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This study aims to investigate the effect of different types of performance measurement systems (PMSs) use (diagnostic use and interactive use) on Industry 4.0 maturity, examining whether there is a need for digital governance to facilitate the relationship between different types of PMS use (diagnostic use and interactive use) and Industry 4.0 maturity. Although the use of PMSs has been identified as beneficial in the Industry 4.0 context, relatively little research exists on the digital governance that enables firms to lead and control digital processes. The paper posits that digital governance plays an important role in mediating the relationship between PMS use and Industry 4.0 maturity. The data were gathered from 280 small- and medium-sized enterprises (SMEs), which operate in the service and manufacturing industry in Finland. The results demonstrate that different types of PMSs use cannot provide Industry 4.0 maturity alone, so there is a need for digital governance to fuel different types of PMS use, hence leading to Industry 4.0 maturity. However, diagnostic use of PMSs significantly hinders digital governance, while the interactive use of PMSs significantly drives digital governance. Finally, digital governance facilitates Industry 4.0 maturity. [ABSTRACT FROM AUTHOR]

We study how managers interactively use management control systems (MCS) in response to shareholder activism in a context of performance declines. We predict that broad-scope MCS design is a key factor that helps explain variation in the level of interactive use. In addition, we argue that the extent to which diagnostic use of MCS alleviates shareholder pressures depends on analysts' recommendations. We empirically test our hypotheses with survey and archival data. Data on shareholder activism is hand-collected. The results provide support for our predictions, suggesting that managers use MCS interactively to assuage shareholder activism in the context of performance declines. This effect is less pronounced for managers equipped with broad-scope information from their MCS. Our findings indicate that in a setting of favorable analysts' recommendations, managers use MCS diagnostically instead of interactively to cope with shareholder activism. Overall, the findings may help inform our understanding of how firms manage shareholder activism from a management control perspective. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzes the influence of diagnostic and interactive use of the performance measurement system (PMS) on job satisfaction and affective organizational commitment. Originality/value: The study provides empirical evidence that contributes to highlighting the contrasting findings in the literature on how the use of PMS influences job satisfaction and the affective organizational commitment of individuals. Design/methodology/approach: A survey was carried out with middlelevel managers of companies featured in the Best Companies to Work For ranking by the Você S/A magazine, where a sample of 167 valid responses was obtained. We applied the structural equation modeling to test the hypotheses. Findings: The results show a direct relationship between the interactive use of PMS and job satisfaction. They also indicate a direct connection between job satisfaction and affective organizational commitment. Furthermore, they show that diagnostic use directly impacts affective organizational commitment, while interactive use indirectly impacts affective organizational commitment by mediating job satisfaction. These results contribute to the literature by revealing that PMS's diagnostic and interactive uses result in different psychological consequences, such as job satisfaction and affective organizational commitment. They also contribute by reinforcing the previous literature regarding the complementarity and interdependence of the dual role of the PMS in the organizational context since the interactive use provides a flexible basis for the performance of activities, and the diagnostic use requires alignment of individual behaviors with organizational standards. [ABSTRACT FROM AUTHOR]

This study investigates the impact of subordinates' use of accounting controls on their job performance in circumstances where their supervisor adopts an empowering leadership style. We surveyed 98 Australian managers in the disability and manufacturing industries. The results show that diagnostic and scanning use mediate the relationship between supervisors' empowering leadership style and subordinates' creativity and goal productivity. When supervisors engage in empowering behaviours, subordinates are more likely to draw on accounting controls to cope with the greater information demands and job ambiguity inherent to such a leadership style. Furthermore, scanning use increases creativity whilst diagnostic use reduces creativity. [ABSTRACT FROM AUTHOR]

This study examines the associations between top management's interactive and diagnostic use of financial and non-financial performance measures with individual manager's (i.e. middle and lower level managers) creativity, and the mediating role of middle and lower level manager's perceived fairness of their performance appraisal on such associations. Using data from a survey of 220 middle and lower level managers from manufacturing organisations in Australia, the structural equation model revealed direct positive associations between both the diagnostic use of financial performance measures and the interactive use of non-financial performance measures with individual creativity. Further, the positive effect of the interactive use of financial performance measures on individual creativity is positively and fully mediated by distributive, interpersonal and informational fairness, while the positive effect of the interactive use of non-financial measures is positively and partially mediated by interpersonal and informational fairness. In addition, procedural fairness positively and partially mediates the effect of the diagnostic use of financial performance measures on individual creativity, and interpersonal fairness positively and fully mediates the effect of the diagnostic use of non-financial performance measures on individual creativity. The findings contribute to the performance measurement and appraisal literature examining the interactive and diagnostic use of both financial and non-financial performance measures and extends the sparse literature on the role of perceived fairness in explaining the behavioural effect of performance measurement systems. The findings also provide implications for practice, revealing the importance of the interactive and diagnostic use of financial and non-financial performance measures, and manager's perception of the fairness of performance appraisal processes as a mechanism through which individual manager's creativity can be enhanced. [ABSTRACT FROM AUTHOR]

The objective of this study is to evaluate the influence of the diagnostic and interactive use of the budget on managerial performance, as mediated by organizational commitment. A survey was carried out using Brazilian textile industry companies as a population, and the sample consists of 133 respondents to the questionnaire. Structural equation modeling was used to test the hypotheses. The results showed that the diagnostic and/or interactive use of the budget influences organizational commitment, as well as influencing managerial performance. The organizational commitment variable had a total mediating effect on the relationship between the use of budgetary control system and managerial performance, indicating that forms of budget use affect managerial performance only when managers are committed to the organization. Based on the results, we concluded that forms of budget use had influence on organizational commitment and on the managerial performance in the surveyed companies. These results advance the literature as they reveal that the diagnostic use and interactive use of the budget are antecedent variables of organizational commitment, leading to behaviors at work that can contribute to increasing managerial performance.

Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid-PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid-PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan.

Cerebral microbleeds are microscopic hemorrhages with deposits of blood products in the brain, which can be visualized with MRI and are implicated in cerebrovascular diseases. Hematoxylin and eosin (H&E) and Perl's Prussian blue are popular staining methods used to localize cerebral microbleeds in pathology. This paper compared these two staining techniques in a mouse model of cerebral microbleeds. We used lipopolysaccharide (LPS) to induce cerebral microhemorrhages. C57B6 mice were treated with LPS (5 mg/kg, i.p.) or vehicle at baseline and at 24 hr. The brains were extracted 48 hr after the first injection and adjacent coronal sections were stained with H&E and Prussian blue to compare the effectiveness of the two staining techniques. H&E-positive stains were increased with LPS treatment and were correlated with grossly visible microhemorrhages on the brain surface; Prussian blue-positive stains, by comparison, showed no significant increase with LPS treatment and did not correlate with either H&E-positive stains or surface microhemorrhages. H&E staining is thus a more reliable indicator of acute bleeding events induced by LPS in this model within a short time span.

Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ~100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects.

urpose: This study analyzes the influence of the interactive and the diagnostic use of Management Control Systems (MCS) and slack time on process innovation in incubated companies. Originality/value: Organizational characteristics are associated with processes innovation in organizations with contemporary configuration. The study brings evidence to the contrasting findings of the MCS literature with slack time and process innovation. Design/methodology/approach: A survey was conducted with managers of companies listed on websites of incubators associated with the Associação Nacional de Entidades Promotoras de Empreendimentos Inovadores (National Association of Entities Promoting Innovative Enterprises), obtaining a sample of 106 valid responses. To analyze the data, the Structural Equation Modeling technique was applied to analyze the data. Findings: The results indicated that the interactive use of MCS promotes slack time at work, and the diagnostic use inhibits its creation. However, slack time was not significantly associated with processes innovation, which reveals a dysfunctional role of the slack. The interactive use of MCS had a significant influence on processes innovation. It is concluded that the interactive use prevails when the purpose is to promote processes innovation, as it favors contacts between different hierarchical levels and learning, while the diagnostic use highlights its relevance by inhibiting the creation of slack time, understood as a dysfunction for not leading to processes innovation. This denotes that the interactive and the diagnostic use of MCS are complementary in incubated companies. / Objetivo: Este estudo analisa a influência dos usos interativo e diagnóstico dos Sistemas de Controle Gerencial (SCG) e da folga de tempo na inovação de processos, em empresas incubadas. Originalidade/valor: Características organizacionais são associadas com a inovação de processos em organizações de configuração contemporânea. O estudo traz evidências aos achados contrastantes da literatura dos SCG com a folga de tempo e a inovação de processos. Design/metodologia/abordagem: Pesquisa de levantamento foi realizada com gestores das empresas listadas nos sites de incubadoras associadas à Associação Nacional de Entidades Promotoras de Empreendimentos Inovadores e obteve-se uma amostra de 106 respostas válidas. Para analisar os dados, aplicou-se a técnica de Modelagem de Equações Estruturais. Resultados: Os resultados indicaram que o uso interativo dos SCG promove a folga de tempo no trabalho e o uso diagnóstico inibe sua criação. Porém, a folga de tempo não apresentou associação significativa com a inovação de processos, o que revela um papel disfuncional da folga. O uso interativo dos SCG apresentou influência significativa na inovação de processos. Conclui-se que o uso interativo prevalece quando a finalidade é promover a inovação de processos, pois favorece contatos entre diferentes níveis hierárquicos e aprendizagem, enquanto o uso diagnóstico evidencia sua relevância ao inibir a criação de folga de tempo, entendida como uma disfunção por não levar à inovação de processos. Isso denota complementaridade dos usos interativo e diagnóstico dos SCG nas empresas incubadas.

It is well known that both management control systems (MCSs) and operations management (OM) are related to firm performance; however, an integrated st udy that involves MCS and OM within the context of firm performance is still lacking. This research aimed to examine the relationships among the use of MCSs and OM techniques and firm performance in the Brazilian auto parts industry. Simons’ levers of cont rol framework was used to characterise the uses of MCSs, and OM techniques, such as total quality management (TQM) and continuous improvement programmes, were adopted. The results obtained through the structural equation modelling indicated that the diagno stic use of MCSs is positively associated with the goals of cost reduction. In addition, the interactive use of MCSs is positively associated with the objectives of introducing new products, which is consistent with previous research. Additionally, OM tech niques are positively related to cost reduction but have no direct relationship with the introduction of new products.

