Occupational asthma due to manual metal-arc welding of special stainless steels.

PubMed

Hannu, T; Piipari, R; Kasurinen, H; Keskinen, H; Tuppurainen, M; Tuomi, T

2005-10-01

Occupational asthma (OA) can be induced by fumes of manual metal-arc welding on stainless steel. In recent years, the use of special stainless steels (SSS) with high chromium content has increased. This study presents two cases of OA caused by manual metal-arc welding on SSS. In both cases, the diagnosis of OA was based on respiratory symptoms, occupational exposure and positive findings in the specific challenge tests. In the first case, a 46-yr-old welder had experienced severe dyspnoea while welding SSS (SMO steel), but not in other situations. Challenge tests with both mild steel and stainless steel using a common electrode were negative. Welding SSS with a special electrode caused a delayed 37% drop in forced expiratory volume in one second (FEV1). In the second case, a 34-yr-old male had started to experience dyspnoea during the past few years, while welding especially SSS (Duplex steel). The workplace peak expiratory flow monitoring was suggestive of OA. Challenge tests with both mild steel and stainless steel using a common electrode did not cause bronchial obstruction. Welding SSS with a special electrode caused a delayed 31% drop in FEV1. In conclusion, exposure to manual metal-arc welding fumes of special stainless steel should be considered as a new cause of occupational asthma.

Resolution of fish allergy: a case report.

PubMed

Solensky, Roland

2003-10-01

Fish allergy is one of the most common food allergies, and it is believed to be lifelong. There are no published reports, to my knowledge, of resolution of fish allergy. To report a case of resolution of IgE-mediated fish allergy. The patient was a 68-year-old man with a history of fish-induced anaphylaxis who had previously undergone prick-puncture skin testing to several fish species. Additional skin testing was performed in October 2002. Subsequently, he underwent an open challenge with halibut. The patient's previous skin tests showed him to have strongly positive reactions to several fish species. However, testing performed in October 2002 produced negative results to a number of fish species. In addition, he tolerated an open challenge with halibut. In the ensuing 8 months, he has regularly ingested salmon, cod, and halibut without experiencing any allergic reactions. This case illustrates that fish allergy is not invariably lifelong. Hence, allergists should consider reevaluating the allergy status of adults with a history of fish hypersensitivity.

An Investigation into the Challenges In-Service Student Teachers Encounter in Transformational Geometry, "Reflection and Rotation". The Case of Mufulira College of Education

ERIC Educational Resources Information Center

Kambilombilo, Dennis; Sakala, Whyson

2015-01-01

The study was conducted to investigate the challenges in-service mathematics student teachers face in transformational geometry; reflection and rotation. The Van Hiele Theory of levels of Thought was used as the theoretical framework for this study. A case study was undertaken using a written test. The research was carried on second and third…

Clinical history as a predictor of penicillin skin test outcome.

PubMed

Wong, Benjamin B L; Keith, Paul K; Waserman, Susan

2006-08-01

Up to 10% of the population reports an "allergy" to penicillin, whereas approximately 1.1% has positive penicillin skin test results. Where penicillin skin tests are unavailable, some have advocated using history to decide whether to use a penicillin-related antibiotic. To determine if clinical history predicts penicillin skin test results. Retrospective medical record review of 94 consecutive patients who had previously taken penicillin referred for penicillin allergy. Case histories were taken, penicillin skin tests performed, and an oral challenge recommended if skin test results were negative. Of 91 cases studied, the average patient age was 27 years (range, 6 months to 82 years; 36% female). Fifty-two (57%) experienced hives as their main adverse reaction. Sixteen (18%) had at least 1 positive test result. Of this group, 9 had hives as their main symptom, whereas 1 had respiratory problems and 1 had angioedema. Most patients with positive skin test results had experienced their reaction at least 3 years ago. Regression analysis showed that age, sex, and clinical history, including type of reaction, time of reaction after penicillin ingestion, or time since the last reaction, were not associated with skin test positivity. Seventy-two (96%) of the 75 patients who had negative skin test results underwent oral challenge. Seventy had negative challenge results. The negative predictive value of a negative penicillin skin test result was 97%. Clinical history was not predictive of subsequent penicillin skin test results.

A Case-Controlled Investigation of Tactile Reactivity in Young Children with and without Global Developmental Delay

ERIC Educational Resources Information Center

Barney, Chantel C.; Tervo, Raymond; Wilcox, George L.; Symons, Frank J.

2017-01-01

Assessing tactile function among children with intellectual, motor, and communication impairments remains a clinical challenge. A case control design was used to test whether children with global developmental delays (GDD; n = 20) would be more/less reactive to a modified quantitative sensory test (mQST) compared to controls (n = 20). Reactivity…

Antimicrobial Efficacy of Multipurpose Disinfecting Solutions in the Presence of Contact Lenses and Lens Cases.

PubMed

Gabriel, Manal M; McAnally, Cindy; Bartell, John

2018-03-01

The aim of this study was to use antimicrobial efficacy endpoint methodology to determine compatibility of multipurpose disinfecting solutions (MPSs), lens cases, and hydrogel lenses for disinfection (AEEMC) against International Organization for Standardization (ISO)-specified microorganisms and clinical ocular isolates of Stenotrophomonas maltophilia. Six MPSs (PQ/Aldox 1, 2, and 3; PQ/Alexidine; PQ/PHMB; and PHMB) were challenged against ISO-specified microorganisms and S. maltophilia using the AEEMC test. AEEMC tests were performed with and without balafilcon A, etafilcon A, and senofilcon A lenses in lens cases with organic soil. Exposure times included disinfection time (DT) and 24 hr. Additionally, all six MPSs were challenged with two strains of S. maltophilia, based on the ISO Stand-alone test. The efficacy against bacteria for PQ/Aldox and PQ/Alexidine MPSs was not diminished by the presence of lenses. The efficacy of PQ/PHMB and PHMB MPSs against Serratia marcescens was significantly reduced compared with the no-lens control at DT for at least one lens type. The PHMB MPS with lenses present also demonstrated reduced efficacy against Staphylococcus aureus at DT versus the control. PQ/Aldox MPSs retained activity against Fusarium solani with lenses present; however, all other test MPSs demonstrated reduced F. solani efficacy at DT with lenses present. With lenses, all MPSs showed reduced efficacy against Candida albicans. AEEMC antimicrobial efficacy test results vary based on challenge microorganism, contact lenses, and MPS biocide systems. This study highlights the importance of evaluating MPSs for compatibility with lenses and lens cases.

Antimicrobial Efficacy of Multipurpose Disinfecting Solutions in the Presence of Contact Lenses and Lens Cases

PubMed Central

McAnally, Cindy; Bartell, John

2018-01-01

Objective: The aim of this study was to use antimicrobial efficacy endpoint methodology to determine compatibility of multipurpose disinfecting solutions (MPSs), lens cases, and hydrogel lenses for disinfection (AEEMC) against International Organization for Standardization (ISO)–specified microorganisms and clinical ocular isolates of Stenotrophomonas maltophilia. Methods: Six MPSs (PQ/Aldox 1, 2, and 3; PQ/Alexidine; PQ/PHMB; and PHMB) were challenged against ISO-specified microorganisms and S. maltophilia using the AEEMC test. AEEMC tests were performed with and without balafilcon A, etafilcon A, and senofilcon A lenses in lens cases with organic soil. Exposure times included disinfection time (DT) and 24 hr. Additionally, all six MPSs were challenged with two strains of S. maltophilia, based on the ISO Stand-alone test. Results: The efficacy against bacteria for PQ/Aldox and PQ/Alexidine MPSs was not diminished by the presence of lenses. The efficacy of PQ/PHMB and PHMB MPSs against Serratia marcescens was significantly reduced compared with the no-lens control at DT for at least one lens type. The PHMB MPS with lenses present also demonstrated reduced efficacy against Staphylococcus aureus at DT versus the control. PQ/Aldox MPSs retained activity against Fusarium solani with lenses present; however, all other test MPSs demonstrated reduced F. solani efficacy at DT with lenses present. With lenses, all MPSs showed reduced efficacy against Candida albicans. Conclusions: AEEMC antimicrobial efficacy test results vary based on challenge microorganism, contact lenses, and MPS biocide systems. This study highlights the importance of evaluating MPSs for compatibility with lenses and lens cases. PMID:27598555

Visual memory effects on intraoperator study design: determining a minimum time gap between case reviews to reduce recall bias.

PubMed

Campbell, W Scott; Talmon, Geoffrey A; Foster, Kirk W; Baker, John J; Smith, Lynette M; Hinrichs, Steven H

2015-03-01

The objective of this research was to determine test intervals between intraoperator case reviews to minimize the impact of recall. Three pathologists were presented with a group of 120 slides and subsequently challenged with a study set of 120 slides after 2-week and 4-week intervals. The challenge set consisted of 60 slides seen during the initial review and 60 slides previously unseen within the study. Pathologists rendered a diagnosis for each slide and indicated whether they recalled seeing the slide previously (yes/no). Two weeks after having been shown 60 cases from a challenge set of 120 cases, the pathologists correctly remembered 26, 22, and 24 cases or 40% overall. After 4 weeks, the pathologists correctly recalled 31% of cases previously seen. Pathologists were capable of recalling from memory cases seen previously at 2 and 4 weeks. Recall rates may be sufficiently high to affect intraobserver study design. Copyright© by the American Society for Clinical Pathology.

Increasing HIV testing among African immigrants in ireland: challenges and opportunities.

PubMed

Adedimeji, Adebola A; Asibon, Aba; O'Connor, Gerard; Carson, Richard; Cowan, Ethan; McKinley, Philip; Leider, Jason; Mallon, Patrick; Calderon, Yvette

2015-02-01

In 2012, immigrants constitute 63% of new cases of heterosexually transmitted HIV among individuals born outside Ireland. Current strategies to encourage testing can be ineffective if immigrants perceive them as culturally insensitive. We obtained qualitative data to explore challenges to voluntary HIV-testing for immigrants in Ireland. Content analysis was undertaken to identify and describe pertinent themes. Widespread beliefs that HIV is primarily a disease of African immigrants were identified as challenges that constrain access to testing and care. The organization and location of testing services, attitude of health workers, and beliefs regarding mandatory HIV-testing for immigrants seeking access to welfare benefits were also identified. Immigrants in Ireland encounter a variety of structural, cultural and personal constraints to HIV testing. Opportunities exist in the Irish Health system to increase testing among immigrants through greater acknowledgement of cultural sensitivities of immigrant groups.

In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.

PubMed

Khalesi, Maryam; Jafari, Seyed Ali; Kiani, Mohammadali; Picarelli, Antonio; Borghini, Raffaele; Sadeghi, Ramin; Eghtedar, Alireza; Ayatollahi, Hosein; Kianifar, Hamid R

2016-02-01

The in vitro gluten challenge test is an important diagnostic modality in celiac disease (CD), especially in patients who begin treatment with a gluten-free diet before adequate diagnostic workup or in cases with atypical CD. Available literature was reviewed regarding the accuracy of the in vitro gluten challenge test for CD diagnosis. MEDLINE, Scopus, and Google Scholar were searched, and studies that used serology and bowel biopsy as the criterion standard for diagnosis were included in our study. Data on authors, publication year, characteristics of the patient and control groups, patients' diet, duration of the gluten challenge test, histology findings, endomysial antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and intercellular cell adhesion molecule-1, and human leukocyte antigens before and after the gluten challenge test were extracted. Overall, 15 studies were included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti-tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test. Sensitivity/specificity for immunological markers were 89/97 for the percentage of CD25⁺-lamina propria lymphocytes, 96/91 for the percentage of CD3⁺-lamina propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell adhesion molecule-1-lamina propria lymphocytes. The factors that increased the sensitivity of EMA were longer test duration, and the evaluation of patients on a gluten-containing diet or short-term gluten-free diet. The in vitro gluten challenge test can be a useful part of the diagnostic workup of CD, rather than only a model to evaluate its mechanisms.

Skin testing for immediate hypersensitivity to corticosteroids: a case series and literature review.

PubMed

Baker, A; Empson, M; The, R; Fitzharris, P

2015-03-01

Immediate hypersensitivity to corticosteroids is reported to occur with an incidence of 0.1%. The largest previous case series reporting corticosteroid skin testing has seven patients. We identified 23 patients (mean age 50 years, 65% female) from Auckland City Hospital who underwent skin testing (ST) for suspected corticosteroid hypersensitivity between July 2005 and April 2012. We performed a retrospective clinical case note review detailing clinical history of reaction, skin test results and subsequent management. Most patients (21/23) had a standard panel of testing with prednisolone, triamcinolone, methylprednisolone, hydrocortisone and dexamethasone. Skin tests used a 10% steroid stock concentration for skin prick tests (SPT) and dilutions of 1 : 1000, 1 : 100 and 1 : 10 for subsequent intradermal testing. A weal 3 mm greater than the negative control was considered positive. A total of 23 patients were identified who had skin testing for suspected acute hypersensitivity to corticosteroids, eight of which had a history of anaphylaxis. From 28 reactions (in 23 patients), the most common route of administration was intra-articular (13), followed by oral (7), intravenous (3) and other (5). Skin tests were positive in 8/23 patients, and 7/8 of these patients had a history of corticosteroid-associated anaphylaxis. Skin tests were positive at either the skin prick test or intradermal stages. There was evidence suggesting clinical and skin test cross-reactivity between corticosteroids in one patient. One patient had a positive skin test, but negative oral challenge suggesting the skin test was false positive. Skin tests were negative in 15/23 patients. One patient had a negative prednisolone skin test and positive unblinded oral challenge, suggesting a false-negative skin test. Skin testing can provide sufficient evidence to diagnose allergy in patients with a clear history of immediate hypersensitivity to corticosteroids such as anaphylaxis. Both skin prick and intradermal tests should be used. There is evidence of cross-reactivity between steroids, so a panel is recommended. False-positive and false-negative reactions do occur; however, the frequency is unknown. Challenge remains the only definitive way to demonstrate a safe alternative to use. As the largest case series described, this article provides new evidence for the interpretation of skin tests when investigating possible immediate hypersensitivity to corticosteroids. © 2014 John Wiley & Sons Ltd.

Model Based Analysis and Test Generation for Flight Software

NASA Technical Reports Server (NTRS)

Pasareanu, Corina S.; Schumann, Johann M.; Mehlitz, Peter C.; Lowry, Mike R.; Karsai, Gabor; Nine, Harmon; Neema, Sandeep

2009-01-01

We describe a framework for model-based analysis and test case generation in the context of a heterogeneous model-based development paradigm that uses and combines Math- Works and UML 2.0 models and the associated code generation tools. This paradigm poses novel challenges to analysis and test case generation that, to the best of our knowledge, have not been addressed before. The framework is based on a common intermediate representation for different modeling formalisms and leverages and extends model checking and symbolic execution tools for model analysis and test case generation, respectively. We discuss the application of our framework to software models for a NASA flight mission.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population. PMID:29489887

Sharing the Diagnostic Process in the Clinical Teaching Environment: A Case Study

ERIC Educational Resources Information Center

Cuello-Garcia; Carlos

2005-01-01

Revealing or visualizing the thinking involved in making clinical decisions is a challenge. A case study is presented with a visual implement for sharing the diagnostic process. This technique adapts the Bayesian approach to the case presentation. Pretest probabilities and likelihood ratios are gathered to obtain post-test probabilities of every…

Legal Challenges to Testing--Larry P.: A Case in Point.

ERIC Educational Resources Information Center

Lambert, Nadine M.

Several major issues were raised against intelligence testing by the plaintiffs in Larry P. versus Wilson Riles. It was argued that since California used intelligence tests to ascertain who should be placed in programs for the educable mentally retarded (EMR), and since blacks performed less well on the tests than whites, it was the tests which…

Eosinophilic airway disease in a patient with a negative skin prick test, but a positive patch test with platinum salts--implications for medical surveillance.

PubMed

Merget, Rolf; Fartasch, Manigé; Sander, Ingrid; Van Kampen, Vera; Raulf, Monika; Brüning, Thomas

2015-09-01

We present the case of a 52-year-old woman with a topic dermatitis since adolescence who developed work-related hand eczema, cough and runny nose 12 years after she had started working as a laboratory technician at a precious metals refinery. While skin prick test with sodium hexachloroplatinate (SPTPt ) was negative, patch testing with ammonium tetrachloroplatinate was positive after 24, 48, 72, and 96 hr. Inhalation challenge with sodium hexachloroplatinate yielded cough, mild shortness of breath, and a maximal decrease of FEV1 of 8% from baseline 24 hr after the challenge. Significant increases of bronchial hyperresponsiveness, exhaled nitric monoxide and sputum eosinophils were documented after the challenge. We conclude that eosinophilic airway disease due to platinum salts may occur in SPTPt negative subjects. Both, patch testing and inhalation challenge with platinum salts should be considered in SPT negative subjects with occupational exposure to precious metal salts and work-related allergic symptoms. © 2015 Wiley Periodicals, Inc.

The challenges of detecting and responding to a Lassa fever outbreak in an Ebola-affected setting.

PubMed

Hamblion, E L; Raftery, P; Wendland, A; Dweh, E; Williams, G S; George, R N C; Soro, L; Katawera, V; Clement, P; Gasasira, A N; Musa, E; Nagbe, T K

2018-01-01

Lassa fever (LF), a priority emerging pathogen likely to cause major epidemics, is endemic in much of West Africa and is difficult to distinguish from other viral hemorrhagic fevers, including Ebola virus disease (EVD). Definitive diagnosis requires laboratory confirmation, which is not widely available in affected settings. The public health action to contain a LF outbreak and the challenges encountered in an EVD-affected setting are reported herein. In February 2016, a rapid response team was deployed in Liberia in response to a cluster of LF cases. Active case finding, case investigation, contact tracing, laboratory testing, environmental investigation, risk communication, and community awareness raising were undertaken. From January to June 2016, 53 suspected LF cases were reported through the Integrated Disease Surveillance and Response system (IDSR). Fourteen cases (26%) were confirmed for LF, 14 (26%) did not have a sample tested, and 25 (47%) were classified as not a case following laboratory analysis. The case fatality rate in the confirmed cases was 29%. One case of international exportation was reported from Sweden. Difficulties were identified in timely specimen collection, packaging, and transportation (in confirmed cases, the time from sample collection to sample result ranged from 2 to 64 days) and a lack of response interventions for early cases. The delay in response to this outbreak could have been related to a number of challenges in this EVD-affected setting: a need to strengthen the IDSR system, develop preparedness plans, train rapid response teams, and build laboratory capacity. Prioritizing these actions will aid in the timely response to future outbreaks. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cholinergic urticaria with anaphylaxis: hazardous duty of a deployed US marine.

PubMed

Handfield, Kent S; Dolan, Christopher K; Kaplan, Michael

2015-04-01

Cholinergic urticaria (CU) is triggered by a rise in body temperature and can be complicated by bronchial hyperresponsiveness and anaphylaxis. It primarily affects young adults who actively engage in strenuous exercise, such as servicemen and servicewomen. If the patient reports a history of wheezing or difficulty breathing with urticaria, a water challenge test in a warm bath can be performed to confirm the presence of anaphylaxis. The test should be conducted in an environment in which the patient's airway can be secured and epinephrine can be administered if necessary. Nonsedating antihistamines commonly are used to treat CU, but few other treatments have been thoroughly evaluated for cases that are refractory to antihistamines. We present the case of a 27-year-old US Marine with CU and anaphylaxis confirmed by a water challenge test in a warm bath.

Testing Methods for Challenging the National Wetland Plant List: Using Tsuga canadensis (L.) Carr. (Eastern Hemlock) as a Case Study

DTIC Science & Technology

2017-07-01

ESRI (Nature Conservancy and Environmental Systems Research Institute). 1994. Field Methods . In Field Methods for Vegetation Mapping: United States...ER D C/ CR RE L TR -1 7- 9 Wetlands Regulatory Assistance Program (WRAP) Testing Methods for Challenging the National Wetland Plant List...Robert W. Lichvar and Jennifer J. Goulet July 2017 Approved for public release; distribution is unlimited. The U.S. Army Engineer Research

[Occupational allergic "march". Rapid evolution of contact dermatitis to ammonium persulfate into airborne contact dermatitis with rhinitis and asthma in a hairdresser].

PubMed

Poltronieri, Anna; Patrini, L; Pigatto, P; Riboldi, L; Marsili, Chiara; Previdi, M; Margonari, M; Marraccini, P

2010-01-01

Hairdressers are exposed to irritants and allergenic compounds that may cause contact dermatitis, rhinitis and asthma. In this paper we describe the case of a female, age 33 years, who developed contact dermatitis after 10 years of exposure to ammonium persulfate. After 7 months of progressively extensive and persistent skin lesions, respiratory symptoms appeared that were related to the occupational exposure (on-off test). SIDAPA and specific occupational patch test for hairdressers and occupational challenge with ammonium persulfate were performed. Clinical parameters of inflammation, ECP (eosinophil cationic protein) and exhaled nitric oxide (FeNO) were detected before and after the specific bronchial challenge. The patch test was positive to ammonium persulfate (++), and bronchial challenge for ammonium persulfate showed a significant late response (FEV1 decrease--33%). Both FeNO and ECP showed a significant increase after 24 hours. Dermatitis, urticaria and angioedema occurred on the uncovered skin due to airborne contact. Topic steroids and anti-histaminic drugs resolved the clinical symptoms. Bronchial challenge is, in fact, considered to be the gold standard for the diagnosis of occupational asthma, although new inflammatory parameters can contribute to the diagnosis and can be useful for monitoring after a specific inhalation test with occupational agents. The described case summarizes the evolution from contact dermatitis to inhalation allergy, suggesting the occurrence of an allergic "march" for occupational allergy.

An Explanatory Item Response Theory Approach for a Computer-Based Case Simulation Test

ERIC Educational Resources Information Center

Kahraman, Nilüfer

2014-01-01

Problem: Practitioners working with multiple-choice tests have long utilized Item Response Theory (IRT) models to evaluate the performance of test items for quality assurance. The use of similar applications for performance tests, however, is often encumbered due to the challenges encountered in working with complicated data sets in which local…

Diagnostic Challenges of Central Nervous System Tuberculosis

PubMed Central

Loeffler, Ann M.; Honarmand, Somayeh; Flood, Jennifer M.; Baxter, Roger; Jacobson, Susan; Alexander, Rick; Glaser, Carol A.

2008-01-01

Central nervous system tuberculosis (TB) was identified in 20 cases of unexplained encephalitis referred to the California Encephalitis Project. Atypical features (encephalitic symptoms, rapid onset, age) and diagnostic challenges (insensitive cerebrospinal fluid [CSF] TB PCR result, elevated CSF glucose levels in patients with diabetes, negative result for tuberculin skin test) complicated diagnosis. PMID:18760024

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

PubMed

Sesé, L; Gaouar, H; Autegarden, J-E; Alari, A; Amsler, E; Vial-Dupuy, A; Pecquet, C; Francès, C; Soria, A

2016-03-01

The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%). © 2016 John Wiley & Sons Ltd.

Aerothermodynamics of Blunt Body Entry Vehicles. Chapter 3

NASA Technical Reports Server (NTRS)

Hollis, Brian R.; Borrelli, Salvatore

2011-01-01

In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of Computational Fluid Dynamics (CFD) code predictions.

Aerothermodynamics of blunt body entry vehicles

NASA Astrophysics Data System (ADS)

Hollis, Brian R.; Borrelli, Salvatore

2012-01-01

In this chapter, the aerothermodynamic phenomena of blunt body entry vehicles are discussed. Four topics will be considered that present challenges to current computational modeling techniques for blunt body environments: turbulent flow, non-equilibrium flow, rarefied flow, and radiation transport. Examples of comparisons between computational tools to ground and flight-test data will be presented in order to illustrate the challenges existing in the numerical modeling of each of these phenomena and to provide test cases for evaluation of computational fluid dynamics (CFD) code predictions.

Methotrexate Hypersensitivity Reactions in Pediatrics: Evaluation and Management

PubMed Central

Dilley, Meredith A.; Lee, Joyce P.; Broyles, Ana Dioun

2017-01-01

Reports of hypersensitivity reactions (HSRs) to MTX are limited to single case studies. We retrospectively reviewed HSRs to MTX during a 12-year period in our tertiary care pediatric center. Seven patients were evaluated for HSRs to MTX. Skin testing was positive in one of the 4 patients tested. One patient underwent successful graded challenge to MTX. Seventeen desensitizations to MTX were successfully performed in the other 6 patients. Skin testing, graded challenge, and desensitization were safe and effective procedures in the evaluation and management of patients with HSRs to MTX in our pediatric population. PMID:27786403

Occupational asthma caused by cellulase and lipase in the detergent industry.

PubMed

Brant, A; Hole, A; Cannon, J; Helm, J; Swales, C; Welch, J; Taylor, A Newman; Cullinan, P

2004-09-01

Three employees from two different detergent companies were investigated for occupational asthma, using skin prick tests, serum specific IgE, and specific bronchial challenge. Two were challenged with lipase and one with cellulase. All three cases had immunological evidence of sensitisation to the detergent enzymes with which they worked. Bronchial challenge in each provoked a reproducible dual asthmatic response, which reproduced their work related symptoms. These are the first reported cases of occupational asthma attributable to cellulase and lipase in the detergent industry. Four of the most common enzymes used in this industry have now been reported to cause occupational asthma; continued vigilance and caution are needed when working with these or other enzymes.

The Teacher as Examiner of L2 Oral Tests: A Challenge to Standardization

ERIC Educational Resources Information Center

Sundqvist, Pia; Wikström, Peter; Sandlund, Erica; Nyroos, Lina

2018-01-01

The present paper looks at the issue of standardization in L2 oral testing. Whereas external examiners are frequently used globally, some countries opt for test-takers' own teachers as examiners instead. In the present study, Sweden is used as a case in point, with a focus on the mandatory, high-stakes, summative, ninth-grade national test in…

First evidence of occupational asthma to argan powder in a cosmetic factory.

PubMed

Paris, C; Herin, F; Penven, E; Thaon, I; Richard, C; Jacquenet, S; Barbaud, A; Poussel, M

2016-04-01

Argan is used worldwide in numerous cosmetic products, as this fruit is supposed to have many beneficial properties on health. New cases of allergy can be expected with the growing use of argan. We investigated all workers (9) employed by a cosmetic factory and exposed to argan powder to identify possible allergies related to exposure to argan powder. Patients were investigated in the occupational disease department and, according to their symptoms, underwent pulmonary function testing, methacholine challenge, specific inhalation challenge to argan powder, skin prick tests, and immunoblotting analysis. We report three cases of occupational asthma to argan powder and a probable case of rhinitis. Fifteen argan proteins were recognized by the patients' IgE. Identification of proteins, cross-reactions to nuts, and ELISA inhibition tests suggested that some argan allergens can cross-react in vitro with hazelnut allergens, including 11S globulin and vicilin. High-level exposure to argan powder should be considered to be a potential cause of IgE-mediated allergy, and workers handling argan powder should be carefully investigated. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Case Study on a Capsule Robot in the Gastrointestinal Tract to Teach Robot Programming and Navigation

ERIC Educational Resources Information Center

Guo, Yi; Zhang, Shubo; Ritter, Arthur; Man, Hong

2014-01-01

Despite the increasing importance of robotics, there is a significant challenge involved in teaching this to undergraduate students in biomedical engineering (BME) and other related disciplines in which robotics techniques could be readily applied. This paper addresses this challenge through the development and pilot testing of a bio-microrobotics…

Powassan Virus-A New Reemerging Tick-Borne Disease.

PubMed

Fatmi, Syed Soheb; Zehra, Rija; Carpenter, David O

2017-01-01

Powassan virus is a neurovirulent flavivirus consisting of two lineages causing meningoencephalitis. It is the only member of the tick-borne encephalitis serogroup which is present in mainland North America. With a total number of 27 cases from 1958 to 1998 and 98 cases from 1999 to 2016, reported cases have increased by 671% over the last 18 years. Powassan infection is transmitted by different tick species in different geographical regions. Ixodes scapularis is the primary vector that transmits the virus on the East Coast of US and Ixodes cookei in the Midwest and Canada, while Hemaphysalis longicornis is the vector in Russia. Powassan has no singular pathognomonic finding and presents with a wide spectrum of symptoms including severe neurological symptoms. The clinical challenge lies within the management of the disease as there is no standard diagnostic protocol and most cases are only diagnosed after a patient goes through an extensive workup for other infectious disease. The diagnosis is established by a combination of imaging and serologic tests. In case of Powassan meningoencephalitis, computed tomography scan and magnetic resonance imaging show vascular insults, which are also seen in cases of tick-borne encephalitis virus, another flavivirus of medical importance. Serologic tests are the gold standard for diagnosis, although testing is not widely available and only state health departments and Center for Disease Control and Prevention can perform Powassan-specific IgM antibody testing utilizing enzyme-linked immunosorbent assay and immunofluorescence antibody. Powassan is also of veterinary medical importance. Wildlife animals act as a reservoir to the pathogens, hence possessing threat to humans and domestic animals. This review highlights Powassan's neurotropic presentation, epidemiology, diagnostic challenges, and prevalence. Strong emphasis is placed on establishing diagnostic protocols, widespread Powassan-specific IgM testing, role of the vector in disease presentation, and necessary preventive research.

The management of isolated positive syphilis enzyme immunoassay results in HIV-negative patients attending a sexual health clinic.

PubMed

Thorley, Nicola; Adebayo, Michael; Smit, Erasmus; Radcliffe, Keith

2016-08-01

An unconfirmed positive treponemal enzyme immunoassay (enzyme immunoassay positive, Treponema pallidum particle agglutination negative and rapid plasma reagin negative) presents a clinical challenge to distinguish early syphilis infection from false-positive results. These cases are referred for syphilis line assay (INNO-LIA) and recalled for repeat syphilis serology. We performed a retrospective audit to establish the proportion of HIV-negative cases with unconfirmed positive enzyme immunoassay results, the proportion of these cases that received an INNO-LIA test and repeat syphilis serology testing and reviewed the clinical outcomes; 0.35% (80/22687) cases had an unconfirmed positive treponemal enzyme immunoassay result. Repeat syphilis serology was performed in 80% (64/80) cases, but no additional cases of syphilis were identified. Eighty-eight per cent (70/80) received an INNO-LIA test; 14% (5/37) unconfirmed enzyme immunoassay-positive cases with no prior history of syphilis were confirmed on INNO-LIA assay, supporting a diagnosis of latent syphilis. As a confirmatory treponemal test, the INNO-LIA assay may be more useful than repeat syphilis serological testing. © The Author(s) 2016.

Radiation from Cardiac Imaging Tests

MedlinePlus

... Bridging Disciplines Circulation at Major Meetings Special Themed Issues Global Impact of the 2017 ACC/AHA Hypertension Guidelines Circulation Supplements Cardiovascular Case Series ECG Challenge Hospitals of History Brigham and ...

Hypersensitivity pneumonia-nonspecific interstitial pneumonia/fibrosis histopathologic presentation: a study in diagnosis and long-term management.

PubMed

Jacobs, Robert L; Andrews, Charles P

2003-02-01

Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic improvement, but may convert a patient from an acute to an insidious presenter. The environmental challenge obviates a need for specific challenges to determine specific causation. Remediation of or moving from an environmental contamination to achieve reversibility or prevent progression was the treatment of choice to avoid use of long-term immunosuppressive agents.

A study of myocardial perfusion in patients with panic disorder and low risk coronary artery disease after 35% CO2 challenge.

PubMed

Fleet, Richard; Foldes-Busque, Guillaume; Grégoire, Jean; Harel, François; Laurin, Catherine; Burelle, Denis; Lavoie, Kim

2014-01-01

We have previously reported that 35% CO2 challenge induced myocardial ischemia in 81% of coronary artery disease (CAD) patients with comorbid panic disorder (PD) and previous positive nuclear exercise stress tests. However, it is yet unclear whether this is the case among CAD patients with PD and normal nuclear exercise stress test results. We hypothesized that a potent mental stressor such as a panic challenge among CAD patients with PD would also induce ischemia in patients with normal exercise stress tests. Forty-one coronary artery disease patients with normal nuclear exercise stress tests (21 patients with PD and 20 without PD) were submitted to a well-established panic challenge test (with 1 vital capacity inhalation of a gas mixture containing 35% CO2 and 65% O2) and injected with Tc-99m-tetrofosmin (Myoview), upon inhalation. Single photon emission computed tomography imaging was used to assess per-panic challenge reversible myocardial ischemia and HR, BP, and a 12 lead ECG was continuously measured during the procedure. Fifty-eight percent of panic disorder patients (12/21) had a panic attack during the panic challenge vs 15% (3/20) of controls (p=0.005). Only 10% of patients in each group displayed myocardial ischemia per panic challenge. These findings suggest that panic attacks among panic disorder patients with lower-risk coronary artery disease may not confer a risk for myocardial ischemia. © 2013.

Where do we go from here: Challenges and the future of endocrine disrupting compound screening and testing

EPA Science Inventory

ABSTRACTWorldwide concern about the impacts of endocrine disrupting compounds on both human and environmental health has led to implementation of multiple screening and testing programs. In most cases these programs have focused on impacts to the estrogen, androgen and thyroid h...

Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study.

PubMed

Deloria Knoll, Maria; Fu, Wei; Shi, Qiyuan; Prosperi, Christine; Wu, Zhenke; Hammitt, Laura L; Feikin, Daniel R; Baggett, Henry C; Howie, Stephen R C; Scott, J Anthony G; Murdoch, David R; Madhi, Shabir A; Thea, Donald M; Brooks, W Abdullah; Kotloff, Karen L; Li, Mengying; Park, Daniel E; Lin, Wenyi; Levine, Orin S; O'Brien, Katherine L; Zeger, Scott L

2017-06-15

In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case-control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case-control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

A challenging case of an ectopic cushing syndrome.

PubMed

Menezes Nunes, Joana; Pinho, Elika; Camões, Isabel; Maciel, João; Cabral Bastos, Pedro; Souto de Moura, Conceição; Bettencourt, Paulo

2014-01-01

Bronchopulmonary carcinoids are rare pulmonary neoplasms although they account for most cases of ectopic ACTH syndromes. When feasible, the mainstay treatment is surgical resection of the tumor. We report the case of a 52-year-old woman with signs and symptoms suggestive of hypercortisolism for 12 months, admitted to our department because of community acquired pneumonia. Blood hormone analysis showed increased levels of ACTH and urinary free cortisol and nonsuppressibility to high- and low-dose dexamethasone tests. Pituitary MRI showed no lesion and no central-to-peripheral ACTH gradient was present in bilateral inferior petrosal sinus sampling. CRH stimulation test suggested an ectopic ACTH source. Thoracic CT scan revealed a nodular region measuring 12 mm located in the inferior lingular lobule of the left superior lung with negative uptake by (18)-FDG-PET scan and negative SRS. The patient was successfully treated with an atypical lung resection and histology revealed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. This was an interesting case because the patient was admitted due to pneumonia that may have been associated with her untreated and chronic hypercortisolism and a challenging case of ectopic ACTH syndrome due to conflicting results on the diagnostic exams.

Malaria in Brazil, Colombia, Peru and Venezuela: current challenges in malaria control and elimination.

PubMed

Recht, Judith; Siqueira, André M; Monteiro, Wuelton M; Herrera, Sonia M; Herrera, Sócrates; Lacerda, Marcus V G

2017-07-04

In spite of significant progress towards malaria control and elimination achieved in South America in the 2000s, this mosquito-transmitted tropical disease remains an important public health concern in the region. Most malaria cases in South America come from Amazon rain forest areas in northern countries, where more than half of malaria is caused by Plasmodium vivax, while Plasmodium falciparum malaria incidence has decreased in recent years. This review discusses current malaria data, policies and challenges in four South American Amazon countries: Brazil, Colombia, Peru and the Bolivarian Republic of Venezuela. Challenges to continuing efforts to further decrease malaria incidence in this region include: a significant increase in malaria cases in recent years in Venezuela, evidence of submicroscopic and asymptomatic infections, peri-urban malaria, gold mining-related malaria, malaria in pregnancy, glucose-6-phosphate dehydrogenase (G6PD) deficiency and primaquine use, and possible under-detection of Plasmodium malariae. Some of these challenges underscore the need to implement appropriate tools and procedures in specific regions, such as a field-compatible molecular malaria test, a P. malariae-specific test, malaria diagnosis and appropriate treatment as part of regular antenatal care visits, G6PD test before primaquine administration for P. vivax cases (with weekly primaquine regimen for G6PD deficient individuals), single low dose of primaquine for P. falciparum malaria in Colombia, and national and regional efforts to contain malaria spread in Venezuela urgently needed especially in mining areas. Joint efforts and commitment towards malaria control and elimination should be strategized based on examples of successful regional malaria fighting initiatives, such as PAMAFRO and RAVREDA/AMI.

Allergen Challenge Chamber: an innovative solution in allergic rhinitis diagnosis.

PubMed

Krzych-Fałta, Edyta; Sowa, Jerzy; Wojas, Oksana; Piekarska, Barbara; Sybilski, Adam; Samoliński, Bolesław

2015-12-01

The Allergen Challenge Chamber (ACC) is definitely a serious challenge on the one hand and an innovative solution in allergic rhinitis diagnosis on the other. The gradual validation of the chamber (according to the test protocol) will allow for standardisation, which is a process undertaken by centres worldwide. The process of designing a consistent system that allows for creating conditions as those in the case of natural inhalation took into account all the aspects (technical specification) necessary to ensure appropriate inhalation.

[Clinical microbiology laboratory and imported parasitic diseases].

PubMed

Martín-Rabadán, Pablo; Martínez-Ruiz, Rocío; Cuadros, Juan; Cañavate, Carmen

2010-12-01

Imported parasitosis represents an increasingly frequent diagnostic challenge for microbiology laboratories. A surge in immigration and international travel has led to a rise in the number of imported cases of parasitosis, and this trend is expected to continue in the future. The present article addresses this challenge by reviewing recommended diagnostic approaches and tests. Currently, microscopy is always recommended when analysing blood samples for parasites. If malaria is suspected, rapid antigen testing (including at least HRP2 antigen) should also be performed. The work-up for suspected leishmaniasis should include serology, culture, and in selected cases detection of antigen in urine. In suspected Chagas disease, two different serological tests should be performed. PCR for blood protozoa is highly sensitive, although it cannot be used to rule out Chagas disease, since this condition may be present without parasitemia. Accurate diagnosis of intestinal amebiasis usually requires PCR or antigen detection tests. In helminthiasis, traditional microscopy may need to be complemented with other tests, such as agar plate culture for strongyloidiasis, Og4C3 antigen detection for bancroftian filariasis, and antibody detection test for filariasis and schistosomiasis. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Monophasic synovial sarcoma of posterior pharyngeal wall: a rare case report with unique reconstruction using lateral trapezius flap.

PubMed

Agarwal, Mudit; Singh, Abhishek; Abrari, Adleeb; Singh, Naveen

2017-04-01

Synovial sarcoma is a rare entity to be encountered in the head and neck region and is always a challenge in terms of diagnosis, treatment planning and reconstruction of the surgical defect. In our case, we faced a similar challenge for diagnosis and also have ventured for lateral trapezius flap as a new reconstructive option for such bulky tumour defects. We hereby present a 25-year old male patient with monophasic synovial sarcoma of posterior pharyngeal wall. The radiological and clinicopathological features along with various diagnostic tests and treatment options are discussed.

Histological features associated with diagnostic agreement in atypical ductal hyperplasia of the breast: illustrative cases from the B-Path study.

PubMed

Allison, Kimberly H; Rendi, Mara H; Peacock, Sue; Morgan, Tom; Elmore, Joann G; Weaver, Donald L

2016-12-01

This study examined the case-specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast. Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histological features, which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists' perceptions of case difficulty, borderline features or whether they would obtain a second opinion were also examined for associations with agreement. Of the 2070 participant interpretations of the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (P < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (P < 0.001). Diagnostic agreement ranged from 10% to 89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytological monotony were associated with higher agreement. Lower agreement rates were associated with solid or micropapillary architecture, borderline cytological monotony, or cases without a diagnostic area that was obvious on low power. The results of this study suggest that pathologists frequently recognize the challenge of ADH cases, with some cases being more prone to diagnostic variability. In addition, there are specific histological features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. © 2016 John Wiley & Sons Ltd.

Histologic Features associated with Diagnostic Agreement in Atypical Ductal Hyperplasia of the Breast: Illustrative Cases from the B-Path Study

PubMed Central

Allison, Kimberly H.; Rendi, Mara H.; Peacock, Sue; Morgan, Tom; Elmore, Joann G.; Weaver, Donald L.

2016-01-01

Background Case specific characteristics associated with interobserver diagnostic agreement in atypical ductal hyperplasia (ADH) of the breast are poorly understood. Methods Seventy-two test set cases with a consensus diagnosis of ADH from the B-Path study were evaluated. Cases were scored for 17 histologic features which were then correlated with the participant agreement with the consensus ADH diagnosis. Participating pathologists’ perceptions of case difficulty, borderline features, or if they would obtain a second opinion were also examined for associations with agreement. Results Of the 2,070 participant interpretations on the 72 consensus ADH cases, 48% were scored by participants as difficult and 45% as borderline between two diagnoses; the presence of both of these features was significantly associated with increased agreement (p < 0.001). A second opinion would have been obtained in 80% of interpretations, and this was associated with increased agreement (p < 0.001). Diagnostic agreement ranged from 10–89% on a case-by-case basis. Cases with papillary lesions, cribriform architecture and obvious cytologic monotony were associated with higher agreement. Lower agreement rates were associated with solid or micro-papillary architecture, borderline cytologic monotony or cases without a diagnostic area that was obvious on low power. Conclusions The results of this study suggest that pathologists frequently recognize the challenge of ADH cases with some cases more prone to diagnostic variability. In addition, there are specific histologic features associated with diagnostic agreement on ADH cases. Multiple example images from cases in this test set are provided to serve as educational illustrations of these challenges. PMID:27398812

Malaria elimination in Botswana, 2012-2014: achievements and challenges.

PubMed

Chihanga, Simon; Haque, Ubydul; Chanda, Emmanuel; Mosweunyane, Tjantilili; Moakofhi, Kense; Jibril, Haruna Baba; Motlaleng, Mpho; Zhang, Wenyi; Glass, Gregory E

2016-02-24

Botswana significantly reduced its malaria burden between 2000 and 2012. Incidence dropped from 0.99 to 0.01 % and deaths attributed to malaria declined from 12 to 3. The country initiated elimination strategies in October 2012. We examine the progress and challenges during implementation and identify future needs for a successful program in Botswana. A national, rapid notification and response strategy was developed. Cases detected through the routine passive surveillance system at health facilities were intended to initiate screening of contacts around a positive case during follow up. Positive cases were reported to district health management teams to activate district rapid response teams (DRRT). The health facility and the DRRT were to investigate the cases, and screen household members within 100 m of case households within 48 h of notification using rapid diagnostic tests (RDT) and microscopy. Positive malaria cases detected in health facilities were used for spatial analysis. There were 1808 malaria cases recorded in Botswana during 26 months from October, 2012 to December, 2014. Males were more frequently infected (59%) than females. Most cases (60%) were reported from Okavango district which experienced an outbreak in 2013 and 2014. Among the factors creating challenges for malaria eradication, only 1148 cases (63.5%) were captured by the required standardized notification forms. In total, 1080 notified cases were diagnosed by RDT. Of the positive malaria cases, only 227 (12.6%) were monitored at the household level. One hundred (8.7%) cases were associated with national or transnational movement of patients. Local movements of infected individuals within Botswana accounted for 31 cases while 69 (6.01%) cases were imported from other countries. Screening individuals in and around index households identified 37 additional, asymptomatic infections. Oscillating, sporadic and new malaria hot-spots were detected in Botswana during the study period. Botswana's experience shows some of the practical challenges of elimination efforts. Among them are the substantial movements of human infections within and among countries, and the persistence of asymptomatic reservoir infections. Programmatically, challenges include improving the speed of communicating and improving the thoroughness when responding to newly identified cases. The country needs further sustainable interventions to target infections if it is to successfully achieve its elimination goal.

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.

PubMed

Di Lorenzo, Gabriele; Pacor, Maria Luisa; Mansueto, Pasquale; Martinelli, Nicola; Esposito-Pellitteri, Maria; Lo Bianco, Claudia; Ditta, Vito; Leto-Barone, Maria Stefania; Napoli, Nicola; Di Fede, Gaetana; Rini, Giovambattista; Corrocher, Roberto

2005-11-01

Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU. Copyright (c) 2005 S. Karger AG, Basel.

Central nervous system Aspergillus infection after epidural analgesia: diagnosis, therapeutic challenges, and literature review

PubMed Central

Genzen, Jonathan R.; Kenney, Barton

2009-01-01

Aspergillus terreus was identified in an intra-dural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid (CSF) was non-diagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case. PMID:19717262

Baker's asthma in a child.

PubMed

Alonso, E; Ausín, A; Elices, A; Moreno-Escobosa, M; Ibáñez, M; Laso, M

2001-01-01

baker's asthma is a well-known occupational lung disease which usually develops in adults. We report the case of a two years old boy who suffered from asthma, urticaria and atopic dermatitis for twelve months, whose symptoms were associated to visits to his grandfather's bakery. skin prick tests (SPT) were made to dust mites, moulds, flours, alfa-amylase and egg. It was also determined total IgE and specific IgE antibodies to alfa-amylase and flours. Subsequently, a challenge test was carried out with wheat flour. The SPTs were positive to flours, alfa-amylase and egg. The determination of specific IgE antibodies showed 2.64 kU/L to wheat, 0.79 kU/L to glyadin and 2.98 kU/L to alfa-amylase. The patient developed asthma and rhinitis after manipulating wheat flour for 10 min. we demonstrated a type I hypersensitivity to wheat flour and alfa-amylase in a two years old child by SPT, specific IgE antibodies and challenge test. This case in the childhood equivalent of occupational baker's asthma.

Factoring quality laboratory diagnosis into the malaria control agenda for sub-Saharan Africa.

PubMed

Aidoo, Michael

2013-09-01

Recent progress in malaria control in sub-Saharan Africa has been achieved primarily through provision of insecticide-treated nets, indoor residual spraying, and antimalarial drugs. Although these interventions are important, proper case identification and accurate measurement of their impact depend on quality diagnostic testing. Current availability of diagnostic testing for malaria in sub-Saharan Africa is inadequate to support disease management, prevention programs, and surveillance needs. Challenges faced include a dearth of skilled workforce, inadequate health systems infrastructure, and lack of political will. A coordinated approach to providing pre-service clinical and laboratory training together with systems that support a scale-up of laboratory services could provide means not only for effective malaria case management but also, management of non-malaria febrile illnesses, disease surveillance, and accurate control program evaluation. A synthesis of the challenges faced in ensuring quality malaria testing and how to include this information in the malaria control and elimination agenda are presented.

Automated Simultaneous Assembly of Multistage Testlets for a High-Stakes Licensing Examination

ERIC Educational Resources Information Center

Breithaupt, Krista; Hare, Donovan R.

2007-01-01

Many challenges exist for high-stakes testing programs offering continuous computerized administration. The automated assembly of test questions to exactly meet content and other requirements, provide uniformity, and control item exposure can be modeled and solved by mixed-integer programming (MIP) methods. A case study of the computerized…

A multi-case report of the pathways to and through genetic testing and cancer risk management for BRCA mutation-positive women aged 18–25

PubMed Central

Werner-Lin, Allison

2012-01-01

Much of the extant literature addressing the psychosocial aspects of BRCA1/2 mutation testing and risk management aggregates mutation carriers of all ages in study recruitment, data analysis, and interpretation. This analytic strategy does not adequately address the needs of the youngest genetic testing consumers, i.e., women aged 18–25. Despite low absolute cancer risk estimates before age 30, BRCA1/2 mutation-positive women aged 18–25 feel vulnerable to a cancer diagnosis but find themselves in a management quandary because the clinical utility of screening and prevention options are not yet well defined for such young carriers. We present three cases, selected from a larger study of 32 BRCA1/2 mutation-positive women who completed or considered genetic testing before age 25, to demonstrate the unique developmental, relational and temporal influences, as well as the challenges, experienced by very young BRCA mutation-positive women as they complete genetic testing and initiate cancer risk management. The first case describes the maturation of a young woman whose family participated in a national cancer registry. The second addresses the experiences and expectations of a young woman who completed genetic testing after learning that her unaffected father was a mutation carrier. The third case highlights the experiences of a young woman parentally bereaved in childhood, who presented for genetic counseling and testing due to intense family pressure. Together, these cases suggest that BRCA1/2-positive women aged 18–25 are challenged to reconcile their burgeoning independence from their families with risk-related support needs. Loved ones acting in ways meant to care for these young women may inadvertently apply pressure, convoluting family support dynamics and autonomous decision-making. Ongoing support from competent healthcare professionals will enable these young women to remain informed and receive objective counsel about their risk-management decisions. PMID:22864682

Challenges in Rotorcraft Acoustic Flight Prediction and Validation

NASA Technical Reports Server (NTRS)

Boyd, D. Douglas, Jr.

2003-01-01

Challenges associated with rotorcraft acoustic flight prediction and validation are examined. First, an outline of a state-of-the-art rotorcraft aeroacoustic prediction methodology is presented. Components including rotorcraft aeromechanics, high resolution reconstruction, and rotorcraft acoustic prediction arc discussed. Next, to illustrate challenges and issues involved, a case study is presented in which an analysis of flight data from a specific XV-15 tiltrotor acoustic flight test is discussed in detail. Issues related to validation of methodologies using flight test data are discussed. Primary flight parameters such as velocity, altitude, and attitude are discussed and compared for repeated flight conditions. Other measured steady state flight conditions are examined for consistency and steadiness. A representative example prediction is presented and suggestions are made for future research.

The constitutionality of random drug and alcohol testing of students in secondary schools.

PubMed

Estrin, Irene; Sher, Leo

2006-01-01

Adolescent drug and alcohol use is a major public health problem. Multiple studies indicate that substance use is a risk factor for physical and mental disorders in adolescents. Secondary schools and the communities they serve have been facing a long-standing problem of substance abuse. American adolescents have become quite accustomed to drug prevention being a part of their curriculum. However, some policy decisions made by school administrators have been legally challenged. In 1989, Vernonia School District serving a small community in Oregon, instituted a random drug testing policy of its athletes. In 1991, the parents of a seventh grader refused to give their consent for random drug testing. The seventh grader was denied participation in the sport and sued the School District arguing that the school policy violated the Fourth and Fourteenth Amendments to the United States Constitution, and Article I, Section 9 of the Oregon Constitution. In 1995, on appeal to the Supreme Court of the United States, the School District won the case. The Vernonia School District versus Acton case became a landmark case, but random drug and alcohol testing in secondary schools has been a subject of multiple court cases. The authors discuss three of them. Both Federal and State Courts have recognized that a secondary school environment in itself represents "a special need," for which suspicionless searches are sometimes necessary to maintain order, safety, and discipline. Drug and alcohol testing programs in secondary schools may still be challenged on its legality. Therefore, examining court sanctioned programs and their long-term efficacy statistics is recommended.

Challenges with controlling varicella in prison settings: Experience of California, 2010–2011

PubMed Central

Leung, Jessica; Lopez, Adriana S.; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H.; Preas, Christopher P.; Cosentino, Giorgio; Bialek, Stephanie R.; Marin, Mona

2015-01-01

We describe the epidemiology of varicella in one state prison in California during 2010–2011, control measures implemented, and associated costs. Eleven varicella cases were reported, 9 associated with 2 outbreaks. One outbreak consisted of 3 cases and the second consisted of 6 cases with 2 generations of spread. Among exposed inmates serologically tested, 98% (643/656) were VZV sero-positive. The outbreaks resulted in >1,000 inmates exposed, 444 staff exposures, and >$160,000 in costs. We documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary for managing cases and outbreaks. PMID:25201912

Increase in Testing Efficiency through the Development of an IT-Based Adaptive Testing Tool for Competency Measurement Applied to a Health Worker Training Test Case

ERIC Educational Resources Information Center

Kleinhans, Janne; Schumann, Matthias

2015-01-01

In the context of education and training, competency measurement (CM) is a central challenge in competency management. For complex CMs, a compromise must be addressed between the time available and the number of dimensions to be measured or the quality of the measurements. Increasing the efficiency of existing tests for CMs therefore poses a key…

Parallel ALLSPD-3D: Speeding Up Combustor Analysis Via Parallel Processing

NASA Technical Reports Server (NTRS)

Fricker, David M.

1997-01-01

The ALLSPD-3D Computational Fluid Dynamics code for reacting flow simulation was run on a set of benchmark test cases to determine its parallel efficiency. These test cases included non-reacting and reacting flow simulations with varying numbers of processors. Also, the tests explored the effects of scaling the simulation with the number of processors in addition to distributing a constant size problem over an increasing number of processors. The test cases were run on a cluster of IBM RS/6000 Model 590 workstations with ethernet and ATM networking plus a shared memory SGI Power Challenge L workstation. The results indicate that the network capabilities significantly influence the parallel efficiency, i.e., a shared memory machine is fastest and ATM networking provides acceptable performance. The limitations of ethernet greatly hamper the rapid calculation of flows using ALLSPD-3D.

Illustrative case studies in the return of exome and genome sequencing results

PubMed Central

Amendola, Laura M; Lautenbach, Denise; Scollon, Sarah; Bernhardt, Barbara; Biswas, Sawona; East, Kelly; Everett, Jessica; Gilmore, Marian J; Himes, Patricia; Raymond, Victoria M; Wynn, Julia; Hart, Ragan; Jarvik, Gail P

2015-01-01

Whole genome and exome sequencing tests are increasingly being ordered in clinical practice, creating a need for research exploring the return of results from these tests. A goal of the Clinical Sequencing and Exploratory Research (CSER) consortium is to gain experience with this process to develop best practice recommendations for offering exome and genome testing and returning results. Genetic counselors in the CSER consortium have an integral role in the return of results from these genomic sequencing tests and have gained valuable insight. We present seven emerging themes related to return of exome and genome sequencing results accompanied by case descriptions illustrating important lessons learned, counseling challenges specific to these tests and considerations for future research and practice. PMID:26478737

New Mass Properties Engineers Aerospace Ballasting Challenge Facilitated by the SAWE Community

NASA Technical Reports Server (NTRS)

Cutright, Amanda; Shaughnessy, Brendan

2010-01-01

The discipline of Mass Properties Engineering tends to find the engineers; not typically vice versa. In this case, two engineers quickly found their new responsibilities deep in many aspects of mass properties engineering and required to meet technical challenges in a fast paced environment. As part of NASA's Constellation Program, a series of flight tests will be conducted to evaluate components of the new spacecraft launch vehicles. One of these tests is the Pad Abort 1 (PA-1) flight test which will test the Launch Abort System (LAS), a system designed to provide escape for astronauts in the event of an emergency. The Flight Test Articles (FTA) used in this flight test are required to match mass properties corresponding to the operational vehicle, which has a continually evolving design. Additionally, since the structure and subsystems for the Orion Crew Module (CM) FTA are simplified versions of the final product, thousands of pounds of ballast are necessary to achieve the desired mass properties. These new mass properties engineers are responsible for many mass properties aspects in support of the flight test, including meeting the ballasting challenge for the CM Boilerplate FTA. SAWE expert and experienced mass properties engineers, both those that are directly on the team and many that supported via a variety of Society venues, significantly contributed to facilitating the success of addressing this particular mass properties ballasting challenge, in addition to many other challenges along the way. This paper discusses the details regarding the technical aspects of this particular mass properties challenge, as well as identifies recommendations for new mass properties engineers that were learned from the SAWE community along the way.

Ensemble method for dengue prediction.

PubMed

Buczak, Anna L; Baugher, Benjamin; Moniz, Linda J; Bagley, Thomas; Babin, Steven M; Guven, Erhan

2018-01-01

In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru.

Ensemble method for dengue prediction

PubMed Central

Baugher, Benjamin; Moniz, Linda J.; Bagley, Thomas; Babin, Steven M.; Guven, Erhan

2018-01-01

Background In the 2015 NOAA Dengue Challenge, participants made three dengue target predictions for two locations (Iquitos, Peru, and San Juan, Puerto Rico) during four dengue seasons: 1) peak height (i.e., maximum weekly number of cases during a transmission season; 2) peak week (i.e., week in which the maximum weekly number of cases occurred); and 3) total number of cases reported during a transmission season. A dengue transmission season is the 12-month period commencing with the location-specific, historical week with the lowest number of cases. At the beginning of the Dengue Challenge, participants were provided with the same input data for developing the models, with the prediction testing data provided at a later date. Methods Our approach used ensemble models created by combining three disparate types of component models: 1) two-dimensional Method of Analogues models incorporating both dengue and climate data; 2) additive seasonal Holt-Winters models with and without wavelet smoothing; and 3) simple historical models. Of the individual component models created, those with the best performance on the prior four years of data were incorporated into the ensemble models. There were separate ensembles for predicting each of the three targets at each of the two locations. Principal findings Our ensemble models scored higher for peak height and total dengue case counts reported in a transmission season for Iquitos than all other models submitted to the Dengue Challenge. However, the ensemble models did not do nearly as well when predicting the peak week. Conclusions The Dengue Challenge organizers scored the dengue predictions of the Challenge participant groups. Our ensemble approach was the best in predicting the total number of dengue cases reported for transmission season and peak height for Iquitos, Peru. PMID:29298320

Powassan Virus—A New Reemerging Tick-Borne Disease

PubMed Central

Fatmi, Syed Soheb; Zehra, Rija; Carpenter, David O.

2017-01-01

Powassan virus is a neurovirulent flavivirus consisting of two lineages causing meningoencephalitis. It is the only member of the tick-borne encephalitis serogroup which is present in mainland North America. With a total number of 27 cases from 1958 to 1998 and 98 cases from 1999 to 2016, reported cases have increased by 671% over the last 18 years. Powassan infection is transmitted by different tick species in different geographical regions. Ixodes scapularis is the primary vector that transmits the virus on the East Coast of US and Ixodes cookei in the Midwest and Canada, while Hemaphysalis longicornis is the vector in Russia. Powassan has no singular pathognomonic finding and presents with a wide spectrum of symptoms including severe neurological symptoms. The clinical challenge lies within the management of the disease as there is no standard diagnostic protocol and most cases are only diagnosed after a patient goes through an extensive workup for other infectious disease. The diagnosis is established by a combination of imaging and serologic tests. In case of Powassan meningoencephalitis, computed tomography scan and magnetic resonance imaging show vascular insults, which are also seen in cases of tick-borne encephalitis virus, another flavivirus of medical importance. Serologic tests are the gold standard for diagnosis, although testing is not widely available and only state health departments and Center for Disease Control and Prevention can perform Powassan-specific IgM antibody testing utilizing enzyme-linked immunosorbent assay and immunofluorescence antibody. Powassan is also of veterinary medical importance. Wildlife animals act as a reservoir to the pathogens, hence possessing threat to humans and domestic animals. This review highlights Powassan’s neurotropic presentation, epidemiology, diagnostic challenges, and prevalence. Strong emphasis is placed on establishing diagnostic protocols, widespread Powassan-specific IgM testing, role of the vector in disease presentation, and necessary preventive research. PMID:29312918

Seeing Chemistry through the Eyes of the Blind: A Case Study Examining Multiple Gas Law Representations

ERIC Educational Resources Information Center

Harshman, Jordan; Bretz, Stacey Lowery; Yezierski, Ellen

2013-01-01

Adequately accommodating students who are blind or low-vision (BLV) in the sciences has been a focus of recent inquiry, but much of the research to date has addressed broad accommodations rather than devising and testing specific teaching strategies that respond to the unique challenges of BLV students learning chemistry. This case study seeks to…

A Case Study of Middle School Teachers' Preparations for High-Stakes Assessments

ERIC Educational Resources Information Center

Yeary, David Lee

2017-01-01

Students, educators, and schools across the country have been presented with challenges as a result of rigorous standards and high-complexity tests. The problem addressed in this case study was that teachers in a rural middle school in a southeastern state were preparing students to take a new high-stakes state-mandated assessment in English…

CoopEUS Case Study: Tsunami Modelling and Early Warning Systems for Near Source Areas (Mediterranean, Juan de Fuca).

