of single-trial SEPs using Kalman filtering and time-frequency multiple linear regression (TF-MLR) and measure their single-trial parameters, both in the time domain and in the time-frequency domain. We first showed that, Kalman filtering and TF-MLR can effectively capture the single-trial SEP responses and provide accurate estimates of single-trial SEP parameters in the time domain and time-frequency domain, respectively. Furthermore, we identified significant correlations between the stimulus intensity and a set of indicative single-trial SEP parameters, including the correlation coefficient (between each single-trial SEPs and their average), P37 amplitude, N45 amplitude, P37-N45 amplitude, and phase value (at the zero-crossing points between P37 and N45). Finally, based on each indicative single-trial SEP parameter, we investigated the minimum number of trials required on a single-trial basis to suggest the existence of SEP responses, thus providing important information for fast SEP extraction in intraoperative monitoring.

  10. Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS).

    PubMed

    Xu, Rong; Wang, Quanqiu

    2014-02-01

    Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug-cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with

  11. Discovery potential for directional dark matter detection with nuclear emulsions

    NASA Astrophysics Data System (ADS)

    Guler, A. M.; NEWSdm Collaboration

    2017-06-01

    Direct Dark Matter searches are nowadays one of the most exciting research topics. Several Experimental efforts are concentrated on the development, construction, and operation of detectors looking for the scattering of target nuclei with Weakly Interactive Massive Particles (WIMPs). In this field a new frontier can be opened by directional detectors able to reconstruct the direction of the WIMP-recoiled nucleus thus allowing to extend dark matter searches beyond the neutrino floor. Exploiting directionality would also give a proof of the galactic origin of dark matter making it possible to have a clear and unambiguous signal to background separation. The angular distribution of WIPM-scattered nuclei is indeed expected to be peaked in the direction of the motion of the Solar System in the Galaxy, i.e. toward the Cygnus constellation, while the background distribution is expected to be isotropic. Current directional experiments are based on the use of gas TPC whose sensitivity is limited by the small achievable detector mass. In this paper we show the potentiality in terms of exclusion limit of a directional experiment based on the use of a solid target made by newly developed nuclear emulsions and read-out systems reaching sub-micrometric resolution.

  12. Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events

    PubMed Central

    2013-01-01

    Background Treatment with ipilimumab, a fully human anti-CTLA-4 antibody approved for the treatment of advanced melanoma, is associated with some immune-related adverse events (irAEs) such as colitis (gastrointestinal irAE, or GI irAE) and skin rash, which are managed by treatment guidelines. Nevertheless, predictive biomarkers that can help identify patients more likely to develop these irAEs could enhance the management of these toxicities. Methods To identify candidate predictive biomarkers associated with GI irAEs, gene expression profiling was performed on whole blood samples from 162 advanced melanoma patients at baseline, 3 and 11 weeks after the start of ipilimumab treatment in two phase II clinical trials (CA184004 and CA184007). Overall, 49 patients developed Grade 2 or higher (grade 2+) GI irAEs during the course of treatment. A repeated measures analysis of variance (ANOVA) was used to evaluate the differences in mean expression levels between the GI irAE and No-GI irAE groups of patients at the three time points. Results In baseline samples, 27 probe sets showed differential mean expression (≥ 1.5 fold, P ≤ 0.05) between the GI irAE and No-GI irAE groups. Most of these probe sets belonged to three functional categories: immune system, cell cycle, and intracellular trafficking. Changes in gene expression over time were also characterized. In the GI irAE group, 58 and 247 probe sets had a ≥ 1.5 fold change in expression from baseline to 3 and 11 weeks after first ipilimumab dose, respectively. In particular, on-treatment expression increases of CD177 and CEACAM1, two neutrophil-activation markers, were closely associated with GI irAEs, suggesting a possible role of neutrophils in ipilimumab-associated GI irAEs. In addition, the expression of several immunoglobulin genes increased over time, with greater increases in patients with grade 2+ GI irAEs. Conclusions Gene expression profiling of peripheral blood, sampled before or early in the course of

  13. Data mining for prospective early detection of safety signals in the Vaccine Adverse Event Reporting System (VAERS): a case study of febrile seizures after a 2010-2011 seasonal influenza virus vaccine.

    PubMed

    Martin, David; Menschik, David; Bryant-Genevier, Marthe; Ball, Robert

    2013-07-01

    Reports of data mining results as an initial indication of a prospectively detected safety signal in the US Vaccine Adverse Event Reporting System (VAERS) have been limited. In April 2010 a vaccine safety signal for febrile seizures after Fluvax(®) and Fluvax(®) Junior was identified in Australia without the aid of data mining. In order to refine Northern Hemisphere influenza vaccine safety surveillance, VAERS data mining analyses based on vaccine brand name were initiated during the 2010-2011 influenza season. We describe the strategies that led to the finding of a novel safety signal using empirical Bayesian data mining. The primary US VAERS analysis calculated an empirical Bayesian geometric mean (EBGM), which was adjusted for age group, sex and year received. A secondary age-stratified analysis calculated a separate EBGM for 11 pre-defined age subsets. These bi-weekly analyses were generated with database restrictions that separated live and inactivated vaccines as well as with the US VAERS database. A cutoff of 2.0 at the fifth percentile of the confidence interval (CI) for the EBGM, the EB05, was used to identify vaccine adverse event combinations for further evaluation. Examination of potential interactions among concomitantly administered vaccines is based on the Interaction Signal Score (INTSS), which is a relative measure of how much excess disproportionality is present in the three-dimensional combination of two vaccines and one adverse event term. An INTSS >1 indicates that the CI for the three-dimensional analysis is larger than and does not overlap with the CI from the highest two-dimensional analysis. We subsequently examined the possibility of masking by removing all 2,095 Fluzone(®) 2010-2011 reports from the 10 December 2010 version of the VAERS database. In addition, we calculated relative reporting ratios to observe the relative contribution of adjustment and the Multi-Item Gamma Poisson Shrinker (MGPS) algorithm to EBGM values. On 10

  14. Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

    PubMed

    Ilekis, John V; Tsilou, Ekaterini; Fisher, Susan; Abrahams, Vikki M; Soares, Michael J; Cross, James C; Zamudio, Stacy; Illsley, Nicholas P; Myatt, Leslie; Colvis, Christine; Costantine, Maged M; Haas, David M; Sadovsky, Yoel; Weiner, Carl; Rytting, Erik; Bidwell, Gene

    2016-07-01

    Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental

  15. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer.

    PubMed

    Dahl, Edgar; En-Nia, Abdelaziz; Wiesmann, Frank; Krings, Renate; Djudjaj, Sonja; Breuer, Elisabeth; Fuchs, Thomas; Wild, Peter J; Hartmann, Arndt; Dunn, Sandra E; Mertens, Peter R

    2009-11-24

    Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample size

  16. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

  17. Design and validation of an automated method to detect known adverse drug reactions in MEDLINE: a contribution from the EU–ADR project

    PubMed Central

    Avillach, Paul; Dufour, Jean-Charles; Diallo, Gayo; Salvo, Francesco; Joubert, Michel; Thiessard, Frantz; Mougin, Fleur; Trifirò, Gianluca; Fourrier-Réglat, Annie; Pariente, Antoine; Fieschi, Marius

    2013-01-01

    Objectives The aim of this research was to automate the search of publications concerning adverse drug reactions (ADR) by defining the queries used to search MEDLINE and by determining the required threshold for the number of extracted publications to confirm the drug/event association in the literature. Methods We defined an approach based on the medical subject headings (MeSH) ‘descriptor records’ and ‘supplementary concept records’ thesaurus, using the subheadings ‘chemically induced’ and ‘adverse effects’ with the ‘pharmacological action’ knowledge. An expert-built validation set of true positive and true negative drug/adverse event associations (n=61) was used to validate our method. Results Using a threshold of three of more extracted publications, the automated search method presented a sensitivity of 90% and a specificity of 100%. For nine different drug/event pairs selected, the recall of the automated search ranged from 24% to 64% and the precision from 93% to 48%. Conclusions This work presents a method to find previously established relationships between drugs and adverse events in the literature. Using MEDLINE, following a MeSH approach to filter the signals, is a valid option. Our contribution is available as a web service that will be integrated in the final European EU–ADR project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) automated system. PMID:23195749

  18. A Community Detection Algorithm Based on Topology Potential and Spectral Clustering

    PubMed Central

    Wang, Zhixiao; Chen, Zhaotong; Zhao, Ya; Chen, Shaoda

    2014-01-01

    Community detection is of great value for complex networks in understanding their inherent law and predicting their behavior. Spectral clustering algorithms have been successfully applied in community detection. This kind of methods has two inadequacies: one is that the input matrixes they used cannot provide sufficient structural information for community detection and the other is that they cannot necessarily derive the proper community number from the ladder distribution of eigenvector elements. In order to solve these problems, this paper puts forward a novel community detection algorithm based on topology potential and spectral clustering. The new algorithm constructs the normalized Laplacian matrix with nodes' topology potential, which contains rich structural information of the network. In addition, the new algorithm can automatically get the optimal community number from the local maximum potential nodes. Experiments results showed that the new algorithm gave excellent performance on artificial networks and real world networks and outperforms other community detection methods. PMID:25147846

  19. Adverse reactions to vaccines.

    PubMed

    Martin, Bryan L; Nelson, Michael R; Hershey, Joyce N; Engler, Renata J M

    2003-06-01

    (The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.) Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prolonged disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rare reaction risk. There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced risk communication intervention. When they occur, vaccine related adverse events must be treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

  20. Potential of the melanophore pigment response for detection of bacterial toxicity.

    PubMed

    Dukovcic, Stephanie R; Hutchison, Janine R; Trempy, Janine E

    2010-12-01

    Chromatophore cells have been investigated as potential biodetectors for function-based detection of chemically and biologically toxic substances. Oncorhynchus tshawytscha (chinook salmon) melanophores, a chromatophore cell type containing brown pigment, rapidly detect the salmonid pathogens Aeromonas salmonicida, Yersinia ruckeri, and Flavobacterium psychrophilum and the human pathogen Bacillus cereus.

  1. Potential of the Melanophore Pigment Response for Detection of Bacterial Toxicity ▿

    PubMed Central

    Dukovcic, Stephanie R.; Hutchison, Janine R.; Trempy, Janine E.

    2010-01-01

    Chromatophore cells have been investigated as potential biodetectors for function-based detection of chemically and biologically toxic substances. Oncorhynchus tshawytscha (chinook salmon) melanophores, a chromatophore cell type containing brown pigment, rapidly detect the salmonid pathogens Aeromonas salmonicida, Yersinia ruckeri, and Flavobacterium psychrophilum and the human pathogen Bacillus cereus. PMID:20952639

  2. Could chiropractors screen for adverse drug events in the community? Survey of US chiropractors

    PubMed Central

    2010-01-01

    Background The "Put Prevention into Practice" campaign of the US Public Health Service (USPHS) was launched with the dissemination of the Clinician's Handbook of Preventive Services that recommended standards of clinical care for various prevention activities, including preventive clinical strategies to reduce the risk of adverse drug events. We explored whether nonprescribing clinicians such as chiropractors may contribute to advancing drug safety initiatives by identifying potential adverse drug events in their chiropractic patients, and by bringing suspected adverse drug events to the attention of the prescribing clinicians. Methods Mail survey of US chiropractors about their detection of potential adverse drug events in their chiropractic patients. Results Over half of responding chiropractors (62%) reported having identified a suspected adverse drug event occurring in one of their chiropractic patients. The severity of suspected drug-related events detected ranged from mild to severe. Conclusions Chiropractors or other nonprescribing clinicians may be in a position to detect potential adverse drug events in the community. These detection and reporting mechanisms should be standardized and policies related to clinical case management of suspected adverse drug events occurring in their patients should be developed. PMID:21083911

  3. Influenza surveillance in animals: what is our capacity to detect emerging influenza viruses with zoonotic potential?

    PubMed

    VON Dobschuetz, S; DE Nardi, M; Harris, K A; Munoz, O; Breed, A C; Wieland, B; Dauphin, G; Lubroth, J; Stärk, K D C

    2015-07-01

    A survey of national animal influenza surveillance programmes was conducted to assess the current capacity to detect influenza viruses with zoonotic potential in animals (i.e. those influenza viruses that can be naturally transmitted between animals and humans) at regional and global levels. Information on 587 animal influenza surveillance system components was collected for 99 countries from Chief Veterinary Officers (CVOs) (n = 94) and published literature. Less than 1% (n = 4) of these components were specifically aimed at detecting influenza viruses with pandemic potential in animals (i.e. those influenza viruses that are capable of causing epidemic spread in human populations over large geographical regions or worldwide), which would have zoonotic potential as a prerequisite. Those countries that sought to detect influenza viruses with pandemic potential searched for such viruses exclusively in domestic pigs. This work shows the global need for increasing surveillance that targets potentially zoonotic influenza viruses in relevant animal species.

  4. Optical magnetic detection of single-neuron action potentials using NV-diamond

    NASA Astrophysics Data System (ADS)

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

  5. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  6. Somatosensory evoked potential monitoring detection of carotid compression during ACDF surgery in a patient with a vascularly isolated hemisphere.

    PubMed

    Legatt, Alan D; Laarakker, Avra S; Nakhla, Jonathan P; Nasser, Rani; Altschul, David J

    2016-11-01

    The authors report herein a case of anterior cervical discectomy and fusion (ACDF) surgery in which findings on somatosensory evoked potential (SSEP) monitoring led to the correction of carotid artery compression in a patient with a vascularly isolated hemisphere (no significant collateral blood vessels to the carotid artery territory). The amplitude of the cortical SSEP component to left ulnar nerve stimulation progressively decreased in multiple runs, but there were no changes in the cervicomedullary SSEP component to the same stimulus. When the lateral (right-sided) retractor was removed, the cortical SSEP component returned to baseline. The retraction was then intermittently relaxed during the rest of the operation, and the patient suffered no neurological morbidity. Magnetic resonance angiography demonstrated a vascularly isolated right hemisphere. During anterior cervical spine surgery, carotid artery compression by the retractor can cause hemispheric ischemia and infarction in patients with inadequate collateral circulation. The primary purpose of SSEP monitoring during ACDF surgery is to detect compromise of the dorsal column somatosensory pathways within the cervical spinal cord, but intraoperative SSEP monitoring can also detect hemispheric ischemia. Concurrent recording of cervicomedullary SSEPs can help differentiate cortical SSEP changes due to hemispheric ischemia from those due to compromise of the dorsal column pathways. If there are adverse changes in the cortical SSEPs but no changes in the cervicomedullary SSEPs, the possibility of hemispheric ischemia due to carotid artery compression by the retractor should be considered.

  7. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review

    PubMed Central

    Reddy-Kantharaj, Yashoda-Bhoomi; Rakesh, Nagaraju; Janardhan-Reddy, Sujatha; Sahu, Shashikant

    2016-01-01

    Background Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. Material and Methods The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Results Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Conclusions Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct

  8. Potential role of a hybrid intraoperative probe based on OCT and positron detection for ovarian cancer detection and characterization.

    PubMed

    Yang, Yi; Biswal, Nrusingh C; Wang, Tianheng; Kumavor, Patrick D; Karimeddini, Mozafareddin; Vento, John; Sanders, Melinda; Brewer, Molly; Zhu, Quing

    2011-07-01

    Ovarian cancer has the lowest survival rate of the gynecologic cancers because it is predominantly diagnosed in the late stages due to the lack of reliable symptoms and efficacious screening techniques. A novel hybrid intraoperative probe has been developed and evaluated for its potential role in detecting and characterizing ovarian tissue. The hybrid intraoperative dual-modality device consists of multiple scintillating fibers and an optical coherence tomography imaging probe for simultaneously mapping the local activities of (18)F-FDG uptake and imaging of local morphological changes of the ovary. Ten patients were recruited to the study and a total of 18 normal, abnormal and malignant ovaries were evaluated ex vivo using this device. Positron count rates of 7.5/8.8-fold higher were found between malignant and abnormal/normal ovaries. OCT imaging of malignant and abnormal ovaries revealed many detailed morphologic features that could be potentially valuable for evaluating local regions with high metabolic activities and detecting early malignant changes in the ovary. These initial results have demonstrated that our novel hybrid imager has great potential for ovarian cancer detection and characterization during minimally invasive endoscopic procedures.

  9. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  10. A comparison of the potential for acute cardiopulmonary adverse effects in dogs during continuous veno-venous hemofiltration with accusol 35 solution with and without induced calcium carbonate particles.

    PubMed

    McKee, Jeffrey S; Brooks, Benjamin D; Daller, Justin R; Safron, Joseph; Gass, Jerome H; Pantaleone, David P; Zieske, Paul A; Mussi, Paola; Moreaux, Benoit

    2013-01-01

    Baxter received reports of visible precipitate, identified as calcium carbonate, forming during hemofiltration with Accusol 35 solution. To evaluate the potential for acute cardiopulmonary adverse effects of Accusol 35 containing exaggerated calcium carbonate particles. Anesthetized dogs underwent continuous veno-venous hemofiltration (CVVH) with Accusol 35 containing visible and subvisible particles (≥10 µm) 36 times higher than the maximum concentration specified in the European Pharmacopoeia (P-Accusol), or Accusol 35 conforming to specification (Accusol). Select cardiovascular and blood gas parameters were evaluated during CVVH. Lung tissue samples were collected following CVVH. No differences were observed in cardiovascular and blood gas parameters or lung histology between P-Accusol and Accusol. Accusol 35 containing visible and subvisible particles (≥10 µm) 36 times higher than the maximum concentration specified in the European Pharmacopoeia resulted in no acute cardiopulmonary adverse effects compared with Accusol 35 containing no visible particles and subvisible particles within European Pharmacopoeia specification. Copyright © 2013 S. Karger AG, Basel.

  11. Optical coherence tomography for detection of compound action potential in Xenopus Laevis sciatic nerve

    NASA Astrophysics Data System (ADS)

    Troiani, Francesca; Nikolic, Konstantin; Constandinou, Timothy G.

    2016-03-01

    Due to optical coherence tomography (OCT) high spatial and temporal resolution, this technique could be used to observe the quick changes in the refractive index that accompany action potential. In this study we explore the use of time domain Optical Coherence Tomography (TD-OCT) for real time action potential detection in ex vivo Xenopus Laevis sciatic nerve. TD-OCT is the easiest and less expensive OCT technique and, if successful in detecting real time action potential, it could be used for low cost monitoring devices. A theoretical investigation into the order of magnitude of the signals detected by a TD-OCT setup is provided by this work. A linear dependence between the refractive index and the intensity changes is observed and the minimum SNR for which the setup could work is found to be SNR = 2 x 104.

  12. DETECTION OF POTENTIAL TRANSIT SIGNALS IN THE FIRST THREE QUARTERS OF Kepler MISSION DATA

    SciTech Connect

    Tenenbaum, Peter; Christiansen, Jessie L.; Jenkins, Jon M.; Rowe, Jason F.; Seader, Shawn; Caldwell, Douglas A.; Clarke, Bruce D.; Li, Jie; Quintana, Elisa V.; Smith, Jeffrey C.; Stumpe, Martin C.; Thompson, Susan E.; Twicken, Joseph D.; Van Cleve, Jeffrey; Girouard, Forrest R.; Klaus, Todd C. [Orbital Sciences Corporation and others

    2012-03-01

    We present the results of a search for potential transit signals in the first three quarters of photometry data acquired by the Kepler mission. The targets of the search include 151,722 stars which were observed over the full interval and an additional 19,132 stars which were observed for only one or two quarters. From this set of targets we find a total of 5392 detections which meet the Kepler detection criteria: those criteria are periodicity of signal, an acceptable signal-to-noise ratio, and a composition test which rejects spurious detections which contain non-physical combinations of events. The detected signals are dominated by events with relatively low signal-to-noise ratio and by events with relatively short periods. The distribution of estimated transit depths appears to peak in the range between 40 and 100 parts per million, with a few detections down to fewer than 10 parts per million. The detections exhibit signal-to-noise ratios from 7.1{sigma}, which is the lower cutoff for detections, to over 10,000{sigma}, and periods ranging from 0.5 days, which is the lower cutoff used in the procedure, to 109 days, which is the upper limit of achievable periods given the length of the data set and the criteria used for detections. The detected signals are compared to a set of known transit events in the Kepler field of view which were derived by a different method using a longer data interval; the comparison shows that the current search correctly identified 88.1% of the known events. A tabulation of the detected transit signals, examples which illustrate the analysis and detection process, a discussion of future plans and open, potentially fruitful, areas of further research are included.

  13. Dynamic role and importance of surrogate species for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

    USDA-ARS?s Scientific Manuscript database

    Surrogate species have a long history of use in research and regulatory settings to understand the potentially harmful effects of toxic substances including pesticides. More recently, surrogate species have been used to evaluate the potential effects of proteins contained in genetically engineered ...

  14. Potential fault region detection in TFDS images based on convolutional neural network

    NASA Astrophysics Data System (ADS)

    Sun, Junhua; Xiao, Zhongwen

    2016-10-01

    In recent years, more than 300 sets of Trouble of Running Freight Train Detection System (TFDS) have been installed on railway to monitor the safety of running freight trains in China. However, TFDS is simply responsible for capturing, transmitting, and storing images, and fails to recognize faults automatically due to some difficulties such as such as the diversity and complexity of faults and some low quality images. To improve the performance of automatic fault recognition, it is of great importance to locate the potential fault areas. In this paper, we first introduce a convolutional neural network (CNN) model to TFDS and propose a potential fault region detection system (PFRDS) for simultaneously detecting four typical types of potential fault regions (PFRs). The experimental results show that this system has a higher performance of image detection to PFRs in TFDS. An average detection recall of 98.95% and precision of 100% are obtained, demonstrating the high detection ability and robustness against various poor imaging situations.

  15. Detection and classification of movement-related cortical potentials associated with task force and speed

    NASA Astrophysics Data System (ADS)

    Jochumsen, Mads; Niazi, Imran Khan; Mrachacz-Kersting, Natalie; Farina, Dario; Dremstrup, Kim

    2013-10-01

    Objective. In this study, the objective was to detect movement intentions and extract different levels of force and speed of the intended movement from scalp electroencephalography (EEG). We then estimated the performance of the closed loop system. Approach. Cued movements were detected from continuous EEG recordings using a template of the initial phase of the movement-related cortical potential in 12 healthy subjects. The temporal features, extracted from the movement intention, were classified with an optimized support vector machine. The system performance was evaluated when combining detection with classification. Main results. The system detected 81% of the movements and correctly classified 75 ± 9% and 80 ± 10% of these at the point of detection when varying the force and speed, respectively. When the detector was combined with the classifier, the system detected and correctly classified 64 ± 13% and 67 ± 13% of these movements. The system detected and incorrectly classified 21 ± 7% and 16 ± 9% of the movements. The movements were detected 317 ± 73 ms before the movement onset. Significance. The results indicate that it is possible to detect movement intentions with limited latencies, and extract and classify different levels of force and speed, which may be combined with assistive technologies for patient-driven neurorehabilitation.

  16. Pulsed amperometric detection of carbohydrates at gold electrodes with a two-step potential waveform

    SciTech Connect

    Neuburger, G.G.; Johnson, D.C.

    1987-01-01

    A two-step potential waveform is demonstrated for the detection of carbohydrates at a Au electrode in alkaline solutions for application in flow injection and liquid chromatography systems. Pulsed amperometric detection of carbohydrates previously based on a three-step waveform is now extended to potentiostats capable of programming an asymmetric square waveform (e.g., normal-pulse voltammetric waveforms). Detection limits for glucose, sorbitol, and sucrose are approximately 1 nmol in a 50-..mu..L sample (i.e., ca. 200 ng of glucose and 360 ng of sucrose) in a flow injection system.

  17. The potential protective effect of green, black, red and white tea infusions against adverse effect of cadmium and lead during chronic exposure - A rat model study.