Abstract Until recently, estimation of β‐amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid‐positron emission tomography (amyloid‐PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid‐PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid‐PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid‐PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan.

Introduction: In bone metastases, the disruption of normal bone processes results in increased resorption and formation rates, which can often be quantitatively measured by biomarkers in the urine and blood. The purpose of this review is to summarize relevant studies of urinary markers used as a diagnostic and/or prognostic tool, as well as its potential and advances in directing therapy. Methods: A literature search was conducted using Ovid MEDLINE (1950 to July 2014), EMBASE (1950 to 2014 week 30) and Cochrane Central Register of Controlled Trials (3rd Quarter 2014) to identify studies that detailed the use of urinary markers in the cancer setting, specifically involving markers for bone metastases. Search terms included “urinary markers”, “cancer”, and “bone metastases”. Results: A total of 35 articles, with 24 original studies, were identified. In general, urinary markers can be used to detect early signs of bone metastases prior to skeletal imaging, but still must be used in conjunction with imaging to avoid false positive results. The use of urinary markers, such as N-telopeptide, as a prognostic tool remains controversial, but can provide information on the relative risk of skeletal related events (SREs), disease progression, as well as death. Finally, while urinary markers have shown to be potentially useful in confirming the efficacy of bone metastases treatments, exploring the appropriate dosages for treatment, and directing therapy, it is still unclear to what extent urinary markers should be reduced by. Conclusion: The potential use of urinary markers in the management of bone metastases is promising as it can allow for earlier and more convenient detection of bone metastases in comparison to other techniques. However, additional studies involving prospective clinical trials are suggested to further examine the potential of urinary markers in developing appropriate treatment strategies and endpoints, especially in developing a clearer protocol on the extent urinary markers should be reduced by to correlate with achievement of clinical benefit.

The paper examines how rolling forecasting is used in planning and linked to other practices in a management control system. The paper combines a function-based view of budgeting with a more disaggregation-based conceptualisation, considering individual control systems. A multiple-case-study approach was adopted to investigate differences in the design and use of control systems across three industrial firms that had recently sought to improve their planning. The findings reveal two approaches to forecasting. In proactive-type planning, rolling forecasting was employed to promote information oriented toward more realistic forecasts and ideas emerging from interactive discussion were often put into action before quantified monetary deviations between plans and targets emerged. In reactive planning, rolling forecasting supported the supremacy of annual budgeting, and a more stable, joint process for both enabled analysing variances formally in a diagnostically oriented manner and revising plans accordingly. Synergies between budgetary practices were also found—for instance, in the process of setting targets, wherein the forecasts informed managers of the outcome level that was likely to be achievable and hence served as a realistic basis for setting more demanding targets. [ABSTRACT FROM AUTHOR]

Hurdles to develop point of care diagnostic methods restrict the translation of progress in the health care sector from bench side to bedside. In this article a simple, cost effective fluorescent as well as colorimetric nanosensor was developed for the early and easy detection of hyperbilirubinemia. A stable, water soluble bovine serum albumin stabilised copper nanocluster (BSA CuNC) was used as the fluorescent probe which exhibited strong blue emission (404 nm) upon 330 nm excitation. The fluorescence of the BSA CuNC can be effectively quenched by the addition of bilirubin by the formation of copper-bilirubin complex. Meanwhile the copper-bilirubin complex resulted in an observable colour change from pale violet to green facilitating colorimetric detection. The prepared sensor displayed good selectivity and sensitivity over other co-existing molecules, and can be used for quantifying bilirubin with a detection limit down to 257 fM. Additionally, the as-prepared probe was coated on a paper strip to develop a portable paper strip sensor of bilirubin. Moreover, the method was successfully applied in real sample analysis and obtained promising result. [ABSTRACT FROM AUTHOR]

In most cases, persistent left superior vena cava (PLSVC) is asymptomatic and discovered accidentally. This case involves a 43-year-old male who underwent an emergency cadaveric liver transplantation. Postoperatively, the left internal jugular vein was cannulated using a sono-guided Seldinger technique in the intensive care unit. But the chest X-ray showed that the catheter followed the left paramediastinal course instead of crossing midline to the right to enter the superior vena cava. In consideration of the patient's status, an intra-arterial or extra-vascular placement could be excluded. For a diagnosis, we performed a bed-side transthoracic echocardiography with an agitated saline micro-bubble test. When agitated saline was injected through the catheter, the coronary sinus was initially opacified, and then the right atrium followed. In conclusion, we were able to make a diagnosis of PLSVC by a bedside test without radiation exposure.