NASA Astrophysics Data System (ADS)

Beranzoli, Laura; Best, Mairi; Chierici, Francesco; Embriaco, Davide; Galbraith, Nan; Heeseman, Martin; Kelley, Deborah; Pirenne, Benoit; Scofield, Oscar; Weller, Robert

2015-04-01

There is a need for tsunami modeling and early warning systems for near-source areas. For example this is a common public safety threat in the Mediterranean and Juan de Fuca/NE Pacific Coast of N.A.; Regions covered by the EMSO, OOI, and ONC ocean observatories. Through the CoopEUS international cooperation project, a number of environmental research infrastructures have come together to coordinate efforts on environmental challenges; this tsunami case study tackles one such challenge. There is a mutual need of tsunami event field data and modeling to deepen our experience in testing methodology and developing real-time data processing. Tsunami field data are already available for past events, part of this use case compares these for compatibility, gap analysis, and model groundtruthing. It also reviews sensors needed and harmonizes instrument settings. Sensor metadata and registries are compared, harmonized, and aligned. Data policies and access are also compared and assessed for gap analysis. Modelling algorithms are compared and tested against archived and real-time data. This case study will then be extended to other related tsunami data and model sources globally with similar geographic and seismic scenarios.

Black-Box System Testing of Real-Time Embedded Systems Using Random and Search-Based Testing

NASA Astrophysics Data System (ADS)

Arcuri, Andrea; Iqbal, Muhammad Zohaib; Briand, Lionel

Testing real-time embedded systems (RTES) is in many ways challenging. Thousands of test cases can be potentially executed on an industrial RTES. Given the magnitude of testing at the system level, only a fully automated approach can really scale up to test industrial RTES. In this paper we take a black-box approach and model the RTES environment using the UML/MARTE international standard. Our main motivation is to provide a more practical approach to the model-based testing of RTES by allowing system testers, who are often not familiar with the system design but know the application domain well-enough, to model the environment to enable test automation. Environment models can support the automation of three tasks: the code generation of an environment simulator, the selection of test cases, and the evaluation of their expected results (oracles). In this paper, we focus on the second task (test case selection) and investigate three test automation strategies using inputs from UML/MARTE environment models: Random Testing (baseline), Adaptive Random Testing, and Search-Based Testing (using Genetic Algorithms). Based on one industrial case study and three artificial systems, we show how, in general, no technique is better than the others. Which test selection technique to use is determined by the failure rate (testing stage) and the execution time of test cases. Finally, we propose a practical process to combine the use of all three test strategies.

Economic assessments of small-scale drinking-water interventions in pursuit of MDG target 7C.

PubMed

Cameron, John; Jagals, Paul; Hunter, Paul R; Pedley, Steve; Pond, Katherine

2011-12-01

This paper uses an applied rural case study of a safer water intervention in South Africa to illustrate how three levels of economic assessment can be used to understand the impact of the intervention on people's well-being. It is set in the context of Millennium Development Goal 7 which sets a target (7C) for safe drinking-water provision and the challenges of reaching people in remote rural areas with relatively small-scale schemes. The assessment moves from cost efficiency to cost effectiveness to a full social cost-benefit analysis (SCBA) with an associated sensitivity test. In addition to demonstrating techniques of analysis, the paper brings out many of the challenges in understanding how safer drinking-water impacts on people's livelihoods. The SCBA shows the case study intervention is justified economically, though the sensitivity test suggests 'downside' vulnerability. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study | Office of Cancer Genomics

Cancer.gov

Motivation: Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging.

Genetic variation at the Th2 immune gene IL13 is associated with IgE-mediated paediatric food allergy.

PubMed

Ashley, S E; Tan, H-T T; Peters, R; Allen, K J; Vuillermin, P; Dharmage, S C; Tang, M L K; Koplin, J; Lowe, A; Ponsonby, A-L; Molloy, J; Matheson, M C; Saffery, R; Ellis, J A; Martino, D

2017-08-01

Food allergies pose a considerable world-wide public health burden with incidence as high as one in ten in 12-month-old infants. Few food allergy genetic risk variants have yet been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells. Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge-proven IgE-mediated food allergy. We genotyped nine IL13 "tag" single nucleotide polymorphisms (tag SNPs) in 367 challenge-proven food allergic cases, 199 food-sensitized tolerant cases and 156 non-food allergic controls from the HealthNuts study. 12-month-old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran-Mantel-Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non-food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed. IL13 rs1295686 was associated with challenge-proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20-2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03-1.82) and further supported by a meta-analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE. We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge-proven food allergy. © 2017 John Wiley & Sons Ltd.

T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.

PubMed

Knackstedt, Thomas J; Zug, Kathryn A

2015-02-01

Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Challenges with controlling varicella in prison settings: experience of California, 2010 to 2011.

PubMed

Leung, Jessica; Lopez, Adriana S; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H; Preas, Christopher P; Cosentino, Giorgio; Bialek, Stephanie R; Marin, Mona

2014-10-01

This article describes the epidemiology of varicella in one state prison in California during 2010 and 2011, control measures implemented, and associated costs. Eleven varicella cases were reported, of which nine were associated with two outbreaks. One outbreak consisted of three cases and the second consisted of six cases with two generations of spread. Among exposed inmates serologically tested, 98% (643/656) were varicella-zoster virus seropositive. The outbreaks resulted in > 1,000 inmates exposed, 444 staff exposures, and > $160,000 in costs. The authors documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary to manage cases and outbreaks. © The Author(s) 2014.

Prevalence of IgE mediated cow's milk and egg allergy in children under 2 years of age in Sanliurfa, Turkey: the city that isn't almost allergic to cow's milk.

PubMed

Zeyrek, D; Koruk, I; Kara, B; Demir, C; Cakmak, A

2015-12-01

Food allergy is a common problem in children and adults. The aim of this study was to determine the frequency of cow's milk and egg allergy based on skin prick test and oral food challenge results We recruited 614 children aged 1 month-2 years in from different areas of Sanliurfa. An interview was conducted with each parents and family demographic, and prenatal-antenatal-postnatal information was recorded, then skin prick test was applied to the children for egg white, egg yolk and cow's milk. Cases that are required, sIgE levels for cow's milk, egg white and egg yolk were measured and food challenge tests were applied. Cow's milk and egg allergy was determined in 1 case (0.16%) and 8 cases (1.30%) respectively from the results of the tests applied. Six cases (0.97%) were accepted as sensitive to egg white and egg yolk. Within the factors which were questioned, (only the egg allergy evaluation was made without the cow's milk allergy case) of those with parental consanguinity was determined at a statistically significantly high level (OR=5.8, 95% CI: 1.2-27.2, P=0.01). The prevalence of cow's milk allergy in Sanliurfa is the lowest reported prevalence rate to date in children under 2 years of age. When infants develop a food allergy, this takes the form of egg allergy. Within the several factors evaluated to explain this situation, a significant relationship was determined only with parental consanguinity. However, as reported above, to date there is no genetic or epidemiological study to explain this situation.

Chromosomal microarray analysis as the first-tier test for the identification of pathogenic copy number variants in chromosome 9 pericentric regions and its challenge.

PubMed

Wang, Jia-Chi; Boyar, Fatih Z

2016-01-01

Chromosomal microarray analysis (CMA) has been recommended and practiced routinely in the large reference laboratories of U.S.A. as the first-tier test for the postnatal evaluation of individuals with intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies. Using CMA as a diagnostic tool and without a routine setting of fluorescence in situ hybridization with labeled bacterial artificial chromosome probes (BAC-FISH) in the large reference laboratories becomes a challenge in the characterization of chromosome 9 pericentric region. This region has a very complex genomic structure and contains a variety of heterochromatic and euchromatic polymorphic variants. These variants were usually studied by G-banding, C-banding and BAC-FISH analysis. Chromosomal microarray analysis (CMA) was not recommended since it may lead to false positive results. Here, we presented a cohort of four cases, in which high-resolution CMA was used as the first-tier test or simultaneously with G-banding analysis on the proband to identify pathogenic copy number variants (CNVs) in the whole genome. CMA revealed large pathogenic CNVs from chromosome 9 in 3 cases which also revealed different G-banding patterns between the two chromosome 9 homologues. Although we demonstrated that high-resolution CMA played an important role in the identification of pathogenic copy number variants in chromosome 9 pericentric regions, the lack of BAC-FISH analysis or other useful tools renders significant challenges in the characterization of chromosome 9 pericentric regions. None; it is not a clinical trial, and the cases were retrospectively collected and analyzed.

Utilising family-based designs for detecting rare variant disease associations.

PubMed

Preston, Mark D; Dudbridge, Frank

2014-03-01

Rare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family-based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case-control rare variant tests. However, we show that transmission- (or within-family-) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo-case-control design allows a greater range of statistical tests to be applied to family data. © 2014 The Authors. Annals of Human Genetics published by John Wiley & Sons Ltd/University College London.

Simple F Test Reveals Gene-Gene Interactions in Case-Control Studies

PubMed Central

Chen, Guanjie; Yuan, Ao; Zhou, Jie; Bentley, Amy R.; Adeyemo, Adebowale; Rotimi, Charles N.

2012-01-01

Missing heritability is still a challenge for Genome Wide Association Studies (GWAS). Gene-gene interactions may partially explain this residual genetic influence and contribute broadly to complex disease. To analyze the gene-gene interactions in case-control studies of complex disease, we propose a simple, non-parametric method that utilizes the F-statistic. This approach consists of three steps. First, we examine the joint distribution of a pair of SNPs in cases and controls separately. Second, an F-test is used to evaluate the ratio of dependence in cases to that of controls. Finally, results are adjusted for multiple tests. This method was used to evaluate gene-gene interactions that are associated with risk of Type 2 Diabetes among African Americans in the Howard University Family Study. We identified 18 gene-gene interactions (P < 0.0001). Compared with the commonly-used logistical regression method, we demonstrate that the F-ratio test is an efficient approach to measuring gene-gene interactions, especially for studies with limited sample size. PMID:22837643

The US Army War College: Gearing Up for the 21st Century

DTIC Science & Technology

1988-12-01

modality. The Committee also identified a need for increased emphasis on active learning as well as greater academic rigor and challenge...and to involve them more directly in an active learning process, case studies, exercises, gaming, and analytical discussions have been increased...in the active learning process; that most challenging test which occurs when the student is perform- ing or reciting in front of his or her peers as

Confidence intervals for single-case effect size measures based on randomization test inversion.

PubMed

Michiels, Bart; Heyvaert, Mieke; Meulders, Ann; Onghena, Patrick

2017-02-01

In the current paper, we present a method to construct nonparametric confidence intervals (CIs) for single-case effect size measures in the context of various single-case designs. We use the relationship between a two-sided statistical hypothesis test at significance level α and a 100 (1 - α) % two-sided CI to construct CIs for any effect size measure θ that contain all point null hypothesis θ values that cannot be rejected by the hypothesis test at significance level α. This method of hypothesis test inversion (HTI) can be employed using a randomization test as the statistical hypothesis test in order to construct a nonparametric CI for θ. We will refer to this procedure as randomization test inversion (RTI). We illustrate RTI in a situation in which θ is the unstandardized and the standardized difference in means between two treatments in a completely randomized single-case design. Additionally, we demonstrate how RTI can be extended to other types of single-case designs. Finally, we discuss a few challenges for RTI as well as possibilities when using the method with other effect size measures, such as rank-based nonoverlap indices. Supplementary to this paper, we provide easy-to-use R code, which allows the user to construct nonparametric CIs according to the proposed method.

Challenges in the Management of Mucopolysaccharidosis Type II (Hunter's Syndrome) in a Developing Country: a Case Report.

PubMed

Rasheeedah, Ibraheem; Patrick, Oladele; Abdullateef, AbdulAzeez; Mohammed, Abdulkadri; Sherifat, Katibi; Gbadebo, Ibraheem

2015-07-01

Mucopolysaccharidosis type II (Hunter's syndrome) is an X-linked chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase with patients rarely living till adulthood. Failure to identify patients early could contribute to an increased morbidity as identified in this case report. An eight year old patient with Hunter's syndrome identified five years after disease onset with severe cardiovascular complications exemplifies the challenges faced in resource-limited countries towards making diagnosis and treatment of rare conditions. Elevated urinary glycosaminoglycans levels or a strong clinical suspicion of Hunter's syndrome, as identified in the index case, is a prerequisite for enzyme activity testing. Urinary mucopolysaccharide(MPS) level was 69.6 mg/mmol(normal range is 0.0 - 11.6 mg/mmol), and the confirming MPS electrophoresis analysis showed elevated heparan sulphate in the urine sample. Enzyme activity testing, with absent or very low iduronate-2-sulfatase activity, is diagnostic. However, the scarce availability and high cost of these tests is another constraint in making a diagnosis. Identification and management of mucopolysaccharidosis type II pose a problem in resource-constrained countries due to late presentation, lack of facility for diagnosis and treatment, cost and expertise required for the management.

Transgender Day of Remembrance and a Prospective Student Open House: How One Student Inspired a School to Do Both

ERIC Educational Resources Information Center

Fusarelli, Bonnie C.; Eaton, Lucy E.

2011-01-01

This case study explores the challenges a school leader faced when her commitment to diversity was tested by a scheduling conflict. The school principal approved a Transgender Day of Remembrance but then realized that it was scheduled for the same night as the school's Open House to recruit prospective students. The case study provides an…

Conservative chiropractic management of urinary incontinence using applied kinesiology: a retrospective case-series report.

PubMed

Cuthbert, Scott C; Rosner, Anthony L

2012-03-01

The purpose of this case series is to describe the chiropractic management of 21 patients with daily stress and occasional total urinary incontinence (UI). Twenty-one case files of patients 13 to 90 years of age with UI from a chiropractic clinic were reviewed. The patients had a 4-month to 49-year history of UI and associated muscle dysfunction and low back and/or pelvic pain. Eighteen wore an incontinence pad throughout the day and night at the time of their appointments because of unpredictable UI. Patients were evaluated for muscle impairments in the lumbar spine, pelvis, and pelvic floor and low back and/or hip pain. Positive manual muscle test results of the pelvis, lumbar spine muscles, and pelvic floor muscles were the most common findings. Lumbosacral dysfunction was found in 13 of the cases with pain provocation tests (applied kinesiology sensorimotor challenge); in 8 cases, this sensorimotor challenge was absent. Chiropractic manipulative therapy and soft tissue treatment addressed the soft tissue and articular dysfunctions. Chiropractic manipulative therapy involved high-velocity, low-amplitude manipulation; Cox flexion distraction manipulation; and/or use of a percussion instrument for the treatment of myofascial trigger points. Urinary incontinence symptoms resolved in 10 patients, considerably improved in 7 cases, and slightly improved in 4 cases. Periodic follow-up examinations for the past 6 years, and no less than 2 years, indicate that for each participant in this case-series report, the improvements of UI remained stable. The patients reported in this retrospective case series showed improvement in UI symptoms that persisted over time.

A Prototype of a Receptive Lexical Test for a Polysynthetic Heritage Language: The Case of Inuttitut in Labrador

ERIC Educational Resources Information Center

Sherkina-Lieber, Marina; Helms-Park, Rena

2015-01-01

This paper describes the process of designing, administering, and assessing a language-sensitive and culture-specific lexical test of Labrador Inuttitut (a dialect of Inuktitut, an Eskimo-Aleut language). This process presented numerous challenges, from choosing citation forms in a polysynthetic language to dealing with a lack of word frequency…

Creation and pilot testing of cases for case-based learning: A pedagogical approach for pathology cancer diagnosis.

PubMed

Sayed, Shahin; Lester, Susan C; Wilson, Michael; Berney, Daniel; Masia, Ricard; Moloo, Zahir; Stall, Jennifer; Eslan, Alexia; Ayers, Stephanie; Mutuku, Angela; Guarner, Jeannette

2017-01-01

Case-based learning (CBL) is an established pedagogical active learning method used in various disciplines and defined based on the field of study and type of case. The utility of CBL for teaching specific aspects of cancer diagnosis to practising pathologists has not been previously studied in sub-Saharan Africa. We aimed to pilot test standardised cancer cases on a group of practising pathologists in sub-Saharan Africa to evaluate case content, clarity of questions and delivery of content. Expert faculty created cases for the four most commonly diagnosed cancers. The format included mini-cases and bullet cases which were all open-ended. The questions dealt with interpretation of clinical information, gross specimen examination, morphologic characteristics of tumours, ancillary testing, reporting and appropriate communication to clinicians. Cases on breast, cervical, prostate and colorectal cancers were tested on seven practising pathologists. Each case took an average of 45-90 min to complete.Questions that were particularly challenging to testers were on: Specimens they should have been but for some reason were not exposed to in routine practice.Ancillary testing and appropriate tumour staging.New knowledge gained included tumour grading and assessment of radial margins. Revisions to cases were made based on testers' feedback, which included rewording of questions to reduce ambiguity and adding of tables to clarify concepts. Cases were created for CBL in Kenya, but these are applicable elsewhere in Africa and beyond to teach cancer diagnosis. The pilot testing of cases prepared faculty for the actual CBL course and feedback provided by the testers assisted in improving the questions and impact on day-to-day practice.

Creation and pilot testing of cases for case-based learning: A pedagogical approach for pathology cancer diagnosis

PubMed Central

Wilson, Michael; Masia, Ricard; Moloo, Zahir; Stall, Jennifer; Eslan, Alexia; Ayers, Stephanie; Mutuku, Angela

2017-01-01

Background Case-based learning (CBL) is an established pedagogical active learning method used in various disciplines and defined based on the field of study and type of case. The utility of CBL for teaching specific aspects of cancer diagnosis to practising pathologists has not been previously studied in sub-Saharan Africa. Objectives We aimed to pilot test standardised cancer cases on a group of practising pathologists in sub-Saharan Africa to evaluate case content, clarity of questions and delivery of content. Methods Expert faculty created cases for the four most commonly diagnosed cancers. The format included mini-cases and bullet cases which were all open-ended. The questions dealt with interpretation of clinical information, gross specimen examination, morphologic characteristics of tumours, ancillary testing, reporting and appropriate communication to clinicians. Results Cases on breast, cervical, prostate and colorectal cancers were tested on seven practising pathologists. Each case took an average of 45–90 min to complete. Questions that were particularly challenging to testers were on: Specimens they should have been but for some reason were not exposed to in routine practice.Ancillary testing and appropriate tumour staging. New knowledge gained included tumour grading and assessment of radial margins. Revisions to cases were made based on testers’ feedback, which included rewording of questions to reduce ambiguity and adding of tables to clarify concepts. Conclusion Cases were created for CBL in Kenya, but these are applicable elsewhere in Africa and beyond to teach cancer diagnosis. The pilot testing of cases prepared faculty for the actual CBL course and feedback provided by the testers assisted in improving the questions and impact on day-to-day practice. PMID:29147646

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)- benzoic acid: a new cause of sensitiser induced occupational asthma, rhinitis and urticaria.

PubMed

Suojalehto, Hille; Karvala, Kirsi; Ahonen, Saana; Ylinen, Katriina; Airaksinen, Liisa; Suuronen, Katri; Suomela, Sari; Lindström, Irmeli

2018-04-01

3-(Bromomethyl)-2-chloro-4-(methylsulfonyl)-benzoic acid (BCMBA) has not previously been identified as a respiratory sensitiser. We detected two cases who presented respiratory and urticaria symptoms related to BCMBA and had positive skin prick tests to the agent. Subsequently, we conducted outbreak investigations at the BCMBA-producing factory and performed clinical examinations to confirm occupational diseases. The outbreak investigations included observations of work processes, assessment of exposure, a medical survey with a questionnaire and skin prick tests with 0.5% BCMBA water solution on 85 exposed workers and 9 unexposed workers. We used specific inhalation or nasal challenge and open skin application test to investigate BCMBA-related occupational asthma, rhinitis and contact urticaria. We identified nine workers with respiratory and/or skin symptoms and positive skin prick tests to BCMBA in a chemical factory. A survey among chemical factory workers indicated a BCMBA-related sensitisation rate of 8% among all exposed workers; the rate was highest (25%) among production workers in the production hall. Sensitisation was detected only in workers with the estimated highest exposure levels. Six cases of occupational asthma, rhinitis and/or contact urticaria caused by BCMBA were confirmed with challenge tests. Asthma-provoking doses in specific inhalation challenges were very low (0.03% or 0.3% BCMBA in lactose). We identified a new low molecular weight agent causing occupational asthma, rhinitis and contact urticaria. A typical clinical picture of allergic diseases and positive skin prick tests suggest underlying IgE-mediated disease mechanisms. Stringent exposure control measures are needed in order to prevent BCMBA-related diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Critical evaluation of the EU-technical guidance on shelf-life studies for L. monocytogenes on RTE-foods: a case study for smoked salmon.

PubMed

Vermeulen, A; Devlieghere, F; De Loy-Hendrickx, A; Uyttendaele, M

2011-01-31

In November 2008, a technical guidance document on the challenge test protocol was published by the EU CRL (Community of Reference Laboratory) for L. monocytogenes. This document describes the practical aspects on the execution of a challenge test in order to comply to the EU Commission regulation N° 2073/2005 on microbiological criteria for foodstuff. In this guideline two approaches are specified. On the one hand challenge tests, based on actual data measurements at the beginning and end of the shelf-life of products stored under reasonably foreseen T-profile, are described. On the other hand, growth potential is calculated by predictive models using a validated maximum specific growth rate. The present study evaluates the two above mentioned approaches on cold smoked salmon, a typical risk product for L. monocytogenes. The focus is on: (i) the relative importance of intrabatch versus interbatch variability, (ii) the concept of a simple challenge test based on actual data at start and end of shelf life versus a modelling approach and (iii) the interpretation of challenge tests. Next to this, available tertiary models were used to estimate the growth potential of these products based on their initial physicochemical characteristics. From the results it could be concluded that in some batches considerable intrabatch variability was obtained. In general, however, the interbatch variability was significantly higher than intrabatch variability. Concerning the two above mentioned methods for challenge tests, it can be stated that the first approach (simple challenge test) can be set up rather rapidly and is cost-effective for SMEs (small and medium enterprises) but provides only a single isolated outcome. This implies that challenge tests should be redone if changes occur in composition or production process. The second (modelling) approach, using extended challenge tests to establish growth parameters needs larger set ups and more complicated data analysis, which makes them more expensive. Using available tertiary models has the major advantage that the most important intrinsic and extrinsic factors can be included for the prediction of the growth parameter. It was clear that product specific models, taking into account the interaction effects with background flora, performed the best. Regarding the challenge tests, it can be concluded that the best approach to choose will depend on the particular context as in the end both approaches will lead to the same conclusion. Copyright © 2010 Elsevier B.V. All rights reserved.

Identifying newly acquired cases of hepatitis C using surveillance: a literature review.

PubMed

Sacks-Davis, R; VAN Gemert, C; Bergeri, I; Stoove, M; Hellard, M

2012-11-01

Surveillance of newly acquired hepatitis C virus (HCV) infection is crucial for understanding the epidemiology of HCV and informing public health practice. However, monitoring such infections via surveillance systems is challenging because they are commonly asymptomatic. A literature review was conducted to identify methodologies used by HCV surveillance systems to identify newly acquired infections; relevant surveillance systems in 15 countries were identified. Surveillance systems used three main strategies to identify newly acquired infections: (1) asking physicians to classify cases; (2) identifying symptomatic cases or cases with elevated alanine aminotransferases; and (3) identifying cases with documented evidence of anti-HCV antibody seroconversion within a specific time-frame. Case-ascertainment methods varied with greater completeness of data in enhanced compared to passive surveillance systems. Automated systems that extract and link testing data from multiple laboratory and clinic databases may provide an opportunity for collecting testing histories for individuals that is less resource intensive than enhanced surveillance.

Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results.

PubMed

Permaul, Perdita; Stutius, Lisa M; Sheehan, William J; Rangsithienchai, Pitud; Walter, Jolan E; Twarog, Frank J; Young, Michael C; Scott, Jordan E; Schneider, Lynda C; Phipatanakul, Wanda

2009-01-01

There are conflicting data regarding the diagnostic value of sesame-specific IgE and sesame skin test. Currently, there are no established thresholds that predict clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin-prick test (SPT) results with oral challenge outcomes in children suspected of having a sesame food allergy. We conducted a retrospective chart review of children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food challenge from January 2004 to August 2008 at Children's Hospital Boston and affiliated allergy clinics. Food challenges were conducted in cases of questionable clinical history or a negative ImmunoCAP and/or negative SPT despite a convincing history. Thirty-three oral sesame challenges were conducted. Of the 33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame-specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic (ROC) curve analysis for sesame-specific IgE revealed an area under the curve (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To our knowledge, this study represents the largest number of sesame challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Based on our sample, both tests are not good predictors of true sesame allergy as determined by an oral challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT.

Repaglinide-induced factitious hypoglycemia.

PubMed

Hirshberg, B; Skarulis, M C; Pucino, F; Csako, G; Brennan, R; Gorden, P

2001-02-01

We report the first case of repaglinide-induced factitious hypoglycemia in a young male. This case posed a challenging diagnostic dilemma because commercial assays for repaglinide are not available. Furthermore, the patient had a series of positive diagnostic tests such as high proinsulin and localizing intra-arterial calcium stimulation suggestive of insulinoma. This case, again, demonstrates the importance of pure clinical judgment in the face of often-conflicting laboratory data in making a correct diagnosis and the requirement of definitive data for an appropriate therapeutic resolution.

Postmortem diagnosis and toxicological validation of illicit substance use

PubMed Central

Lehrmann, E; Afanador, ZR; Deep-Soboslay, A; Gallegos, G; Darwin, WD; Lowe, RH; Barnes, AJ; Huestis, MA; Cadet, JL; Herman, MM; Hyde, TM; Kleinman, JE; Freed, WJ

2008-01-01

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine, and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and 9 opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine, and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine, and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use. PMID:18201295

Initial Multidisciplinary Design and Analysis Framework

NASA Technical Reports Server (NTRS)

Ozoroski, L. P.; Geiselhart, K. A.; Padula, S. L.; Li, W.; Olson, E. D.; Campbell, R. L.; Shields, E. W.; Berton, J. J.; Gray, J. S.; Jones, S. M.;

Multilevel Research and the Challenges of Implementing Genomic Medicine

PubMed Central

Coates, Ralph J.; Fennell, Mary L.; Glasgow, Russell E.; Scheuner, Maren T.; Schully, Sheri D.; Williams, Marc S.; Clauser, Steven B.

2012-01-01

Advances in genomics and related fields promise a new era of personalized medicine in the cancer care continuum. Nevertheless, there are fundamental challenges in integrating genomic medicine into cancer practice. We explore how multilevel research can contribute to implementation of genomic medicine. We first review the rapidly developing scientific discoveries in this field and the paucity of current applications that are ready for implementation in clinical and public health programs. We then define a multidisciplinary translational research agenda for successful integration of genomic medicine into policy and practice and consider challenges for successful implementation. We illustrate the agenda using the example of Lynch syndrome testing in newly diagnosed cases of colorectal cancer and cascade testing in relatives. We synthesize existing information in a framework for future multilevel research for integrating genomic medicine into the cancer care continuum. PMID:22623603

Multilevel research and the challenges of implementing genomic medicine.

PubMed

Khoury, Muin J; Coates, Ralph J; Fennell, Mary L; Glasgow, Russell E; Scheuner, Maren T; Schully, Sheri D; Williams, Marc S; Clauser, Steven B

2012-05-01

Advances in genomics and related fields promise a new era of personalized medicine in the cancer care continuum. Nevertheless, there are fundamental challenges in integrating genomic medicine into cancer practice. We explore how multilevel research can contribute to implementation of genomic medicine. We first review the rapidly developing scientific discoveries in this field and the paucity of current applications that are ready for implementation in clinical and public health programs. We then define a multidisciplinary translational research agenda for successful integration of genomic medicine into policy and practice and consider challenges for successful implementation. We illustrate the agenda using the example of Lynch syndrome testing in newly diagnosed cases of colorectal cancer and cascade testing in relatives. We synthesize existing information in a framework for future multilevel research for integrating genomic medicine into the cancer care continuum.

The Survival of Arts Education in the NCLB Era: A Case Study of One K-8th Grade Arts-Focused Charter School in a California Program Improvement School District

ERIC Educational Resources Information Center

Kratochvil, Kathie R.

2009-01-01

This research study presents one in-depth case study that investigates the successes, challenges, and processes of developing and enacting arts education programming at the elementary school level given the time limitations and other constraints associated with the high stakes testing environment that currently characterizes many of California's…

Ecology and geography of avian influenza (HPAI H5N1) transmission in the Middle East and northeastern Africa

PubMed Central

Williams, Richard AJ; Peterson, A Townsend

2009-01-01

Background The emerging highly pathogenic avian influenza strain H5N1 ("HPAI-H5N1") has spread broadly in the past decade, and is now the focus of considerable concern. We tested the hypothesis that spatial distributions of HPAI-H5N1 cases are related consistently and predictably to coarse-scale environmental features in the Middle East and northeastern Africa. We used ecological niche models to relate virus occurrences to 8 km resolution digital data layers summarizing parameters of monthly surface reflectance and landform. Predictive challenges included a variety of spatial stratification schemes in which models were challenged to predict case distributions in broadly unsampled areas. Results In almost all tests, HPAI-H5N1 cases were indeed occurring under predictable sets of environmental conditions, generally predicted absent from areas with low NDVI values and minimal seasonal variation, and present in areas with a broad range of and appreciable seasonal variation in NDVI values. Although we documented significant predictive ability of our models, even between our study region and West Africa, case occurrences in the Arabian Peninsula appear to follow a distinct environmental regime. Conclusion Overall, we documented a variable environmental "fingerprint" for areas suitable for HPAI-H5N1 transmission. PMID:19619336

Burkholderia pseudomallei: Challenges for the Clinical Microbiology Laboratory.

PubMed

Hemarajata, Peera; Baghdadi, Jonathan D; Hoffman, Risa; Humphries, Romney M

2016-12-01

Melioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei Clinical diagnosis of melioidosis can be challenging since there is no pathognomonic clinical syndrome, and the organism is often misidentified by methods used routinely in clinical laboratories. Although the disease is more prevalent in Thailand and northern Australia, sporadic cases may be encountered in areas where it is not endemic, including the United States. Since the organism is considered a tier 1 select agent according to the Centers for Disease Control and Prevention and the U.S. Department of Agriculture Animal and Plant Health Inspection Service, clinical laboratories must be proficient at rapidly recognizing isolates suspicious for B. pseudomallei, be able to safely perform necessary rule-out tests, and to refer suspect isolates to Laboratory Response Network reference laboratories. In this minireview, we report a case of melioidosis encountered at our institution and discuss the laboratory challenges encountered when dealing with clinical isolates suspicious for B. pseudomallei or clinical specimens from suspected melioidosis cases. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

Software Defined Networking challenges and future direction: A case study of implementing SDN features on OpenStack private cloud

NASA Astrophysics Data System (ADS)

Shamugam, Veeramani; Murray, I.; Leong, J. A.; Sidhu, Amandeep S.

2016-03-01

Cloud computing provides services on demand instantly, such as access to network infrastructure consisting of computing hardware, operating systems, network storage, database and applications. Network usage and demands are growing at a very fast rate and to meet the current requirements, there is a need for automatic infrastructure scaling. Traditional networks are difficult to automate because of the distributed nature of their decision making process for switching or routing which are collocated on the same device. Managing complex environments using traditional networks is time-consuming and expensive, especially in the case of generating virtual machines, migration and network configuration. To mitigate the challenges, network operations require efficient, flexible, agile and scalable software defined networks (SDN). This paper discuss various issues in SDN and suggests how to mitigate the network management related issues. A private cloud prototype test bed was setup to implement the SDN on the OpenStack platform to test and evaluate the various network performances provided by the various configurations.

Case report of occupational asthma induced by polyvinyl chloride and nickel.

PubMed

Song, Ga-Won; Ban, Ga-Young; Nam, Young-Hee; Park, Hae-Sim; Ye, Young-Min

2013-10-01

Polyvinyl chloride (PVC) is a widely used chemical for production of plastics. However occupational asthma (OA) caused by PVC has been reported only rarely. We report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room due to an asthma attack with moderate airflow obstruction and markedly increased sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5 mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late asthmatic responses, respectively. Moreover, the fractional concentration of exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our knowledge, this is the first case of OA in Korea induced by exposure to both PVC and Ni. We suggest that eosinophilic inflammation may be involved in the pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its diagnosis.

Case Report of Occupational Asthma Induced by Polyvinyl Chloride and Nickel

PubMed Central

Song, Ga-Won; Ban, Ga-Young; Nam, Young-Hee; Park, Hae-Sim

2013-01-01

Polyvinyl chloride (PVC) is a widely used chemical for production of plastics. However occupational asthma (OA) caused by PVC has been reported only rarely. We report a 34-yr-old male wallpaper factory worker with OA due to PVC and nickel (Ni) whose job was mixing PVC with plasticizers. He visited the emergency room due to an asthma attack with moderate airflow obstruction and markedly increased sputum eosinophil numbers. A methacholine challenge test was positive (PC20 2.5 mg/mL). Bronchoprovocation tests with both PVC and Ni showed early and late asthmatic responses, respectively. Moreover, the fractional concentration of exhaled nitric oxide (FeNO) was increased after challenge with PVC. To our knowledge, this is the first case of OA in Korea induced by exposure to both PVC and Ni. We suggest that eosinophilic inflammation may be involved in the pathogenesis of PVC-induced OA and that FeNO monitoring can be used for its diagnosis. PMID:24133363

Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study

PubMed Central

Fu, Wei; Shi, Qiyuan; Prosperi, Christine; Wu, Zhenke; Hammitt, Laura L.; Feikin, Daniel R.; Baggett, Henry C.; Howie, Stephen R.C.; Scott, J. Anthony G.; Murdoch, David R.; Madhi, Shabir A.; Thea, Donald M.; Brooks, W. Abdullah; Kotloff, Karen L.; Li, Mengying; Park, Daniel E.; Lin, Wenyi; Levine, Orin S.; O’Brien, Katherine L.; Zeger, Scott L.

2017-01-01

Abstract In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case–control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case–control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods. PMID:28575370

Conservative chiropractic management of urinary incontinence using applied kinesiology: a retrospective case-series report

PubMed Central

Cuthbert, Scott C.; Rosner, Anthony L.

2012-01-01

Objective The purpose of this case series is to describe the chiropractic management of 21 patients with daily stress and occasional total urinary incontinence (UI). Clinical Features Twenty-one case files of patients 13 to 90 years of age with UI from a chiropractic clinic were reviewed. The patients had a 4-month to 49-year history of UI and associated muscle dysfunction and low back and/or pelvic pain. Eighteen wore an incontinence pad throughout the day and night at the time of their appointments because of unpredictable UI. Intervention and Outcome Patients were evaluated for muscle impairments in the lumbar spine, pelvis, and pelvic floor and low back and/or hip pain. Positive manual muscle test results of the pelvis, lumbar spine muscles, and pelvic floor muscles were the most common findings. Lumbosacral dysfunction was found in 13 of the cases with pain provocation tests (applied kinesiology sensorimotor challenge); in 8 cases, this sensorimotor challenge was absent. Chiropractic manipulative therapy and soft tissue treatment addressed the soft tissue and articular dysfunctions. Chiropractic manipulative therapy involved high-velocity, low-amplitude manipulation; Cox flexion distraction manipulation; and/or use of a percussion instrument for the treatment of myofascial trigger points. Urinary incontinence symptoms resolved in 10 patients, considerably improved in 7 cases, and slightly improved in 4 cases. Periodic follow-up examinations for the past 6 years, and no less than 2 years, indicate that for each participant in this case-series report, the improvements of UI remained stable. Conclusion The patients reported in this retrospective case series showed improvement in UI symptoms that persisted over time. PMID:22942842

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

The role of food allergy in atopic dermatitis.

PubMed

Greenhawt, Matthew

2010-01-01

Atopic dermatitis (AD) affects ∼10% of children. Food allergy is a known provoking cause of AD in a subset of affected children. A literature search of PubMed and Medline was conducted to review the epidemiology and pathophysiology of AD, with special focus on the role of food allergy in the development of AD, its management, and its long-term preventive strategies. A literature search of PubMed and Medline was conducted. Food allergens readily provoke AD in ∼35% of patients, as proven through double-blind placebo-controlled food challenge studies. Milk, egg, wheat, soy, and peanut account for 75% of the cases of food-induced AD. However, the positive predictive values of the parental history, skin-prick tests, or serum tests for detecting food-specific IgE are low, making these unsuitable for use as single diagnostic modalities. Therefore, the use of a food challenge test is very helpful in objectively confirming the history or positive tests. Elimination diets are often helpful in challenge-proven cases, but care must be taken to evaluate the nutritional status of the child. There are few effective long-term strategies to prevent the development of food allergen-induced AD. Early onset of AD has been shown to be a risk factor for the development of other allergic diseases, including other food allergy/sensitization, as part of the atopic march. Treatment of other causes of AD, such as barrier dysfunction and cutaneous infection, are of equal importance to food allergen avoidance. Food allergy is an important provoking cause of AD, but it is only relevant in ∼35% of affected individuals.

Challenging Aerospace Problems for Intelligent Systems

NASA Technical Reports Server (NTRS)

Krishnakumar, Kalmanje; Kanashige, John; Satyadas, A.; Clancy, Daniel (Technical Monitor)

2002-01-01

In this paper we highlight four problem domains that are well suited and challenging for intelligent system technologies. The problems are defined and an outline of a probable approach is presented. No attempt is made to define the problems as test cases. In other words, no data or set of equations that a user can code and get results are provided. The main idea behind this paper is to motivate intelligent system researchers to examine problems that will elevate intelligent system technologies and applications to a higher level.

Challenging Aerospace Problems for Intelligent Systems

NASA Technical Reports Server (NTRS)

KrishnaKumar, K.; Kanashige, J.; Satyadas, A.

2003-01-01

In this paper we highlight four problem domains that are well suited and challenging for intelligent system technologies. The problems are defined and an outline of a probable approach is presented. No attempt is made to define the problems as test cases. In other words, no data or set of equations that a user can code and get results are provided. The main idea behind this paper is to motivate intelligent system researchers to examine problems that will elevate intelligent system technologies and applications to a higher level.

Asthma caused by potassium aluminium tetrafluoride: a case series.

PubMed

Laštovková, Andrea; Klusáčková, Pavlina; Fenclová, Zdenka; Bonneterre, Vincent; Pelclová, Daniela

2015-01-01

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF(4))-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF(4) - with fluorides' workplace air concentrations ranging between 1.7 and 2.8 mg/m(3). No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients' exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation.

Asthma caused by potassium aluminium tetrafluoride: a case series

PubMed Central

LAŠTOVKOVÁ, Andrea; KLUSÁČKOVÁ, Pavlina; FENCLOVÁ, Zdenka; BONNETERRE, Vincent; PELCLOVÁ, Daniela

2015-01-01

The objective of this study is to describe a case-series of potassium aluminium tetrafluoride (KAlF4)-induced occupational asthma (OA) and/or occupational rhinitis (OR). The study involves five patients from a heat-exchanger production line who were examined (including specific inhalation challenge tests) for suspected OA and/or OR caused by a flux containing almost 100% KAlF4 − with fluorides’ workplace air concentrations ranging between 1.7 and 2.8 mg/m3. No subject had a previous history of asthma. All five patients had a positive specific challenge test (three patients were diagnosed with OA alone, one with OR and one with both OR and OA). At the follow-up visit, after three years on average, all patients needed permanent corticosteroid therapy (four topical, one oral). After elimination from the exposure, only one of the observed subjects gave an indication of an improvement, two subjects stabilized and two worsened. Our case series focuses on the correlation between patients’ exposure to fluorides in air-conditioner production and the subsequent occurrence of OR/OA. Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or irritation. PMID:26212411

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data.

PubMed

Hammitt, Laura L; Feikin, Daniel R; Scott, J Anthony G; Zeger, Scott L; Murdoch, David R; O'Brien, Katherine L; Deloria Knoll, Maria

2017-06-15

Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Addressing the Analytic Challenges of Cross-Sectional Pediatric Pneumonia Etiology Data

PubMed Central

Feikin, Daniel R.; Scott, J. Anthony G.; Zeger, Scott L.; Murdoch, David R.; O’Brien, Katherine L.; Deloria Knoll, Maria

2017-01-01

Abstract Despite tremendous advances in diagnostic laboratory technology, identifying the pathogen(s) causing pneumonia remains challenging because the infected lung tissue cannot usually be sampled for testing. Consequently, to obtain information about pneumonia etiology, clinicians and researchers test specimens distant to the site of infection. These tests may lack sensitivity (eg, blood culture, which is only positive in a small proportion of children with pneumonia) and/or specificity (eg, detection of pathogens in upper respiratory tract specimens, which may indicate asymptomatic carriage or a less severe syndrome, such as upper respiratory infection). While highly sensitive nucleic acid detection methods and testing of multiple specimens improve sensitivity, multiple pathogens are often detected and this adds complexity to the interpretation as the etiologic significance of results may be unclear (ie, the pneumonia may be caused by none, one, some, or all of the pathogens detected). Some of these challenges can be addressed by adjusting positivity rates to account for poor sensitivity or incorporating test results from controls without pneumonia to account for poor specificity. However, no classical analytic methods can account for measurement error (ie, sensitivity and specificity) for multiple specimen types and integrate the results of measurements for multiple pathogens to produce an accurate understanding of etiology. We describe the major analytic challenges in determining pneumonia etiology and review how the common analytical approaches (eg, descriptive, case-control, attributable fraction, latent class analysis) address some but not all challenges. We demonstrate how these limitations necessitate a new, integrated analytical approach to pneumonia etiology data. PMID:28575372

A Metric-Based Validation Process to Assess the Realism of Synthetic Power Grids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Birchfield, Adam; Schweitzer, Eran; Athari, Mir

Public power system test cases that are of high quality benefit the power systems research community with expanded resources for testing, demonstrating, and cross-validating new innovations. Building synthetic grid models for this purpose is a relatively new problem, for which a challenge is to show that created cases are sufficiently realistic. This paper puts forth a validation process based on a set of metrics observed from actual power system cases. These metrics follow the structure, proportions, and parameters of key power system elements, which can be used in assessing and validating the quality of synthetic power grids. Though wide diversitymore » exists in the characteristics of power systems, the paper focuses on an initial set of common quantitative metrics to capture the distribution of typical values from real power systems. The process is applied to two new public test cases, which are shown to meet the criteria specified in the metrics of this paper.« less

Implementing Stakeholders' Access to Expertise: Experimenting on Nuclear Installations' Safety Cases - 12160

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilli, Ludivine; Charron, Sylvie

2012-07-01

In 2009 and 2010, the Institute for Nuclear Safety and Radiation Protection (IRSN) led two pilot actions dealing with nuclear installations' safety cases. One concerned the periodical review of the French 900 MWe nuclear reactors, the other concerned the decommissioning of a workshop located on the site of Areva's La Hague fuel-reprocessing plant site in Northwestern France. The purpose of both these programs was to test ways for IRSN and a small number of stakeholders (Non-Governmental Organizations (NGOs) members, local elected officials, etc.) to engage in technical discussions. The discussions were intended to enable the stakeholders to review future applicationsmore » and provide valuable input. The test cases confirmed there is a definite challenge in successfully opening a meaningful dialogue to discuss technical issues, in particular the fact that most expertise reports were not public and the conflict that exists between the contrary demands of transparency and confidentiality of information. The test case also confirmed there are ways to further improvement of stakeholders' involvement. (authors)« less

A Metric-Based Validation Process to Assess the Realism of Synthetic Power Grids

DOE PAGES

Birchfield, Adam; Schweitzer, Eran; Athari, Mir; ...

2017-08-19

Public power system test cases that are of high quality benefit the power systems research community with expanded resources for testing, demonstrating, and cross-validating new innovations. Building synthetic grid models for this purpose is a relatively new problem, for which a challenge is to show that created cases are sufficiently realistic. This paper puts forth a validation process based on a set of metrics observed from actual power system cases. These metrics follow the structure, proportions, and parameters of key power system elements, which can be used in assessing and validating the quality of synthetic power grids. Though wide diversitymore » exists in the characteristics of power systems, the paper focuses on an initial set of common quantitative metrics to capture the distribution of typical values from real power systems. The process is applied to two new public test cases, which are shown to meet the criteria specified in the metrics of this paper.« less

LUNGx Challenge for computerized lung nodule classification

DOE PAGES

Armato, Samuel G.; Drukker, Karen; Li, Feng; ...

2016-12-19

The purpose of this work is to describe the LUNGx Challenge for the computerized classification of lung nodules on diagnostic computed tomography (CT) scans as benign or malignant and report the performance of participants’ computerized methods along with that of six radiologists who participated in an observer study performing the same Challenge task on the same dataset. The Challenge provided sets of calibration and testing scans, established a performance assessment process, and created an infrastructure for case dissemination and result submission. We present ten groups that applied their own methods to 73 lung nodules (37 benign and 36 malignant) thatmore » were selected to achieve approximate size matching between the two cohorts. Area under the receiver operating characteristic curve (AUC) values for these methods ranged from 0.50 to 0.68; only three methods performed statistically better than random guessing. The radiologists’ AUC values ranged from 0.70 to 0.85; three radiologists performed statistically better than the best-performing computer method. The LUNGx Challenge compared the performance of computerized methods in the task of differentiating benign from malignant lung nodules on CT scans, placed in the context of the performance of radiologists on the same task. Lastly, the continued public availability of the Challenge cases will provide a valuable resource for the medical imaging research community.« less

LUNGx Challenge for computerized lung nodule classification

PubMed Central

Armato, Samuel G.; Drukker, Karen; Li, Feng; Hadjiiski, Lubomir; Tourassi, Georgia D.; Engelmann, Roger M.; Giger, Maryellen L.; Redmond, George; Farahani, Keyvan; Kirby, Justin S.; Clarke, Laurence P.

2016-01-01

Abstract. The purpose of this work is to describe the LUNGx Challenge for the computerized classification of lung nodules on diagnostic computed tomography (CT) scans as benign or malignant and report the performance of participants’ computerized methods along with that of six radiologists who participated in an observer study performing the same Challenge task on the same dataset. The Challenge provided sets of calibration and testing scans, established a performance assessment process, and created an infrastructure for case dissemination and result submission. Ten groups applied their own methods to 73 lung nodules (37 benign and 36 malignant) that were selected to achieve approximate size matching between the two cohorts. Area under the receiver operating characteristic curve (AUC) values for these methods ranged from 0.50 to 0.68; only three methods performed statistically better than random guessing. The radiologists’ AUC values ranged from 0.70 to 0.85; three radiologists performed statistically better than the best-performing computer method. The LUNGx Challenge compared the performance of computerized methods in the task of differentiating benign from malignant lung nodules on CT scans, placed in the context of the performance of radiologists on the same task. The continued public availability of the Challenge cases will provide a valuable resource for the medical imaging research community. PMID:28018939

LUNGx Challenge for computerized lung nodule classification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armato, Samuel G.; Drukker, Karen; Li, Feng

The purpose of this work is to describe the LUNGx Challenge for the computerized classification of lung nodules on diagnostic computed tomography (CT) scans as benign or malignant and report the performance of participants’ computerized methods along with that of six radiologists who participated in an observer study performing the same Challenge task on the same dataset. The Challenge provided sets of calibration and testing scans, established a performance assessment process, and created an infrastructure for case dissemination and result submission. We present ten groups that applied their own methods to 73 lung nodules (37 benign and 36 malignant) thatmore » were selected to achieve approximate size matching between the two cohorts. Area under the receiver operating characteristic curve (AUC) values for these methods ranged from 0.50 to 0.68; only three methods performed statistically better than random guessing. The radiologists’ AUC values ranged from 0.70 to 0.85; three radiologists performed statistically better than the best-performing computer method. The LUNGx Challenge compared the performance of computerized methods in the task of differentiating benign from malignant lung nodules on CT scans, placed in the context of the performance of radiologists on the same task. Lastly, the continued public availability of the Challenge cases will provide a valuable resource for the medical imaging research community.« less

Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases.

PubMed

Giori, L; Giordano, A; Giudice, C; Grieco, V; Paltrinieri, S

2011-03-01

Feline infectious peritonitis (FIP) can be difficult to diagnose. Histopathology is considered the gold standard test but immunohistochemistry (IHC) is mandatory to confirm/exclude the disease. This study aimed to assess the performances of tests carried out in vivo or at postmortem examination in challenging cases in which FIP was confirmed or excluded based on IHC or on adequate follow-up. Twelve cases (four without FIP, eight with FIP) were retrospectively studied. Clinical findings, serum protein electrophoresis (SPE), analysis of the effusions (AE), antifeline coronavirus serology, serum concentration of α1-acid glycoprotein (AGP) and histopathology were classified as consistent, doubtful or non-consistent with FIP. Sensitivity, specificity and concordance (κ) with the final diagnosis were calculated. Concordance was absent for serology (κ=-0·08) and AE (κ=-0·52), poor for histopathology (κ=0·09), fair for SPE (κ=0·25) and perfect for AGP (κ=1·00). Sensitivity was high for AGP (100%) and low for AE (50%), SPE (37·5%) and histopathology (37·5%). Specificity was high for AGP or histopathology (100%) and low for SPE (50%) and AE (0%). IHC must always be performed to confirm FIP. If this is not possible, when histopathology is controversial, elevated AGP concentrations may support the diagnosis of FIP. © 2011 British Small Animal Veterinary Association.

[Methodology of psychiatric case histories].

PubMed

Scherbaum, N; Mirzaian, E

1999-05-01

This paper deals with the methodology of psychiatric case histories. Three types of case histories are differentiated. The didactic case history teaches about the typical aspects of a psychiatric disorder or treatment by using an individual patient as an example. In the heuristic case history the individual case gives rise to challenging established concepts or to generate new hypotheses. Such hypotheses drawn from inductive reasoning have then to be tested using representative samples. The focus of hermeneutic case histories is the significance of pathological behaviour and experience in the context of the biography of an individual patient. So-called psychopathographies of important historical figures can also be differentiated according to these types. Based on these methodological considerations, quality standards for the named types of case histories are stated.

Model-Invariant Hybrid Computations of Separated Flows for RCA Standard Test Cases

NASA Technical Reports Server (NTRS)

Woodruff, Stephen

2016-01-01

NASA's Revolutionary Computational Aerosciences (RCA) subproject has identified several smooth-body separated flows as standard test cases to emphasize the challenge these flows present for computational methods and their importance to the aerospace community. Results of computations of two of these test cases, the NASA hump and the FAITH experiment, are presented. The computations were performed with the model-invariant hybrid LES-RANS formulation, implemented in the NASA code VULCAN-CFD. The model- invariant formulation employs gradual LES-RANS transitions and compensation for model variation to provide more accurate and efficient hybrid computations. Comparisons revealed that the LES-RANS transitions employed in these computations were sufficiently gradual that the compensating terms were unnecessary. Agreement with experiment was achieved only after reducing the turbulent viscosity to mitigate the effect of numerical dissipation. The stream-wise evolution of peak Reynolds shear stress was employed as a measure of turbulence dynamics in separated flows useful for evaluating computations.

Sexually transmitted infections: challenges ahead.

PubMed

Unemo, Magnus; Bradshaw, Catriona S; Hocking, Jane S; de Vries, Henry J C; Francis, Suzanna C; Mabey, David; Marrazzo, Jeanne M; Sonder, Gerard J B; Schwebke, Jane R; Hoornenborg, Elske; Peeling, Rosanna W; Philip, Susan S; Low, Nicola; Fairley, Christopher K

2017-08-01

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Indirect oral immunization of captive vampires, Desmodus rotundus.

PubMed

Almeida, Marilene F; Martorelli, Luzia F A; Aires, Caroline C; Sallum, P C; Massad, Eduardo

2005-07-01

A vaccinia-rabies glycoprotein recombinant virus (V-RG) vaccine was tested in hematophagous bats (Desmodus rotundus) kept in captivity. The vaccine was applied in a neutral vehicle (Vaseline) spread on the back of one or two vector bats, which were then reintroduced into their groups. Our hypothesis was that, as in the case of vampire bat control by vampiricide paste, the administration of V-RG vaccine through paste to one bat could indirectly protect other bats from the same group. Eight groups were tested. The rabies virus strain used to challenge the bats was isolated from a naturally infected hematophagous bat (Desmodus rotundus). The survival proportion after the virus challenge ranged between 42.8 and 71.4%. The results are encouraging because a significant number of bats that did not receive the vaccine survived the challenge. The vaccine was shown to be safe and immunogenic to hematophagous bats. No adverse effects to vaccinia virus were observed.

Testing Transitivity of Preferences on Two-Alternative Forced Choice Data

PubMed Central

Regenwetter, Michel; Dana, Jason; Davis-Stober, Clintin P.

2010-01-01

As Duncan Luce and other prominent scholars have pointed out on several occasions, testing algebraic models against empirical data raises difficult conceptual, mathematical, and statistical challenges. Empirical data often result from statistical sampling processes, whereas algebraic theories are nonprobabilistic. Many probabilistic specifications lead to statistical boundary problems and are subject to nontrivial order constrained statistical inference. The present paper discusses Luce's challenge for a particularly prominent axiom: Transitivity. The axiom of transitivity is a central component in many algebraic theories of preference and choice. We offer the currently most complete solution to the challenge in the case of transitivity of binary preference on the theory side and two-alternative forced choice on the empirical side, explicitly for up to five, and implicitly for up to seven, choice alternatives. We also discuss the relationship between our proposed solution and weak stochastic transitivity. We recommend to abandon the latter as a model of transitive individual preferences. PMID:21833217

Diplopia after Strabismus Surgery.

PubMed

Sharma, Medha; Hunter, David G

2018-01-01

Diplopia is a disappointing and, at times, unanticipated consequence of what might otherwise be considered anatomically successful strabismus surgery. In this study, we review the existing literature regarding diplopia after strabismus surgery in the context of the senior author's experience. We divide postoperative diplopia types into cases that occur in the setting of normal binocular vision (or "normal" suppression) vs. cases that are the consequence of rare or anomalous sensorial adaptations. We then discuss how to identify patients at greatest risk based on history and preoperative testing, and we offer strategies for managing these sometimes-challenging cases.

Remote control missile model test

NASA Technical Reports Server (NTRS)

Allen, Jerry M.; Shaw, David S.; Sawyer, Wallace C.

1989-01-01

An extremely large, systematic, axisymmetric body/tail fin data base was gathered through tests of an innovative missile model design which is described herein. These data were originally obtained for incorporation into a missile aerodynamics code based on engineering methods (Program MISSILE3), but can also be used as diagnostic test cases for developing computational methods because of the individual-fin data included in the data base. Detailed analysis of four sample cases from these data are presented to illustrate interesting individual-fin force and moment trends. These samples quantitatively show how bow shock, fin orientation, fin deflection, and body vortices can produce strong, unusual, and computationally challenging effects on individual fin loads. Comparisons between these data and calculations from the SWINT Euler code are also presented.

Failure of introduction of food allergens after negative oral food challenge tests in children.

PubMed

van der Valk, J P M; Gerth van Wijk, R; Vergouwe, Y; de Jong, N W

2015-08-01

One of the purposes to perform an oral food challenge (FC) test is to avoid unnecessary elimination of food allergens. In case of a negative FC test result, the food can be introduced. It is, however, unknown if patients act according to the outcome of the test. This study evaluates the rate of introduction of peanut, hazelnut, cow's milk or hen's egg allergens after a negative FC test. We investigated the introduction rate of children (0-18 years) with a negative FC test visiting the Department of Allergology, Erasmus Medical Centre Rotterdam from 2008 till 2013 and the factors that influence the rate of introduction. Patients were asked to complete a comprehensive questionnaire about their FC test. In total, 157 (38% girls, mean age during challenge 6.9 years) participated in the study. Of these FC tests, 104 (56%) were followed by a successful introduction, 30 (16%) by a partly introduction (traces or processed foods) and 52 (28%) by a failed introduction. Peanut and hazelnut showed a statistically significant lower successful introduction rate. Age, gender, symptoms during FC test, dietary advice and time period to introduction significantly influenced the rate of introduction. One fourth of the children with failure of introducing foods experienced symptoms during the introduction. More than one quarter of all children with a negative FC test result did not introduce the food. The FC test in its current form does not achieve its objective for this group of children.

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing.

PubMed

Araúz, Ana Belen; Caceres, Diego H; Santiago, Erika; Armstrong, Paige; Arosemena, Susan; Ramos, Carolina; Espinosa-Bode, Andres; Borace, Jovanna; Hayer, Lizbeth; Cedeño, Israel; Jackson, Brendan R; Sosa, Nestor; Berkow, Elizabeth L; Lockhart, Shawn R; Rodriguez-French, Amalia; Chiller, Tom

2018-01-01

Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing. © 2017 Blackwell Verlag GmbH.

Mutational analysis using Sanger and next generation sequencing in sporadic spindle cell hemangiomas: A study of 19 cases.

PubMed

Ten Broek, Roel W; Bekers, Elise M; de Leng, Wendy W J; Strengman, Eric; Tops, Bastiaan B J; Kutzner, Heinz; Leeuwis, Jan Willem; van Gorp, Joost M; Creytens, David H; Mentzel, Thomas; van Diest, Paul J; Eijkelenboom, Astrid; Flucke, Uta

2017-12-01

Spindle cell hemangioma (SCH) is a distinct vascular soft-tissue lesion characterized by cavernous blood vessels and a spindle cell component mainly occurring in the distal extremities of young adults. The majority of cases harbor heterozygous mutations in IDH1/2 sporadically or rarely in association with Maffucci syndrome. However, based on mosaicism and accordingly a low percentage of lesional cells harboring a mutant allele, detection can be challenging. We tested 19 sporadic SCHs by Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), conventional next generation sequencing (NGS), and NGS using a single molecule molecular inversion probes (smMIP)-based library preparation to compare their diagnostic value. Out of 10 cases tested by Sanger sequencing and 2 analyzed using MLPA, 4 and 1, respectively, revealed a mutation in IDH1 (p.R132C). The 7 remaining negative cases and additional 6 cases were investigated using smMIP/NGS, showing hot spot mutations in IDH1 (p.R132C) (8 cases) and IDH2 (3 cases; twice p.R172S and once p.R172G, respectively). One case was negative. Owing to insufficient DNA quality and insufficient coverage, 2 cases were excluded. In total, in 16 out of 17 cases successfully tested, an IDH1/2 mutation was found. Given that IDH1/2 mutations were absent in 161 other vascular lesions tested by smMIP/NGS, the mutation can be considered as highly specific for SCH. © 2017 Wiley Periodicals, Inc.

Diagnostic challenges and case management of the first imported case of Plasmodium knowlesi in Sri Lanka.

PubMed

Dewanee Ranaweera, A; Danansuriya, Manjula N; Pahalagedera, Kusumawathie; de A W Gunasekera, W M Kumudunayana T; Dharmawardena, Priyani; Mak, Keng Wai; Wong, Pei-Sze Jeslyn; Li, Mei-Zhi Irene; Tan, Cheong Huat; Hapuarachchi, Hapuarachchige C; Herath, Hema D B; Fernando, Deepika

2017-03-21

Sri Lanka has achieved 'malaria-free' status and is now in the phase of prevention of re-introduction of malaria. Imported malaria remains a challenge to resurgence of the disease. The diagnostic challenges encountered and the rapid response initiated to manage a Plasmodium infection, which was later confirmed as Plasmodium knowlesi, the first reported case from Sri Lanka, is discussed. An army officer who returned from Malaysia in October 2016 was found to be positive for Plasmodium both by microscopy and rapid diagnostic test (RDT) by the Anti Malaria Campaign Sri Lanka (AMC) during his third visit to a health care provider. Microscopy findings were suspicious of P. knowlesi infection as the smears showed parasite stages similar to both Plasmodium malariae and Plasmodium falciparum. Nested PCR at AMC confirmed Plasmodium genus, but not the species. In the absence of species confirmation, the patient was treated as a case of P. falciparum. The presence of P. knowlesi was later confirmed by a semi-nested PCR assay performed at the Environmental Health Institute, National Environmental Agency in Singapore. The parasite strain was also characterized by sequencing the circumsporozoite gene. Extensive case investigation including parasitological and entomological surveillance was carried out. Plasmodium knowlesi should be suspected in patients returning from countries in the South Asian region where the parasite is prevalent and when blood smear results are inconclusive.