    PubMed

    Winiarska-Mieczan, Anna

    2015-11-01

    The protective effect of green (GT), black (BT), red (RT) and white (WT) tea infusions on the lungs, brains, hearts, livers and kidneys of adult Wistar rats exposed to Cd (7 mg/kg) and Pb (50 m/kg) was studied. The degree of reduction in the absorption of Cd and Pb in the organs compared to control group and the activity of SOD, CAT and GPx as well as GSH level was evaluated. It was determined that tea significant reduced the accumulation of Cd in the tissues. A significant reduction in the accumulation of Pb was recorded in the brain (WT), liver (GT, WT) and kidneys (BT, GT, RT, WT). A significant increase was observed in the activity of SOD, CAT and GPx in the organs of all rats from tea groups. It was found that the results obtained in rats receiving black, red and white tea were overall not worse than those recorded for rats receiving green tea. The obtained results suggest that drinking tea could be an effective method of reducing the adverse effect of environmental Cd and Pb pollution on the human body.

  18. Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

    PubMed

    Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

    2011-04-01

    Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced. Copyright © 2011. Published by Elsevier Ltd.

  19. DETECTION OF POTENTIAL TRANSIT SIGNALS IN 16 QUARTERS OF KEPLER MISSION DATA

    SciTech Connect

    Tenenbaum, Peter; Jenkins, Jon M.; Seader, Shawn; Burke, Christopher J.; Christiansen, Jessie L.; Rowe, Jason F.; Caldwell, Douglas A.; Clarke, Bruce D.; Coughlin, Jeffrey L.; Li, Jie; Quintana, Elisa V.; Smith, Jeffrey C.; Thompson, Susan E.; Twicken, Joseph D.; Campbell, Jennifer R.; Girouard, Forrest R. [Orbital Sciences Corporation and others

    2014-03-01

    We present the results of a search for potential transit signals in 4 yr of photometry data acquired by the Kepler mission. The targets of the search include 111,800 stars which were observed for the entire interval and 85,522 stars which were observed for a subset of the interval. We found that 9743 targets contained at least one signal consistent with the signature of a transiting or eclipsing object where the criteria for detection are periodicity of the detected transits, adequate signal-to-noise ratio, and acceptance by a number of tests which reject false positive detections. When targets that had produced a signal were searched repeatedly, an additional 6542 signals were detected on 3223 target stars, for a total of 16,285 potential detections. Comparison of the set of detected signals with a set of known and vetted transit events in the Kepler field of view shows that the recovery rate for these signals is 96.9%. The ensemble properties of the detected signals are reviewed.

  20. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review.

    PubMed

    Nagi, R; Reddy-Kantharaj, Y-B; Rakesh, N; Janardhan-Reddy, S; Sahu, S

    2016-07-01

    Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct tool in early diagnosis of OSCC and OPMD.

  1. Label-free optical detection of action potential in mammalian neurons (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra K.; Davé, Digant P.

    2017-02-01

    Electrophysiology techniques are the gold standard in neuroscience for studying functionality of a single neuron to a complex neuronal network. However, electrophysiology techniques are not flawless, they are invasive nature, procedures are cumbersome to implement with limited capability of being used as a high-throughput recording system. Also, long term studies of neuronal functionality with aid of electrophysiology is not feasible. Non-invasive stimulation and detection of neuronal electrical activity has been a long standing goal in neuroscience. Introduction of optogenetics has ushered in the era of non-invasive optical stimulation of neurons, which is revolutionizing neuroscience research. Optical detection of neuronal activity that is comparable to electro-physiology is still elusive. A number of optical techniques have been reported recording of neuronal electrical activity but none is capable of reliably measuring action potential spikes that is comparable to electro-physiology. Optical detection of action potential with voltage sensitive fluorescent reporters are potential alternatives to electrophysiology techniques. The heavily rely on secondary reporters, which are often toxic in nature with background fluorescence, with slow response and low SNR making them far from ideal. The detection of one shot (without averaging)-single action potential in a true label-free way has been elusive so far. In this report, we demonstrate the optical detection of single neuronal spike in a cultured mammalian neuronal network without using any exogenous labels. To the best of our knowledge, this is the first demonstration of label free optical detection of single action potentials in a mammalian neuronal network, which was achieved using a high-speed phase sensitive interferometer. We have carried out stimulation and inhibition of neuronal firing using Glutamate and Tetrodotoxin respectively to demonstrate the different outcome (stimulation and inhibition) revealed in

  2. Detection of hepatotoxicity potential with metabolite profiling (metabolomics) of rat plasma.

    PubMed

    Mattes, W; Davis, K; Fabian, E; Greenhaw, J; Herold, M; Looser, R; Mellert, W; Groeters, S; Marxfeld, H; Moeller, N; Montoya-Parra, G; Prokoudine, A; van Ravenzwaay, B; Strauss, V; Walk, T; Kamp, H

    2014-11-04

    While conventional parameters used to detect hepatotoxicity in drug safety assessment studies are generally informative, the need remains for parameters that can detect the potential for hepatotoxicity at lower doses and/or at earlier time points. Previous work has shown that metabolite profiling (metabonomics/metabolomics) can detect signals of potential hepatotoxicity in rats treated with doxorubicin at doses that do not elicit hepatotoxicity as monitored with conventional parameters. The current study extended this observation to the question of whether such signals could be detected in rats treated with compounds that can elicit hepatotoxicity in humans (i.e., drug-induced liver injury, DILI) but have not been reported to do so in rats. Nine compounds were selected on the basis of their known DILI potential, with six other compounds chosen as negative for DILI potential. A database of rat plasma metabolite profiles, MetaMap(®)Tox (developed by metanomics GmbH and BASF SE) was used for both metabolite profiles and mode of action (MoA) metabolite signatures for a number of known toxicities. Eight of the nine compounds with DILI potential elicited metabolite profiles that matched with MoA patterns of various rat liver toxicities, including cholestasis, oxidative stress, acetaminophen-type toxicity and peroxisome proliferation. By contrast, only one of the six non-DILI compounds showed a weak match with rat liver toxicity. These results suggest that metabolite profiling may indeed have promise to detect signals of hepatotoxicity in rats treated with compounds having DILI potential. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Shared Physiological and Molecular Responses in Marine Fish and Invertebrates to Environmental Hypoxia: Potential Biomarkers of Adverse Impacts on Marine Communities

    NASA Astrophysics Data System (ADS)

    Thomas, P.; Rahman, S.

    2016-02-01

    Knowledge of the effects of environmental exposure to hypoxia (dissolved oxygen: <2 mg/L) on critical physiological functions such as reproduction, growth and metabolism in both fish and invertebrates is essential for accurate predictions of its chronic impacts on marine communities. Marked disruption of reproduction and its endocrine control was observed in Atlantic croaker collected from the hypoxic region in the northern Gulf of Mexico. Recent research has shown that growth and its physiological upregulation is also impaired in hypoxia-exposed marine fish. Expression of insulin-like growth factor (IGF) binding protein (IGFBP), which inhibits growth, was increased in croaker livers, whereas plasma levels of IGF, the primary regulator of growth, were decreased in snapper after hypoxia exposure. In addition, hypoxia inducible factor-1 (HIF-1), which regulates changes in metabolism during adaptation to hypoxia, was upregulated in croaker collected from hypoxic environments. Interestingly, similar changes in the expression of IGFBP and HIF-1 have been found in marine crustaceans after hypoxia exposure, suggesting these responses to hypoxia are common to marine fish and invertebrates. Preliminary field studies indicate that hypoxia exposure also causes epigenetic modifications, including increases in global DNA methylation, and that these epigenetic changes can influence reproduction and growth in croaker. Epigenetic modifications can be passed to offspring and persist in future generations no longer exposed to an environmental stressor further aggravating its long-term adverse impacts on population abundance and delaying recovery. The growing availability of complete invertebrate genomes and high-throughput DNA sequencing indicates similar epigenetic studies can now be conducted with marine invertebrates. Collectively, the results indicate that environmental hypoxia exposure disrupts major physiological functions in fish and invertebrates critical for maintenance of

  4. Combining in vitro protein detection and in vivo antibody detection identifies potential vaccine targets against Staphylococcus aureus during osteomyelitis.

    PubMed

    den Reijer, P Martijn; Sandker, Marjan; Snijders, Susan V; Tavakol, Mehri; Hendrickx, Antoni P A; van Wamel, Willem J B

    2017-02-01

    Currently, little is known about the in vivo human immune response against Staphylococcus aureus during a biofilm-associated infection, such as osteomyelitis, and how this relates to protein production in biofilms in vitro. Therefore, we characterized IgG responses in 10 patients with chronic osteomyelitis against 50 proteins of S. aureus, analyzed the presence of these proteins in biofilms of the infecting isolates on polystyrene (PS) and human bone in vitro, and explored the relation between in vivo and in vitro data. IgG levels against 15 different proteins were significantly increased in patients compared to healthy controls. Using a novel competitive Luminex-based assay, eight of these proteins [alpha toxin, Staphylococcus aureus formyl peptide receptor-like 1 inhibitor (FlipR), glucosaminidase, iron-responsive surface determinants A and H, the putative ABC transporter SACOL0688, staphylococcal complement inhibitor (SCIN), and serine-aspartate repeat-containing protein E (SdrE)] were also detected in a majority of the infecting isolates during biofilm formation in vitro. However, 4 other proteins were detected in only a minority of isolates in vitro while, vice versa, 7 proteins were detected in multiple isolates in vitro but not associated with significantly increased IgG levels in patients. Detection of proteins was largely confirmed using a transcriptomic approach. Our data provide further insights into potential therapeutic targets, such as for vaccination, to reduce S. aureus virulence and biofilm formation. At the same time, our data suggest that either in vitro or immunological in vivo data alone should be interpreted cautiously and that combined studies are necessary to identify potential targets.

  5. Wavelet transform for real-time detection of action potentials in neural signals.

    PubMed

    Quotb, Adam; Bornat, Yannick; Renaud, Sylvie

    2011-01-01

    We present a study on wavelet detection methods of neuronal action potentials (APs). Our final goal is to implement the selected algorithms on custom integrated electronics for on-line processing of neural signals; therefore we take real-time computing as a hard specification and silicon area as a price to pay. Using simulated neural signals including APs, we characterize an efficient wavelet method for AP extraction by evaluating its detection rate and its implementation cost. We compare software implementation for three methods: adaptive threshold, discrete wavelet transform (DWT), and stationary wavelet transform (SWT). We evaluate detection rate and implementation cost for detection functions dynamically comparing a signal with an adaptive threshold proportional to its SD, where the signal is the raw neural signal, respectively: (i) non-processed; (ii) processed by a DWT; (iii) processed by a SWT. We also use different mother wavelets and test different data formats to set an optimal compromise between accuracy and silicon cost. Detection accuracy is evaluated together with false negative and false positive detections. Simulation results show that for on-line AP detection implemented on a configurable digital integrated circuit, APs underneath the noise level can be detected using SWT with a well-selected mother wavelet, combined to an adaptive threshold.

  6. DETECTION OF POTENTIAL TRANSIT SIGNALS IN THE FIRST 12 QUARTERS OF KEPLER MISSION DATA

    SciTech Connect

    Tenenbaum, Peter; Jenkins, Jon M.; Seader, Shawn; Burke, Christopher J.; Christiansen, Jessie L.; Rowe, Jason F.; Caldwell, Douglas A.; Clarke, Bruce D.; Li, Jie; Quintana, Elisa V.; Smith, Jeffrey C.; Thompson, Susan E.; Twicken, Joseph D.; Girouard, Forrest R. [Orbital Sciences Corporation and others

    2013-05-01

    We present the results of a search for potential transit signals in the first three years of photometry data acquired by the Kepler mission. The targets of the search include 112,321 targets that were observed over the full interval and an additional 79,992 targets that were observed for a subset of the full interval. From this set of targets we find a total of 11,087 targets that contain at least one signal that meets the Kepler detection criteria: periodicity of the signal, an acceptable signal-to-noise ratio, and three tests that reject false positives. Each target containing at least one detected signal is then searched repeatedly for additional signals, which represent multi-planet systems of transiting planets. When targets with multiple detections are considered, a total of 18,406 potential transiting planet signals are found in the Kepler mission data set. The detected signals are dominated by events with relatively low signal-to-noise ratios and by events with relatively short periods. The distribution of estimated transit depths appears to peak in the range between 20 and 30 parts per million, with a few detections down to fewer than 10 parts per million. The detections exhibit signal-to-noise ratios from 7.1{sigma}, which is the lower cutoff for detections, to over 10,000{sigma}, and periods ranging from 0.5 days, which is the shortest period searched, to 525 days, which is the upper limit of achievable periods given the length of the data set and the requirement that all detections include at least three transits. The detected signals are compared to a set of known transit events in the Kepler field of view, many of which were identified by alternative methods; the comparison shows that the current search recovery rate for targets with known transit events is 98.3%.

  7. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

    PubMed

    Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Spatial Modeling of Industrial Windfall on Soils to Detect Woody Species with Potential for Bioremediation

    Treesearch

    S. Salazar; M. Mendoza; A. M. Tejeda

    2006-01-01

    A spatial model is presented to explain the concentration of heavy metals (Fe, Cu, Zn, Ni, Cr, Co and Pb), in the soils around the industrial complex near the Port of Veracruz, Mexico. Unexpected low concentration sites where then tested to detect woody plant species that may have the capability to hiperacumulate these contaminants, hence having a potential for...

  9. MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES

    EPA Science Inventory

    MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL
    ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES.
    Authors: L E Gray 1 , J Furr 1 , M G Price 2 , C J Wolf 3 and J S Ostby 1
    Institutions: 1. Endocrinology Branch, Reproductive Toxicology Division, NH...

  10. MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES

    EPA Science Inventory

    MAMMALIAN SCREENING ASSAYS FOR THE DETECTION OF POTENTIAL
    ENDOCRINE DISRUPTING CHEMICALS WITH AN EMPHASIS ON MALES.
    Authors: L E Gray 1 , J Furr 1 , M G Price 2 , C J Wolf 3 and J S Ostby 1
    Institutions: 1. Endocrinology Branch, Reproductive Toxicology Division, NH...

  11. Remote identification of potential boll weevil host plants: Airborne multispectral detection of regrowth cotton

    USDA-ARS?s Scientific Manuscript database

    Regrowth cotton plants can serve as potential hosts for boll weevils during and beyond the production season. Effective methods for timely areawide detection of these host plants are critically needed to expedite eradication in south Texas. We acquired airborne multispectral images of experimental...

  12. Pediatric multiple sclerosis: detection of clinically silent lesions by multimodal evoked potentials.

    PubMed

    Pohl, Daniela; Rostasy, Kevin; Treiber-Held, Stephanie; Brockmann, Knut; Gärtner, Jutta; Hanefeld, Folker

    2006-07-01

    Pediatric patients with multiple sclerosis (MS) frequently do not meet MRI criteria for diagnosis because of lack of evidence of dissemination in space. We assessed the diagnostic utility of multimodal evoked potentials (EP). In 46% of 85 childhood patients with MS, spatial dissemination was detected by EP before the second clinical attack. EP may constitute an important tool for earlier diagnosis of pediatric MS.

  13. Online detection of error-related potentials boosts the performance of mental typewriters.

    PubMed

    Schmidt, Nico M; Blankertz, Benjamin; Treder, Matthias S

    2012-02-15

    Increasing the communication speed of brain-computer interfaces (BCIs) is a major aim of current BCI-research. The idea to automatically detect error-related potentials (ErrPs) in order to veto erroneous decisions of a BCI has been existing for more than one decade, but this approach was so far little investigated in online mode. In our study with eleven participants, an ErrP detection mechanism was implemented in an electroencephalography (EEG) based gaze-independent visual speller. Single-trial ErrPs were detected with a mean accuracy of 89.1% (AUC 0.90). The spelling speed was increased on average by 49.0% using ErrP detection. The improvement in spelling speed due to error detection was largest for participants with low spelling accuracy. The performance of BCIs can be increased by using an automatic error detection mechanism. The benefit for patients with motor disorders is potentially high since they often have rather low spelling accuracies compared to healthy people.

  14. Detection of a strongly negative surface potential at Saturn's moon Hyperion

    PubMed Central

    Nordheim, T A; Jones, G H; Roussos, E; Leisner, J S; Coates, A J; Kurth, W S; Khurana, K K; Krupp, N; Dougherty, M K; Waite, J H

    2014-01-01

    On 26 September 2005, Cassini conducted its only close targeted flyby of Saturn's small, irregularly shaped moon Hyperion. Approximately 6 min before the closest approach, the electron spectrometer (ELS), part of the Cassini Plasma Spectrometer (CAPS) detected a field-aligned electron population originating from the direction of the moon's surface. Plasma wave activity detected by the Radio and Plasma Wave instrument suggests electron beam activity. A dropout in energetic electrons was observed by both CAPS-ELS and the Magnetospheric Imaging Instrument Low-Energy Magnetospheric Measurement System, indicating that the moon and the spacecraft were magnetically connected when the field-aligned electron population was observed. We show that this constitutes a remote detection of a strongly negative (∼ −200 V) surface potential on Hyperion, consistent with the predicted surface potential in regions near the solar terminator. PMID:26074639

  15. Detection of a strongly negative surface potential at Saturn's moon Hyperion

    NASA Astrophysics Data System (ADS)

    Nordheim, T. A.; Jones, G. H.; Roussos, E.; Leisner, J. S.; Coates, A. J.; Kurth, W. S.; Khurana, K. K.; Krupp, N.; Dougherty, M. K.; Waite, J. H.

    2014-10-01

    On 26 September 2005, Cassini conducted its only close targeted flyby of Saturn's small, irregularly shaped moon Hyperion. Approximately 6 min before the closest approach, the electron spectrometer (ELS), part of the Cassini Plasma Spectrometer (CAPS) detected a field-aligned electron population originating from the direction of the moon's surface. Plasma wave activity detected by the Radio and Plasma Wave instrument suggests electron beam activity. A dropout in energetic electrons was observed by both CAPS-ELS and the Magnetospheric Imaging Instrument Low-Energy Magnetospheric Measurement System, indicating that the moon and the spacecraft were magnetically connected when the field-aligned electron population was observed. We show that this constitutes a remote detection of a strongly negative (~ -200 V) surface potential on Hyperion, consistent with the predicted surface potential in regions near the solar terminator.

  16. Advances in Optical Adjunctive Aids for Visualisation and Detection of Oral Malignant and Potentially Malignant Lesions

    PubMed Central

    Bhatia, Nirav; Lalla, Yastira; Vu, An N.; Farah, Camile S.

    2013-01-01

    Traditional methods of screening for oral potentially malignant disorders and oral malignancies involve a conventional oral examination with digital palpation. Evidence indicates that conventional examination is a poor discriminator of oral mucosal lesions. A number of optical aids have been developed to assist the clinician to detect oral mucosal abnormalities and to differentiate benign lesions from sinister pathology. This paper discusses advances in optical technologies designed for the detection of oral mucosal abnormalities. The literature regarding such devices, VELscope and Identafi, is critically analysed, and the novel use of Narrow Band Imaging within the oral cavity is also discussed. Optical aids are effective in assisting with the detection of oral mucosal abnormalities; however, further research is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant and malignant lesions. PMID:24078812

  17. Detection of a strongly negative surface potential at Saturn's moon Hyperion.

    PubMed

    Nordheim, T A; Jones, G H; Roussos, E; Leisner, J S; Coates, A J; Kurth, W S; Khurana, K K; Krupp, N; Dougherty, M K; Waite, J H

    2014-10-28

    On 26 September 2005, Cassini conducted its only close targeted flyby of Saturn's small, irregularly shaped moon Hyperion. Approximately 6 min before the closest approach, the electron spectrometer (ELS), part of the Cassini Plasma Spectrometer (CAPS) detected a field-aligned electron population originating from the direction of the moon's surface. Plasma wave activity detected by the Radio and Plasma Wave instrument suggests electron beam activity. A dropout in energetic electrons was observed by both CAPS-ELS and the Magnetospheric Imaging Instrument Low-Energy Magnetospheric Measurement System, indicating that the moon and the spacecraft were magnetically connected when the field-aligned electron population was observed. We show that this constitutes a remote detection of a strongly negative (∼ -200 V) surface potential on Hyperion, consistent with the predicted surface potential in regions near the solar terminator.

  18. Early presence of anti-angiogenesis-related adverse events as a potential biomarker of antitumor efficacy in metastatic gastric cancer patients treated with apatinib: a cohort study.

    PubMed

    Liu, Xinyang; Qin, Shukui; Wang, Zhichao; Xu, Jianming; Xiong, Jianping; Bai, Yuxian; Wang, Zhehai; Yang, Yan; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Xu, Nong; Cheng, Ying; Guo, Weijian; Yu, Hao; Liu, Tianshu; Lagiou, Pagona; Li, Jin

    2017-09-05

    Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria, or hand and foot syndrome (HFS) in the first 4 weeks. Time-to-event variables were assessed using Kaplan-Meier methods and Cox proportional hazard regression models. Binary endpoints were assessed using logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model was analyzed, and risk scores were calculated to predict overall survival. Presence of AEs in the first 4 weeks was associated with prolonged median overall survival (169 vs. 103 days, log-rank p = 0.0039; adjusted hazard ratio (HR) 0.64, 95% confidence interval [CI] 0.64-0.84, p = 0.001), prolonged median progression-free survival (86.5 vs. 62 days, log-rank p = 0.0309; adjusted HR 0.69, 95% CI 0.53-0.91, p = 0.007), and increased disease control rate (54.67 vs. 32.77%; adjusted odds ratio 2.67, p < 0.001). Results remained significant in landmark analyses. The onset of any single AE or any combinations of the AEs were all statistically significantly associated with prolonged OS, except for the presence of proteinuria. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting overall survival. Presence of HTN, proteinuria, or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients.

  19. Proactive management strategies for potential gastrointestinal adverse reactions with ceritinib in patients with advanced ALK-positive non-small-cell lung cancer

    PubMed Central

    Schaefer, Eric S; Baik, Christina

    2016-01-01

    Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%–7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg

  20. Electroanalytical biosensors and their potential for food pathogen and toxin detection.

    PubMed

    Palchetti, Ilaria; Mascini, Marco

    2008-05-01

    The detection and identification of foodborne pathogens continue to rely on conventional culturing techniques. These are very elaborate, time-consuming, and have to be completed in a microbiology laboratory and are therefore not suitable for on-site monitoring. The need for a more rapid, reliable, specific, and sensitive method of detecting a target analyte, at low cost, is the focus of a great deal of research. Biosensor technology has the potential to speed up the detection, increase specificity and sensitivity, enable high-throughput analysis, and to be used for monitoring of critical control points in food production. This article reviews food pathogen detection methods based on electrochemical biosensors, specifically amperometric, potentiometric, and impedimetric biosensors. The underlying principles and application of these biosensors are discussed with special emphasis on new biorecognition elements, nanomaterials, and lab on a chip technology.

  1. Vertex evoked potentials in a rating-scale detection task: Relation to signal probability

    NASA Technical Reports Server (NTRS)

    Squires, K. C.; Squires, N. K.; Hillyard, S. A.

    1974-01-01

    Vertex evoked potentials were recorded from human subjects performing in an auditory detection task with rating scale responses. Three values of a priori probability of signal presentation were tested. The amplitudes of the N1 and P3 components of the vertex potential associated with correct detections of the signal were found to be systematically related to the strictness of the response criterion and independent of variations in a priori signal probability. No similar evoked potential components were found associated with signal absent judgements (misses and correct rejections) regardless of the confidence level of the judgement or signal probability. These results strongly support the contention that the form of the vertex evoked response is closely correlated with the subject's psychophysical decision regarding the presence or absence of a threshold level signal.