The central venous pressure, CVP, is an important variable in the management of selected perioperative and intensive care cases and in clinical decision support systems, CDSS. In current routine, when measuring CVP the health care provider may use anatomical landmarks and a spirit level, SL, to adjust the pressure transducer to the level of the tricuspid valve, i.e. the phlebostatic axis. The aim of the study was to assess the agreement in the postoperative setting between the SL method and electromagnetic 3D positioning (EM). CVP was measured with patients in positions dictated by nursing routines. The staff members measured CVP using SL to position the transducer at the perceived phlebostatic level. This position was compared to coordinates based on an electromagnetic field with external sensors at anatomical landmarks and an internal sensor in the CV catheter for 3D determination of the phlebostatic axis. An electronic survey took bearing on the accepted error in measurement among colleagues at the department. There was a clinically relevant difference between the CVP measured by the staff members and the CVP based on the 3D EM positioning. The limits of agreement extended in excess of ±8 mmHg and half of the measurements had deviations outside an accepted error range of ±2.5 mmHg. There was a large variation in CVP measurements when assessing the agreement with the current method. This may indicate the need for improvement in accuracy, e.g. using the electromagnetic field positioning system, in association with routine monitoring and clinical decision support systems. [ABSTRACT FROM AUTHOR]

Glycosylated haemoglobin (HbA1c) has been in use since 1980s as the 'gold standard' for monitoring glycaemic control and as a predictor of diabetic complications. Even though several conditions, such as, haemolytic anaemia (lowers HbA1c) and aplastic anaemia (raises HbA1c) tend to confound and interfere with HbA1c measurement, in most circumstances HbA1c is a valid and reliable index of glycaemic status. Recently, HbA1c has also been recommended as a diagnostic test for diabetes mellitus by the American Diabetes Association (ADA); HbA1c offers logistical advantages over the conventional oral glucose tolerance test as it requires a non-fasting random sample. In this article the history of discovery of HbA1c, biochemical processes behind its formation, its assay techniques, various factors influencing HbA1c, importance of standardization of its assay so as to make the results reported from different laboratories much more comparable are critically reviewed. This review also provides an update on the optimal HbA1c targets, its reliability in control of diabetic complications, limitations of test results and its importance in control of diabetes patients and their complications, various cut-off values obtained in studies performed both in India and worldwide and its role as a surrogate marker of metabolic syndrome, among others.

O propósito deste estudo de natureza empírico-teórica foi entender os relacionamentos entre o Uso do Sistema de Controle Gerencial; o desenvolvimento de Competências Organizacionais e Desempenho usando o framework proposto por Henri 2006 . A dimensão Uso do Sistema de Controle Gerencial proposta por Simons 1995; 2000 em Uso Diagnóstico e Uso Interativo é pouco estudada no Brasil; contrariamente à literatura internacional; embora esta tenha mostrado alguns resultados que são contraditórios. A pesquisa foi realizada em 2008; por meio de um survey em uma amostra de 104 empresas constantes da relação das 1.000 Maiores Empresas da Revista Exame. Com a aplicação da Modelagem de Equação Estrutural; os principais resultados mostram que não existem evidências de relacionamento negativo entre o Uso Diagnóstico e o desenvolvimento de Competências Organizacionais; o que contradiz os resultados de Henri 2006 . Também se identificou que o Uso Interativo influencia positivamente as competências Aprendizagem Organizacional e Orientação para Mercado e estas influenciam positivamente o Desempenho medido por auto-avaliação . O estudo contribui para a literatura nacional ao abordar um tema que integra Contabilidade Gerencial e Estratégia; e também por operacionalizar o construto Tensões Dinâmicas. O resultado contribui para a prática ao mostrar que as empresas devem continuar usando diagnosticamente o Controle Gerencial; pois este auxilia a organização a corrigir desvios; ao mesmo tempo que recomenda a utilização da forma interativa para ativar as competências organizacionais.The purpose of this study was to understand the relationship among Management Control System Use, development of company's organizational competences and performance using Henri's framework (HENRI, 2006). The dimension Use of Management Control System, proposed by Simons (1995, 2000) in diagnostic use and interactive use is scarcely studied in Brazil, in spite of the international research that has shown some contradictory results. The research was carried out in 2008, by a survey in a sample of 104 companies from Exame Magazine 1000 Biggest Brazilian Companies. Using the Structural Equation Model, the main results indicate no evidence of negative relationships between the diagnostic use and the organizational competences development, what contradicts Henri's results (2006). It was also identified that the interactive use has positive influences in the competences of Organizational Learning and Market Orientation, and these have positive influences in Performance (measured by self-evaluation). This study contributes to Brazilian research as its subject integrates Management Accounting and Strategy and also for measurement the construct Dynamic Tensions. For the practice, the result is important as it shows that companies should continue to use Management Control for diagnostic, as it helps the organization to correct errors, simultaneously recommending the use of interactive way to activate organizational ompetences.

Cancer is the result of the accumulation ofchanges in molecules with important functionsin processes such as cell proliferation, apoptosis,cell death and gene repair. Molecules,substances or altered pathways constitutetumor markers or biomarkers useful in clinicalmonitoring of cancer patients, because theyhave demonstrated to be suitable for the valuationof the patient’s treatment and it efficiency.Determination of tumor markers has not beenvery successful due to the low sensitivity andspecificity of the techniques used and the requirementof large volumes of biological samplesor the use of invasive methods for collecting them. The serum tumor markers arise, as a usefultool to obtain information about the diseaseprogress and constitute as a scientific challengeto improve its applicability in early diagnosis,prognosis, monitoring of the disease and evaluationof therapeutic efficacy.