The challenge of juvenile Huntington disease: to test or not to test.

PubMed

Koutsis, Georgios; Karadima, Georgia; Kladi, Athina; Panas, Marios

2013-03-12

In a cohort of patients with suspected juvenile-onset Huntington disease (HD), we compared HD expansion-positive and -negative cases in order to identify parameters that may allow differentiating between them and may act as a guide to clinicians contemplating genetic testing. We analyzed the clinical and genetic characteristics of 76 juvenile-onset patients referred consecutively for HD genetic testing over a 16-year period. In total, 24 patients were positive for the HD expansion (7.8% of our HD cohort). Mean age at onset of expanded cases was similar to unexpanded cases. All expanded cases had a family history of genetically confirmed HD compared to only 13.5% of unexpanded cases (p = 0.000). Clinical symptoms at onset or at presentation could not differentiate between expanded and unexpanded patients. Although criteria suggested by previous reports allowed statistical differentiation between the 2 groups, they were not sufficiently sensitive and specific to be used in clinical context and performed less satisfactorily than presence of a family history of HD alone. A diagnosis of juvenile HD should be primarily contemplated in symptomatic children with a family history of HD, although a proportion of these will test negative. With no family history of HD, juvenile HD is very unlikely and genetic testing should never delay searching for other causes. The specific nature of symptoms at onset or at presentation is of limited value in guiding the decision to test or not to test.

Bridging the gap between regulatory acceptance and industry use of non-animal methods.

PubMed

Clippinger, Amy J; Hill, Erin; Curren, Rodger; Bishop, Patricia

2016-01-01

Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case-by-case basis, to conventional pesticide products. Despite the collaborative effort, the availability of relevant non-animal methods, and the EPA's change in policy, only a limited number of AMCPs have been registered using the framework. Companies continue to conduct animal tests when registering AMCPs due to various challenges surrounding adoption of the new testing framework; however, recent discussions between industry, regulators, and other interested parties have identified ways these challenges may be overcome. In this article we explore how use of the alternate framework could be expanded through efforts such as increasing international harmonization, more proactively publicizing the framework, and enhancing the training of regulatory reviewers. Not only can these strategies help to increase use of the EPA alternate eye irritation framework, they can also be applied to facilitate the uptake of other alternative approaches to animal testing in the future.

[Early congenital syphilis: a case report].

PubMed

Cavagnaro S M, Felipe; Pereira R, Teresita; Pérez P, Carla; Vargas Del V, Fernanda; Sandoval C, Carmen

2014-02-01

Congenital syphilis (CS) is a multisystemic infection of the newborn (NB) which can produce severe symptoms, and in some cases, even be fatal. In recent years, the incidence of syphilis has increased worldwide and similarly, the cases of CS in neonates have increased. To report two cases of early and severe presentation of CS, focusing on the importance of prevention of vertical transmission and monitoring of treated mothers. The diagnostic difficulties are discussed. Two premature newborns that were diagnosed with probable CS present in the newborn period are presented. In the first case, due to a high index of suspicion, but without confirmatory testing, treatment was started with good clinical response. In the second case, CS was confirmed through positive serology and the specific treatment was given. CS has significant diagnostic challenges as there is no test for early confirmation, therefore, a high index of suspicion might be key in the treatment and consequent prognosis. Due to the current epidemiology of the condition, it is also important to focus on preventive measures.

Evaluation of the filtration performance of NIOSH-approved N95 filtering facepiece respirators by photometric and number-based test methods.

PubMed

Rengasamy, Samy; Miller, Adam; Eimer, Benjamin C

2011-01-01

N95 particulate filtering facepiece respirators are certified by measuring penetration levels photometrically with a presumed severe case test method using charge neutralized NaCl aerosols at 85 L/min. However, penetration values obtained by photometric methods have not been compared with count-based methods using contemporary respirators composed of electrostatic filter media and challenged with both generated and ambient aerosols. To better understand the effects of key test parameters (e.g., particle charge, detection method), initial penetration levels for five N95 model filtering facepiece respirators were measured using NaCl aerosols with the aerosol challenge and test equipment employed in the NIOSH respirator certification method (photometric) and compared with an ultrafine condensation particle counter method (count based) for the same NaCl aerosols as well as for ambient room air particles. Penetrations using the NIOSH test method were several-fold less than the penetrations obtained by the ultrafine condensation particle counter for NaCl aerosols as well as for room particles indicating that penetration measurement based on particle counting offers a more difficult challenge than the photometric method, which lacks sensitivity for particles < 100 nm. All five N95 models showed the most penetrating particle size around 50 nm for room air particles with or without charge neutralization, and at 200 nm for singly charged NaCl monodisperse particles. Room air with fewer charged particles and an overwhelming number of neutral particles contributed to the most penetrating particle size in the 50 nm range, indicating that the charge state for the majority of test particles determines the MPPS. Data suggest that the NIOSH respirator certification protocol employing the photometric method may not be a more challenging aerosol test method. Filter penetrations can vary among workplaces with different particle size distributions, which suggests the need for the development of new or revised "more challenging" aerosol test methods for NIOSH certification of respirators.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy.

PubMed

Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten

According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Occupational Rhinoconjunctivitis due to Maize in a Snack Processor: A Cross-Reactivity Study Between Lipid Transfer Proteins From Different Cereals and Peach.

PubMed

Guillen, Daiana; Barranco, Pilar; Palacín, Arantxa; Quirce, Santiago

2014-09-01

We report the case of a snack processor who developed occupational rhinoconjunctivitis due to maize brand exposure during the extrusion process, and who experienced abdominal pain upon drinking beer. The allergens implicated and the cross-reactivity between non-specific lipid transfer proteins (LTPs) from different cereals and peach were investigated. Skin prick tests and specific IgE to cereal flours, pulmonary functions tests and specific conjunctival and inhalation challenges to maize extract were performed. In vitro studies included IgE immunoblotting and ELISA inhibition assays. Skin prick tests with maize flour, maize brand and wheat flour extracts were positive, whereas serum specific IgE was positive only to maize flour. Specific inhalation challenge (SIC) to maize flour did not elicit an asthmatic reaction; however, conjunctival challenge test with the same extract was positive. Patient's serum recognized IgE-binding bands in the maize and beer extracts corresponding to LTPs. In the ELISA inhibition assays, a significant degree of allergenic cross-reactivity was found between maize and beer LTPs, whereas no cross-reactivity was observed between maize LTP and wheat and peach LTPs.

Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.

PubMed

Schön, T; Miotto, P; Köser, C U; Viveiros, M; Böttger, E; Cambau, E

2017-03-01

Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis. They are also used to detect resistance in tuberculosis cases with risk factors, in combination with genotypic tests. In low-income countries, genotypic methods screening hot-spot mutations known to confer resistance were found to be easier to perform because they avoid the culture and biosafety constraint. Given that genotypic tests can rapidly detect the prominent mechanisms of resistance, such as the rpoB mutation for rifampicin resistance, we are facing new challenges with the observation of false-resistance (mutations not conferring resistance) and false-susceptibility (mutations different from the common mechanism) results. Phenotypic and genotypic approaches are therefore complementary for obtaining a high sensitivity and specificity for detecting drug resistances and susceptibilities to accurately predict MDR/XDR cure and to gather relevant data for resistance surveillance. Although AST-MTB was established in the 1960s, there is no consensus reference method for MIC determination against which the numerous AST-MTB techniques can be compared. This information is necessary for assessing in vitro activity and setting breakpoints for future anti-tuberculosis agents. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The opportunity to collaborate increases preschoolers' motivation for challenging tasks.

PubMed

Butler, Lucas P; Walton, Gregory M

2013-12-01

Collaborating on challenging endeavors is a foundation of human society. Recent research suggests that young children are not only motivated to cooperate with others-for instance, to help others accomplish their goals-but may also be motivated to collaborate with others-to pursue shared goals. However, a primary reason why collaboration is so important is because opportunities to collaborate can bring people together to work hard to overcome challenges. Two studies (N=70) tested whether the collaborative nature of an activity itself can cause preschoolers to enjoy challenging tasks more and to persist longer on them. To isolate the psychological feeling of collaboration, we tested this hypothesis by manipulating purely psychological cues of collaboration; in all cases, children worked while physically alone. Both studies found that such cues substantially increased preschoolers' motivation on a challenging puzzle, including their persistence on and liking for the puzzle, relative to two non-collaborative control conditions. We suggest that an early emerging drive to engage in shared collaborative activities leads children to find collaborative activities to be intrinsically motivating. This may represent an important basis of motivation as children embark on formal schooling. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparing Standard and Selective Degradation DNA Extraction Methods: Results from a Field Experiment with Sexual Assault Kits^.

PubMed

Campbell, Rebecca; Pierce, Steven J; Sharma, Dhruv B; Shaw, Jessica; Feeney, Hannah; Nye, Jeffrey; Schelling, Kristin; Fehler-Cabral, Giannina

2017-01-01

A growing number of U.S. cities have large numbers of untested sexual assault kits (SAKs) in police property facilities. Testing older kits and maintaining current case work will be challenging for forensic laboratories, creating a need for more efficient testing methods. We evaluated selective degradation methods for DNA extraction using actual case work from a sample of previously unsubmitted SAKs in Detroit, Michigan. We randomly assigned 350 kits to either standard or selective degradation testing methods and then compared DNA testing rates and CODIS entry rates between the two groups. Continuation-ratio modeling showed no significant differences, indicating that the selective degradation method had no decrement in performance relative to customary methods. Follow-up equivalence tests indicated that CODIS entry rates for the two methods could differ by more than ±5%. Selective degradation methods required less personnel time for testing and scientific review than standard testing. © 2016 American Academy of Forensic Sciences.

Towards a Rigorous Assessment of Systems Biology Models: The DREAM3 Challenges

PubMed Central

Prill, Robert J.; Marbach, Daniel; Saez-Rodriguez, Julio; Sorger, Peter K.; Alexopoulos, Leonidas G.; Xue, Xiaowei; Clarke, Neil D.; Altan-Bonnet, Gregoire; Stolovitzky, Gustavo

2010-01-01

Background Systems biology has embraced computational modeling in response to the quantitative nature and increasing scale of contemporary data sets. The onslaught of data is accelerating as molecular profiling technology evolves. The Dialogue for Reverse Engineering Assessments and Methods (DREAM) is a community effort to catalyze discussion about the design, application, and assessment of systems biology models through annual reverse-engineering challenges. Methodology and Principal Findings We describe our assessments of the four challenges associated with the third DREAM conference which came to be known as the DREAM3 challenges: signaling cascade identification, signaling response prediction, gene expression prediction, and the DREAM3 in silico network challenge. The challenges, based on anonymized data sets, tested participants in network inference and prediction of measurements. Forty teams submitted 413 predicted networks and measurement test sets. Overall, a handful of best-performer teams were identified, while a majority of teams made predictions that were equivalent to random. Counterintuitively, combining the predictions of multiple teams (including the weaker teams) can in some cases improve predictive power beyond that of any single method. Conclusions DREAM provides valuable feedback to practitioners of systems biology modeling. Lessons learned from the predictions of the community provide much-needed context for interpreting claims of efficacy of algorithms described in the scientific literature. PMID:20186320

Solar powered rotorcraft: a multidisciplinary engineering challenge for undergraduate students

NASA Astrophysics Data System (ADS)

Danner, Aaron J.; Henz, Martin; Teo, Brian Shohei

2017-08-01

Controlled, fully solar-powered flight in a rotorcraft is a difficult engineering challenge. Over the past five years, multidiciplinary teams of undergraduate engineering students at the National University of Singapore have built and test-flown a succession of increasingly impressive and larger, more efficient aircraft. While many other multidisciplinary or purely photonics projects are available to students in our programme, this particular project attracts an unusual level of excitement and devotion among students working on it. Why is that the case, and what, in general, makes a good final year undergraduate design project? These questions will be explored. Additionally, videos of solar helicopter test flights and spectacular crashes will be shown in the presentation for which the proceedings below have been prepared.

Addressing challenges to MMPI-2-RF-based testimony: questions and answers.

PubMed

Ben-Porath, Yossef S

2012-11-01

Introduction of a new version of a psychological test brings with it challenges that can be accentuated by the adversarial nature of the legal process. In the case of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF), these challenges can be addressed by becoming familiar with the rationale for and the methods used in revising the inventory, the information contained in the test manuals, and the growing peer-reviewed literature on the test. Potential challenges to MMPI-2-RF-based testimony are identified in this article and discussed in question and answer format. The questions guiding this discussion are based on the Daubert factors, established in 1993 by the US Supreme Court as criteria for gauging the scientific validity of proffered expert testimony. The answers to these questions apply more broadly to testimony in depositions, pre-trial hearings, and at trial. Consideration of the MMPI-2-RF in light of the Daubert factors indicates that the instrument has been subjected to extensive empirical testing and that a substantial peer-reviewed literature is available to guide and support its use. Information about the known and potential rate of error associated with MMPI-2-RF scores is available, and standard procedures for administration, scoring, and interpretation of the inventory are detailed in the test administration manual. Indicators of MMPI-2-RF acceptance can be cited, and criticisms of the MMPI-2-RF can be addressed with information available in the test documents and an extensive, modern, and actively growing peer-reviewed literature.

Management of HIV-associated tuberculosis in resource-limited settings: a state-of-the-art review.

PubMed

Lawn, Stephen D; Meintjes, Graeme; McIlleron, Helen; Harries, Anthony D; Wood, Robin

2013-12-02

The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB.

Role of atopy patch test for diagnosis of food allergy-related gastrointestinal symptoms in children.

PubMed

Boonyaviwat, Onsuree; Pacharn, Punchama; Jirapongsananuruk, Orathai; Vichyanond, Pakit; Visitsunthorn, Nualanong

2015-12-01

Double-blind, placebo-controlled food challenge is the gold standard for diagnosing food allergy. However, it is a time-consuming procedure and requires onsite medical supervision and resuscitating medicines and devices on hand. The objective of this study was to compare the atopy patch test (APT) with the oral food challenge test (OFC) in children with suspected food allergy-related gastrointestinal (GI) symptoms. A prospective self-controlled study enrolled children with a history of suspected food allergy-related GI symptoms. Skin prick test (SPT) and APT using lyophilized and commercial allergen extracts for cow's milk, egg, wheat, soy, and shrimp were evaluated, and OFC was performed. Thirty-nine patients (25 boys, median age 2.4 yrs) with 76 events of suspected food allergy-related GI symptoms were enrolled. SPT was positive in 11/76 events (14.5%). Sensitivity, specificity, predictive values, and likelihood ratio were calculated related to the food challenge outcome. Of 41 OFC, 30 (73.2%) were positive. APT using lyophilized allergen extracts yielded high sensitivity (80%) and high positive predictive value (85.7%). APT using commercial allergen extracts yielded low sensitivity (30%) but high specificity (90%). The negative predictive value of APT using lyophilized and commercial allergen extracts was 53.8% and 32.2%, respectively. All cases with positive APT using lyophilized allergen extracts together with positive SPT also had positive OFC. In contrast to commercial extracts, APT with lyophilized allergen extracts is reliable, safe, and maybe useful for the diagnosis of suspected food allergy-related GI symptoms in children. OFC is still needed in most of the cases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lessons learned from the manufacture of the W7-X planar coils

NASA Astrophysics Data System (ADS)

Viebke, H.; Gustke, D.; Rummel, T.; Sborchia, C.; Schroeder, R.; Williams, D.; Bates, S.; Leigh, B.; Winter, R.

2006-06-01

WENDELSTEIN 7-X (W7-X) is a superconducting stellarator. The planar coils are in charge to modify the magnetic filed configuration of the W7-X. The major challenges during manufacturing were the fabrication of the cable-in-conduit conductor, the accuracy of the coil cases after welding and machining and the development of electrical joints with a resistance below 1 nΩ. Leaks were detected during repetitive in the case cooling system, which were caused by stress corrosion cracking. High voltage tests in a reduced vacuum environment (Paschen conditions) revealed that the insulation had to be reinforced and the quench detection wires had to be exchanged. This paper gives an overview about the main technical challenges of the planar coils and the lessons learned during production.

Implementing antiretroviral resistance testing in a primary health care HIV treatment programme in rural KwaZulu-Natal, South Africa: early experiences, achievements and challenges.

PubMed

Lessells, Richard J; Stott, Katharine E; Manasa, Justen; Naidu, Kevindra K; Skingsley, Andrew; Rossouw, Theresa; de Oliveira, Tulio

2014-03-07

Antiretroviral drug resistance is becoming increasingly common with the expansion of human immunodeficiency virus (HIV) treatment programmes in high prevalence settings. Genotypic resistance testing could have benefit in guiding individual-level treatment decisions but successful models for delivering resistance testing in low- and middle-income countries have not been reported. An HIV Treatment Failure Clinic model was implemented within a large primary health care HIV treatment programme in northern KwaZulu-Natal, South Africa. Genotypic resistance testing was offered to adults (≥16 years) with virological failure on first-line antiretroviral therapy (one viral load >1000 copies/ml after at least 12 months on a standard first-line regimen). A genotypic resistance test report was generated with treatment recommendations from a specialist HIV clinician and sent to medical officers at the clinics who were responsible for patient management. A quantitative process evaluation was conducted to determine how the model was implemented and to provide feedback regarding barriers and challenges to delivery. A total of 508 specimens were submitted for genotyping between 8 April 2011 and 31 January 2013; in 438 cases (86.2%) a complete genotype report with recommendations from the specialist clinician was sent to the medical officer. The median turnaround time from specimen collection to receipt of final report was 18 days (interquartile range (IQR) 13-29). In 114 (26.0%) cases the recommended treatment differed from what would be given in the absence of drug resistance testing. In the majority of cases (n = 315, 71.9%), the subsequent treatment prescribed was in line with the recommendations of the report. Genotypic resistance testing was successfully implemented in this large primary health care HIV programme and the system functioned well enough for the results to influence clinical management decisions in real time. Further research will explore the impact and cost-effectiveness of different implementation models in different settings.

Influence of Cultural, Organizational, and Automation Capability on Human Automation Trust: A Case Study of Auto-GCAS Experimental Test Pilots

NASA Technical Reports Server (NTRS)

Koltai, Kolina; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Cacanindin, Artemio; Johnson, Walter; Lyons, Joseph

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Force's newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the case's politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerability/ high risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Fabrication and testing of U–7Mo monolithic plate fuel with Zircaloy cladding

DOE PAGES

Pasqualini, E. E.; Robinson, A. B.; Porter, D. L.; ...

2016-07-15

The Materials Management and Minimization program is developing fuel designs to replace highly enriched fuel with fuels of low enrichment. In the most challenging cases, U–(7–10wt%)Mo monolithic plate fuel are proposed. The chosen design includes aluminum-alloy cladding, which provides some challenges in fabrication and fuel/cladding interaction in service. We investigated zircaloy cladding, specifically Zry–4as an alternative cladding, and development of a fabrication method was performed by researchers with the Comisión Nacionalde Energia Atómica (CNEA) in Argentina, resulting in test fuel plates (Zry–4 clad U–7Mo) which were subsequently tested in the Advanced Test Reactor in Idaho. Because Zry–4 and U–(7–10)Mo havemore » similar high-temperature mechanical properties, fabrication was simplified in that the fuel foil and cladding could be co-rolled and bonded. The challenge was to prevent a thermal-expansion mismatch which could destroy the fuel/cladding bond before complete bonding was achieved; the solution was to prevent the composites from cooling significantly between roll passes. Our final product performed very well in-reactor, showing good bonding, very little fuel/cladding interaction, either from fabrication or in-reactor testing, and little swelling, especially no detectable heterogeneous bubble formation at the fuel/cladding interface tested to a fission density of up to 2.54E+21« less

Fabrication and testing of U–7Mo monolithic plate fuel with Zircaloy cladding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasqualini, E. E.; Robinson, A. B.; Porter, D. L.

The Materials Management and Minimization program is developing fuel designs to replace highly enriched fuel with fuels of low enrichment. In the most challenging cases, U–(7–10wt%)Mo monolithic plate fuel are proposed. The chosen design includes aluminum-alloy cladding, which provides some challenges in fabrication and fuel/cladding interaction in service. We investigated zircaloy cladding, specifically Zry–4as an alternative cladding, and development of a fabrication method was performed by researchers with the Comisión Nacionalde Energia Atómica (CNEA) in Argentina, resulting in test fuel plates (Zry–4 clad U–7Mo) which were subsequently tested in the Advanced Test Reactor in Idaho. Because Zry–4 and U–(7–10)Mo havemore » similar high-temperature mechanical properties, fabrication was simplified in that the fuel foil and cladding could be co-rolled and bonded. The challenge was to prevent a thermal-expansion mismatch which could destroy the fuel/cladding bond before complete bonding was achieved; the solution was to prevent the composites from cooling significantly between roll passes. Our final product performed very well in-reactor, showing good bonding, very little fuel/cladding interaction, either from fabrication or in-reactor testing, and little swelling, especially no detectable heterogeneous bubble formation at the fuel/cladding interface tested to a fission density of up to 2.54E+21« less

Direct-field acoustic testing of a flight system : logistics, challenges, and results.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stasiunas, Eric Carl; Gurule, David Joseph; Babuska, Vit

2010-10-01

Before a spacecraft can be considered for launch, it must first survive environmental testing that simulates the launch environment. Typically, these simulations include vibration testing performed using an electro-dynamic shaker. For some spacecraft however, acoustic excitation may provide a more severe loading environment than base shaker excitation. Because this was the case for a Sandia Flight System, it was necessary to perform an acoustic test prior to launch in order to verify survival due to an acoustic environment. Typically, acoustic tests are performed in acoustic chambers, but because of scheduling, transportation, and cleanliness concerns, this was not possible. Instead, themore » test was performed as a direct field acoustic test (DFAT). This type of test consists of surrounding a test article with a wall of speakers and controlling the acoustic input using control microphones placed around the test item, with a closed-loop control system. Obtaining the desired acoustic input environment - proto-flight random noise input with an overall sound pressure level (OASPL) of 146.7 dB-with this technique presented a challenge due to several factors. An acoustic profile with this high OASPL had not knowingly been obtained using the DFAT technique prior to this test. In addition, the test was performed in a high-bay, where floor space and existing equipment constrained the speaker circle diameter. And finally, the Flight System had to be tested without contamination of the unit, which required a contamination bag enclosure of the test unit. This paper describes in detail the logistics, challenges, and results encountered while performing a high-OASPL, direct-field acoustic test on a contamination-sensitive Flight System in a high-bay environment.« less

MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

MS lesion segmentation using a multi-channel patch-based approach with spatial consistency

NASA Astrophysics Data System (ADS)

Mechrez, Roey; Goldberger, Jacob; Greenspan, Hayit

2015-03-01

This paper presents an automatic method for segmentation of Multiple Sclerosis (MS) in Magnetic Resonance Images (MRI) of the brain. The approach is based on similarities between multi-channel patches (T1, T2 and FLAIR). An MS lesion patch database is built using training images for which the label maps are known. For each patch in the testing image, k similar patches are retrieved from the database. The matching labels for these k patches are then combined to produce an initial segmentation map for the test case. Finally a novel iterative patch-based label refinement process based on the initial segmentation map is performed to ensure spatial consistency of the detected lesions. A leave-one-out evaluation is done for each testing image in the MS lesion segmentation challenge of MICCAI 2008. Results are shown to compete with the state-of-the-art methods on the MICCAI 2008 challenge.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

PubMed

Lutterloh, Emily; Likaka, Andrew; Sejvar, James; Manda, Robert; Naiene, Jeremias; Monroe, Stephan S; Khaila, Tadala; Chilima, Benson; Mallewa, Macpherson; Kampondeni, Sam D; Lowther, Sara A; Capewell, Linda; Date, Kashmira; Townes, David; Redwood, Yanique; Schier, Joshua G; Nygren, Benjamin; Tippett Barr, Beth; Demby, Austin; Phiri, Abel; Lungu, Rudia; Kaphiyo, James; Humphrys, Michael; Talkington, Deborah; Joyce, Kevin; Stockman, Lauren J; Armstrong, Gregory L; Mintz, Eric

2012-04-01

Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Usability Testing with Online Research Panels: A Case Study from the Field of Instructional Design

ERIC Educational Resources Information Center

Williams Van Rooij, Shahron

2013-01-01

One of the challenges experienced by students of instructional design is eliciting user participation when designing and developing products for course or program projects, particularly over multiple cycles of evaluation. Student projects do not normally have budgets to engage recruitment companies or provide participant incentives. This paper…

The Custody Evaluation Handbook: Research-Based Solutions and Applications.

ERIC Educational Resources Information Center

Bricklin, Barry

Three of the most challenging problems in the custody evaluation field follow from: (1) the difficulties involved in adapting data derived from group studies or traditional tests into a form for individual cases; (2) the absence of clear and compelling guidelines to aggregate the information collected in a comprehensive evaluation; and (3) the…

Enterprising University Put to the Test: Transnational Education in the Middle East

ERIC Educational Resources Information Center

Fusilier, Marcelline; Munro, Douglas

2014-01-01

Educational leaders are increasingly required to become effective change agents as schools and universities are faced with pressures to cut costs and adapt to stakeholder demands. This case details the administrative challenges of restructuring a private-sector higher education provider from a traditional to an enterprising university capable of…

From SOPs to Reports to Evaluations: Learning and Memory as a Case Study of how Missing Data and Methods Impact Interpretation

EPA Science Inventory

In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential. Because there is flexibility in the selection of test method(s), consistency can be especially challenging for lea...

High School Students' Understanding of Acid-Base Concepts: An Ongoing Challenge for Teachers

ERIC Educational Resources Information Center

Damanhuri, Muhd Ibrahim Muhamad; Treagust, David F.; Won, Mihye; Chandrasegaran, A. L.

2016-01-01

Using a quantitative case study design, the "Acids-Bases Chemistry Achievement Test" ("ABCAT") was developed to evaluate the extent to which students in Malaysian secondary schools achieved the intended curriculum on acid-base concepts. Responses were obtained from 260 Form 5 (Grade 11) students from five schools to initially…

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

PubMed

Mehta, Shyamal H; Prakash, Rajan; Prisant, L Michael; Isales, Carlos M; Morgan, John C; Williams, Hadyn; Sethi, Kapil D

2009-06-01

A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Artificial viscosity to cure the carbuncle phenomenon: The three-dimensional case

NASA Astrophysics Data System (ADS)

Rodionov, Alexander V.

2018-05-01

The carbuncle phenomenon (also known as the shock instability) has remained a serious computational challenge since it was first noticed and described [1,2]. In [3] the author presented a summary on this subject and proposed a new technique for curing the problem. Its idea is to introduce some dissipation in the form of right-hand sides of the Navier-Stokes equations into the basic method of solving Euler equations; in so doing, the molecular viscosity coefficient is replaced by the artificial viscosity coefficient. The new cure for the carbuncle flaw was tested and tuned for the case of using first-order schemes in two-dimensional simulations. Its efficiency was demonstrated on several well-known test problems. In this paper we extend the technique of [3] to the case of three-dimensional simulations.

Forensic science: the truth is out there

NASA Astrophysics Data System (ADS)

Herold, Lynne D.

2002-06-01

Criminalistics, one of the many sub-divisions of forensic science, is an applied science in which items of evidence are analyzed to provide investigative information and scientific evidence to be used in courts of law. Laboratories associated with governmental public agencies are typically involved in criminal cases as opposed to civil cases, and those types of cases that fall within the jurisdiction of the particular agency. Common analytical divisions within criminalistics laboratories include blood alcohol testing, toxicology, narcotics, questioned documents, biology, firearms, latent fingerprints, physical and trace evidence sections. Specialized field investigative services may be provided in the areas of clandestine drug laboratories and major crimes (firearms, biology, trace, arson/explosives). Forensic science best practice requires the use of non-destructive testing whenever reasonably possible. Several technically difficult situations (bodies and evidence encased in cement and metal) are presented as a challenge to audience.

The Cost of Penicillin Allergy Evaluation.

PubMed

Blumenthal, Kimberly G; Li, Yu; Banerji, Aleena; Yun, Brian J; Long, Aidan A; Walensky, Rochelle P

2017-09-22

Unverified penicillin allergy leads to adverse downstream clinical and economic sequelae. Penicillin allergy evaluation can be used to identify true, IgE-mediated allergy. To estimate the cost of penicillin allergy evaluation using time-driven activity-based costing (TDABC). We implemented TDABC throughout the care pathway for 30 outpatients presenting for penicillin allergy evaluation. The base-case evaluation included penicillin skin testing and a 1-step amoxicillin drug challenge, performed by an allergist. We varied assumptions about the provider type, clinical setting, procedure type, and personnel timing. The base-case penicillin allergy evaluation costs $220 in 2016 US dollars: $98 for personnel, $119 for consumables, and $3 for space. In sensitivity analyses, lower cost estimates were achieved when only a drug challenge was performed (ie, no skin test, $84) and a nurse practitioner provider was used ($170). Adjusting for the probability of anaphylaxis did not result in a changed estimate ($220); although other analyses led to modest changes in the TDABC estimate ($214-$246), higher estimates were identified with changing to a low-demand practice setting ($268), a 50% increase in personnel times ($269), and including clinician documentation time ($288). In a least/most costly scenario analyses, the lowest TDABC estimate was $40 and the highest was $537. Using TDABC, penicillin allergy evaluation costs $220; even with varied assumptions adjusting for operational challenges, clinical setting, and expanded testing, penicillin allergy evaluation still costs only about $540. This modest investment may be offset for patients treated with costly alternative antibiotics that also may result in adverse consequences. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The challenge of managing extensively drug-resistant tuberculosis at a referral hospital in the state of São Paulo, Brazil: a report of three cases

PubMed Central

Arbex, Marcos Abdo; de Siqueira, Hélio Ribeiro; D'Ambrosio, Lia; Migliori, Giovanni Battista

2015-01-01

ABSTRACT Here, we report the cases of three patients diagnosed with extensively drug-resistant tuberculosis and admitted to a referral hospital in the state of São Paulo, Brazil, showing the clinical and radiological evolution, as well as laboratory test results, over a one-year period. Treatment was based on the World Health Organization guidelines, with the inclusion of a new proposal for the use of a combination of antituberculosis drugs (imipenem and linezolid). In the cases studied, we show the challenge of creating an acceptable, effective treatment regimen including drugs that are more toxic, are more expensive, and are administered for longer periods. We also show that treatment costs are significantly higher for such patients, which could have an impact on health care systems, even after hospital discharge. We highlight the fact that in extreme cases, such as those reported here, hospitalization at a referral center seems to be the most effective strategy for providing appropriate treatment and increasing the chance of cure. In conclusion, health professionals and governments must make every effort to prevent cases of multidrug-resistant and extensively drug-resistant tuberculosis. PMID:26785966

Teicoplanin allergy - an emerging problem in the anaesthetic allergy clinic.

PubMed

Savic, L C; Garcez, T; Hopkins, P M; Harper, N J N; Savic, S

2015-10-01

Anaphylaxis to teicoplanin appears to be extremely rare, with only one confirmed case report worldwide. Two anaesthetic allergy clinics in the UK have received a number of suspected cases referred for investigation, and we present here the first case series of teicoplanin allergy. We investigated 20 cases of suspected teicoplanin allergy, identified from the two clinics over a period of two years. We devised a set of five criteria to categorize the certainty of their diagnosis. These included: (1) reaction within 15 min of administration of teicoplanin, (2) ≥2 features of anaphylaxis present, (3) positive skin testing or challenge testing, (4) raised serum mast cell tryptase (MCT), (5) alternative diagnosis excluded. Based on these criteria we defined the likelihood of IgE-mediated allergy to teicoplanin as: definite-met all criteria; probable-met criteria 1.2 and 5, plus 3 or 4; uncertain-met criteria 1.2 and 5; excluded- any others. We identified 7 'definite', 7 'probable' and 2 'uncertain' cases of teicoplanin allergy. Four cases were excluded. IgE-mediated anaphylaxis to teicoplanin appears to be more common than previously thought. This is true even if only definitive cases are considered. Investigation of teicoplanin allergy is hampered by the lack of standardized skin test concentrations. In some cases, there was a severe clinical reaction, but without any skin test evidence of histamine release. The mechanism of reaction in these cases is not known and requires further study. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Herpes simplex encephalitis as a complication of neurosurgical procedures: report of 3 cases and review of the literature.

PubMed

Jaques, David A; Bagetakou, Spyridoula; L'Huillier, Arnaud G; Bartoli, Andrea; Vargas, Maria-Isabel; Fluss, Joel; Kaiser, Laurent

2016-05-23

Herpes simplex virus (HSV) is the most common identified cause of focal encephalitis worldwide. However, postoperative HSV encephalitis (HSVE) is a rare complication of neurosurgical procedures and a significant clinical challenge We describe 3 cases of postoperative HSVE and review all published reports. A total of 23 cases were identified. Clinical heterogeneity represents a diagnostic challenge in the postoperative setting. Cerebral magnetic resonance imaging showed typical findings in a minority of patients only, whereas HSV-specific polymerase chain reaction on the cerebrospinal fluid proved to be a valuable test. The postoperative viral pathophysiology remains a subject of debate. The rate of adverse outcome is high and early antiviral treatment seems to be a strong predictor of clinical outcome. We recommend early empirical treatment for any patient presenting with post-neurosurgical lymphocytic meningo-encephalitis, and prophylactic antiviral treatment for patients with a history of previous HSVE who will undergo a neurosurgical procedure.

Fabrication and testing of U-7Mo monolithic plate fuel with Zircaloy cladding

NASA Astrophysics Data System (ADS)

Pasqualini, E. E.; Robinson, A. B.; Porter, D. L.; Wachs, D. M.; Finlay, M. R.

2016-10-01

Nuclear fuel designs are being developed to replace highly enriched fuel used in research and test reactors with fuels of low enrichment. In the most challenging cases, U-(7-10 wt%)Mo monolithic plate fuels are proposed. One of the considered designs includes aluminum-alloy cladding, which provides some challenges in fabrication and fuel/cladding interaction during service. Zircaloy cladding, specifically Zry-4, was investigated as an alternative cladding, and development of a fabrication method was performed by researchers with the Comisión Nacionalde Energia Atómica (CNEA) in Argentina, resulting in test fuel plates (Zry-4 clad U-7Mo) which were subsequently tested in the Advanced Test Reactor in Idaho. Because Zry-4 and U-(7-10)Mo have similar high-temperature mechanical properties, fabrication was simplified in that the fuel foil and cladding could be co-rolled and bonded. The challenge was to prevent a thermal-expansion mismatch, which could destroy the fuel/cladding bond before complete bonding was achieved; the solution was to prevent the composites from cooling significantly during or between roll passes. The final product performed very well in-reactor, showing good bonding, very little fuel/cladding interaction-either from fabrication or in-reactor testing-and little swelling, especially no detectable heterogeneous bubble formation at the fuel/cladding interface tested to a fission density of up to 2.7E+21 (average) fissions/cm3, 3.8E+21 (peak).

Severe reaction in a child with asymptomatic codfish allergy: Food challenge reactivating recurrent pancreatitis

PubMed Central

2012-01-01

An 8-year-old child during the first year of life manifested severe atopic dermatitis and chronic diarrhea with mucorrhea and rectal bleeding; a fish-free diet was started based on weakly positive skin-prick tests to codfish extract. At the age of 4 years the child began to suffer of recurrent pancreatitis. When he came to our attention for the evaluation of his fish allergy, he was asymptomatic; a weak reactivity to codfish was observed (SPTs: cod, 4 mm, sIgE ImmunoCAP: cod, 1.30kU/l). The food challenge test with cod was negative. When the child ate cod again, within 5 minutes, developed anaphylactic reaction and complained of abdominal pain compatible with pancreatitis (enzyme serum levels risen and parenchymal oedema at ultrasonography), that resolved within 7 days after specific therapy. This case raises two issues: the elimination diet in asymptomatic food allergy on the basis only of SPT and the ethicality of food challenge in gastrointestinal chronic disease. PMID:22571554

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases

PubMed Central

Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

2015-01-01

Study Objectives: The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Methods and Results: Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Conclusions: Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. Citation: Baiardi S, Vandi S, Pizza F, Alvisi L, Toscani L, Zambrelli E, Tinuper P, Mayer G, Plazzi G. Narcolepsy type 1 and idiopathic generalized epilepsy: diagnostic and therapeutic challenges in dual cases. J Clin Sleep Med 2015;11(11):1257–1262. PMID:26156948

A Multi-center Milestone Study of Clinical Vertebral CT Segmentation

PubMed Central

Yao, Jianhua; Burns, Joseph E.; Forsberg, Daniel; Seitel, Alexander; Rasoulian, Abtin; Abolmaesumi, Purang; Hammernik, Kerstin; Urschler, Martin; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Castro-Mateos, Isaac; Pozo, Jose M.; Frangi, Alejandro F.; Summers, Ronald M.; Li, Shuo

2017-01-01

A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention. PMID:26878138

Intraocular cysts of toxoplasma gondii in patients with necrotizing retinitis following periocular/intraocular triamcinolone injection.

PubMed

Nijhawan, Raje; Bansal, Reema; Gupta, Nalini; Beke, Nikhil; Kulkarni, Pandurang; Gupta, Amod

2013-10-01

To report the detection of Toxoplasma gondii cysts in intraocular aspirates of patients with necrotizing retinitis following periocular/intraocular corticosteroid injection. Case report. Two patients (2 eyes) with widespread necrotizing retinitis in a steroid-exposed eye posed a diagnostic challenge and underwent pars plana vitrectomy (PPV). Intraocular samples (vitreous fluid, retinal tissue, and subretinal aspirate in case 1, and vitreous fluid in case 2) were subjected to cytological examination. The subretinal aspirate (case 1) revealed encysted bradyzoites of Toxoplasma gondii. Vitreous fluid (case 2) tested positive for anti-toxoplasma antibodies and the smear showed encysted forms of Toxoplasma gondii on cytology. CONCLUSION. Toxoplasma gondii cysts were detected in eyes with necrotizing retinitis that developed secondary to injudicious use of corticosteroids.

Challenges in fitting a hearing aid to a severely collapsed ear canal and mixed hearing loss.

PubMed

Oeding, Kristi; Valente, Michael; Chole, Richard

2012-04-01

Collapsed ear canals typically occur when an outside force, such as a headset for audiometric testing, is present. However, when a collapsed ear canal occurs without external pressure, this creates a challenge not only for performing audiometric testing but also for coupling a hearing aid to the ear canal. This case report highlights the challenges associated with fitting a hearing aid on a patient with a severe anterior-posterior collapsed ear canal with a mixed hearing loss. A 67-yr-old female originally presented to Washington University in St. Louis School of Medicine in 1996 with a long-standing history of bilateral otosclerosis. She had chronic ear infections in the right ear and a severely collapsed ear canal in the left ear and was fit with a bone anchored hearing aid (BAHA®) on the right side in 2003. However, benefit from the BAHA started to decrease due to changes in hearing, and a different hearing solution was needed. It was proposed that a hearing aid be fit to her collapsed left ear canal; however, trying to couple a hearing aid to the collapsed ear canal required unique noncustom earmold solutions. This case study highlights some of the obstacles and potential solutions for coupling a hearing aid to a severely collapsed ear canal. American Academy of Audiology.

Considerations in the Diagnosis and Accelerated Return to Sport of a Professional Basketball Player With a Triceps Surae Injury: A Case Report.

PubMed

Anloague, Philip A; Strack, Donald S

2018-05-01

Study Design Case report. Background Acute injuries of the triceps surae and Achilles tendon are common in sports. Rupture of the plantaris tendon can be challenging to diagnose. There is limited evidence detailing the diagnosis, rehabilitation, and accelerated return to sport of elite professional basketball players who have sustained calf injuries. Case Description A 25-year-old male professional basketball player sustained an injury to his calf during a professional basketball game. This case report details the presumptive diagnosis, graduated progression of intervention, and return to play of a professional athlete with a likely isolated plantaris tendon tear. Outcomes The patient returned to postseason competition 10 days post injury. Objective measures were tracked throughout rehabilitation and compared to baseline assessments. Before returning to play, the athlete showed improvements beyond the minimal clinically important difference for calf girth (2 cm) and numeric pain-rating scale score (4 points, 0-10 scale). Functional testing was conducted that included the Y Balance Test lower quarter and the Functional Movement Screen, with results that exceeded or returned the athlete to preseason levels. Discussion This report details the case of a professional basketball player who returned to competitive play in an accelerated time frame following injury to his calf. Diagnosing a plantaris tendon rupture can be challenging, and anatomical variations of this muscle should be considered. It was demonstrated in this case that physical therapy rehabilitation was helpful in making a treatment-based clinical diagnosis when imaging was unclear. Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther 2018;48(5):388-397. Epub 6 Apr 2018. doi:10.2519/jospt.2018.7192.

Anonymous HIV testing: what does it mean in policy and practice? A case study in Newfoundland and Labrador, Canada.

PubMed

Hancock, Amanda; Gustafson, Diana L

2014-01-01

HIV infection is not a legally notifiable disease at the national level in Canada; however, provincial and territorial officials voluntarily undertake notification to the Public Health Agency of Canada. A case study involving four community-based sites in Newfoundland and Labrador found that the absence of clear legislation concerning HIV testing presented challenges for nurses who had to interpret and comply with provincial legislation and agency policy while meeting the needs of test-seekers. This ambiguous messaging is part of other conflicting information about the availability of anonymous HIV testing that, along with other factors, may contribute to under-testing and under-diagnosis in the province. From a social justice perspective, developing a national HIV strategy and amending legislation to facilitate anonymous HIV testing might provide clearer direction to nurses and agencies, and promote public health by improving service delivery and increasing testing in under-tested, higher-risk-taking populations. Copyright © 2014 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Assessment of coliphage surrogates for testing drinking water treatment devices.

PubMed

Gerba, Charles P; Abd-Elmaksoud, Sherif; Newick, Huikheng; El-Esnawy, Nagwa A; Barakat, Ahmed; Ghanem, Hossam

2015-03-01

Test protocols have been developed by the United States Environmental Protection Agency (USEPA) and the World Health Organization (WHO) to test water treatment devices/systems that are used at the individual and home levels to ensure the removal of waterborne viruses. The goal of this study was to assess if coliphage surrogates could be used in this testing in place of the currently required use of animal or human enteric viruses. Five different coliphages (MS-2, PRD1, ΦX-174, Qβ, and fr) were compared to the removal of poliovirus type 1 (LSc-2ab) by eight different water treatment devices/systems using a general case and a challenge case (high organic load, dissolved solids, and turbidity) test water as defined by the USEPA. The performance of the units was rated as a pass/fail based on a 4 log removal/inactivation of the viruses. In all cases, a failure or a pass of the units/system for poliovirus also corresponded to a pass/fail by all of the coliphages. In summary, in using pass/fail criteria as recommended under USEPA guidelines for testing water treatment device/systems, the use of coliphages should be considered as an alternative to reduce cost and time of testing such devices/systems.

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.

PubMed

Gaeta, Francesco; Valluzzi, Rocco Luigi; Alonzi, Cristiana; Maggioletti, Michela; Caruso, Cristiano; Romano, Antonino

2015-04-01

Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[A study of food-dependent exercise-induced anaphylaxis by analyzing the Japanese cases reported in the literature].

PubMed

Harada, S; Horikawa, T; Icihashi, M

2000-11-01

We surveyed and analyzed cases of food-dependent exercise-induced anaphylaxis (FDEIA) in the Japanese literature. We found 167 cases which were reported as FDEIA since 1983. Analyzing these case, following characteristic features were revealed: 1) Recent upward trend in the number of reports of FDEIA was noted. 2) Male cases were more frequent than female cases, while about half of the cases were teenager. 3) More than half of the cases were proved to be induced by wheat followed by shrimp. In those under 20, shrimp was the most popular cause rather than wheat. 4) Skin test and/or IgE RAST showed positive results in most cases, suggesting that the response itself is linked to type I allergic reaction. 5) About 40% of the patients had history of atopic disease, indicating that atopic condition may play some role in FDEIA. 6) All cases who performed provocation test with aspirin responded to food challenge and/or exercise in combination with aspirin. This indicates that aspirin plays a key provoking factor in FDEIA. 7) In 17 cases FDEIA attacks were observed during noon recess or physical education class after lunch at school. We stress here the importance of a nation-wide education to school teachers the potential danger of this disorder.

Online High School Student Achievement on State-Issued Standardized Tests: A Case Study

ERIC Educational Resources Information Center

Gifford, William M., III

2017-01-01

Online education has increased greatly in recent years among K-12 learners and post-secondary learners. Online learning provides opportunities such as course remediation or access to courses not typically offered, which have benefited many learners. The growth of online learning has also presented educators with challenges as well. Students in…

Increasing Teachers' Use of Evidence-Based Classroom Management Strategies through Consultation: Overview and Case Studies

ERIC Educational Resources Information Center

MacSuga, Ashley S.; Simonsen, Brandi

2011-01-01

Many classroom teachers are faced with challenging student behaviors that impact their ability to facilitate learning in productive, safe environments. At the same time, high-stakes testing, increased emphasis on evidence-based instruction, data-based decision making, and response-to-intervention models have put heavy demands on teacher time and…

Acquisition and Use of Linguistic Knowledge: Scrambling in Child Japanese as a Test Case

ERIC Educational Resources Information Center

Minai, Utako; Isobe, Miwa; Okabe, Reiko

2015-01-01

The current study investigates preschool-age children's comprehension of scrambled sentences in Japanese. While scrambling has been known to be challenging for children, biasing them to exhibit non-adult-like interpretations (e.g., Hayashibe in "Descr Appl Linguist" 8:1-18, 1975; Sano in "Descr Appl Linguist" 10:213-233, 1977;…

Elementary Students' Learning of Materials Science Practices through Instruction Based on Engineering Design Tasks

ERIC Educational Resources Information Center

Wendell, Kristen Bethke; Lee, Hee-Sun

2010-01-01

Materials science, which entails the practices of selecting, testing, and characterizing materials, is an important discipline within the study of matter. This paper examines how third grade students' materials science performance changes over the course of instruction based on an engineering design challenge. We conducted a case study of nine…

Podcasts: Are They an Effective Tool to Enhance Student Learning? A Case Study from McMaster University, Hamilton Canada

ERIC Educational Resources Information Center

Vajoczki, Susan; Watt, Susan; Marquis, Nick; Holshausen, Katherine

2010-01-01

As universities turn to technology to become more learner-centred and address challenges created by increasing class sizes, changing consumer expectations, and increasing numbers of disability accommodation requests it is important to test the utility of technology solutions. This presentation describes a study to determine the effects of…

Promising Practices in Young Adult Employment: Lessons Learned from EMT Career Pathway Programs

ERIC Educational Resources Information Center

Leung, Loh-Sze

2015-01-01

The National Fund for Workforce Solution's Young Adult Initiatives aim to test and implement new strategies for targeting America's young adults and share this information so that employers and workforce development can join forces in investing in the millions of young adults across the nation. This case study will focus on challenges and…

Evaluating the Impact of Leadership Development: A Case Study

ERIC Educational Resources Information Center

Dexter, Barbara; Prince, Christopher

2007-01-01

Purpose: The relevance of business education is coming under increasing challenge from many quarters, who argue that business schools are not delivering research and programmes that are relevant to the needs of business and society. The purpose of this paper is to test these claims by evaluating the impact of a leadership development programme on…

Predicting Item Difficulty of Science National Curriculum Tests: The Case of Key Stage 2 Assessments

ERIC Educational Resources Information Center

El Masri, Yasmine H.; Ferrara, Steve; Foltz, Peter W.; Baird, Jo-Anne

2017-01-01

Predicting item difficulty is highly important in education for both teachers and item writers. Despite identifying a large number of explanatory variables, predicting item difficulty remains a challenge in educational assessment with empirical attempts rarely exceeding 25% of variance explained. This paper analyses 216 science items of key stage…

Application of the Levenshtein Distance Metric for the Construction of Longitudinal Data Files

ERIC Educational Resources Information Center

Doran, Harold C.; van Wamelen, Paul B.

2010-01-01

The analysis of longitudinal data in education is becoming more prevalent given the nature of testing systems constructed for No Child Left Behind Act (NCLB). However, constructing the longitudinal data files remains a significant challenge. Students move into new schools, but in many cases the unique identifiers (ID) that should remain constant…

Two ESP Projects under the Test of Time: The Case of Brazil and Tunisia

ERIC Educational Resources Information Center

Labassi, Tahar

2010-01-01

The paper is a response to Holmes and Celani's (2006) invitation to learn from the Brazilian ESP experience. It discusses the conditions which sustained this experience, and compares the Brazilian situation to the Tunisian one. The paper also discusses the challenges that ESP projects in EFL environments face, the opportunities that ESP…

The microeconomics of personalized medicine: today's challenge and tomorrow's promise.

PubMed

Davis, Jerel C; Furstenthal, Laura; Desai, Amar A; Norris, Troy; Sutaria, Saumya; Fleming, Edd; Ma, Philip

2009-04-01

'Personalized medicine' promises to increase the quality of clinical care and, in some cases, decrease health-care costs. Despite this, only a handful of diagnostic tests have made it to market, with mixed success. Historically, the challenges in this field were scientific. However, as discussed in this article, with the maturation of the '-omics' sciences, it now seems that the major barriers are increasingly related to economics. Overcoming the poor microeconomic alignment of incentives among key stakeholders is therefore crucial to catalysing the further development and adoption of personalized medicine, and we propose several actions that could help achieve this goal.

Immediate hypersensitivity to moxifloxacin with tolerance to ciprofloxacin: report of three cases and review of the literature.

PubMed

Chang, Brenda; Knowles, Sandra R; Weber, Elizabeth

2010-04-01

To report 3 cases of immediate hypersensitivity reactions to moxifloxacin in patients who tolerated ciprofloxacin. A 71-year-old man, a 44-year-old woman, and a 70-year-old woman with a history of a moxifloxacin reaction developed an immediate hypersensitivity reaction upon oral challenge with moxifloxacin in our Drug Safety Clinic. The reaction was mainly characterized by pruritus and urticaria, although dyspnea and hypotension were noted in the first and second patient, respectively. Two of the patients had negative oral challenge tests with ciprofloxacin and all 3 patients tolerated full treatment courses of oral ciprofloxacin. In all 3 cases, use of the Naranjo probability scale indicated a highly probable adverse drug reaction. Moxifloxacin, similar to other fluoroquinolones, can cause immediate hypersensitivity reactions. Previous publications have reported both cross-reactivity and a lack of cross-reactivity among various fluoroquinolones. The 3 patients discussed demonstrated a lack of cross-reactivity between moxifloxacin and ciprofloxacin since they tolerated oral challenge tests and full treatment courses of ciprofloxacin. Moxifloxacin has unique side chains at positions 7 and 8 on its bicyclic ring structure. Antigenic specificity to particular side chains at positions 7 and 8 on the bicyclic ring structure of moxifloxacin may explain this lack of cross-reactivity. Higher reporting rates of anaphylaxis to moxifloxacin compared to other fluoroquinolones may also be related to side chain specificity, although definitive evidence for this is lacking. Based on our experience, patients who develop immediate hypersensitivity reactions to moxifloxacin may receive ciprofloxacin therapy in an appropriately monitored setting if they have previously tolerated full treatment courses of ciprofloxacin. Research into whether there is a specific side chain reaction unique to moxifloxacin is warranted.

The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer

PubMed Central

Wang, Shu; Yu, Bing; Ng, Chiu Chin; Mercorella, Belinda; Selinger, Christina I.; O’Toole, Sandra A.

2015-01-01

Background Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the majority of NSCLC patients present with advanced disease, cytology and small biopsy specimens are frequently the only tissue available for mutation testing, but can pose challenges due to low tumor content. We aim to better define the suitability of these specimens for mutation testing. Methods NSCLC cases referred to our institution for mutation testing over a 15-month period were retrospectively reviewed. Specimens were tested for mutations including EGFR, KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed on the Agena Bioscience MassARRAY platform. Results A total of 146 specimens were tested, comprising 53 (36.3%) resection specimens (including 28 lung resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and BRAF mutations in three specimens (2.1%). There was no significant difference in the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%). Conclusions Our results support the utility of small biopsy and cytology specimens for mutation testing. Careful evaluation of the adequacy of small specimens is required to minimize the risk of false negative or positive results. PMID:25870794

Lost in Translation: the Case for Integrated Testing

NASA Technical Reports Server (NTRS)

Young, Aaron

2017-01-01

The building of a spacecraft is complex and often involves multiple suppliers and companies that have their own designs and processes. Standards have been developed across the industries to reduce the chances for critical flight errors at the system level, but the spacecraft is still vulnerable to the introduction of critical errors during integration of these systems. Critical errors can occur at any time during the process and in many cases, human reliability analysis (HRA) identifies human error as a risk driver. Most programs have a test plan in place that is intended to catch these errors, but it is not uncommon for schedule and cost stress to result in less testing than initially planned. Therefore, integrated testing, or "testing as you fly," is essential as a final check on the design and assembly to catch any errors prior to the mission. This presentation will outline the unique benefits of integrated testing by catching critical flight errors that can otherwise go undetected, discuss HRA methods that are used to identify opportunities for human error, lessons learned and challenges over ownership of testing will be discussed.

Recurrent stingers in an adolescent American football player: dilemmas of return to play. A case report and review of the literature.

PubMed

Zaremski, Jason L; Horodyski, MaryBeth; Herman, Daniel C

2017-01-01

We present the case of a 16-year-old football linebacker with a history of recurrent stingers. Initial physical examination was normal as were cervical spine radiographs. MRI of the cervical spine revealed relative stenosis. Electrodiagnostic testing revealed chronic bilateral neurogenic changes of the superior trunk of the brachial plexus. A Kerr Collar was obtained to minimize head acceleration and force transmission through the neck. While there are return-to-play guidelines for recurrent stingers, there are inconsistencies with those recommendations. Our case highlights the challenges in contact sport athletes with recurrent stingers.

Challenges of measles and rubella laboratory diagnostic in the era of elimination.

PubMed

Hübschen, J M; Bork, S M; Brown, K E; Mankertz, A; Santibanez, S; Ben Mamou, M; Mulders, M N; Muller, C P

2017-08-01

The Member States of the WHO European Region adopted the goal of measles and rubella elimination more than 10 years ago, but so far only 21 of 53 countries have reached this target. Laboratory investigation of suspected cases is essential to support disease elimination efforts. Therefore, WHO maintains a network of accredited laboratories providing high-quality testing. Laboratory investigation heavily relies on specific IgM serology and increasingly on virus detection by reverse transcription (RT)-PCR, but other methods such as IgG avidity testing and genetic characterization of virus strains have gained in importance. In elimination settings, often few samples from suspected cases are available for testing, but testing proficiency must be maintained. The predictive value of an IgM-positive result decreases and other rash-fever disease aetiologies become more important. In addition, cases with a rash after measles/rubella vaccination or with mild disease after waning of vaccine-induced antibodies are seen more often. Thus, it is necessary to perform comprehensive and potentially time-consuming and costly investigations of every suspected case using quality-controlled laboratory methods. At the same time rapid feedback to public health officers is required for timely interventions. The introduction of new laboratory methods for comprehensive case investigations requires training of staff under the supervision of WHO-accredited reference laboratories and the definition of appropriate test algorithms. Clinical, laboratory, and epidemiological data are essential for final case classification and investigation of chains of transmission in the endgame of measles and rubella elimination. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

One-week oral challenge with penicillin in diagnosis of penicillin allergy.

PubMed

Hjortlund, Janni; Mortz, Charlotte Gotthard; Skov, Per Stahl; Eller, Esben; Poulsen, Johan Milling; Borch, Jakob Eli; Bindslev-Jensen, Carsten

2012-05-01

Many patients experience reactions during penicillin treatment. The diagnosis may be difficult and is mainly based on short-term tests. The European Network for Drug Allergy (ENDA) guidelines proposed for diagnosing penicillin allergy do not include long-term challenge. In this study a total of 405 patients were evaluated. The ENDA guidelines were extended, to include a 7-day oral treatment (p.o.7) with penicillin for all patients who were negative in the ENDA programme. Among the 405 patients; 85 had an immediate reaction to penicillin, and a further 13 reacted during p.o.7. Among the 307 patients with a negative outcome, 88 had a case history of reaction to other β-lactam antibiotics and were subsequently tested with the culprit drug. Thirteen patients had a positive outcome: 3 on single-dose challenge and 10 during p.o.7. The extended penicillin diagnostic work-up was positive in 111 patients, 30.0% showed immediate reactions and 5.7% reacted during p.o.7. Approximately 20% of all patients with positive outcome during penicillin challenge are detected by adding p.o.7 with penicillin to the original ENDA guidelines.

Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

PubMed

Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin A; Yen, Catherine; Parashar, Umesh D

2016-05-01

Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Narcolepsy Type 1 and Idiopathic Generalized Epilepsy: Diagnostic and Therapeutic Challenges in Dual Cases.

PubMed

Baiardi, Simone; Vandi, Stefano; Pizza, Fabio; Alvisi, Lara; Toscani, Lucia; Zambrelli, Elena; Tinuper, Paolo; Mayer, Geert; Plazzi, Giuseppe

2015-11-15

The aim of this study is to describe the possible co-occurrence of narcolepsy type 1 and generalized epilepsy, focusing on diagnostic challenge and safety of dual treatments. Four patients with comorbidity for narcolepsy type 1 and idiopathic generalized epilepsy are reported: in three cases the onset of epilepsy preceded narcolepsy type 1 appearance, whereas in one case epileptic spells onset was subsequent. Patients presented with absences, myoclonic and tonic-clonic seizure type: in the patient with tonic-clonic seizures the dual pathology was easily recognized, in the other cases the first diagnosis caused the comorbid disease to be overlooked, independent of the time-course sequence. All four patients underwent neurological examination, video-electroencephalogram during which ictal and interictal epileptic discharges were recorded, and sleep polysomnographic studies. Repeated sleep onset rapid eye movement periods (SOREMPs) were documented with the multiple sleep latency test (MLST) in all the four cases. All patients had unremarkable brain magnetic resonance imaging studies and cerebrospinal hypocretin-1 was assessed in two patients, revealing undetectable levels. The association of antiepileptic drugs and substances currently used to treat narcolepsy type 1, including sodium oxybate, was effective in improving seizures, sleep disturbance, and cataplexy. Narcolepsy type 1 may occur in association with idiopathic generalized epilepsy, leading to remarkable diagnostic and therapeutic challenges. Electrophysiological studies as well as a comprehensive somnologic interview can help confirm the diagnosis in patients with ambiguous neurological history. Sodium oxybate in combination with antiepileptic drugs is safe and effective in treating cataplexy and excessive daytime sleepiness. © 2015 American Academy of Sleep Medicine.

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Automated Generation and Assessment of Autonomous Systems Test Cases

NASA Technical Reports Server (NTRS)

Barltrop, Kevin J.; Friberg, Kenneth H.; Horvath, Gregory A.

2008-01-01

This slide presentation reviews some of the issues concerning verification and validation testing of autonomous spacecraft routinely culminates in the exploration of anomalous or faulted mission-like scenarios using the work involved during the Dawn mission's tests as examples. Prioritizing which scenarios to develop usually comes down to focusing on the most vulnerable areas and ensuring the best return on investment of test time. Rules-of-thumb strategies often come into play, such as injecting applicable anomalies prior to, during, and after system state changes; or, creating cases that ensure good safety-net algorithm coverage. Although experience and judgment in test selection can lead to high levels of confidence about the majority of a system's autonomy, it's likely that important test cases are overlooked. One method to fill in potential test coverage gaps is to automatically generate and execute test cases using algorithms that ensure desirable properties about the coverage. For example, generate cases for all possible fault monitors, and across all state change boundaries. Of course, the scope of coverage is determined by the test environment capabilities, where a faster-than-real-time, high-fidelity, software-only simulation would allow the broadest coverage. Even real-time systems that can be replicated and run in parallel, and that have reliable set-up and operations features provide an excellent resource for automated testing. Making detailed predictions for the outcome of such tests can be difficult, and when algorithmic means are employed to produce hundreds or even thousands of cases, generating predicts individually is impractical, and generating predicts with tools requires executable models of the design and environment that themselves require a complete test program. Therefore, evaluating the results of large number of mission scenario tests poses special challenges. A good approach to address this problem is to automatically score the results based on a range of metrics. Although the specific means of scoring depends highly on the application, the use of formal scoring - metrics has high value in identifying and prioritizing anomalies, and in presenting an overall picture of the state of the test program. In this paper we present a case study based on automatic generation and assessment of faulted test runs for the Dawn mission, and discuss its role in optimizing the allocation of resources for completing the test program.