  2. Potential Landslide Detection with Fractal and Roughness by LiDAR Data in Taiwan

    NASA Astrophysics Data System (ADS)

    Cheng, Youg-Sin; Yu, Teng-To

    2015-04-01

    The purpose of this study is to detect the potential landslides since they would be triggered by heavy rain, earthquake and/or larger degree of geomorphology alteration under different terrain characteristics. Not only the newly area but also the past landslide area would generate landslide after serious events. To gather the newly landslides and past landslides overwhelmed by thick vegetation, LiDAR could produce the high resolution DEM, denote actual surface terrain information and identify landform with a spatial resolution of 1m in different time interval. The 1-m interval DEM of Laonong watershed of southern Taiwan is utilized by fractal and roughness calculating with MATLAB code. DEM, aspect, and slope images are adopted to improve the accuracy of potential landslide detection with the random forest (RF) classifier. In present study, we provide the analysis results of the potential landslide area including these features calculation.

  3. Disclosing adverse events to patients.

    PubMed

    Cantor, Michael D; Barach, Paul; Derse, Arthur; Maklan, Claire W; Wlody, Ginger Schafer; Fox, Ellen

    2005-01-01

    The rationale for, and recommended approaches to, disclosing adverse events to patients are examined on the basis of the experience of the Veterans Health Administration (VHA). The VHA's National Ethics Committee endorses a general policy requiring the routine disclosure of adverse events to patients and offers practical recommendations for implementation. Disclosure is required when the adverse event (1) has a perceptible effect on the patient that was not discussed in advance as a known risk; (2) necessitates a change in the patient's care; (3) potentially poses an important risk to the patient's future health, even if that risk is extremely small; (4) involves providing a treatment or procedure without the patient's consent. From an ethical perspective, disclosure is required and should not be limited to cases in which the injury is obvious or severe. Disclosure of near misses is also discretionary but is advisable at times. In general, disclosure by a clinician involved in the patient's care is appropriate. Although a variety of psychological and cultural factors may make clinicians and organizations reluctant to disclose adverse events to patients, the arguments favoring routine disclosure are compelling. Organizations should develop clear policies supporting disclosure and should create supportive environments that enable clinicians to meet their ethical obligations to disclose adverse events to patients and families.

  4. Numerical study on CO2 leakage detection using electrical streaming potential data

    NASA Astrophysics Data System (ADS)

    Büsing, Henrik; Vogt, Christian; Ebigbo, Anozie; Klitzsch, Norbert

    2017-01-01

    We study the feasibility of detecting carbon dioxide (CO2) movement in the overburden of a storage reservoir due to CO2 leakage through an abandoned well by self-potential (SP) measurements at the surface. This is achieved with three-dimensional numerical (SP) modeling of two-phase fluid flow and electrokinetic coupling between flow and streaming potential. We find that, in typical leakage scenarios, for leaky and/or injection wells with conductive metal casing, self-potential signals originating from injection can be identified at the surface. As the injection signal is also observed at the leaky well with metal casing, SP monitoring can be applied for detecting abandoned wells. However, leakage signals are much smaller than the injection signal and thus masked by the latter. We present three alternatives to overcome this problem: (i) simulate the streaming potential of the nonleaky scenario and subtract the result from the measured streaming potential data; (ii) exploit the symmetry of the injection signal by analyzing the potential difference of dipoles with the dipole center at the injection well; or (iii) measure SP during periods where the injection is interrupted. In our judgement, the most promising approach for detecting a real-world CO2 leakage is by combining methods (i) and (ii), because this would give the highest signal from the leakage and omit signals originating from the injection well. Consequently, we recommend SP as monitoring method for subsurface CO2 storage, especially because a leakage can be detected shortly after the injection started even before CO2 arrives at the leaky well.

  5. Detection of movement intention from single-trial movement-related cortical potentials

    NASA Astrophysics Data System (ADS)

    Niazi, Imran Khan; Jiang, Ning; Tiberghien, Olivier; Feldbæk Nielsen, Jørgen; Dremstrup, Kim; Farina, Dario

    2011-10-01

    Detection of movement intention from neural signals combined with assistive technologies may be used for effective neurofeedback in rehabilitation. In order to promote plasticity, a causal relation between intended actions (detected for example from the EEG) and the corresponding feedback should be established. This requires reliable detection of motor intentions. In this study, we propose a method to detect movements from EEG with limited latency. In a self-paced asynchronous BCI paradigm, the initial negative phase of the movement-related cortical potentials (MRCPs), extracted from multi-channel scalp EEG was used to detect motor execution/imagination in healthy subjects and stroke patients. For MRCP detection, it was demonstrated that a new optimized spatial filtering technique led to better accuracy than a large Laplacian spatial filter and common spatial pattern. With the optimized spatial filter, the true positive rate (TPR) for detection of movement execution in healthy subjects (n = 15) was 82.5 ± 7.8%, with latency of -66.6 ± 121 ms. Although TPR decreased with motor imagination in healthy subject (n = 10, 64.5 ± 5.33%) and with attempted movements in stroke patients (n = 5, 55.01 ± 12.01%), the results are promising for the application of this approach to provide patient-driven real-time neurofeedback.

  6. Detection of movement intention from single-trial movement-related cortical potentials.

    PubMed

    Niazi, Imran Khan; Jiang, Ning; Tiberghien, Olivier; Nielsen, Jørgen Feldbæk; Dremstrup, Kim; Farina, Dario

    2011-12-01

    Detection of movement intention from neural signals combined with assistive technologies may be used for effective neurofeedback in rehabilitation. In order to promote plasticity, a causal relation between intended actions (detected for example from the EEG) and the corresponding feedback should be established. This requires reliable detection of motor intentions. In this study, we propose a method to detect movements from EEG with limited latency. In a self-paced asynchronous BCI paradigm, the initial negative phase of the movement-related cortical potentials (MRCPs), extracted from multi-channel scalp EEG was used to detect motor execution/imagination in healthy subjects and stroke patients. For MRCP detection, it was demonstrated that a new optimized spatial filtering technique led to better accuracy than a large Laplacian spatial filter and common spatial pattern. With the optimized spatial filter, the true positive rate (TPR) for detection of movement execution in healthy subjects (n = 15) was 82.5 ± 7.8%, with latency of -66.6 ± 121 ms. Although TPR decreased with motor imagination in healthy subject (n = 10, 64.5 ± 5.33%) and with attempted movements in stroke patients (n = 5, 55.01 ± 12.01%), the results are promising for the application of this approach to provide patient-driven real-time neurofeedback.

  7. Dynamic role and importance of surrogate species for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    PubMed

    Wach, Michael; Hellmich, Richard L; Layton, Raymond; Romeis, Jörg; Gadaleta, Patricia G

    2016-08-01

    Surrogate species have a long history of use in research and regulatory settings to understand the potentially harmful effects of toxic substances including pesticides. More recently, surrogate species have been used to evaluate the potential effects of proteins contained in genetically engineered insect resistant (GEIR) crops. Species commonly used in GEIR crop testing include beneficial organisms such as honeybees, arthropod predators, and parasitoids. The choice of appropriate surrogates is influenced by scientific factors such as the knowledge of the mode of action and the spectrum of activity as well as societal factors such as protection goals that assign value to certain ecosystem services such as pollination or pest control. The primary reasons for using surrogates include the inability to test all possible organisms, the restrictions on using certain organisms in testing (e.g., rare, threatened, or endangered species), and the ability to achieve greater sensitivity and statistical power by using laboratory testing of certain species. The acceptance of surrogate species data can allow results from one region to be applied or "transported" for use in another region. On the basis of over a decade of using surrogate species to evaluate potential effects of GEIR crops, it appears that the current surrogates have worked well to predict effects of GEIR crops that have been developed (Carstens et al. GM Crops Food 5:1-5, 2014), and it is expected that they should work well to predict effects of future GEIR crops based on similar technologies.

  8. Cortical membrane potential signature of optimal states for sensory signal detection

    PubMed Central

    McGinley, Matthew J.; David, Stephen V.; McCormick, David A.

    2015-01-01

    The neural correlates of optimal states for signal detection task performance are largely unknown. One hypothesis holds that optimal states exhibit tonically depolarized cortical neurons with enhanced spiking activity, such as occur during movement. We recorded membrane potentials of auditory cortical neurons in mice trained on a challenging tone-in-noise detection task while assessing arousal with simultaneous pupillometry and hippocampal recordings. Arousal measures accurately predicted multiple modes of membrane potential activity, including: rhythmic slow oscillations at low arousal, stable hyperpolarization at intermediate arousal, and depolarization during phasic or tonic periods of hyper-arousal. Walking always occurred during hyper-arousal. Optimal signal detection behavior and sound-evoked responses, at both sub-threshold and spiking levels, occurred at intermediate arousal when pre-decision membrane potentials were stably hyperpolarized. These results reveal a cortical physiological signature of the classically-observed inverted-U relationship between task performance and arousal, and that optimal detection exhibits enhanced sensory-evoked responses and reduced background synaptic activity. PMID:26074005

  9. Potential problems of detecting and treating psychosis in the White House. Potential psychosis in the White House.

    PubMed

    Gambill, J

    1980-01-01

    Numerous books and articles have described the emotional difficulties suffered by President Nixon and how they influenced functioning in the White House and other branches of government during his presidency. I am not able to ascertain whether Nixon was temporarily psychotic; but the reported emotional turmoil suggests he may have been at high risk for committing suicide or developing a psychosis. This article analyzes the reactions of numerous people to the questionably irrational behaviour of Richard Nixon. Examples of psychiatric risks in other Presidents, presidential candidates, and public figures are also discussed. The potential difficulties in detecting and treating severe psychiatric illness in Presidents and other public figures should not prevent us from taking action now to minimize future risks. It is recommended that future Presidents appoint a psychiatrist, at least on a part-time basis, as one of their personal physicians in order to increase Presidential access to psychiatric evaluation and treatment.

  10. Using medical imaging for the detection of adverse events ("incidents") during the utilization of left ventricular assist devices in adult patients with advanced heart failure.

    PubMed

    Kaufmann, Friedrich; Krabatsch, Thomas

    2016-05-01

    Ventricular assist devices (VAD) are used for mechanical support of the terminally failing heart. Failure of these life supporting systems can be fatal. Early and reliable detection of any upcoming problems is mandatory and is crucial for the outcome. Medical imaging methods are described within this review, which are not only essential for diagnosis of typically VAD-related complications but also for the detection or verification of technical issues. Within this review the utilization of medical imaging equipment for the diagnosis of technical malfunctions or damages of implanted system components is discussed. A newly developed specialized acoustic imaging method for pump thrombosis detection will also be described along with the most common VAD-related medical complications and their respective imaging methods and the limitations induced by the use of the VAD-system.

  11. Potential technique for tiny crystalline detection in lycopene-loaded SLN and NLC development.

    PubMed

    Okonogi, Siriporn; Riangjanapatee, Pornthida

    2014-10-01

    The advantage of solid nanocarriers like solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) is related to some degree of crystalline characteristics of the lipid. However, the detection of tiny content of crystalline structure in such nanoparticles is difficult. The aim of this study was to explore a potential method for detection of low degree of crystalline characteristics of lycopene-loaded SLN and NLC. Crystalline characteristics investigation was done by polarized light microscope (PLM), differential scanning calorimeter (DSC), X-ray diffractometer (XRD) and transmission electron microscope (TEM). It was found that high crystalline characteristics as anisotropic molecular organization crystal of pure orange wax and lycopene could be investigated by PLM, DSC and WAXS. Low crystallinity of lycopene-loaded SLN and NLC could not be detected by those techniques. Electron diffraction mode of TEM showed potential detection of tiny crystalline characteristics of such systems. The diffraction pattern of lycopene-loaded SLN and NLC exhibited obvious zero order laue zone indicating an isotropic fine grained polycrystalline of the nanoparticles. It could be concluded that TEM is a promising method for detection of low-level crystallinity of solid nanocarriers.

  12. Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

    PubMed

    Tokunaga, Jin; Takamura, Norito; Kourogi, Yasuyuki; Imada, Misato; Kozasa, Ayaka; Komori, Kanako; Ono, Chisa; Nishimura, Akie; Ogata, Kenji; Setoguchi, Nao; Matsuoka, Toshikazu; Kai, Mitsuhiro; Sato, Keizo; Arimori, Kazuhiko

    2016-01-01

     We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore. Illustrations of a virtual patient's avatar before and after taking the medicines were incorporated in the learning materials. The virtual training includes a stethoscope that was used in examining sounds (heart, pulmonary and bowel sounds) that served as evidences in the confirmation of drug efficacy and its possible adverse effects. In addition, we included the images of each body part, the 24 format question items, the palpation (rate and rhythm) of the radial artery, brachial artery and pedal artery, the clinical data obtained from several medical equipment, the pupillary reflex, and the urine dipstick test. This way, learners are able to experience PA with reference to the subjective and objective data from patient reception and questions. The virtual patient's avatar displayed on the monitor features auscultatory sounds on the stethoscope. It also features clinical data obtained from other medical equipment that can give the learners an interactive way of learning about various medical conditions. For evaluation, we gave out questionnaires on the virtual PA to pharmacy students. As a result, a high evaluation was reflected in terms of the degree of usefulness for both case learning and basic learning.

  13. Non-invasive electrocardiogram detection of in vivo zebrafish embryos using electric potential sensors

    NASA Astrophysics Data System (ADS)

    Rendon-Morales, E.; Prance, R. J.; Prance, H.; Aviles-Espinosa, R.

    2015-11-01

    In this letter, we report the continuous detection of the cardiac electrical activity in embryonic zebrafish using a non-invasive approach. We present a portable and cost-effective platform based on the electric potential sensing technology, to monitor in vivo electrocardiogram activity from the zebrafish heart. This proof of principle demonstration shows how electrocardiogram measurements from the embryonic zebrafish may become accessible by using electric field detection. We present preliminary results using the prototype, which enables the acquisition of electrophysiological signals from in vivo 3 and 5 days-post-fertilization zebrafish embryos. The recorded waveforms show electrocardiogram traces including detailed features such as QRS complex, P and T waves.

  14. Reverse engineering adverse outcome pathways.

    PubMed

    Perkins, Edward J; Chipman, J Kevin; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-01

    The toxicological effects of many stressors are mediated through unknown, or incompletely characterized, mechanisms of action. The application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) can be used to overcome these limitations. This approach was used to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows (FHM, Pimephales promelas). Gene expression changes in FHM ovaries in response to seven different chemicals, over different times, doses, and in vivo versus in vitro conditions, were captured in a large data set of 868 arrays. Potential AOPs of the antiandrogen flutamide were examined using two mutual information-based methods to infer gene regulatory networks and potential AOPs. Representative networks from these studies were used to predict network paths from stressor to adverse outcome as candidate AOPs. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment, thus leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biological processes, biomarkers, or alternative endpoints that can be used to monitor an AOP. Finally, the unique challenges facing the application of this approach in ecotoxicology were identified and a road map for the utilization of these tools presented.

  15. A clinically feasible method for the detection of potential collision in proton therapy

    SciTech Connect

    Zou Wei; Lin Haibo; Plastaras, John P.; Wang Huanshu; Bui, Viet; Vapiwala, Neha; McDonough, James; Tochner, Zelig; Both, Stefan

    2012-11-15

    Purpose: Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. Methods: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. Results: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning phase

  16. Statins as Targeted "Magical Pills" for the Conservative Treatment of Endometriosis: May Potential Adverse Effects on Female Fertility Represent the "Dark Side of the Same Coin"? A Systematic Review of Literature.

    PubMed

    Vitagliano, Amerigo; Noventa, Marco; Quaranta, Michela; Gizzo, Salvatore

    2016-04-01

    The aim of the study was to analyze all the available evidence from both in vitro and in vivo studies regarding the efficacy of statin therapy in the treatment of endometriosis, evaluating the potential efficacy, side effects, and contraindications of their administration in humans. We focused on defining the potential benefits that the administration of statins may have on patients affected by endometriosis and the possible adverse effects of such a therapy on ovarian function and fertility profile. According to our article selection criteria, we included in the review in vitro and in vivo studies performed on human or animal models. The systematic review of literature identified 24 eligible articles, 12 of which reported evidence regarding the effects of statins on endometrial/endometriotic cells and 12 regarding their effects on ovarian function and fertility. All articles seem to emphasize the utility of statin administration in the treatment of endometriosis due to their anti-proliferative/proapoptotic effects, their ability to reduce cell viability and migration, and the inhibition of angiogenesis and anti-inflammatory activities. Regarding the potential adverse effects on gonadal activities, steroidogenesis and fertility function, no conclusive data were collected in human models (excluding women affected by polycystic ovary syndrome in which significant decline of androgen levels was reported after statin treatment), while contrasting results were reported by studies conducted in in vitro and in vivo in animal models. Despite evidence supporting statins as the potential therapeutic agent for a targeted conservative treatment of endometriosis, the uncertainties regarding their impact on gonadal function may not define them as an appropriate therapy for all young fertile women.

  17. Gridless retarding potential analyzer for use in very-low-energy charged particle detection

    NASA Technical Reports Server (NTRS)

    Shyn, T. W.; Sharp, W. E.; Hays, P. B.

    1976-01-01

    The theory of the hyperbolic retarding potential analyzer in the electrostatic mode is developed in detail and verified in the laboratory. A monoenergetic electron beam is used for the laboratory investigation. The analyzer (acronym HARP) has advantages over other conventional electrostatic analyzers; among them are less contact potential influence and high throughput because of the symmetry shape of the analyzer. The most useful application of the HARP is in detecting low-energy charged particles. A sample of low-energy particle data obtained in the earth's ionosphere is given.

  18. Gridless retarding potential analyzer for use in very-low-energy charged particle detection

    NASA Technical Reports Server (NTRS)

    Shyn, T. W.; Sharp, W. E.; Hays, P. B.

    1976-01-01

    The theory of the hyperbolic retarding potential analyzer in the electrostatic mode is developed in detail and verified in the laboratory. A monoenergetic electron beam is used for the laboratory investigation. The analyzer (acronym HARP) has advantages over other conventional electrostatic analyzers; among them are less contact potential influence and high throughput because of the symmetry shape of the analyzer. The most useful application of the HARP is in detecting low-energy charged particles. A sample of low-energy particle data obtained in the earth's ionosphere is given.

  19. System for Detecting Potential Lost Person based on Conditional Random Field

    NASA Astrophysics Data System (ADS)

    Kusuma, R. S.; Saptawati, G. A. P.

    2017-01-01

    Global Positioning System (GPS) technology has been used widely in transsportation industry to help company in managing taxis. The most popular GPS utilization for taxi company is to identify the position of taxis and monitor theirs the mobility. Nowdays, data collected from GPS tracker is combined with data from taxi meter are analyzed to provide region information regarding potential passengers. Zicheng Liao’s proposed a system based on GPS taxi data to detect anomalous area/region which was then interpreted as region with to predict rare passengers. The system was developed based on conditional random field (CRF) method and features position, velocity, passenger loading information. Our research was aimed to develop tool based on GPS data to detect potential lost person. We motivated by Liao research and modified the algorithms and features of CRF. Our experiments showed that the system has precision of 98.86% and recall of 87.478%.

  20. Evaluation of potential cationic probes for the detection of proline and betaine.

    PubMed

    Kalsoom, Umme; Breadmore, Michael C; Guijt, Rosanne M; Boyce, Mary C

    2014-12-01

    Osmoregulants are the substances that help plants to tolerate environmental extremes such as salinity and drought. Proline and betaine are two of the most commonly studied osmoregulants. An indirect UV CE method has been developed for simultaneous determination of these osmoregulants. A variety of reported probes and compounds were examined as potential probes for the indirect detection of proline and betaine. Mobility and UV-absorption properties highlighted sulfanilamide as a potential probe for indirect analysis of proline and betaine. Using 5 mM sulfanilamide at pH 2.2 with UV detection at 254 nm, proline and betaine were separated in less than 15 min. The LODs for proline and betaine were 11.6 and 28.3 μM, respectively. The developed method was successfully applied to quantification of these two osmoregulants in spinach and beetroot samples.

  1. Monitoring for potential adverse effects of prenatal gene therapy: genotoxicity analysis in vitro and on small animal models ex vivo and in vivo.

    PubMed

    Themis, Michael

    2012-01-01

    Gene delivery by integrating vectors has the potential to cause genotoxicity in the host by insertional mutagenesis (IM). Previously, the risk of IM by replication incompetent retroviral vectors was believed to be small. However, the recent observation of leukaemic events due to gamma retroviral vector insertion and activation of the LMO-2 proto-oncogene in patients enrolled in the French and British gene therapy trials for X-SCID demonstrates the need to understand vector associated genotoxicity in greater detail. These findings have led to the development of in vitro, ex vivo, and in vivo assays designed to predict genotoxic risk and to further our mechanistic understanding of this process at the molecular level. In vitro assays include transformation of murine haematopoietic stem cells by integrating retroviral (RV) or lentiviral (LV) vectors and measurement of cell survival resulting from transformation due to integration mainly into the Evi1 oncogene. Ex vivo assays involve harvesting haematopoietic stem cells from mice followed by gene transfer and re-infusion of RV or LV infected cells to reconstitute the immune system. Insertional mutagenesis is then determined by analysis of clonally dominant populations of cells. The latter model has also been made highly sensitive using cells from mice predisposed to oncogenesis by lack of the P53 and Rb pathways. Our investigations on fetal gene therapy discovered a high incidence of liver tumour development that appears to be associated with vector insertions into cancer-related genes. Many genes involved in growth and differentiation are actively transcribed in early developmental and are therefore in an open chromatin configuration, which favours provirus insertion. Some of these genes are known oncogenes or anti-oncogenes and are not usually active during adulthood. We found that in utero injection of primate HIV-1, HR'SIN-cPPT-S-FIX-W does not result in oncogenesis as opposed to administration of non-primate equine

  2. The potential of CO2 laser photoacoustic spectrometry for detection of methanol in alcoholic beverage

    NASA Astrophysics Data System (ADS)

    Lin, J.-W.; Shaw, S.-Y.

    2009-03-01

    The first use of CO2 laser photoacoustic measurements for detecting the methanol contents in alcohol-like solutions is presented. With an intracavity cell configuration, the minimum detectable concentration was ˜200 ppm for methanol and the linear range of the calibration curve for methanol was from 200 to 70000 ppm. For demonstrating the reliability of analysis in alcoholic beverages, a series of different concentrations of two-component samples was prepared and measured by the same procedures. The results showed the feasibility on determining methanol and ethanol contents accurately within a specific tolerance, limited mainly by background signal and laser stability. This potential method with no pre-treatment of samples takes only ˜10 min to finish one single measurement. It suggests that the PA detection is suitable for routine diagnosis of adulterated wines in commercial products.

  3. The temporal reliability of sound modulates visual detection: an event-related potential study.

    PubMed

    Li, Qi; Wu, Yan; Yang, Jingjing; Wu, Jinglong; Touge, Tetsuo

    2015-01-01

    Utilizing the high temporal resolution of event-related potentials (ERPs), we examined the effects of temporal reliability of sounds on visual detection. Significantly faster reaction times to visual target stimuli were observed when reliable temporal information was provided by a task-irrelevant auditory stimulus. Three main ERP components related to the effects of auditory temporal reliability were found: the first at 180-240 ms over a wide central area, the second at 300-400 ms over an anterior area, and the third at 300-380 ms over bilateral temporal areas. Our results support the hypothesis that temporal reliability affects visual detection and indicate that auditory facilitation of visual detection is partly due to spread of attention and thus results from implicit temporal linking of auditory and visual information at a relatively late processing stage.