Recent three-dimensional multidetector row computed tomography (3D MDCT) can provide detailed images of a gastric tumor, including its general contour, location and depth. We therefore evaluated the efficacy of MDCT in the differential diagnosis and staging of gastric tumors in patients prepared for surgery. Methods: Seventy-nine patients with gastric tumors identified by gastric optical endoscopy were admitted for preoperative evaluation. All patients received double-contrast barium meal (DCBM) study and abdominal MDCT with 3D reconstruction before surgery. We compared the accuracy of MDCT with DCBM study in detecting and differentiating gastric tumors. In addition, the MDCT findings were correlated with surgical and pathologic results in gastric cancers for Borrmann type, T and N stages. Results: Among the 79 patients with gastric tumors, there were 24 cases of early gastric cancer, 40 cases of advanced gastric cancer, 12 cases of gastrointestinal stromal tumor, and three cases of gastric lymphoma. Both MDCT and DCBM were very accurate in picking up the lesions (100%). The diagnostic accuracies of MDCT and DCBM were similar (94% vs. 96%) in differentiating mucosal and submucosal lesions as well as classification of Borrmann type in advanced gastric cancer (70% vs. 63%). In 64 patients with gastric cancers, there was good correlation between MDCT images and pathology in 73% of T staging and 69% of N staging. Conclusion: MDCT has a similar high accuracy in the preoperative diagnosis of different gastric tumors compared with DCBM and provides additional information including tumor depth, lymph node and hepatic metastasis. Therefore, MDCT may be used as a primary tool for preoperative tumor diagnosis and staging.

Many mutations responsible of Fabry disease destabilize lysosomal alpha-galactosidase, but retain the enzymatic activity. These mutations are associated to a milder phenotype and are potentially curable with a pharmacological therapy either with chaperones or with drugs that modulate proteostasis. We demonstrate the effectiveness of molecular dynamics simulations to correlate the genotype to the severity of the disease. We studied the relation between protein flexibility and residual enzymatic activity of pathological missense mutants in the cell. We found that mutations occurring at flexible sites are likely to retain activity in vivo . The usefulness of molecular dynamics for diagnostic purposes is not limited to lysosomal galactosidase because destabilizing mutations are widely encountered in other proteins, too, and represent a large share of all the ones associated to human diseases. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to evaluate the effect of fluorescence cystoscopy and immediate post-transurethral resection of the bladder (TURB) chemoprophylaxis on the risk of recurrence of non-muscle-invasive bladder cancer (NMIBC) under routine clinical conditions. Materials and methods. Fluorescence cystoscopy using hexyl-aminolevulinate and post-TURB chemoprophylaxis using mitomycin C were simultaneously introduced in an effort to reduce the recurrence of NMIBC. In total, 190 consecutive patients were enrolled over a 2 year period and followed as the intervention group; 216 patients treated over a 2 year period before introduction served as controls. An intention-to-treat analysis was performed with baseline control. Results. The recurrence risk was reduced by 41% (hazard ratio 0.59, 95% confidence interval 0.45-0.78) (intention-to-treat analysis). Median recurrence-free survival was extended from 13.6 months to 36.8 months. Every third follow-up TURB was avoided. Patients with low-risk tumors and patients with primary as well as recurrent disease benefited from the treatment. Conclusions. Fluorescence cystoscopy and immediate post-TURB chemoprophylaxis effectively reduced the recurrence risk and numbers of follow-up procedures under clinical routine conditions. [ABSTRACT FROM AUTHOR]

Introduction In bone metastases, the disruption of normal bone processes results in increased resorption and formation rates, which can often be quantitatively measured by biomarkers in the urine and blood. The purpose of this review is to summarize relevant studies of urinary markers used as a diagnostic and/or prognostic tool, as well as its potential and advances in directing therapy. Methods A literature search was conducted using Ovid MEDLINE (1950 to July 2014), EMBASE (1950 to 2014 week 30) and Cochrane Central Register of Controlled Trials (3rd Quarter 2014) to identify studies that detailed the use of urinary markers in the cancer setting, specifically involving markers for bone metastases. Search terms included “urinary markers”, “cancer”, and “bone metastases”. Results A total of 35 articles, with 24 original studies, were identified. In general, urinary markers can be used to detect early signs of bone metastases prior to skeletal imaging, but still must be used in conjunction with imaging to avoid false positive results. The use of urinary markers, such as N-telopeptide, as a prognostic tool remains controversial, but can provide information on the relative risk of skeletal related events (SREs), disease progression, as well as death. Finally, while urinary markers have shown to be potentially useful in confirming the efficacy of bone metastases treatments, exploring the appropriate dosages for treatment, and directing therapy, it is still unclear to what extent urinary markers should be reduced by. Conclusion The potential use of urinary markers in the management of bone metastases is promising as it can allow for earlier and more convenient detection of bone metastases in comparison to other techniques. However, additional studies involving prospective clinical trials are suggested to further examine the potential of urinary markers in developing appropriate treatment strategies and endpoints, especially in developing a clearer protocol on the extent urinary markers should be reduced by to correlate with achievement of clinical benefit. [ABSTRACT FROM AUTHOR]