Balance training using an iPhone application in people with familial dysautonomia: three case reports.

PubMed

Gefen, Rosalee; Dunsky, Ayelet; Hutzler, Yeshayahu

2015-03-01

Familial dysautonomia (FD) is a rare genetic autosomal recessive disease that impairs vital functions and causes neural and motor deficiency. These motor deficits often are characterized by static and dynamic instability and an ataxic gait. As a result, people with FD are at risk for significant physical impairment and falls and pose unique challenges for delivering rehabilitation exercise. Consequently, there is a need for challenging ways to safely and feasibly deliver active exercise rehabilitation to these individuals. This case report describes 3 people with FD (ages 11, 12, and 22 years) with gait and stability problems who attended rehabilitation exercises augmented by the use of an iPhone application specifically developed for the program. The Berg Balance Scale and the Four Square Step Test were conducted prior to training, after training, and after 2 months of follow-up without training. Two patients showed improvements on both measures at the posttest, which were maintained throughout follow-up testing. Although greater experience is needed to more fully evaluate the efficiency of the iPhone application used in this program for people with FD, the results of these initial cases are encouraging. Systematically and prospectively tracking motor abilities and other functional outcomes during rehabilitation of individuals with FD who use the suggested application in balance training is recommended in order to provide greater evidence in this area. © 2015 American Physical Therapy Association.

Early detection and response for measles and rubella cases through the (Nursery) School Absenteeism Surveillance System in Ibaraki Prefecture.

PubMed

Watanabe, Miki; Kurita, Junko; Takagi, Takeshi; Nagata, Noriko; Nagasu, Natsuki; Sugawara, Tamie; Ohkusa, Yasushi

2016-01-01

Objectives In Ibaraki Prefecture, all (nursery) schools have joined the (Nursery) School Absenteeism Surveillance System (hereafter denoted as (N)SASSy), which is operated by the Japan School Health Association to monitor the prevalence of infectious diseases, the early detection and response for outbreaks, and prevention of large outbreaks. Prefectural government officers also utilize it as a control measure for infectious diseases. In particular, when cases of measles or rubella are registered, (N)SASSy sends e-mails automatically to prefectural government officers to activate control measures. This paper summarizes administrative responses by prefectural government officers for measles or rubella cases using (N)SASSy and discusses the future challenges.Methods We summarized registration, detection, and first response data for measles or rubella cases in (N)SASSy and compared the number of detected and reported cases enforced by the Infectious Diseases Control Law from January 1, 2013 to December 31, 2014.Results The public health center questioned hospitals/clinics and (nursery) schools about all registered measles or rubella cases in (N)SASSy on the same day to check the entered information. In the past 2 years, there were 5 measles and 56 rubella cases in 2013 and 1 measles and 19 rubella cases in 2014 registered with (N)SASSy. All cases were checked and investigated by the public health center. Of all cases detected by (N)SASSy, 7 rubella cases in 2013 and 1 rubella case in 2014 were reported based on the law. No measles cases were reported in the 2 years. The results of investigations and laboratory tests were given as feedback to the (nursery) schools. If the case did not case definition determined by the law, we changed the status in (N)SASSy to suspected or discarded cases.Conclusion Since (N)SASSy assists prefectural government officers with earlier detection of and response for infectious diseases, it definitely contributes to infection control. Immediate feedback of the laboratory test results to the (nursery) schools was also useful to confirm cases of measles or rubella. As data entry in (nursery) schools is needed for stable operation and utilization of (N)SASSy, it is important that workshops for (N)SASSy are held for (nursery) school teachers every year to maintain accuracy. Our future challenges include the coordination among (nursery) schools, hospitals/clinics, and prefectural government and their applications for infection control.

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

PubMed

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

2014-01-01

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

The Challenges of Diagnosing Primary Ciliary Dyskinesia

PubMed Central

O'Callaghan, Christopher; Knowles, Michael R.

2011-01-01

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of ciliary structure and function. The diagnosis can be challenging, particularly when using nongenetic assays. The “gold standard” diagnostic test is ultrastructural analysis of respiratory cilia obtained by nasal scrape or brush biopsy. A few specialized centers use high-speed videomicroscopy to examine ciliary beat. Certain beat patterns correlate with ultrastructural defects, and, in some cases, subtle alterations in beat pattern can be seen when ultrastructure is normal. Recent studies have shown that nasal nitric oxide (NO) is very low in patients with PCD compared with healthy control subjects; therefore, this assay may be a useful screening or adjunctive test for PCD. Because acute respiratory illnesses may yield alterations in ciliary ultrastructure, ciliary beat, and nasal NO values, these tests should be performed during a stable baseline period. Identification of an array of PCD genes has provided the opportunity for making a definitive genetic diagnosis for PCD in some cases. All of these approaches have a role in diagnosing PCD. For example, PCD has been confirmed by identifying disease-causing mutations in a heavy dynein chain gene in individuals with normal ciliary ultrastructure but subtle defects in ciliary beat and low nasal NO. Priorities to improve nongenetic diagnostic capability include standardization of nasal NO as a screening test and the development of specialized centers using uniform approaches for the analysis of ciliary ultrastructure and ciliary beat pattern. Another chapter in this issue (see Zariwala and colleagues, pp. 430) addresses the progress toward improved capabilities for definitive genetic testing PMID:21926395

Tuberculous otitis media: a significant diagnostic challenge.

PubMed

Vaamonde, Pedro; Castro, Crisanto; García-Soto, Nicolas; Labella, Torcuato; Lozano, Ascensión

2004-06-01

This study was undertaken to revise the diagnostic characteristics of tuberculous otitis media (TOM), a disorder that is often diagnosed late, leading to delay in specific treatment. Retrospective study of a longitudinal series of 10 TOM patients over a 7-year period at an institutional referral center. Most patients showed intractable otorrhea, moderately severe hearing loss, and necrotic eardrums with granulation tissue and single perforations. Multiple perforations, facial palsy, and cervical adenopathies were rare (<10% of patients). CT generally showed soft tissue involvement of the middle ear without bone erosion. The most effective laboratory test microbiological culture of exudate (diagnostic efficacy 71%). Specific antibiotic treatment was effective in all cases. The diagnosis of TOM remains a significant challenge for otorhinolaryngologists. If there are strong clinical grounds for suspicion, standard laboratory tests for tuberculosis should be repeated even if initially negative.

Changes in Student Perceptions and Study Strategies Over Time in a Veterinary Clinical Pathology Course Using Case-Based Instruction.

PubMed

Fernandez, Nicole J; Wagg, Catherine R; Warren, Amy L

2018-06-13

Veterinary students are challenged to develop new, nonlinear ways of thinking as they learn diagnostic reasoning skills. To support this process, we use real-life cases in our clinical pathology course. Changes in student perceptions regarding the use of cases and changes in study strategies over time have not been previously investigated or compared to student grades. Students participated in three voluntary online surveys that included 4-point Likert scale questions and open-ended questions on the helpfulness of cases for learning and study strategies used during the course. We used Friedman tests to detect any differences in perceptions over time; McNemar's test and "Wilcoxon signed-rank tests were used to detect any differences in study strategies over time. Fisher's exact tests'were used to examine the association between the Likert scale responses and grades in quartiles. Before beginning the course, 29% of students responded that cases were very helpful to their learning, with similar "responses for helpfulness in applying course material and grasping important concepts. There was a significant trend of increasing positivity over the duration of the course, with 74% responding that cases were very helpful at the end of the course. The most-reported study strategy was working individually on cases before the midterm (74% of students), and the most helpful study strategy was attending class regularly (88% reported it as very "helpful). Study strategies did not change significantly over time. Overall, perceptions and study strategies did not vary significantly with grades.

Identifying multidrug resistant tuberculosis transmission hotspots using routinely collected data12

PubMed Central

Manjourides, Justin; Lin, Hsien-Ho; Shin, Sonya; Jeffery, Caroline; Contreras, Carmen; Cruz, Janeth Santa; Jave, Oswaldo; Yagui, Martin; Asencios, Luis; Pagano, Marcello; Cohen, Ted

2012-01-01

SUMMARY In most countries with large drug resistant tuberculosis epidemics, only those cases that are at highest risk of having MDRTB receive a drug sensitivity test (DST) at the time of diagnosis. Because of this prioritized testing, identification of MDRTB transmission hotspots in communities where TB cases do not receive DST is challenging, as any observed aggregation of MDRTB may reflect systematic differences in how testing is distributed in communities. We introduce a new disease mapping method, which estimates this missing information through probability–weighted locations, to identify geographic areas of increased risk of MDRTB transmission. We apply this method to routinely collected data from two districts in Lima, Peru over three consecutive years. This method identifies an area in the eastern part of Lima where previously untreated cases have increased risk of MDRTB. This may indicate an area of increased transmission of drug resistant disease, a finding that may otherwise have been missed by routine analysis of programmatic data. The risk of MDR among retreatment cases is also highest in these probable transmission hotspots, though a high level of MDR among retreatment cases is present throughout the study area. Identifying potential multidrug resistant tuberculosis (MDRTB) transmission hotspots may allow for targeted investigation and deployment of resources. PMID:22401962

What is the Ability Emotional Intelligence Test (MSCEIT) good for? An evaluation using item response theory.

PubMed

Fiori, Marina; Antonietti, Jean-Philippe; Mikolajczak, Moira; Luminet, Olivier; Hansenne, Michel; Rossier, Jérôme

2014-01-01

The ability approach has been indicated as promising for advancing research in emotional intelligence (EI). However, there is scarcity of tests measuring EI as a form of intelligence. The Mayer Salovey Caruso Emotional Intelligence Test, or MSCEIT, is among the few available and the most widespread measure of EI as an ability. This implies that conclusions about the value of EI as a meaningful construct and about its utility in predicting various outcomes mainly rely on the properties of this test. We tested whether individuals who have the highest probability of choosing the most correct response on any item of the test are also those who have the strongest EI ability. Results showed that this is not the case for most items: The answer indicated by experts as the most correct in several cases was not associated with the highest ability; furthermore, items appeared too easy to challenge individuals high in EI. Overall results suggest that the MSCEIT is best suited to discriminate persons at the low end of the trait. Results are discussed in light of applied and theoretical considerations.

Sterilization validation for medical devices at IRASM microbiological laboratory—Practical approaches

NASA Astrophysics Data System (ADS)

Trandafir, Laura; Alexandru, Mioara; Constantin, Mihai; Ioniţă, Anca; Zorilă, Florina; Moise, Valentin

2012-09-01

EN ISO 11137 established regulations for setting or substantiating the dose for achieving the desired sterility assurance level. The validation studies can be designed in particular for different types of products. Each product needs distinct protocols for bioburden determination and sterility testing. The Microbiological Laboratory from Irradiation Processing Center (IRASM) deals with different types of products, mainly for the VDmax25 method. When it comes to microbiological evaluation the most challenging was cotton gauze. A special situation for establishing the sterilization validation method appears in cases of cotton packed in large quantities. The VDmax25 method cannot be applied for items with average bioburden more than 1000 CFU/pack, irrespective of the weight of the package. This is a method limitation and implies increased costs for the manufacturer when choosing other methods. For microbiological tests, culture condition should be selected in both cases of the bioburden and sterility testing. Details about choosing criteria are given.

Future Sex Educator Perceptions of Rural versus Urban Instruction: A Case for Community-Centered Sexual Health Education

ERIC Educational Resources Information Center

Jones, Christina L.; Jensen, Robin E.; Selzer King, Abigail

2014-01-01

Instructors of sexual health courses in rural areas face unique challenges as they are often forced to use school-based prevention curricula field-tested in urban areas. Research has yet to consider what future sex educators' regional expectations are for their profession and how those expectations might have an impact on the classroom. Drawing…

Navigating the Turbulent Seas of Education Reform for English Language Learners: How Leadership Affects Teacher Quality and Educational Opportunity

ERIC Educational Resources Information Center

da Silva, Catarina Alexandra

2010-01-01

The purpose of this case study was to provide insight into the challenges educational leaders face in their efforts to improve teaching and learning for English language learners within a context of increased testing and accountability. I examine the assumptions underpinning leadership practices to understand how teacher quality and student…

Scheduling Mission-Critical Flows in Congested and Contested Airborne Network Environments

DTIC Science & Technology

2018-03-01

precision agriculture [64–71]. However, designing, implementing, and testing UAV networks poses numerous interdisciplinary challenges because the...applications including search and rescue, disaster relief, precision agriculture , environmental monitoring, and surveillance. Many of these applications...monitoring enabling precision agriculture ,” in Automation Science and Engineering (CASE), 2015 IEEE International Conference on. IEEE, 2015, pp. 462–469. [65

Real-time Affective Indices of Potential CRM Breakdown: Qualitative Testing of an Operational Hypothesis

NASA Technical Reports Server (NTRS)

Dickerson, Mark

2007-01-01

This viewgraph presentation begins by showing several cases where poor crew resource management (CRM) resulted in aircraft accidents. The presenter reviews the emotional states that are present in a situation that frequently leads to an accident. The operational answer suggested is given as an acronym: PACE, which stand for Probe, Alert, Challenge, Emergency Action.

First Year Engagement & Retention: A Goal-Setting Approach

ERIC Educational Resources Information Center

Tuffley, David; Antonio, Amy

2013-01-01

First year students face a daunting range of challenges as they make the transition to university life. Their experiences in the first months of university have a defining influence on their success or otherwise in their studies. The purpose of this paper is to report on the results of a case study that tests the efficacy of a student engagement…

Exploring the Downside of Open Knowledge Resources: The Case of Indigenous Knowledge Systems and Practices in the Philippines

ERIC Educational Resources Information Center

Flor, Alexander Gonzalez

2013-01-01

The paper is based on the challenges encountered by the researcher while conducting a study titled "Design, Development and Testing of an Indigenous Knowledge Management System Using Mobile Device Video Capture and Web 2.0 Protocols." During the conduct of the study the researcher observed a marked reluctance from organized indigenous…

Motivating Grade 1 Children to Read: Exploring the Role of Choice, Curiosity, and Challenge in Mobile Ebooks

ERIC Educational Resources Information Center

Ciampa, Katia

2016-01-01

A pre-experimental case study design was used to explore the value of intrinsic motivation in mobile eBook reading among 30 Grade 1 child participants. Data collection comprised pre- and post-test motivation questionnaires and researcher field notes. Child participants' enjoyment of mobile eBooks corresponded to 3 motivational aspects of intrinsic…

Physicians’ Perspectives on the Uncertainties and Implications of Chromosomal Microarray Testing of Children and Families

PubMed Central

Reiff, Marian; Ross, Kathryn; Mulchandani, Surabhi; Propert, Kathleen Joy; Pyeritz, Reed E.; Spinner, Nancy B.; Bernhardt, Barbara A.

2012-01-01

Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians’ perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians’ comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings. PMID:22989118

Structural and Kinetic Characterization of the Intrinsically Disordered Protein SeV NTAIL through Enhanced Sampling Simulations.

PubMed

Bernetti, Mattia; Masetti, Matteo; Pietrucci, Fabio; Blackledge, Martin; Jensen, Malene Ringkjobing; Recanatini, Maurizio; Mollica, Luca; Cavalli, Andrea

2017-10-19

Intrinsically disordered proteins (IDPs) are emerging as an important class of the proteome. Being able to interact with different molecular targets, they participate in many physiological and pathological activities. However, due to their intrinsically heterogeneous nature, determining the equilibrium properties of IDPs is still a challenge for biophysics. Herein, we applied state-of-the-art enhanced sampling methods to Sev N TAIL , a test case of IDPs, and constructed a bin-based kinetic model to unveil the underlying kinetics. To validate our simulation strategy, we compared the predicted NMR properties against available experimental data. Our simulations reveal a rough free-energy surface comprising multiple local minima, which are separated by low energy barriers. Moreover, we identified interconversion rates between the main kinetic states, which lie in the sub-μs time scales, as suggested in previous works for Sev N TAIL . Therefore, the emerging picture is in agreement with the atomic-level properties possessed by the free IDP in solution. By providing both a thermodynamic and kinetic characterization of this IDP test case, our study demonstrates how computational methods can be effective tools for studying this challenging class of proteins.

Cementum as a source of DNA in challenging forensic cases.

PubMed

Mansour, Hussam; Krebs, Oliver; Sperhake, Jan Peter; Augustin, Christa; Koehne, Till; Amling, Michael; Püschel, Klaus

2018-02-01

Each forensic case is characterized by its own uniqueness. Deficient forensic cases require additional sources of human identifiers to assure the identity. We report on two different cases illustrating the role of teeth in answering challenging forensic questions. The first case involves identification of an adipocere male found in a car submersed in water for approximately 2 years. The second scenario, which involves paternity DNA testing of an exhumed body, was performed approximately 2.8 years post-mortem. The difficulty in anticipating the degradation of the DNA is one of the main obstacles. DNA profiling of dental tissues, DNA quantification by using real-time PCR (PowerQuant™ System/Promega) and a histological dental examination have been performed to address the encountered impediments of adverse post-mortem changes. Our results demonstrate that despite the adverse environmental conditions, a successful STR profile of DNA isolated from the root of teeth can be generated with respect to tooth type and apportion. We conclude that cementocytes are a fruitful source of DNA. Cementum resists DNA degradation in comparison to other tissues with respect to the intra- and inter-individual variation of histological and anatomical structures. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Point-of-care diagnostics: extending the laboratory network to reach the last mile.

PubMed

Drain, Paul K; Rousseau, Christine

2017-03-01

More point-of-care (POC) diagnostic tests are becoming available for HIV diagnosis and treatment in resource-limited settings. These novel technologies have the potential to foster decentralized HIV care and treatment for the benefit of clinical laboratories, HIV clinics, and HIV-infected patients. There continue to be many business, technological, and operational challenges that limit product development and regulatory approval, which limits products available for the required operational and cost-effectiveness studies and delays policy adoption and implementation. Although the rapid HIV diagnostic test has been widely successful, the pathways for POC CD4 cell count and HIV viral load assay analyzers have been more challenging. We describe significant hurdles for product development, approval, and implementation, which include the business case, technical development, clinical impact, and integrating laboratory and clinical networks. The objective of this review is to highlight the obstacles for developing and implementing appropriate strategies for POC HIV testing assays to improve the clinical services for HIV-infected patients in resource-limited settings.

First Nine Cases of Candida auris Infection Reported in Central America: Importance of Acurate Diagnosis and Susceptibility Testing

PubMed Central

Rodriguez, Ana Belen Arauz; Caceres, Diego H; Santiago, Erika; Armstrong, Paige; French, Amalia Rodriguez; Arosemena, Susan; Ramos, Carolina; Espinosa-Bode, Andres; Borace, Jovanna; Hayer, Lizbeth; Cedeño, Israel; Sosa, Nestor; Berkow, Elizabeth L; Lockhart, Shawn R; Jackson, Brendan R; Chiller, Tom

2017-01-01

Abstract Background Candida auris is an emerging multidrug-resistant pathogen associated with invasive infections and high mortality. This report describes the first 9 cases of C. auris in Central America in a hospital in Panama City, Panama, and highlights the challenges of accurate identification and methods for susceptibility testing. Methods Isolates initially identified at a Panama City acute care hospital during July–October 2016 as Candida haemulonii (a common misidentification for C. auris) or Candida species by Vitek® 2 automated system (bioMérieux) were further characterized by molecular methods. Antifungal susceptibility testing was performed and results were compared between standard and reference methodologies. Patient demographic, clinical, and laboratory data were collected from the medical record. Results A total of 14 isolates from 9 hospitalized patients were confirmed as C. auris. Isolates were from urine (11), blood (1), catheter tip (1) and pleural fluid (1). Results of susceptibility testing were highly discrepant between automated and reference techniques for fluconazole (92% resistant vs. 77%, respectively) and amphotericin B (100% vs. 8%). Six (67%) patients were male, and the mean age was 53 years (range 42–78). All patients were admitted to the intensive care unit and were mechanically ventilated. Seven (78%) patients died. Conclusion C. auris is present in Central America. Healthcare facilities in the region should be vigilant for this concerning pathogen, particularly given challenges in its identification and need for infection control precautions. Although automated testing overestimated amphotericin B resistance, most initial isolates were susceptible by reference testing. Disclosures All authors: No reported disclosures.

Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, northeast Kenya, March-July 2005.

PubMed

Ari, Mary D; Guracha, Argata; Fadeel, Moustafa Abdel; Njuguna, Charles; Njenga, M Kariuki; Kalani, Rosalia; Abdi, Hassan; Warfu, Osman; Omballa, Victor; Tetteh, Christopher; Breiman, Robert F; Pimentel, Guillermo; Feikin, Daniel R

2011-11-01

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed.

Challenges of Establishing the Correct Diagnosis of Outbreaks of Acute Febrile Illnesses in Africa: The Case of a Likely Brucella Outbreak among Nomadic Pastoralists, Northeast Kenya, March–July 2005

PubMed Central

Ari, Mary D.; Guracha, Argata; Fadeel, Moustafa Abdel; Njuguna, Charles; Njenga, M. Kariuki; Kalani, Rosalia; Abdi, Hassan; Warfu, Osman; Omballa, Victor; Tetteh, Christopher; Breiman, Robert F.; Pimentel, Guillermo; Feikin, Daniel R.

2011-01-01

An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed. PMID:22049048

IN SEARCH OF A FATHER: LEGAL CHALLENGES SURROUNDING POSTHUMOUS PATERNITY TESTING.

PubMed

Stirton, Ruth H; Wilkinson, Mark J

2015-01-01

This article interrogates the workings of the Human Tissue Act 2004, as it applies to paternity testing by DNA analysis after the death of the putative father. We use a case series methodology more usually seen in medical research, through which we present three real case studies involving posthumous paternity testing of retained tissue. We argue that the criminal offence in section 45 of the Human Tissue Act 2004, which is being used to regulate this activity, is inappropriate and inadequate to do so. The threat of the shadow of the criminal law is too blunt an instrument to address the subtleties of the issues that arise in the context of posthumous paternity testing. We call for reform of the Human Tissue Act 2004 and the creation of a specific exception to properly deal with requests of this nature. © The Author 2015. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypersensitivity reaction to mizolastine: study of cross reactions.

PubMed

Gonzalo-Garijo, M A; Jiménez-Ferrera, G; Bobadilla-González, P; Cordobés-Durán, C

2006-01-01

A 26-year-old male suffering from acute rhinitis took the first dose of Zolistan (mizolastine, 10 mg), orally, and 15 minutes later he developed intense generalized pruritus, cutaneous rash, oropharyngeal pruritus, edema on his face, difficulty in swallowing, and mild dyspnea. He was treated with methylprednisolone and epinephrine and improved within 30 minutes. The patient had not taken mizolastine before and he has avoided it since the reaction. Cutaneous tests with Zolistan and its excipients proved negative. Simple-blind oral challenge tests with the excipients and then with Zolistan were positive only with Zolistan. In order to confirm the absence of cross-reactivity between mizolastine and other benzimidazoles, we tested omeprazole, domperidone and mebendazole, all of which yielded negative results. To our knowledge, this is the second case of immediate hypersensitivity to mizolastine documented to date. In our case, the clinical history, physical examination and provocation tests allow us to establish the diagnosis of hypersensitivity to mizolastine and exclude the cross reactivity with other benzimidazole derivatives.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Clinical significance of atypical glandular cells in Pap tests: An analysis of more than 3000 cases at a large academic women's center.

PubMed

Pradhan, Dinesh; Li, Zaibo; Ocque, Rebecca; Patadji, Stell; Zhao, Chengquan

2016-08-01

The interpretation of atypical glandular cells (AGC) in Papanicolaou (Pap) tests and screening for glandular neoplasia remain challenging. Pap tests with an AGC interpretation from January 2008 to December 2013 were retrieved from a pathology database, and cases with histologic follow-up within 1 year were included in the study. There were 589,830 Pap tests during the study period, and 3709 cases (0.6%) were reported as AGC, which included the following: AGC, not otherwise specified (52.0%); atypical endocervical cells (28.0%); and other categories. There were 3007 cases (81.1%) with histologic follow-up results within 1 year. Cervical intraepithelial neoplasia 2/3 (CIN2/3), cervical adenocarcinoma in situ (AIS)/adenocarcinoma, and endometrial carcinoma were identified in 5.6%, 1.9%, and 5.5% of cases, respectively. Glandular neoplasia was more likely to be identified in cases with pure AGC subcategories than cases with AGC and squamous abnormalities. Endometrial neoplasia was more likely to be identified in cases with atypical endometrial cells than other categories. Overall, the most common severe abnormality on histologic follow-up was CIN2/3. Although CIN2/3 was the most common severe lesion in patients younger than 30 years (10.0%) and in patients aged 30 to 49 years (6.4%), endometrial carcinoma was the most common lesion in women who were 50 years old or older (13.7%). Endocervical glandular lesions (AIS and adenocarcinoma) occurred in only 1.9% of women. AGC subtypes and ages significantly affect histological follow-up results; 90.5% of cases with carcinoma on histologic follow-up were either endometrial or metastatic carcinoma. This study supports the recommendation that women with AGC Pap test results should be followed up with both endocervical and endometrial sampling. Cancer Cytopathol 2016;124:589-95. © 2016 American Cancer Society. © 2016 American Cancer Society.

Should sputum-negative presumptive TB patients be actively followed to identify missing cases in India?

PubMed

Waikar, S; Pathak, A; Ghule, V; Kapoor, A; Sagili, K; Babu, E R; Chadha, S

2017-12-21

Setting: Sputum smear microscopy, the primary diagnostic tool used for diagnosis of tuberculosis (TB) in India's Revised National TB Control Programme (RNTCP), has low sensitivity, resulting in a significant number of TB cases reported as sputum-negative. As the revised guidelines pose challenges in implementation, sputum-negative presumptive TB (SNPT) patients are subjected to 2 weeks of antibiotics, followed by chest X-ray (CXR), resulting in significant loss to care among these cases. Objective: To determine whether reducing delays in CXR would yield additional TB cases and reduce initial loss to follow-up for diagnosis among SNPT cases. Methods: In an ongoing intervention in five districts of Maharashtra, SNPT patients were offered upfront CXR. Results: Of 119 male and 116 female SNPT patients with a mean age of 45 years who were tested by CXR, 32 (14%) were reported with CXR suggestive of TB. Administering upfront CXR in SNPT patients yielded twice as many additional cases, doubling the proportion of cases detected among all those tested as against administering CXR 2 weeks after smear examination. Conclusion: Our interventional study showed that the yield of TB cases was significantly greater when upfront CXR examination was undertaken without waiting for a 2-week antibiotic trial.

Use of existing systematic reviews for evidence assessments in infectious disease prevention: a comparative case study.

PubMed

Harder, Thomas; Remschmidt, Cornelius; Haller, Sebastian; Eckmanns, Tim; Wichmann, Ole

2016-10-11

Given limited resources and time constraints, the use of existing systematic reviews (SR) for the development of evidence-based public health recommendations has become increasingly important. Recently, a five-step approach for identifying, analyzing, appraising and using existing SRs based on recent guidance by the US Agency for Healthcare Research and Quality (AHRQ) was proposed within the Project on a Framework for Rating Evidence in Public Health (PRECEPT). However, case studies are needed to test whether this approach is useful, what challenges arise and how problems can be solved. In two case studies, the five-step approach was applied to integrate existing SRs in the development of evidence-based public health recommendations. Case study A focused on the role of neonatal sepsis as a risk factor for adverse neurodevelopmental outcome. Case study B examined the efficacy, effectiveness and safety of influenza vaccination during pregnancy. For each step, we report the approach of the review team, discuss challenges and describe solutions. For case study A, one existing SR was identified, while in case study B four SRs were eligible for analysis. We found that comparison of inclusion criteria alone was sufficient to judge on relevance of SRs in case study A, but not B. Although methodological quality of all identified SRs was acceptable, risk of bias assessments of individual studies included in the SRs had to be repeated in both case studies. Particular challenges appeared in case study B where multiple SRs addressed the same research question. With the help of spreadsheets comparing the characteristics of the existing SR we decided to use the most comprehensive one for our evidence synthesis and supplemented the results with those from the other SRs. In both case studies using the complete SR was not possible. The five-step approach provided useful and structured guidance and should be routinely applied when using existing SRs as a basis for evidence-based recommendations in public health. In situations where more than one SR has to be considered, the development of spreadsheets comparing characteristics, inclusion criteria, risk of bias, included studies and outcomes seems useful.

Recycled poly(ethylene terephthalate) for direct food contact applications: challenge test of an inline recycling process.

PubMed

Franz, R; Welle, F

2002-05-01

Of all the plastics used for packaging, due to its low diffusivity and chemical inertness, poly(ethylene terephthalate) (PET) is one of the favoured candidate plastics for closed-loop recycling for new packaging applications. In the work reported here, a PET-recycling process was investigated with respect to its cleaning efficiency and compliance of the PET recyclate with food law. The key technology of the investigated PET-recycling process to remove contaminants consists of a predecontamination-extruder combination. At the end of the recycling process, there is either a pelletizing system or downstream equipment to produce preforms or flat sheets. Therefore, the process has two process options, an inline production of PET preforms and a batch option producing PET pellets. In the case of possible misuse of PET bottles by the consumer, the inline process produces higher concentrations in the bottle wall of the recyclate containing preforms. Owing to the dilution of the PET output material by large amounts of uncontaminated PET, the batch option is the less critical process in terms of consumer protection. Regarding an appropriate testing procedure for the evaluation of a bottle-to-bottle recycling process, both process options have their own specific requirements with respect to the design of a challenge test. A novel challenge test approach to the inline mode of a recycling process is presented here.

Lessons learned in induced fit docking and metadynamics in the Drug Design Data Resource Grand Challenge 2

NASA Astrophysics Data System (ADS)

Baumgartner, Matthew P.; Evans, David A.

2018-01-01

Two of the major ongoing challenges in computational drug discovery are predicting the binding pose and affinity of a compound to a protein. The Drug Design Data Resource Grand Challenge 2 was developed to address these problems and to drive development of new methods. The challenge provided the 2D structures of compounds for which the organizers help blinded data in the form of 35 X-ray crystal structures and 102 binding affinity measurements and challenged participants to predict the binding pose and affinity of the compounds. We tested a number of pose prediction methods as part of the challenge; we found that docking methods that incorporate protein flexibility (Induced Fit Docking) outperformed methods that treated the protein as rigid. We also found that using binding pose metadynamics, a molecular dynamics based method, to score docked poses provided the best predictions of our methods with an average RMSD of 2.01 Å. We tested both structure-based (e.g. docking) and ligand-based methods (e.g. QSAR) in the affinity prediction portion of the competition. We found that our structure-based methods based on docking with Smina (Spearman ρ = 0.614), performed slightly better than our ligand-based methods (ρ = 0.543), and had equivalent performance with the other top methods in the competition. Despite the overall good performance of our methods in comparison to other participants in the challenge, there exists significant room for improvement especially in cases such as these where protein flexibility plays such a large role.

A multilevel meta-analysis of single-case and small-n research on interventions for reducing challenging behavior in persons with intellectual disabilities.

PubMed

Heyvaert, M; Maes, B; Van den Noortgate, W; Kuppens, S; Onghena, P

2012-01-01

The effectiveness of different interventions for challenging behavior (CB) in persons with intellectual disabilities (ID) was reviewed by means of a two-phase study. First, a systematic review of 137 meta-analyses and reviews on group-study interventions for CB in persons with ID was conducted. Based on this review, hypotheses concerning the effectiveness of divergent interventions for CB and concerning the impact of variables moderating treatment effectiveness were systematically generated. Second, these hypotheses were tested by means of a multilevel meta-analysis of single-case and small-n research. Two hundred and eighty-five studies reporting on 598 individuals were examined. The average treatment effect was large and statistically significant. However, this effect varied significantly over the included studies and participants. Compared to the meta-analyses and reviews focusing on group-studies in this research domain, the results of the present multilevel meta-analysis of single-case and small-n intervention research provided more detailed knowledge on which specific CB and intervention components moderate the interventions' effectiveness. Copyright © 2011 Elsevier Ltd. All rights reserved.

Challenges with diagnosing and investigating suspected active tuberculosis disease in military trainees.

PubMed

Chang, David; Webber, Bryant J; Hetrick, Steven M; Owen, Jerry B; Blasi, Audra A; Steele, Bernadette M; Yun, Heather C

2017-08-01

Between 1 January 2010 and 31 December 2016, a total of 14 U.S. and international military personnel in training at Joint Base San Antonio-Lackland, TX, were hospitalized due to suspected pulmonary tuberculosis (TB); of these, five personnel were diagnosed with active TB disease. Only one TB case had pulmonary symptoms, but these symptoms were not suggestive of TB. The incidence rate in the training population was 1.89 per 100,000 population (95% CI: 0.81, 4.42), with a higher rate when restricted to international military students attending the Defense Language Institute English Language Center. No instances of TB transmission were identified. The variety of atypical presentations and their resulting diagnostic and public health challenges prompted this retrospective review of all hospitalized cases. This case series highlights both the importance of a high index of clinical suspicion when TB is being considered in close congregate settings as well as the risk of overreliance on acid-fast bacilli staining and nucleic acid amplification testing for ruling out active pulmonary disease in young, otherwise healthy trainees. Practical solutions are suggested.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012–2013

PubMed Central

Zucker, Jane R.; Giancotti, Francesca R.; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L.; Rosen, Jennifer B.

2017-01-01

ABSTRACT The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. PMID:28701468

Active Case Finding for Communicable Diseases in Prison Settings: Increasing Testing Coverage and Uptake Among the Prison Population in the European Union/European Economic Area

PubMed Central

Vroling, Hilde; Babudieri, Sergio; Monarca, Roberto; Vonk Noordegraaf-Schouten, Marije; Beer, Netta; Gomes Dias, Joana; O’Moore, Éamonn; Hedrich, Dagmar; Oordt-Speets, Anouk

2018-01-01

Abstract Prison populations are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors. Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs. We investigated the available evidence on modalities and effectiveness of active case-finding interventions in prisons by searching PubMed, Embase, and the Cochrane Library for records on prison and active case finding with no language limit. Conference abstracts and unpublished research reports also were retrieved. We analyzed the findings by testing modality, outcomes, and study quality. The included 90 records—63 peer-reviewed, 26 from gray literature, and 1 systematic review—reported variously on viral hepatitis, human immunodeficiency virus, sexually transmitted infections, and tuberculosis. No records were retrieved for other communicable diseases. Provider-initiated opt-in testing was the most frequently investigated modality. Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges. However, no comparative studies were identified that reported statistically significant differences between testing modalities. Positivity rates among tested inmates ranged broadly but were generally high for all diseases. The evidence on active case finding in correctional facilities is limited, heterogeneous, and of low quality, making it challenging to draw conclusions on the effect of different testing modalities. Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and, hence, prevent additional disease transmission in both prison settings and the community at large. PMID:29648594

Carol Anne Bond v the United States of America: how a woman scorned threatened the Chemical Weapons Convention.

PubMed

Muldoon, Anna; Kornblet, Sarah; Katz, Rebecca

2011-09-01

The case of Carol Anne Bond v the United States of America stemmed from a domestic dispute when Ms. Bond attempted to retaliate against her best friend by attacking her with chemical agents. What has emerged is a much greater issue--a test of standing on whether a private citizen can challenge the Tenth Amendment. Instead of being prosecuted in state court for assault, Ms. Bond was charged and tried in district court under a federal criminal statute passed as part of implementation of the Chemical Weapons Convention (CWC). Ms. Bond's argument rests on the claim that the statute exceeded the federal government's enumerated powers in criminalizing her behavior and violated the Constitution, while the government contends legislation implementing treaty obligations is well within its purview. This question remains unanswered because there is dispute among the lower courts as to whether Ms. Bond, as a citizen, even has the right to challenge an amendment guaranteeing states rights when a state is not a party to the action. The Supreme Court heard the case on February 22, 2011, and, if it decides to grant Ms. Bond standing to challenge her conviction, the case will be returned to the lower courts. Should the court decide Ms. Bond has the standing to challenge her conviction and further questions the constitutionality of the law, it would be a significant blow to implementation of the CWC in the U.S. and the effort of the federal government to ensure we are meeting our international obligations.

Evidence-Informed, Individual Treatment of a Child with Sexual Behavior Problems: A Case Study.

PubMed

Allen, Brian; Berliner, Lucy

2015-11-01

Children with sexual behavior problems pose a significant challenge for community-based mental health clinicians. Very few clinical trials are available to guide intervention and those interventions that are available are based in a group format. The current case study demonstrates the application of evidence-informed treatment techniques during the individual treatment of a 10-year-old boy displaying interpersonal sexual behavior problems. Specifically, the clinician adapts and implements a group-based model developed and tested by Bonner et al. (1999) for use with an individual child and his caregivers. Key points of the case study are discussed within the context of implementing evidence-informed treatments for children with sexual behavior problems.

Facing the challenges of ventricular hypertrophy: the eyes don't lie.

PubMed

Rodrigues, Patrícia; Santos, Mário; Marinho, António; Cabral, Sofia; Vieira, Miguel; Reis, Hipólito; Palma, Paulo; Torres, Severo

2014-10-01

We describe the case of a 47-year-old man with new-onset heart failure who was found to have severe biventricular wall thickening. We present comprehensive data from invasive and non-invasive multimodality imaging, genetic and histologic tests, and briefly describe their importance in the final diagnosis. To our knowledge, this is the first case of the Portuguese variant of familial amyloid polyneuropathy presenting with heart failure in the fifth decade of life. This is an unusual case report, but also an illustration of how to approach any patient with suspected infiltrative cardiomyopathy. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Role of bilateral inferior petrosal sinus sampling (BIPSS) in the diagnosis of Cushing’s disease in a patient with double superior vena cava

PubMed Central

Tashi, Sonam; Ng, Keng Sin

2015-01-01

Cushing’s syndrome is known to have a wide spectrum of clinical presentation with debilitating consequences and morbidity if not diagnosed and treated in time. Sometimes the diagnosis of Cushing’s syndrome can be challenging to the endocrinologist, especially when the usual battery of biochemical tests and advanced cross-sectional imaging is negative or inconclusive. We described a case in which the use of bilateral inferior petrosal sinus sampling (BIPSS) was conclusive albeit being technically challenging (due to a rare incidental finding of double superior vena cava) and invasive in nature. PMID:26629301

Heparin allergy: delayed-type non-IgE-mediated allergic hypersensitivity to subcutaneous heparin injection.

PubMed

Trautmann, Axel; Seitz, Cornelia S

2009-08-01

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and clinical symptoms of delayed-type non-IgE-mediated allergic hypersensitivity (DTH) to heparin. For diagnosis, intradermal, patch, and subcutaneous challenge tests with heparins are suitable. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement because of extensive cross-reactivity. Hirudin polypeptides, which exhibit a different chemical structure, are a safe therapeutic alternative for subcutaneous application, however. Importantly, despite DTH to subcutaneously injected heparins, most patients tolerate heparin intravenously. Moreover, in case of therapeutic necessity and DTH to heparins, the simple shift from subcutaneous to intravenous heparin administration without prior testing may be justified.

Analysis of selected data from the triservice missile data base

NASA Technical Reports Server (NTRS)

Allen, Jerry M.; Shaw, David S.; Sawyer, Wallace C.

1989-01-01

An extremely large, systematic, axisymmetric-body/tail-fin data base has been gathered through tests of an innovative missile model design which is described herein. These data were originally obtained for incorporation into a missile aerodynamics code based on engineering methods (Program MISSILE3), but these data are also valuable as diagnostic test cases for developing computational methods because of the individual-fin data included in the data base. Detailed analyses of four sample cases from these data are presented to illustrate interesting individual-fin force and moment trends. These samples quantitatively show how bow shock, fin orientation, fin deflection, and body vortices can produce strong, unusual, and computationally challenging effects on individual fin loads. Flow-visualization photographs are examined to provide physical insight into the cause of these effects.

Barriers to community case management of malaria in Saraya, Senegal: training, and supply-chains.

PubMed

Blanas, Demetri A; Ndiaye, Youssoupha; Nichols, Kim; Jensen, Andrew; Siddiqui, Ammar; Hennig, Nils

2013-03-14

Health workers in sub-Saharan Africa can now diagnose and treat malaria in the field, using rapid diagnostic tests and artemisinin-based combination therapy in areas without microscopy and widespread resistance to previously effective drugs. This study evaluates communities' perceptions of a new community case management of malaria programme in the district of Saraya, south-eastern Senegal, the effectiveness of lay health worker trainings, and the availability of rapid diagnostic tests and artemisinin-based combination therapy in the field. The study employed qualitative and quantitative methods including focus groups with villagers, and pre- and post-training questionnaires with lay health workers. Communities approved of the community case management programme, but expressed concern about other general barriers to care, particularly transportation challenges. Most lay health workers acquired important skills, but a sizeable minority did not understand the rapid diagnostic test algorithm and were not able to correctly prescribe arteminisin-based combination therapy soon after the training. Further, few women lay health workers participated in the programme. Finally, the study identified stock-outs of rapid tests and anti-malaria medication products in over half of the programme sites two months after the start of the programme, thought due to a regional shortage. This study identified barriers to implementation of the community case management of malaria programme in Saraya that include lay health worker training, low numbers of women participants, and generalized stock-outs. These barriers warrant investigation into possible solutions of relevance to community case management generally.

Occupational asthma in the furniture industry: is it due to styrene?

PubMed

Oner, Ferda; Mungan, Dilşad; Numanoglu, Numan; Demirel, Yavuz

2004-01-01

Styrene, a volatile monomer, has been reported as a cause of occupational asthma in a few case reports. The aim of this study was to investigate the risk for asthma in relation to exposure to styrene in a large number of workers. A total of 47 workers with a history of exposure to styrene were included in the study. To establish whether asthma was present, each patient underwent a clinical interview, pulmonary function testing and bronchial challenge with methacholine. Specific bronchial challenges with styrene and serial peak expiratory flow (PEF) measurement at home and at work were carried out in subjects with a diagnosis of asthma to evaluate the relationship between their asthma and exposure to styrene in the workplace. Among the 47 subjects, 5 workers had given a history of work-related symptoms, and 3 of them had a positive methacholine challenge test. Specific bronchial challenges with styrene and serial PEF measurement were subsequently carried out in these 3 subjects. Although provocation tests with styrene were negative in the 3 workers, 1 worker had PEF rate records compatible with occupational asthma. We established one patient with occupational asthma from a group of people who have excessive styrene exposure. This finding may be suggestive but is not conclusive about the causative role of styrene in occupational asthma. Since styrene is a frequently used substance in the furniture industry, it is worth performing further studies to investigate the relationship between styrene and occupational asthma. Copyright 2004 S. Karger AG, Basel

Diagnostic approach in cases with suspected work-related asthma

PubMed Central

2013-01-01

Background Work-related asthma (WRA) is a major cause of respiratory disease in modern societies. The diagnosis and consequently an opportunity for prevention are often missed in practice. Methods Based on recent studies and systematic reviews of the literature methods for detection of WRA and identification of specific causes of allergic WRA are discussed. Results and Conclusions All workers should be asked whether symptoms improve on days away from work or on holidays. Positive answers should lead to further investigation. Spirometry and non-specific bronchial responsiveness should be measured, but carefully performed and validly analysed serial peak expiratory flow or forced expiratory volume in one second (FEV1) measurements are more specific and confirm occupational asthma in about 82% of those still exposed to the causative agent. Skin prick testing or specific immunoglobulin E assays are useful to document allergy to high molecular weight allergens. Specific inhalational challenge tests come closest to a gold standard test, but lack standardisation, availability and sensitivity. Supervised workplace challenges can be used when specific challenges are unavailable or the results non-diagnostic, but methodology lacks standardisation. Finally, if the diagnosis remains unclear a follow-up with serial measurements of FEV1 and non-specific bronchial hyperresponsiveness should detect those likely to develop permanent impairment from their occupational exposures. PMID:23768266

Injection of a Body into a Geodesic: Lessons Learnt from the LISA Pathfinder Case

NASA Technical Reports Server (NTRS)

Bortoluzzi, Daniele; Armano, M.; Audley, H.; Auger, G.; Baird, J.; Binetruy, P.; Born, M.; Bortoluzzi, D.; Brandt, N.; Bursi, A.;

Accelerated Schools as Learning Organizations: Cases from the University of New Orleans Accelerated School Network.

ERIC Educational Resources Information Center

Brunner, Ilse; And Others

Organizations are the product of the ideas and interactions of those who work in them. The challenge for learning in organizations is to have a shared purpose and vision of the organization, to develop new ideas arising out of the vision and purpose, to test the ideas in the organizational reality, and to communicate that knowledge to other…

Targeted selection of brownfields from portfolios for sustainable regeneration: User experiences from five cases testing the Timbre Brownfield Prioritization Tool.

PubMed

Bartke, Stephan; Martinát, Stanislav; Klusáček, Petr; Pizzol, Lisa; Alexandrescu, Filip; Frantál, Bohumil; Critto, Andrea; Zabeo, Alex

2016-12-15

Prioritizing brownfields for redevelopment in real estate portfolios can contribute to more sustainable regeneration and land management. Owners of large real estate and brownfield portfolios are challenged to allocate their limited resources to the development of the most critical or promising sites, in terms of time and cost efficiency. Authorities worried about the negative impacts of brownfields - in particular in the case of potential contamination - on the environment and society also need to prioritize their resources to those brownfields that most urgently deserve attention and intervention. Yet, numerous factors have to be considered for prioritizing actions, in particular when adhering to sustainability principles. Several multiple-criteria decision analysis (MCDA) approaches and tools have been suggested in order to support these actors in managing their brownfield portfolios. Based on lessons learned from the literature on success factors, sustainability assessment and MCDA approaches, researchers from a recent EU project have developed the web-based Timbre Brownfield Prioritization Tool (TBPT). It facilitates assessment and prioritization of a portfolio of sites on the basis of the probability of successful and sustainable regeneration or according to individually specified objectives. This paper introduces the challenges of brownfield portfolio management in general and reports about the application of the TBPT in five cases: practical test-uses by two large institutional land owners from Germany, a local and a regional administrative body from the Czech Republic, and an expert from a national environmental authority from Romania. Based on literature requirements for sustainability assessment tools and on the end-users' feedbacks from the practical tests, we discuss the TBPT's strengths and weaknesses in order to inform and give recommendations for future development of prioritization tools. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry.

PubMed

Nagarajan, P; Tetzlaff, M T; Curry, J L; Prieto, V G

Melanoma remains one of the most aggressive forms of cutaneous malignancies. While its diagnosis based on histologic parameters is usually straight forward in most cases, distinguishing a melanoma from a melanocytic nevus can be challenging in some instances, especially when there are overlapping clinical and histopathologic features. Occasionally, melanomas can histologically mimic other tumors and even demonstration of melanocytic origin can be challenging. Thus, several ancillary tests may be employed to arrive at the correct diagnosis. The objective of this review is to summarize these tests, including the well-established and commonly used ones such as immunohistochemistry, with specific emphasis on emerging techniques such as comparative genomic hybridization, fluorescence in situ hybridization and imaging mass spectrometry. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of a chromosome X STR Decaplex in deficiency paternity cases.

PubMed

Trindade-Filho, Aluisio; Ferreira, Samuel; Oliveira, Silviene F

2013-12-01

Deficiency paternity cases, characterized by the absence of the alleged father, are a challenge for forensic genetics. Here we present four cases with a female child and a deceased alleged father in which the analysis of a set of 21 or 22 autosomal STRs (AS STRs) produced results within a range of doubt when genotyping relatives of the alleged father. Aiming to increase the Paternity Index (PI) and obtain more reliable results, a set of 10 X-linked STR markers, developed by the Spanish and Portuguese Group of the International Society for Forensic Genetics (ISFG), was then added. Statistical analysis substantially shifted the results towards the alleged fatherhood in all four cases, with more dramatic changes when the supposed half-sister and respective mother were the relatives tested.

Impact of a chromosome X STR Decaplex in deficiency paternity cases

PubMed Central

Trindade-Filho, Aluisio; Ferreira, Samuel; Oliveira, Silviene F.

2013-01-01

Deficiency paternity cases, characterized by the absence of the alleged father, are a challenge for forensic genetics. Here we present four cases with a female child and a deceased alleged father in which the analysis of a set of 21 or 22 autosomal STRs (AS STRs) produced results within a range of doubt when genotyping relatives of the alleged father. Aiming to increase the Paternity Index (PI) and obtain more reliable results, a set of 10 X-linked STR markers, developed by the Spanish and Portuguese Group of the International Society for Forensic Genetics (ISFG), was then added. Statistical analysis substantially shifted the results towards the alleged fatherhood in all four cases, with more dramatic changes when the supposed half-sister and respective mother were the relatives tested. PMID:24385853

EEG and Eye Tracking Demonstrate Vigilance Enhancement with Challenge Integration

PubMed Central

Bodala, Indu P.; Li, Junhua; Thakor, Nitish V.; Al-Nashash, Hasan

2016-01-01

Maintaining vigilance is possibly the first requirement for surveillance tasks where personnel are faced with monotonous yet intensive monitoring tasks. Decrement in vigilance in such situations could result in dangerous consequences such as accidents, loss of life and system failure. In this paper, we investigate the possibility to enhance vigilance or sustained attention using “challenge integration,” a strategy that integrates a primary task with challenging stimuli. A primary surveillance task (identifying an intruder in a simulated factory environment) and a challenge stimulus (periods of rain obscuring the surveillance scene) were employed to test the changes in vigilance levels. The effect of integrating challenging events (resulting from artificially simulated rain) into the task were compared to the initial monotonous phase. EEG and eye tracking data is collected and analyzed for n = 12 subjects. Frontal midline theta power and frontal theta to parietal alpha power ratio which are used as measures of engagement and attention allocation show an increase due to challenge integration (p < 0.05 in each case). Relative delta band power of EEG also shows statistically significant suppression on the frontoparietal and occipital cortices due to challenge integration (p < 0.05). Saccade amplitude, saccade velocity and blink rate obtained from eye tracking data exhibit statistically significant changes during the challenge phase of the experiment (p < 0.05 in each case). From the correlation analysis between the statistically significant measures of eye tracking and EEG, we infer that saccade amplitude and saccade velocity decrease with vigilance decrement along with frontal midline theta and frontal theta to parietal alpha ratio. Conversely, blink rate and relative delta power increase with vigilance decrement. However, these measures exhibit a reverse trend when challenge stimulus appears in the task suggesting vigilance enhancement. Moreover, the mean reaction time is lower for the challenge integrated phase (RTmean = 3.65 ± 1.4s) compared to initial monotonous phase without challenge (RTmean = 4.6 ± 2.7s). Our work shows that vigilance level, as assessed by response of these vital signs, is enhanced by challenge integration. PMID:27375464

Challenges to using a business case for addressing health disparities.

PubMed

Lurie, Nicole; Somers, Stephen A; Fremont, Allen; Angeles, January; Murphy, Erin K; Hamblin, Allison

2008-01-01

The authors consider the challenges to quantifying both the business case and the social case for addressing disparities, which is central to achieving equity in the U.S. health care system. They describe the practical and methodological challenges faced by health plans exploring the business and social cases for undertaking disparity-reducing interventions. Despite these challenges, sound business and quality improvement principles can guide health care organizations seeking to reduce disparities. Place-based interventions may help focus resources and engage health care and community partners who can share in the costs of-and gains from-such efforts.

Ibopamine challenge testing differentiates glaucoma suspect, stable glaucoma and progressive glaucoma cases.

PubMed

Landers, John; Ullrich, Katja; Craig, Jamie E

2015-12-01

An ibopamine challenge is a novel technique for assessing glaucoma using ibopamine, a topical drug which temporarily increases aqueous production. We aimed to determine whether change in intraocular pressure (IOP) and/or optic cup volume (OCV) during the test differentiated between glaucoma patients at different stages of disease; namely, glaucoma suspects (GS), glaucoma patients who are stable (SG) and glaucoma patients who have demonstrated rapid progression (PG). Non-randomized clinical trial evaluating a diagnostic test. Sixty-one patients were recruited through glaucoma clinics at the Flinders Medical Centre (24 GS, 24 SG and 13 PG). Patients underwent IOP measurement and OCV assessment using optical coherence tomography. Two drops of ibopamine 2% solution were instilled into the study eye of each patient. After 45 min, IOP and OCV were reassessed. Changes from baseline were compared between groups. Change in IOP and OCV after ibopamine challenge. Following the ibopamine challenge, IOP increased by 1.8 mmHg for GS patients, 4.5 mmHg for SG patients (P = 0.003) and 8.1 mmHg for PG patients (P < 0.0001). OCV increased by 0.2% for GS patients, 0.6% for SG patients and 5.5% for PG patients. This was not significantly different between GS patients and SG patients; however, it was significantly different between GS patients and PG patients (P < 0.0001), and between SG and PG patients (P = 0.001). GS patients may be differentiated from those with SG or PG by their IOP response, and SG may be differentiated from PG patients by their change in OCV following an ibopamine challenge. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Diagnosing a Failed Proof in Fault-Tolerance: A Disproving Challenge Problem

NASA Technical Reports Server (NTRS)

Pike, Lee; Miner, Paul; Torres-Pomales, Wilfredo

2006-01-01

This paper proposes a challenge problem in disproving. We describe a fault-tolerant distributed protocol designed at NASA for use in a fly-by-wire system for next-generation commercial aircraft. An early design of the protocol contains a subtle bug that is highly unlikely to be caught in fault injection testing. We describe a failed proof of the protocol's correctness in a mechanical theorem prover (PVS) with a complex unfinished proof conjecture. We use a model checking suite (SAL) to generate a concrete counterexample to the unproven conjecture to demonstrate the existence of a bug. However, we argue that the effort required in our approach is too high and propose what conditions a better solution would satisfy. We carefully describe the protocol and bug to provide a challenging but feasible case study for disproving research.

Deriving a no expected sensitization induction level for fragrance ingredients without animal testing: An integrated approach applied to specific case studies.

PubMed

Natsch, Andreas; Emter, Roger; Haupt, Tina; Ellis, Graham

2018-06-01

Cosmetic regulations prohibit animal testing for the purpose of safety assessment and recent REACH guidance states that the local lymph node assay (LLNA) in mice shall only be conducted if in vitro data cannot give sufficient information for classification and labelling. However, Quantitative Risk Assessment (QRA) for fragrance ingredients requires a NESIL, a dose not expected to cause induction of skin sensitization in humans. In absence of human data, this is derived from the LLNA and it remains a key challenge for risk assessors to derive this value from non-animal data. Here we present a workflow using structural information, reactivity data and KeratinoSens results to predict a LLNA result as a point of departure. Specific additional tests (metabolic activation, complementary reactivity tests) are applied in selected cases depending on the chemical domain of a molecule. Finally, in vitro and in vivo data on close analogues are used to estimate uncertainty of the prediction in the specific chemical domain. This approach was applied to three molecules which were subsequently tested in the LLNA and 22 molecules with available and sometimes discordant human and LLNA data. Four additional case studies illustrate how this approach is being applied to recently developed molecules in the absence of animal data. Estimation of uncertainty and how this can be applied to determine a final NESIL for risk assessment is discussed. We conclude that, in the data-rich domain of fragrance ingredients, sensitization risk assessment without animal testing is possible in most cases by this integrated approach.

Powassan Virus and Other Arthropod-Borne Viruses in Wildlife and Ticks in Ontario, Canada.

PubMed

Smith, Kathryn; Oesterle, Paul T; Jardine, Claire M; Dibernardo, Antonia; Huynh, Chris; Lindsay, Robbin; Pearl, David L; Bosco-Lauth, Angela M; Nemeth, Nicole M

2018-06-04

Powassan virus (POWV) is a tick-borne zoonosis maintained in natural enzootic cycles between ixodid ticks and wild mammals. Reported human cases have increased in recent years; these infections can be fatal or lead to long-term neurologic sequelae. However, both the geographic distribution and the role of common, potential mammalian hosts in POWV transmission are poorly understood, creating challenges to public health surveillance. We looked for evidence of POWV infection among candidate wildlife host species and ticks collected from mammals and birds in southern Ontario. Tissues (including blood) and ticks from trapped wild mammals were collected in the summers of 2015 and 2016. Ticks removed from dogs in 2015-2016 and wildlife diagnostic cases from 2011 to 2013 were also included. Tissue and tick ( Ixodes spp.) homogenates were tested for POWV by reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, sera from wild mammals were tested for antibodies to POWV, West Nile virus (WNV), and heartland virus (HRTV) by plaque reduction neutralization test. All 724 tissue samples were negative for POWV by RT-PCR. One of 53 pools of Ixodes cookei (among 98 total tick pools) was RT-PCR positive for deer tick virus (POWV) lineage. Antibodies to POWV and WNV were detected in 0.4% of 265 and 6.1% of 264 samples, respectively, and all of 219 serum samples tested negative for anti-HRTV antibodies. These results reveal low POWV detection rates in southern Ontario, while highlighting the challenges and need for continued efforts into understanding POWV epidemiology and targeted surveillance strategies.

Analysis of patient data from laboratories during the Ebola virus disease outbreak in Liberia, April 2014 to March 2015

PubMed Central

Fallah, Mosoka; Oshitani, Hitoshi; Kituyi, Ling; Mahmoud, Nuha; Musa, Emmanuel; Gasasira, Alex; Nyenswah, Tolbert; Dahn, Bernice; Bawo, Luke

2017-01-01

An outbreak of Ebola virus disease (EVD) in Liberia began in March 2014 and ended in January 2016. Epidemiological information on the EVD cases was collected and managed nationally; however, collection and management of the data were challenging at the time because surveillance and reporting systems malfunctioned during the outbreak. EVD diagnostic laboratories, however, were able to register basic demographic and clinical information of patients more systematically. Here we present data on 16,370 laboratory samples that were tested between April 4, 2014 and March 29, 2015. A total of 10,536 traceable individuals were identified, of whom 3,897 were confirmed cases (positive for Ebola virus RNA). There were significant differences in sex, age, and place of residence between confirmed and suspected cases that tested negative for Ebola virus RNA. Age (young children and the elderly) and place of residence (rural areas) were the risk factors for death due to the disease. The case fatality rate of confirmed cases decreased from 80% to 63% during the study period. These findings may help support future investigations and lead to a fuller understanding of the outbreak in Liberia. PMID:28732038

Analysis of patient data from laboratories during the Ebola virus disease outbreak in Liberia, April 2014 to March 2015.

PubMed

Furuse, Yuki; Fallah, Mosoka; Oshitani, Hitoshi; Kituyi, Ling; Mahmoud, Nuha; Musa, Emmanuel; Gasasira, Alex; Nyenswah, Tolbert; Dahn, Bernice; Bawo, Luke

2017-07-01

An outbreak of Ebola virus disease (EVD) in Liberia began in March 2014 and ended in January 2016. Epidemiological information on the EVD cases was collected and managed nationally; however, collection and management of the data were challenging at the time because surveillance and reporting systems malfunctioned during the outbreak. EVD diagnostic laboratories, however, were able to register basic demographic and clinical information of patients more systematically. Here we present data on 16,370 laboratory samples that were tested between April 4, 2014 and March 29, 2015. A total of 10,536 traceable individuals were identified, of whom 3,897 were confirmed cases (positive for Ebola virus RNA). There were significant differences in sex, age, and place of residence between confirmed and suspected cases that tested negative for Ebola virus RNA. Age (young children and the elderly) and place of residence (rural areas) were the risk factors for death due to the disease. The case fatality rate of confirmed cases decreased from 80% to 63% during the study period. These findings may help support future investigations and lead to a fuller understanding of the outbreak in Liberia.

Spinal meningioma, aortic aneurysms and the missing link of observation: the anchoring heuristic approach.