  4. Application of conjugated heparin-albumin microparticles with laser-balloon angioplasty: a potential method for reducing adverse biologic reactivity after angioplasty

    NASA Astrophysics Data System (ADS)

    Kundu, Sourav K.; McMath, Linda P.; Zaidan, Jonathan T.; Spears, J. Richard

    1991-05-01

    Laser-balloon angioplasty (LBA) may potentially be used for local application of pharmacologically active agents which will reduce thrombogenic and proliferative responses after the angioplasty. In this study, the feasibility of applying covalently conjugated heparin- albumin microparticles onto arterial luminal surface was demonstrated. The covalent linkages were formed by reaction with 1-ethyl-3-dimethyl-aminopropyl-carbodiimide (EDC), and the resultant conjugates were used for preparation of microparticles by employing standard emulsification and heat-crosslinking techniques. The heparin release rate from the microparticles was found to be dependent upon the degree of crosslinking. When a thin coagulum of a suspension of microparticles was formed with heat on a glass surface, the treated surface demonstrated resistance to clot formation in contact with non-anticoagulated blood. A suspension of the microparticles applied during laser-balloon angioplasty onto the luminal surface of dog carotid and femoral arteries showed persistence for up to one week without thrombus formation or occlusion of the vessel. Since the rate of biodegradation is primarily dictated by the extent of crosslinking, an optimal degree of thermal denaturation will permit longer persistence of the carrier while allowing adequate release of the entrapped pharmacologic agent. A variety of antithrombotic and antiinflammatory agents are being considered as candidate bioprotective materials for local application after angioplasty.

  5. Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

    PubMed Central

    Byrne, Barry; Stack, Edwina; Gilmartin, Niamh; O'Kennedy, Richard

    2009-01-01

    Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided. PMID:22408533

  6. Visual change detection: event-related potentials are dependent on stimulus location in humans.

    PubMed

    Czigler, István; Balázs, László; Pató, Lívia G

    2004-07-08

    Infrequent colored patterns within sequences of patterns of frequent color elicited a posterior negative event-related potential component only in case of lower half-field stimulation. This negativity in the 140-200 ms latency range is considered as a correlate of automatic visual change detection (visual mismatch negativity, vMMN). Retinotopic prestriate visual areas are suggested to be the generating loci of vMMN.

  7. Potential role of infrared imaging for detecting facial seal leaks in filtering facepiece respirator users.

    PubMed

    Harber, Philip; Su, Jing; Badilla, Alejandro D; Rahimian, Rombod; Lansey, Kirsten R

    2015-01-01

    Infrared imaging (IRI) can detect airflow through and near respirator masks based upon temperature differences between ambient and exhaled air. This study investigated the potential usefulness of IRI for detecting leaks and providing insight into the sites and significance of leaks. Subjects (n = 165) used filtering facepiece N95 respirators (N95 FFR) in the course of a research study concerning training modalities. Short sequence video infrared images were obtained during use and with intentionally introduced facial seal leaks. Fit factor (FF) was measured with condensation nuclei count methods. IRI detected leaks were scored on a four-point scale and summarized as the Total Leak Score (TLS) over six coding regions and the presence or absence of a "Big Leak" (BL) in any location. A semi-automated interpretation algorithm was also developed. IRI detected leaks are particularly common in the nasal region, but these are of limited significance. IR imaging could effectively identify many large leaks. The TLS was related to FF. Although IRI scores were related to FF, the relationship is insufficiently close for IRI to substitute for quantitative fit-testing. Using FFRs infrared techniques have potential for identifying situations with very inadequate respiratory protection.

  8. Combustion-Generated Nanoparticulates in the El Paso, TX, USA / Juarez, Mexico Metroplex: Their Comparative Characterization and Potential for Adverse Health Effects

    PubMed Central

    Murr, L. E.; Soto, K. F.; Garza, K. M.; Guerrero, P. A.; Martinez, F.; Esquivel, E. V.; Ramirez, D. A.; Shi, Y.; Bang, J. J.; Venzor, J.

    2006-01-01

    In this paper we report on the collection of fine (PM1) and ultrafine (PM0.1), or nanoparticulate, carbonaceous materials using thermophoretic precipitation onto silicon monoxide/formvar-coated 3 mm grids which were examined in the transmission electron microscope (TEM). We characterize and compare diesel particulate matter (DPM), tire particulate matter (TPM), wood burning particulate matter, and other soot (or black carbons (BC)) along with carbon nanotube and related fullerene nanoparticle aggregates in the outdoor air, as well as carbon nanotube aggregates in the indoor air; and with reference to specific gas combustion sources. These TEM investigations include detailed microstructural and microdiffraction observations and comparisons as they relate to the aggregate morphologies as well as their component (primary) nanoparticles. We have also conducted both clinical surveys regarding asthma incidence and the use of gas cooking stoves as well as random surveys by zip code throughout the city of El Paso. In addition, we report on short term (2 day) and longer term (2 week) in vitro assays for black carbon and a commercial multiwall carbon nanotube aggregate sample using a murine macrophage cell line, which demonstrate significant cytotoxicity; comparable to a chrysotile asbestos nanoparticulate reference. The multi-wall carbon nanotube aggregate material is identical to those collected in the indoor and outdoor air, and may serve as a surrogate. Taken together with the plethora of toxic responses reported for DPM, these findings prompt concerns for airborne carbonaceous nanoparticulates in general. The implications of these preliminary findings and their potential health effects, as well as directions for related studies addressing these complex issues, will also be examined. PMID:16823077

  9. Combustion-generated nanoparticulates in the El Paso, TX, USA / Juarez, Mexico Metroplex: their comparative characterization and potential for adverse health effects.

    PubMed

    Murr, L E; Soto, K F; Garza, K M; Guerrero, P A; Martinez, F; Esquivel, E V; Ramirez, D A; Shi, Y; Bang, J J; Venzor, J

    2006-03-01

    In this paper we report on the collection of fine (PM1) and ultrafine (PM0.1), or nanoparticulate, carbonaceous materials using thermophoretic precipitation onto silicon monoxide/formvar-coated 3 mm grids which were examined in the transmission electron microscope (TEM). We characterize and compare diesel particulate matter (DPM), tire particulate matter (TPM), wood burning particulate matter, and other soot (or black carbons (BC)) along with carbon nanotube and related fullerene nanoparticle aggregates in the outdoor air, as well as carbon nanotube aggregates in the indoor air; and with reference to specific gas combustion sources. These TEM investigations include detailed microstructural and microdiffraction observations and comparisons as they relate to the aggregate morphologies as well as their component (primary) nanoparticles. We have also conducted both clinical surveys regarding asthma incidence and the use of gas cooking stoves as well as random surveys by zip code throughout the city of El Paso. In addition, we report on short term (2 day) and longer term (2 week) in vitro assays for black carbon and a commercial multiwall carbon nanotube aggregate sample using a murine macrophage cell line, which demonstrate significant cytotoxicity; comparable to a chrysotile asbestos nanoparticulate reference. The multi-wall carbon nanotube aggregate material is identical to those collected in the indoor and outdoor air, and may serve as a surrogate. Taken together with the plethora of toxic responses reported for DPM, these findings prompt concerns for airborne carbonaceous nanoparticulates in general. The implications of these preliminary findings and their potential health effects, as well as directions for related studies addressing these complex issues, will also be examined.

  10. Detecting single-trial EEG evoked potential using a wavelet domain linear mixed model: application to error potentials classification

    NASA Astrophysics Data System (ADS)

    Spinnato, J.; Roubaud, M.-C.; Burle, B.; Torrésani, B.

    2015-06-01

    Objective. The main goal of this work is to develop a model for multisensor signals, such as magnetoencephalography or electroencephalography (EEG) signals that account for inter-trial variability, suitable for corresponding binary classification problems. An important constraint is that the model be simple enough to handle small size and unbalanced datasets, as often encountered in BCI-type experiments. Approach. The method involves the linear mixed effects statistical model, wavelet transform, and spatial filtering, and aims at the characterization of localized discriminant features in multisensor signals. After discrete wavelet transform and spatial filtering, a projection onto the relevant wavelet and spatial channels subspaces is used for dimension reduction. The projected signals are then decomposed as the sum of a signal of interest (i.e., discriminant) and background noise, using a very simple Gaussian linear mixed model. Main results. Thanks to the simplicity of the model, the corresponding parameter estimation problem is simplified. Robust estimates of class-covariance matrices are obtained from small sample sizes and an effective Bayes plug-in classifier is derived. The approach is applied to the detection of error potentials in multichannel EEG data in a very unbalanced situation (detection of rare events). Classification results prove the relevance of the proposed approach in such a context. Significance. The combination of the linear mixed model, wavelet transform and spatial filtering for EEG classification is, to the best of our knowledge, an original approach, which is proven to be effective. This paper improves upon earlier results on similar problems, and the three main ingredients all play an important role.

  11. Detecting single-trial EEG evoked potential using a wavelet domain linear mixed model: application to error potentials classification.

    PubMed

    Spinnato, J; Roubaud, M-C; Burle, B; Torrésani, B

    2015-06-01

    The main goal of this work is to develop a model for multisensor signals, such as magnetoencephalography or electroencephalography (EEG) signals that account for inter-trial variability, suitable for corresponding binary classification problems. An important constraint is that the model be simple enough to handle small size and unbalanced datasets, as often encountered in BCI-type experiments. The method involves the linear mixed effects statistical model, wavelet transform, and spatial filtering, and aims at the characterization of localized discriminant features in multisensor signals. After discrete wavelet transform and spatial filtering, a projection onto the relevant wavelet and spatial channels subspaces is used for dimension reduction. The projected signals are then decomposed as the sum of a signal of interest (i.e., discriminant) and background noise, using a very simple Gaussian linear mixed model. Thanks to the simplicity of the model, the corresponding parameter estimation problem is simplified. Robust estimates of class-covariance matrices are obtained from small sample sizes and an effective Bayes plug-in classifier is derived. The approach is applied to the detection of error potentials in multichannel EEG data in a very unbalanced situation (detection of rare events). Classification results prove the relevance of the proposed approach in such a context. The combination of the linear mixed model, wavelet transform and spatial filtering for EEG classification is, to the best of our knowledge, an original approach, which is proven to be effective. This paper improves upon earlier results on similar problems, and the three main ingredients all play an important role.

  12. Adverse drug reactions and their measurement in the rheumatic diseases.

    PubMed

    Day, R O; Quinn, D I; Conaghan, P G; Tett, S E

    1995-05-01

    Drugs administered as therapy for rheumatological disorders are a relatively common cause of adverse events. Important data regarding the effects of drugs on patients with rheumatological conditions is being lost or rendered inaccessible because of deficiencies in classification, measurement, and collection methods for adverse drug reactions. A significant number of adverse reactions to drugs will not be known before marketing, and hence vigilance on the part of clinicians and patients in observing and documenting these reactions is paramount in building our knowledge and modifying our practice accordingly. A variety of systems and methods for detecting adverse drug reactions are described, critically evaluated, and compared for cost, potential bias, ethical concerns, and subject recruitment required for necessary statistical power. Systems need to be developed to give access to the wealth of clinical experimental data available in the individual practices of a broad spectrum of clinicians. To facilitate this, representative organizations need to make adverse drug reactions a high priority as well as contributing expertise and finance to database formulation and accessibility.

  13. [Pain as adverse drug reaction].

    PubMed

    Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard

    2012-09-01

    We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.

  14. Discriminative Manifold Learning Based Detection of Movement-Related Cortical Potentials.

    PubMed

    Lin, Chuang; Wang, Bing-Hui; Jiang, Ning; Xu, Ren; Mrachacz-Kersting, Natalie; Farina, Dario

    2016-09-01

    The detection of voluntary motor intention from EEG has been applied to closed-loop brain-computer interfacing (BCI). The movement-related cortical potential (MRCP) is a low frequency component of the EEG signal, which represents movement intention, preparation, and execution. In this study, we aim at detecting MRCPs from single-trial EEG traces. For this purpose, we propose a detector based on a discriminant manifold learning method, called locality sensitive discriminant analysis (LSDA), and we test it in both online and offline experiments with executed and imagined movements. The online and offline experimental results demonstrated that the proposed LSDA approach for MRCP detection outperformed the Locality Preserving Projection (LPP) approach, which was previously shown to be the most accurate algorithm so far tested for MRCP detection. For example, in the online tests, the performance of LSDA was superior than LPP in terms of a significant reduction in false positives (FP) (passive FP: 1.6 ±0.9/min versus 2.9 ±1.0/min, p = 0.002, active FP: 2.2 ±0.8/min versus 2.7 ±0.6/min , p = 0.03 ), for a similar rate of true positives. In conclusion, the proposed LSDA based MRCP detection method is superior to previous approaches and is promising for developing patient-driven BCI systems for motor function rehabilitation as well as for neuroscience research.

  15. Enhancing detection of steady-state visual evoked potentials using individual training data.

    PubMed

    Wang, Yijun; Nakanishi, Masaki; Wang, Yu-Te; Jung, Tzyy-Ping

    2014-01-01

    Although the performance of steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) has improved gradually in the past decades, it still does not meet the requirement of a high communication speed in many applications. A major challenge is the interference of spontaneous background EEG activities in discriminating SSVEPs. An SSVEP BCI using frequency coding typically does not have a calibration procedure since the frequency of SSVEPs can be recognized by power spectrum density analysis (PSDA). However, the detection rate can be deteriorated by the spontaneous EEG activities within the same frequency range because phase information of SSVEPs is ignored in frequency detection. To address this problem, this study proposed to incorporate individual SSVEP training data into canonical correlation analysis (CCA) to improve the frequency detection of SSVEPs. An eight-class SSVEP dataset recorded from 10 subjects in a simulated online BCI experiment was used for performance evaluation. Compared to the standard CCA method, the proposed method obtained significantly improved detection accuracy (95.2% vs. 88.4%, p<0.05) and information transfer rates (ITR) (104.6 bits/min vs. 89.1 bits/min, p<0.05). The results suggest that the employment of individual SSVEP training data can significantly improve the detection rate and thereby facilitate the implementation of a high-speed BCI.

  16. Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial

    PubMed Central

    Mullen, Keena AE; Beasley, Erin; Rizzo, Julio Q; Washburn, Steven P; Baynes, Ronald E; Mason, Sharon E

    2017-01-01

    Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta-lactam test, or to interfere with the detection of antibiotics by these tests. The three phytoceuticals tested were labelled for intramammary, topical or intravulvar administration. Testing was performed in vitro using the products diluted in milk obtained from healthy organic dairy cows. Phytoceuticals were tested at concentrations ranging from 1.5 per cent to 100 per cent. Concentration levels were replicated at least twice on each milk antibiotic residue screening test. The Delvotest P is based on detection of bacterial inhibitors and no positive results were obtained for any product at concentrations less than 50 per cent. The Charm SL Beta-lactam test uses a receptor for the detection of beta-lactam antibiotics and no concentration of phytoceuticals caused an interference with these tests. Based on dilution of the products in bovine milk at physiologically achievable levels, phytoceutical products tested at levels expected after treatment do not cause positive test results for the Delvotest P nor do they interfere with the Charm SL Beta-lactam test in detection of various antibiotics. PMID:28890791

  17. Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial.

    PubMed

    Mullen, Keena Ae; Beasley, Erin; Rizzo, Julio Q; Washburn, Steven P; Baynes, Ronald E; Mason, Sharon E; Anderson, Kevin L

    2017-01-01

    Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta-lactam test, or to interfere with the detection of antibiotics by these tests. The three phytoceuticals tested were labelled for intramammary, topical or intravulvar administration. Testing was performed in vitro using the products diluted in milk obtained from healthy organic dairy cows. Phytoceuticals were tested at concentrations ranging from 1.5 per cent to 100 per cent. Concentration levels were replicated at least twice on each milk antibiotic residue screening test. The Delvotest P is based on detection of bacterial inhibitors and no positive results were obtained for any product at concentrations less than 50 per cent. The Charm SL Beta-lactam test uses a receptor for the detection of beta-lactam antibiotics and no concentration of phytoceuticals caused an interference with these tests. Based on dilution of the products in bovine milk at physiologically achievable levels, phytoceutical products tested at levels expected after treatment do not cause positive test results for the Delvotest P nor do they interfere with the Charm SL Beta-lactam test in detection of various antibiotics.

  18. Faces of adversity.

    PubMed

    Bunkers, Sandra Schmidt

    2008-04-01

    This column introduces ideas for a nursing curriculum addressing living with adversity. The question is posed: How do we educate professional nurses to be with others in compassionate and helpful ways at times of calamitous or disastrous experiences? To answer this question the following possibilities for curriculum development are presented: (a) undergird nursing knowledge with value-laden nursing theory, (b) provide "away experiences" for both undergraduate and graduate students in nursing; (c) include theoretical literature on adversity in the curriculum; and (d) develop programs of research addressing phenomena of health experienced by those living with adversity. The column concludes with a personal story of an "away experience" by Vickie Britson.

  19. Advancing the detection of steady-state visual evoked potentials in brain-computer interfaces

    NASA Astrophysics Data System (ADS)

    Abu-Alqumsan, Mohammad; Peer, Angelika

    2016-06-01

    Objective. Spatial filtering has proved to be a powerful pre-processing step in detection of steady-state visual evoked potentials and boosted typical detection rates both in offline analysis and online SSVEP-based brain-computer interface applications. State-of-the-art detection methods and the spatial filters used thereby share many common foundations as they all build upon the second order statistics of the acquired Electroencephalographic (EEG) data, that is, its spatial autocovariance and cross-covariance with what is assumed to be a pure SSVEP response. The present study aims at highlighting the similarities and differences between these methods. Approach. We consider the canonical correlation analysis (CCA) method as a basis for the theoretical and empirical (with real EEG data) analysis of the state-of-the-art detection methods and the spatial filters used thereby. We build upon the findings of this analysis and prior research and propose a new detection method (CVARS) that combines the power of the canonical variates and that of the autoregressive spectral analysis in estimating the signal and noise power levels. Main results. We found that the multivariate synchronization index method and the maximum contrast combination method are variations of the CCA method. All three methods were found to provide relatively unreliable detections in low signal-to-noise ratio (SNR) regimes. CVARS and the minimum energy combination methods were found to provide better estimates for different SNR levels. Significance. Our theoretical and empirical results demonstrate that the proposed CVARS method outperforms other state-of-the-art detection methods when used in an unsupervised fashion. Furthermore, when used in a supervised fashion, a linear classifier learned from a short training session is able to estimate the hidden user intention, including the idle state (when the user is not attending to any stimulus), rapidly, accurately and reliably.

  20. Decision-related cortical potentials during an auditory signal detection task with cued observation intervals

    NASA Technical Reports Server (NTRS)

    Squires, K. C.; Squires, N. K.; Hillyard, S. A.

    1975-01-01

    Cortical-evoked potentials were recorded from human subjects performing an auditory detection task with confidence rating responses. Unlike earlier studies that used similar procedures, the observation interval during which the auditory signal could occur was clearly marked by a visual cue light. By precisely defining the observation interval and, hence, synchronizing all perceptual decisions to the evoked potential averaging epoch, it was possible to demonstrate that high-confidence false alarms are accompanied by late-positive P3 components equivalent to those for equally confident hits. Moreover the hit and false alarm evoked potentials were found to covary similarly with variations in confidence rating and to have similar amplitude distributions over the scalp. In a second experiment, it was demonstrated that correct rejections can be associated with a P3 component larger than that for hits. Thus it was possible to show, within the signal detection paradigm, how the two major factors of decision confidence and expectancy are reflected in the P3 component of the cortical-evoked potential.

  1. Adverse food-drug interactions.

    PubMed

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.

  2. The value of time-to-onset in statistical signal detection of adverse drug reactions: a comparison with disproportionality analysis in spontaneous reports from the Netherlands.

    PubMed

    Scholl, Joep H G; van Puijenbroek, Eugène P

    2016-12-01

    In pharmacovigilance, the commonly used disproportionality analysis (DPA) in statistical signal detection is known to have its limitations. The aim of this study was to investigate the value of the time to onset (TTO) of ADRs in addition to DPA. We performed a pilot study using individual case safety reports (ICSRs) for three drugs (Cervarix®, nitrofurantoin and simvastatin) from the Lareb spontaneous reporting database. TTO distributions for drug - ADR associations were compared to other ADRs for the same drug and to other drugs for the same ADR using two-sample Anderson-Darling testing. Statistically significant associations were considered true positive (TP) signals if the association was present in the official product information of the drug. Sensitivity and specificity for the TTO method were compared with the DPA method. As a measure of disproportionality, the reporting odds ratio (ROR) was used. In general, sensitivity was lower, and specificity was higher for the TTO method compared to DPA. The TTO method showed similar sensitivity for all three drugs, whereas specificity was lower for Cervarix®. Eight additional TP signals were found using the TTO method compared to DPA. Our study shows that statistical signal detection based on the TTO alone resulted in a limited number of additional signals compared to DPA. We therefore conclude that the TTO method is of limited value for full database statistical screening in our setting. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Topological quantum phase transition in synthetic non-Abelian gauge potential: gauge invariance and experimental detections.

    PubMed

    Sun, Fadi; Yu, Xiao-Lu; Ye, Jinwu; Fan, Heng; Liu, Wu-Ming

    2013-01-01

    The method of synthetic gauge potentials opens up a new avenue for our understanding and discovering novel quantum states of matter. We investigate the topological quantum phase transition of Fermi gases trapped in a honeycomb lattice in the presence of a synthetic non-Abelian gauge potential. We develop a systematic fermionic effective field theory to describe a topological quantum phase transition tuned by the non-Abelian gauge potential and explore its various important experimental consequences. Numerical calculations on lattice scales are performed to compare with the results achieved by the fermionic effective field theory. Several possible experimental detection methods of topological quantum phase transition are proposed. In contrast to condensed matter experiments where only gauge invariant quantities can be measured, both gauge invariant and non-gauge invariant quantities can be measured by experimentally generating various non-Abelian gauges corresponding to the same set of Wilson loops.

  4. Determination of set potential voltages for cucumber mosaic virus detection using screen printed carbon electrode

    NASA Astrophysics Data System (ADS)

    Uda, M. N. A.; Hasfalina, C. M.; Samsuzana, A. A.; Faridah, S.; Rafidah A., R.; Hashim, U.; Ariffin, Shahrul A. B.; Gopinath, Subash C. B.

    2017-03-01

    Cucumber Mosaic Virus (CMV) is a most dangerous pathogen among the cucurbit plant which it striking cucumbers, zucchinis, squashes, watermelons but it also striking to non-cucurbit such as peppers, tobaccos, celeries, beans and tomatoes. Symptoms shown by this virus when they starting to strike are very significant and at the end can kill the hosts they infected. In order to detect these viruses, biosensor such as screen-printed carbon electrode (SPCE) is developed and fixes a set potential voltage is defined using Chronoamperometry (CM) immunosensor technique. For short introduction, CM is a process which is a constant applied potential voltage between the working and reference electrode is maintained in order to create an electrons transfer for the oxidation or reduction species taking place at the surface of working electrode is measured and in this manuscript, complete details about measurement were used to finding the stable set potential voltages will be pointed out.

  5. Topological Quantum Phase Transition in Synthetic Non-Abelian Gauge Potential: Gauge Invariance and Experimental Detections

    PubMed Central

    Sun, Fadi; Yu, Xiao-Lu; Ye, Jinwu; Fan, Heng; Liu, Wu-Ming

    2013-01-01

    The method of synthetic gauge potentials opens up a new avenue for our understanding and discovering novel quantum states of matter. We investigate the topological quantum phase transition of Fermi gases trapped in a honeycomb lattice in the presence of a synthetic non-Abelian gauge potential. We develop a systematic fermionic effective field theory to describe a topological quantum phase transition tuned by the non-Abelian gauge potential and explore its various important experimental consequences. Numerical calculations on lattice scales are performed to compare with the results achieved by the fermionic effective field theory. Several possible experimental detection methods of topological quantum phase transition are proposed. In contrast to condensed matter experiments where only gauge invariant quantities can be measured, both gauge invariant and non-gauge invariant quantities can be measured by experimentally generating various non-Abelian gauges corresponding to the same set of Wilson loops. PMID:23846153

  6. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  7. All optical experimental design for neuron excitation, inhibition, and action potential detection

    NASA Astrophysics Data System (ADS)

    Walsh, Alex J.; Tolstykh, Gleb; Martens, Stacey; Sedelnikova, Anna; Ibey, Bennett L.; Beier, Hope T.