Reticulated platelets are immature platelets circulating in blood; they reflect the activity of megakaryopoiesis in the bone marrow. Therefore, they can be used as a non-invasive test in patients with thrombocytopenia in various clinical conditions. The preferred method of analysis is by flow cytometry. However, there is an evident lack of analytical standardization, making it difficult to compare results obtained in different laboratories. Currently, two types of hematology analyzers are on the market offering fully automated measurement of reticulated or immature platelets: the high end analyzers manufactured by Sysmex (XE- and XN-series) and Abbott (CELL-DYN Sapphire). Although the methods are essentially different and cannot be used interchangeably, both have been proven to have clinical utility. Reticulated or immature platelet assays are useful for the differential diagnosis of thrombocytopenia and for monitoring bone marrow recovery after chemotherapy or stem cell transplantation. These assays may aid clinicians in platelet transfusion decisions when recovery from thrombocytopenia is imminent. In addition, preliminary findings indicate that there is a rationale for reticulated or immature platelets for risk stratification in acute coronary syndromes and for monitoring the effect of treatment with antiplatelet drugs in patients with coronary artery diseases. The aim of this paper is to present the present technology available for measuring reticulated platelets as well as an overview of the current status of clinical application. This overview also indicates that more research is needed before reticulated or immature platelet assays can be applied in other clinical conditions than thrombocytopenia and after transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To test the sensitivity of urinary cytology at a tertiary academic institution and to assess the impact of pathologist'' experience on detection of urothelial carcinoma of the bladder (UCB). Materials and methods: Between April 1999 and September 2008, 8,574 cytology specimens were evaluated. There were 882 consecutive patients (612 males, 270 females) who underwent bladder biopsy or transurethral resection of bladder tumor for UCB. Sensitivity rates of prior urinary cytology were determined. We tested the influence of experience of pathologist on sensitivity. Results: Urinary cytology detected 237 out of 503 UCB (overall sensitivity 47.1%). Cytology after bladder washing resulted in higher sensitivity than in voided urine (50.4% vs. 36.2%; P = 0.008). Sensitivity rates significantly increased by UCB stage; 30.6% in pTa (n = 245), 60.5% in patients with any form of CIS (n = 119), 62.9% in pT1 (n = 89), and 69.6% in ≥pT2 (n = 46; P < 0.001). Similarly, higher sensitivity was observed with increasing grade, ranging from 16.7% in low (n = 108) to 62.2% in high grade tumors (n = 283; P < 0.001). No statistically significant difference between more and less experienced investigators was observed. Conclusions: Sensitivity rates of urinary cytology at our institution are not superior to those reported in the literature. Cytology missed many high grade cancers, pointing to inherent methodological limitations of urinary cytology. A higher experience level of the pathologist was not significantly associated with higher sensitivity rates. Urinary cytology represents a flawed adjunct to cystoscopy with limited potential of improvement even in the hands of experienced pathologists. [Copyright &y& Elsevier]

Objective: To assess the impact of oral ranitidine on the imaging quality in magnetic resonance cholangiopancreatography (MRCP). Materials and Methods: Thirty-two patients underwent MRCP with 3D and 2D acquisitions, and three strategies for suppression of the gastrointestinal fluid signal: a) only at fasting; b) 12 hours after ingestion of 300 mg ranitidine; c) after oral administration of gadolinium solution. Three observers reviewed the images with a focus on the degree of visualization of the biliopancreatic tree. The interobserver agreement was evaluated with the kappa test. The difference between techniques and acquisition modalities were evaluated by means of average grading scores. Results: The three strategies for suppression of the gastrointestinal fluid signal presented high reproducibility. The results with suppression of the gastrointestinal fluid signal with ranitidine where similar to those obtained with fasting, and both were worse than those obtained with gadolinium solution. The 3D acquisitions surpassed 2D only in terms of visibility of the cystic duct and gallbladder, and were inferior or equivalent in the other biliopancreatic ductal segments. Conclusion: The use of ranitidine does not seem justified in the evaluation of the biliopancreatic tree at MRCP, since 2D MRCP with fasting allows the visualization of ductal structures with high quality and reproducibility in the majority of cases. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To screen serum biomarker of knee osteoarthritis (OA) using a phage random peptide library. Design and methods: A phage random peptide library of random peptide 12-mers was screened with purified immunoglobulin G (IgG) from sera of knee OA patients. Patients with knee rheumatoid arthritis (RA), hip OA, non-erosive hand OA or erosive hand OA, and healthy volunteers were used as controls. Results: A phage clone with inserted peptide TGLESGHGPGDS (named KOA1) showed 90% positive reaction rate with the knee OA patients, significantly higher than that with the knee RA patients (27.8%), the non-erosive hand OA patients (34.3%), the erosive hand OA patients (31.3%) and the healthy controls (12.0%), but not the hip OA patients (82.5%). Conclusions: The novel knee OA mimic peptide KOA1 identified with a random phage display peptide library and sera from knee OA patients could be a potential serum biomarker for knee OA. [Copyright &y& Elsevier]