PubMed

Floros, Nikolaos; Papadakis, Marios; Schelzig, Hubert; Oberhuber, Alexander

2018-03-10

Over the last three decades, the development of systematic and protocol-based algorithms, and advances in available diagnostic tests have become the indispensable parts of practising medicine. Naturally, despite the implementation of meticulous protocols involving diagnostic tests or even trials of empirical therapies, the cause of one's symptoms may still not be obvious. We herein report a case of chronic back pain, which took about 5 years to get accurately diagnosed. The case challenges the diagnostic assumptions and sets ground of discussion for the diagnostic reasoning pitfalls and heuristic biases that mislead the caring physicians and cost years of low quality of life to our patient. This case serves as an example of how anchoring heuristics can interfere in the diagnostic process of a complex and rare entity when combined with a concurrent potentially life-threatening condition. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Implicit Large Eddy Simulation of a wingtip vortex at Rec =1.2x106

NASA Astrophysics Data System (ADS)

Lombard, Jean-Eloi; Moxey, Dave; Sherwin, Spencer; SherwinLab Team

2015-11-01

We present recent developments in numerical methods for performing a Large Eddy Simulation (LES) of the formation and evolution of a wingtip vortex. The development of these vortices in the near wake, in combination with the large Reynolds numbers present in these cases, make these types of test cases particularly challenging to investigate numerically. To demonstrate the method's viability, we present results from numerical simulations of flow over a NACA 0012 profile wingtip at Rec = 1.2 x106 and compare them against experimental data, which is to date the highest Reynolds number achieved for a LES that has been correlated with experiments for this test case. Our model correlates favorably with experiment, both for the characteristic jetting in the primary vortex and pressure distribution on the wing surface. The proposed method is of general interest for the modeling of transitioning vortex dominated flows over complex geometries. McLaren Racing/Royal Academy of Engineering Research Chair.

Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey.

PubMed

Dumortier, Jérôme; Cottin, Judith; Lavie, Caroline; Guillaud, Olivier; Hervieu, Valérie; Chambon-Augoyard, Christine; Scoazec, Jean-Yves; Vukusic, Sandra; Vial, Thierry

2017-09-01

Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug. In addition, 3 of these 5 patients underwent unintended single or multiple positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to 10 (highly probable). MP-induced liver injury is probably very rare, since only less than 30 cases have been reported in the literature. Nevertheless, our cases strongly illustrates that many cases could have been unrecognized; final diagnosis in 3 of 5 of our patients was made after the second or third episode of acute hepatitis. In conclusion, these cases we report here strongly illustrates that high-dose MP-induced liver injury can occur in patients treated for MS or auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can help to distinguish it from autoimmune hepatitis. Performing liver function tests routinely both before and after MP administration would be beneficial, as the timely recognition of this complication and early drug withdrawal may prevent progression of severe necrosis hepatic injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Empowering Personalized Medicine with Big Data and Semantic Web Technology: Promises, Challenges, and Use Cases.

PubMed

Panahiazar, Maryam; Taslimitehrani, Vahid; Jadhav, Ashutosh; Pathak, Jyotishman

2014-10-01

In healthcare, big data tools and technologies have the potential to create significant value by improving outcomes while lowering costs for each individual patient. Diagnostic images, genetic test results and biometric information are increasingly generated and stored in electronic health records presenting us with challenges in data that is by nature high volume, variety and velocity, thereby necessitating novel ways to store, manage and process big data. This presents an urgent need to develop new, scalable and expandable big data infrastructure and analytical methods that can enable healthcare providers access knowledge for the individual patient, yielding better decisions and outcomes. In this paper, we briefly discuss the nature of big data and the role of semantic web and data analysis for generating "smart data" which offer actionable information that supports better decision for personalized medicine. In our view, the biggest challenge is to create a system that makes big data robust and smart for healthcare providers and patients that can lead to more effective clinical decision-making, improved health outcomes, and ultimately, managing the healthcare costs. We highlight some of the challenges in using big data and propose the need for a semantic data-driven environment to address them. We illustrate our vision with practical use cases, and discuss a path for empowering personalized medicine using big data and semantic web technology.

Containing a Lassa fever epidemic in a resource-limited setting: outbreak description and lessons learned from Abakaliki, Nigeria (January-March 2012).

PubMed

Ajayi, Nnennaya A; Nwigwe, Chinedu G; Azuogu, Ben N; Onyire, Benson N; Nwonwu, Elizabeth U; Ogbonnaya, Lawrence U; Onwe, Francis I; Ekaete, Tobin; Günther, Stephan; Ukwaja, Kingsley N

2013-11-01

Despite the epidemic nature of Lassa fever (LF), details of outbreaks and response strategies have not been well documented in resource-poor settings. We describe the course of a LF outbreak in Ebonyi State, Nigeria, during January to March 2012. We analyzed clinical, epidemiological, and laboratory data from surveillance records and hospital statistics during the outbreak. Fisher's exact tests were used to compare proportions and t-tests to compare differences in means. The outbreak response consisted of effective coordination, laboratory testing, active surveillance, community mobilization, contact and suspected case evaluation, and case management. Twenty LF cases (10 confirmed and 10 suspected) were recorded during the outbreak. Nosocomial transmission to six health workers occurred through the index case. Only 1/110 contacts had an asymptomatic infection. Overall, there was high case fatality rate among all cases (6/20; 30%). Patients who received ribavirin were less likely to die than those who did not (p=0.003). The mean delay to presentation for patients who died was 11 ± 3.5 days, while for those who survived was 6 ± 2.6 days (p<0.001). The response strategies contained the epidemic. Challenges to control efforts included poor local laboratory capacity, inadequate/poor quality of protective materials, fear among health workers, and inadequate emergency preparedness. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Mental health and fitness to plead proposals in England and Wales.

PubMed

Mudathikundan, Faisal; Chao, Oriana; Forrester, Andrew

2014-01-01

Proposals to reform fitness to plead legislation have been published by the Law Commission in England and Wales; they include a new test of decision making capacity and a new psychiatric test that has yet to be fully developed. Although proposals have met with some support, there have also been detractors. The history of fitness to plead is reviewed and current case law (including the 1836 Pritchard criteria) is examined. Although existing arrangements have been criticised, this may be attributable to inconsistent practical application, rather than inherent conceptual flaws. The Pritchard test has largely stood the test of time and has emerged relatively unscathed. Fitness to plead is not a medical construct, but rather a legal entity and any new test would be likely to introduce its own difficulties. A capacity based assessment could enhance debate and disagreement and increase court time in many cases, presenting new resource implications with questionable benefit. As the existing Pritchard criteria, amended by case law, already include a five limb test that closely resembles a capacity assessment (ability to plead to the indictment, to understand the course of the proceedings, to instruct a lawyer, to challenge a juror and to understand the evidence) and given the difficulties in introducing a functional test format in other jurisdictions, the Law Commission's proposals should now be set aside, perhaps for another day: reconsideration may be possible some decades hence, pending enhanced scientific developments within psychiatry and better understanding of the mind. Copyright © 2013 Elsevier Ltd. All rights reserved.

Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

PubMed

Mangupli, Ruth; Rostomyan, Liliya; Castermans, Emilie; Caberg, Jean-Hubert; Camperos, Paul; Krivoy, Jaime; Cuauro, Elvia; Bours, Vincent; Daly, Adrian F; Beckers, Albert

2016-10-01

Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases.

Potential application of the consistency approach for vaccine potency testing.

PubMed

Arciniega, J; Sirota, L A

2012-01-01

The Consistency Approach offers the possibility of reducing the number of animals used for a potency test. However, it is critical to assess the effect that such reduction may have on assay performance. Consistency of production, sometimes referred to as consistency of manufacture or manufacturing, is an old concept implicit in regulation, which aims to ensure the uninterrupted release of safe and effective products. Consistency of manufacture can be described in terms of process capability, or the ability of a process to produce output within specification limits. For example, the standard method for potency testing of inactivated rabies vaccines is a multiple-dilution vaccination challenge test in mice that gives a quantitative, although highly variable estimate. On the other hand, a single-dilution test that does not give a quantitative estimate, but rather shows if the vaccine meets the specification has been proposed. This simplified test can lead to a considerable reduction in the number of animals used. However, traditional indices of process capability assume that the output population (potency values) is normally distributed, which clearly is not the case for the simplified approach. Appropriate computation of capability indices for the latter case will require special statistical considerations.

Automated Test Case Generation for an Autopilot Requirement Prototype

NASA Technical Reports Server (NTRS)

Giannakopoulou, Dimitra; Rungta, Neha; Feary, Michael

2011-01-01

Designing safety-critical automation with robust human interaction is a difficult task that is susceptible to a number of known Human-Automation Interaction (HAI) vulnerabilities. It is therefore essential to develop automated tools that provide support both in the design and rapid evaluation of such automation. The Automation Design and Evaluation Prototyping Toolset (ADEPT) enables the rapid development of an executable specification for automation behavior and user interaction. ADEPT supports a number of analysis capabilities, thus enabling the detection of HAI vulnerabilities early in the design process, when modifications are less costly. In this paper, we advocate the introduction of a new capability to model-based prototyping tools such as ADEPT. The new capability is based on symbolic execution that allows us to automatically generate quality test suites based on the system design. Symbolic execution is used to generate both user input and test oracles user input drives the testing of the system implementation, and test oracles ensure that the system behaves as designed. We present early results in the context of a component in the Autopilot system modeled in ADEPT, and discuss the challenges of test case generation in the HAI domain.

MER : from landing to six wheels on Mars ... twice

NASA Technical Reports Server (NTRS)

Krajewski, Joel; Burke, Kevin; Lewicki, Chris; Limonadi, Daniel; Trebi-Ollennu, Ashitey; Voorhees, Chris

2005-01-01

Application of the Pathfinder landing system design to enclose the much larger Mars Exploration Rover required a variety of Rover deployments to achieve the surface driving configuration. The project schedule demanded that software design, engineering model test, and flight hardware build to be accomplished in parallel. This challenge was met through (a) bounding unknown environments against which to design and test, (b) early mechanical prototype testing, (c) constraining the scope of on-board autonomy to survival-critical deployments, (d) executing a balance of nominal and off-nominal test cases, (e) developing off-nominal event mitigation techniques before landing, (f) flexible replanning in response to surprises during operations. Here is discussed several specific events encountered during initial MER surface operations.

Identifying viable regulatory and innovation pathways for regenerative medicine: a case study of cultured red blood cells.

PubMed

Mittra, J; Tait, J; Mastroeni, M; Turner, M L; Mountford, J C; Bruce, K

2015-01-25

The creation of red blood cells for the blood transfusion markets represents a highly innovative application of regenerative medicine with a medium term (5-10 year) prospect for first clinical studies. This article describes a case study analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical Good Manufacturing Practice (GMP) standard. The method used for case study analysis (Analysis of Life Science Innovation Systems (ALSIS)) is also innovative, demonstrating a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

PCR analysis of a prescription vegetarian diet and use in three dogs with cutaneous adverse food reactions.

PubMed

Aufox, Erin E; May, Elizabeth R; Frank, Linda A; Kania, Stephen A

2018-04-24

Cutaneous adverse food reaction (CAFR) is diagnosed by performing an elimination diet trial utilizing prescription or home-cooked diets followed by provocative challenge. To report findings of PCR analysis of a prescription vegetarian diet (RCV) for undeclared proteins of animal origin, as well as to describe its utilization for diagnosis and management of dogs suspected of having CAFR. Three client-owned dogs. PCR analysis of RCV for 11 mammalian species and poultry. In three dogs, clinical examination, cytology, aerobic culture (if indicated) and at least one elimination diet trial with RCV. In our case series, all dogs had a history of pruritus and recurrent pyoderma that resolved with infection control and an elimination diet trial. In cases 1 and 2, a diagnosis of CAFR was made following an elimination trial with RCV and provocative challenge. Case 3 had a previously confirmed diagnosis of CAFR and RCV was successfully used to maintain remission of CAFR-related signs. PCR testing of RCV was negative for 11 mammalian species and poultry. The RCV diet was found not to contain any undeclared mammalian or avian proteins. In this case series, the RCV was successfully used to diagnose and maintain three dogs with CAFR. © 2018 ESVD and ACVD.

Radiation Hardness Assurance (RHA): Challenges and New Considerations

NASA Technical Reports Server (NTRS)

Campola, Michael J.

2017-01-01

Use of commercial-off-the-shelf (COTS) components and emerging technologies often require space flight missions to accept elevated risk. The Radiation Hardness Assurance (RHA) flow includes environment definition, hazard evaluation, requirements definition, evaluation of design, and design trades to accommodate and mitigate the risk a project or program takes. Depending on the mission profile and environment, different missions may not necessarily benefit from the same risk reduction efforts or cost reduction attempts. While this poses challenges for the radiation engineer, it also presents opportunities to tailor the RHA flow to minimize risk based on the environment or design criticality while remaining within budget. This presentation will focus on an approach to RHA amidst the present challenges, using the same RHA flow as in the past, with examples from recent radiation test results. The current challenges and the types of risk will be identified. How these risks drive requirements development and realization will be explained with examples of device results and data for single event effects (SEE) and in one case total ionizing dose (TID).

Practical Results from the Application of Model Checking and Test Generation from UML/SysML Models of On-Board Space Applications

NASA Astrophysics Data System (ADS)

Faria, J. M.; Mahomad, S.; Silva, N.

2009-05-01

The deployment of complex safety-critical applications requires rigorous techniques and powerful tools both for the development and V&V stages. Model-based technologies are increasingly being used to develop safety-critical software, and arguably, turning to them can bring significant benefits to such processes, however, along with new challenges. This paper presents the results of a research project where we tried to extend current V&V methodologies to be applied on UML/SysML models and aiming at answering the demands related to validation issues. Two quite different but complementary approaches were investigated: (i) model checking and the (ii) extraction of robustness test-cases from the same models. These two approaches don't overlap and when combined provide a wider reaching model/design validation ability than each one alone thus offering improved safety assurance. Results are very encouraging, even though they either fell short of the desired outcome as shown for model checking, or still appear as not fully matured as shown for robustness test case extraction. In the case of model checking, it was verified that the automatic model validation process can become fully operational and even expanded in scope once tool vendors help (inevitably) to improve the XMI standard interoperability situation. For the robustness test case extraction methodology, the early approach produced interesting results but need further systematisation and consolidation effort in order to produce results in a more predictable fashion and reduce reliance on expert's heuristics. Finally, further improvements and innovation research projects were immediately apparent for both investigated approaches, which point to either circumventing current limitations in XMI interoperability on one hand and bringing test case specification onto the same graphical level as the models themselves and then attempting to automate the generation of executable test cases from its standard UML notation.

Migraine with Aura or Sports-Related Concussion: Case Report, Pathophysiology, and Multidisciplinary Approach to Management.

PubMed

Ellis, Michael J; Cordingley, Dean; Girardin, Richard; Ritchie, Lesley; Johnston, Janine

The evaluation and management of athletes presenting with clinical features of migraine headache with aura in the setting of sports-related head trauma is challenging. We present a case report of a 15-yr-old boy with a history of migraine with visual aura that developed acute visual disturbance and headache after a head injury during an ice hockey game. The patient underwent comprehensive assessment at a multidisciplinary concussion program, including neuro-ophthalmological examination, neurocognitive testing, and graded aerobic treadmill testing. Clinical history and multidisciplinary assessment was consistent with the diagnosis of coexisting sports-related concussion and migraine with brainstem aura. The authors discuss the pearls and pitfalls of managing patients who develop migraine headache with visual aura after sports-related head injury and the value of a comprehensive multidisciplinary approach to this unique patient population.

Project Career: A qualitative examination of five college students with traumatic brain injuries.

PubMed

Nardone, Amanda; Sampson, Elaine; Stauffer, Callista; Leopold, Anne; Jacobs, Karen; Hendricks, Deborah J; Elias, Eileen; Chen, Hui; Rumrill, Phillip

2015-01-01

Project Career is an interprofessional five-year development project designed to improve the employment success of undergraduate college and university students with traumatic brain injury (TBI). The case study information was collected and synthesized by the project's Technology and Employment Coordinators (TECs) at each of the project's three university sites. The project's evaluation is occurring independently through JBS International, Inc. Five case studies are presented to provide an understanding of student participants' experiences within Project Career. Each case study includes background on the student, engagement with technology, vocational supports, and interactions with his/her respective TEC. A qualitative analysis from the student's case notes is provided within each case study, along with a discussion of the overall qualitative analysis. Across all five students, the theme Positive Outcomes was mentioned most often in the case notes. Of all the different type of challenges, Cognitive Challenges were most often mentioned during meetings with the TECs, followed by Psychological Challenges, Physical Challenges, Other Challenges, and Academic Challenges, respectively. Project Career is providing academic enrichment and career enhancement that may substantially improve the unsatisfactory employment outcomes that presently await students with TBI following graduation.

Employment of telemedicine in emergency medicine. Clinical requirement analysis, system development and first test results.

PubMed

Czaplik, M; Bergrath, S; Rossaint, R; Thelen, S; Brodziak, T; Valentin, B; Hirsch, F; Beckers, S K; Brokmann, J C

2014-01-01

Demographic change, rising co-morbidity and an increasing number of emergencies are the main challenges that emergency medical services (EMS) in several countries worldwide are facing. In order to improve quality in EMS, highly trained personnel and well-equipped ambulances are essential. However several studies have shown a deficiency in qualified EMS physicians. Telemedicine emerges as a complementary system in EMS that may provide expertise and improve quality of medical treatment on the scene. Hence our aim is to develop and test a specific teleconsultation system. During the development process several use cases were defined and technically specified by medical experts and engineers in the areas of: system administration, start-up of EMS assistance systems, audio communication, data transfer, routine tele-EMS physician activities and research capabilities. Upon completion, technical field tests were performed under realistic conditions to test system properties such as robustness, feasibility and usability, providing end-to-end measurements. Six ambulances were equipped with telemedical facilities based on the results of the requirement analysis and 55 scenarios were tested under realistic conditions in one month. The results indicate that the developed system performed well in terms of usability and robustness. The major challenges were, as expected, mobile communication and data network availability. Third generation networks were only available in 76.4% of the cases. Although 3G (third generation), such as Universal Mobile Telecommunications System (UMTS), provides beneficial conditions for higher bandwidth, system performance for most features was also acceptable under adequate 2G (second generation) test conditions. An innovative concept for the use of telemedicine for medical consultations in EMS was developed. Organisational and technical aspects were considered and practical requirements specified. Since technical feasibility was demonstrated in these technical field tests, the next step would be to prove medical usefulness and technical robustness under real conditions in a clinical trial.

Allergenicity of casein containing chalk in milk allergic schoolchildren.

PubMed

Larramendi, Carlos H; Marco, Francisco M; Llombart, Mónica; de la Vega, Ana; Chiner, Eusebi; García-Abujeta, José Luis; Sempere, José Miguel

2013-05-01

Nondietary exposure to milk proteins may be a risk for children who do not outgrow milk allergy by school age. To study the allergenicity of casein containing chalk. A 6-year-old, milk allergic child developed asthma and rhinoconjunctivitis while in school. The suspected cause was dust-free chalk containing casein. To study the relationship of dust-free chalk containing casein with asthma and rhinoconjunctivitis, 13 additional milk allergic patients were studied: 3 school-aged children, 8 preschool-aged infants, and 2 children with outgrown milk allergy. Skin tests and/or specific IgE with chalk and casein were performed. A chalk use test was performed in older children. Milk allergens contained in chalk were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot, and IgE inhibition experiments. All school-aged, milk allergic children were exposed to chalk and reported symptoms attributed to chalk exposure. The skin test result to chalk was positive in 5 of 12 cases, and the specific IgE test result was positive in all 12 study participants in which it was performed. Casein strongly inhibited the binding of IgE to chalk. Chalk sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed proteins with molecular weight similar to caseins. Immunoblot demonstrated strong binding of IgE to chalk in a blurred pattern and a band at 30 kDa, inhibited by casein. The chalk challenge test result was positive in 2 school-age children who had a positive skin test result to chalk. Their symptoms improved after avoidance of chalk in the school. In 2 other cases in which the challenge test result was negative, chalk was reintroduced without problems. Inhalation of chalk dust containing casein can induce asthma symptoms in milk allergic patients. Hidden and nondietary sources of exposure should always be considered in food allergic patients. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Case for the Application of Worldwide Marine Radioactivity Studies In the Search for Undeclared Facilities and Activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mark Schanfein

2013-06-01

Undeclared nuclear facilities unequivocally remain the most difficult safeguards challenge facing the International Atomic Energy Agency (IAEA). Recent cases of undeclared facilities revealed in Iran and Syria, which are NPT signatory States, show both the difficulty and the seriousness of this threat to nonproliferation. In the case of undeclared nuclear facilities, the most effective deterrent against proliferation is the application of Wide-Area Environmental Sampling (WAES); however, WAES is currently cost-prohibitive. As with any threat, the most effective countering strategy is a multifaceted approach. Some of the approaches applied by the IAEA include: open source analysis, satellite imagery, on-site environmental sampling,more » complementary access under the Additional Protocol (where in force), traditional safeguards inspections, and information provided by member States. These approaches, naturally, are focused on specific States. Are there other opportunities not currently within the IAEA purview to assess States that may provide another opportunity to detect clandestine facilities? In this paper, the author will make the case that the IAEA Department of Safeguards should explore the area of worldwide marine radioactivity studies as one possible opportunity. One such study was released by the IAEA Marine Environment Laboratory in January 2005. This technical document focused on 90Sr, 137Cs, and 239/240Pu. It is clearly a challenging area because of the many sources of anthropogenic radionuclides in the world’s oceans and seas including: nuclear weapons testing, reprocessing, accidents, waste dumping, and industrial and medical radioisotopes, whose distributions change based on oceanographic, geochemical, and biological processes, and their sources. It is additionally challenging where multiple States share oceans, seas, and rivers. But with the application of modern science, historical sampling to establish baselines, and a focus on the most relevant radionuclides, the potential is there to support this challenging IAEA safeguards mission.« less

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Toxoplasma, toxocara and tuberculosis co-infection in a four year old child.

PubMed

Guneratne, Randeewari; Mendis, Devan; Bandara, Tharaka; Fernando, Sumadhya Deepika

2011-05-26

Tuberculosis. toxocariasis and toxoplasmosis are among the common infectious causes of lymphadenitis in children. Cases of Toxoplasma gondii and Toxocara spp co-infection have been reported. This case report describes a co-infection of Toxoplasma gondii, Toxocara spp and tuberculosis in a child with chronic lymphadenopathy and eosinophilia. The case report highlights two important points. First is the diagnostic challenges that are encountered by clinicians in tropical countries such as Sri Lanka, where lymphadenopathy and eosinophilia with a positive serology commonly point towards a parasitic infection. Secondly the importance of proper history taking and performing the Mantoux test as a first line investigation in a country where the incidence of tuberculosis is low, even in the absence of a positive contact history.

Applying Role-Playing Strategy to Enhance Learners' Writing and Speaking Skills in EFL Courses Using Facebook and Skype as Learning Tools: A Case Study in Taiwan

ERIC Educational Resources Information Center

Yen, Yen-Chen; Hou, Huei-Tse; Chang, Kuo En

2015-01-01

English as a foreign language (EFL) instruction faces many challenges in Asia because of many cultural and environmental factors, such as the lack of interactive speaking environments, emphasis placed on test scores, and foreign language anxiety. The purpose of this research is to conduct an EFL instructional course by integrating Facebook…

The Rewards of Perseverance, Aldine Texas: The Power of a Systemwide Focus on Students, Teachers, and Leaders. School System 20/20 Case Study

ERIC Educational Resources Information Center

Baroody, Karen; Rho, Lois

2016-01-01

"The Rewards of Perseverance" tells the story of a district with a clear vision, stable leadership, and deliberate evolution in response to change. Located just north of Houston, AISD has faced daunting challenges since the 1990s--including a significant increase in high-need students, and more rigorous state tests. At the same time, the…

An Improved Rank Correlation Effect Size Statistic for Single-Case Designs: Baseline Corrected Tau.

PubMed

Tarlow, Kevin R

2017-07-01

Measuring treatment effects when an individual's pretreatment performance is improving poses a challenge for single-case experimental designs. It may be difficult to determine whether improvement is due to the treatment or due to the preexisting baseline trend. Tau- U is a popular single-case effect size statistic that purports to control for baseline trend. However, despite its strengths, Tau- U has substantial limitations: Its values are inflated and not bound between -1 and +1, it cannot be visually graphed, and its relatively weak method of trend control leads to unacceptable levels of Type I error wherein ineffective treatments appear effective. An improved effect size statistic based on rank correlation and robust regression, Baseline Corrected Tau, is proposed and field-tested with both published and simulated single-case time series. A web-based calculator for Baseline Corrected Tau is also introduced for use by single-case investigators.

Occupational asthma caused by stainless steel welding fumes: a clinical study.

PubMed

Hannu, T; Piipari, R; Tuppurainen, M; Nordman, H; Tuomi, T

2007-01-01

The aim of the present study was to describe the cases of occupational asthma (OA) due to stainless steel welding fumes diagnosed at the Finnish Institute of Occupational Health during the period 1994-2003. OA was diagnosed according to patient history, lung function examinations and welding challenge tests with measurements of the forced expiratory volume in one second (FEV(1)) and peak expiratory flow (PEF) values. The present series comprised 34 patients, all male, with a mean age of 44.7 yrs (range 22-57), mainly working as welders. The mean duration of exposure was 22.4 yrs, and the mean duration of exposure before the onset of respiratory symptoms was 18 yrs. Dyspnoea was the most frequently reported work-related respiratory symptom. During the inhalation challenge tests, the mode of the asthmatic FEV(1)/PEF reaction was delayed in 16 (47%) patients, immediate in nine (26%) patients and dual (both immediate and delayed) in nine (26%) patients. In the follow-up assessment 6 months later, only six patients were considered able to continue performing welding tasks, whereas occupational injury pension was recommended for seven, and measures of vocational rehabilitation for 14 patients. In most cases, after the diagnosis of occupational asthma, the continuation of welding work was not possible.

Consensus training: an effective tool to minimize variations in periodontal diagnosis and treatment planning among dental faculty and students.

PubMed

John, Vanchit; Lee, Seung-Jun; Prakasam, Sivaraman; Eckert, George J; Maupome, Gerardo

2013-08-01

Considerable disagreements and variations exist in diagnosis and treatment planning of periodontal disease. Achieving high interrater periodontal diagnosis can prove challenging. The objectives of this study were to measure variations in periodontal diagnosis and treatment planning among predoctoral periodontics faculty members after consensus training and to compare such variation with those identified in third- and fourth-year dental students. Nine electronically stored case vignettes and survey instruments were made available to eighteen faculty members and twenty dental students under standardized conditions. A chi-square test was used to compare responses between groups, and multirater kappa tests were used to evaluate interrater agreement/reliability. Of the nine cases, only one differed between groups significantly in terms of treatment. Also, third-year students differed from fourth-year students on the diagnosis of aggressive periodontitis versus chronic periodontitis. Most respondents were able to distinguish clearly among diagnoses of chronic periodontitis, aggressive periodontitis, and gingivitis. This study established a baseline assessment of the current status of consensus after training. We will reassess variations after addressing the specific challenges identified. Programs designed and implemented to help decrease the variation in periodontal diagnosis and treatment planning among faculty members may ultimately translate into better agreement and better standardization of dental instruction.

THE CASE OF A 14-YEAR-OLD BOY WHO EXPERIENCED ANAPHYLAXIS DUE TO JELLYFISH (MASTIGIAS PAPUA) INGESTION.

PubMed

Kubota, Shohei; Nozawa, Asako; Yanai, Takanori; Ozasa, Koji; Mori, Satomi; Kurihara, Kazuyuki

2017-01-01

We report a case of jellyfish allergy diagnosed via an oral food challenge. A 14-year-old boy had no history of jellyfish stings and had been eating commercially available jellyfish products twice yearly for the past 5-6 years. Five minutes after eating a commercially available boiled jellyfish product (100g), he experienced nausea, wheezing, and erythema and had visited our hospital. We suspected an anaphylactic reaction and treated him with intramuscular adrenaline injection, corticosteroid and antihistamine infusions, volume resuscitation, and salbutamol sulfate inhalation, which resulted in an improvement of the symptoms. One-month later in our hospital, we administered an oral food challenge of the same boiled jellyfish product bought at the same grocery store to the patient. After ingesting 14g of boiled jellyfish, he experienced erythema, wheezing, nausea, and abdominal pain. Several reports have described anaphylaxis caused by the ingestion of jellyfish, but the allergens in jellyfish have not been analyzed. A skin prick test for poly-gamma-glutamic acid (PGA) which is a component of jellyfish stings was negative. This suggests that he was sensitized to some allergen other than PGA via a route different from that of jellyfish sting. Our skin prick test for several kinds of edible jellyfish suggests that allergenicity may be different for different jellyfish.

Evaluating laboratory approaches to the identification of lupus anticoagulants: a diagnostic challenge from the RCPA Haematology QAP.

PubMed

Bonar, Roslyn; Favaloro, Emmanuel; Zebeljan, Diane; Rosenfeld, David; Kershaw, Geoff; Mohammed, Soma; Marsden, Katherine; Hertzberg, Mark

2012-04-01

Laboratory identification of lupus anticoagulants (LA), an important component of the clinical diagnosis of the autoimmune disorder antiphospholipid syndrome (APS), is challenged by the heterogeneity of tests available, the diagnostic and laboratory approach undertaken, and the heterogeneity of the autoantibodies present. : To assess the laboratory approach for investigation of LA, as well as the utility of various tests and test approaches, given a difficult clinical scenario in which LA might or might not be present. Ninety-three participants in the Royal College of Pathologists of Australasia (RCPA) Haematology Quality Assurance Program (QAP) were sent 4  mL of a complex but strongly positive LA sample blinded to the nature of the abnormality. Seventy-three (79%) participants returned results and in most cases diagnostic interpretations. The laboratory approach to LA investigation of this sample was quite varied: 34.7% of participants concluded the sample was LA negative, with 91.7% of these performing dilute Russell viper venom time (dRVVT) testing without mixing, whereas 43.5% of participants identified a strong LA, with 96.7% of these having performed mixing studies. Most laboratories reporting negative LA instead identified the false presence of specific factor inhibitors against a variety of factors, including II, V and VIII. For this difficult challenge, performance of non-mixing dRVVT was associated with a high false negative LA rate. (C) 2012 Royal College of Pathologists of Australasia.

Rubella Surveillance and Diagnostic Testing among a Low-Prevalence Population, New York City, 2012-2013.

PubMed

Isaac, Beth M; Zucker, Jane R; Giancotti, Francesca R; Abernathy, Emily; Icenogle, Joseph; Rakeman, Jennifer L; Rosen, Jennifer B

2017-09-01

The New York City Department of Health and Mental Hygiene (DOHMH) receives clinical and laboratory reports for rubella. Because rubella immunoglobulin M (IgM) assays may produce false-positive results and rubella infections may be asymptomatic, interpretation of positive IgM results can be challenging. Rubella reports received by DOHMH in 2012 to 2013 were reviewed. The rubella IgM testing purpose was determined through case investigation. Results of IgM testing by indirect enzyme-linked immunosorbent assay (ELISA) and capture enzyme immunoassay (EIA) were compared to determine positive predictive value (PPV) and specificity. DOHMH received 199 rubella reports; 2 were true cases. Of all reports, 77.9% were tested for rubella IgM erroneously, 19.6% were tested for diagnostic purposes, 2.0% had unknown test purpose, and 0.5% were not tested. PPV of indirect ELISA was 6% overall, 14% for diagnostic tests, and 0% for tests ordered erroneously. PPV of capture EIA was 29% overall, 50% for diagnostic tests, and 0% for tests ordered erroneously. Overall, specificity was 52% for indirect ELISA and 85% for capture EIA. Limiting rubella IgM testing to patients for whom rubella diagnosis is suspected and using a more specific IgM assay have the potential to reduce false-positive rubella IgM results. Copyright © 2017 American Society for Microbiology.

Mars Solar Power

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.; Kerslake, Thomas W.; Jenkins, Phillip P.; Scheiman, David A.

2004-01-01

NASA missions to Mars, both robotic and human, rely on solar arrays for the primary power system. Mars presents a number of challenges for solar power system operation, including a dusty atmosphere which modifies the spectrum and intensity of the incident solar illumination as a function of time of day, degradation of the array performance by dust deposition, and low temperature operation. The environmental challenges to Mars solar array operation will be discussed and test results of solar cell technology operating under Mars conditions will be presented, along with modeling of solar cell performance under Mars conditions. The design implications for advanced solar arrays for future Mars missions is discussed, and an example case, a Martian polar rover, are analyzed.

A controlled experiment in ground water flow model calibration

USGS Publications Warehouse

Hill, M.C.; Cooley, R.L.; Pollock, D.W.

1998-01-01

Nonlinear regression was introduced to ground water modeling in the 1970s, but has been used very little to calibrate numerical models of complicated ground water systems. Apparently, nonlinear regression is thought by many to be incapable of addressing such complex problems. With what we believe to be the most complicated synthetic test case used for such a study, this work investigates using nonlinear regression in ground water model calibration. Results of the study fall into two categories. First, the study demonstrates how systematic use of a well designed nonlinear regression method can indicate the importance of different types of data and can lead to successive improvement of models and their parameterizations. Our method differs from previous methods presented in the ground water literature in that (1) weighting is more closely related to expected data errors than is usually the case; (2) defined diagnostic statistics allow for more effective evaluation of the available data, the model, and their interaction; and (3) prior information is used more cautiously. Second, our results challenge some commonly held beliefs about model calibration. For the test case considered, we show that (1) field measured values of hydraulic conductivity are not as directly applicable to models as their use in some geostatistical methods imply; (2) a unique model does not necessarily need to be identified to obtain accurate predictions; and (3) in the absence of obvious model bias, model error was normally distributed. The complexity of the test case involved implies that the methods used and conclusions drawn are likely to be powerful in practice.Nonlinear regression was introduced to ground water modeling in the 1970s, but has been used very little to calibrate numerical models of complicated ground water systems. Apparently, nonlinear regression is thought by many to be incapable of addressing such complex problems. With what we believe to be the most complicated synthetic test case used for such a study, this work investigates using nonlinear regression in ground water model calibration. Results of the study fall into two categories. First, the study demonstrates how systematic use of a well designed nonlinear regression method can indicate the importance of different types of data and can lead to successive improvement of models and their parameterizations. Our method differs from previous methods presented in the ground water literature in that (1) weighting is more closely related to expected data errors than is usually the case; (2) defined diagnostic statistics allow for more effective evaluation of the available data, the model, and their interaction; and (3) prior information is used more cautiously. Second, our results challenge some commonly held beliefs about model calibration. For the test case considered, we show that (1) field measured values of hydraulic conductivity are not as directly applicable to models as their use in some geostatistical methods imply; (2) a unique model does not necessarily need to be identified to obtain accurate predictions; and (3) in the absence of obvious model bias, model error was normally distributed. The complexity of the test case involved implies that the methods used and conclusions drawn are likely to be powerful in practice.

Diagnosis and predictive molecular analysis of non-small-cell lung cancer in the Africa-Middle East region: challenges and strategies for improvement.

PubMed

Slavik, Tomas; Asselah, Fatima; Fakhruddin, Najla; El Khodary, Ahmed; Torjman, Fairouz; Anis, Elia; Quinn, Martin; Khankan, Azzam; Kerr, Keith M

2014-11-01

The identification of tumor biomarkers provides information on the prognosis and guides the implementation of appropriate treatment in patients with many different cancer types. In non-small cell lung cancer (NSCLC), targeted treatment plans based on biomarker identification have already been used in the clinic. However, such predictive molecular testing is not currently a universally used practice. This is the case, in particular, in developing countries where lung cancer is increasingly prevalent. In September 2012 and November 2013, a committee of 16 lung cancer experts from Africa and the Middle East met to discuss key issues related to diagnosis and biomarker testing in NSCLC and the implementation of personalized medicine in the region. The committee identified current challenges for effective diagnosis and predictive analysis in Africa and the Middle East. Moreover, strategies to encourage the implementation of biomarker testing were discussed. A practical approach for the effective diagnosis and predictive molecular testing of NSCLC in these regions was derived. We present the key issues and recommendations arising from the meetings. Copyright © 2014 Elsevier Inc. All rights reserved.

Challenges and Opportunities for Testing Students Who Are Deaf or Hard of Hearing: Information for Educators on Creating Test Equity. Test Equity Considerations: Schools

ERIC Educational Resources Information Center

PEPNet-West, 2010

2010-01-01

For most students, test taking is a challenge. For students who are deaf or hard of hearing, classroom quizzes, tests, and exams are even more challenging. Standardized tests--The SAT, ACT, state proficiency tests, No Child Left Behind annual tests, and psychoeducational evaluations--present additional challenges for students who are deaf or hard…

Automated microaneurysm detection method based on double ring filter in retinal fundus images

NASA Astrophysics Data System (ADS)

Mizutani, Atsushi; Muramatsu, Chisako; Hatanaka, Yuji; Suemori, Shinsuke; Hara, Takeshi; Fujita, Hiroshi

2009-02-01

The presence of microaneurysms in the eye is one of the early signs of diabetic retinopathy, which is one of the leading causes of vision loss. We have been investigating a computerized method for the detection of microaneurysms on retinal fundus images, which were obtained from the Retinopathy Online Challenge (ROC) database. The ROC provides 50 training cases, in which "gold standard" locations of microaneurysms are provided, and 50 test cases without the gold standard locations. In this study, the computerized scheme was developed by using the training cases. Although the results for the test cases are also included, this paper mainly discusses the results for the training cases because the "gold standard" for the test cases is not known. After image preprocessing, candidate regions for microaneurysms were detected using a double-ring filter. Any potential false positives located in the regions corresponding to blood vessels were removed by automatic extraction of blood vessels from the images. Twelve image features were determined, and the candidate lesions were classified into microaneurysms or false positives using the rule-based method and an artificial neural network. The true positive fraction of the proposed method was 0.45 at 27 false positives per image. Forty-two percent of microaneurysms in the 50 training cases were considered invisible by the consensus of two co-investigators. When the method was evaluated for visible microaneurysms, the sensitivity for detecting microaneurysms was 65% at 27 false positives per image. Our computerized detection scheme could be improved for helping ophthalmologists in the early diagnosis of diabetic retinopathy.

Backtracking Depth-Resolved Microstructures for Crystal Plasticity Identification—Part 1: Backtracking Microstructures

NASA Astrophysics Data System (ADS)

Shi, Qiwei; Latourte, Félix; Hild, François; Roux, Stéphane

2017-12-01

In situ mechanical tests performed on polycrystalline materials in a scanning electron microscope suffer from the lack of information on depth-resolved three-dimensional microstructures. The latter ones can be accessed with focused ion beam technology only postmortem, because it is destructive. The present study considers the challenge of backtracking this deformed microstructure to the reference state. This theoretical question is tackled on a numerical (synthetic) test case. A two-dimensional microstructure with one dimension along the depth is considered, and deformed using a crystal plasticity law. The proposed numerical strategy is shown to retrieve accurately the reference state.

Isolated Rhabdomyolysis of the Infraspinatus Muscle Following the CrossFit "Sissy Test": A Report of Two Cases.

PubMed

Routman, Howard D; Triplet, Jacob J; Kurowicki, Jennifer; Singh, Neil

2018-01-01

Following the completion of a CrossFit-style challenge (the "Sissy Test"), 2 patients presented with severe pain and swelling over the posterior aspect of the scapula. Magnetic resonance imaging demonstrated isolated edema of the infraspinatus muscle in both patients; the compartments were compressible. Neurovascular checks and observation of range of motion were performed. The patients were treated nonoperatively and were discharged with the diagnosis of overuse syndrome with rhabdomyolysis of the infraspinatus muscle. With marked increase in the popularity of extreme fitness, monitoring for rhabdomyolysis and potential renal dysfunction is essential.

[Allergy to ranitidine: one case report and literature review].

PubMed

Cuevas-Castillejos, Héctor; Cuevas-Castillejos, José Elihú; García-Murray, Oscar; Larenas-Linnemann, Désirée

2013-01-01

Ranitidine is a drug, which seldom causes adverse reactions, nevertheless, allergic reactions have been described varying in type and intensity after its administration. In contrast to other drugs, there are not many validated and standardized diagnostic tests in order to demonstrate this drug produces an allergic reaction. In this article we present a 9-months-old girl with a ranitidine allergic reaction with the diagnosis established by a non-intentional challenge test. We also provide information from the National Drug Surveillance Center in Mexico concerning ranitidine adverse drug reactions (including allergic reactions) in a 10-year period.

Experiment for validation of fluid-structure interaction models and algorithms.

PubMed

Hessenthaler, A; Gaddum, N R; Holub, O; Sinkus, R; Röhrle, O; Nordsletten, D

2017-09-01

In this paper a fluid-structure interaction (FSI) experiment is presented. The aim of this experiment is to provide a challenging yet easy-to-setup FSI test case that addresses the need for rigorous testing of FSI algorithms and modeling frameworks. Steady-state and periodic steady-state test cases with constant and periodic inflow were established. Focus of the experiment is on biomedical engineering applications with flow being in the laminar regime with Reynolds numbers 1283 and 651. Flow and solid domains were defined using computer-aided design (CAD) tools. The experimental design aimed at providing a straightforward boundary condition definition. Material parameters and mechanical response of a moderately viscous Newtonian fluid and a nonlinear incompressible solid were experimentally determined. A comprehensive data set was acquired by using magnetic resonance imaging to record the interaction between the fluid and the solid, quantifying flow and solid motion. Copyright © 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Social contract theory and just decision making: lessons from genetic testing for the BRCA mutations.

PubMed

Williams-Jones, Bryn; Burgess, Michael M

2004-06-01

Decisions about funding health services are crucial to controlling costs in health care insurance plans, yet they encounter serious challenges from intellectual property protection--e.g., patents--of health care services. Using Myriad Genetics' commercial genetic susceptibility test for hereditary breast cancer (BRCA testing) in the context of the Canadian health insurance system as a case study, this paper applies concepts from social contract theory to help develop more just and rational approaches to health care decision making. Specifically, Daniel's and Sabin's "accountability for reasonableness" is compared to broader notions of public consultation, demonstrating that expert assessments in specific decisions must be transparent and accountable and supplemented by public consultation.

A gravitational puzzle.

PubMed

Caldwell, Robert R

2011-12-28

The challenge to understand the physical origin of the cosmic acceleration is framed as a problem of gravitation. Specifically, does the relationship between stress-energy and space-time curvature differ on large scales from the predictions of general relativity. In this article, we describe efforts to model and test a generalized relationship between the matter and the metric using cosmological observations. Late-time tracers of large-scale structure, including the cosmic microwave background, weak gravitational lensing, and clustering are shown to provide good tests of the proposed solution. Current data are very close to proving a critical test, leaving only a small window in parameter space in the case that the generalized relationship is scale free above galactic scales.

Meeting the challenges of case management with remote patient monitoring technology.

PubMed

Cherry, J C; Colliflower, S J; Tsiperfal, A

2000-01-01

The article presents an overview of some of the current trends in health care and the challenges faced by nurse case managers who are providing disease management services. It discusses some of the emerging technologies available today for innovative case management. In particular, this article describes a program run by a healthcare system in Sacramento, California that uses an Internet-based technology to enhance their nurse case management model. The article demonstrates how the Health Hero platform enables interactive communication between nurse case managers and their patients, thereby meeting some of the challenges the nurse case managers are faced with in the modern disease-management world.

50 Grams Oral Glucose Challenge Test: Is It an Effective Screening Test for Gestational Diabetes Mellitus?

PubMed

Abu-Heija, Adel; Al-Bash, Majeda; Ishrat, Noreen; Al-Kharausi, Lamya

2016-10-01

To find out whether 50 g oral glucose challenge test (OGCT) is an effective screening test for all pregnant women between 24 and 28 weeks gestation. A 50 g OGCT test was administered to 307 unselected women at 24-28 weeks of gestation. When venous plasma glucose (VPG) concentration after 1 h was >7.8 mmol/l, OGCT was positive. Women with a positive OGCT underwent 2 h 75 grams oral glucose tolerance test (OGTT) as a confirmatory diagnosis of GDM. When fasting and 2 h post 75 g OGTT values were >5.5 mmol/I and >8 mmol/l, respectively, women were considered diabetic. We screened 307 women for GDM by OGCT. Total number of women with positive OGCT was 83 (27.03 %). In the low-risk group, total number of women with GDM was 9/168 (5.35 %) while the total number of women with GDM in the high-risk group was 14/139 (10.07 %). There was no significant difference with respect to the total number of women with GDM in the groups. A 50 g OGCT seems to be an effective screening test for both groups. More cases of GDM can be discovered when universal rather than risk-related screening is applied.

Predicting Bobsled Pushing Ability from Various Combine Testing Events.

PubMed

Tomasevicz, Curtis L; Ransone, Jack W; Bach, Christopher W

2018-03-12

The requisite combination of speed, power, and strength necessary for a bobsled push athlete coupled with the difficulty in directly measuring pushing ability makes selecting effective push crews challenging. Current practices by USA Bobsled and Skeleton (USABS) utilize field combine testing to assess and identify specifically selected performance variables in an attempt to best predict push performance abilities. Combine data consisting of 11 physical performance variables were collected from 75 subjects across two winter Olympic qualification years (2009 and 2013). These variables were sprints of 15-, 30-, and 60 m, a flying 30 m sprint, a standing broad jump, a shot toss, squat, power clean, body mass, and dry-land brake and side bobsled pushes. Discriminant Analysis (DA) in addition to Principle Component Analysis (PCA) was used to investigate two cases (Case 1: Olympians vs. non-Olympians; Case 2: National Team vs. non-National Team). Using these 11 variables, DA led to a classification rule that proved capable of identifying Olympians from non-Olympians and National Team members from non-National Team members with 9.33% and 14.67% misclassification rates, respectively. The PCA was used to find similar test variables within the combine that provided redundant or useless data. After eliminating the unnecessary variables, DA on the new combinations showed that 8 (Case 1) and 20 (Case 2) other combinations with fewer performance variables yielded misclassification rates as low as 6.67% and 13.33% respectively. Utilizing fewer performance variables can allow governing bodies in many other sports to create more appropriate combine testing that maximize accuracy, while minimizing irrelevant and redundant strategies.

Field Testing and Modeling of Supermarket Refrigeration Systems as a Demand Response Resource

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deru, Michael; Hirsch, Adam; Clark, Jordan

Supermarkets offer a substantial demand response (DR) resource because of their high energy intensity and use patterns; however, refrigeration as the largest load has been challenging to access. Previous work has analyzed supermarket DR using heating, ventilating, and air conditioning; lighting; and anti-sweat heaters. This project evaluated and quantified the DR potential inherent in supermarket refrigeration systems in the Bonneville Power Administration service territory. DR events were carried out and results measured in an operational 45,590-ft2 supermarket located in Hillsboro, Oregon. Key results from the project include the rate of temperature increase in freezer reach-in cases and walk-ins when refrigerationmore » is suspended, the load shed amount for DR tests, and the development of calibrated models to quantify available DR resources. Simulations showed that demand savings of 15 to 20 kilowatts (kW) are available for 1.5 hours for a typical store without precooling and for about 2.5 hours with precooling using only the low-temperature, non-ice cream cases. This represents an aggregated potential of 20 megawatts within BPA's service territory. Inability to shed loads for medium-temperature (MT) products because of the tighter temperature requirements is a significant barrier to realizing larger DR for supermarkets. Store owners are reluctant to allow MT case set point changes, and laboratory tests of MT case DR strategies are needed so that owners become comfortable testing, and implementing, MT case DR. The next-largest barrier is the lack of proper controls in most supermarket displays over ancillary equipment, such as anti-sweat heaters, lights, and fans.« less

Marrow hypoplasia: a rare complication of untreated Grave's disease.

PubMed

Garcia, Juliana; França, Larissa de; Ellinger, Vivian; Wolff, Mônica

2014-12-01

Atypical presentation forms of hyperthyroidism are always a challenge to the clinician. We present a female patient with the typical symptoms of thyrotoxicosis, without any thionamides treatment before, associated with pancytopenia, which recovered after euthyroidism state was achieved. Although the major cases of pancytopenia in Grave's disease are seen as a complication of antithyroid drugs (thioamides), in this case report the alteration in blood tests was associated with untreated hyperthyroidism. In the literature review, we found 19 case reports between 1981 to 2012, but it has been related to a hypercellular bone marrow with periferic destruction. Our case, however, is about a hypocellular bone marrow without fibrosis or fat tissue replacement, which proceeded with a periferic improvement following thyroid treatment. Although rare, pancytopenia, when present, may develop as an unusual and severe manifestation in untreated subjects.

Case Series of Fatal Leptospira spp./Dengue Virus Co-Infections—Puerto Rico, 2010–2012

PubMed Central

Pérez Rodríguez, Nicole M.; Galloway, Renee; Blau, Dianna M.; Traxler, Rita; Bhatnagar, Julu; Zaki, Sherif R.; Rivera, Aidsa; Torres, Jose V.; Noyd, David; Santiago-Albizu, Xavier E.; García, Brenda Rivera; Tomashek, Kay M.; Bower, William A.; Sharp, Tyler M.

2014-01-01

Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of Leptospira species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue. PMID:25092820

A Testing Framework for Critical Space SW

NASA Astrophysics Data System (ADS)

Fernandez, Ignacio; Di Cerbo, Antonio; Dehnhardt, Erik; Massimo, Tipaldi; Brünjes, Bernhard

2015-09-01

This paper describes a testing framework for critical space SW named Technical Specification Validation Framework (TSVF). It provides a powerful and flexible means and can be used throughout the SW test activities (test case specification & implementation, test execution and test artifacts analysis). In particular, tests can be run in an automated and/or step-by-step mode. The TSVF framework is currently used for the validation of the Satellite Control Software (SCSW), which runs on the Meteosat Third Generation (MTG) satellite on-board computer. The main purpose of the SCSW is to control the spacecraft along with its various subsystems (AOCS, Payload, Electrical Power, Telemetry Tracking & Command, etc.) in a way that guarantees a high degree of flexibility and autonomy. The TSVF framework serves the challenging needs of the SCSW project, where a plan-driven approach has been combined with an agile process in order to produce preliminary SW versions (with a reduced scope of implemented functionality) in order to fulfill the stakeholders needs ([1]). The paper has been organised as follows. Section 2 gives an overview of the TSVF architecture and interfaces versus the test bench along with the technology used for its implementation. Section 3 describes the key elements of the XML based language for the test case implementation. Section 4 highlights all the benefits compared to conventional test environments requiring a manual test script development, whereas section 5 concludes the paper.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kapil, Sanjay; Oberst, R. D.; Bieker, Jill Marie

Chemical disinfection and inactivation of viruses is largely understudied, but is very important especially in the case of highly infectious viruses. The purpose of this LDRD was to determine the efficacy of the Sandia National Laboratories developed decontamination formulations against Bovine Coronavirus (BCV) as a surrogate for the coronavirus that causes Severe Acute Respiratory Syndrome (SARS) in humans. The outbreak of SARS in late 2002 resulted from a highly infectious virus that was able to survive and remain infectious for extended periods. For this study, preliminary testing with Escherichia coli MS-2 (MS-2) and Escherichia coli T4 (T4) bacteriophages was conductedmore » to develop virucidal methodology for verifying the inactivation after treatment with the test formulations following AOAC germicidal methodologies. After the determination of various experimental parameters (i.e. exposure, concentration) of the formulations, final testing was conducted on BCV. All experiments were conducted with various organic challenges (horse serum, bovine feces, compost) for results that more accurately represent field use condition. The MS-2 and T4 were slightly more resistant than BCV and required a 2 minute exposure while BCV was completely inactivated after a 1 minute exposure. These results were also consistent for the testing conducted in the presence of the various organic challenges indicating that the test formulations are highly effective for real world application.« less

Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test.

PubMed

Chełmińska, Marta; Specjalski, Krzysztof; Różyło, Anna; Kołakowska, Agata; Jassem, Ewa

2016-04-01

Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens.

Challenges to promoting health for amateur athletes through anti-doping policy.

PubMed

Henning, April

2017-01-01

Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making.

Challenges to promoting health for amateur athletes through anti-doping policy

PubMed Central

Henning, April

2017-01-01

Anti-doping regulations are intended, at least in part, to promote the health of athletes. While most anti-doping efforts target elite and professional competitors, there have been recent moves by sport governing bodies to expand anti-doping testing to include amateur athletes. Drawing on previous critiques of anti-doping policies and illustrating cases, this article outlines five of the challenges to health promotion of applying the current detect and ban model to the amateur level of sport. I argue that the current approach is not effective and, in some ways, may undermine the goal of health promotion at the amateur level. In order to address these challenges, I propose alternative, health-centred strategies that focus on athlete empowerment and choice through critical awareness of a variety of substances, associated risks and rewards, and the role of expertise in decision-making. PMID:28736489

Challenges and opportunities in clinical translation of biomedical optical spectroscopy and imaging

NASA Astrophysics Data System (ADS)

Wilson, Brian C.; Jermyn, Michael; Leblond, Frederic

2018-03-01

Medical devices face many hurdles before they enter routine clinical practice to address unmet clinical needs. This is also the case for biomedical optical spectroscopy and imaging systems that are used here to illustrate the opportunities and challenges involved. Following initial concept, stages in clinical translation include instrument development, preclinical testing, clinical prototyping, clinical trials, prototype-to-product conversion, regulatory approval, commercialization, and finally clinical adoption and dissemination, all in the face of potentially competing technologies. Optical technologies face additional challenges from their being extremely diverse, often targeting entirely different diseases and having orders-of-magnitude differences in resolution and tissue penetration. However, these technologies can potentially address a wide variety of unmet clinical needs since they provide rich intrinsic biochemical and structural information, have high sensitivity and specificity for disease detection and localization, and are practical, safe (minimally invasive, nonionizing), and relatively affordable.

Safety Challenges and Improvement Strategies of Ethnic Minority Construction Workers: A Case Study in Hong Kong.

PubMed

Wu, Chunlin; Luo, Xiaowei; Wang, Tao; Wang, Yue; Sapkota, Bibek

2018-04-18

Due to cultural differences, ethnic minority construction workers are more difficult to manage and more vulnerable to accidents. This study aims to identify the major barriers faced by ethnic minority workers from their own perspectives and determine potential strategies to enhance safety climate of construction projects, thus ultimately improve their safety performance. A survey with modified Nordic safety climate questionnaire was conducted in a certain sub-contractor in Hong Kong. In-depth interviews, status quo description, major challenge investigation and safety knowledge tests were carried as well. The top three most important safety challenges identified are improper stereotypes from the whole industry, lack of opportunities for job assignment, and language barriers. To improve the safety performance, employers should allocate sufficient personal protective equipment and governments should organize unannounced site visits more frequently. Besides, the higher-level management should avoid giving contradictory instructions to foremen against to the standards of supervisors.

Humidity Testing for Human Rated Spacecraft

NASA Technical Reports Server (NTRS)

Johnson, Gary B.

2009-01-01

Determination that equipment can operate in and survive exposure to the humidity environments unique to human rated spacecraft presents widely varying challenges. Equipment may need to operate in habitable volumes where the atmosphere contains perspiration, exhalation, and residual moisture. Equipment located outside the pressurized volumes may be exposed to repetitive diurnal cycles that may result in moisture absorption and/or condensation. Equipment may be thermally affected by conduction to coldplate or structure, by forced or ambient air convection (hot/cold or wet/dry), or by radiation to space through windows or hatches. The equipment s on/off state also contributes to the equipment s susceptibility to humidity. Like-equipment is sometimes used in more than one location and under varying operational modes. Due to these challenges, developing a test scenario that bounds all physical, environmental and operational modes for both pressurized and unpressurized volumes requires an integrated assessment to determine the "worst-case combined conditions." Such an assessment was performed for the Constellation program, considering all of the aforementioned variables; and a test profile was developed based on approximately 300 variable combinations. The test profile has been vetted by several subject matter experts and partially validated by testing. Final testing to determine the efficacy of the test profile on actual space hardware is in the planning stages. When validation is completed, the test profile will be formally incorporated into NASA document CxP 30036, "Constellation Environmental Qualification and Acceptance Testing Requirements (CEQATR)."

Cough-variant asthma: a diagnostic dilemma in the occupational setting.

PubMed

Lipińska-Ojrzanowska, A; Wiszniewska, M; Walusiak-Skorupa, J

2015-03-01

Cough-variant asthma (Corrao's syndrome) is defined as the presence of chronic non-productive cough in patients with bronchial hyperresponsiveness (BHR) and response to bronchodilator therapy. This variant of asthma may present a diagnostic problem in occupational medicine. To describe additional evaluation of cough-variant asthma in a cyanoacrylate-exposed worker in whom standard diagnostic testing was negative. A female beautician was evaluated for suspected occupational allergic rhinitis and asthma. A specific inhalation challenge test (SICT) was performed with cyanoacrylate glues used for applying artificial eyelashes and nails. Spirometry and peak expiratory flow (PEF) measurements were recorded hourly for 24h; methacholine challenge testing was performed and nasal lavage (NL) samples were analysed for eosinophilia. After SICT, the patient developed sneezing, nasal airflow obstruction and cough. Declines in forced expiratory volume in 1 s and PEF were not observed. Eosinophil proportions in NL fluid increased markedly at 4 and 24h after SICT. A significant increase in BHR also occurred 24h after SICT. Clinical symptoms, post-challenge BHR and increased NL eosinophil counts confirmed a positive response to SICT and validated the diagnosis of cough-variant occupational asthma. SICT may be useful in cases where history and clinical data suggest cough-variant asthma and spirometric indices are negative. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Bilateral isolated submandibular gland mumps.

PubMed

Cheung, Linnea; Henderson, Arthur Harry; Banfield, Graham; Carswell, Andrew

2017-06-05

Isolated submandibular swellings pose a diagnostic challenge to the practising otolaryngologist. We report an unusual case of mumps isolated to bilateral submandibular glands. We discuss the case and the literature surrounding this condition and remind clinicians that mumps should be considered as a diagnosis in the presence of submandibular gland swelling in the absence of typical parotid swelling associated with mumps. Early consideration of this differential diagnosis, serological testing and a multidisciplinary approach may help to clinch the diagnosis earlier and prevent spread of the virus. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mumps outbreak and laboratory diagnosis.

PubMed

Maillet, Mylène; Bouvat, Eric; Robert, Nicole; Baccard-Longère, Monique; Morel-Baccard, Christine; Morand, Patrice; Vabret, Astrid; Stahl, Jean-Paul

2015-01-01

Several mumps outbreaks have been reported in Europe and in the United States among highly vaccinated populations. Biological diagnosis is classically based on the detection of mumps-specific IgM, but the ability of serological tests to confirm mumps infection seems to be limited among vaccinated patients. We aim to report a mumps outbreak in an engineering school in Grenoble, France, from February to June 2013 and results of the biological testing. WHO definitions were used to define cases. Mumps--specific IgM and IgG were assessed by a commercially available EIA. Mumps RNA detection by real time reverse transcriptase polymerase chain reaction tests (RT-PCR) and mumps genotyping were performed by the French National Reference Centre for Paramyxoviridae. Sixty two mumps patient-cases were identified using WHO case definitions, 20 being biologically explored, of which 17 were confirmed by biological tests. Vaccination status was documented for 27 patients/62: 4 (14.8%) patients had received one dose of MMR vaccine, and 23 (85.2) two doses of MMR vaccine. Among the biologically explored patients, 83% had a positive RT PCR at the first sampling whereas only 45% had positive or equivocal IgM. All the genotyped strains were genotype G. Mumps laboratory diagnosis in a highly vaccinated population is challenging. Serological tests among vaccinated patients should be interpreted cautiously and confirmed by RT-PCR tests at the beginning of a mumps outbreak. Copyright © 2014 Elsevier B.V. All rights reserved.

Generalized reactions during skin testing with clindamycin in drug hypersensitivity: a report of 3 cases and review of the literature.

PubMed

Papakonstantinou, Eleni; Müller, Sabine; Röhrbein, Jan H; Wieczorek, Dorothea; Kapp, Alexander; Jakob, Thilo; Wedi, Bettina

2018-04-01

The diagnostic approach to drug hypersensitivity includes a detailed medical history, clinical examination, and skin testing and/or oral challenge with a culprit or alternative drug, depending on the type of reaction and the suspected drugs. Although skin testing is considered to be rather safe, cutaneous and systemic, including fatal, reactions have been described. To report 3 cases with generalized delayed reactions after skin testing with clindamycin, and to review the existing literature. Thorough clinical examination, blood tests and prick, intradermal and patch tests were performed in 3 patients. All patients experienced generalized maculopapular exanthema after intradermal and patch testing with clindamycin and amoxicillin in the first patient, and clindamycin alone in the second and third patient. None of the patients showed immediate reactions to skin tests, while positive intradermal reactions after 24 h to amoxicillin and clindamycin were observed in the first patient, and positive intradermal reactions after 24 h to clindamycin were observed in the second and third patients. Skin testing with clindamycin in the diagnosis of drug hypersensitivity carries some risk of adverse reactions. A stepwise and individual diagnostic work-up, considering potential risk factors, and testing in a specialized centre with emergency equipment available is highly recommended. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges

PubMed Central

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-01-01

Abstract Background While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. Methods We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)–coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. Results The overall tuberculosis burden was estimated to be 532005 cases (range, 333760–764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Conclusion Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. PMID:29117342

On the suitability of different representations of solid catalysts for combinatorial library design by genetic algorithms.