    2016-03-01

    Recently, infrared light has been shown to both stimulate and inhibit excitatory cells. However, studies of infrared light for excitatory cell inhibition have been constrained by the use of invasive and cumbersome electrodes for cell excitation and action potential recording. Here, we present an all optical experimental design for neuronal excitation, inhibition, and action potential detection. Primary rat neurons were transfected with plasmids containing the light sensitive ion channel CheRiff. CheRiff has a peak excitation around 450 nm, allowing excitation of transfected neurons with pulsed blue light. Additionally, primary neurons were transfected with QuasAr2, a fast and sensitive fluorescent voltage indicator. QuasAr2 is excited with yellow or red light and therefore does not spectrally overlap CheRiff, enabling imaging and action potential activation, simultaneously. Using an optic fiber, neurons were exposed to blue light sequentially to generate controlled action potentials. A second optic fiber delivered a single pulse of 1869nm light to the neuron causing inhibition of the evoked action potentials (by the blue light). When used in concert, these optical techniques enable electrode free neuron excitation, inhibition, and action potential recording, allowing research into neuronal behaviors with high spatial fidelity.

  8. A novel multiplex polymerase chain reaction assay for detection of both HLA-A*31:01/HLA-B*15:02 alleles, which confer susceptibility to carbamazepine-induced severe cutaneous adverse reactions.

    PubMed

    Nguyen, D V; Vidal, C; Chi, H C; Do, N T Q; Fulton, R; Li, J; Fernando, S L

    2017-09-08

    HLA-A*31:01 and HLA-B*15:02 have been widely reported to confer genetic susceptibility to carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCARs). Accordingly, the screening for these alleles has been highly recommended to prevent SCAR prior to introducing CBZ therapy. Although a number of methods are available for screening of HLA-A*31:01 or HLA-B*15:02 alleles separately, developing an assay that can detect both these alleles would be more clinically practical, cost-effective and less time-consuming. Therefore, in this study, a multiplex polymerase chain reaction (PCR) using TaqMan Probe was designed and validated to be able to detect HLA-A*31:01 and HLA-B*15:02. In comparison with Luminex-SSO/SBT/SSB, the multiplex PCR assay for detection of HLA-A*31:01 and HLA-B*15:02 had a perfect agreement in the validation group of 125 samples. The method was able to detect the target genes at the DNA concentration of 0.037 ng/μL. The unit cost of this assay is less than $5 USD with total time of 110 minutes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Detection and characterization of potentially zoonotic viruses in faeces of pigs at slaughter in Germany.

    PubMed

    Machnowska, Patrycja; Ellerbroek, Lüppo; Johne, Reimar

    2014-01-10

    Pigs can harbour a variety of viruses in their gastrointestinal tract. Some of them are closely related to human viruses and are therefore suspected to have a zoonotic potential. Only little is known about the presence of those viruses in pigs at slaughter. However, by contamination of meat with zoonotic viruses during the slaughtering process, food-borne transmission to humans may be possible. Here we analyzed 120 faecal samples of pigs at slaughter from 3 different geographical regions of Germany for the presence of astrovirus (AstV), encephalomyocarditis virus (EMCV), hepatitis E virus (HEV), norovirus genogroup II (NoV GII) and group A rotavirus (GARV). Using real-time RT-PCR, the most frequently detected virus was AstV, which was present in 20.8% of the samples, followed by NoV GII with a detection rate of 14.2%. EMCV, HEV and GARV were found only occasionally with detection rates of 4.2%, 2.5% and 0.8%, respectively. Analyses of partial genome sequences of the viruses indicated that the detected AstV and NoV GII mainly represented typical pig virus strains, which have not been detected in humans so far. However, the GARV and HEV strains were more closely related to human strains. The results indicate that enteric viruses, some of them with zoonotic potential, are present in pig faeces at slaughter. Application of good hygiene practice is necessary to minimize the risk of introducing these viruses into the food and to prevent virus transmission to highly exposed persons such as slaughterers and veterinarians. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Real-Time Detection and Monitoring of Acute Brain Injury Utilizing Evoked Electroencephalographic Potentials.

    PubMed

    Fisher, Jonathan A N; Huang, Stanley; Ye, Meijun; Nabili, Marjan; Wilent, W Bryan; Krauthamer, Victor; Myers, Matthew R; Welle, Cristin G

    2016-09-01

    Rapid detection and diagnosis of a traumatic brain injury (TBI) can significantly improve the prognosis for recovery. Helmet-mounted sensors that detect impact severity based on measurements of acceleration or pressure show promise for aiding triage and transport decisions in active, field environments such as professional sports or military combat. The detected signals, however, report on the mechanics of an impact rather than directly indicating the presence and severity of an injury. We explored the use of cortical somatosensory evoked electroencephalographic potentials (SSEPs) to detect and track, in real-time, neural electrophysiological abnormalities within the first hour following head injury in an animal model. To study the immediate electrophysiological effects of injury in vivo, we developed an experimental paradigm involving focused ultrasound that permits continuous, real-time measurements and minimizes mechanical artifact. Injury was associated with a dramatic reduction of amplitude over the damaged hemisphere directly after the injury. The amplitude systematically improved over time but remained significantly decreased at one hour, compared with baseline. In contrast, at one hour there was a concomitant enhancement of the cortical SSEP amplitude evoked from the uninjured hemisphere. Analysis of the inter-trial electroencephalogram (EEG) also revealed significant changes in low-frequency components and an increase in EEG entropy up to 30 minutes after injury, likely reflecting altered EEG reactivity to somatosensory stimuli. Injury-induced alterations in SSEPs were also observed using noninvasive epidermal electrodes, demonstrating viability of practical implementation. These results suggest cortical SSEPs recorded at just a few locations by head-mounted sensors and associated multiparametric analyses could potentially be used to rapidly detect and monitor brain injury in settings that normally present significant levels of mechanical and electrical

  11. Detection of Fatigue Crack in Basalt FRP Laminate Composite Pipe using Electrical Potential Change Method

    NASA Astrophysics Data System (ADS)

    Altabey, Wael A.; Noori, Mohammed

    2017-05-01

    Novel modulation electrical potential change (EPC) method for fatigue crack detection in a basalt fibre reinforced polymer (FRP) laminate composite pipe is carried out in this paper. The technique is applied to a laminate pipe with an embedded crack in three layers [0º/90º/0º]s. EPC is applied for evaluating the dielectric properties of basalt FRP pipe by using an electrical capacitance sensor (ECS) to discern damages in the pipe. Twelve electrodes are mounted on the outer surface of the pipe and the changes in the modulation dielectric properties of the piping system are analyzed to detect damages in the pipe. An embedded crack is created by a fatigue internal pressure test. The capacitance values, capacitance change and node potential distribution of ECS electrodes are calculated before and after crack initiates using a finite element method (FEM) by ANSYS and MATLAB, which are combined to simulate sensor characteristics and fatigue behaviour. The crack lengths of the basalt FRP are investigated for various number of cycles to failure for determining crack growth rate. Response surfaces are adopted as a tool for solving inverse problems to estimate crack lengths from the measured electric potential differences of all segments between electrodes to validate the FEM results. The results show that, the good convergence between the FEM and estimated results. Also the results of this study show that the electrical potential difference of the basalt FRP laminate increases during cyclic loading, caused by matrix cracking. The results indicate that the proposed method successfully provides fatigue crack detection for basalt FRP laminate composite pipes.

  12. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    PubMed Central

    Barry, John F.; Turner, Matthew J.; Schloss, Jennifer M.; Glenn, David R.; Song, Yuyu; Lukin, Mikhail D.; Park, Hongkun; Walsworth, Ronald L.

    2016-01-01

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution—e.g., magnetic resonance imaging methods and magnetoencephalography—or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector. PMID:27911765

  13. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond.

    PubMed

    Barry, John F; Turner, Matthew J; Schloss, Jennifer M; Glenn, David R; Song, Yuyu; Lukin, Mikhail D; Park, Hongkun; Walsworth, Ronald L

    2016-12-06

    Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution-e.g., magnetic resonance imaging methods and magnetoencephalography-or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.

  14. EEG error potentials detection and classification using time-frequency features for robot reinforcement learning.

    PubMed

    Boubchir, Larbi; Touati, Youcef; Daachi, Boubaker; Chérif, Arab Ali

    2015-08-01

    In thought-based steering of robots, error potentials (ErrP) can appear when the action resulting from the brain-machine interface (BMI) classifier/controller does not correspond to the user's thought. Using the Steady State Visual Evoked Potentials (SSVEP) techniques, ErrP, which appear when a classification error occurs, are not easily recognizable by only examining the temporal or frequency characteristics of EEG signals. A supplementary classification process is therefore needed to identify them in order to stop the course of the action and back up to a recovery state. This paper presents a set of time-frequency (t-f) features for the detection and classification of EEG ErrP in extra-brain activities due to misclassification observed by a user exploiting non-invasive BMI and robot control in the task space. The proposed features are able to characterize and detect ErrP activities in the t-f domain. These features are derived from the information embedded in the t-f representation of EEG signals, and include the Instantaneous Frequency (IF), t-f information complexity, SVD information, energy concentration and sub-bands' energies. The experiment results on real EEG data show that the use of the proposed t-f features for detecting and classifying EEG ErrP achieved an overall classification accuracy up to 97% for 50 EEG segments using 2-class SVM classifier.

  15. Stochastic Resonance in an Underdamped System with Pinning Potential for Weak Signal Detection

    PubMed Central

    Zhang, Haibin; He, Qingbo; Kong, Fanrang

    2015-01-01

    Stochastic resonance (SR) has been proved to be an effective approach for weak sensor signal detection. This study presents a new weak signal detection method based on a SR in an underdamped system, which consists of a pinning potential model. The model was firstly discovered from magnetic domain wall (DW) in ferromagnetic strips. We analyze the principle of the proposed underdamped pinning SR (UPSR) system, the detailed numerical simulation and system performance. We also propose the strategy of selecting the proper damping factor and other system parameters to match a weak signal, input noise and to generate the highest output signal-to-noise ratio (SNR). Finally, we have verified its effectiveness with both simulated and experimental input signals. Results indicate that the UPSR performs better in weak signal detection than the conventional SR (CSR) with merits of higher output SNR, better anti-noise and frequency response capability. Besides, the system can be designed accurately and efficiently owing to the sensibility of parameters and potential diversity. The features also weaken the limitation of small parameters on SR system. PMID:26343662

  16. Microchip electrophoresis with wall-jet electrochemical detector: influence of detection potential upon resolution of solutes.

    PubMed

    Pumera, Martin; Merkoçi, Arben; Alegret, Salvador

    2006-12-01

    This report studies the electrochemical response of wall-jet detector for microchip electrophoresis (microCE). It shows that in wall-jet configuration, the electrochemical detector operates in coulometric mode and that there is an influence of detection potential upon peak width and therefore upon the resolution of solutes. Upon raising the detection potential from +0.3 to +0.9 V, the resolution between model analytes, dopamine and catechol, increases from 0.63 to 2.90. The reasons for this behavior originate in wall-jet detector design and in its typically significant higher detector volume than the volume of injected sample. The conversion efficiency of the wall-jet electrochemical detection cell was found to be 97.4% for dopamine and 98.0% for catechol. The paper brings deeper understanding of operations of wall-jet electrochemical detectors for microchip devices, and it explains previously reported significantly sharper peaks when electrocatalytic electrodes (i.e., palladium and carbon nanotube) were used in microCE-electrochemistry wall-jet detector.

  17. Potential Use of HF Radar for Tsunami Detection in the Central and Eastern Mediterranean

    NASA Astrophysics Data System (ADS)

    Cokacar, Tulay; Necmioglu, Ocal; Ozer, Ceren

    2016-04-01

    Today, HF radar is recognized as internationally cost-effective and efficient solution to provide near-real time measurements that cover a large area continuously over time for ocean hazards warning and long term ocean monitoring studies such as, seasonal forecasts of climate, hurricanes, s torm surges and large-scale ocean circulation changes. These radar systems recently became an operational tool in coastal monitoring worldwide. They are used for many operational applications that include ship detection, tracking, guidance, distribution of pollutants, fishery and oceanography. HF radar data used for the tsunami warnings, can also be used for the other purposes and be of potential interest to wide application area users and stakeholders. Moreover multi user applications will ensure the system is maintained operationally over the long term. Hence the system is cost effective also with regards to maintenance. New algorithms allow useful detection and verification for tsunami detection. While technical monitoring capacity and the algorithms for tsunami detection is improved significantly, further studies are required to obtain complete wave height determination. We analysed the available technology and algorithms for the purpose of tsunami detection in the central-eastern Mediterranean and its connected Seas (Aegean and Black Sea). Since the study area is characterized by narrow continental shelf area, the HF radar observation for the purpose of tsunami detection is possible in restricted areas. While extensive continental shelves in the northeastern Black Sea and along the coast of Tunisia in the central Mediterranean let tsunami detection 2.5 hours before tsunami waves hit the coast, the detection is possible around 1 hr or less in advance for the remaining basins with wide continental shelf areas. The bathymetric structure is important for deciding the applicability of HF radar systems for the tsunami detection in continental shelf areas, which can be covered by

  18. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  19. Role of community pharmacists in the detection of potentially inappropriate benzodiazepines prescriptions for insomnia.

    PubMed

    Urru, Silvana Anna Maria; Pasina, Luca; Minghetti, Paola; Giua, Corrado

    2015-12-01

    The appropriate management of chronic insomnia is crucial and prescribing of hypnotic drugs is common. Regular and prolonged use of hypnotics should be avoided because of the risk of tolerance to effects, dependence and an increased risk of adverse events. In 2012, updated Beers criteria for potentially inappropriate medication in older adults suggested to avoid all benzodiazepines in older adults to treat insomnia. In addition, successful discontinuation may result in improvements on cognitive and psychomotor function, particularly in older people. To investigate the appropriateness of benzodiazepines prescription for insomnia and explore the role that community pharmacists can have in identifying signals of potential inappropriate drug prescriptions. Community pharmacies in Italy. This is an observational study conducted in 8 community pharmacies. Each pharmacist was asked to interview a sample of patients with the prescriptions of at least one benzodiazepine and to complete a minimum data set collecting information about socio-demographic characteristics, drug indication, duration of drug prescription, number of hypnotic-drugs, previous attempt to drug-discontinuation, preference of patients about benzodiazepine withdrawal and modality of drug tapering. Main outcome measure Indications, treatment duration, dosage and drug discontinuation attempts and modalities. A total of 181 participants were interviewed. About half of respondents (n = 81) reported to be treated for insomnia and 62 % were elderly (mean age 68, range 27-93). Fifty-two patients (64 %) were on long term treatment (>3 years) while for thirteen patients (16 %) duration of treatment was comprised between 1 and 3 years. Thirty-three patients were in favour of benzodiazepine-discontinuation but in all cases discontinuation was unsuccessful. Use of community pharmacy survey data allowed us to obtain information about incorrect management of insomnia and inappropriate benzodiazepines prescriptions

  20. ITIH3 Is a Potential Biomarker for Early Detection of Gastric Cancer

    PubMed Central

    Chong, Poh Kuan; Lee, Huiyin; Zhou, Jianbiao; Liu, Shaw-Cheng; Shia Loh, Marie Chiew; Wang, Ting Ting; Chan, Siew Pang; Smoot, Duane T.; Ashktorab, Hassan; Yan So, Jimmy Bok; Lim, Khong Hee; Yeoh, Khay Guan; Lim, Yoon Pin

    2013-01-01

    Gastric cancer has one of the highest morbidities and mortalities worldwide. Early detection is key measure to improve the outcome of gastric cancer patients. In our efforts to identify potential markers for gastric cancer detection, we coupled xenotransplantation mouse model with a plasma proteomic approach. MKN45 gastric cancer cells were subcutaneously injected into nude mice and plasma samples from mice bearing different sizes of tumors were collected and subjected to iTRAQ and mass spectrometry analysis. ITIH3 protein was found to be more highly expressed in plasma of tumor bearing mice compared to control. Subsequent screening of ITIH3 expression in 167 clinical plasma samples, including 83 cancer-free subjects and 84 gastric cancer patients, revealed higher ITIH3 level in the plasma of gastric cancer patients. A receiver operating characteristics (ROC) curve estimated a maximal sensitivity of 96% at 66% specificity for ITIH3 in gastric cancer detection. In addition, plasma from early stage gastric cancer patient has significantly (p < 0.001) higher level of ITIH3 compared to that from noncancer subject. Our data suggest that ITIH3 may be a useful biomarker for early detection of gastric cancer. PMID:20515073

  1. Early Seizure Detection Using Neuronal Potential Similarity: A Generalized Low-Complexity and Robust Measure.

    PubMed

    Bandarabadi, Mojtaba; Rasekhi, Jalil; Teixeira, Cesar A; Netoff, Theoden I; Parhi, Keshab K; Dourado, Antonio

    2015-08-01

    A novel approach using neuronal potential similarity (NPS) of two intracranial electroencephalogram (iEEG) electrodes placed over the foci is proposed for automated early seizure detection in patients with refractory partial epilepsy. The NPS measure is obtained from the spectral analysis of space-differential iEEG signals. Ratio between the NPS values obtained from two specific frequency bands is then investigated as a robust generalized measure, and reveals invaluable information about seizure initiation trends. A threshold-based classifier is subsequently applied on the proposed measure to generate alarms. The performance of the method was evaluated using cross-validation on a large clinical dataset, involving 183 seizure onsets in 1785 h of long-term continuous iEEG recordings of 11 patients. On average, the results show a high sensitivity of 86.9% (159 out of 183), a very low false detection rate of 1.4 per day, and a mean detection latency of 13.1 s from electrographic seizure onsets, while in average preceding clinical onsets by 6.3 s. These high performance results, specifically the short detection latency, coupled with the very low computational cost of the proposed method make it adequate for using in implantable closed-loop seizure suppression systems.

  2. Common DNA sequences with potential for detection of genetically manipulated organisms in food.

    PubMed

    MacCormick, C A; Griffin, H G; Underwood, H M; Gasson, M J

    1998-06-01

    Foods produced by genetic engineering technology are now appearing on the market and many more are likely to emerge in the future. The safety aspects, regulation, and labelling of these foods are still contentious issues in most countries and recent surveys highlight consumer concerns about the safety and labelling of genetically modified food. In most countries it is necessary to have approval for the use of genetically manipulated organisms (GMOs) in the production of food. In order to police regulations, a technology to detect such foods is desirable. In addition, a requirement to label approved genetically modified food would necessitate a monitoring system. One solution is to 'tag' approved GMOs with some form of biological or genetic marker, permitting the surveillance of foods for the presence of approved products of genetic engineering. While non-approved GMOs would not be detected by such a surveillance, they might be detected by a screen for DNA sequences common to all or most GMOs. This review focuses on the potential of using common DNA sequences as detection probes for GMOs. The identification of vector sequences, plant transcription terminators, and marker genes by PCR and hybridization techniques is discussed.

  3. Potential Biomarkers and Their Applications for Rapid and Reliable Detection of Malaria

    PubMed Central

    Jain, Priyamvada; Chakma, Babina; Patra, Sanjukta; Goswami, Pranab

    2014-01-01

    Malaria has been responsible for the highest mortality in most malaria endemic countries. Even after decades of malaria control campaigns, it still persists as a disease of high mortality due to improper diagnosis and rapidly evolving drug resistant malarial parasites. For efficient and economical malaria management, WHO recommends that all malaria suspected patients should receive proper diagnosis before administering drugs. It is thus imperative to develop fast, economical, and accurate techniques for diagnosis of malaria. In this regard an in-depth knowledge on malaria biomarkers is important to identify an appropriate biorecognition element and utilize it prudently to develop a reliable detection technique for diagnosis of the disease. Among the various biomarkers, plasmodial lactate dehydrogenase and histidine-rich protein II (HRP II) have received increasing attention for developing rapid and reliable detection techniques for malaria. The widely used rapid detection tests (RDTs) for malaria succumb to many drawbacks which promotes exploration of more efficient economical detection techniques. This paper provides an overview on the current status of malaria biomarkers, along with their potential utilization for developing different malaria diagnostic techniques and advanced biosensors. PMID:24804253

  4. Automatic roof plane detection and analysis in airborne lidar point clouds for solar potential assessment.

    PubMed

    Jochem, Andreas; Höfle, Bernhard; Rutzinger, Martin; Pfeifer, Norbert

    2009-01-01

    A relative height threshold is defined to separate potential roof points from the point cloud, followed by a segmentation of these points into homogeneous areas fulfilling the defined constraints of roof planes. The normal vector of each laser point is an excellent feature to decompose the point cloud into segments describing planar patches. An object-based error assessment is performed to determine the accuracy of the presented classification. It results in 94.4% completeness and 88.4% correctness. Once all roof planes are detected in the 3D point cloud, solar potential analysis is performed for each point. Shadowing effects of nearby objects are taken into account by calculating the horizon of each point within the point cloud. Effects of cloud cover are also considered by using data from a nearby meteorological station. As a result the annual sum of the direct and diffuse radiation for each roof plane is derived. The presented method uses the full 3D information for both feature extraction and solar potential analysis, which offers a number of new applications in fields where natural processes are influenced by the incoming solar radiation (e.g., evapotranspiration, distribution of permafrost). The presented method detected fully automatically a subset of 809 out of 1,071 roof planes where the arithmetic mean of the annual incoming solar radiation is more than 700 kWh/m(2).

  5. Automatic Roof Plane Detection and Analysis in Airborne Lidar Point Clouds for Solar Potential Assessment

    PubMed Central

    Jochem, Andreas; Höfle, Bernhard; Rutzinger, Martin; Pfeifer, Norbert

    2009-01-01

    A relative height threshold is defined to separate potential roof points from the point cloud, followed by a segmentation of these points into homogeneous areas fulfilling the defined constraints of roof planes. The normal vector of each laser point is an excellent feature to decompose the point cloud into segments describing planar patches. An object-based error assessment is performed to determine the accuracy of the presented classification. It results in 94.4% completeness and 88.4% correctness. Once all roof planes are detected in the 3D point cloud, solar potential analysis is performed for each point. Shadowing effects of nearby objects are taken into account by calculating the horizon of each point within the point cloud. Effects of cloud cover are also considered by using data from a nearby meteorological station. As a result the annual sum of the direct and diffuse radiation for each roof plane is derived. The presented method uses the full 3D information for both feature extraction and solar potential analysis, which offers a number of new applications in fields where natural processes are influenced by the incoming solar radiation (e.g., evapotranspiration, distribution of permafrost). The presented method detected fully automatically a subset of 809 out of 1,071 roof planes where the arithmetic mean of the annual incoming solar radiation is more than 700 kWh/m2. PMID:22346695

  6. Peripheral electrical stimulation triggered by self-paced detection of motor intention enhances motor evoked potentials.

    PubMed

    Niazi, Imran Khan; Mrachacz-Kersting, Natalie; Jiang, Ning; Dremstrup, Kim; Farina, Dario

    2012-07-01

    This paper proposes the development and experimental tests of a self-paced asynchronous brain-computer interfacing (BCI) system that detects movement related cortical potentials (MRCPs) produced during motor imagination of ankle dorsiflexion and triggers peripheral electrical stimulations timed with the occurrence of MRCPs to induce corticospinal plasticity. MRCPs were detected online from EEG signals in eight healthy subjects with a true positive rate (TPR) of 67.15 ± 7.87% and false positive rate (FPR) of 22.05 ±9.07%. The excitability of the cortical projection to the target muscle (tibialis anterior) was assessed before and after the intervention through motor evoked potentials (MEP) using transcranial magnetic stimulation (TMS). The peak of the evoked potential significantly (P=0.02) increased after the BCI intervention by 53 ± 43% (relative to preintervention measure), although the spinal excitability (tested by stretch reflexes) did not change. These results demonstrate for the first time that it is possible to alter the corticospinal projections to the tibialis anterior muscle by using an asynchronous BCI system based on online motor imagination that triggered peripheral stimulation. This type of repetitive proprioceptive feedback training based on self-generated brain signal decoding may be a requirement for purposeful skill acquisition in intact humans and in the rehabilitation of persons with brain damage.