Copyright of Revista de Salud Pública is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista de Saúde Pública is the property of Faculdade de Educacao da Universidade de Sao Paulo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copper is used extensively in semiconductor circuits as the multilayer metal. In addition to copper, waste streams often contain chelating agents like EDTA, which is widely used in the process to enhance solubility of copper, and it tends to form copper-chelated complexes. PEI-agarose adsorbents in a packed-bed column are capable of removing these anionic complexes, but the competitive binding between this chelating agent and PEI for copper is not well understood and needs to be explored.The currentworkfocuseson investigating copper sorption by PEI-agarose adsorbent in the presence of EDTA. The pH of the column is fixed at 5.5 using 0.1 M acetate buffer. The ratio of chelator to copper ions is varied. Copper binding capacity and copper breakthrough curves are compared and contrasted to results without additional chelator present An excess of EDTA leads to an increase in the fraction of free dissociated (anionic) ligand that competes for electrostatic attraction on protonated amine groups and therefore leads to a decrease in sorption capacity in the column. However, this waste treatment technique is still feasible for the semiconductor industry as large volumes of copper-contaminated solutions from actual waste can be concentrated 12-fold. When equimolar (copper to EDTA) or higher concentrations of EDTA are present, acetate can be utilized to recover the metal; for low ratios of copper to EDTA, metal recovery is achieved using hydrochloric acid. [ABSTRACT FROM AUTHOR]

Background/purpose: Recent three-dimensional multidetector row computed tomography (3D MDCT) can provide detailed images of a gastric tumor, including its general contour, location and depth. We therefore evaluated the efficacy of MDCT in the differential diagnosis and staging of gastric tumors in patients prepared for surgery.Methods: Seventy-nine patients with gastric tumors identified by gastric optical endoscopy were admitted for preoperative evaluation. All patients received double-contrast barium meal (DCBM) study and abdominal MDCT with 3D reconstruction before surgery. We compared the accuracy of MDCT with DCBM study in detecting and differentiating gastric tumors. In addition, the MDCT findings were correlated with surgical and pathologic results in gastric cancers for Borrmann type, T and N stages.Results: Among the 79 patients with gastric tumors, there were 24 cases of early gastric cancer, 40 cases of advanced gastric cancer, 12 cases of gastrointestinal stromal tumor, and three cases of gastric lymphoma. Both MDCT and DCBM were very accurate in picking up the lesions (100%). The diagnostic accuracies of MDCT and DCBM were similar (94% vs. 96%) in differentiating mucosal and submucosal lesions as well as classification of Borrmann type in advanced gastric cancer (70% vs. 63%). In 64 patients with gastric cancers, there was good correlation between MDCT images and pathology in 73% of T staging and 69% of N staging.Conclusion: MDCT has a similar high accuracy in the preoperative diagnosis of different gastric tumors compared with DCBM and provides additional information including tumor depth, lymph node and hepatic metastasis. Therefore, MDCT may be used as a primary tool for preoperative tumor diagnosis and staging. [ABSTRACT FROM AUTHOR]

Abstract: Clinical gene sequencing is growing in importance and cost-effectiveness. In the past two years, the number of genes associated with disease has grown by roughly 25%. Knowledge of genetic variations will soon guide drug selection and dosages, predict risks from toxin exposures, and inform nutritional needs. Despite the significance of sequencing, methods for reporting results are problematic. Frequent use of paper and infrequent use of naming standards impede data exchange and make incorporation into the electronic medical record difficult. Reports often describe only variations found, rather than all data (all patient bases sequenced). Also, reports frequently do not describe reference data used to define variations. These practices create risks for loss of both data and information. Standardized electronic reporting of all data (all bases sequenced and all reference data) and electronic record systems capable of storing these results would both prevent data loss and simplify the preservation of information those data provide. [Copyright &y& Elsevier]

Purpose: Transferrin saturation of more than 60% has been identified as a cancer risk factor. It is unclear whether dietary iron intake increases the risk of cancer among individuals with transferrin saturation of less than 60%. The purpose of this study was to examine the association of dietary iron intake and the risk of cancer among adults with increased transferrin saturation.Methods: Analysis of a cohort study, the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study, was performed. US adults (aged 25 to 74 years at baseline) were followed up from baseline in 1971-1974 to 1992 (N = 6,309).Results: A total of 7.3% of the US population had a serum transferrin saturation of more than 45% at baseline. Intake of dietary iron was essentially uncorrelated with transferrin saturation (r = 0.04). Compared with individuals who had normal serum transferrin saturation and low dietary iron intake, individuals whose serum transferrin saturation was more than 45% and who had high dietary iron intake also had an increased adjusted relative risk of cancer (2.24; 95% confidence interval [CI], 1.02-4.89). Increased risk was not found for individuals with a transferrin saturation of more than 45% but a normal dietary iron intake (hazard ratio, 1.02; 95% CI, 0.69-1.49). Transferrin saturation levels could be set as low as 41%, and the individuals with high transferrin saturation and high dietary iron intake would still have an increased adjusted relative risk of cancer (hazard ratio, 2.00; 95% CI, 1.04-3.82).Conclusions: Among persons with increased transferrin saturation, a daily intake of dietary iron more than 18 mg is associated with an increased risk of cancer. Future research might focus on the benefits of dietary changes in those individuals with increased serum transferrin saturation. [ABSTRACT FROM AUTHOR]