PubMed

Gobin, Oliver C; Schüth, Ferdi

2008-01-01

Genetic algorithms are widely used to solve and optimize combinatorial problems and are more often applied for library design in combinatorial chemistry. Because of their flexibility, however, their implementation can be challenging. In this study, the influence of the representation of solid catalysts on the performance of genetic algorithms was systematically investigated on the basis of a new, constrained, multiobjective, combinatorial test problem with properties common to problems in combinatorial materials science. Constraints were satisfied by penalty functions, repair algorithms, or special representations. The tests were performed using three state-of-the-art evolutionary multiobjective algorithms by performing 100 optimization runs for each algorithm and test case. Experimental data obtained during the optimization of a noble metal-free solid catalyst system active in the selective catalytic reduction of nitric oxide with propene was used to build up a predictive model to validate the results of the theoretical test problem. A significant influence of the representation on the optimization performance was observed. Binary encodings were found to be the preferred encoding in most of the cases, and depending on the experimental test unit, repair algorithms or penalty functions performed best.

Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards

PubMed Central

Sun, Y.; Tang, L.; Procop, G. W.; Hillyard, D. R.; Young, S. A.; Caliendo, A. M.

2016-01-01

ABSTRACT It has been hoped that the recent availability of WHO quantitative standards would improve interlaboratory agreement for viral load testing; however, insufficient data are available to evaluate whether this has been the case. Results from 554 laboratories participating in proficiency testing surveys for quantitative PCR assays of cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), adenovirus (ADV), and human herpesvirus 6 (HHV6) were evaluated to determine overall result variability and then were stratified by assay manufacturer. The impact of calibration to international units/ml (CMV and EBV) on variability was also determined. Viral loads showed a high degree of interlaboratory variability for all tested viruses, with interquartile ranges as high as 1.46 log10 copies/ml and the overall range for a given sample up to 5.66 log10 copies/ml. Some improvement in result variability was seen when international units were adopted. This was particularly the case for EBV viral load results. Variability in viral load results remains a challenge across all viruses tested here; introduction of international quantitative standards may help reduce variability and does so more or less markedly for certain viruses. PMID:27852673

Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward

PubMed Central

Dadu, A.; Ramsay, A.; Dara, M.

2014-01-01

Encouragingly, global rates of new tuberculosis (TB) cases have been falling since 2005, in line with the Millennium Development Goal targets; however, cases of multidrug-resistant (MDR-) and extensively drug-resistant TB (XDR-TB) have been increasing. Fifteen of the world's 27 high MDR- and XDR-TB burden countries are in the World Health Organization (WHO) European Region, of which 10 are in Eastern Europe (including Baltic and Caucasus countries). To address the MDR- and XDR-TB situation in the WHO European Region, a Consolidated Action Plan to Prevent and Combat M/XDR-TB (2011–2015) was developed for all 53 Member States and implemented in 2011. Since the implementation of the Action Plan, the proportion of MDR-TB appears largely to have levelled off among bacteriologically confirmed TB cases in high-burden countries with universal or near universal (>95%) first-line drug susceptibility testing (DST). The treatment success rate, however, continues to decrease. A contributing factor is the substantial proportion of MDR-TB cases that are additionally resistant to either a fluoroquinolone, a second-line injectable agent or both (XDR-TB); high-burden country proportions range from 12.6% to 80.4%. Proportions of XDR-TB range from 5% to 24.8%. Despite much progress in Eastern Europe, critical challenges remain as regards access to appropriate treatment regimens; patient hospitalisation; scale-up of laboratory capacity, including the use of rapid diagnostics and second-line DST; vulnerable populations; human resources; and financing. Solutions to these challenges are aligned with the Post-2015 Global TB strategy. As a first step, the global strategy should be adapted at regional and country levels to serve as a framework for immediate actions as well as longer-term ways forward. PMID:26393095

Acquisition Challenge: The Importance of Incompressibility in Comparing Learning Curve Models

DTIC Science & Technology

2015-10-01

parameters for all four learning mod- els used in the study . The learning rate factor, b, is the slope of the linear regression line, which in this case is...incorporated within the DoD acquisition environment. This study tested three alternative learning models (the Stanford-B model, DeJong’s learning formula...appropriate tools to calculate accurate and reliable predictions. However, conventional learning curve methodology has been in practice since the pre

Correlation of in vitro challenge testing with consumer use testing for cosmetic products.

PubMed Central

Brannan, D K; Dille, J C; Kaufman, D J

1987-01-01

An in vitro microbial challenge test has been developed to predict the likelihood of consumer contamination of cosmetic products. The challenge test involved inoculating product at four concentrations (30, 50, 70, and 100%) with microorganisms known to contaminate cosmetics. Elimination of these microorganisms at each concentration was followed over a 28-day period. The test was used to classify products as poorly preserved, marginally preserved, or well preserved. Consumer use testing was then used to determine whether the test predicted the risk of actual consumer contamination. Products classified by the challenge test as poorly preserved returned 46 to 90% contaminated after use. Products classified by the challenge test as well preserved returned with no contamination. Marginally preserved products returned with 0 to 21% of the used units contaminated. As a result, the challenge test described can be accurately used to predict the risk of consumer contamination of cosmetic products. PMID:3662517

Single-Case Experimental Designs to Evaluate Novel Technology-Based Health Interventions

PubMed Central

Cassidy, Rachel N; Raiff, Bethany R

2013-01-01

Technology-based interventions to promote health are expanding rapidly. Assessing the preliminary efficacy of these interventions can be achieved by employing single-case experiments (sometimes referred to as n-of-1 studies). Although single-case experiments are often misunderstood, they offer excellent solutions to address the challenges associated with testing new technology-based interventions. This paper provides an introduction to single-case techniques and highlights advances in developing and evaluating single-case experiments, which help ensure that treatment outcomes are reliable, replicable, and generalizable. These advances include quality control standards, heuristics to guide visual analysis of time-series data, effect size calculations, and statistical analyses. They also include experimental designs to isolate the active elements in a treatment package and to assess the mechanisms of behavior change. The paper concludes with a discussion of issues related to the generality of findings derived from single-case research and how generality can be established through replication and through analysis of behavioral mechanisms. PMID:23399668

[Analysis of a case series of workers with mobbing syndrome].

PubMed

Marinoni, B; Minelli, C M; Franzina, B; Martellosio, V; Scafa, F; Giorgi, I; Mazzacane, F; Stancanelli, M; Mennoia, N V; Candura, S M

2007-01-01

Mobbing represents nowadays a major challenge for Occupational Medicine. We examined, during the last seven years, 253 patients who asked medical assistance for psychopathological problems by them ascribed to mobbing in the working environment. All patients underwent occupational health visit, psychological counselling (including personality tests administration), and psychiatric evaluation. A clinical picture probably due to mobbing was diagnosed in 37 workers: 2 cases of Post-Traumatic Stress Disorder (PTSD), 33 of Adjustment Disorder (AD), and 2 of anxiety disorder. Regarding mobbing typology, we found 19 cases of vertical mobbing (by an employer/manager to employees), 14 cases of strategic mobbing, 3 cases of horizontal mobbing (among colleagues), and one non intentional mobbing. In conclusion, a pure mobbing syndrome was diagnosed in a lower proportion than that reported by other investigators. The described interdisciplinary approach appears useful for the diagnostic assessment of suspect mobbing cases, that in turn is crucial for prognosis and treatment, as well as in relation to medico-legal issues and work-related compensation claims.

Application-level regression testing framework using Jenkins

DOE PAGES

Budiardja, Reuben; Bouvet, Timothy; Arnold, Galen

2017-09-26

Monitoring and testing for regression of large-scale systems such as the NCSA's Blue Waters supercomputer are challenging tasks. In this paper, we describe the solution we came up with to perform those tasks. The goal was to find an automated solution for running user-level regression tests to evaluate system usability and performance. Jenkins, an automation server software, was chosen for its versatility, large user base, and multitude of plugins including collecting data and plotting test results over time. We also describe our Jenkins deployment to launch and monitor jobs on remote HPC system, perform authentication with one-time password, and integratemore » with our LDAP server for its authorization. We show some use cases and describe our best practices for successfully using Jenkins as a user-level system-wide regression testing and monitoring framework for large supercomputer systems.« less

Application-level regression testing framework using Jenkins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budiardja, Reuben; Bouvet, Timothy; Arnold, Galen

Monitoring and testing for regression of large-scale systems such as the NCSA's Blue Waters supercomputer are challenging tasks. In this paper, we describe the solution we came up with to perform those tasks. The goal was to find an automated solution for running user-level regression tests to evaluate system usability and performance. Jenkins, an automation server software, was chosen for its versatility, large user base, and multitude of plugins including collecting data and plotting test results over time. We also describe our Jenkins deployment to launch and monitor jobs on remote HPC system, perform authentication with one-time password, and integratemore » with our LDAP server for its authorization. We show some use cases and describe our best practices for successfully using Jenkins as a user-level system-wide regression testing and monitoring framework for large supercomputer systems.« less

Ice Growth Measurements from Image Data to Support Ice Crystal and Mixed-Phase Accretion Testing

NASA Technical Reports Server (NTRS)

Struk, Peter M.; Lynch, Christopher J.

2012-01-01

This paper describes the imaging techniques as well as the analysis methods used to measure the ice thickness and growth rate in support of ice-crystal icing tests performed at the National Research Council of Canada (NRC) Research Altitude Test Facility (RATFac). A detailed description of the camera setup, which involves both still and video cameras, as well as the analysis methods using the NASA Spotlight software, are presented. Two cases, one from two different test entries, showing significant ice growth are analyzed in detail describing the ice thickness and growth rate which is generally linear. Estimates of the bias uncertainty are presented for all measurements. Finally some of the challenges related to the imaging and analysis methods are discussed as well as methods used to overcome them.

Ice Growth Measurements from Image Data to Support Ice-Crystal and Mixed-Phase Accretion Testing

NASA Technical Reports Server (NTRS)

Struk, Peter, M; Lynch, Christopher, J.

2012-01-01

This paper describes the imaging techniques as well as the analysis methods used to measure the ice thickness and growth rate in support of ice-crystal icing tests performed at the National Research Council of Canada (NRC) Research Altitude Test Facility (RATFac). A detailed description of the camera setup, which involves both still and video cameras, as well as the analysis methods using the NASA Spotlight software, are presented. Two cases, one from two different test entries, showing significant ice growth are analyzed in detail describing the ice thickness and growth rate which is generally linear. Estimates of the bias uncertainty are presented for all measurements. Finally some of the challenges related to the imaging and analysis methods are discussed as well as methods used to overcome them.

[A case of loxoprofen-induced pulmonary eosinophilia].

PubMed

Ii, T; Doutsu, Y; Ashitani, J; Taniguchi, H; Mizuta, M; Toshimori, H; Matsukura, S

1992-05-01

A 65-year-old female suffering from lumbago, headache, and hypertension had been treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. On June 13, 1990, 2 weeks after the commencement of loxoprofen administration, she developed cough and low grade fever. She was treated with antibiotics and NSAIDs without improvement. Laboratory data showed marked eosinophilia (2200/mm3), elevation of IgE (3090 IU/ml), and liver dysfunction. Her chest X-ray revealed no active lesion, but the percentage of eosinophils in BALF was elevated (38%). Because drug-induced eosinophilic pneumonia was suspected, all drugs were discontinued. Her symptoms improved and the abnormalities of laboratory data normalized. The lymphocyte stimulation test was weakly positive with three NSAIDs (loxoprofen, pranoprofen, and alminoprofen). The challenge test by loxoprofen reproduced eosinophilia and liver dysfunction, suggesting that she had loxoprofen-induced eosinophilic pneumonia. To our knowledge, this is the first reported case of loxoprofen-induced lung injury.

Radiocontrast media-associated exanthema: identification of cross-reactivity and tolerability by allergologic testing.

PubMed

Seitz, Cornelia S; Pfeuffer, Petra; Raith, Petra; Bröcker, Eva-B; Trautmann, Axel

2009-10-01

All iodinated radiocontrast media (RCM) may cause hypersensitivity reactions, either immediate-type within 5-10 min of RCM injection or delayed-type, which become apparent more than 1h after RCM exposure. Delayed-type hypersensitivity to RCM may pose a problem for future radiologic investigations because due to possible immunological cross-reactivity all iodinated RCM are usually avoided. The aim of this study was not only to identify the causal RCM for the exanthema but also to demonstrate that patients may receive alternative iodinated RCM despite a history of RCM-induced allergic exanthema. We evaluated 32 patients with a history of exanthema after RCM application using standardized patch, prick and intradermal skin testing. In case of positive skin tests intravenous challenges with skin-test-negative RCM were performed to identify non-ionic monomer RCM which are tolerated. In 6 out of 32 patients skin tests strongly suggested a delayed-type non-IgE-mediated allergic hypersensitivity to the RCM iomeprol (3x), iopromide (2x), and iopamidol. In 4 patients alternative non-ionic monomer RCM (2x iosarcol, iopromide, and iomeprol) were identified by controlled challenge tests. The evaluation of patients with RCM-associated exanthema should always include appropriate skin tests ensuring that patients with a delayed-type allergic RCM-induced exanthema are not missed. Moreover, allergologic testing may identify alternative RCM of the group of non-ionic monomers, which are tolerated in future radiologic investigations.

International Approaches for Nuclear Waste Disposal in Geological Formations: Geological Challenges in Radioactive Waste Isolation—Fifth Worldwide Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faybishenko, Boris; Birkholzer, Jens; Sassani, David

The overall objective of the Fifth Worldwide Review (WWR-5) is to document the current state-of-the-art of major developments in a number of nations throughout the World pursuing geological disposal programs, and to summarize challenging problems and experience that have been obtained in siting, preparing and reviewing cases for the operational and long-term safety of proposed and operating nuclear waste repositories. The scope of the Review is to address current specific technical issues and challenges in safety case development along with the interplay of technical feasibility, siting, engineering design issues, and operational and post-closure safety. In particular, the chapters included inmore » the report present the following types of information: the current status of the deep geological repository programs for high level nuclear waste and low- and intermediate level nuclear waste in each country, concepts of siting and radioactive waste and spent nuclear fuel management in different countries (with the emphasis of nuclear waste disposal under different climatic conditions and different geological formations), progress in repository site selection and site characterization, technology development, buffer/backfill materials studies and testing, support activities, programs, and projects, international cooperation, and future plans, as well as regulatory issues and transboundary problems.« less

[Airway management in Ludwig's angina - a challenge: case report].

PubMed

Fellini, Roberto Taboada; Volquind, Daniel; Schnor, Otávio Haygert; Angeletti, Marcelo Gustavo; Souza, Olívia Egger de

Ludwig's angina (LA) is an infection of the submandibular space, first described by Wilhelm Frederick von Ludwig in 1836. It represents an entity difficult to manage due to the rapid progression and difficulty in maintaining airway patency, a major challenge in medical practice, resulting in asphyxia and death in 8-10% of patients. Describe a case of a patient with Ludwig's angina undergoing surgery, with emphasis on airway management, in addition to reviewing the articles published in the literature on this topic. Male patient, 21 years, drug addict, admitted by the emergency department and diagnosed with LA. Difficult airway was identified during the anesthetic examination. In additional tests, significant deviation from the tracheal axis was seen. Undergoing bilateral thoracoscopic pleural drainage, we opted for airway management through tracheal intubation using fiberoptic bronchoscopy, and balanced general anesthesia was proposed. There were no complications during the surgical-anesthetic act. After the procedure, the patient remained intubated and mechanically ventilated in the intensive care unit. Airway management in patients with Ludwig's angina remains challenging. The choice of the safest technique should be based on clinical signs, technical conditions available, and the urgent need to preserve the patient's life. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Presentation and Treatment of Histoplasmosis in Pediatric Oncology Patients: Case Series and Review of the Literature.

PubMed

Hess, Jennifer; Fondell, Andrew; Fustino, Nicholas; Malik, Jeff; Rokes, Christopher

2017-03-01

Histoplasmosis is an endemic fungus in several regions of the United States. The diagnosis and treatment of this infection can be challenging in pediatric oncology patients. We present 5 patients diagnosed with histoplasmosis while receiving treatment at a midsize pediatric oncology center in Iowa. Two cases occurred in patients with acute lymphoblastic leukemia and 3 cases in patients with solid tumors. All patients were treated with antifungal therapy and demonstrated excellent clinical response. Histoplasmosis should be considered as a potential cause of nonspecific febrile illness, pulmonary masses, and bone marrow suppression in immunocompromised patients in endemic regions. Prompt and accurate diagnosis can facilitate timely antifungal therapy and avoidance of prolonged hospital stays, invasive testing, unnecessary antibiotics, and unwarranted anticancer therapies.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States – A Case-Series

PubMed Central

Cantey, Paul T.; Weeks, Jessica; Edwards, Morven; Rao, Suchitra; Ostovar, G. Amin; Dehority, Walter; Alzona, Maria; Swoboda, Sara; Christiaens, Brooke; Ballan, Wassim; Hartley, John; Terranella, Andrew; Weatherhead, Jill; Dunn, James J.; Marx, Douglas P.; Hicks, M. John; Rauch, Ronald A.; Smith, Christiana; Dishop, Megan K.; Handler, Michael H.; Dudley, Roy W. R.; Chundu, Kote; Hobohm, Dan; Feiz-Erfan, Iman; Hakes, Joseph; Berry, Ryan S.; Stepensaski, Shelly; Greenfield, Benjamin; Shroeder, Laura; Bishop, Henry; de Almeida, Marcos; Mathison, Blaine; Eberhard, Mark

2016-01-01

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies. PMID:26611778

Still's Disease in a Pediatric Patient after Liver Transplantation.

PubMed

Meza, Juan-Carlos; Muñoz-Buitrón, Evelyn; Bonilla-Abadía, Fabio; Cañas, Carlos Alberto; Tobón, Gabriel J

2013-01-01

Still's disease (SD) is a multisystemic inflammatory disease characterized by persistent arthritis and in many cases with fever of unknown origin. Diagnosis of SD is challenging because of nonspecific characteristics and especially in the case of a patient with solid organ transplantation and immunosuppressive therapy where multiple causes of fever are possible. There is no diagnostic test for SD, even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, and useful imaging studies for the diagnosis or followup of SD have not been developed. We report the case of a 9-year-old child who presented with high grade fever associated with joint pain after a history of liver transplantation and immunosuppressive therapy. Laboratory tests showed increased acute phase reactants, elevated ferritin, and leukocytosis. An 18 F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) was performed identifying abnormal hypermetabolic areas localized in spleen, transplanted liver, and bone marrow secondary to inflammatory process. All infectious, autoimmune, and malignant causes were ruled out. A diagnosis of SD was performed and a steroid-based regimen was initiated with adequate response and no evidence of recurrence. To our knowledge this is the first case of SD following a solid organ transplant.

[Reflex epilepsy evoked by decision making: report of a case (author's transl)].

PubMed

Mutani, R; Ganga, A; Agnetti, V

1980-01-01

A 17-year-old girl with a story of Gran Mal attacks occurring during lessons of mathematics or solving mathematical problems, was investigated with prolonged EEG recordings. During the sessions, relax periods were alternated with arithmetical or mathematical testing, with card or checkers games and solution of puzzles and crossword problems, and with different neuropsychological tests. EGG recordings were characterized by the appearance, on a normal background, of bilaterally synchronous and symmetrical spike-and-wave and polispike-and-wave discharges, associated with loss of consciousness. During relax their mean frequency was one/54 min., it doubled during execution of tests involved with nonsequential decision making, and was eight times as high (one/7 min.) during tests involving sequential decision making. Some tension, challenge and complexity of the performance were also important as precipitating factors. Their lack deprived sequential tests of their efficacy, while on the contrary their presence sometimes gave nonsequential tests full efficacy.

Visual inspection with acetic acid and Lugol's iodine in cervical cancer screening at the general referral hospital Kayembe in Mbuji-Mayi, Democratic Republic of Congo

PubMed Central

Desire, Banza Kamba; Philippe, Cilundika Mulenga; Thierry, Kabengele; Félix, Kitenge Wa Momat; Wembodinga, Gilbert Utshudienyema; Prosper, Kakudji Luhete; Oscar, Luboya Numbi

2016-01-01

Introduction Cervical cancer is the leading cause of morbidity and mortality of women from cancer in the developing World. It is the primary cause of reduced life expectancy in Sub-Saharan countries such as Democratic Republic of Congo. The aim of this work was to determinate the socio-demographic profile of women with precancerous and cancerous lesions of the cervix, to determinate the frequency of VIA and VILI positive cases and to show the challenges that can be faced in managing patients with abnormalities in the city of Mbuji-Mayi in the Democratic Republic of Congo. Methods As part of its activities, the “Association de Lutte contre le Cancer du Col utérin” (ALCC) organized a community outreach followed by free voluntary testing for cervical cancer for two weeks (26thMarch to 10th April 2011) at the General Referral Hospital Kayembe in Mbuji-Mayi (Democratic Republic of Congo). Results A total of 229 women were examined. 38% of tests (VIA + VILI) were positive with 6 clinically suspected cases of invasive cancer at stage 1 (7% of cases). Nearly 70% of patients were still of childbearing age and had started their first sexual intercourse before 18 years of age and 86% of cases were multiparous. Given the material, financial and technical constraints, 75% of patients were placed in a monitoring program of 9 months to 1 year (= expectation and another test) while 11% of them were selected for a biopsy to be locally practiced and sent to the pathologist. Nearly 8% of the cases were candidates for hysterectomy. Conclusion Given the difficulties encountered and the frequency of positive tests, we recommend another study with a larger sample, improved working conditions (mainly equipment) and the association of another test such as the Human Papilloma Virus (HPV) test. PMID:27217888

AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.

PubMed

Ben-Shimon, Avraham; Niv, Masha Y

2015-05-05

The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mars Ascent Vehicle Test Requirements and Terrestrial Validation

NASA Technical Reports Server (NTRS)

Dankanich, John W.; Cathey, Henry M.; Smith, David A.

2011-01-01

The Mars robotic sample return mission has been a potential flagship mission for NASA s science mission directorate for decades. The Mars Exploration Program and the planetary science decadal survey have highlighted both the science return of the Mars Sample Return mission, but also the need for risk reduction through technology development. One of the critical elements of the MSR mission is the Mars Ascent Vehicle, which must launch the sample from the surface of Mars and place it into low Mars orbit. The MAV has significant challenges to overcome due to the Martian environments and the Entry Descent and Landing system constraints. Launch vehicles typically have a relatively low success probability for early flights, and a thorough system level validation is warranted. The MAV flight environments are challenging and in some cases impossible to replicate terrestrially. The expected MAV environments have been evaluated and a first look of potential system test options has been explored. The terrestrial flight requirements and potential validation options are presented herein.

Track reconstruction at LHC as a collaborative data challenge use case with RAMP

NASA Astrophysics Data System (ADS)

Amrouche, Sabrina; Braun, Nils; Calafiura, Paolo; Farrell, Steven; Gemmler, Jochen; Germain, Cécile; Gligorov, Vladimir Vava; Golling, Tobias; Gray, Heather; Guyon, Isabelle; Hushchyn, Mikhail; Innocente, Vincenzo; Kégl, Balázs; Neuhaus, Sara; Rousseau, David; Salzburger, Andreas; Ustyuzhanin, Andrei; Vlimant, Jean-Roch; Wessel, Christian; Yilmaz, Yetkin

2017-08-01

Charged particle track reconstruction is a major component of data-processing in high-energy physics experiments such as those at the Large Hadron Collider (LHC), and is foreseen to become more and more challenging with higher collision rates. A simplified two-dimensional version of the track reconstruction problem is set up on a collaborative platform, RAMP, in order for the developers to prototype and test new ideas. A small-scale competition was held during the Connecting The Dots / Intelligent Trackers 2017 (CTDWIT 2017) workshop. Despite the short time scale, a number of different approaches have been developed and compared along a single score metric, which was kept generic enough to accommodate a summarized performance in terms of both efficiency and fake rates.

Outbreak of hepatitis A in an extended family after importation by non-immune travellers.

PubMed

Kumbang, J; Ejide, S; Tedder, R S; Ngui, S L

2012-10-01

The incidence of hepatitis A in England has declined in recent years, but travel-related cases and imported infections remain a challenge. We report an outbreak of hepatitis A in an extended family where two primary cases were infected while in Pakistan and two secondary cases were infected in England. All four were infected by the same genotype IIIA virus. Testing of the children in the extended family by dried blood spots (DBS) determined that three had evidence of recent past infections (anti-HAV IgM positive), one had a current asymptomatic infection (anti-HAV IgM and HAV RNA positive) and one was incubating the virus (anti-HAV IgM negative, HAV RNA positive). HAV RNA from the DBS was identical to the adult cases. This outbreak demonstrates secondary spread of hepatitis A by asymptomatic children after importation from abroad and highlights the importance of preventing travel-associated hepatitis A infection.

Microfollicular adenoma of ectopic thyroid gland masquerading as salivary gland tumor - a diagnostic and therapeutic challenge: a case report.

PubMed

Deshmukh, Sanjay D; Khandeparkar, Siddhi G Sinai; Gulati, Harveen K; Naik, Chetana S

2014-08-07

Ectopic thyroid tissue may appear in any location along the trajectory of the thyroglossal duct from the foramen cecum to the mediastinum. Rarely, there is incomplete descent of the gland where the final resting point may be high resulting in sublingual ectopic thyroid tissue. Ectopic thyroid tissue carries a low risk of malignancy. Most recently reported neoplasms in ectopic thyroid tissue have been papillary carcinoma of thyroid. Individual case reports of clear cell type of follicular adenoma within the ectopic thyroid tissue have been described in the literature. We present a rare case of microfollicular follicular adenoma in an ectopic sublingual thyroid tissue presenting as submental swelling in a euthyroid 24-year-old Dravidian woman. Findings in this case emphasize that when confronted with a submental/sublingual mass lesion, the evaluation of thyroid function tests and ultrasonography of the neck should be included in a pre-operative workup.

[Ketoconazole-induced hepatitis. Case report].

PubMed

Henning, H; Kasper, B; Lüders, C J

1983-12-01

Since Oct. 1981 a new systemic antifungal drug Ketoconazole is available in the Federal Republic of Germany that has proven effective even in severe cases with fungal infections. This case-study will call attention on a rare but important side effect, namely Ketoconazole induced hepatitis. As an acute icteric viral hepatitis, type Non-A-Non-B-hepatitis possibly misdiagnosed only a carefully compiled history of the recent intake of drugs points at the real cause of hepatitis. In our case-report we observed a considerable increase in serum enzymes, especially GOT, GPT and GLDH after a drug-challenge with two tablets. We recommend so-called liver functions tests 2 to 3 weeks after beginning of therapy and further-on in monthly intervals. Histologically at that time toxic hydropic changes of the liver cells and a mesenchymal reaction with portal and intralobular mainly eosinophilic infiltration could be established. The serum enzymes came to normal only after 12 weeks.

A Chinese patient with peritoneal dialysis-related peritonitis caused by Gordonia terrae: a case report.

PubMed

Hou, Chenrui; Yang, Yun; Li, Ziyang

2017-02-28

Gordonia terrae is a rare cause of clinical infections, with only 23 reported cases. We report the first case of peritoneal dialysis-related peritonitis caused by Gordonia terrae in mainland China. A 52-year-old man developed peritoneal dialysis-related peritonitis and received preliminary antibiotic treatment. After claiming that his symptoms had been resolved, the patient insisted on being discharged (despite our recommendations) and did not receive continued treatment after leaving the hospital. A telephone follow-up with the patient's relatives revealed that the patient died 3 months later. Routine testing did not identify the bacterial strain responsible for the infection, although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry identified the strain as Gordonia rubropertincta. However, a 16S rRNA sequence analysis using an isolate from the peritoneal fluid culture revealed that the responsible strain was actually Gordonia terrae. Similar to this case, all previously reported cases have involved a delayed diagnosis and initial treatment failure, and the definitive diagnosis required a 16S rRNA sequence analysis. Changes from an inappropriate antibiotic therapy to an appropriate one have relied on microbiological testing and were performed 7-32 days after the initial treatment. The findings from our case and the previously reported cases indicate that peritoneal dialysis-related peritonitis caused by Gordonia terrae can be difficult to identify and treat. It may be especially challenging to diagnose these cases in countries with limited diagnostic resources.

Laboratory-Based Surveillance of Extensively Drug-Resistant Tuberculosis in Eastern China.

PubMed

Huang, Yu; Wu, Qingqing; Xu, Shuiyang; Zhong, Jieming; Chen, Songhua; Xu, Jinghang; Zhu, Liping; He, Haibo; Wang, Xiaomeng

2017-03-01

With 25% of the global burden, China has the highest incidence of drug-resistant tuberculosis (TB) in the world. However, surveillance data on extensively drug-resistant TB (XDR-TB) from China are scant. To estimate the prevalence of XDR-TB in Zhejiang, Eastern China, 30 of 90 TB treatment centers in Zhejiang were recruited. Patients with suspected TB who reported to the clinics for diagnosis were requested to undergo a smear sputum test. Positive sputum samples were tested for drug susceptibility. Data on anti-TB drug resistance from 1999 to 2008 were also collected to assess drug resistance trends. A total of 931 cases were recruited for drug susceptibility testing (DST). Among these, 23.6% (95% confidence interval [CI], 18.8-24.4) were resistant to any of the following drugs: isoniazid, rifampin, streptomycin, and ethambutol. Multidrug resistant (MDR) strains were identified in 5.1% of all cases (95% CI, 3.61-6.49). Among MDR-TB cases, 6.4% were XDR (95% CI, 1.7-18.6) and 8.9% (95% CI, 7.0-10.8) of all cases were resistant to either isoniazid or rifampin (but not both). Among MDR-TB cases, 23.4% (95% CI, 12.8-38.4) were resistant to either fluoroquinolones or a second-line anti-TB injectable drug, but not both. From 1999 to 2014, the percentage of MDR cases decreased significantly, from 8.6% to 5.1% (p = 0.00). The Global Fund to Fight TB program showed signs of success in Eastern China. However, drug-resistant TB, MDR-TB, and XDR-TB still pose a challenge for TB control in Eastern China. High-quality directly observed treatment, short-course, and universal DST for TB cases to determine appropriate treatment regimens are urgently needed to prevent acquired drug resistance.

Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology▿ † ‡

PubMed Central

Helb, Danica; Jones, Martin; Story, Elizabeth; Boehme, Catharina; Wallace, Ellen; Ho, Ken; Kop, JoAnn; Owens, Michelle R.; Rodgers, Richard; Banada, Padmapriya; Safi, Hassan; Blakemore, Robert; Lan, N. T. Ngoc; Jones-López, Edward C.; Levi, Michael; Burday, Michele; Ayakaka, Irene; Mugerwa, Roy D.; McMillan, Bill; Winn-Deen, Emily; Christel, Lee; Dailey, Peter; Perkins, Mark D.; Persing, David H.; Alland, David

2010-01-01

Current nucleic acid amplification methods to detect Mycobacterium tuberculosis are complex, labor-intensive, and technically challenging. We developed and performed the first analysis of the Cepheid Gene Xpert System's MTB/RIF assay, an integrated hands-free sputum-processing and real-time PCR system with rapid on-demand, near-patient technology, to simultaneously detect M. tuberculosis and rifampin resistance. Analytic tests of M. tuberculosis DNA demonstrated a limit of detection (LOD) of 4.5 genomes per reaction. Studies using sputum spiked with known numbers of M. tuberculosis CFU predicted a clinical LOD of 131 CFU/ml. Killing studies showed that the assay's buffer decreased M. tuberculosis viability by at least 8 logs, substantially reducing biohazards. Tests of 23 different commonly occurring rifampin resistance mutations demonstrated that all 23 (100%) would be identified as rifampin resistant. An analysis of 20 nontuberculosis mycobacteria species confirmed high assay specificity. A small clinical validation study of 107 clinical sputum samples from suspected tuberculosis cases in Vietnam detected 29/29 (100%) smear-positive culture-positive cases and 33/39 (84.6%) or 38/53 (71.7%) smear-negative culture-positive cases, as determined by growth on solid medium or on both solid and liquid media, respectively. M. tuberculosis was not detected in 25/25 (100%) of the culture-negative samples. A study of 64 smear-positive culture-positive sputa from retreatment tuberculosis cases in Uganda detected 63/64 (98.4%) culture-positive cases and 9/9 (100%) cases of rifampin resistance. Rifampin resistance was excluded in 54/55 (98.2%) susceptible cases. Specificity rose to 100% after correcting for a conventional susceptibility test error. In conclusion, this highly sensitive and simple-to-use system can detect M. tuberculosis directly from sputum in less than 2 h. PMID:19864480

Usefulness of routine preoperative testing in a developing country: a prospective study

PubMed Central

Bordes, Julien; Cungi, Pierre-Julien; Savoie, Pierre-Henry; Bonnet, Stéphane; Kaiser, Eric

2015-01-01

Introduction The assessment of anesthetic risks is an essential component of preoperative evaluation. In developing world, preanesthesia evaluation may be challenging because patient's medical history and records are scare, and language barrier limits physical examination. Our objective was to evaluate the impact of routine preoperative testing in a low-resources setting. Methods Prospective observational study performed in a French forward surgical unit in Abidjan, Ivory Coast. 201 patients who were scheduled for non urgent surgery were screened with routine laboratory exams during preoperative evaluation. Changes in surgery were assessed (delayed or scheduled). Results Abnormal hemoglobin findings were reported in 35% of patients, abnormal WBC count in 11,1% of patients, abnormal platelets in 15,3% of patients. Positive HIV results were found in 8,3% of cases. Routine tests represented 43,6% of changes causes. Conclusion Our study showed that in a developing country, routine preoperative tests showed abnormal results up to 35% of cases, and represented 43,5% of delayed surgery causes. The rate of tests leading to management changes varied widely, from 0% to 8,3%. These results suggested that selected tests would be useful to diagnose diseases that required treatment before non urgent surgery. However, larger studies are needeed to evaluate the cost/benefit ratio and the clinical impact of such a strategy. PMID:26516395

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

PubMed

Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

2014-09-01

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

Experimental Data from the Benchmark SuperCritical Wing Wind Tunnel Test on an Oscillating Turntable

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Piatak, David J.

2013-01-01

The Benchmark SuperCritical Wing (BSCW) wind tunnel model served as a semi-blind testcase for the 2012 AIAA Aeroelastic Prediction Workshop (AePW). The BSCW was chosen as a testcase due to its geometric simplicity and flow physics complexity. The data sets examined include unforced system information and forced pitching oscillations. The aerodynamic challenges presented by this AePW testcase include a strong shock that was observed to be unsteady for even the unforced system cases, shock-induced separation and trailing edge separation. The current paper quantifies these characteristics at the AePW test condition and at a suggested benchmarking test condition. General characteristics of the model's behavior are examined for the entire available data set.

Patch-testing for the management of hypersensitivity reactions to second-line anti-tuberculosis drugs: a case report.

PubMed

Khan, Samsuddin; Andries, Aristomo; Pherwani, Asha; Saranchuk, Peter; Isaakidis, Petros

2014-08-15

The second-line anti-tuberculosis drugs used in the treatment of multidrug-resistant tuberculosis often cause adverse events, especially in patients co-infected with the human immunodeficiency virus. Severe hypersensitivity reactions due to these drugs are rare and there is little published experience to guide their management. A 17-year old Indian female multidrug-resistant tuberculosis patient co-infected with human immunodeficiency virus developed a hypersensitivity reaction after starting second-line anti-tuberculosis treatment in Mumbai, India. The patient was being treated with kanamycin, moxifloxacin, para-aminosalicylic acid, cycloserine, clofazimine, and amoxicillin-clavulanic acid. Twenty-four hours later, the patient developed generalized urticaria, morbilliform rash and fever. All drugs were suspended and the patient was hospitalised for acute management. Skin patch-testing was used to identify drugs that potentially caused the hypersensitivity reaction; results showed a strong reaction to clofazimine, moderate reaction to kanamycin and mild reaction to cycloserine. An interim second-line anti-tuberculosis regimen was prescribed; cycloserine and kanamycin were then re-challenged one-by-one using incremental dosing, an approach that allowed clinicians to re-introduce these drugs promptly and safely. The patient is currently doing well. This is the first case-report of a multidrug-resistant tuberculosis patient co-infected with the human immunodeficiency virus with hypersensitivity reaction to multiple second-line anti-tuberculosis drugs. Skin patch-testing and controlled re-challenge can be a useful management strategy in such patients. There is an urgent need for second-line anti-tuberculosis regimens that are more effective, safe and better tolerated.

Value of PAX1 Methylation Analysis by MS-HRM in the Triage of Atypical Squamous Cells of Undetermined Significance.

PubMed

Li, Shi-Rong; Wang, Zhen-Ming; Wang, Yu-Hui; Wang, Xi-Bo; Zhao, Jian-Qiang; Xue, Hai-Bin; Jiang, Fu-Guo

2015-01-01

Detection of cervical high grade lesions in patients with atypical squamous cells of undetermined significance (ASCUS) is still a challenge. Our study tested the efficacy of the paired boxed gene 1 (PAX1) methylation analysis by methylation-sensitive high-resolution melting (MS-HRM) in the detection of high grade lesions in ASCUS and compared performance with the hybrid capture 2 (HC2) human papillomavirus (HPV) test. A total of 463 consecutive ASCUS women from primary screening were selected. Their cervical scrapings were collected and assessed by PAX1 methylation analysis (MS-HRM) and high-risk HPV-DNA test (HC2). All patients with ASCUS were admitted to colposcopy and cervical biopsies. The Chi- square test was used to test the differences of PAX1 methylation or HPV infection between groups. The specificity, sensitivity, and accuracy for detecting CIN2 + lesions were: 95.6%, 82.4%, and 94.6%, respectively, for the PAX1 MS-HRM test; and 59.7%, 64.7%, and 60.0% for the HC2 HPV test. The PAX1 methylation analysis by MS-HRM demonstrated a better performance than the high-risk HPV-DNA test for the detection of high grade lesions (CIN2 +) in ASCUS cases. This approach could screen out the majority of low grade cases of ASCUS, and thus reduce the referral rate to colposcopy.

A Case of Munchausen Syndrome Presenting with Hematemesis: A Case Report

PubMed Central

Aadil, Muhammad; Faraz, Aniqa; Anwar, Muhammad Jahanzaib; Nasir, Usama; Akhlaq, Anum

2017-01-01

Munchausen syndrome (MS) was first reported in 1951 by Richard Alan John Asher as a factitious disorder. It is a condition in which the patient intentionally produces symptoms to assume a sick role and gain medical attention. Underdiagnosis of this disorder results in the unnecessary use of medical resources, i.e. unnecessary medical tests and evaluations. This makes it one of the most challenging diagnosis in any medical set up. We present this rare case of a patient with chronic factitious disorder who presented to the emergency with hematemesis. The patient was successfully treated with psychotherapy with no recurrence. It is the need of the hour to create awareness amongst the medical and nonmedical population about factitious disorders so that they can easily be diagnosed and treated with efficiency. Further research is needed to find the risks leading to this syndrome and discover the cultural and social aspects of this disease, which may help us explore treatment strategies and avoid unnecessary tests and treatment.​ PMID:28979830

Development and pilot testing of an online case-based approach to shared decision making skills training for clinicians.

PubMed

Volk, Robert J; Shokar, Navkiran K; Leal, Viola B; Bulik, Robert J; Linder, Suzanne K; Mullen, Patricia Dolan; Wexler, Richard M; Shokar, Gurjeet S

2014-11-01

Although research suggests that patients prefer a shared decision making (SDM) experience when making healthcare decisions, clinicians do not routinely implement SDM into their practice and training programs are needed. Using a novel case-based strategy, we developed and pilot tested an online educational program to promote shared decision making (SDM) by primary care clinicians. A three-phased approach was used: 1) development of a conceptual model of the SDM process; 2) development of an online teaching case utilizing the Design A Case (DAC) authoring template, a well-tested process used to create peer-reviewed web-based clinical cases across all levels of healthcare training; and 3) pilot testing of the case. Participants were clinician members affiliated with several primary care research networks across the United States who answered an invitation email. The case used prostate cancer screening as the clinical context and was delivered online. Post-intervention ratings of clinicians' general knowledge of SDM, knowledge of specific SDM steps, confidence in and intention to perform SDM steps were also collected online. Seventy-nine clinicians initially volunteered to participate in the study, of which 49 completed the case and provided evaluations. Forty-three clinicians (87.8%) reported the case met all the learning objectives, and 47 (95.9%) indicated the case was relevant for other equipoise decisions. Thirty-one clinicians (63.3%) accessed supplementary information via links provided in the case. After viewing the case, knowledge of SDM was high (over 90% correctly identified the steps in a SDM process). Determining a patient's preferred role in making the decision (62.5% very confident) and exploring a patient's values (65.3% very confident) about the decisions were areas where clinician confidence was lowest. More than 70% of the clinicians intended to perform SDM in the future. A comprehensive model of the SDM process was used to design a case-based approach to teaching SDM skills to primary care clinicians. The case was favorably rated in this pilot study. Clinician skills training for helping patients clarify their values and for assessing patients' desire for involvement in decision making remain significant challenges and should be a focus of future comparative studies.

Animal Use and Lessons Learned in the U.S. High Production Volume Chemicals Challenge Program

PubMed Central

Manuppello, Joseph R.; Willett, Catherine E.; Sandler, Jessica T.

2012-01-01

Background: Launched by the U.S. Environmental Protection Agency (EPA) in 1998, the High Production Volume (HPV) Challenge Program was developed to address the perceived gap in basic hazard information for the 2,800 chemicals produced or imported into the United States in quantities of ≥ 1 million pounds per year. Health and environmental effects data obtained from either existing information or through new vertebrate animal testing were voluntarily submitted by chemical companies (sponsors) to the U.S. EPA. Despite the potential for extensive animal testing, animal welfare guidelines were not provided until after the start of the program. Objectives: We evaluated compliance with the animal welfare principles that arose from an agreement reached between the U.S. EPA and animal protection organizations and tracked the HPV program’s use of animals for testing. Discussion: Under a worst-case scenario, the HPV program had the potential to consume 3.5 million animals in new testing. After application of animal-saving measures, approximately 127,000 were actually used. Categorization of chemicals based on similar structure–activity and application of read-across, along with use of existing test data, were the most effective means of reducing animal testing. However, animal-saving measures were inconsistently used by both sponsors and the U.S. EPA. Conclusions: Lessons learned from the HPV program can be applied to future programs to minimize animal testing and promote more human-relevant chemical risk assessment. PMID:23033452

Ethiopian New Public Universities: Achievements, Challenges and Illustrative Case Studies

ERIC Educational Resources Information Center

van Deuren, Rita; Kahsu, Tsegazeab; Mohammed, Seid; Woldie, Wondimu

2016-01-01

Purpose: This paper aims to analyze and illustrate achievements and challenges of Ethiopian higher education, both at the system level and at the level of new public universities. Design/methodology/approach: Achievements and challenges at the system level are based on literature review and secondary data. Illustrative case studies are based on…

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 2 Challenge Problem Design and Test Specification

DTIC Science & Technology

2014-11-01

intelligence. No. Title of Case Study P U Pc Pt Ft Pa 1 Clinical vs. Actuarial Geospatial Profiling Strategies X X 2 Route Security in Baghdad X...support. Information Sciences , 176, 1570-1589. Burns, K. (2005). Mental models and normal errors. In Montgomery, H., Lipshitz, & Brehmer, B. (eds...utilities. Information Sciences , 179, 1599-1607. Davis, M. (1997). Game Theory: A Nontechnical Introduction. New York: Dover. Edwards, W. (1982

Scientists' attitudes on science and values: Case studies and survey methods in philosophy of science.

PubMed

Steel, Daniel; Gonnerman, Chad; O'Rourke, Michael

2017-06-01

This article examines the relevance of survey data of scientists' attitudes about science and values to case studies in philosophy of science. We describe two methodological challenges confronting such case studies: 1) small samples, and 2) potential for bias in selection, emphasis, and interpretation. Examples are given to illustrate that these challenges can arise for case studies in the science and values literature. We propose that these challenges can be mitigated through an approach in which case studies and survey methods are viewed as complementary, and use data from the Toolbox Dialogue Initiative to illustrate this claim. Copyright © 2017 Elsevier Ltd. All rights reserved.

Laboratory Diagnosis of Tuberculosis in Resource-Poor Countries: Challenges and Opportunities

PubMed Central

Parsons, Linda M.; Somoskövi, Ákos; Gutierrez, Cristina; Lee, Evan; Paramasivan, C. N.; Abimiku, Alash'le; Spector, Steven; Roscigno, Giorgio; Nkengasong, John

2011-01-01

Summary: With an estimated 9.4 million new cases globally, tuberculosis (TB) continues to be a major public health concern. Eighty percent of all cases worldwide occur in 22 high-burden, mainly resource-poor settings. This devastating impact of tuberculosis on vulnerable populations is also driven by its deadly synergy with HIV. Therefore, building capacity and enhancing universal access to rapid and accurate laboratory diagnostics are necessary to control TB and HIV-TB coinfections in resource-limited countries. The present review describes several new and established methods as well as the issues and challenges associated with implementing quality tuberculosis laboratory services in such countries. Recently, the WHO has endorsed some of these novel methods, and they have been made available at discounted prices for procurement by the public health sector of high-burden countries. In addition, international and national laboratory partners and donors are currently evaluating other new diagnostics that will allow further and more rapid testing in point-of-care settings. While some techniques are simple, others have complex requirements, and therefore, it is important to carefully determine how to link these new tests and incorporate them within a country's national diagnostic algorithm. Finally, the successful implementation of these methods is dependent on key partnerships in the international laboratory community and ensuring that adequate quality assurance programs are inherent in each country's laboratory network. PMID:21482728

ALK ambiguous-positive non-small cell lung cancers are tumors challenged by diagnostic and therapeutic issues.

PubMed

Uguen, Arnaud; Andrieu-Key, Sophie; Vergne, Florence; Descourt, Renaud; Quéré, Gilles; Quintin-Roué, Isabelle; Key, Stéphane; Guéguen, Paul; Talagas, Matthieu; De Braekeleer, Marc; Marcorelles, Pascale

2016-09-01

Searching for ALK rearrangements using the approved fluorescent in situ hybridization (FISH) test and complementary immunohistochemistry (IHC) has become the rule to treat patients with advanced non‑small cell lung cancer (NSCLC) with anti‑ALK targeted therapy. The concordance between the two techniques is reported to be strong but imperfect. We report our experience with cases of ALK‑rearranged lung adenocarcinomas pointing out particularly ambiguous cases. FISH and IHC data on ALK but also c‑MET IHC as well as EGFR and KRAS mutation screening are considered, together with response to crizotinib treatment. We classified the 55 FISH ALK‑rearranged tumors into two groups according to the FISH and IHC results: a concordant FISH+IHC+ group (31 tumors) and an ambiguous group (24 tumors). These tumors were considered as 'ambiguous' ALK‑positive due to negative (21 tumors) or non‑contributive (3 tumors) IHC. In addition, the percentage of FISH-positive nuclei was between 15 and 20% in 17 tumors belonging to one or the other group (now called borderline tumors). We discuss the accuracy of the different tests with intent to determine whether ambiguous and borderline tumors are real positive ALK‑rearranged tumors. To conclude, ambiguous ALK‑positive lung cancers are challenging tumors with diagnosis and therapeutic issues that can justify parallel FISH, IHC and molecular screening strategy.

Pisgah Lava Cave Communication Test: Science Case Study for the Networked Constellations Initiative

NASA Technical Reports Server (NTRS)

Belov, K.; Ellison, D.; Fraeman, A.

2017-01-01

As part of the science case study for the Networked Constellations initiative, a team of JPL scientists explore the possibility of a mission to study the lava caves on Mars. Natural caves on Mars and the Moon present a unique opportunity to learn about the planetary geology and to provide a shelter for human explorers. Due to power and communication challenges, a network of assets has significant advantages over a single asset sent inside a cave. However, communication between the assets and the data downlink present significant difficulties due to the presence of rough walls, boulders, and other obstacles with unknown dielectric constant inside a typical cave, disturbing the propagation of the radio waves. A detailed study is needed to establish the limitations of the current communication technologies and to develop requirements for the new communication technology applicable to the cave environment. On May 4 of 2017, Konstantin Belov, Doug Ellison, and Abby Fraeman visited a lava cave in Pisgah, CA. The purpose of the visit was to build a 3D map of the cave, which could be used to create a model of radio wave propagation, and to conduct a series of communication tests using off-the-shelf equipment to verify the in-cave communication challenges. This experiment should be considered as a simple 'proof of concept' and is the subject of this report.

Progressive respiratory distress in a 42-year-old HIV-positive woman with systemic lupus erythematosus.

PubMed

Mutengo, Katongo; Mukomena, Patrice; Lambwe, Nason; Ngalamika, Owen

2017-06-17

Identifying and treating the cause of pulmonary symptoms in HIV patients with underlying systemic lupus erythematosus (SLE) can be very challenging. Delays in diagnosing active SLE in HIV patients can lead to significant morbidity and even mortality. We report the case of an HIV-positive woman with SLE who presented with severe respiratory distress. A 42-year-old HIV-positive woman presented with a 7-month history of anorexia, progressive dyspnoea, and a productive cough. She had been put on treatment for pulmonary tuberculosis and pneumocystis jiroveci pneumonia for several months by the referring hospital without any significant improvement in her symptoms. Her initial laboratory investigations showed highly elevated d-dimer test results but confirmatory investigations for pulmonary embolism proved otherwise. An autoimmune screen revealed highly positive antinuclear antibody and anti-double-stranded DNA tests, and she responded very well to SLE treatment. Our case represents a situation where two diseases with antagonizing pathways of disease pathogenesis occur concurrently in the same patient. SLE is usually not among the differential diagnoses in HIV patients with respiratory distress. Management of patients with both SLE and HIV is also very challenging because improvement in one condition can lead to worsening of the other. Despite opportunistic infections being the likely cause of pulmonary symptoms in HIV patients, clinicians are encouraged to have a high index of suspicion for autoimmune interstitial lung disease in these patients.

The dilemma of allergy to food additives.

PubMed

Bahna, Sami L; Burkhardt, Joshua G

2018-01-01

To provide a brief summary on food additives and to outline a practical approach for evaluating subjects suspected of having reactions to food additives. Information was derived from selected reviews and original articles published in peer-reviewed journals, supplemented by the clinical experience of the authors. Priority was given to studies that used blinded, placebo controlled, oral challenges to confirm adverse reactions to food additives. In addition, selected, appropriately evaluated case reports were included. A large number of food additives are widely used in the food industry. Allergic reactions to additives seem to be rare but are very likely underdiagnosed, primarily due to a low index of suspicion. A wide variety of symptoms to food additives have been reported, but a cause-and-effect relationship has not been well documented in the majority of cases. Reactions to food additives should be suspected in patients who report symptoms related to multiple foods or to a certain food when commercially prepared but not when home made. It is also prudent to investigate food additives in subjects considered to have "idiopathic" reactions. Except for a limited number of natural additives, there is a small role for skin tests or in vitro testing. Oral challenge, in stages, with commonly used additives is the definitive procedure for detecting the offending agent. Once the specific additive is identified, management is strict avoidance, which can be difficult.

A 'Turing' Test for Landscape Evolution Models

NASA Astrophysics Data System (ADS)

Parsons, A. J.; Wise, S. M.; Wainwright, J.; Swift, D. A.

2008-12-01

Resolving the interactions among tectonics, climate and surface processes at long timescales has benefited from the development of computer models of landscape evolution. However, testing these Landscape Evolution Models (LEMs) has been piecemeal and partial. We argue that a more systematic approach is required. What is needed is a test that will establish how 'realistic' an LEM is and thus the extent to which its predictions may be trusted. We propose a test based upon the Turing Test of artificial intelligence as a way forward. In 1950 Alan Turing posed the question of whether a machine could think. Rather than attempt to address the question directly he proposed a test in which an interrogator asked questions of a person and a machine, with no means of telling which was which. If the machine's answer could not be distinguished from those of the human, the machine could be said to demonstrate artificial intelligence. By analogy, if an LEM cannot be distinguished from a real landscape it can be deemed to be realistic. The Turing test of intelligence is a test of the way in which a computer behaves. The analogy in the case of an LEM is that it should show realistic behaviour in terms of form and process, both at a given moment in time (punctual) and in the way both form and process evolve over time (dynamic). For some of these behaviours, tests already exist. For example there are numerous morphometric tests of punctual form and measurements of punctual process. The test discussed in this paper provides new ways of assessing dynamic behaviour of an LEM over realistically long timescales. However challenges remain in developing an appropriate suite of challenging tests, in applying these tests to current LEMs and in developing LEMs that pass them.

Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

PubMed

Kanthaswamy, S

2015-10-01

This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample handling, evidence testing, statistical analysis and reporting that meet the rules of scientific acceptance, reliability and human forensic identification standards. © 2015 Stichting International Foundation for Animal Genetics.

Effectiveness of screening for gestational diabetes during the late gestational period among pregnant Turkish women.

PubMed

Kurtbas, Handan; Keskin, H Levent; Avsar, A Filiz

2011-06-01

To assess the incidence of gestational diabetes mellitus (GDM) beyond 30 gestational weeks (GW) in pregnant Turkish women and to determine the criteria for repeating the test during the late period of gestation when the results were normal after the initial screen. Two hundred pregnant women were enrolled. Maternal age, gravidity, parity and presence of other risk factors (family history of diabetes mellitus, habitual abortions, prior fetal macrosomia, obesity, gestational hypertension history) were collected. First, GDM was evaluated between the 24th and 28th GW by screening (50-g glucose challenge test) and diagnostic tests. This protocol was repeated again at least 1 month from the first screen at the 30th-34th GW in all patients, except those diagnosed with GDM due to an abnormal 3-h test. The results were compared with the clinical risk factors. In total, 19.5% of the cases had positive results in the first screening test. Six patients were diagnosed with GDM. Among the remaining 194 pregnancies, another 10 cases were diagnosed as having GDM with repeated tests, and the incidence of newly diagnosed GDM was 5.2%. Only the mean age (34.2 years) (P = 0.010) and a history of delivering a macrosomic infant (P < 0.010) were significantly high in the late-gestation GDM-positive cases. Even when early screening tests are negative, pregnancies with advanced maternal ages and those with a history of delivering a macrosomic infant should be re-evaluated for GDM during the late gestational period with screening and diagnostic tests. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test

PubMed Central

Chełmińska, Marta; Różyło, Anna; Kołakowska, Agata; Jassem, Ewa

2016-01-01

Introduction Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. Aim To differentiate cross-reactions accompanying latex allergy with the use of the ISAC test. Material and methods Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. Results Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. Conclusions ImmunoCAP ISAC test could be useful in differentiating between cross-reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens. PMID:27279821

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial – challenges, enablers and lessons learned

PubMed Central

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

ABSTRACT A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research. PMID:29382251

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial - challenges, enablers and lessons learned.

PubMed

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research.

Testing Scientific Software: A Systematic Literature Review.

PubMed

Kanewala, Upulee; Bieman, James M

2014-10-01

Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques.

Through a glass darkly: economics and personalised medicine.

PubMed

Haycox, Alan; Pirmohamed, Munir; McLeod, Claire; Houten, Rachel; Richards, Sarah

2014-11-01

Personalised medicine and pharmacogenetic-test-guided treatment strategies will be of increasing importance in the future, both in terms of healthcare provision and evaluation. It is well recognised that significant variability exists in the response of patients to drugs resulting from genetic or biological variations; however, we are only now gradually becoming aware of the complexities involved. Enormous variability occurs in the risk-benefit ratio that will be experienced by each individual patient as a consequence of their overall genetic make-up. Although not a panacea, enhanced scientific knowledge of the genetic basis for such variability offers the potential for a more 'tailored' approach to prescribing in the future, making it more closely attuned to the needs of the individual patient. Such 'personalised' medicine has the potential to revolutionise care provision in a manner that provides a range of challenges to current structures and processes of 'conventional' healthcare delivery. The aim of this paper is to outline such challenges and analyse potential ways in which they may be addressed in the future. It provides non-expert readers with a non-technical case study of the complexities inherent in the evaluation of a pharmacogenetic-test-guided treatment strategy from a health economic perspective. Wherever possible, technical issues have been minimised; however, references are provided for readers who wish to enhance their knowledge of the pharmacological basis of the case study of cytochrome P450 test-guided treatment. The case study aims simply to illustrate the approach and difficulties encountered in the health economic evaluation of complex pharmacogenetic technologies. Such technologies present a range of new and complex issues which have crucial implications for health economists attempting to obtain an accurate assessment of the 'value' of the technology in clinical practice in an array of patient subgroups. Personalised medicine is the future and this paper highlights how pharmaceutical manufacturers, clinicians, regulators and other stakeholders must all play their part in the inevitable and accelerating move into this complex and uncertain future.

Pervasive assistive technology for people with dementia: a UCD case

PubMed Central

Rønn-Andersen, Kristoffer V.H.; Bień, Paulina; Özkil, Ali Gürcan; Forchhammer, Birgitte Hysse; Maier, Anja M.

2016-01-01

Smart mobile and wearable technology offers exciting opportunities to support people with dementia (PwD). Its ubiquity and popularity could even benefit user adoption – a great challenge for assistive technology (AT) for PwD that calls for user-centred design (UCD) methods. This study describes a user-centred approach to developing and testing AT based on off-the-shelf pervasive technologies. A prototype is created by combining a smartphone, smartwatch and various applications to offer six support features. This is tested among five end-users (PwD) and their caregivers. Controlled usability testing was followed by field testing in a real-world context. Data is gathered from video recordings, interaction logs, system usability scale questionnaires, logbooks, application usage logs and interviews structured on the unified theory of acceptance and use of technology model. The data is analysed to evaluate usability, usefulness and user acceptance. Results show some promise for user adoption, but highlight challenges to be overcome, emphasising personalisation and familiarity as key considerations. The complete findings regarding usability issues, usefulness of support features and four identified adoption profiles are used to provide a set of recommendations for practitioners and further research. These contribute toward UCD practices for improved smart, pervasive AT for dementia. PMID:28008366

Virus removal retention challenge tests performed at lab scale and pilot scale during operation of membrane units.

PubMed

Humbert, H; Machinal, C; Labaye, Ivan; Schrotter, J C

2011-01-01

The determination of the virus retention capabilities of UF units during operation is essential for the operators of drinking water treatment facilities in order to guarantee an efficient and stable removal of viruses through time. In previous studies, an effective method (MS2-phage challenge tests) was developed by the Water Research Center of Veolia Environnement for the measurement of the virus retention rates (Log Removal Rate, LRV) of commercially available hollow fiber membranes at lab scale. In the present work, the protocol for monitoring membrane performance was transferred from lab scale to pilot scale. Membrane performances were evaluated during pilot trial and compared to the results obtained at lab scale with fibers taken from the pilot plant modules. PFU culture method was compared to RT-PCR method for the calculation of LRV in both cases. Preliminary tests at lab scale showed that both methods can be used interchangeably. For tests conducted on virgin membrane, a good consistency was observed between lab and pilot scale results with the two analytical methods used. This work intends to show that a reliable determination of the membranes performances based on RT-PCR analytical method can be achieved during the operation of the UF units.

Locate the Lesion: A Project-Based Learning Case that Stimulates Comprehension and Application of Neuroanatomy.