  7. MicroRNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity.

    PubMed

    Hollis, Michael; Nair, Kavitha; Vyas, Arpita; Chaturvedi, Lakshmi Shankar; Gambhir, Sahil; Vyas, Dinesh

    2015-07-21

    Over the past decade, research has shown that aberrant expression of microRNA (miRNA) is involved in colorectal cancer development and progression. MicroRNAs are small sequences of non-coding RNA that regulate expression of genes involved in important cellular functions, such as cell differentiation, multiplication, and apoptosis. A specific miRNA may display the effects of a tumor suppressor or oncogene. Altered miRNA expression is found in colorectal cancer (CRC) and patterns of miRNA expression correlate with CRC detection and outcome. Studies also have examined the use of circulating serum miRNA and fecal miRNA expression as non-invasive markers for early detection. Here, we review recent evidence demonstrating the potential role of miRNA in CRC and the implications of its use in the diagnosis, prognosis, and management of CRC.

  8. Potential Adverse Effects of Competitive Prototype Validation

    DTIC Science & Technology

    1974-11-01

    dearth of literature on this subject, the best source of information was the persons charged with materiel acquisition responsibilities in the U.S. Army...that the best method of collecting information on this subject was by personal interview with knowledgeable persons . The persons selecte for interview...program experience prior to being asked. Names of persone interviewed are in the bibliography. The objective of interviewing General Miley was twofold

  9. Evaluating the utility of syndromic surveillance algorithms for screening to detect potentially clonal hospital infection outbreaks

    PubMed Central

    Talbot, Thomas R; Schaffner, William; Bloch, Karen C; Daniels, Titus L; Miller, Randolph A

    2011-01-01

    Objective The authors evaluated algorithms commonly used in syndromic surveillance for use as screening tools to detect potentially clonal outbreaks for review by infection control practitioners. Design Study phase 1 applied four aberrancy detection algorithms (CUSUM, EWMA, space-time scan statistic, and WSARE) to retrospective microbiologic culture data, producing a list of past candidate outbreak clusters. In phase 2, four infectious disease physicians categorized the phase 1 algorithm-identified clusters to ascertain algorithm performance. In phase 3, project members combined the algorithms to create a unified screening system and conducted a retrospective pilot evaluation. Measurements The study calculated recall and precision for each algorithm, and created precision-recall curves for various methods of combining the algorithms into a unified screening tool. Results Individual algorithm recall and precision ranged from 0.21 to 0.31 and from 0.053 to 0.29, respectively. Few candidate outbreak clusters were identified by more than one algorithm. The best method of combining the algorithms yielded an area under the precision-recall curve of 0.553. The phase 3 combined system detected all infection control-confirmed outbreaks during the retrospective evaluation period. Limitations Lack of phase 2 reviewers' agreement indicates that subjective expert review was an imperfect gold standard. Less conservative filtering of culture results and alternate parameter selection for each algorithm might have improved algorithm performance. Conclusion Hospital outbreak detection presents different challenges than traditional syndromic surveillance. Nevertheless, algorithms developed for syndromic surveillance have potential to form the basis of a combined system that might perform clinically useful hospital outbreak screening. PMID:21606134

  10. Dichoptic stimulation improves detection of glaucoma with multifocal visual evoked potentials.

    PubMed

    Arvind, Hemamalini; Klistorner, Alexander; Graham, Stuart; Grigg, John; Goldberg, Ivan; Klistorner, Asya; Billson, Frank A

    2007-10-01

    To determine whether simultaneous binocular (dichoptic) stimulation for multifocal visual evoked potentials (mfVEP) detects glaucomatous defects and decreases intereye variability. Twenty-eight patients with glaucoma and 30 healthy subjects underwent mfVEP on monocular and dichoptic stimulation. Dichoptic stimulation was presented with the use of virtual reality goggles (recording time, 7 minutes). Monocular mfVEPs were recorded sequentially for each eye (recording time, 10 minutes). Comparison of mean relative asymmetry coefficient (RAC; calculated as difference in amplitudes between eyes/sum of amplitudes of both eyes at each segment) on monocular and dichoptic mfVEP revealed significantly lower RAC on dichoptic (0.003 +/- 0.03) compared with monocular testing (-0.02 +/- 0.04; P = 0.002). In all 28 patients, dichoptic mfVEP identified defects with excellent topographic correspondence. Of 56 hemifields (28 eyes), 33 had Humphrey visual field (HFA) scotomas, all of which were detected by dichoptic mfVEP. Among 23 hemifields with normal HFA, two were abnormal on monocular and dichoptic mfVEP. Five hemifields (five patients) normal on HFA and monocular mfVEP were abnormal on dichoptic mfVEP. In all five patients, corresponding rim changes were observed on disc photographs. Mean RAC of glaucomatous eyes was significantly higher on dichoptic (0.283 +/- 0.18) compared with monocular (0.199 +/- 0.12) tests (P = 0.0006). Dichoptic mfVEP not only detects HFA losses, it may identify early defects in areas unaffected on HFA and monocular mfVEP while reducing testing time by 30%. Asymmetry was tighter among healthy subjects but wider in patients with glaucoma on simultaneous binocular stimulation, which is potentially a new tool in the early detection of glaucoma.

  11. Detection of Potential Transit Signals in 17 Quarters of Kepler Mission Data

    NASA Astrophysics Data System (ADS)

    Seader, Shawn; Jenkins, Jon M.; Tenenbaum, Peter; Twicken, Joseph D.; Smith, Jeffrey C.; Morris, Rob; Catanzarite, Joseph; Clarke, Bruce D.; Li, Jie; Cote, Miles T.; Burke, Christopher J.; McCauliff, Sean; Girouard, Forrest R.; Campbell, Jennifer R.; Kamal Uddin, Akm; Zamudio, Khadeejah A.; Sabale, Anima; Henze, Christopher E.; Thompson, Susan E.; Klaus, Todd C.

    2015-03-01

    We present the results of a search for potential transit signals in the full 17-quarter data set collected during Kepler's primary mission that ended on 2013 May 11, due to the on board failure of a second reaction wheel needed to maintain high precision, fixed, pointing. The search includes a total of 198,646 targets, of which 112,001 were observed in every quarter and 86,645 were observed in a subset of the 17 quarters. For the first time, this multi-quarter search is performed on data that have been fully and uniformly reprocessed through the newly released version of the Data Processing Pipeline. We find a total of 12,669 targets that contain at least one signal that meets our detection criteria: periodicity of the signal, a minimum of three transit events, an acceptable signal-to-noise ratio, and four consistency tests that suppress many false positives. Each target containing at least one transit-like pulse sequence is searched repeatedly for other signals that meet the detection criteria, indicating a multiple planet system. This multiple planet search adds an additional 7698 transit-like signatures for a total of 20,367. Comparison of this set of detected signals with a set of known and vetted transiting planet signatures in the Kepler field of view shows that the recovery rate of the search is 90.3%. We review ensemble properties of the detected signals and present various metrics useful in validating these potential planetary signals. We highlight previously undetected transit-like signatures, including several that may represent small objects in the habitable zone of their host stars.

  12. DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential.

    PubMed

    Hänsel-Hertsch, Robert; Di Antonio, Marco; Balasubramanian, Shankar

    2017-05-01

    Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy.

  13. The potential detection of low-level aerosol isotopes from new civilian nuclear processes.

    PubMed

    Miley, H S; Burnett, J L; Foxe, M P; Haas, D A; Keillor, M E; Lowrey, J D; Mayer, M F; McIntyre, J I; Wood, J S

    2017-08-01

    As the world faces a challenging future in maintaining the commercial availability of radioactive isotopes for medical use, new methods of medical isotope production are being pursued. Many of these are small in size and could effectively operate continuously. With the potential for much shorter retention times, a new suite of isotopes may soon be found in the environment. The authors estimate that many more aerosols containing low-level isotopes of gas/volatile origin could be detectable at short range and times, and a few at longer ranges and times as compared to those released in more common nuclear reactor operations. Copyright © 2017. Published by Elsevier Ltd.

  14. Development of Alternating Current Potential Drop (ACPD) procedures for crack detection in aluminum aircraft panels

    NASA Astrophysics Data System (ADS)

    Jablonski, D. A.

    1993-12-01

    The Alternating Current Potential Drop (ACPD) method is investigated as a means of making measurements in laboratory experiments on the initiation and growth of multiple site damage (MSD) cracks in a common aluminum alloy used for aircraft construction. Procedures for instrumenting MSD test specimens are recommended. The ACPD method is found to be capable of the following: (1) detecting crack initiation at a crack length of the order of 1 mm; (2) monitoring crack propagation at a resolution of the order of 5 micrometers; and (3) providing an indirect measurement of crack extension in R-curve type tests of fastener hole details.

  15. Signal detection on spontaneous reports of adverse events following immunisation: a comparison of the performance of a disproportionality-based algorithm and a time-to-onset-based algorithm

    PubMed Central

    van Holle, Lionel; Bauchau, Vincent

    2014-01-01

    Purpose Disproportionality methods measure how unexpected the observed number of adverse events is. Time-to-onset (TTO) methods measure how unexpected the TTO distribution of a vaccine-event pair is compared with what is expected from other vaccines and events. Our purpose is to compare the performance associated with each method. Methods For the disproportionality algorithms, we defined 336 combinations of stratification factors (sex, age, region and year) and threshold values of the multi-item gamma Poisson shrinker (MGPS). For the TTO algorithms, we defined 18 combinations of significance level and time windows. We used spontaneous reports of adverse events recorded for eight vaccines. The vaccine product labels were used as proxies for true safety signals. Algorithms were ranked according to their positive predictive value (PPV) for each vaccine separately; amedian rank was attributed to each algorithm across vaccines. Results The algorithm with the highest median rank was based on TTO with a significance level of 0.01 and a time window of 60 days after immunisation. It had an overall PPV 2.5 times higher than for the highest-ranked MGPS algorithm, 16th rank overall, which was fully stratified and had a threshold value of 0.8. A TTO algorithm with roughly the same sensitivity as the highest-ranked MGPS had better specificity but longer time-to-detection. Conclusions Within the scope of this study, the majority of the TTO algorithms presented a higher PPV than for any MGPS algorithm. Considering the complementarity of TTO and disproportionality methods, a signal detection strategy combining them merits further investigation. PMID:24038719

  16. Potential utility of environmental DNA for early detection of Eurasian watermilfoil (Myriophyllum spicatum)

    USGS Publications Warehouse

    Newton, Jeremy; Sepulveda, Adam; Sylvester, K; Thum, Ryan

    2016-01-01

    EWM invasions have negative impacts on native biodiversity, recreational boating, fishing, and other types of aquatic tourism (e.g., Eiswerth et al. 2000). On a broader scale, EWM can also be harmful to man-made aquatic infrastructure, such as hydroelectric dams. If an EWM invasion can be detected in an early stage where eradication is still a possibility, many of these negative consequences can be limited or prevented altogether (e.g., Madsen et al. 2002). The purpose of this research was to develop and validate a traditional polymerase chain reaction (PCR) assay for the detection of pure and hybridized EWM DNA using both laboratory and field experiments. We performed a pilot experiment in outdoor tanks to determine the basic functionality and sensitivity of the assay. Following this initial test, we collected field samples from Michigan and Montana lakes with and without known EWM populations. Taken together, our findings suggest that eDNA techniques have potential to be a useful strategy for the early detection of EWM.

  17. Label-free optical detection of action potential in mammalian neurons

    PubMed Central

    Batabyal, Subrata; Satpathy, Sarmishtha; Bui, Loan; Kim, Young-Tae; Mohanty, Samarendra; Bachoo, Robert; Davé, Digant P.

    2017-01-01

    We describe an optical technique for label-free detection of the action potential in cultured mammalian neurons. Induced morphological changes due to action potential propagation in neurons are optically interrogated with a phase sensitive interferometric technique. Optical recordings composed of signal pulses mirror the electrical spike train activity of individual neurons in a network. The optical pulses are transient nanoscale oscillatory changes in the optical path length of varying peak magnitude and temporal width. Exogenous application of glutamate to cortical neuronal cultures produced coincident increase in the electrical and optical activity; both were blocked by application of a Na-channel blocker, Tetrodotoxin. The observed transient change in optical path length in a single optical pulse is primarily due to physical fluctuations of the neuronal cell membrane mediated by a yet unknown electromechanical transduction phenomenon. Our analysis suggests a traveling surface wave in the neuronal cell membrane is responsible for the measured optical signal pulses. PMID:28856044

  18. In vivo Raman spectroscopy detects increased epidermal antioxidative potential with topically applied carotenoids

    NASA Astrophysics Data System (ADS)

    Lademann, J.; Caspers, P. J.; van der Pol, A.; Richter, H.; Patzelt, A.; Zastrow, L.; Darvin, M.; Sterry, W.; Fluhr, J. W.

    2009-01-01

    In the present study, the distribution of the carotenoids as a marker for the complete antioxidative potential in human skin was investigated before and after the topical application of carotenoids by in vivo Raman spectroscopy with an excitation wavelength of 785 nm. The carotenoid profile was assessed after a short term topical application in 4 healthy volunteers. In the untreated skin, the highest concentration of natural carotenoids was detected in different layers of the stratum corneum (SC) close to the skin surface. After topical application of carotenoids, an increase in the antioxidative potential in the skin could be observed. Topically applied carotenoids penetrate deep into the epidermis down to approximately 24 μm. This study supports the hypothesis that antioxidative substances are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Subsequently they penetrate into the different layers of the SC.

  19. Adverse responses to local anaesthetics.

    PubMed

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  20. A novel software program for detection of potential air emboli during cardiac surgery.

    PubMed

    Secretain, Frank; Pollard, Andrew; Uddin, Mesbah; Ball, Christopher G; Hamilton, Andrew; Tanzola, Robert C; Thorpe, Joelle B; Milne, Brian

    2015-01-12

    Risks associated with air emboli introduced during cardiac surgery have been highlighted by reports of postoperative neuropsychological dysfunction, myocardial dysfunction, and mortality. Presently, there are no standard effective methods for quantifying potential emboli in the bloodstream during cardiac surgery. Our objective was to develop software that can automatically detect and quantify air bubbles within the ascending aorta and/or cardiac chambers during cardiac surgery in real time. We created a software algorithm ("Detection of Emboli using Transesophageal Echocardiography for Counting, Total volume, and Size estimation", or DETECTS™) to identify and measure potential emboli present during cardiac surgery using two-dimensional ultrasound. An in vitro experiment was used to validate the accuracy of DETECTS™ at identifying and measuring air emboli. An experimental rig was built to correlate the ultrasound images to high definition camera images of air bubbles created in water by an automatic bubbler system. There was a correlation between true bubble size and the size reported by DETECTS™ in our in vitro experiment (r = 0.76). We also tested DETECTS™ using TEE images obtained during cardiac surgery, and provide visualization of the software interface. While monitoring the heart during cardiac surgery using existing ultrasound technology and DETECTS™, the operative team can obtain real-time data on the number and volume of potential air emboli. This system will potentially allow de-airing techniques to be evaluated and improved upon. This could lead to reduced air in the cardiac chambers after cardiopulmonary bypass, possibly reducing the risk of neurological dysfunction following cardiac surgery.

  1. [Allergies and adverse events associated with fluoroquinolones].

    PubMed

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  2. Design of Adverse Drug Events-Scorecards.

    PubMed

    Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M

    2011-01-01

    This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.

  3. Linezolid-related adverse effects in clinical practice in children.

    PubMed

    Bayram, Nuri; Düzgöl, Mine; Kara, Ahu; Özdemir, Fatih M; Devrim, İlker

    2017-10-01

    Linezolid may cause adverse effects such as thrombocytopenia, which were found to be dependent on receiving linezolid for longer than 2 weeks. There are limited studies concerning the safety and timing of linezolid-related adverse effects in children. Objective of this study was to evaluate the incidence of adverse effects associated with linezolid, with especially focusing on the time of occurrence. All children (<18 years of age) who received >3 days of linezolid therapy were included in this study. Adverse effects attributed to linezolid and time of occurrence of side effects was evaluated. A total of 179 children were enrolled to the study. The patients' median age was 4 years (6 days to 17 years). During linezolid treatment, 36 (20.1%) patients experienced adverse effects. The most common adverse effect was thrombocytopenia that was detected in 26 patients (14.5%). Other adverse effects were as following; elevated liver enzymes in 4 patients, leucopenia and anemia in 2 patients, renal function impairment in one patient, and serious skin reactions in 3 patients. Adverse effects were detected within median 7.5 days of therapy (ranging from 4 to 18 days). Among 36 patients, 26 (72.2%) patients had adverse effect on the first 10 days of therapy. Transient adverse effects were detected in 20.1% of the patients during linezolid therapy. These adverse effects may be detected earlier than ten days of treatment. Linezolid should be prescribed safely in children with monitoring adverse effects especially platelet count and level of liver enzymes.

  4. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  5. Global trends, potential mechanisms and early detection of organ damage in SLE.

    PubMed

    Mak, Anselm; Isenberg, David A; Lau, Chak-Sing

    2013-05-01

    Increased longevity of patients with systemic lupus erythematosus (SLE) leads to chronic organ damage accrual, which reduces the possibility of further survival improvement in patients with the disease. Observations from lupus centres worldwide revealed that the prevalence of damage occurring in the cardiovascular system in patients with SLE has increased over the past four decades. The results of a meta-analysis involving over 70 observational studies demonstrated that lupus-related organ damage involving the neuropsychiatric and renal systems also remains a major factor that limits survival improvement in patients with this disease. While efforts to halt acute lupus-related injury are continuing, through early diagnosis and effective use of immunosuppressive agents, a concomitant strategy to improve survival of patients with SLE would be early detection and timely treatment of lupus-related organ damage with meticulous monitoring. This Review discusses the pattern and trend of organ damage in patients with SLE worldwide, the potential serological and genetic mechanisms of organ damage, and the advances in research on potential tools for early detection of lupus-related organ damage, such as functional brain imaging techniques, measurement of endothelial function, identification of biomarkers from body fluids, and development of risk calculation models.

  6. Detection of bacterial pathogens including potential new species in human head lice from Mali

    PubMed Central

    Amanzougaghene, Nadia; Fenollar, Florence; Sangaré, Abdoul Karim; Sissoko, Mahamadou S.; Doumbo, Ogobara K.; Raoult, Didier

    2017-01-01

    In poor African countries, where no medical and biological facilities are available, the identification of potential emerging pathogens of concern at an early stage is challenging. Head lice, Pediculus humanus capitis, have a short life, feed only on human blood and do not transmit pathogens to their progeny. They are, therefore, a perfect tool for the xenodiagnosis of current or recent human infection. This study assessed the occurrence of bacterial pathogens from head lice collected in two rural villages from Mali, where a high frequency of head lice infestation had previously been reported, using molecular methods. Results show that all 600 head lice, collected from 117 individuals, belonged to clade E, specific to West Africa. Bartonella quintana, the causative agent of trench fever, was identified in three of the 600 (0.5%) head lice studied. Our study also shows, for the first time, the presence of the DNA of two pathogenic bacteria, namely Coxiella burnetii (5.1%) and Rickettsia aeschlimannii (0.6%), detected in human head lice, as well as the DNA of potential new species from the Anaplasma and Ehrlichia genera of unknown pathogenicity. The finding of several Malian head lice infected with B. quintana, C. burnetii, R. aeschlimannii, Anaplasma and Ehrlichia is alarming and highlights the need for active survey programs to define the public health consequences of the detection of these emerging bacterial pathogens in human head lice. PMID:28931077

  7. Biophoton detection and low-intensity light therapy: a potential clinical partnership.

    PubMed

    Tafur, Joseph; Van Wijk, Eduard P A; Van Wijk, Roeland; Mills, Paul J

    2010-02-01

    Low-intensity light therapy (LILT) is showing promise in the treatment of a wide variety of medical conditions. Concurrently, our knowledge of LILT mechanisms continues to expand. We are now aware of LILT's potential to induce cellular effects through, for example, accelerated ATP production and the mitigation of oxidative stress. In clinical use, however, it is often difficult to predict patient response to LILT. It appears that cellular reduction/oxidation (redox) state may play a central role in determining sensitivity to LILT and may help explain variability in patient responsiveness. In LILT, conditions associated with elevated reactive oxygen species (ROS) production, e.g. diabetic hyperglycemia, demonstrate increased sensitivity to LILT. Consequently, assessment of tissue redox conditions in vivo may prove helpful in identifying responsive tissues. A noninvasive redox measure may be useful in advancing investigation in LILT and may one day be helpful in better identifying responsive patients. The detection of biophotons, the production of which is associated with cellular redox state and the generation of ROS, represents just such an opportunity. In this review, we will present the case for pursuing further investigation into the potential clinical partnership between biophoton detection and LILT.

  8. Biophoton Detection and Low-Intensity Light Therapy: A Potential Clinical Partnership

    PubMed Central

    Van Wijk, Eduard P.A.; Van Wijk, Roeland; Mills, Paul J.

    2010-01-01

    Abstract Low-intensity light therapy (LILT) is showing promise in the treatment of a wide variety of medical conditions. Concurrently, our knowledge of LILT mechanisms continues to expand. We are now aware of LILT's potential to induce cellular effects through, for example, accelerated ATP production and the mitigation of oxidative stress. In clinical use, however, it is often difficult to predict patient response to LILT. It appears that cellular reduction/oxidation (redox) state may play a central role in determining sensitivity to LILT and may help explain variability in patient responsiveness. In LILT, conditions associated with elevated reactive oxygen species (ROS) production, e.g. diabetic hyperglycemia, demonstrate increased sensitivity to LILT. Consequently, assessment of tissue redox conditions in vivo may prove helpful in identifying responsive tissues. A noninvasive redox measure may be useful in advancing investigation in LILT and may one day be helpful in better identifying responsive patients. The detection of biophotons, the production of which is associated with cellular redox state and the generation of ROS, represents just such an opportunity. In this review, we will present the case for pursuing further investigation into the potential clinical partnership between biophoton detection and LILT. PMID:19754267

  9. 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

  10. Potential of treatment-specific protein biomarker profiles for detection of hormone abuse in cattle.

    PubMed

    Ludwig, Susann Katrina Julie; Smits, Nathalie Gabriëlle Esther; Cannizzo, Francesca Tiziana; Nielen, Michel Wilhelmus Franciscus

    2013-05-15

    Targeted protein biomarker profiling is suggested as a fast screening approach for detection of illegal hormone treatment in meat production. The advantage of using biomarkers is that they mark the biological response and, thus, are responsive to a panel of substances with similar effects. In a preliminary feasibility study, a 4-plex protein biomarker flow cytometric immunoassay (FCIA) previously developed for the detection of recombinant bovine somatotropin (rbST) was applied to cattle treated with steroids, such as estradiol, dexamethasone, and prednisolone. Each treatment resulted in a specific plasma biomarker profile for insulin-like growth factor-1 (IGF-1), IGF binding protein 2, osteocalcin, and anti-rbST antibodies, which could be distinguished from the profile of untreated animals. In summary, the 4-plex biomarker FCIA is, apart from rbST, also capable of detecting treatment with other growth-promoting agents and therefore clearly shows the potential of biomarker profiling as a screening method in veterinary control. It is proposed to perform additional validation studies covering high numbers of treated and untreated animals to support inclusion or adaptation of protein biomarker approaches in future monitoring regulations.