Barrett’s esophagus is a condition that develops in approximately 10–15% of patients with chronic gastroesophageal reflux disease and is the only known major risk factor for esophageal adenocarcinoma. The incidence of esophageal adenocarcinoma has increased by 350% over the last 3 decades and the reasons for this dramatic increase are unclear. At the time of cancer diagnosis up to 50% of patients will have advanced regional or distant metastatic disease, with little or no chance of cure. The overall 5-year survival rate with advanced disease remains poor at <10%. Several studies have demonstrated an early stage of diagnosis and a marked improvement in the survival of patients with esophageal cancer detected by routine endoscopic surveillance in patients known to have pre-existing Barrett’s esophagus. The aim of endoscopic surveillance in patients with Barrett’s esophagus is the early diagnosis of esophageal cancer, when it is still potentially curable. The desired outcome is to further decrease the mortality rate associated with esophageal adenocarcinoma and identify and screen populations at risk for the development of dysplasia arising from Barrett’s esophagus. This is the principle of the current screening and surveillance guidelines set out by several societies, including the American College of Gastroenterology, the American Society of Gastrointestinal Endoscopy, and the European Society of Gastrointestinal Endoscopy. However, as most patients with Barrett’s esophagus do not develop adenocarcinoma, the cost effectiveness of endoscopic screening and surveillance strategies is questionable. To date, no prospective, randomized trials have been performed to evaluate the effectiveness of surveillance, the survival benefit in patients undergoing surveillance or the subsequent impact on healthcare costs. In this article, we focus on the basic principles and reasoning underlying the surveillance guidelines for Barrett’s esophagus. In particular, that the disease is clinically important and has a high prevalence; the transition to adenocarcinoma could have a high death and/or disability rate; early diagnosis of adenocarcinoma should reduce mortality; and the screening method should be easily applied, safe, relatively inexpensive, and applicable to a large number of patients. We then review arguments for and against screening and surveillance as they apply to these principles and discuss the current literature that reviews the effectiveness of such surveillance strategies, including an outline of cost analysis. [ABSTRACT FROM AUTHOR]

Background and objective: Although electrocardiography (ECG) guidance of central venous catheters (CVCs) is traditionally thought to detect the entrance into the right atrium (RA), there is little evidence in the literature to confirm this. We previously observed a high incidence of left-sided CVCs abutting the wall of the superior vena cava (SVC), even when the catheters were advanced past the point of increased P-wave amplitude. Our hypothesis was that this ECG amplitude signal is actually detecting the pericardial reflection rather than the RA. The goal of the study was to position catheter tips under ECG guidance outside the RA. Methods: One-hundred central venous triple-Lumen catheters inserted either via the right or the left internal jugular veins, respectively, were analysed in cardiac surgical patients. The position of the catheter tip was ascertained by ECG. Method A: A Seldinger guide-wire in the distal lumen served as exploring electrode, the respective insertion depth was recorded. Method B: The middle lumen (port opening 2.5 cm from the catheter tip, thus the catheter was advanced more towards the atrium) tilled with a saline 10% fluid column served as the exploring electrode, and the insertion depth was recorded again. Descriptive data are given as mean ± standard deviation. Results: On average, the catheters were advanced by the expected 2 ± 0.3 cm using Method B beyond the initial insertion by Method A. All 100 CVCs were finally correctly positioned in the SVC and confirmed by transoesophageal echocardiography. When chest radiography was performed after surgery not a single catheter abutted the lateral wall of the SVC. Conclusion: Since both methods detected the same structure, and catheters placed by Method B did not result in intra-atrial CVC tip position, the first increase in P-wave amplitude does correspond to a structure in the SVC, most likely the pericardial reflection. [ABSTRACT FROM AUTHOR]

Functional magnetic resonance imaging (MRI) with a new intravascular contrast agent, monocrystalline iron oxide nanoparticles (MION), was applied to assess the effect of transpupillary thermotherapy in a rabbit model of choroidal melanoma. 3D-spoiled gradient recalled sequences were used for quantitative assessment of blood volume. The MRI-parameters were 5/22/35° (time of repetition (TR)/echo delay (TE)/flip angle (FA)) for T1- and 50/61/10° for T2-weighted sequences. Images were collected before and at different times after MION injection. In all untreated tissues studied, MION reduced the T2-weighted signal intensity within 0.5 h and at 24 h (all p ≤ 0.012), whereas no significant changes were detected in treated tumors. T1-weighted images also revealed differences of MION-related signal changes between treated tumors and other tissues, yet at lower sensitivity and specificity than T2. The change of T2-weighted MRI signal caused by intravascular MION allows early distinction of laser-treated experimental melanomas from untreated tissues. Further study is necessary to determine whether MRI can localize areas of tumor regrowth within tumors treated incompletely. [Copyright &y& Elsevier]

Purpose. To evaluate factors that may influence the ibopamine provocative test for the diagnosis of glaucoma. Methods. Two ibopamine (3,4 di-isobutyrylester of N-methyldopamine) 2% eyedrops were instilled 5 minutes apart in one eye selected at random in both glaucoma and normal subjects. The intraocular pressure (IOP) was assessed prior to the drops and 30, 60 and 180 minutes after instillation. The test was considered positive when there was an IOP increase of greater than 4 mmHg at any one of the timepoints. The amount of IOP change was compared to the severity of glaucomatous visual field loss and to the types of medical treatment. Results. The sensitivity (glaucoma patients with a positive result) and specificity (normal individuals with a negative result) of the ibopamine test was 87 and 95%, respectively. Glaucoma patients using prostaglandin analogues did not have a significant IOP elevation. Conclusion. The Ibopamine provocative test may be an auxiliary test in glaucoma diagnosis. Concurrent use of prostaglandin analogues reduces the test's sensitivity. [ABSTRACT FROM AUTHOR]