PubMed

Lemons, Michele L

2017-01-01

A fictitious patient, Mr. Challenge, is admitted to the emergency room and displays symptoms consistent with damage to the central nervous system. In this problem-based learning case, students are challenged to determine the location of a lesion that is consistent with Mr. Challenge's symptoms. Students discover details about Mr. Challenge's symptoms while exploring three anatomical pathways: corticospinal tract, spinothalamic tract and medial lemniscal pathway. Students make predictions as to which of these pathways may be damaged in Mr. Challenge and defend their predictions based on their research of the function and anatomical location of these tracts. This ultimately leads the student to identifying a single lesion site that can account for Mr. Challenge's symptoms. This case is executed in an undergraduate neuroscience course and would be useful in anatomy and physiology course, as well as other courses that serve students interested in health science related careers.

Perampanel and Challenging Behaviour in Intellectual Disability and Epilepsy: A Management Dilemma

PubMed Central

Choudry, Ansar

2014-01-01

We describe a case of a patient with a diagnosis of moderate learning disability with challenging behaviour and treatment refractory epilepsy. Antiepileptics can increase challenging behaviour; however, antipsychotics can provoke seizures. This results in a difficult balance for patient care. Due to worsening seizures, the patient was prescribed perampanel. This increased her aggression and agitation resulting in admission. We trialled four antipsychotic drugs to reduce her challenging behaviour, two of which worsened her seizures. It was necessary to continue antiepileptic medication to maintain adequate seizure control. However, the resulting uncontrolled challenging behaviour persisted, meaning she was unable to return to her family home on discharge. This case emphasises the difficult scenario clinician's encounter when balancing the use of antipsychotics and antiepileptics. The case demonstrates the significant functional loss due to challenging behaviour, balanced against controlling life threatening seizures. PMID:25580340

A Case Study of Small Group Decision-Making as Influenced by the Abilene Paradox: The ’Challenger’ Mishap

DTIC Science & Technology

1988-05-01

RESEARCH REPORT O A CASE STUDY OF SMALL GROUP DECISION-MAKING AS INFLUENCED BY THE ABILENE PARADOX: N THE " CHALLENGER " MISHAP COMMANDER JAMES Y...1.09_240 AIR WAR COLLEGE AIR UNIVERSITY A CASE STIJI)Y OF SMALL GROUP DECISION-MAKING AS INFLUENCED BY THE ABILENE PARADOX: THE " CHALLENGER " MISHAP by...representing the public and private sectors of leadership in our national space exploration program evaluated the risk associated with known discrepancies

Seronegative myasthenia gravis associated with malignant thymoma.

PubMed

Richards, Jason; Howard, James F

2017-05-01

Myasthenia gravis (MG) is generally caused by antibodies directed against the neuromuscular junction, including antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR). Pathologic abnormalities of the thymus gland, including thymoma, are associated with MG. We report a 56-year-old woman who presented with double vision. Single fiber EMG confirmed myasthenia gravis. AChR, striational muscle and MuSK antibodies were absent in the serum. Chest CT demonstrated a malignant thymoma. We report the first case of seronegative myasthenia gravis associated with malignant thymoma. The case challenges the conventional wisdom that all patients with thymoma associated MG test positive for antibodies against AChR. Copyright © 2017 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Driel, Tim Brandt; Herrmann, Sven; Carini, Gabriella

The pulsed free-electron laser light sources represent a new challenge to photon area detectors due to the intrinsic spontaneous X-ray photon generation process that makes single-pulse detection necessary. Intensity fluctuations up to 100% between individual pulses lead to high linearity requirements in order to distinguish small signal changes. In real detectors, signal distortions as a function of the intensity distribution on the entire detector can occur. Here a robust method to correct this nonlinear response in an area detector is presented for the case of exposures to similar signals. The method is tested for the case of diffuse scattering frommore » liquids where relevant sub-1% signal changes appear on the same order as artifacts induced by the detector electronics.« less

The Case for Universal Screening of Private Well Water Quality in the U.S. and Testing Requirements to Achieve It: Evidence from Arsenic.

PubMed

Zheng, Yan; Flanagan, Sara V

2017-08-03

The 1974 Safe Drinking Water Act (SDWA) regulates >170,000 public water systems to protect health, but not >13 million private wells. State and local government requirements for private well water testing are rare and inconsistent; the responsibility to ensure water safety remains with individual households. Over the last two decades, geogenic arsenic has emerged as a significant public health concern due to high prevalence in many rural American communities. We build the case for universal screening of private well water quality around arsenic, the most toxic and widespread of common private water contaminants. We argue that achieving universal screening will require policy intervention, and that testing should be made easy, accessible, and in many cases free to all private well households in the United States, considering the invisible, tasteless, odorless, and thus silent nature of arsenic. Our research has identified behavioral, situational and financial barriers to households managing their own well water safety, resulting in far from universal screening despite traditional public health outreach efforts. We observe significant socioeconomic disparities in arsenic testing and treatment when private water is unregulated. Testing requirements can be a partial answer to these challenges. Universal screening, achieved through local testing requirements complemented by greater community engagement targeting biologically and socioeconomically vulnerable groups, would reduce population arsenic exposure greater than any promotional efforts to date. Universal screening of private well water will identify the dangers hidden in America's drinking water supply and redirect attention to ensure safe water among affected households. https://doi.org/10.1289/EHP629.

Approach to a case of multiple irregular red cell antibodies in a liver transplant recipient: Need for developing competence

PubMed Central

Dara, Ravi C.; Tiwari, Aseem K.; Pandey, Prashant; Arora, Dinesh

2015-01-01

Liver transplant procedure acts as a challenge for transfusion services in terms of specialized blood components, serologic problems, and immunologic effects of transfusion. Red cell alloimmunization in patients awaiting a liver transplant complicate the process by undue delay or unavailability of compatible red blood cell units. Compatible blood units can be provided by well-equipped immunohematology laboratory, which has expertise in resolving these serological problems. This report illustrates resolution of a case with multiple alloantibodies using standard techniques, particularly rare antisera. Our case re-emphasizes the need for universal antibody screening in all patients as part of pretransfusion testing, which helps to identify atypical antibodies and plan for appropriate transfusion support well in time. We recommend that the centers, especially the ones that perform complex procedures like solid organ transplants and hematological transplants should have the necessary immunohematological reagents including rare antisera to resolve complex cases of multiple antibodies as illustrated in this case. PMID:25722585

An Extended Case Study Methoology for Investigating Influence of Cultural, Organizational, and Automation Factors on Human-Automation Trust

NASA Technical Reports Server (NTRS)

Koltai, Kolina Sun; Ho, Nhut; Masequesmay, Gina; Niedober, David; Skoog, Mark; Johnson, Walter; Cacanindin, Artemio

2014-01-01

This paper discusses a case study that examined the influence of cultural, organizational and automation capability upon human trust in, and reliance on, automation. In particular, this paper focuses on the design and application of an extended case study methodology, and on the foundational lessons revealed by it. Experimental test pilots involved in the research and development of the US Air Forces newly developed Automatic Ground Collision Avoidance System served as the context for this examination. An eclectic, multi-pronged approach was designed to conduct this case study, and proved effective in addressing the challenges associated with the cases politically sensitive and military environment. Key results indicate that the system design was in alignment with pilot culture and organizational mission, indicating the potential for appropriate trust development in operational pilots. These include the low-vulnerabilityhigh risk nature of the pilot profession, automation transparency and suspicion, system reputation, and the setup of and communications among organizations involved in the system development.

Providers' Perspectives on Case Management of a Healthy Start Program: A Qualitative Study

PubMed Central

Moise, Imelda K.; Mulhall, Peter F.

2016-01-01

Although Healthy Start case managers recognized the benefits of case management for facilitating optimal service delivery to women and their families, structural factors impact effective implementation. This study investigated case managers' views of 1) the structural challenges faced in implementing case management for program participants, and 2) possible strategies to enhance case management in medical home settings. Two focus groups were conducted separately with case managers from the four program service sites to gain insight into these issues noted above. Each group was co-facilitated by two evaluators using a previously developed semi-structured interview guide. The group discussions were audio recorded and the case managers' comments were transcribed verbatim. Transcripts were analyzed using thematic analysis, a deductive approach. Data were collected in 2013 and analyzed in 2015. Case managers are challenged by externalities (demographic shifts in target populations, poverty); contractual requirements (predefined catchment neighborhoods, caseload); limited support (client incentives, tailored training, and a high staff turnover rate); and logistic difficulties (organizational issues). Their approach to case management tends to be focused on linking Although Healthy Start case managers recognized the benefits of case management for facilitating optimal service delivery to women and their families, structural factors impact effective implementation. This study investigated case managers' views of 1) the structural challenges faced in implementing case management for program participants, and 2) possible strategies to enhance case management in medical home settings. Two focus groups were conducted separately with case managers from the four program service sites to gain insight into these issues noted above. Each group was co-facilitated by two evaluators using a previously developed semi-structured interview guide. The group discussions were audio recorded and the case managers' comments were transcribed verbatim. Transcripts were analyzed using thematic analysis, a deductive approach. Data were collected in 2013 and analyzed in 2015. Case managers are challenged by externalities (demographic shifts in target populations, poverty); contractual requirements (predefined catchment neighborhoods, caseload); limited support (client incentives, tailored training, and a high staff turnover rate); and logistic difficulties (organizational issues). Their approach to case management tends to be focused on linking clients to adequate services rather than reporting performance. Case managers favored measurable deliverables rather than operational work products. A proposed solution to current challenges emphasizes and encourages the iterative learning process and shared decision making between program targets, funders and providers. Case managers are aware of the challenging environment in which they operate for their clients and for themselves. However, future interventions will require clearly identified performance measures and increased systems support. PMID:27149061

Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk.

PubMed

West, Allison H; Blazer, Kathleen R; Stoll, Jessica; Jones, Matthew; Weipert, Caroline M; Nielsen, Sarah M; Kupfer, Sonia S; Weitzel, Jeffrey N; Olopade, Olufunmilayo I

2018-02-14

Comprehensive genomic cancer risk assessment (GCRA) helps patients, family members, and providers make informed choices about cancer screening, surgical and chemotherapeutic risk reduction, and genetically targeted cancer therapies. The increasing availability of multigene panel tests for clinical applications allows testing of well-defined high-risk genes, as well as moderate-risk genes, for which the penetrance and spectrum of cancer risk are less well characterized. Moderate-risk genes are defined as genes that, when altered by a pathogenic variant, confer a 2 to fivefold relative risk of cancer. Two such genes included on many comprehensive cancer panels are the DNA repair genes ATM and CHEK2, best known for moderately increased risk of breast cancer development. However, the impact of screening and preventative interventions and spectrum of cancer risk beyond breast cancer associated with ATM and/or CHEK2 variants remain less well characterized. We convened a large, multidisciplinary, cross-sectional panel of GCRA clinicians to review challenging, peer-submitted cases of patients identified with ATM or CHEK2 variants. This paper summarizes the inter-professional case discussion and recommendations generated during the session, the level of concordance with respect to recommendations between the academic and community clinician participants for each case, and potential barriers to implementing recommended care in various practice settings.

Major improvements in the quality of malaria case-management under the "test and treat" policy in Kenya.

PubMed

Zurovac, Dejan; Githinji, Sophie; Memusi, Dorothy; Kigen, Samuel; Machini, Beatrice; Muturi, Alex; Otieno, Gabriel; Snow, Robert W; Nyandigisi, Andrew

2014-01-01

Monitoring implementation of the "test and treat" case-management policy for malaria is an important component of all malaria control programmes in Africa. Unfortunately, routine information systems are commonly deficient to provide necessary information. Using health facility surveys we monitored health systems readiness and malaria case-management practices prior to and following implementation of the 2010 "test and treat" policy in Kenya. Between 2010 and 2013 six national, cross-sectional, health facility surveys were undertaken. The number of facilities assessed ranged between 172 and 176, health workers interviewed between 216 and 237 and outpatient consultations for febrile patients evaluated between 1,208 and 2,408 across six surveys. Comparing baseline and the last survey results, all readiness indicators showed significant (p<0.005) improvements: availability of parasitological diagnosis (55.2% to 90.7%); RDT availability (7.5% to 69.8%); total artemether-lumefantrine (AL) stock-out (27.2% to 7.0%); stock-out of one or more AL packs (59.5% to 21.6%); training coverage (0 to 50.2%); guidelines access (0 to 58.1%) and supervision (17.9% to 30.8%). Testing increased by 34.0% (23.9% to 57.9%; p<0.001) while testing and treatment according to test result increased by 34.2% (15.7% to 49.9%; p<0.001). Treatment adherence for test positive patients improved from 83.3% to 90.3% (p = 0.138) and for test negative patients from 47.9% to 83.4% (p<0.001). Significant testing and treatment improvements were observed in children and adults. There was no difference in practices with respect to the type and result of malaria test (RDT vs microscopy). Of eight dosing, dispensing and counseling tasks, improvements were observed for four tasks. Overall AL use for febrile patients decreased from 63.5% to 35.6% (p<0.001). Major improvements in the implementation of "test and treat" policy were observed in Kenya. Some gaps towards universal targets still remained. Other countries facing similar needs and challenges may consider health facility surveys to monitor malaria case-management.

Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

PubMed

Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

2016-02-01

The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

Toxicological perspectives of inhaled therapeutics and nanoparticles.

PubMed

Hayes, Amanda J; Bakand, Shahnaz

2014-07-01

The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

Do recent US Supreme Court rulings on patenting of genes and genetic diagnostics affect the practice of genetic screening and diagnosis in prenatal and reproductive care?

PubMed Central

Chandrasekharan, Subhashini; McGuire, Amy L.; Van den Veyver, Ignatia B.

2015-01-01

Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. vs. Myriad Genetics, Inc., et al., the United States Supreme Court ruled that genes are natural occurring substances and therefore not patentable through “composition of matter” claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing, and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies. PMID:24989832

Design, Development and Test Challenges: Separation Mechanisms for the Orion Pad Abort-1 Flight Test

NASA Technical Reports Server (NTRS)

Dinsel, Alison; Morrey, Jeremy M.; OMalley, Patrick; Park, Samuel

2011-01-01

On May 6, 2010, NASA launched the first successful integrated flight test, Pad Abort-1, of the Orion Project from the White Sands Missile Range in Las Cruces, New Mexico. This test demonstrated the ability to perform an emergency pad abort of a full-scale 4.8 m diameter, 8200 kg crew capsule. During development of the critical separation mechanisms for this flight test, various challenges were overcome related to environments definition, installation complications, separation joint retraction speed, thruster ordnance development issues, load path validation and significant design loads increases. The Launch Abort System retention and release (LAS R&R) mechanism consisted of 6 discrete structural connections between the LAS and the crew module (CM) simulator, each of which had a preloaded tension tie, Superbolt torque-nut and frangible nut. During the flight test, the frangible nuts were pyrotechnically split, permitting the CM to separate from the LAS. The LAS separation event was the driving case in the shock environment for many co-located hardware items. During development testing, it was necessary to measure the source shock during the separation event so the predicted shock environment could be validated and used for certification testing of multiple hardware items. The Lockheed Martin test team measured the source separation shock due to the LAS R&R function, which dramatically decreased the predicted environment by 90% at 100 Hz. During development testing a hydraulic tensioner was used to preload the joint; however, the joint relaxation with the tensioner proved unsatisfactory so the design was modified to include a Superbolt torque-nut. The observed preload creep during lab testing was 4% after 30 days, with 2.5% occurring in the first 24 hours. The conversion of strain energy (preload) to kinetic energy (retraction) was measured to be 50-75%. Design features and careful monitoring of multiple strain gauges on each tension tie allowed a pure tensile load to be applied after stacking at the launch pad. Following installation, preload in each joint was monitored for 24 hours. Due to unforeseen complications and the influence of temperature on the portable data acquisition system, the team encountered difficulty in tracking the joint relaxation. In some cases, bond-line failure of the strain gauges occurred.

Artificial neural network model to distinguish follicular adenoma from follicular carcinoma on fine needle aspiration of thyroid.

PubMed

Savala, Rajiv; Dey, Pranab; Gupta, Nalini

2018-03-01

To distinguish follicular adenoma (FA) and follicular carcinoma (FC) of thyroid in fine needle aspiration cytology (FNAC) is a challenging problem. In this article, we attempted to build an artificial neural network (ANN) model from the cytological and morphometric features of the FNAC smears of thyroid to distinguish FA from FC. The cytological features and morphometric analysis were done on the FNAC smears of histology proven cases of FA (26) and FC (31). The cytological features were analysed semi-quantitatively by two independent observers (RS and PD). These data were used to make an ANN model to differentiate FA versus FC on FNAC material. The performance of this ANN model was assessed by analysing the confusion matrix and receiving operator curve. There were 39 cases in training set, 9 cases each in validation and test sets. In the test group, ANN model successfully distinguished all cases (9/9) of FA and FC. The area under receiver operating curve was 1. The present ANN model is efficient to diagnose follicular adenoma and carcinoma cases on cytology smears without any error. In future, this ANN model will be able to diagnose follicular adenoma and carcinoma cases on thyroid aspirate. This study has immense potential in future. This is an open ended ANN model and more parameters and more cases can be included to make the model much stronger. © 2017 Wiley Periodicals, Inc.

A review of eleven cases of tuberculosis presenting as sternal wound abscess after open heart surgery.

PubMed

Tabaja, Hussam; Hajar, Zeina; Kanj, Souha S

2017-10-01

Sternal wound infection with Mycobacterium tuberculosis is an uncommon yet highly challenging disease that can be quite insidious with various presentations. We hereby provide a review of 10 cases in current literature and describe an additional case which illustrates the difficulties associated with diagnosis. We used PubMed and Google search engine to search the literature for all published papers reporting on cases of sternal M. tuberculosis infections post open-heart surgeries. A total of 11 cases were presented, including a case of our own. The majority were males and were exposed to endemic areas. The average age was 59.6 ± 15.5 years. Coronary artery bypass surgery accounted for 73% of procedures and the average time to symptoms onset was 12.2 ± 16.6 months. Diabetes was the most reported non-cardiac comorbidity. Presenting symptoms varied and only 5 patients had other organs involved. Blood tests and radiographic studies were neither sensitive nor specific. M. tuberculosis culture on debrided tissues was the most sensitive test but often forgotten initially. Diagnostic delay was seen in almost all cases, often leading to unnecessary courses of antibiotics and aggressive surgical interventions. Finally, all patients responded well to anti-tuberculosis treatment, with reported treatment duration ranging from 9 to 12 months. M. tuberculosis infection of the sternum should be suspected in late-onset sternal wound infections post open-heart surgery especially when the course is chronic and indolent.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.

PubMed

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-11-06

While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)-coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. The overall tuberculosis burden was estimated to be 532005 cases (range, 333760-764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Red flags: a case series of clinician-family communication challenges in the context of CHD.

PubMed

Sekar, Priya; Marcus, Katie L; Williams, Erin P; Boss, Renee D

2017-07-01

We describe three cases of newborns with complex CHD characterised by communication challenges. These communication challenges were categorised as patient, family, or system-related red flags. Strategies for addressing these red flags were proposed, for the goal of optimising care and improving quality of life in this vulnerable population.

Salmonella Enteritidis with double deletion in phoP fliC and a competitive exclusion culture elicit substantial additive protective effects against Salmonella exposure in newly hatched chicks.

PubMed

Methner, U; Berndt, A; Locke, M

2017-10-27

A live Salmonella Enteritidis vaccine (SE147N ΔphoP fliC), able to express both a homologous intestinal colonisation-inhibition effect and a systemic invasion-inhibition effect, was tested for its potential to generate a postulated additive protective effect in case of combined application with a competitive exclusion (CE) culture against Salmonella exposure in very young chicks. Both, SE147N ΔphoP fliC and the CE culture alone were highly protective against systemic and intestinal colonisation of the challenge strain in case of moderate Salmonella exposure, consequently, additive protective effects in combined use could not be detected. However, in case of high Salmonella Enteritidis challenge with 10 6 cfu/bird at day 3 of life the combination of the ΔphoP fliC vaccine and the CE culture resulted in a protective effect much more pronounced than either of the single preparations and most substantial compared to untreated control birds. The term additive protective effects reflects the recognition that exclusion effects by gut flora cultures and inhibition effects by Salmonella vaccines are caused by different mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rat Lungworm Disease in Hawai‘i: Community Outreach and Education on the Island of Hawai‘i (the ‘Big Island’)

PubMed Central

2013-01-01

Due to an increase in severity of cases of rat lungworm disease and increased media attention, community outreach efforts on the island of Hawai‘i (the Big Island) were revisited in 2009, to include an updated flier, radio interviews, and community presentations. The Puna district of the island has been impacted the greatest by rat lungworm disease. The biggest challenge in disseminating information was that residents could not accept that limited information, testing, and treatment options were available. Some people wanted basic information while others requested great detail. Some responded better to information in “pidgin” but others preferred English. Another challenge was to provide information to communities where residents did not read newspapers or watch television news. As a result, a community education group formed and assisted in disseminating information to these communities. But some residents never received information and there has been no decrease in cases. Information must be sent repeatedly and through different media, including free journals, local community newspapers, local television stations, and even social networking.

Co-existence of Blau syndrome and NAID? Diagnostic challenges associated with presence of multiple pathogenic variants in NOD2 gene: a case report.

PubMed

Dziedzic, Magdalena; Marjańska, Agata; Bąbol-Pokora, Katarzyna; Urbańczyk, Anna; Grześk, Elżbieta; Młynarski, Wojciech; Kołtan, Sylwia

2017-07-27

Pediatric autoinflammatory diseases are rare and still poorly understood conditions resulting from defective genetic control of innate immune system, inter alia from anomalies of NOD2 gene. The product of this gene is Nod2 protein, taking part in maintenance of immune homeostasis. Clinical form of resultant autoinflammatory condition depends on NOD2 genotype; usually patients with NOD2 defects present with Blau syndrome, NOD2-associated autoinflammatory disease (NAID) or Crohn's disease. We present the case of a 7-year-old girl with co-existing symptoms of two rare diseases, Blau syndrome and NAID. Overlapping manifestations of two syndromes raised a significant diagnostic challenge, until next-generation molecular test (NGS) identified presence of three pathogenic variants of NOD2 gene: P268S, IVS8 +158 , 1007 fs, and established the ultimate diagnosis. Presence of multiple genetical abnormalities resulted in an ambiguous clinical presentation with overlapping symptoms of Blau syndrome and NAID. Final diagnosis of autoinflammatory disease opened new therapeutic possibilities, including the use of biological treatments.

Developing Use Cases for Evaluation of ADMS Applications to Accelerate Technology Adoption: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veda, Santosh; Wu, Hongyu; Martin, Maurice

Grid modernization for the distribution systems comprise of the ability to effectively monitor and manage unplanned events while ensuring reliable operations. Integration of Distributed Energy Resources (DERs) and proliferation of autonomous smart controllers like microgrids and smart inverters in the distribution networks challenge the status quo of distribution system operations. Advanced Distribution Management System (ADMS) technologies are being increasingly deployed to manage the complexities of operating distribution systems. The ability to evaluate the ADMS applications in specific utility environments and for future scenarios will accelerate wider adoption of the ADMS and will lower the risks and costs of their implementation.more » This paper addresses the first step - identify and define the use cases for evaluating these applications. The applications that are selected for this discussion include Volt-VAr Optimization (VVO), Fault Location Isolation and Service Restoration (FLISR), Online Power Flow (OLPF)/Distribution System State Estimation (DSSE) and Market Participation. A technical description and general operational requirements for each of these applications is presented. The test scenarios that are most relevant to the utility challenges are also addressed.« less

Managing healthcare information: analyzing trust.

PubMed

Söderström, Eva; Eriksson, Nomie; Åhlfeldt, Rose-Mharie

2016-08-08

Purpose - The purpose of this paper is to analyze two case studies with a trust matrix tool, to identify trust issues related to electronic health records. Design/methodology/approach - A qualitative research approach is applied using two case studies. The data analysis of these studies generated a problem list, which was mapped to a trust matrix. Findings - Results demonstrate flaws in current practices and point to achieving balance between organizational, person and technology trust perspectives. The analysis revealed three challenge areas, to: achieve higher trust in patient-focussed healthcare; improve communication between patients and healthcare professionals; and establish clear terminology. By taking trust into account, a more holistic perspective on healthcare can be achieved, where trust can be obtained and optimized. Research limitations/implications - A trust matrix is tested and shown to identify trust problems on different levels and relating to trusting beliefs. Future research should elaborate and more fully address issues within three identified challenge areas. Practical implications - The trust matrix's usefulness as a tool for organizations to analyze trust problems and issues is demonstrated. Originality/value - Healthcare trust issues are captured to a greater extent and from previously unchartered perspectives.

Testing Scientific Software: A Systematic Literature Review

PubMed Central

Kanewala, Upulee; Bieman, James M.

2014-01-01

Context Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. Objective This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. Method We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. Results We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Conclusions Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques. PMID:25125798

One of These Things Is Not Like the Others: The Idea of Precedence in Health Technology Assessment and Coverage Decisions

PubMed Central

Giacomini, Mita

2005-01-01

Health plans often deliberate covering technologies with challenging purposes, effects, or costs. They must integrate quantitative evidence (e.g., how well a technology works) with qualitative, normative assessments (e.g., whether it works well enough for a worthwhile purpose). Arguments from analogy and precedent help integrate these criteria and establish standards for their policy application. Examples of arguments are described for three technologies (ICSI, genetic tests, and Viagra). Drawing lessons from law, ethics, philosophy, and the social sciences, a framework is developed for case-based evaluation of new technologies. The decision-making cycle includes (1) taking stock of past decisions and formulating precedents, (2) deciding new cases, and (3) assimilating decisions into the case history and evaluation framework. Each stage requires distinctive decision maker roles, information, and methods. PMID:15960769

Challenges in Recruiting Aging Women Holocaust Survivors to a Case Control Study of Breast Cancer.

PubMed

Vin-Raviv, Neomi; Dekel, Rachel; Barchana, Micha; Linn, Shai; Keinan-Boker, Lital

2015-01-01

Older adults are underrepresented in medical research for many reasons, including recruitment difficulties. Recruitment of older adults for research studies is often a time-consuming process and can be more challenging when the study involves older adults with unique exposures to traumatic events and from minority groups. The current article provides a brief overview of (a) challenges encountered while recruiting aging women Holocaust survivors for a case control study and (b) strategies used for meeting those challenges. The case group comprised women Holocaust survivors who were recently diagnosed with breast cancer and the control group comprised healthy women from a Holocaust-survivor community in Israel. Copyright 2015, SLACK Incorporated.

When courts intervene: public health, legal and ethical issues surrounding HIV, pregnant women, and newborn infants.

PubMed

Tessmer-Tuck, Jennifer A; Poku, Joseph K; Burkle, Christopher M

2014-11-01

Ninety-three percent of pediatric AIDS cases are the result of perinatal HIV transmission, a disease that is almost entirely preventable with early intervention, which reduces the risk of perinatal HIV infection from 25% to <2%. The American College of Obstetricians and Gynecologists and the American Academy of Pediatrics both recommend routine HIV testing of all pregnant women and at-risk newborn infants. When pregnant women decline HIV testing and/or treatment, public health, legal, and ethical dilemmas can result. Federal courts consistently uphold a woman's right to refuse medical testing and treatment, even though it may benefit her fetus/newborn infant. Federal courts also reliably respect the rights of parents to make health care decisions for their newborn infants, which may include declining medical testing and treatment. Confusing the issue of HIV testing and treatment, however, is the fact that there is no definitive United States Supreme Court ruling on the issue. State laws and standards vary widely and serve as guiding principles for practicing clinicians, who must be vigilant of ongoing legal challenges and changes in the states in which they practice. We present a case of an HIV-positive pregnant woman who declined treatment and then testing or treatment of her newborn infant. Ultimately, the legal system intervened. Given the rarity of such cases, we use this as a primer for the practicing clinician to highlight the public health, legal, and ethical issues surrounding prenatal and newborn infant HIV testing and treatment in the United States, including summarizing key state-to-state regulatory differences. Copyright © 2014 Elsevier Inc. All rights reserved.

Leadership Strategies for Department Chairs and Program Directors: A Case Study Approach.

ERIC Educational Resources Information Center

Comer, Robert W.; Haden, N. Karl; Taylor, Robert L.; Thomas, D. Denee

2002-01-01

Reviews leadership challenges and management concepts in academic dentistry as they were applied in a case-based faculty development workshop, in order to provide a foundation for three cases that follow in subsequent articles. The workshop was structured to address leadership challenges relating to managing people, mission management, conflict…

The Consulting Challenge: A Case Competition

ERIC Educational Resources Information Center

Sachau, Daniel A.; Naas, Patricia A.

2010-01-01

The Consulting Challenge is a yearly case competition in which teams of graduate students respond to a request for proposals (RFP) for consulting services. The case and RFP are based on a problem that a host organization has experienced. Over 3 days, students meet with representatives of the host organization, analyze data, prepare a proposal for…

Prenatal molecular testing for Beckwith–Wiedemann and Silver–Russell syndromes: a challenge for molecular analysis and genetic counseling

PubMed Central

Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia; Lombardi, Maria P; Bliek, Jet; Maher, Eamonn R; Larizza, Lidia; Prawitt, Dirk; Netchine, Irène; Gonzales, Marie; Grønskov, Karen; Tümer, Zeynep; Monk, David; Mannens, Marcel; Chrzanowska, Krystyna; Walasek, Malgorzata K; Begemann, Matthias; Soellner, Lukas; Eggermann, Katja; Tenorio, Jair; Nevado, Julián; Moore, Gudrun E; Mackay, Deborah JG; Temple, Karen; Gillessen-Kaesbach, Gabriele; Ogata, Tsutomu; Weksberg, Rosanna; Algar, Elizabeth; Lapunzina, Pablo

2016-01-01

Beckwith–Wiedemann and Silver–Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders. PMID:26508573

Recommendations for provoked challenge urine testing.

PubMed

Ruha, Anne-Michelle

2013-12-01

"Urine mobilization test," "challenge test," and "provoked urine test" are all terms used to describe the administration of a chelating agent to a person prior to collection of their urine to test for metals. There is no standard, validated challenge test. Despite recommendations by professional and government organizations against the use of provoked urine testing, the tests are still commonly used and recommended by some practitioners. Challenge testing utilizes a variety of chelating agents, including dimercaptosuccinic acid (DMSA), dimercaptopropanesulfonate (DMPS), and ethylenediaminetetraacetic acid (EDTA). The agents are given by a variety of routes of administration, doses used are inconsistent, and urine collection procedures vary. Additional problems with challenge tests include comparison of results to inappropriate reference ranges and creatinine correction of urine obtained within hours of chelator administration. Human volunteer studies demonstrate that mercury is detected in the urine of most people even in the absence of known exposure or chelator administration, and that urinary mercury excretion rises after administration of a chelator, regardless of exposure history and in an unpredictable fashion. Studies also demonstrate that challenge testing fails to reveal a "body burden" of mercury due to remote exposure. Chelating agents have been associated with adverse reactions. Current evidence does not support the use of DMPS, DMSA, or other chelation challenge tests for the diagnosis of metal toxicity. Since there are no established reference ranges for provoked urine samples in healthy subjects, no reliable evidence to support a diagnostic value for the tests, and potential harm, these tests should not be utilized.

PROSPECTIVE MULTICENTER SURVEY ON PREDICTIVE FACTORS FOR POSITIVE ORAL FOOD CHALLENGE TESTS IN DIAGNOSIS OF GASTROINTESTINAL FOOD ALLERGY IN NEONATES.

PubMed

Miyazawa, Tokuo; Imai, Takanori; Itabashi, Kazuo

2016-01-01

To assess predictors of positive oral food challenge test (OFC) in neonates that are suggestive of gastrointestinal food allergy. A prospective case accumulations study on neonates suspected of having gastrointestinal food allergy was conducted in 126 neonatal intensive care units in Japan between April 2010 and September 2011. Neonates who underwent an OFC for the diagnosis of gastrointestinal food allergy were enrolled. Clinical backgrounds, clinical symptoms, and laboratory findings were compared between neonates with a positive OFC and those with a negative OFC. An analysis was performed in 32 neonates. The OFC results were positive in 9 neonates (28.1%), pseudo-positive in 4, and negative in 19. There were no significant differences in clinical backgrounds between the positive OFC group and the negative OFC group. Vomiting and bloody stool were frequently observed in both groups (approximately 70%), although there were no significant differences in the clinical symptoms between the two groups. Additional diagnostic tests included those for eosinophils in the peripheral blood and stool mucus and allergen-specific lymphocyte stimulation test. There were no significant differences in laboratory findings between the two groups, and many neonates showed pseudo-positive in all of the tests. It was difficult to predict OFC results based on clinical symptoms and additional diagnostic test results. In order to obtain an accurate diagnosis of gastrointestinal food allergy in neonates, OFC should be performed proactively under conditions that enable complete understanding of risks to neonates.

Trends in Testing for Mycobacterium tuberculosis Complex From US Public Health Laboratories, 2009-2013.

PubMed

Tyrrell, Frances; Stafford, Cortney; Yakrus, Mitchell; Youngblood, Monica; Hill, Andrew; Johnston, Stephanie

We investigated data from US public health laboratories funded through the Centers for Disease Control and Prevention's Tuberculosis Elimination and Laboratory Cooperative Agreement to document trends and challenges in meeting national objectives in tuberculosis (TB) laboratory diagnoses. We examined data on workload and turnaround time from public health laboratories' progress reports during 2009-2013. We reviewed methodologies, laboratory roles, and progress toward rapid detection of Mycobacterium tuberculosis complex through nucleic acid amplification (NAA) testing. We compared selected data with TB surveillance reports to estimate public health laboratories' contribution to national diagnostic services. During the study period, culture and drug susceptibility tests decreased, but NAA testing increased. Public health laboratories achieved turnaround time benchmarks for drug susceptibility tests at lower levels than for acid-fast bacilli smear and identification from culture. NAA positivity in laboratories among surveillance-reported culture-positive TB cases increased from 26.6% (2355 of 8876) in 2009 to 40.0% (2948 of 7358) in 2013. Public health laboratories provided an estimated 50.9% (4285 of 8413 in 2010) to 57.2% (4210 of 7358 in 2013) of culture testing and 88.3% (6822 of 7727 in 2011) to 94.4% (6845 of 7250 in 2012) of drug susceptibility tests for all US TB cases. Public health laboratories contribute substantially to TB diagnoses in the United States. Although testing volumes mostly decreased, the increase in NAA testing indicates continued progress in rapid M tuberculosis complex detection.

A Hybrid Lesion of Lung Cancer and Aspergillosis

PubMed Central

Takeoka, Hiroaki; Koga, Takeharu; Yano, Hirohisa; Ikeda, Jiro; Nishimura, Munetsugu; Kamimura, Tomoko; Aizawa, Hisamichi

2008-01-01

A 74-year-old man presented with gradual wall thickening of a cystic lung lesion. Serologic tests indicated Aspergillus infection, but neither fungal organisms nor evidence of malignant disease were recovered from repeated sputum collections, a bronchoscopic lung biopsy specimen, or bronchial washings. Treatment with antifungal agents did not result in clinical improvement. Surgical resection of the lesion demonstrated both squamous cell carcinoma and aspergillosis. These distinct disorders share common radiologic manifestations that can present a diagnostic challenge, as in the present case. PMID:21892273

Determination of organic carbon and ionic accountability of various waste and product waters derived from ECLSS water recovery tests and Spacelab humidity condensate

NASA Technical Reports Server (NTRS)

Carter, Donald L.; Cole, Harold; Habercom, Mark; Griffith, Guy

1992-01-01

The development of a closed-loop water recovery system for Space Station Freedom involves many technical challenges associated with contaminant removal. Attention is presently given to the characterization of contaminants constituting total organic carbon (TOC), and to the Hubaux and Vos (1970) statistical model for low level TOC that has been employed. A tabulation is given for TOC accountability in the case of both potable and hygiene waters.

Design Flexibility for Uncertain Distributed Generation from Photovoltaics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmintier, Bryan; Krishnamurthy, Dheepak; Wu, Hongyu

2016-12-12

Uncertainty in the future adoption patterns for distributed energy resources (DERs) introduces a challenge for electric distribution system planning. This paper explores the potential for flexibility in design - also known as real options - to identify design solutions that may never emerge when future DER patterns are treated as deterministic. A test case for storage system design with uncertain distributed generation for solar photovoltaics (DGPV) demonstrates this approach and is used to study sensitivities to a range of techno-economic assumptions.

Challenging evidence-based decision-making: a hypothetical case study about return to work.

PubMed

Aas, Randi W; Alexanderson, Kristina

2012-03-01

A hypothetical case study about return to work was used to explore the process of translating research into practice. The method involved constructing a case study derived from the characteristics of a typical, sick-listed employee with non-specific low back pain in Norway. Next, the five-step evidence-based process, including the Patient, Intervention, Co-Interventions and Outcome framework (PICO), was applied to the case study. An inductive analysis produced 10 technical and more fundamental challenges to incorporate research into intervention decisions for an individual with comorbidity. A more dynamic, interactive approach to the evidence-based practice process is proposed. It is recommended that this plus the 10 challenges are validated with real life cases, as the hypothetical case study may not be replicable. Copyright © 2011 John Wiley & Sons, Ltd.

DOE Challenge Home Case Study: e2 Homes – Winter Park, Florida

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

2013-01-01

This Challenge Home case study describes the first certified DOE Challenge Home as constructed by e2 Homes. Completed in May 2012, the “Wilson Residence” in Winter Park, Florida, is a 4,305-ft2 custom home that scores a HERS 57 without solar and a better than zero net-energy HERS -7 with solar.

Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia.

PubMed

Darton, Thomas C; Zhou, Liqing; Blohmke, Christoph J; Jones, Claire; Waddington, Claire S; Baker, Stephen; Pollard, Andrew J

2017-04-01

Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures. Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had ≥1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had ≥1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia. Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Burden of asymptomatic malaria among a tribal population in a forested village of central India: a hidden challenge for malaria control in India.

PubMed

Chourasia, M K; Raghavendra, K; Bhatt, R M; Swain, D K; Valecha, N; Kleinschmidt, I

2017-06-01

Chhattisgarh in India is a malaria-endemic state with seven southern districts that contributes approximately 50-60% of the reported malaria cases in the state every year. The problem is further complicated due to asymptomatic malaria cases which are largely responsible for persistent transmission. This study was undertaken in one of the forested villages of the Keshkal subdistrict in Kondagaon district to ascertain the proportion of the population harbouring subclinical malarial infections. Community-based cross-sectional study. Mass blood surveys were undertaken of the entire population of the village in the post-monsoon seasons of 2013 and 2014. Fingerprick blood smears were prepared from individuals of all ages to detect malaria infections in their blood. Individuals with fever at the time of the survey were tested with rapid diagnostic tests, and parasitaemia in thick blood smears was confirmed by microscopy. Malaria-positive cases were treated with anti-malarials in accordance with the national drug policy. Peripheral blood smears of 134 and 159 individuals, including children, were screened for malaria infection in 2013 and 2014, respectively. Overall, the malaria slide positivity rates were 27.6% and 27.7% in 2013 and 2014, respectively, and the prevalence rates of asymptomatic malaria were 20% and 22.8%. This study showed that, for two consecutive years, the prevalence of asymptomatic malaria infection was significantly higher among children aged ≤14 years (34.4% and 34.1% for 2013 and 2014, respectively) compared with adults (15.2% and 18.2% for 2013 and 2014, respectively; P = 0.023 and 0.04, respectively). The number of asymptomatic malaria cases, especially Plasmodium falciparum, is significant, reinforcing the underlying challenge facing the malaria elimination programme in India. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Changing tracks as situations change: humanitarian and health response along the Liberia-Côte d'Ivoire border.

PubMed

Derderian, Katharine

2014-10-01

In recent years, protracted crises and fragile post-conflict settings have challenged the co-existence, and even the linear continuum, of relief and development aid. Forced migration has tested humanitarian and development paradigms where sudden-onset emergencies, violence and displacement arise alongside ongoing development work. Drawing on Médecins Sans Frontières interventions in the region from December 2010 to May 2011, this paper examines aid and healthcare responses to displacement in Côte d'Ivoire and Liberia; it focuses on challenges to the maintenance of preparedness for such foreseeable emergencies and to adaptation in response to changing situations of displacement and insecurity. This 'backsliding' from development to emergency remains a substantial challenge to aid; yet, in exactly such cases, it also presents the opportunity to ensure access to medical care that is much more urgently needed in times of crisis, including the suspension of user fees for medical care. © 2014 The Author(s). Disasters © Overseas Development Institute, 2014.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

PubMed

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Performance of a malaria microscopy image analysis slide reading device.

PubMed

Prescott, William R; Jordan, Robert G; Grobusch, Martin P; Chinchilli, Vernon M; Kleinschmidt, Immo; Borovsky, Joseph; Plaskow, Mark; Torrez, Miguel; Mico, Maximo; Schwabe, Christopher

2012-05-06

Viewing Plasmodium in Romanovsky-stained blood has long been considered the gold standard for diagnosis and a cornerstone in management of the disease. This method however, requires a subjective evaluation by trained, experienced diagnosticians and establishing proficiency of diagnosis is fraught with many challenges. Reported here is an evaluation of a diagnostic system (a "device" consisting of a microscope, a scanner, and a computer algorithm) that evaluates scanned images of standard Giemsa-stained slides and reports species and parasitaemia. The device was challenged with two independent tests: a 55 slide, expert slide reading test the composition of which has been published by the World Health Organization ("WHO55" test), and a second test in which slides were made from a sample of consenting subjects participating in a malaria incidence survey conducted in Equatorial Guinea (EGMIS test). These subjects' blood was tested by malaria RDT as well as having the blood smear diagnosis unequivocally determined by a worldwide panel of a minimum of six reference microscopists. Only slides with unequivocal microscopic diagnoses were used for the device challenge, n = 119. On the WHO55 test, the device scored a "Level 4" using the WHO published grading scheme. Broken down by more traditional analysis parameters this result was translated to 89% and 70% sensitivity and specificity, respectively. Species were correctly identified in 61% of the slides and the quantification of parasites fell within acceptable range of the validated parasitaemia in 10% of the cases. On the EGMIS test it scored 100% and 94% sensitivity/specificity, with 64% of the species correct and 45% of the parasitaemia within an acceptable range. A pooled analysis of the 174 slides used for both tests resulted in an overall 92% sensitivity and 90% specificity with 61% species and 19% quantifications correct. In its current manifestation, the device performs at a level comparable to that of many human slide readers. Because its use requires minimal additional equipment and it uses standard stained slides as starting material, its widespread adoption may eliminate the current uncertainty about the quality of microscopic diagnoses worldwide.

Performance of a malaria microscopy image analysis slide reading device

PubMed Central

2012-01-01

Background Viewing Plasmodium in Romanovsky-stained blood has long been considered the gold standard for diagnosis and a cornerstone in management of the disease. This method however, requires a subjective evaluation by trained, experienced diagnosticians and establishing proficiency of diagnosis is fraught with many challenges. Reported here is an evaluation of a diagnostic system (a “device” consisting of a microscope, a scanner, and a computer algorithm) that evaluates scanned images of standard Giemsa-stained slides and reports species and parasitaemia. Methods The device was challenged with two independent tests: a 55 slide, expert slide reading test the composition of which has been published by the World Health Organization (“WHO55” test), and a second test in which slides were made from a sample of consenting subjects participating in a malaria incidence survey conducted in Equatorial Guinea (EGMIS test). These subjects’ blood was tested by malaria RDT as well as having the blood smear diagnosis unequivocally determined by a worldwide panel of a minimum of six reference microscopists. Only slides with unequivocal microscopic diagnoses were used for the device challenge, n = 119. Results On the WHO55 test, the device scored a “Level 4” using the WHO published grading scheme. Broken down by more traditional analysis parameters this result was translated to 89% and 70% sensitivity and specificity, respectively. Species were correctly identified in 61% of the slides and the quantification of parasites fell within acceptable range of the validated parasitaemia in 10% of the cases. On the EGMIS test it scored 100% and 94% sensitivity/specificity, with 64% of the species correct and 45% of the parasitaemia within an acceptable range. A pooled analysis of the 174 slides used for both tests resulted in an overall 92% sensitivity and 90% specificity with 61% species and 19% quantifications correct. Conclusions In its current manifestation, the device performs at a level comparable to that of many human slide readers. Because its use requires minimal additional equipment and it uses standard stained slides as starting material, its widespread adoption may eliminate the current uncertainty about the quality of microscopic diagnoses worldwide. PMID:22559294

A 'difficult' insect allergy patient: reliable history of a sting, but all testing negative.

PubMed

Tracy, James M; Olsen, Jonathan A; Carlson, John

2015-08-01

Few conditions are as treatable as allergy to stinging insects, with venom immunotherapy (VIT) providing up to 98% protection to subsequent stings. The challenge with VIT is not in the treatment, but in the diagnosis. To offer VIT, one must determine a history of a systemic reaction to a stinging insect in conjunction with the presence venom-specific IgE. Current diagnostic methods, although sensitive and specific, are imperfect, and some newer testing options are not widely available. A conundrum occasionally faced is the patient with a reliable and compelling history of a systemic allergic reaction yet negative venom-specific testing. This diagnostic dilemma presents an opportunity to consider possible causes for this diagnostic challenge. Our evolving understanding of the role of occult mast cell disease may begin to help us understand this situation and develop appropriate management strategies. Venom-specific skin testing has long been the cornerstone of the evaluation of venom sensitivity and is often combined with in-vitro assays to add clarity, but even these occasionally may fall short. Exploring novel venom diagnostic testing methods may help to fill in some of the diagnostic gaps. Do currently available venom vaccines contain all the key venom species? Are there enough differences between insect species that we may simply be missing the relevant allergens? What is the significance of the antigenicity of carbohydrate moieties in venoms? What is the role of recombinant venom extracts? VIT is the definitive treatment for insect allergic individuals. To utilize VIT, identification of the relevant Hymenoptera is necessary. Unfortunately, this cannot always be accomplished. This deficiency can have several causes: a potential comorbid condition such as occult mast cell disease, limitations of currently available diagnostic resources, or testing vaccines with an insufficient coverage of relevant venom allergens. Exploring these potential causes may help to provide important insight into this important diagnostic conundrum. The use of a case report may help clarify this challenge.

Observational methods to assess the effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: SCOLAR.

PubMed

Goodman, Michael; Fletcher, Robert H; Doria-Rose, V Paul; Jensen, Christopher D; Zebrowski, Alexis M; Becerra, Tracy A; Quinn, Virginia P; Zauber, Ann G; Corley, Douglas A; Doubeni, Chyke A

2015-11-01

Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of 'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'. SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. The lessons of SCOLAR's design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.

Malaria profiles and challenges in artemisinin resistance containment in Myanmar.

PubMed

Nwe, Thet Wai; Oo, Tin; Wai, Khin Thet; Zhou, Shuisen; van Griensven, Johan; Chinnakali, Palanivel; Shah, Safieh; Thi, Aung

2017-04-25

This study examined evolving malaria profiles from January, 2010 to December, 2014 to evaluate achievements and challenges of implementing measures to prevent and control spread of artemisinin resistance in Myanmar. Using National Malaria Control Programme (NMCP) data, a cross-sectional descriptive study of 52 townships in artemisinin-resistant containment areas in Myanmar was conducted. Annual program data were analysed, and trends over time are graphically presented. In the 52 study townships populated by 8.7 million inhabitants, malaria incidence showed a decreasing trend from 10.54 per 1 000 population in 2010 to 2.53 in 2014, and malaria mortalities also decreased from 1.83 per 100 000 population in 2010 to 0.17 in 2014. The proportion of confirmed to total tested malaria cases also decreased from 6 to 1%, while identification of cases improved. All cases from all parasites species, including Plasmodium falciparum, decreased. Coverage of LLIN (long-lasting insecticidal net)/ITN (insecticide-treated mosquito nets) and indoor residual spraying (IRS) was high in targeted areas with at-risk persons, even though the total population was not covered. In addition to passive case detection (PCD), active case detection (ACD) was conducted in hard-to-reach areas and worksites where mobile migrant populations were present. ACD improved in most areas from 2012 to 2014, but continues to need to be strengthened. The findings provide useful data on the malaria situation in artemisinin-resistant initiative areas, which may be useful for the NMCP to meet its elimination goal. These profiles could contribute to better planning, implementation, and evaluation of intervention activities.

Tolerability to dogfish in children with fish allergy.

PubMed

Calderon-Rodriguez, S; Pineda, F; Perez, R; Muñoz, C

2016-01-01

Fish is a potent food allergen. The aim of this work is to demonstrate that dogfish, a small shark, has low allergenicity in both its clinical tolerance as well as its molecular structure. We present a study of 34 paediatric patients with IgE-mediated immediate reactions after eating fish. The diagnosis of several fish allergies was demonstrated by skin prick techniques and determination of specific IgE, in all the cases excluding sensitisation to Anisakis simplex. Open oral challenge test was checked with dogfish. Analysis was by SDS-PAGE of dogfish and other fish (megrim, shark, hake, sole, cod, anchovy and tuna) and Western-blot with "pool" of patients polysensitised sera against extracts of dogfish and other fish, and ELISA - inhibition with the "pool" sera. The prick-prick with raw dogfish was slightly positive in six patients, however cooked was negative in 34 cases. The specific IgE showed in the 34 cases class ≥2 for megrim, hake, sole, cod and anchovy, class 0 for tuna in 26 patients, class 0 for emperor in 18 patients and class 0 to Anisakis simplex in all cases. The IgE binding capacity for proteins of allergenic extracts of tested fish revealed, in immunoblotting, the absence of IgE-mediated recognition abstract dogfish by the "pool" of polysensitised patient sera. Testing in vivo and in vitro demonstrated the low allergenicity of dogfish. Dogfish brings an alternative to eating fish in polysensitised patients. Copyright © 2015 SEICAP. Published by Elsevier Espana. All rights reserved.

Performance of nested RT-PCR on CSF for tuberculous meningitis diagnosis in HIV-infected patients.

PubMed

Gualberto, F A S; Gonçalves, M G; Fukasawa, L O; Santos, A M Ramos Dos; Sacchi, C T; Harrison, L H; Boulware, D R; Vidal, J E

2017-10-01

Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.

Cobalt asthma in metalworkers from an automotive engine valve manufacturer.

PubMed

Walters, G I; Robertson, A S; Moore, V C; Burge, P S

2014-07-01

Cobalt asthma has previously been described in cobalt production workers, diamond polishers and glassware manufacturers. To describe a case series of occupational asthma (OA) due to cobalt, identified at the Birmingham Heartlands Occupational Lung Disease Unit, West Midlands, UK. Cases of cobalt asthma from a West Midlands' manufacturer of automotive engine valves, diagnosed between 1996 and 2005, were identified from the SHIELD database of OA. Case note data on demographics, employment status, asthma symptoms and diagnostic tests, including spirometry, peak expiratory flow (PEF) measurements, skin prick testing (SPT) and specific inhalational challenge (SIC) tests to cobalt chloride, were gathered, and descriptive statistics used to illustrate the data. The natural history of presentations has been described in detail, as well as a case study of one of the affected workers. Fourteen metalworkers (86% male; mean age 44.9 years) were diagnosed with cobalt asthma between 1996 and 2005. Workers were principally stellite grinders, stellite welders or machine setter-operators. All workers had positive Occupational Asthma SYStem analyses of serial PEF measurements, and sensitization to cobalt chloride was demonstrated in nine workers, by SPT or SIC. We have described a series of 14 workers with cobalt asthma from the automotive manufacturing industry, with objective evidence for sensitization. Health care workers should remain vigilant for cobalt asthma in the automotive manufacturing industry. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ukrainian prisoners and community reentry challenges: implications for transitional care

PubMed Central

Morozova, Olga; Azbel, Lyuba; Grishaev, Yevgeny; Dvoryak, Sergii; Wickersham, Jeffrey A.; Altice, Frederick L.

2013-01-01

Purpose The study aims to assess reentry challenges faced by Ukrainian prisoners and to determine the factors associated with having a greater number of challenges in order to suggest pre- and post-release interventions with the aim of facilitating community reintegration. Design/methodology/approach A representative national cross-sectional study with a sample size of 402 prisoners was conducted among imprisoned adults within six months of release. The study consisted of interviews and biological testing for infectious diseases. Anticipated reentry challenges were assessed using a structured questionnaire. Findings The most difficult and relatively important challenges identified were finding a job or a stable source of income and staying out of prison following release. Risk-specific challenges pertinent to drug users and HIV-infected individuals were assessed as difficult, but generally less important. Similarly, challenges associated with reducing drug relapse were ranked as less important, with only 0.6 percent identifying opioid substitution therapy as a helpful measure. In the multivariate analysis, having a greater number of challenges is associated with previous incarcerations, drug use immediately before incarceration and lower levels of social support. Practical implications To facilitate community re-integration, it is vital to design interventions aimed at reducing recidivism and improvement of social support through comprehensive case management as well as to improve understanding about and address drug dependence issues among inmates by implementing evidence-based treatment both within prisons and after release. Originality/value This is the first comprehensive assessment of community reentry challenges by prisoners in the former Soviet Union. PMID:25152767

Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders.

PubMed

Canellas, Francesca; Lin, Ling; Julià, Maria Rosa; Clemente, Antonio; Vives-Bauza, Cristofol; Ollila, Hanna M; Hong, Seung Chul; Arboleya, Susana M; Einen, Mali A; Faraco, Juliette; Fernandez-Vina, Marcelo; Mignot, Emmanuel

2014-09-15

Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. © 2014 American Academy of Sleep Medicine.

Oral challenges with four apple cultivars result in significant differences in oral allergy symptoms.

PubMed

Nybom, Hilde; Cervin-Hoberg, Charlotte; Andersson, Morgan

2013-01-01

We analyzed the hypoallergenic potential of a recently bred apple selection with unusually low content of Mal d 1, using an oral challenge model with three additional apple cultivars for comparison. Sixty-six birch pollen-allergic individuals with a history of oral allergy syndrome after apple intake were subjected to a double-blind oral provocation with two apple cultivars (B:0654 and 'Discovery'). Thirteen also tested two other apple cultivars ('Ingrid Marie' and 'Gloster'). Three doses were given consecutively, 30 min apart: 10 g without peel, and 10 and 50 g with peel. A final assessment was conducted 30 min after the last intake. Oral symptoms were graded from 0 to 5. Total oral symptom score (TOS) included all scores for each cultivar at all time points. B:0654 induced significantly higher TOS than 'Discovery' when tested by 66 individuals, in spite of its lower Mal d 1 content. TOS values were higher in females and increased with increasing age of the individuals when challenged with 'Discovery'. Among the 13 individuals who tested all four cultivars, B:0654 produced a higher score after the second dose compared to 'Ingrid Marie'. This was also the case after the third dose compared to 'Ingrid Marie' and 'Gloster', and again 30 min after the last intake compared to each of the other three cultivars, as well as a higher TOS compared to each of the other three cultivars (all p < 0.01). Our test was safe and well tolerated, and produced significant differences among the apple cultivars. Contrary to expectations, B:0654 was less well tolerated than the other three cultivars. Copyright © 2013 S. Karger AG, Basel.

System-Level Instructional Leadership--A District-Level Leadership Case: Implementing PLCs in Schools

ERIC Educational Resources Information Center

Archbald, Doug

2016-01-01

Objective of the Case--There is a large volume of theoretical and "how to" literature on professional learning communities (PLCs), but little documenting the challenges of implementation and even less on the challenges of system-wide implementation of PLCs. This case is about the role of the central office in initiating and supporting…

Lessons Learned During Instrument Testing for the Thermal Infrared Sensor (TIRS)

NASA Technical Reports Server (NTRS)

Peabody, Hume L.; Otero, Veronica; Neuberger, David

2013-01-01

The Themal InfraRed Sensor (TIRS) instrument, set to launch on the Landsat Data Continuity Mission in 2013, features a passively cooled telescope and IR detectors which are actively cooled by a two stage cryocooler. In order to proceed to the instrument level test campaign, at least one full functional test was required, necessitating a thermal vacuum test to sufficiently cool the detectors and demonstrate performance. This was fairly unique in that this test occurred before the Pre Environmental Review, but yielded significant knowledge gains before the planned instrument level test. During the pre-PER test, numerous discrepancies were found between the model and the actual hardware, which were revealed by poor correlation between model predictions and test data. With the inclusion of pseudo-balance points, the test also provided an opportunity to perform a pre-correlation to test data prior to the instrument level test campaign. Various lessons were learned during this test related to modeling and design of both the flight hardware and the Ground Support Equipment and test setup. The lessons learned in the pre-PER test resulted in a better test setup for the nstrument level test and the completion of the final instrument model correlation in a shorter period of time. Upon completion of the correlation, the flight predictions were generated including the full suite of off-nominal cases, including some new cases defined by the spacecraft. For some of these ·new cases, some components now revealed limit exceedances, in particular for a portion of the hardware that could not be tested due to its size and chamber limitations.. Further lessons were learned during the completion of flight predictions. With a correlated detalled instrument model, significant efforts were made to generate a reduced model suitable for observatory level analyses. This proved a major effort both to generate an appropriate network as well as to convert to the final model to the required format and yielded additional lessons learned. In spite of all the challenges encountered by TIRS, the instrument was successfully delivered to the spacecraft and will soon be tested at observatory level in preparation for a successful mission launch.

Impact of electric vehicles on the IEEE 34 node distribution infrastructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Zeming; Shalalfel, Laith; Beshir, Mohammed J.

With the growing penetration of the electric vehicles to our daily life owing to their economic and environmental benefits, there will be both opportunities and challenges to the utilities when adopting plug-in electric vehicles (PEV) to the distribution network. In this study, a thorough analysis based on real-world project is conducted to evaluate the impacts of electric vehicles infrastructure on the grid relating to system load flow, load factor, and voltage stability. IEEE 34 node test feeder was selected and tested along with different case scenarios utilizing the electrical distribution design (EDD) software to find out the potential impacts tomore » the grid.« less

Impact of electric vehicles on the IEEE 34 node distribution infrastructure

DOE PAGES

Jiang, Zeming; Shalalfel, Laith; Beshir, Mohammed J.

2014-10-01

With the growing penetration of the electric vehicles to our daily life owing to their economic and environmental benefits, there will be both opportunities and challenges to the utilities when adopting plug-in electric vehicles (PEV) to the distribution network. In this study, a thorough analysis based on real-world project is conducted to evaluate the impacts of electric vehicles infrastructure on the grid relating to system load flow, load factor, and voltage stability. IEEE 34 node test feeder was selected and tested along with different case scenarios utilizing the electrical distribution design (EDD) software to find out the potential impacts tomore » the grid.« less

A Patient Presenting with Cardiac Tamponade and the Challenges of Finding Its Cause: A Cardiac Angiosarcoma.

PubMed

Habibi, Roshanak; Faramarzi, Negar; Altamirano, Alvaro J; Dadkhah, Shahriar

2018-01-01

Primary malignancies of the heart are so rare that most of the available data come from case reports or large single-center-based studies, with the overall incidence of 0.02% in the United States. Diagnosis in case of an isolated pericardial effusion as presentation is challenging, and determining that an angiosarcoma is even more challenging. Here, we presented a rare case of pericardial angiosarcoma which presented to us with tamponade. The patient eventually was diagnosed through pericardiectomy. A multimodality approach was attempted to treat the cancer. The clinical details of such a unique disease entity inspired us to present it as a case report.

Formal Foundations for Hierarchical Safety Cases

NASA Technical Reports Server (NTRS)

Denney, Ewen; Pai, Ganesh; Whiteside, Iain

2015-01-01

Safety cases are increasingly being required in many safety-critical domains to assure, using structured argumentation and evidence, that a system is acceptably safe. However, comprehensive system-wide safety arguments present appreciable challenges to develop, understand, evaluate, and manage, partly due to the volume of information that they aggregate, such as the results of hazard analysis, requirements analysis, testing, formal verification, and other engineering activities. Previously, we have proposed hierarchical safety cases, hicases, to aid the comprehension of safety case argument structures. In this paper, we build on a formal notion of safety case to formalise the use of hierarchy as a structuring technique, and show that hicases satisfy several desirable properties. Our aim is to provide a formal, theoretical foundation for safety cases. In particular, we believe that tools for high assurance systems should be granted similar assurance to the systems to which they are applied. To this end, we formally specify and prove the correctness of key operations for constructing and managing hicases, which gives the specification for implementing hicases in AdvoCATE, our toolset for safety case automation. We motivate and explain the theory with the help of a simple running example, extracted from a real safety case and developed using AdvoCATE.