  11. Leptospira wolffii, a potential new pathogenic Leptospira species detected in human, sheep and dog.

    PubMed

    Zakeri, Sedigheh; Khorami, Nargess; Ganji, Zahra F; Sepahian, Neda; Malmasi, Abdol-Ali; Gouya, Mohammad Mehdi; Djadid, Navid D

    2010-03-01

    Leptospirosis is the most common zoonotic disease, which is transmitted to humans through contaminated water or direct exposure to the urine of infected animals. In this study, the presence and prevalence of Leptospira species in the infected samples of human (n=369) and sheep (n=75) sera and also dogs' urine (n=150), collected from four provinces of Iran, were investigated by using nested-PCR/RFLP assay followed by sequencing analysis. Nested-PCR assay detected that 98/369 (26.5%) human, 13/75 (17.33%) of sheep's sera and 33/150 (22%) dogs' urine samples were positive for Leptospira DNA. RFLP assay detected that all positive cases had either pathogenic or intermediate Leptospira species. By sequence analysis, Leptospira interrogans was the most prevalent species among the examined samples of human (53/82, 64.6%) and sheep (11/13, 84.6%). However, in dog samples, Leptospira wolffii (27/29, 93.1%) was detected for the first time and was the dominant species. The presence of L. wolffii with 100% identity in clinical human samples and animals suspected with Leptospira may provide evidence for circulation of L. wolffii and its role in transmission cycle within human and animal hosts. In addition, this species can be potentially pathogenic to human and probably animal hosts. A large epidemiology survey would be needed to define the presence and the prevalence of this species in global endemic regions.

  12. Nanoelectrode-Gated Detection of Individual Molecules with Potential for Rapid DNA Sequencing

    SciTech Connect

    Lee, James Weifu

    2007-01-01

    A systematic nanoelectrode-gated electron-tunneling molecular-detection concept with potential for rapid DNA sequencing has recently been invented at Oak Ridge National Laboratory (ORNL). A DNA molecule is a polymer that typically contains four different types of nucleotide bases: adenine (A), thymine (T), guanine (G), and cytosine (C) on its phosphate-deoxyribose chain. According to the nanoelectrode-gated molecular-detection concept, it should be possible to obtain genetic sequence information by probing through a DNA molecule base by base at a nanometer scale, as if looking at a strip of movie film. The nanoscale reading of DNA sequences is envisioned to take place at a nanogap (gate) defined by a pair of nanoelectrode tips as a DNA molecule moves through the gate base by base. The rationale is that sample molecules, such as the four different nucleotide bases, each with a distinct chemical composition and structure, should produce a specific perturbation effect on the tunneling electron beam across the two nanoelectrode tips. A sample molecule could thus be detected when it enters the gate. This nanoscience-based approach could lead to a new DNA sequencing technology that could be thousands of times faster than the current technology (Sanger's 'dideoxy' protocol-based capillary electrophoresis systems). Both computational and experimental studies are underway at ORNL towards demonstrating this nanotechnology concept.

  13. Fourier Transform Infrared Spectroscopy: A Potential Technique for Noninvasive Detection of Spermatogenesis

    PubMed Central

    Gilany, Kambiz; Pouracil, Roudabeh Sadat Moazeni; Sadeghi, Mohammad Reza

    2014-01-01

    Background The seminal plasma is an excellent source for noninvasive detection of spermatogenesis. The seminal plasma of normospermic and azoospermic men has been analyzed for detection of spermatogenesis. Methods Optical spectroscopy (Attenuated Total Reflectance-Infrared spectroscopy (ATR-IR) and Fourier Transform infrared spectroscopy (FT-IR) has been used to analyze the seminal plasma and the metabolome of seminal plasma for detection of spermatogenesis. Results The seminal plasma of normospermic and azoospermic men has been analyzed by ATR-IR. The results show that there is a pattern variation in the azoospermic men compared to normospermic men. However, the seminal plasma is too complex to show significant pattern variation. Therefore, the metabolome which is a subcomponent of the seminal plasma was analyzed. The seminal plasma metabolome of normospermic and azoospermic men has been analyzed by FT-IR. A significant pattern change was observed. The data combined with chemometrics analysis showed that significant changes are observed at metabolome level. Conclusion We suggest that FT-IR has the potential as a diagnostic tool instead of testicular biopsy. PMID:24523955

  14. Potential role of coregistered photoacoustic and ultrasound imaging in ovarian cancer detection and characterization.

    PubMed

    Aguirre, Andres; Ardeshirpour, Yasaman; Sanders, Mary M; Brewer, Molly; Zhu, Quing

    2011-02-01

    Currently, there is no adequate technology to detect early stage ovarian cancers. Most of the cancers in the ovary are detected when the cancer has already metastasized to other parts of the body. As a result, ovarian cancer has the highest mortality of all gynecologic cancers with a 5-year survival rate of 30% or less. Thus, there is an urgent need to improve the current diagnostic techniques. Photoacoustic imaging (PAI) is an emerging modality with a great potential to assist ultrasound for detecting ovarian cancer noninvasively. In this article, we report the first study of coregistered ultrasound and PAI of 33 ex vivo human ovaries. An assessment of the photoacoustic images has revealed light absorption distribution in the ovary, which is directly related to the vasculature distribution and amount. Quantification of the light absorption levels in the ovary has indicated that, in the postmenopausal group, malignant ovaries showed significantly higher light absorption than normal ones (P = .0237). For these two groups, we have obtained a sensitivity of 83% and a specificity of 83%. This result suggests that PAI is a promising modality for improving ultrasound diagnosis of ovarian cancer.

  15. Detection of potentially skin sensitizing hydroperoxides of linalool in fragranced products.

    PubMed

    Kern, Susanne; Dkhil, Hafida; Hendarsa, Prisca; Ellis, Graham; Natsch, Andreas

    2014-10-01

    On prolonged exposure to air, linalool can form sensitizing hydroperoxides. Positive hydroperoxide patch tests in dermatitis patients have frequently been reported, but their relevance has not been established. Owing to a lack of analytical methods and data, it is unclear from which sources the public might be exposed to sufficient quantities of hydroperoxides for induction of sensitization to occur. To address this knowledge gap, we developed analytical methods and performed stability studies for fine fragrances and deodorants/antiperspirants. In parallel, products recalled from consumers were analysed to investigate exposure to products used in everyday life. Liquid chromatography-mass spectrometry with high mass resolution was found to be optimal for the selective and sensitive detection of the organic hydroperoxide in the complex product matrix. Linalool hydroperoxide was detected in natural linalool, but the amount was not elevated by storage in a perfume formulation exposed to air. No indication of hydroperoxide formation in fine fragrances was found in stability studies. Aged fine fragrances recalled from consumers contained a geometric mean linalool concentration of 1,888 μg/g and, corrected for matrix effects, linalool hydroperoxide at a concentration of around 14 μg/g. In antiperspirants, we detected no oxidation products. In conclusion, very low levels of linalool hydroperoxide in fragranced products may originate from raw materials, but we found no evidence for oxidation during storage of products. The levels detected are orders of magnitude below the levels inducing sensitization in experimental animals, and these results therefore do not substantiate a causal link between potential hydroperoxide formation in cosmetics and positive results of patch tests.

  16. The Potential of Hyperspectral Patterns of Winter Wheat to Detect Changes in Soil Microbial Community Composition

    PubMed Central

    Carvalho, Sabrina; van der Putten, Wim H.; Hol, W. H. G.

    2016-01-01

    Reliable information on soil status and crop health is crucial for detecting and mitigating disasters like pollution or minimizing impact from soil-borne diseases. While infestation with an aggressive soil pathogen can be detected via reflected light spectra, it is unknown to what extent hyperspectral reflectance could be used to detect overall changes in soil biodiversity. We tested the hypotheses that spectra can be used to (1) separate plants growing with microbial communities from different farms; (2) to separate plants growing in different microbial communities due to different land use; and (3) separate plants according to microbial species loss. We measured hyperspectral reflectance patterns of winter wheat plants growing in sterilized soils inoculated with microbial suspensions under controlled conditions. Microbial communities varied due to geographical distance, land use and microbial species loss caused by serial dilution. After 3 months of growth in the presence of microbes from the two different farms plant hyperspectral reflectance patterns differed significantly from each other, while within farms the effects of land use via microbes on plant reflectance spectra were weak. Species loss via dilution on the other hand affected a number of spectral indices for some of the soils. Spectral reflectance can be indicative of differences in microbial communities, with the Renormalized Difference Vegetation Index the most common responding index. Also, a positive correlation was found between the Normalized Difference Vegetation Index and the bacterial species richness, which suggests that plants perform better with higher microbial diversity. There is considerable variation between the soil origins and currently it is not possible yet to make sufficient reliable predictions about the soil microbial community based on the spectral reflectance. We conclude that measuring plant hyperspectral reflectance has potential for detecting changes in microbial

  17. Detection of Raman spectra in ocular drugs for potential in vivo application of Raman spectroscopy.

    PubMed

    Elshout, Mari; Erckens, Roel J; Webers, Carroll A; Beckers, Henny J; Berendschot, Tos T; de Brabander, John; Hendrikse, Fred; Schouten, Jan S

    2011-10-01

    Raman spectroscopy holds potential for the assessment of intraocular pharmacokinetics. Raman spectra of ocular drugs were acquired, to determine the drug-specific Raman signature. The ability of the Raman technique to quantify drug concentrations was also investigated. The experimental setup was based on a High Performance Raman Module 2500 Raman module, designed for 180° "backscatter" signal detection in the wavenumber range of 400-1,800 cm(-1). Excitation source was a diode laser emitting a beam with a wavelength of 785 nm and a power of 10 mW. Laser light was focused in the sample with a long-working-distance microscope objective (25×/0.50). Samples were measured in quartz cuvettes in 10 sequential measurements, with exposure time 30 s. The total number of measured drugs was 49. To determine whether signal intensity and drug concentration correlate, 2 drugs were diluted in water and measured with 120 s exposure time at different concentrations. An active ingredient-specific Raman signature was detected in 4 glaucoma drugs, 6 mydriatics, 5 antibiotics, 4 anesthetics, 3 anti-inflammatory drugs, 2 types of artificial tears, and 5 other drugs. In 20 drugs, no specific Raman signature was detected. Linear correlation of drug concentration with signal intensity was high (R(2)≥0.94). Using low laser powers, Raman signatures for 29 commonly used ocular drugs were detected. Correlation of drug concentration with signal intensity is high, which is essential for monitoring drug concentration in ocular media. The presented results encourage the use of Raman spectroscopy to acquire detailed information on the pharmacokinetics of these ocular drugs.

  18. Detection of potential leakage pathways from geological carbon storage by fluid pressure data assimilation

    NASA Astrophysics Data System (ADS)

    González-Nicolás, Ana; Baù, Domenico; Alzraiee, Ayman

    2015-12-01

    One of the main concerns of geological carbon storage (GCS) systems is the risk of leakage through "weak" permeable areas of the sealing formation or caprock. Since the fluid pressure pulse travels faster than the carbon dioxide (CO2) plume across the storage reservoir, the fluid overpressure transmitted into overlying permeable formations through caprock discontinuities is potentially detectable sooner than actual CO2 leakage occurs. In this work, an inverse modeling method based on fluid pressure measurements collected in strata above the target CO2 storage formation is proposed, which aims at identifying the presence, the location, and the extent of possible leakage pathways through the caprock. We combine a three-dimensional subsurface multiphase flow model with ensemble-based data assimilation algorithms to recognize potential caprock discontinuities that could undermine the long-term safety of GCS. The goal of this work is to examine and compare the capabilities of data assimilation algorithms such as the ensemble smoother (ES) and the restart ensemble Kalman filter (REnKF) to detect the presence of brine and/or CO2 leakage pathways, potentially in real-time during GCS operations. For the purpose of this study, changes in fluid pressure in the brine aquifer overlying to CO2 storage formation aquifer are hypothetically observed in monitoring boreholes, or provided by time-lapse seismic surveys. Caprock discontinuities are typically characterized locally by higher values of permeability, so that the permeability distribution tends to fit to a non-Gaussian bimodal process, which hardly complies with the requirements of the ES and REnKF algorithms. Here, issues related to the non-Gaussianity of the caprock permeability field are investigated by developing and applying a normal score transform procedure. Results suggest that the REnKF is more effective than the ES in characterizing caprock discontinuities.

  19. On the potential of ultrasound elastography for pressure ulcer early detection

    PubMed Central

    Deprez, Jean-François; Brusseau, Elisabeth; Fromageau, Jérémie; Cloutier, Guy; Basset, Olivier

    2011-01-01

    Purpose Pressure ulcers are areas of soft tissue breakdown induced by a sustained mechanical stress that damages the skin and underlying tissues. They represent a considerable burden to the society in terms of health care and cost. Yet, techniques for prevention and detection of pressure ulcers still remain very limited. In this article, the authors investigated the potential of ultrasound elastography for pressure ulcer early detection. Elastography is an imaging technique providing local information on biological tissue mechanical properties. It is relevant for pressure ulcer detection as this pathology is associated with a gradual stiffening of damaged tissues, beginning in the deeper tissues and progressing toward the skin surface. Methods A 2D ultrasound elastography method was proposed and its ability in terms of pressure ulcer detection was validated through numerical simulations and physical acquisitions on pressure ulcer mimicking phantoms. In vivo experiments on a rat model are also reported. A maintained pressure was applied on the animal thigh, with a view to generate a pressure ulcer, and ultrasound data were acquired and processed before and after application of this pressure. Results Numerical simulations demonstrated that a pressure ulcer can theoretically be detected at a very early stage with ultrasound elastography. Even when the ulcer region was characterized by a low stiffening (ratio of 1.8 relative to normal tissues), the corresponding elastogram clearly underlined the pathological area. This observation was confirmed by the results obtained on a physical phantom mimicking a pressure ulcer at an early stage. Computed elastograms showed strain differences between areas mimicking healthy and pathological tissues. Results corresponding to in vivo experiments revealed a difference in the way tissues behaved before and after the pressure was applied on the animal thigh, which strongly suggests the presence of a pathological area. Conclusions

  20. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  1. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  2. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis

    PubMed Central

    Morris, R K; Riley, R D; Doug, M; Deeks, J J

    2012-01-01

    Objective To determine the diagnostic accuracy of two “spot urine” tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a

  3. Validation of a Rapid, Robust, Inexpensive Screening Method for Detecting the HLA-B*58:01 Allele in the Prevention of Allopurinol-Induced Severe Cutaneous Adverse Reactions.

    PubMed

    Nguyen, Dinh Van; Vida, Christopher; Chu, Hieu Chi; Fulton, Richard; Li, Jamma; Fernando, Suran L

    2017-01-01

    The HLA B*58:01 allele has been worldwide reported as a pharmacogenetic susceptibility to allopurinol-induced severe cutaneous adverse reactions (SCARs). To prevent these life-threatening conditions, the American College of Rheumatology hingly recommended that the HLA-B*58:01 be screened prior to the initiation of allopurinol therapy. Therefore, we developed a rapid, robust, inexpensive screening method using SYBR® Green real time PCR to detect the HLA-B*58:01 allele. A total of 119 samples were tested. The assay has a sensitivity of 100% (95% CI: 69.15%-100%), a specificity of 100% (95% CI: 96.67%-100%), a positive predictive value of 100% (95% CI: 69.15%-100%) and a negative predictive value of 100% (95% CI: 96.67%-100%). HLA-B*58:01 genotyping results showed 100% agreement with those obtained from Luminex SSO/SBT/SSP. The lowest limit of detection of this method is 0.8 ng/μL of DNA. The unit cost of the test is only $3.8 USD. This novel screening test using SYBR® real time PCR would be appropriate to identify individuals with the HLA-B*58:01 allele for the prevention of allopurinol-induced SCARs.

  4. Validation of a Rapid, Robust, Inexpensive Screening Method for Detecting the HLA-B*58:01 Allele in the Prevention of Allopurinol-Induced Severe Cutaneous Adverse Reactions

    PubMed Central

    Chu, Hieu Chi; Fulton, Richard; Li, Jamma; Fernando, Suran L

    2017-01-01

    The HLA B*58:01 allele has been worldwide reported as a pharmacogenetic susceptibility to allopurinol-induced severe cutaneous adverse reactions (SCARs). To prevent these life-threatening conditions, the American College of Rheumatology hingly recommended that the HLA-B*58:01 be screened prior to the initiation of allopurinol therapy. Therefore, we developed a rapid, robust, inexpensive screening method using SYBR® Green real time PCR to detect the HLA-B*58:01 allele. A total of 119 samples were tested. The assay has a sensitivity of 100% (95% CI: 69.15%-100%), a specificity of 100% (95% CI: 96.67%-100%), a positive predictive value of 100% (95% CI: 69.15%-100%) and a negative predictive value of 100% (95% CI: 96.67%-100%). HLA-B*58:01 genotyping results showed 100% agreement with those obtained from Luminex SSO/SBT/SSP. The lowest limit of detection of this method is 0.8 ng/µL of DNA. The unit cost of the test is only $3.8 USD. This novel screening test using SYBR® real time PCR would be appropriate to identify individuals with the HLA-B*58:01 allele for the prevention of allopurinol-induced SCARs. PMID:27826965

  5. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  6. Potential Applications of Microtesla Magnetic Resonance ImagingDetected Using a Superconducting Quantum Interference Device

    SciTech Connect

    Myers, Whittier Ryan

    2006-01-01

    This dissertation describes magnetic resonance imaging (MRI) of protons performed in a precession field of 132 μT. In order to increase the signal-to-noise ratio (SNR), a pulsed 40-300 mT magnetic field prepolarizes the sample spins and an untuned second-order superconducting gradiometer coupled to a low transition temperature superconducting quantum interference device (SQUID) detects the subsequent 5.6-kHz spin precession. Imaging sequences including multiple echoes and partial Fourier reconstruction are developed. Calculating the SNR of prepolarized SQUID-detected MRI shows that three-dimensional Fourier imaging yields higher SNR than slice-selection imaging. An experimentally demonstrated field-cycling pulse sequence and post-processing algorithm mitigate image artifacts caused by concomitant gradients in low-field MRI. The magnetic field noise of SQUID untuned detection is compared to the noise of SQUID tuned detection, conventional Faraday detection, and the Nyquist noise generated by conducting biological samples. A second-generation microtesla MRI system employing a low-noise SQUID is constructed to increase SNR. A 2.4-m cubic, eddy-current shield with 6-mm thick aluminum walls encloses the experiment to attenuate external noise. The measured noise is 0.75 fT Hz-1/2 referred to the bottom gradiometer loop. Solenoids wound from 30-strand braided wire to decrease Nyquist noise and cooled by either liquid nitrogen or water polarize the spins. Copper wire coils wound on wooden supports produce the imaging magnetic fields and field gradients. Water phantom images with 0.8 x 0.8 x 10 mm3 resolution have a SNR of 6. Three-dimensional 1.6 x 1.9 x 14 mm3 images of bell peppers and 3 x 3 x 26 mm3 in vivo images of the human arm are presented. Since contrast based on the transverse spin relaxation rate (T1) is enhanced at low magnetic fields, microtesla MRI could potentially be used for tumor imaging. The

  7. Long-lasting synaptic potentiation induced by depolarization under conditions that eliminate detectable Ca2+ signals.

    PubMed

    Reyes, Fredy D; Walters, Edgar T

    2010-03-01

    Activity-dependent alterations of synaptic transmission important for learning and memory are often induced by Ca(2+) signals generated by depolarization. While it is widely assumed that Ca(2+) is the essential transducer of depolarization into cellular plasticity, little effort has been made to test whether Ca(2+)-independent responses to depolarization might also induce memory-like alterations. It was recently discovered that peripheral axons of nociceptive sensory neurons in Aplysia display long-lasting hyperexcitability triggered by conditioning depolarization in the absence of Ca(2+) entry (using nominally Ca(2+)-free solutions containing EGTA, "0Ca/EGTA") or the absence of detectable Ca(2+) transients (adding BAPTA-AM, "0Ca/EGTA/BAPTA-AM"). The current study reports that depolarization of central ganglia to approximately 0 mV for 2 min in these same solutions induced hyperexcitability lasting >1 h in sensory neuron processes near their synapses onto motor neurons. Furthermore, conditioning depolarization in these solutions produced a 2.5-fold increase in excitatory postsynaptic potential (EPSP) amplitude 1-3 h afterward despite a drop in motor neuron input resistance. Depolarization in 0 Ca/EGTA produced long-term potentiation (LTP) of the EPSP lasting > or = 1 days without changing postsynaptic input resistance. When re-exposed to extracellular Ca(2+) during synaptic tests, prior exposure to 0Ca/EGTA or to 0Ca/EGTA/BAPTA-AM decreased sensory neuron survival. However, differential effects on neuronal health are unlikely to explain the observed potentiation because conditioning depolarization in these solutions did not alter survival rates. These findings suggest that unrecognized Ca(2+)-independent signals can transduce depolarization into long-lasting synaptic potentiation, perhaps contributing to persistent synaptic alterations following large, sustained depolarizations that occur during learning, neural injury, or seizures.

  8. Detection Of Ventricular Late Potentials Using Wavelet Transform And ANT Colony Optimization

    NASA Astrophysics Data System (ADS)

    Subramanian, A. Sankara; Gurusamy, G.; Selvakumar, G.

    2010-10-01

    Ventricular late Potentials (VLPs) are low-level high frequency signals that are usually found with in the terminal part of the QRS complex from patients after Myocardial Infraction. Patients with VLPs are at risk of developing Ventricular Tachycardia, which is the major cause of death if patients suffering from heart disease. In this paper the Discrete Wavelet Transform was used to detect VLPs and then ANT colony optimization (ACO) was applied to classify subjects with and without VLPs. A set of Discrete Wavelet Transform (DWT) coefficients is selected from the wavelet decomposition. Three standard parameters of VLPs such as QRST, D40 and V40 are also established. After that a novel clustering algorithm based on Ant Colony Optimization is developed for classifying arrhythmia types. The wavelet decomposition enabled us to perform the task efficiently and produced reliable results.

  9. Contributing to the early detection of Rett syndrome: The potential role of auditory Gestalt perception

    PubMed Central

    Marschik, Peter B.; Einspieler, Christa; Sigafoos, Jeff

    2012-01-01

    To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian–German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome. PMID:22119693

  10. Studies on the utilization of a plant SCE test in detecting potential mutagenic agents.

    PubMed

    Zhang, Z L; Yang, J; Zhang, Q A; Cao, X S

    1991-09-01

    In this paper a modified procedure for sister-chromatid differentiation in plant cells is reported. Using this procedure some chemicals were tested for SCE induction in Vicia faba, Hordeum vulgare and Secale cereale. The chemicals tested were ethanol, chromium oxide, sodium saccharin, fluorouracil, ascorbic acid (vitamin c), omethoate and phenol. The experimental results showed that most of them induced SCE increases in mouse spleen cells, human lymphocytes and plant cells. The increase of SCEs per cell in plant cells is in agreement with that found in human lymphocytes or in mouse spleen cells. In our opinion, the utilization of SCE in plants is a simple and inexpensive technique for detecting potential mutagenic agents in the environment.

  11. Straightforward production of encoded microbeads by Flow Focusing: potential applications for biomolecule detection.

    PubMed

    Gañán-Calvo, A M; Martín-Banderas, L; González-Prieto, R; Rodríguez-Gil, A; Berdún-Alvarez, T; Cebolla, A; Chávez, S; Flores-Mosquera, M

    2006-10-31

    Fluorescently encoded polymeric microparticles are acquiring great importance in the development of simultaneous multianalyte screening assays. We have developed a very versatile and straightforward method for the production of dye-labeled microparticles with a very reproducible size distribution and freely-chosen and discernible fluorescent properties. Our method combines Flow Focusing technology with a solvent evaporation/extraction procedure in a single step, yielding spherical, non-aggregate and non-porous particles. We have designed a multi-coloured bead array which includes the possibility of modifying the surface properties of the microparticles, which offer excellent properties for covalent attachment of biomolecules such as peptides, oligonucleotides, proteins, etc. We also show the potential of the fluorescently labeled microspheres for the detection of biomolecule (peptides and oligonucelotides) interactions using flow cytometry.