The IDEA model: A single equation approach to the Ebola forecasting challenge.

PubMed

Tuite, Ashleigh R; Fisman, David N

2018-03-01

Mathematical modeling is increasingly accepted as a tool that can inform disease control policy in the face of emerging infectious diseases, such as the 2014-2015 West African Ebola epidemic, but little is known about the relative performance of alternate forecasting approaches. The RAPIDD Ebola Forecasting Challenge (REFC) tested the ability of eight mathematical models to generate useful forecasts in the face of simulated Ebola outbreaks. We used a simple, phenomenological single-equation model (the "IDEA" model), which relies only on case counts, in the REFC. Model fits were performed using a maximum likelihood approach. We found that the model performed reasonably well relative to other more complex approaches, with performance metrics ranked on average 4th or 5th among participating models. IDEA appeared better suited to long- than short-term forecasts, and could be fit using nothing but reported case counts. Several limitations were identified, including difficulty in identifying epidemic peak (even retrospectively), unrealistically precise confidence intervals, and difficulty interpolating daily case counts when using a model scaled to epidemic generation time. More realistic confidence intervals were generated when case counts were assumed to follow a negative binomial, rather than Poisson, distribution. Nonetheless, IDEA represents a simple phenomenological model, easily implemented in widely available software packages that could be used by frontline public health personnel to generate forecasts with accuracy that approximates that which is achieved using more complex methodologies. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

Predictive genetic testing in children: constitutional mismatch repair deficiency cancer predisposing syndrome.

PubMed

Bruwer, Zandrè; Algar, Ursula; Vorster, Alvera; Fieggen, Karen; Davidson, Alan; Goldberg, Paul; Wainwright, Helen; Ramesar, Rajkumar

2014-04-01

Biallelic germline mutations in mismatch repair genes predispose to constitutional mismatch repair deficiency syndrome (CMMR-D). The condition is characterized by a broad spectrum of early-onset tumors, including hematological, brain and bowel and is frequently associated with features of Neurofibromatosis type 1. Few definitive screening recommendations have been suggested and no published reports have described predictive testing. We report on the first case of predictive testing for CMMR-D following the identification of two non-consanguineous parents, with the same heterozygous mutation in MLH1: c.1528C > T. The genetic counseling offered to the family, for their two at-risk daughters, is discussed with a focus on the ethical considerations of testing children for known cancer-causing variants. The challenges that are encountered when reporting on heterozygosity in a child younger than 18 years (disclosure of carrier status and risk for Lynch syndrome), when discovered during testing for homozygosity, are addressed. In addition, the identification of CMMR-D in a three year old, and the recommended clinical surveillance that was proposed for this individual is discussed. Despite predictive testing and presymptomatic screening, the sudden death of the child with CMMR-D syndrome occurred 6 months after her last surveillance MRI. This report further highlights the difficulty of developing guidelines, as a result of the rarity of cases and diversity of presentation.

When to start paediatric testing of the adult HIV cure research agenda?

PubMed

Shah, Seema K

2017-02-01

Ethical guidelines recommend that experimental interventions should be tested in adults first before they are tested and approved in children. Some challenge this paradigm, however, and recommend initiating paediatric testing after preliminary safety testing in adults in certain cases. For instance, commentators have argued for accelerated testing of HIV vaccines in children. Additionally, HIV cure research on the use of very early therapy (VET) in infants, prompted in part by the Mississippi baby case, is one example of a strategy that is currently being tested in infants before it has been well tested in adults. Because infants' immune systems are still developing, the timing of HIV transmission is easier to identify in infants than in adults, and infants who receive VET might never develop the viral reservoirs that make HIV so difficult to eradicate, infants may be uniquely situated to achieve HIV cure or sustained viral remission. Several commentators have now argued for earlier initiation of HIV cure interventions other than (or in addition to) VET in children. HIV cure research is therefore a good case for re-examining the important question of when to initiate paediatric research. I will argue that, despite the potential for HIV cure research to benefit children and the scientific value of involving children in this research, the HIV cure agenda should not accelerate the involvement of children for the following reasons: HIV cure research is highly speculative, risky, aimed at combination approaches and does not compare favourably with the available alternatives. I conclude by drawing general implications for the initiation of paediatric testing, including that interventions that have to be used in combination with others and cures for chronic diseases may not be valuable enough to justify early paediatric testing. 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/.

Road map for the clinical application of the basophil activation test in food allergy.

PubMed

Santos, A F; Shreffler, W G

2017-09-01

The diagnosis of IgE-mediated food allergy based solely on the clinical history and the documentation of specific IgE to whole allergen extract or single allergens is often ambiguous, requiring oral food challenges (OFCs), with the attendant risk and inconvenience to the patient, to confirm the diagnosis of food allergy. This is a considerable proportion of patients assessed in allergy clinics. The basophil activation test (BAT) has emerged as having superior specificity and comparable sensitivity to diagnose food allergy, when compared with skin prick test and specific IgE. BAT, therefore, may reduce the number of OFC required for accurate diagnosis, particularly positive OFC. BAT can also be used to monitor resolution of food allergy and the clinical response to immunomodulatory treatments. Given the practicalities involved in the performance of BAT, we propose that it can be applied for selected cases where the history, skin prick test and/or specific IgE are not definitive for the diagnosis of food allergy. In the cases that the BAT is positive, food allergy is sufficiently confirmed without OFC; in the cases that BAT is negative or the patient has non-responder basophils, OFC may still be indicated. However, broad clinical application of BAT demands further standardization of the laboratory procedure and of the flow cytometry data analyses, as well as clinical validation of BAT as a diagnostic test for multiple target allergens and confirmation of its feasibility and cost-effectiveness in multiple settings. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Computer-aided detection of bladder wall thickening in CT urography (CTU)

NASA Astrophysics Data System (ADS)

Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon Z.; Gordon, Marshall N.; Samala, Ravi K.

2018-02-01

We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). Bladder wall thickening is a manifestation of bladder cancer and its detection is more challenging than the detection of bladder masses. We first segmented the inner and outer bladder walls using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential lesions. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify regions of wall thickening candidates. Volume-based features of the wall thickening candidates were analyzed with linear discriminant analysis (LDA) to differentiate bladder wall thickenings from false positives. A data set of 112 patients, 87 with wall thickening and 25 with normal bladders, was collected retrospectively with IRB approval, and split into independent training and test sets. Of the 57 training cases, 44 had bladder wall thickening and 13 were normal. Of the 55 test cases, 43 had wall thickening and 12 were normal. The LDA classifier was trained with the training set and evaluated with the test set. FROC analysis showed that the system achieved sensitivities of 93.2% and 88.4% for the training and test sets, respectively, at 0.5 FPs/case.

Evaluation of dengue virus strains for human challenge studies.

PubMed

Mammen, M P; Lyons, A; Innis, B L; Sun, W; McKinney, D; Chung, R C Y; Eckels, K H; Putnak, R; Kanesa-thasan, N; Scherer, J M; Statler, J; Asher, L V; Thomas, S J; Vaughn, D W

2014-03-14

Discordance between the measured levels of dengue virus neutralizing antibody and clinical outcomes in the first-ever efficacy study of a dengue tetravalent vaccine (Lancet, Nov 2012) suggests a need to re-evaluate the process of pre-screening dengue vaccine candidates to better predict clinical benefit prior to large-scale vaccine trials. In the absence of a reliable animal model and established correlates of protection for dengue, a human dengue virus challenge model may provide an approach to down-select vaccine candidates based on their ability to reduce risk of illness following dengue virus challenge. We report here the challenge of flavivirus-naïve adults with cell culture-passaged dengue viruses (DENV) in a controlled setting that resulted in uncomplicated dengue fever (DF). This sets the stage for proof-of-concept efficacy studies that allow the evaluation of dengue vaccine candidates in healthy adult volunteers using qualified DENV challenge strains well before they reach field efficacy trials involving children. Fifteen flavivirus-naïve adult volunteers received 1 of 7 DENV challenge strains (n=12) or placebo (n=3). Of the twelve volunteers who received challenge strains, five (two DENV-1 45AZ5 and three DENV-3 CH53489 cl24/28 recipients) developed DF, prospectively defined as ≥2 typical symptoms, ≥48h of sustained fever (>100.4°F) and concurrent viremia. Based on our study and historical data, we conclude that the DENV-1 and DENV-3 strains can be advanced as human challenge strains. Both of the DENV-2 strains and one DENV-4 strain failed to meet the protocol case definition of DF. The other two DENV-4 strains require additional testing as the illness approximated but did not satisfy the case definition of DF. Three volunteers exhibited effusions (1 pleural/ascites, 2 pericardial) and 1 volunteer exhibited features of dengue (rash, lymphadenopathy, neutropenia and thrombocytopenia), though in the absence of fever and symptoms. The occurrence of effusions in milder DENV infections counters the long-held belief that plasma leakage syndromes are restricted to dengue hemorrhagic fever/dengue shock syndromes (DHF/DSS). Hence, the human dengue challenge model may be useful not only for predicting the efficacy of vaccine and therapeutic candidates in small adult cohorts, but also for contributing to our further understanding of the mechanisms behind protection and virulence. Published by Elsevier Ltd.

Stereochemical analysis of (+)-limonene using theoretical and experimental NMR and chiroptical data

NASA Astrophysics Data System (ADS)

Reinscheid, F.; Reinscheid, U. M.

2016-02-01

Using limonene as test molecule, the success and the limitations of three chiroptical methods (optical rotatory dispersion (ORD), electronic and vibrational circular dichroism, ECD and VCD) could be demonstrated. At quite low levels of theory (mpw1pw91/cc-pvdz, IEFPCM (integral equation formalism polarizable continuum model)) the experimental ORD values differ by less than 10 units from the calculated values. The modelling in the condensed phase still represents a challenge so that experimental NMR data were used to test for aggregation and solvent-solute interactions. After establishing a reasonable structural model, only the ECD spectra prediction showed a decisive dependence on the basis set: only augmented (in the case of Dunning's basis sets) or diffuse (in the case of Pople's basis sets) basis sets predicted the position and shape of the ECD bands correctly. Based on these result we propose a procedure to assign the absolute configuration (AC) of an unknown compound using the comparison between experimental and calculated chiroptical data.

Reconstruction of Orion Engineering Development Unit (EDU) Parachute Inflation Loads

NASA Technical Reports Server (NTRS)

Ray, Eric S.

2013-01-01

The process of reconstructing inflation loads of Capsule Parachute Assembly System (CPAS) has been updated as the program transitioned to testing Engineering Development Unit (EDU) hardware. The equations used to reduce the test data have been re-derived based on the same physical assumptions made by simulations. Due to instrumentation challenges, individual parachute loads are determined from complementary accelerometer and load cell measurements. Cluster inflations are now simulated by modeling each parachute individually to better represent different inflation times and non-synchronous disreefing. The reconstruction procedure is tailored to either infinite mass or finite mass events based on measurable characteristics from the test data. Inflation parameters are determined from an automated optimization routine to reduce subjectivity. Infinite mass inflation parameters have been re-defined to avoid unrealistic interactions in Monte Carlo simulations. Sample cases demonstrate how best-fit inflation parameters are used to generate simulated drag areas and loads which favorably agree with test data.

Interpretation of genetic testing for lynch syndrome in patients with putative familial colorectal cancer.

PubMed

Rybak, Christina; Hall, Michael J

2011-11-01

Colorectal cancer (CRC) risk assessment involves the evaluation of an individual's personal and family history for characteristics of an inherited susceptibility to develop CRC. Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is the most common cause of hereditary CRC, underlying 2% to 3% of patients with newly diagnosed (incident) CRC. Risk assessment for LS is complex, and the interpretation of the many available tests can be challenging even for the genetics specialist. A move toward universal (reflex) LS screening for mismatch repair in all patients with incident CRC supports the importance of improving the awareness and understanding of LS testing, teaching rational testing approaches, and honing interpretive skills among cancer care providers. This article reviews important clinical features of LS genetic evaluation using 3 pedigree-based case examples from the Fox Chase Cancer Center Gastrointestinal Risk Assessment Clinic.

Zika Virus Testing and Outcomes during Pregnancy, Florida, USA, 2016

PubMed Central

Shiu, Colette; Starker, Rebecca; Kwal, Jaclyn; Bartlett, Michelle; Crane, Anise; Greissman, Samantha; Gunaratne, Naiomi; Lardy, Meghan; Picon, Michelle; Rodriguez, Patricia; Gonzalez, Ivan

2018-01-01

Zika virus infection during pregnancy can lead to congenital Zika syndrome. Implementation of screening programs and interpretation of test results can be particularly challenging during ongoing local mosquitoborne transmission. We conducted a retrospective chart review of 2,327 pregnant women screened for Zika virus in Miami–Dade County, Florida, USA, during 2016. Of these, 86 had laboratory evidence of Zika virus infection; we describe 2 infants with probable congenital Zika syndrome. Delays in receipt of laboratory test results (median 42 days) occurred during the first month of local transmission. Odds of screening positive for Zika virus were higher for women without health insurance or who did not speak English. Our findings indicate the increase in screening for Zika virus can overwhelm hospital and public health systems, resulting in delayed receipt of results of screening and confirmatory tests and the potential to miss cases or delay diagnoses. PMID:29260671

Correction of complex nonlinear signal response from a pixel array detector

PubMed Central

van Driel, Tim Brandt; Herrmann, Sven; Carini, Gabriella; Nielsen, Martin Meedom; Lemke, Henrik Till

2015-01-01

The pulsed free-electron laser light sources represent a new challenge to photon area detectors due to the intrinsic spontaneous X-ray photon generation process that makes single-pulse detection necessary. Intensity fluctuations up to 100% between individual pulses lead to high linearity requirements in order to distinguish small signal changes. In real detectors, signal distortions as a function of the intensity distribution on the entire detector can occur. Here a robust method to correct this nonlinear response in an area detector is presented for the case of exposures to similar signals. The method is tested for the case of diffuse scattering from liquids where relevant sub-1% signal changes appear on the same order as artifacts induced by the detector electronics. PMID:25931072

Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome.

PubMed

Polat, Asude Kara; Belli, Asli Akin; Karakus, Volkan; Dere, Yelda

2017-01-01

Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Chemical burns of the oral mucosa: report of a case.

PubMed

Isenberg, S R; Hier, L A; Chauvin, P J

1996-03-01

Clinical diagnosis of a chemical burn of the oral mucous membranes may be a diagnostic challenge. This article's intent is to illustrate the typical appearance of a chemical mucosal burn and to increase awareness of the various compounds which, when in contact with the mucous membranes, can result in a burn. The authors present a case involving a self-inflicted chemical injury of the oral mucous membranes and illustrate how the submission of an easily-obtained tissue specimen for pathologic examination may aid in the diagnosis. Because these superficial tissues can be obtained and submitted without the need for local anesthetic, pathologic examination is a quick, easy, and valuable diagnostic test when a patient's history is difficult to obtain or intentionally misleading.

Correction of complex nonlinear signal response from a pixel array detector.

PubMed

van Driel, Tim Brandt; Herrmann, Sven; Carini, Gabriella; Nielsen, Martin Meedom; Lemke, Henrik Till

2015-05-01

The pulsed free-electron laser light sources represent a new challenge to photon area detectors due to the intrinsic spontaneous X-ray photon generation process that makes single-pulse detection necessary. Intensity fluctuations up to 100% between individual pulses lead to high linearity requirements in order to distinguish small signal changes. In real detectors, signal distortions as a function of the intensity distribution on the entire detector can occur. Here a robust method to correct this nonlinear response in an area detector is presented for the case of exposures to similar signals. The method is tested for the case of diffuse scattering from liquids where relevant sub-1% signal changes appear on the same order as artifacts induced by the detector electronics.

Unilateral eyelid angioedema with congestion of the right bulbar conjunctiva due to loxoprofen sodium.

PubMed

Tsuruta, Daisuke; Oshimo, Tomoko; Sowa, Junko; Ishii, Masamitsu; Kobayashi, Hiromi

2011-01-01

Angioedema is a variant of urticaria that causes deep dermal and subcutaneous swelling. It frequently is a unilateral reaction and usually lasts for several hours but may persist for several days. We report 2 cases of angioedema that involved the right upper and lower eyelids and was associated with congestion of the right bulbar conjunctiva; the symptoms started approximately 1 to 2 hours after taking loxoprofen sodium. All of the symptoms subsided after oral corticosteroid therapy. In both cases, an oral challenge test with 60 mg of loxoprofen sodium (contained in a tablet) caused swelling of the right upper eyelid within several hours, followed by swelling of the right bulbar conjunctiva. We believe the drug reaction in both patients is angioedema.

Polycythemia vera presenting as acute myocardial infarction: An unusual presentation

PubMed Central

Bahbahani, Hussain; Aljenaee, Khaled; Bella, Abdelhaleem

2014-01-01

Acute myocardial infarction (AMI) is usually seen in the setting of atherosclerosis and its associated risk factors. Myocardial infarction in the young poses a particular challenge, as the disease is less likely, due to atherosclerosis. We report the case of a 37-year-old female patient who presented with ST segment elevation anterolateral AMI. The only abnormality on routine blood investigation was raised hemoglobin and hematocrit. After further testing, she was diagnosed according to the World Health Organization (WHO) criteria with polycythemia vera. This case illustrates the importance of recognizing polycythemia vera as an important cause of thrombosis, which can present initially as AMI, and to emphasize the early recognition of the disease in order to initiate appropriate management strategies. PMID:25544823

Occupational and Environmental Bronchiolar Disorders

PubMed Central

Cummings, Kristin J.; Kreiss, Kathleen

2015-01-01

Occupational and environmental causes of bronchiolar disorders are recognized on the basis of case reports, case series, and, less commonly, epidemiologic investigations. Pathology may be limited to the bronchioles or also involve other components of the respiratory tract, including the alveoli. A range of clinical, functional, and radiographic findings, including symptomatic disease lacking abnormalities on noninvasive testing, poses a diagnostic challenge and highlights the value of surgical biopsy. Disease clusters in workplaces and communities have identified new etiologies, drawn attention to indolent disease that may otherwise have been categorized as idiopathic, and expanded the spectrum of histopathologic responses to an exposure. More sensitive noninvasive diagnostic tools, evidence-based therapies, and ongoing epidemiologic investigation of at-risk populations are needed to identify, treat, and prevent exposure-related bronchiolar disorders. PMID:26024345

Stakeholder approach for evaluating organizational change projects.

PubMed

Peltokorpi, Antti; Alho, Antti; Kujala, Jaakko; Aitamurto, Johanna; Parvinen, Petri

2008-01-01

This paper aims to create a model for evaluating organizational change initiatives from a stakeholder resistance viewpoint. The paper presents a model to evaluate change projects and their expected benefits. Factors affecting the challenge to implement change were defined based on stakeholder theory literature. The authors test the model's practical validity for screening change initiatives to improve operating room productivity. Change initiatives can be evaluated using six factors: the effect of the planned intervention on stakeholders' actions and position; stakeholders' capability to influence the project's implementation; motivation to participate; capability to change; change complexity; and management capability. The presented model's generalizability should be explored by filtering presented factors through a larger number of historical cases operating in different healthcare contexts. The link between stakeholders, the change challenge and the outcomes of change projects needs to be empirically tested. The proposed model can be used to prioritize change projects, manage stakeholder resistance and establish a better organizational and professional competence for managing healthcare organization change projects. New insights into existing stakeholder-related understanding of change project successes are provided.

The Effect of Administering a Boundary Course to Third-Year Medical Students During Their Psychiatry Clerkship.

PubMed

Kunaparaju, Sindhura; Hidalgo, Michael Sposito; Bennett, David S; Sedky, Karim

2018-06-01

Due to lack of experience, third-year medical students (MS3) may be vulnerable to boundary violations. Investigators aimed to increase awareness regarding boundary issues among MS3s and assess the effect of using videotaped scenarios and case-based discussion on medical students' comfort in managing boundary issues. A nine-question pre-course survey was administered to MS3s enrolled at Cooper Medical School of Rowan University that asked students to rate their comfort in managing various boundary challenges. MS3s then viewed seven pre-recorded boundary-related cases followed by a 10-15-min discussion after each case. A post-course survey reassessed comfort in managing boundary challenges using the same nine questions, with three additional questions assessing satisfaction with the course. Change in pre- and post-course scores were analyzed using paired t tests and effect sizes. Internal consistency was assessed using Cronbach's alpha. There was a significant difference between pre- and post-course total scores as well as seven of the nine individual scores. Effect sizes were large (d > .08). These findings indicate that students became more comfortable managing boundary issues following the course. In addition, satisfaction ratings were high indicating the course was perceived favorably. Medical students perceived the course to be beneficial and reported that it increased their awareness of boundary issues. A boundary course at the beginning of the psychiatry clerkship can improve MS3s' comfort in managing boundary challenges. With increased comfort in managing boundary, students can better focus on other aspects of their psychiatry education and on building therapeutic alliances with their patients.

In search of novel ligands using a structure-based approach: a case study on the adenosine A2A receptor.

PubMed

Lenselink, Eelke B; Beuming, Thijs; van Veen, Corine; Massink, Arnault; Sherman, Woody; van Vlijmen, Herman W T; IJzerman, Adriaan P

2016-10-01

In this work, we present a case study to explore the challenges associated with finding novel molecules for a receptor that has been studied in depth and has a wealth of chemical information available. Specifically, we apply a previously described protocol that incorporates explicit water molecules in the ligand binding site to prospectively screen over 2.5 million drug-like and lead-like compounds from the commercially available eMolecules database in search of novel binders to the adenosine A 2A receptor (A 2A AR). A total of seventy-one compounds were selected for purchase and biochemical assaying based on high ligand efficiency and high novelty (Tanimoto coefficient ≤0.25 to any A 2A AR tested compound). These molecules were then tested for their affinity to the adenosine A 2A receptor in a radioligand binding assay. We identified two hits that fulfilled the criterion of ~50 % radioligand displacement at a concentration of 10 μM. Next we selected an additional eight novel molecules that were predicted to make a bidentate interaction with Asn253 6.55 , a key interacting residue in the binding pocket of the A 2A AR. None of these eight molecules were found to be active. Based on these results we discuss the advantages of structure-based methods and the challenges associated with finding chemically novel molecules for well-explored targets.

Opportunities and Challenges for Students in an Online Seminar-Style Course in LIS Education: A Qualitative Case Study

ERIC Educational Resources Information Center

Farooq, Omer; Matteson, Miriam

2016-01-01

Online enrollments in U.S. higher education programs continue to grow, a trend that is also seen in LIS education where in some cases entire MLIS programs are being offered online. Synchronous online seminar-style courses present interesting challenges for both radical inclusion and innovation. This qualitative case study explored the…

Conundrums in neurology: diagnosing serotonin syndrome - a meta-analysis of cases.

PubMed

Werneke, Ursula; Jamshidi, Fariba; Taylor, David M; Ott, Michael

2016-07-12

Serotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome's main feature is neuro-muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history. Systematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science. Two of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear-cut. Our findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be captured in any other way but through case reports.

Solitary Fibrous Tumor of Retromolar Pad; a Rare Challenging Case

PubMed Central

Lotfi, Ali; Mokhtari, Sepideh; Moshref, Mohammad; Shahla, Maryam; Atarbashi Moghadam, Saede

2017-01-01

Solitary fibrous tumor has a wide spectrum of histopathologic features and many tumors show similar microscopic features. This similarity poses diagnostic challenges to the pathologists and immunohistochemical analysis is required in many cases. Moreover, it is a rare entity in orofacial region which consequently would make its diagnosis more challenging in oral cavity. The knowledge of various microscopic patterns of this tumor contributes to a proper diagnosis and prevents unnecessary treatment. This study reports a case of solitary fibrous tumor in the retromolar pad area and discusses its various histological features and differential diagnoses. PMID:28620640

Effects of handcuffs on neuropsychological testing: Implications for criminal forensic evaluations.

PubMed

Biddle, Christine M; Fazio, Rachel L; Dyshniku, Fiona; Denney, Robert L

2018-01-01

Neuropsychological evaluations are increasingly performed in forensic contexts, including in criminal settings where security sometimes cannot be compromised to facilitate evaluation according to standardized procedures. Interpretation of nonstandardized assessment results poses significant challenges for the neuropsychologist. Research is limited in regard to the validation of neuropsychological test accommodation and modification practices that deviate from standard test administration; there is no published research regarding the effects of hand restraints upon neuropsychological evaluation results. This study provides preliminary results regarding the impact of restraints on motor functioning and common neuropsychological tests with a motor component. When restrained, performance on nearly all tests utilized was significantly impacted, including Trail Making Test A/B, a coding test, and several tests of motor functioning. Significant performance decline was observed in both raw scores and normative scores. Regression models are also provided in order to help forensic neuropsychologists adjust for the effect of hand restraints on raw scores of these tests, as the hand restraints also resulted in significant differences in normative scores; in the most striking case there was nearly a full standard deviation of discrepancy.

Histopathologic and mutational analysis of a case of blue nevus-like melanoma.

PubMed

Dai, Julia; Tetzlaff, Michael T; Schuchter, Lynn M; Elder, David E; Elenitsas, Rosalie

2016-09-01

Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Barriers, Challenges, and Decision-Making in the Letter Writing Process for Gender Transition.

PubMed

Budge, Stephanie L; Dickey, Lore M

2017-03-01

This article addresses the challenges that clinicians face in writing letters of support for transgender and gender-diverse clients. It addresses common but challenging clinical representations to help the reader understand the nuances associated with writing letters. Three cases are presented. The first addresses systemic challenges, the second addresses management of care, and the third addresses co-occurring mental health concerns. Recommendations for practice are provided based on the experiences included within the 3 case examples. Copyright © 2016 Elsevier Inc. All rights reserved.

Challenging Tasks: What Happens When Challenging Tasks Are Used in Mixed Ability Middle School Mathematics Classrooms?

ERIC Educational Resources Information Center

Perkins, Karen

2016-01-01

The topics of decimals and polygons were taught to two classes by using challenging tasks, rather than the more conventional textbook approach. Students were given a pre-test and a post-test. A comparison between the two classes on the pre- and post-test was made. Prior to teaching through challenging tasks, students were surveyed about their…

Fractions division knowledge of elementary school student: The case of Lala

NASA Astrophysics Data System (ADS)

Purnomo, Yoppy Wahyu; Widowati, Chairunnisa; Aziz, Tian Abdul; Pramudiani, Puri

2017-08-01

Division of fractions is often acknowledged by mysterious rule which is not based on conceptual knowledge. The purpose of the study was to explore elementary school student's knowledge of division fractions. For this purpose, a case study was conducted. The participant of the study was Lala (pseudonym) who enrolled at one elementary school in East Jakarta. The data were collected by administering written test and semi-structured interview respectively. The findings of the study indicated that Lala was able to describe strategy of division fractions as inverse of repeated addition flexibly. She also had basic understanding of fractions division concept as equal sharing, but when she was challenged with advance problems, she performed poorly. Lala also encountered difficulty when dealing with dividing fraction by fraction problem in which she interpreted it as subtraction problem. In this case, her procedural knowledge was likely to be more salient than her conceptual knowledge.

Toxoplasmosis in macropodids: a review.

PubMed

Portas, Timothy J

2010-03-01

Toxoplasmosis is a well-described disease entity that causes significant morbidity and mortality in both captive and free-ranging macropodids. The clinical presentation of toxoplasmosis in macropodids is variable, which reflects the multiple body systems affected by this disease. Animals may die without exhibiting premonitory signs or after the acute development of nonspecific signs of illness. In more chronic cases, clinical signs include neurologic deficits, blindness, respiratory signs, and, in some cases, diarrhea. Histologic lesions can be extensive and affect the pulmonary parenchyma, cardiac and skeletal muscle, lymph nodes, spleen, gastrointestinal tract, adrenal glands, pancreas, central nervous system, liver, and kidney. An antemortem diagnosis can be challenging, although a range of serologic tests are available. Treatment is frequently unrewarding, although recent evidence suggests that the anti-protozoal drug atovaquone may be effective in treating acute cases and eliminating infection. Attempts to vaccinate macropodids against toxoplasmosis have been unsuccessful, and preventive measures are limited to preventing exposure to sporulated oocysts in the environment.

Use of Cardiac Injury Markers in the Postmortem Diagnosis of Sudden Cardiac Death.

PubMed

Carvajal-Zarrabal, Octavio; Hayward-Jones, Patricia M; Nolasco-Hipolito, Cirilo; Barradas-Dermitz, Dulce Ma; Calderón-Garcidueñas, Ana Laura; López-Amador, Noé

2017-09-01

In the daily practice of forensic pathology, sudden cardiac death (SCD) is a diagnostic challenge. Our aim was to determine the usefulness of blood biomarkers [creatine kinase CK-MB, myoglobin, troponins I and T (cTn-I and T), and lactate dehydrogenase] measured by immunoassay technique, in the postmortem diagnosis of SCD. Two groups were compared, 20 corpses with SCD and 8 controls. Statistical significance was determined by variance analysis procedures, with a post hoc Tukey multiple range test for comparison of means (p < 0.05). SCD cases showed significantly higher levels (p < 0.05) of cTn-T and cTn-I compared to the control group. Although only cases within the first 8 h of postmortem interval were included, and the control group consisted mainly of violent death cases, our results suggest that blood troponin levels may be useful to support a diagnosis of SCD. © 2017 American Academy of Forensic Sciences.

Crossing the other side of the algorithm: a challenging case of adrenal Cushing's syndrome.

PubMed

Antonio, Imelda Digna Soberano; Sandoval, Mark Anthony Santiago; Lantion-Ang, Frances Lina

2011-12-01

The diagnosis of endogenous Cushing's syndrome and its aetiology involved documenting the hypercotisolism and then determining whether that hypercortisolism is adrenocorticotropic hormone-dependent (ACTH-dependent) or not. Hence, following the algorithm, an undetected ACTH level points to an adrenal Cushing's while a detectable or elevated ACTH level points to either a pituitary or ectopic Cushing's syndrome. The authors present a case of florid adrenal Cushing's syndrome initially presenting with a normal ACTH level, which led to the investigation for an ACTH-secreting tumour. Adding to the confusion, a MRI done showed an intrasellar focus. Knowledge of how ACTH-dependent (versus ACTH-independent) Cushing's syndrome manifests clinically, supported by results of repeat laboratory tests, led to the true diagnosis. This case illustrates that a detectable ACTH does not rule out an adrenal Cushing's syndrome nor does a positive pituitary imaging confirm Cushing's disease.

In-office microwave disinfection of soft contact lenses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, M.G.; Rechberger, J.; Grant, T.

1990-02-01

We evaluated the effectiveness of an in-office microwave disinfection procedure which allowed for the disinfection of up to 40 soft contact lenses at one time. Ciba AOSept cases filled with sterile unpreserved saline were contaminated with one of six FDA test challenge microorganisms at a concentration of approximately 10(3) colony forming units per milliliter (CFU/ml). Twenty cases were placed on the rotating plate of a standard 2450 MHz 650 W microwave oven in a 10-cm diameter circle. The cases were exposed to high intensity microwave irradiation for periods of 0 to 15 min. None of the 6 microorganisms evaluated survivedmore » 2 min or longer of microwave exposure. Our findings indicated that microwave irradiation can be a convenient, rapid, and effective method of disinfecting a number of soft contact lenses at one time and thus adaptable as an in-office soft contact lens disinfection procedure.« less

Multi-resistant aspergillosis due to cryptic species.

PubMed

Howard, Susan Julie

2014-12-01

Reports of cryptic species causing aspergillosis in humans are increasing in the literature. Cryptic species are defined as those which are morphologically indistinguishable, although their identifications can be confirmed using molecular or other techniques which continue to become more widely available in the clinical setting. Antifungal resistance has often been noted in these cases, and indeed there does appear to be a higher prevalence of reduced susceptibility in cryptic species. Many of these observations are published as individual case reports or as a small component of larger data sets, making it challenging to review and compare the data fully. This review article seeks to describe the susceptibility trends and key learning outcomes of specific cases of infections caused by cryptic species, including Aspergillus alliaceus, Aspergillus calidoustus, Aspergillus felis, Aspergillus lentulus, Aspergillus tubingensis, Aspergillus viridinutans and Neosartorya pseudofischeri. These reports highlight the clinical need for full accurate identification and susceptibility testing to guide patient care.

A model-based test for treatment effects with probabilistic classifications.

PubMed

Cavagnaro, Daniel R; Davis-Stober, Clintin P

2018-05-21

Within modern psychology, computational and statistical models play an important role in describing a wide variety of human behavior. Model selection analyses are typically used to classify individuals according to the model(s) that best describe their behavior. These classifications are inherently probabilistic, which presents challenges for performing group-level analyses, such as quantifying the effect of an experimental manipulation. We answer this challenge by presenting a method for quantifying treatment effects in terms of distributional changes in model-based (i.e., probabilistic) classifications across treatment conditions. The method uses hierarchical Bayesian mixture modeling to incorporate classification uncertainty at the individual level into the test for a treatment effect at the group level. We illustrate the method with several worked examples, including a reanalysis of the data from Kellen, Mata, and Davis-Stober (2017), and analyze its performance more generally through simulation studies. Our simulations show that the method is both more powerful and less prone to type-1 errors than Fisher's exact test when classifications are uncertain. In the special case where classifications are deterministic, we find a near-perfect power-law relationship between the Bayes factor, derived from our method, and the p value obtained from Fisher's exact test. We provide code in an online supplement that allows researchers to apply the method to their own data. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effect of obstacle position in the flow of sheep through a narrow door.

PubMed

Zuriguel, Iker; Olivares, Jorge; Pastor, José M; Martín-Gómez, César; Ferrer, Luis M; Ramos, Juan J; Garcimartín, Angel

2016-09-01

In a recent work [Phys. Rev. E 91, 022808 (2015)PLEEE81539-375510.1103/PhysRevE.91.022808] it was reported that placing an obstacle in front of a gate has a beneficial effect in the flow of sheep through it. Here, we extend such results by implementing three different obstacle positions. We have observed that the flow is improved in two cases, while it worsens in the other one; the last instance happens when the obstacle is too close to the door. In this situation, the outcomes suggest that clogging develops between the doorjamb and the obstacle, contrary to the cases when the obstacle is farther, in which case clogging always occurs at the very door. The effectiveness of the obstacle (a strategy put forward to alleviate clogging in emergency exits) is therefore quite sensitive to its location. In addition, the study of the temporal evolution of the flow rate as the test develops makes evident a steady behavior during the entire duration of the entrance. This result is at odds with recent findings in human evacuation tests where the flow rate varies over time, therefore challenging the fairness of straightforward comparisons between pedestrian behavior and animal experimental observations.

Polymer nanocomposites for sealing microannulus cracks in wellbores cement-steel interface

NASA Astrophysics Data System (ADS)

Genedy, M.; Fernandez, S. G.; Stormont, J.; Matteo, E. N.; Dewers, T. A.; Reda Taha, M.

2017-12-01

Seal integrity of production and storage wellbores has become a critical challenge with the increasing oil and gas leakage incidents. The general consensus is that one of the potential leakage pathways is micro-annuli at the cement-steel interface. In this paper, we examine the efficiency of proposed polymer nanocomposite to seal microannulus cracks at the cement-steel interface. The repair material efficiency is defined as the ability of the repair material to reduce or eliminate the gas permeability of the cement-steel interface. The flow rate of an inert gas (Nitrogen) at the cement-steel interface was investigated for three cases: 1) repaired test samples with traditional repair material (microfine cement), 2) polymer nanocomposites, and 3) unrepaired test samples. Flow rates were measured and compared for all three cases. The experimental results show up to 99.5% seal efficiency achieved by using polymer nanocomposites compared to 20% efficiency achieved in the case of microfine cement. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia, LLC., a wholly owned subsidiary of Honeywell International, Inc., for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA-0003525. SAND2017-8094 A.

Recurrent candidal intertrigo: challenges and solutions

PubMed Central

Metin, Ahmet; Dilek, Nursel; Bilgili, Serap Gunes

2018-01-01

Intertrigo is a common inflammatory dermatosis of opposing skin surfaces that can be caused by a variety of infectious agents, most notably candida, under the effect of mechanical and environmental factors. Symptoms such as pain and itching significantly decrease quality of life, leading to high morbidity. A multitude of predisposing factors, particularly obesity, diabetes mellitus, and immunosuppressive conditions facilitate both the occurrence and recurrence of the disease. The diagnosis of candidal intertrigo is usually based on clinical appearance. However, a range of laboratory studies from simple tests to advanced methods can be carried out to confirm the diagnosis. Such tests are especially useful in treatment-resistant or recurrent cases for establishing a differential diagnosis. The first and key step of management is identification and correction of predisposing factors. Patients should be encouraged to lose weight, followed up properly after endocrinologic treatment and intestinal colonization or periorificial infections should be medically managed, especially in recurrent and resistant cases. Medical treatment of candidal intertrigo usually requires topical administration of nystatin and azole group antifungals. In this context, it is also possible to use magistral remedies safely and effectively. In case of predisposing immunosuppressive conditions or generalized infections, novel systemic agents with higher potency may be required. PMID:29713190

DNA evidence: current perspective and future challenges in India.

PubMed

Verma, Sunil K; Goswami, Gajendra K

2014-08-01

Since the discovery of DNA fingerprinting technology in 1985 it has been used extensively as evidence in the court of law world-wide to establish the individual identity both in civil and criminal matters. In India, the first case of parentage dispute solved by the use of DNA fingerprinting technology was in 1989. Since then till date, the DNA technology has been used not only to resolve the cases of paternity and maternity disputes, but also for the establishment of individual identity in various criminal cases and for wildlife forensic identification. Since last half a decade, India is exercising to enact legislation on the use of DNA in the judicial realm and the draft 'Human DNA Bill-2012' is pending in the parliament. Largely, the promoters of forensic DNA testing have anticipated that DNA tests are nearly infallible and DNA technology could be the greatest single advance step in search for truth, conviction of the perpetrator, and acquittal of the innocent. The current article provides a comprehensive review on the status of DNA testing in India and elucidates the consequences of the admissibility of DNA as 'evidence' in the judicial dominion. In this backdrop of civil and criminal laws and changing ethical and societal attitudes, it is concluded that the DNA legislation in India and world-wide needs to be designed with utmost care. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Determination of disease phenotypes and pathogenic variants from exome sequence data in the CAGI 4 gene panel challenge.

PubMed

Kundu, Kunal; Pal, Lipika R; Yin, Yizhou; Moult, John

2017-09-01

The use of gene panel sequence for diagnostic and prognostic testing is now widespread, but there are so far few objective tests of methods to interpret these data. We describe the design and implementation of a gene panel sequencing data analysis pipeline (VarP) and its assessment in a CAGI4 community experiment. The method was applied to clinical gene panel sequencing data of 106 patients, with the goal of determining which of 14 disease classes each patient has and the corresponding causative variant(s). The disease class was correctly identified for 36 cases, including 10 where the original clinical pipeline did not find causative variants. For a further seven cases, we found strong evidence of an alternative disease to that tested. Many of the potentially causative variants are missense, with no previous association with disease, and these proved the hardest to correctly assign pathogenicity or otherwise. Post analysis showed that three-dimensional structure data could have helped for up to half of these cases. Over-reliance on HGMD annotation led to a number of incorrect disease assignments. We used a largely ad hoc method to assign probabilities of pathogenicity for each variant, and there is much work still to be done in this area. © 2017 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Capturing Multiscale Phenomena via Adaptive Mesh Refinement (AMR) in 2D and 3D Atmospheric Flows

NASA Astrophysics Data System (ADS)

Ferguson, J. O.; Jablonowski, C.; Johansen, H.; McCorquodale, P.; Ullrich, P. A.; Langhans, W.; Collins, W. D.

2017-12-01

Extreme atmospheric events such as tropical cyclones are inherently complex multiscale phenomena. Such phenomena are a challenge to simulate in conventional atmosphere models, which typically use rather coarse uniform-grid resolutions. To enable study of these systems, Adaptive Mesh Refinement (AMR) can provide sufficient local resolution by dynamically placing high-resolution grid patches selectively over user-defined features of interest, such as a developing cyclone, while limiting the total computational burden of requiring such high-resolution globally. This work explores the use of AMR with a high-order, non-hydrostatic, finite-volume dynamical core, which uses the Chombo AMR library to implement refinement in both space and time on a cubed-sphere grid. The characteristics of the AMR approach are demonstrated via a series of idealized 2D and 3D test cases designed to mimic atmospheric dynamics and multiscale flows. In particular, new shallow-water test cases with forcing mechanisms are introduced to mimic the strengthening of tropical cyclone-like vortices and to include simplified moisture and convection processes. The forced shallow-water experiments quantify the improvements gained from AMR grids, assess how well transient features are preserved across grid boundaries, and determine effective refinement criteria. In addition, results from idealized 3D test cases are shown to characterize the accuracy and stability of the non-hydrostatic 3D AMR dynamical core.

Flavivirus cross-reactivity in serological tests and Guillain-Barré syndrome in a hematopoietic stem cell transplant patient: A case report.

PubMed

Raboni, Sonia M; Bonfim, Carmem; Almeida, Bernardo M; Zanluca, Camila; Koishi, Andrea C; Rodrigues, Paula R V P; Kay, Claudia K; Ribeiro, Lisandro L; Scola, Rosana H; Duarte Dos Santos, Claudia N

2017-08-01

Serological diagnosis of flavivirus infection is a challenge, particularly in the context of a disease associated with immune response enhancement in a transplant patient, where aspects such as previous flavivirus infections may be involved with the outcome. We report a case of a pediatric patient who developed Guillain-Barré syndrome (GBS) after matched-unrelated hematopoietic stem cell transplantation (HSCT). The patient lives in a Brazilian region that is experiencing an epidemic of Zika virus (ZIKV) and dengue virus (DENV). Because an increasing number of cases of GBS, likely triggered by ZIKV infection, are being reported in Brazil, samples from the patient were tested for both ZIKV and DENV infection. Serological assays strongly suggested a recent ZIKV infection, although infection by DENV or co-infection with both viruses cannot be ruled out. The presence of anti-DENV immunoglobulin-G in donor serum led to the hypothesis that antibodies from the donor could have enhanced the severity of the ZIKV infection. This hypothesis is in agreement with the recent findings that DENV sero-cross-reactivity drives antibody-dependent enhancement of ZIKV infection. These findings highlight the need for discussion of the indication to perform previous flavivirus tests in HSCT donors, especially in areas where ZIKV and other flaviviruses co-circulate. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-variant and multi-variant trend tests for genetic association with next-generation sequencing that are robust to sequencing error.

PubMed

Kim, Wonkuk; Londono, Douglas; Zhou, Lisheng; Xing, Jinchuan; Nato, Alejandro Q; Musolf, Anthony; Matise, Tara C; Finch, Stephen J; Gordon, Derek

2012-01-01

As with any new technology, next-generation sequencing (NGS) has potential advantages and potential challenges. One advantage is the identification of multiple causal variants for disease that might otherwise be missed by SNP-chip technology. One potential challenge is misclassification error (as with any emerging technology) and the issue of power loss due to multiple testing. Here, we develop an extension of the linear trend test for association that incorporates differential misclassification error and may be applied to any number of SNPs. We call the statistic the linear trend test allowing for error, applied to NGS, or LTTae,NGS. This statistic allows for differential misclassification. The observed data are phenotypes for unrelated cases and controls, coverage, and the number of putative causal variants for every individual at all SNPs. We simulate data considering multiple factors (disease mode of inheritance, genotype relative risk, causal variant frequency, sequence error rate in cases, sequence error rate in controls, number of loci, and others) and evaluate type I error rate and power for each vector of factor settings. We compare our results with two recently published NGS statistics. Also, we create a fictitious disease model based on downloaded 1000 Genomes data for 5 SNPs and 388 individuals, and apply our statistic to those data. We find that the LTTae,NGS maintains the correct type I error rate in all simulations (differential and non-differential error), while the other statistics show large inflation in type I error for lower coverage. Power for all three methods is approximately the same for all three statistics in the presence of non-differential error. Application of our statistic to the 1000 Genomes data suggests that, for the data downloaded, there is a 1.5% sequence misclassification rate over all SNPs. Finally, application of the multi-variant form of LTTae,NGS shows high power for a number of simulation settings, although it can have lower power than the corresponding single-variant simulation results, most probably due to our specification of multi-variant SNP correlation values. In conclusion, our LTTae,NGS addresses two key challenges with NGS disease studies; first, it allows for differential misclassification when computing the statistic; and second, it addresses the multiple-testing issue in that there is a multi-variant form of the statistic that has only one degree of freedom, and provides a single p value, no matter how many loci. Copyright © 2013 S. Karger AG, Basel.

Single variant and multi-variant trend tests for genetic association with next generation sequencing that are robust to sequencing error

PubMed Central

Kim, Wonkuk; Londono, Douglas; Zhou, Lisheng; Xing, Jinchuan; Nato, Andrew; Musolf, Anthony; Matise, Tara C.; Finch, Stephen J.; Gordon, Derek

2013-01-01

As with any new technology, next generation sequencing (NGS) has potential advantages and potential challenges. One advantage is the identification of multiple causal variants for disease that might otherwise be missed by SNP-chip technology. One potential challenge is misclassification error (as with any emerging technology) and the issue of power loss due to multiple testing. Here, we develop an extension of the linear trend test for association that incorporates differential misclassification error and may be applied to any number of SNPs. We call the statistic the linear trend test allowing for error, applied to NGS, or LTTae,NGS. This statistic allows for differential misclassification. The observed data are phenotypes for unrelated cases and controls, coverage, and the number of putative causal variants for every individual at all SNPs. We simulate data considering multiple factors (disease mode of inheritance, genotype relative risk, causal variant frequency, sequence error rate in cases, sequence error rate in controls, number of loci, and others) and evaluate type I error rate and power for each vector of factor settings. We compare our results with two recently published NGS statistics. Also, we create a fictitious disease model, based on downloaded 1000 Genomes data for 5 SNPs and 388 individuals, and apply our statistic to that data. We find that the LTTae,NGS maintains the correct type I error rate in all simulations (differential and non-differential error), while the other statistics show large inflation in type I error for lower coverage. Power for all three methods is approximately the same for all three statistics in the presence of non-differential error. Application of our statistic to the 1000 Genomes data suggests that, for the data downloaded, there is a 1.5% sequence misclassification rate over all SNPs. Finally, application of the multi-variant form of LTTae,NGS shows high power for a number of simulation settings, although it can have lower power than the corresponding single variant simulation results, most probably due to our specification of multi-variant SNP correlation values. In conclusion, our LTTae,NGS addresses two key challenges with NGS disease studies; first, it allows for differential misclassification when computing the statistic; and second, it addresses the multiple-testing issue in that there is a multi-variant form of the statistic that has only one degree of freedom, and provides a single p-value, no matter how many loci. PMID:23594495

Taking Costs and Diagnostic Test Accuracy into Account When Designing Prevalence Studies: An Application to Childhood Tuberculosis Prevalence.

PubMed

Wang, Zhuoyu; Dendukuri, Nandini; Pai, Madhukar; Joseph, Lawrence

2017-11-01

When planning a study to estimate disease prevalence to a pre-specified precision, it is of interest to minimize total testing cost. This is particularly challenging in the absence of a perfect reference test for the disease because different combinations of imperfect tests need to be considered. We illustrate the problem and a solution by designing a study to estimate the prevalence of childhood tuberculosis in a hospital setting. All possible combinations of 3 commonly used tuberculosis tests, including chest X-ray, tuberculin skin test, and a sputum-based test, either culture or Xpert, are considered. For each of the 11 possible test combinations, 3 Bayesian sample size criteria, including average coverage criterion, average length criterion and modified worst outcome criterion, are used to determine the required sample size and total testing cost, taking into consideration prior knowledge about the accuracy of the tests. In some cases, the required sample sizes and total testing costs were both reduced when more tests were used, whereas, in other examples, lower costs are achieved with fewer tests. Total testing cost should be formally considered when designing a prevalence study.

GeneXpert MTB/RIF Assay for the Diagnosis of Tuberculous Lymphadenitis on Concentrated Fine Needle Aspirates in High Tuberculosis Burden Settings.

PubMed

Tadesse, Mulualem; Abebe, Gemeda; Abdissa, Ketema; Aragaw, Dossegnaw; Abdella, Kedir; Bekele, Alemayehu; Bezabih, Mesele; Apers, Ludwig; de Jong, Bouke C; Rigouts, Leen

2015-01-01

The diagnosis of tuberculous lymphadenitis (TBL) remains challenging. The routinely used methods (cytology and smear microscopy) have sub-optimal sensitivity. Recently, WHO recommends GeneXpert to be used as the initial diagnostic test in patients suspected of having extra-pulmonary tuberculosis (EPTB). However, this was a conditional recommendation due to very low-quality evidence available and more studies are needed. In this study we evaluated the performance of Xpert for the diagnosis of TBL on concentrated fine needle aspirates (FNA) in Southwest Ethiopia. FNA was collected from presumptive TBL cases. Two smears were prepared from each aspirate and processed for cytology and conventional microscopy. The remaining aspirate was treated with N-acetyl-L-cysteine-NaOH and centrifuged for 15minutes at 3000g. The concentrated sediment was used for culture and Xpert test. Capilia TB-Neo test was used to differentiate M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM). Composite bacteriological methods (culture and/or smear microscopy) were considered as a reference standard. Out of 143 enrolled suspects, 64.3% (92/143) were confirmed TBL cases by the composite reference standard (CRS). Xpert detected M. tuberculosis complex (MTBC) in 60.1% (86/143) of the presumptive TBL cases. The sensitivity of Xpert compared to CRS was 87.8% [95% CI: 81.0-94.5] and specificity 91.1% [95% CI: 82.8-99.4]. The sensitivity was 27.8% for smear microscopy and 80% for cytology compared to CRS. Cytology showed the lowest specificity (57.8%). Xpert was positive in 4 out of 45 culture- and smear-negative cases. Among 47 cytomorphologically non-TBL cases, 15 were positive on Xpert. More than half of Xpert-positive cases were in the range of very low cut-off threshold values (28

The influence of prototype testing in three-dimensional aortic models on fenestrated endograft design.

PubMed

Taher, Fadi; Falkensammer, Juergen; McCarte, Jamie; Strassegger, Johann; Uhlmann, Miriam; Schuch, Philipp; Assadian, Afshin

2017-06-01

The fenestrated Anaconda endograft (Vascutek/Terumo, Inchinnan, UK) is intended for the treatment of abdominal aortic aneurysms with an insufficient infrarenal landing zone. The endografts are custom-made with use of high-resolution, 1-mm-slice computed tomography angiography images. For every case, a nonsterile prototype and a three-dimensional (3D) model of the patient's aorta are constructed to allow the engineers as well as the physician to test-implant the device and to review the fit of the graft. The aim of this investigation was to assess the impact of 3D model construction and prototype testing on the design of the final sterile endograft. A prospectively held database on fenestrated endovascular aortic repair patients treated at a single institution was completed with data from the Vascutek engineers' prototype test results as well as the product request forms. Changes to endograft design based on prototype testing were assessed and are reported for all procedures. Between April 1, 2013, and August 18, 2015, 60 fenestrated Anaconda devices were implanted. Through prototype testing, engineers were able to identify and report potential risks to technical success related to use of the custom device for the respective patient. Theoretical concerns about endograft fit in the rigid model were expressed in 51 cases (85.0%), and the engineers suggested potential changes to the design of 21 grafts (35.0%). Thirteen cases (21.7%) were eventually modified after the surgeon's testing of the prototype. A second prototype was ordered in three cases (5.0%) because of extensive changes to endograft design, such as inclusion of an additional fenestration. Technical success rates were comparable for grafts that showed a perfect fit from the beginning and cases in which prototype testing resulted in a modification of graft design. Planning and construction of fenestrated endografts for complex aortic anatomies where exact fit and positioning of the graft are paramount to allow cannulation of the aortic branches are challenging. In the current series, approximately one in five endografts was modified after prototype testing in an aortic model. Eventually, success rates were comparable between the groups of patients with a good primary prototype fit and those in which the endograft design was altered. Prototype testing in 3D aortic models is a valuable tool to test the fit of a custom-made endograft before implantation. This may help avoid potentially debilitating adverse events associated with misaligned fenestrations and unconnected aortic branches. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

G6PD testing in support of treatment and elimination of malaria: recommendations for evaluation of G6PD tests.

PubMed

Domingo, Gonzalo J; Satyagraha, Ari Winasti; Anvikar, Anup; Baird, Kevin; Bancone, Germana; Bansil, Pooja; Carter, Nick; Cheng, Qin; Culpepper, Janice; Eziefula, Chi; Fukuda, Mark; Green, Justin; Hwang, Jimee; Lacerda, Marcus; McGray, Sarah; Menard, Didier; Nosten, Francois; Nuchprayoon, Issarang; Oo, Nwe Nwe; Bualombai, Pongwit; Pumpradit, Wadchara; Qian, Kun; Recht, Judith; Roca, Arantxa; Satimai, Wichai; Sovannaroth, Siv; Vestergaard, Lasse S; Von Seidlein, Lorenz

2013-11-04

Malaria elimination will be possible only with serious attempts to address asymptomatic infection and chronic infection by both Plasmodium falciparum and Plasmodium vivax. Currently available drugs that can completely clear a human of P. vivax (known as "radical cure"), and that can reduce transmission of malaria parasites, are those in the 8-aminoquinoline drug family, such as primaquine. Unfortunately, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency risk having severe adverse reactions if exposed to these drugs at certain doses. G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide.Scaling up radical cure regimens will require testing for G6PD deficiency, at two levels: 1) the individual level to ensure safe case management, and 2) the population level to understand the risk in the local population to guide Plasmodium vivax treatment policy. Several technical and operational knowledge gaps must be addressed to expand access to G6PD deficiency testing and to ensure that a patient's G6PD status is known before deciding to administer an 8-aminoquinoline-based drug.In this report from a stakeholder meeting held in Thailand on October 4 and 5, 2012, G6PD testing in support of radical cure is discussed in detail. The focus is on challenges to the development and evaluation of G6PD diagnostic tests, and on challenges related to the operational aspects of implementing G6PD testing in support of radical cure. The report also describes recommendations for evaluation of diagnostic tests for G6PD deficiency in support of radical cure.

Liability of emergency physicians for studies ordered in the emergency department: court cases and legal defenses.

PubMed

Moore, Gregory P

2011-02-01

Laboratory tests are frequently ordered in the Emergency Department (ED), with results returning at a later time. Emergency physicians (EPs) are frequently held liable when the test results are not followed-up. Recent legal malpractice cases are presented to provide examples of the medical-legal risks encountered when poor patient outcomes occur because the results of laboratory tests and other studies done in the ED are not followed-up and communicated to the patient. Emergency physicians are obligated to follow-up with patients when the results of laboratory and radiographic studies ordered in the ED are returned at a later time, and EPs are liable for any poor outcome if there is no follow-up. Appropriate follow-up mechanisms must be in place to improve patient outcomes and reduce the risk for the physician. Knowledge of the legal concepts of contributory negligence and comparative fault allows EPs to place themselves in an optimal position for a legal defense if a challenge is raised. It is imperative that abnormal results of tests done for ED evaluation and orders must be properly noted and followed-up. Optimal communication and relay of information to both the patient and the primary physician will reduce physician liability and enhance patient outcomes. Published by Elsevier Inc.

Evaluation of whole blood IFNgamma test using PPD and recombinant antigen challenge for diagnosis of pulmonary and extra-pulmonary tuberculosis.

PubMed

Kalantri, Yatiraj; Hemvani, Nanda; Chitnis, D S

2009-06-01

Quantiferon TB gold (QFT-G) with recombinant antigen cocktail is well evaluated for diagnosis of pulmonary tuberculosis (PTB). However, diagnosis of extra-pulmonary tuberculosis (EPTB) is more difficult due to limitations of conventional techniques. This study compares recombinant antigens based QFT-G and low cost PPD based interferon test for the diagnosis of PTB and EPTB. IFNgamma release, with recombinant antigens and PPD, was assayed by ELISA from 140 cases of EPTB, 100 cases of PTB along with acid fast bacillus (AFB) detection, AFB culture on LJ and MGIT BACTEC. Sensitivity and specificity for QFT-G recombinant antigens was 84.29% and 96%, while for PPD based interferon was 70% and 84% for EPTB group. The sensitivity was far superior to AFB smear and culture for both the antigens. Nine samples were identified as non-tubercular mycobacteria (NTM) in the EPTB group and all were negative for QFT-G, but six of them were positive for PPD based test. Results of the study show that QFT-G using recombinant antigen is sensitive and specific for both PTB and EPTB diagnosis. The PPD based test is economic and offers comparable performance for PTB and EPTB diagnosis and also useful for diagnosis of NTM.

Costs and epidemiological changes of chronic diseases: implications and challenges for health systems.

PubMed

Arredondo, Armando; Aviles, Raul

2015-01-01

The need to integrate economic and epidemiological aspects in the clinical perspective leads to a proposal for the analysis of health disparities and to an evaluation of the health services and of the new challenges which are now being faced by health system reforms in middle income countries. To identify the epidemiological changes, the demand for health services and economic burden from chronic diseases (diabetes and hypertension) in a middle income county. We conducted longitudinal analyses of costs and epidemiological changes for diabetes and hypertension in the Mexican health system. The study population included both the insured and uninsured populations. The cost-evaluation method was used, based on the instrumentation and consensus techniques. To estimate the epidemiological changes and financial consequences for 2014-2016, six models were constructed according to the Box-Jenkins technique, using confidence intervals of 95%, and the Box-Pierce test. Regarding epidemiological changes expected in both diseases for 2014 vs. 2016, an increase is expected, although results predict a greater increase for diabetes, 8-12% in all three studied institutions, (p < .05). Indeed, in the case of diabetes, the increase was 41469 cases for uninsured population (SSA) and 65737 for the insured population (IMSS and ISSSTE). On hypertension cases the increase was 38109 for uninsured vs 62895 for insured. Costs in US$ ranged from $699 to $748 for annual case management per patient in the case of diabetes, and from $485 to $622 in patients with hypertension. Comparing financial consequences of health services required by insured and uninsured populations, the greater increase (23%) will be for the insured population (p < .05). The financial requirements of both diseases will amount to 19.5% of the total budget for the uninsured and 12.5% for the insured population. If the risk factors and the different health care models remain as they currently are, the economic impact of expected epidemiological changes on the social security system will be particularly strong. Another relevant challenge is the appearance of internal competition in the use and allocation of financial resources with programs for other chronic and infectious diseases.

Costs and Epidemiological Changes of Chronic Diseases: Implications and Challenges for Health Systems

PubMed Central

Arredondo, Armando; Aviles, Raul

2015-01-01

Background The need to integrate economic and epidemiological aspects in the clinical perspective leads to a proposal for the analysis of health disparities and to an evaluation of the health services and of the new challenges which are now being faced by health system reforms in middle income countries. Objective To identify the epidemiological changes, the demand for health services and economic burden from chronic diseases (diabetes and hypertension) in a middle income county. Methods We conducted longitudinal analyses of costs and epidemiological changes for diabetes and hypertension in the Mexican health system. The study population included both the insured and uninsured populations. The cost-evaluation method was used, based on the instrumentation and consensus techniques. To estimate the epidemiological changes and financial consequences for 2014–2016, six models were constructed according to the Box-Jenkins technique, using confidence intervals of 95%, and the Box-Pierce test. Results Regarding epidemiological changes expected in both diseases for 2014 vs. 2016, an increase is expected, although results predict a greater increase for diabetes, 8–12% in all three studied institutions, (p < .05). Indeed, in the case of diabetes, the increase was 41469 cases for uninsured population (SSA) and 65737 for the insured population (IMSS and ISSSTE). On hypertension cases the increase was 38109 for uninsured vs 62895 for insured. Costs in US$ ranged from $699 to $748 for annual case management per patient in the case of diabetes, and from $485 to $622 in patients with hypertension. Comparing financial consequences of health services required by insured and uninsured populations, the greater increase (23%) will be for the insured population (p < .05). The financial requirements of both diseases will amount to 19.5% of the total budget for the uninsured and 12.5% for the insured population. Conclusions If the risk factors and the different health care models remain as they currently are, the economic impact of expected epidemiological changes on the social security system will be particularly strong. Another relevant challenge is the appearance of internal competition in the use and allocation of financial resources with programs for other chronic and infectious diseases. PMID:25781625