  12. [Detection of potentially carcinogenic compounds persisting in atmospheric air and having high priority for hygienic regulation].

    PubMed

    Ingel', F I; Legostaeva, T B; Antipanova, N A; Krivtsova, E K; Iurtseva, N A

    2012-01-01

    The algorithm for the choice of potentially carcinogenic compounds (PCS) among emitted into air and results of the study, undertaken for realization of this algorithm are presented. The investigation was carried out in Magnitogorsk - Russian town of black metallurgy - in frames of the other study, aimed to evaluation of the influence of atmospheric pollution on children's health and genomic instability. The 11 PCS for further profound study of biological activity were selected out of more than 300 PCS, persisting in the air. The carcinogenic activity for 6 compounds out of these 11 ones was already have been found out before, that testifies correctness of the created approach and its adequacy for detection PCS in atmospheric air.

  13. A periodogram-based method for the detection of steady-state visually evoked potentials.

    PubMed

    Liavas, A P; Moustakides, G V; Henning, G; Psarakis, E Z; Husar, P

    1998-02-01

    The task of objective perimetry is to scan the visual field and find an answer about the function of the visual system. Flicker-burst stimulation--a physiological sensible combination of transient and steady-state stimulation--is used to generate deterministic sinusoidal responses or visually evoked potentials (VEP's) at the visual cortex, which are derived from the electroencephalogram by a suitable electrode array. In this paper we develop a new method for the detection of VEP's. Based on the periodogram of a time-series, we test the data for the presence of hidden periodic components, which correspond to steady-state VEP's. The method is applied successfully to real data.

  14. Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

    PubMed Central

    Merrie, A E H; Yun, K; Gunn, J; Phillips, L V; McCall, J L

    1999-01-01

    We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions. © 1999 Cancer Research Campaign PMID:10471055

  15. Contributing to the early detection of Rett syndrome: the potential role of auditory Gestalt perception.

    PubMed

    Marschik, Peter B; Einspieler, Christa; Sigafoos, Jeff

    2012-01-01

    To assess whether there are qualitatively deviant characteristics in the early vocalizations of children with Rett syndrome, we had 400 native Austrian-German speakers listen to audio recordings of vocalizations from typically developing girls and girls with Rett syndrome. The audio recordings were rated as (a) inconspicuous, (b) conspicuous or (c) not able to decide between (a) and (b). The results showed that participants were accurate in differentiating the vocalizations of typically developing children compared to children with Rett syndrome. However, the accuracy for rating verbal behaviors was dependent on the type of vocalization with greater accuracy for canonical babbling compared to cooing vocalizations. The results suggest a potential role for the use of rating child vocalizations for early detection of Rett syndrome. This is important because clinical criteria related to speech and language development remain important for early identification of Rett syndrome.

  16. Polymerase chain reaction detection of potentially pathogenic free-living amoebae in dental units.

    PubMed

    Leduc, Annie; Gravel, Sabrina; Abikhzer, Jérémie; Roy, Stéphane; Barbeau, Jean

    2012-07-01

    Several genera of amoebae can be found in water from dental units and on the inner surface of waterlines. The presence of bacterial biofilms on these surfaces is thought to favor the proliferation of amoebae. Potentially pathogenic Acanthamoeba and Naegleria spp. may be an infection risk for patients through contact with open surgical sites or aerosolization. A polymerase chain reaction of DNA extracted from pelleted samples showed that Acanthamoeba spp. and Naegleria spp. were present in water from dental units, suction lines, and suction filters at the dental clinic of the Université de Montréal. Acanthamoeba spp. were detected in 24.2% of 66 samples and Naegleria spp. in 3.0%. We discuss the infection risk associated with these results.

  17. Novel biological sources of electrochemiluminescence and potential applications to metals detection

    NASA Astrophysics Data System (ADS)

    Bruno, John G.; Collard, Sneed B.; Kuch, David J.; Cornette, Jimmy C.

    1996-11-01

    Electrochemiluminescence (ECL) is an electrochemical means of generating light from certain organic-metal complexes (e.g., Cr, Os, or Ru with bipyridine) and other types of molecules. Thus, it may be possible to develop an ECL-based metals sensor or biosensor consisting of organic molecules coated onto electrodes which emit light only upon complexation of particular metal ions and application of a small voltage. Toxic metals in water sources are of environmental concern. Some marine invertebrates, such as tunicates (i.e., `sea squirts') and molluscs, are noted for their ability to concentrate toxic metals as much as 100 million-fold over ambient seawater concentrations. In the present work, extracts from a tunicate species, as well as synthetic tunicate blood pigments or `tunichromes', oysters, and other organisms are examined for intrinsic ECL in the presence and absence of various metal ions. Results suggest a promising novel, potentially sensitive, and specific means for metal ion detection based on ECL.

  18. Retroactive memory interference: a potential countermeasure technique against psychophysiological knowledge detection methods.

    PubMed

    Gronau, Nurit; Elber, Lotem; Satran, Shai; Breska, Assaf; Ben-Shakhar, Gershon

    2015-03-01

    The concealed information test is designed to detect concealed knowledge through differential physiological responses elicited by the concealed items. This study was designed to examine the role of retroactive interference (RI) as a potential countermeasure that may weaken memory traces of the concealed items and attenuate the physiological responses elicited by them. A total of 120 participants committed a mock crime and were randomly assigned to either an interference condition, where they learned and retrieved an alternative mock crime, or a control condition. Further, each group was randomly assigned to one of three "time-delay" conditions. The results revealed that both memory for the mock crime details and the skin conductance responses (SCRs) to these details were attenuated under the memory-interference condition. Time of testing affected recall, but had no effect on the SCRs. In addition, the memory-interference manipulation had no effect on the respiration measure. Theoretical and practical implications of these results are discussed.

  19. A comparison of airborne wake vortex detection measurements with values predicted from potential theory

    NASA Technical Reports Server (NTRS)

    Stewart, Eric C.

    1991-01-01

    An analysis of flight measurements made near a wake vortex was conducted to explore the feasibility of providing a pilot with useful wake avoidance information. The measurements were made with relatively low cost flow and motion sensors on a light airplane flying near the wake vortex of a turboprop airplane weighing approximately 90000 lbs. Algorithms were developed which removed the response of the airplane to control inputs from the total airplane response and produced parameters which were due solely to the flow field of the vortex. These parameters were compared with values predicted by potential theory. The results indicated that the presence of the vortex could be detected by a combination of parameters derived from the simple sensors. However, the location and strength of the vortex cannot be determined without additional and more accurate sensors.

  20. Detecting moisture status of pecan orchards and the potential of remotely-sensed surface reflectance data

    NASA Astrophysics Data System (ADS)

    Othman, Yahia Abdelrahman

    Demand for New Mexico's limited water resources coupled with periodic drought has increased the need to schedule irrigation of pecan orchards based on tree water status. The overall goal of this research was to develop advanced tree water status sensing techniques to optimize irrigation scheduling of pecan orchards. To achieve this goal, I conducted three studies in the La Mancha and Leyendecker orchards, both mature pecan orchards located in the Mesilla Valley, New Mexico. In the first study, I screened leaf-level physiological changes that occurred during cyclic irrigation to determine parameters that best represented changes in plant moisture status. Then, I linked plant physiological changes to remotely-sensed surface reflectance data derived from Landsat Thematic Mapper (TM) and Enhanced Thematic Mapper (ETM+). In the second study, I assessed the impact of water deficits that developed during the flood irrigation dry-down cycles on photosynthesis (A) and gas exchange and established preliminary water deficit thresholds of midday stem water potential (Psi smd) critical to A and gas exchange of pecans. In a third study, I investigated whether hyperspectral data obtained from a handheld spectroradiometer and multispectral remotely-sensed data derived from Landsat 7 ETM+ and Landsat 8 Operational Land Imager (OLI) could detect moisture status in pecans during cyclic flood irrigations. I conducted the first study simultaneously in both orchards. Leaf-level physiological responses and remotely-sensed surface reflectance data were collected from trees that were either well watered or in water deficit. Midday stem water potential was the best leaf-level physiological response to detect moisture status in pecans. Multiple linear regression between Psismd and vegetation indices revealed a significant relationship (R 2 = 0.54) in both orchards. Accordingly, I concluded that remotely-sensed multispectral data form Landsat TMETM+ holds promise for detecting the moisture

  1. The first detection of potentially toxic Microcystis strains in two Middle Atlas Mountains natural lakes (Morocco).

    PubMed

    Douma, Mountasser; Ouahid, Youness; Loudiki, Mohammed; Del Campo, Francisca F; Oudra, Brahim

    2017-01-01

    Aguelmam Azizgza (LAZ) and Dayet Afourgah (DAF) are two Moroccan natural lakes located in a humid hydrographic basin of the Middle Atlas Mountains. Both are considered important reservoirs of plant and animal biodiversity. In addition, they are extensively used for recreational and fishing activities and as a water source for irrigation of agricultural crops. Recurrent cyanobacteria scum episodes in the two water bodies have been reported, Microcystis being the main genus in the scums. Here, we report on the toxic potential of three Microcystis aeruginosa strains isolated from those lakes: Mic LAZ and Mic B7 from LAZ and Mic DAF isolated from DAF. The toxic potential was checked by their microcystin (MC) content and the presence of mcy genes involved in MC synthesis. The identification and quantification of MC variants were performed by high-performance liquid chromatography-photo-diode array. The detection of mcy genes was achieved by whole-cell multiplex PCR that allowed the simultaneous amplification of DNA sequences corresponding to specific mcy regions. MC content of cultured cells, as MC-LR equivalents per gram cell biomass, was slightly higher in Mic LAZ (ca. 860) than in Mic B7 (ca. 700) and Mic DAF (ca. 690). Four MC variants were identified in the three isolates: MC-WR, MC-RR, MC-DM-WR, and MC-YR. The presence of toxic Microcystis strains in the two studied lakes may be regarded as an environmental and health hazard, especially during periods of bloom proliferation. It would be recommended the use of two complementary techniques, as those utilized herein (HPLC and mcy detection) to alert on highly probable toxicity of such lakes.

  2. Detecting non-relativistic cosmic neutrinos by capture on tritium: phenomenology and physics potential

    NASA Astrophysics Data System (ADS)

    Long, Andrew J.; Lunardini, Cecilia; Sabancilar, Eray

    2014-08-01

    We study the physics potential of the detection of the Cosmic Neutrino Background via neutrino capture on tritium, taking the proposed PTOLEMY experiment as a case study. With the projected energy resolution of Δ ~ 0.15 eV, the experiment will be sensitive to neutrino masses with degenerate spectrum, m1 simeq m2 simeq m3 = mν gtrsim 0.1 eV. These neutrinos are non-relativistic today; detecting them would be a unique opportunity to probe this unexplored kinematical regime. The signature of neutrino capture is a peak in the electron spectrum that is displaced by 2 mν above the beta decay endpoint. The signal would exceed the background from beta decay if the energy resolution is Δ lesssim 0.7 mν . Interestingly, the total capture rate depends on the origin of the neutrino mass, being ΓD simeq 4 and ΓM simeq 8 events per year (for a 100 g tritium target) for unclustered Dirac and Majorana neutrinos, respectively. An enhancement of the rate of up to Script O(1) is expected due to gravitational clustering, with the unique potential to probe the local overdensity of neutrinos. Turning to more exotic neutrino physics, PTOLEMY could be sensitive to a lepton asymmetry, and reveal the eV-scale sterile neutrino that is favored by short baseline oscillation searches. The experiment would also be sensitive to a neutrino lifetime on the order of the age of the universe and break the degeneracy between neutrino mass and lifetime which affects existing bounds.

  3. Detecting non-relativistic cosmic neutrinos by capture on tritium: phenomenology and physics potential

    SciTech Connect

    Long, Andrew J.; Lunardini, Cecilia; Sabancilar, Eray E-mail: Cecilia.Lunardini@asu.edu

    2014-08-01

    We study the physics potential of the detection of the Cosmic Neutrino Background via neutrino capture on tritium, taking the proposed PTOLEMY experiment as a case study. With the projected energy resolution of Δ ∼ 0.15 eV, the experiment will be sensitive to neutrino masses with degenerate spectrum, m{sub 1} ≅ m{sub 2} ≅ m{sub 3} = m{sub ν} ∼> 0.1 eV. These neutrinos are non-relativistic today; detecting them would be a unique opportunity to probe this unexplored kinematical regime. The signature of neutrino capture is a peak in the electron spectrum that is displaced by 2 m{sub ν} above the beta decay endpoint. The signal would exceed the background from beta decay if the energy resolution is Δ ∼< 0.7 m{sub ν} . Interestingly, the total capture rate depends on the origin of the neutrino mass, being Γ{sup D} ≅ 4 and Γ{sup M} ≅ 8 events per year (for a 100 g tritium target) for unclustered Dirac and Majorana neutrinos, respectively. An enhancement of the rate of up to O(1) is expected due to gravitational clustering, with the unique potential to probe the local overdensity of neutrinos. Turning to more exotic neutrino physics, PTOLEMY could be sensitive to a lepton asymmetry, and reveal the eV-scale sterile neutrino that is favored by short baseline oscillation searches. The experiment would also be sensitive to a neutrino lifetime on the order of the age of the universe and break the degeneracy between neutrino mass and lifetime which affects existing bounds.

  4. Ex vivo Confocal Imaging with Contrast Agents for the Detection of Oral Potentially Malignant Lesions

    PubMed Central

    Hallani, S. El; Poh, C. F.; Macaulay, C. E.; Follen, M.; Guillaud, M.; Lane, P.

    2013-01-01

    Objectives We investigated the potential use of real-time confocal microscpy in the non-invasive detection of occult oral potentially malignant lesions. Our objectives were to select the best fluorescence contrast agent for cellular morphology enhancement, to build an atlas of confocal microscopic images of normal human oral mucosa, and to determine the accuracy of confocal microscopy to recognise oral high-grade dysplasia lesions on live human tissue. Materials and Methods Five clinically used fluorescent contrast agents were tested in vitro on cultured human cells and validated ex vivo on human oral mucosa. Images acquired ex vivo from normal and diseased human oral biopsies with bench-top fluorescent confocal microscope were compared to conventional histology. Image analyzer software was used as an adjunct tool to objectively compare high-grade dysplasia versus low-grade dysplasia and normal epithelium. Results Acriflavine Hydrochloride provided the best cellular contrast by preferentially staining the nuclei of the epithelium. Using topical application of Acriflavine Hydrochloride followed by confocal microscopy, we could define morphological characteristics of each cellular layer of the normal human oral mucosa, building an atlas of histology-like images. Applying this technique to diseased oral tissue specimen, we were also able to accurately diagnose the presence of high-grade dysplasia through the increased cellularity and changes in nuclear morphological features. Objective measurement of cellular density by quantitative image analysis was a strong discriminant to differentiate between high-grade dysplasia and low-grade dysplasia lesions. Conclusions Pending clinical investigation, real-time confocal microscopy may become a useful adjunct to detect precancerous lesions that are at high risk of cancer progression, direct biopsy and delineate excision margins. PMID:23415144

  5. [Contribution of cognitive evoked potentials for detecting early cognitive disorders in multiple sclerosis].

    PubMed

    Magnié, M N; Bensa, C; Laloux, L; Bertogliati, C; Faure, S; Lebrun, C

    2007-11-01

    In Multiple Sclerosis (MS), one of the most frequent neurological diseases in young adults, cognitive dysfunctions have been under considered whereas their evolution may produce a fronto-sous-cortical deterioration and more than half of the MS patients present such dysfunctions. Nevertheless sensory evoked-potentials are classically used in this disease, event-related potentials (ERP) are not included in the clinical exploration of MS. Two studies are presented aimed at further tracking the usefulness of ERP for detecting early cognitive dysfunctions in MS. All of the patients presented a relapsing remitting MS for less than 5 years with a moderate physical handicap and complained from their memory. They performed a neuropsychological set and ERP were elicited using the oddball paradigm in both modalities, visual and auditory. In the first study, 10 patients without cognitive dysfunction at the neuropsychological evaluation and 10 patients with an attention deficit participated with 10 age-matched controls. In the second study, 10 patients with memory impairment at the neuropsychological evaluation and 10 age-matched controls were included. Our data argue for an earlier modification of ERP parameters in the visual modality than in the auditory one, even before the modification of cognitive scores. In both studies, P300 parameters were correlated to neuropsychological performances (and especially to the attention examination in the first study and to memory tests in the second study) in both modalities. Taking into account the clinical usefulness of ERPs, it is nowadays important to include this electrophysiological method in evaluation and follow-up of MS, and not only using the auditory modality but also the visual presentation in order to detect earlier cognitive dysfunctions even before modification of neuropsychological performances.

  6. Early detection of potentially invasive invertebrate species in Mytilus galloprovincialis Lamarck, 1819 dominated communities in harbours

    NASA Astrophysics Data System (ADS)

    Preda, Cristina; Memedemin, Daniyar; Skolka, Marius; Cogălniceanu, Dan

    2012-12-01

    Constanţa harbour is a major port on the western coast of the semi-enclosed Black Sea. Its brackish waters and low species richness make it vulnerable to invasions. The intensive maritime traffic through Constanţa harbour facilitates the arrival of alien species. We investigated the species composition of the mussel beds on vertical artificial concrete substrate inside the harbour. We selected this habitat for study because it is frequently affected by fluctuating levels of temperature, salinity and dissolved oxygen, and by accidental pollution episodes. The shallow communities inhabiting it are thus unstable and often restructured, prone to accept alien species. Monthly samples were collected from three locations from the upper layer of hard artificial substrata (maximum depth 2 m) during two consecutive years. Ten alien macro-invertebrate species were inventoried, representing 13.5% of the total number of species. Two of these alien species were sampled starting the end of summer 2010, following a period of high temperatures that triggered hypoxia, causing mass mortalities of benthic organisms. Based on the species accumulation curve, we estimated that we have detected all benthic alien species on artificial substrate from Constanţa harbour, but additional effort is required to detect all the native species. Our results suggest that monitoring of benthic communities at small depths in harbours is a simple and useful tool in early detection of potentially invasive alien species. The selected habitat is easily accessible, the method is low-cost, and the samples represent reliable indicators of alien species establishment.

  7. Predictive potential of photoacoustic spectroscopy in breast tumor detection based on xenograft serum profiles

    NASA Astrophysics Data System (ADS)

    Priya, Mallika; Chandra, Subhas; Rao, Bola Sadashiva Satish; Ray, Satadru; Mahato, Krishna Kishore

    2015-02-01

    Breast cancer is the second most common cancer all over the world. Heterogeneity in breast cancer makes it a difficult task to detect with the existing serum markers at an early stage. With an aim to detect the disease early at the pre-malignant level, MCF-7 cells xenografts were developed using female nude mice and blood serum were extracted on days 0th, 10th, 15th & 20th post tumor cells injection (N=12 for each time point). Photoacoustic spectra were recorded on the serum samples at 281nm pulsed laser excitations. A total of 144 time domain spectra were recorded from 48 serum samples belonging to 4 different time points. These spectra were then converted into frequency domain (0-1250kHz) using MATLAB algorithms. Subsequently, seven features (mean, median, mode, variance, standard deviation, area under the curve & spectral residuals after 10th degree polynomial fit) were extracted from them and used for PCA. Further, using the first three Principal components (PCs) of the data, Linear Discriminate Analysis has been carried out. The performance of the analysis showed 82.64% accuracy in predicting various time points under study. Further, frequency-region wise analysis was also performed on the data and found 95 - 203.13 kHz region most suitable for the discrimination among the 4 time points. The analysis provided a clear discrimination in most of the spectral features under study suggesting that the photoacoustic technique has the potential to be a diagnostic tool for early detection of breast tumor development

  8. Luminescence Decay Dynamics and Trace Biomaterials Detection Potential of Surface-Functionalized Nanoparticles.

    PubMed

    Cheng, Kwan H; Aijmo, Jacob; Ma, Lun; Yao, Mingzhen; Zhang, Xing; Como, John; Hope-Weeks, Louisa J; Huang, Juyang; Chen, Wei

    2008-10-22

    We have studied the luminescence decay and trace biomaterials detection potential of two surface-functionalized nanoparticles, poly(ethylene glycol) bis(carboxymethyl) ether-coated LaF(3):Ce,Tb (~20 nm) and thioglycolic acid-coated ZnS/Mn (~5 nm). Upon UV excitation, these nanoparticles emitted fluorescence peaking at 540 and 597 nm, respectively, in solution. Fluorescence imaging revealed that these nanoparticles targeted the trace biomaterials from fingerprints that were deposited on various nonporous solid substrates. Highly ordered, microscopic sweat pores within the friction ridges of the fingerprints were labeled with good spatial resolutions by the nanoparticles on aluminum and polymethylpentene substrates, but not on glass or quartz. In solution, these nanoparticles exhibited multicomponent fluorescence decays of resolved lifetimes ranging from nano-to microseconds and of average lifetimes of ~24 and 130 micros for the coated LaF(3):Ce,Tb and ZnS:Mn, respectively. The long microsecond-decay components are associated with the emitters at or near the nanocrystal core surface that are sensitive to the size, surface-functionalization, and solvent exposure of the nanoparticles. When the nanoparticles were bound to the surface of a solid substrate and in the dried state, a decrease in the microsecond decay lifetimes was observed, indicative of a change in the coating environment of the nanocrystal surface upon binding and solvent removal. The average decay lifetimes for the surface-bound ZnS:Mn in the dried state were ~60, 30, and 11 micros on quartz, aluminum, and polymethylpentene, respectively. These values were still 2 orders of magnitude longer than the typical fluorescence decay background of most substrates (e.g., ~0.36 micros for polymethylpentene) in trace forensic evidence detections. We conclude that coated ZnS: Mn nanoparticles hold great promise as a nontoxic labeling agent for ultrasensitive, time-gated, trace evidence detections in nanoforensic

  9. Luminescence Decay Dynamics and Trace Biomaterials Detection Potential of Surface-Functionalized Nanoparticles

    PubMed Central

    Cheng, Kwan H.; Aijmo, Jacob; Ma, Lun; Yao, Mingzhen; Zhang, Xing; Como, John; Hope-Weeks, Louisa J.; Huang, Juyang; Chen, Wei

    2009-01-01

    We have studied the luminescence decay and trace biomaterials detection potential of two surface-functionalized nanoparticles, poly(ethylene glycol) bis(carboxymethyl) ether-coated LaF3:Ce,Tb (~20 nm) and thioglycolic acid-coated ZnS/Mn (~5 nm). Upon UV excitation, these nanoparticles emitted fluorescence peaking at 540 and 597 nm, respectively, in solution. Fluorescence imaging revealed that these nanoparticles targeted the trace biomaterials from fingerprints that were deposited on various nonporous solid substrates. Highly ordered, microscopic sweat pores within the friction ridges of the fingerprints were labeled with good spatial resolutions by the nanoparticles on aluminum and polymethylpentene substrates, but not on glass or quartz. In solution, these nanoparticles exhibited multicomponent fluorescence decays of resolved lifetimes ranging from nano-to microseconds and of average lifetimes of ~24 and 130 µs for the coated LaF3:Ce,Tb and ZnS:Mn, respectively. The long microsecond-decay components are associated with the emitters at or near the nanocrystal core surface that are sensitive to the size, surface-functionalization, and solvent exposure of the nanoparticles. When the nanoparticles were bound to the surface of a solid substrate and in the dried state, a decrease in the microsecond decay lifetimes was observed, indicative of a change in the coating environment of the nanocrystal surface upon binding and solvent removal. The average decay lifetimes for the surface-bound ZnS:Mn in the dried state were ~60, 30, and 11 µs on quartz, aluminum, and polymethylpentene, respectively. These values were still