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Terms modified by Mandatory Selected AbstractsThe Nature of the Interaction between Mandatory and Voluntary DisclosuresJOURNAL OF ACCOUNTING RESEARCH, Issue 4 2005ETI EINHORN ABSTRACT This paper demonstrates the crucial role that firms' mandatory disclosures play in determining their voluntary disclosure strategies. It also shows how a firm's propensity for providing voluntary disclosures relates to various features of the mandatory disclosure environment and disclosure regulation. The special case of choosing between aggregated and disaggregated disclosures serves as an illustration of the model's applicability. [source] HPV Vaccination: Should it be Mandatory for Entry into Public School?NURSING FOR WOMENS HEALTH, Issue 2 2007Julie Roach Gray MSN First page of article [source] Projected slabs: approximation of perspective projection and error analysis,COMPUTER ANIMATION AND VIRTUAL WORLDS (PREV: JNL OF VISUALISATION & COMPUTER ANIMATION), Issue 5 2001A. Vilanova Bartrolí Abstract Virtual endoscopy is a promising medical application for volume-rendering techniques where perspective projection is mandatory. Most of the acceleration techniques for direct volume rendering use parallel projection. This paper presents an algorithm to approximate perspective volume rendering using parallel projected slabs. The introduced error due to the approximation is investigated. An analytical study of the maximum and average error is made. This method is applied to VolumePro 500. Based on the error analysis, the basic algorithm is improved. This improvement increases the frame rate, keeping the global maximum error bounded. The usability of the algorithm is shown through the virtual endoscopic investigation of various types of medical data sets. Copyright © 2002 John Wiley & Sons, Ltd. [source] Guidelines for the descriptive presentation and statistical analysis of contact allergy dataCONTACT DERMATITIS, Issue 2 2004Wolfgang Uter The present guidelines aim to support clinical researchers in adequately presenting data on contact allergy, and to use statistical tests appropriate for their data. A description of the mode of selection of patients, and of their relevant demographic details, is an essential prerequisite for the correct interpretation of study results. Proportions and rates, if regarded as estimate of these parameters of a target populations, should normally be supplemented with confidence intervals to address precision. Concordance, i.e., agreement between two ratings in a dependent sample, must be quantified with a chance-corrected measure such as Cohen's kappa coefficient. If the diagnostic quality of an outcome is being assessed, standard measures like sensitivity and specificity, as well as the prevalence-dependent positive and negative predictive values should be calculated. Often, contact allergy to a certain substance depends on several factors. In this situation, depending on the research question, techniques like stratification, standardization or multifactorial analysis should be employed. With increasing complexity of statistical description and analysis, consulting with a biostatistician is often mandatory. [source] Corporate social responsibility in Malaysia , experts' views and perspectivesCORPORATE SOCIAL RESPONSIBILITY AND ENVIRONMENTAL MANAGEMENT, Issue 3 2009Jye Y. Lu Abstract The field of corporate social responsibility (CSR) has grown exponentially in the last decade and is gradually becoming a global trend. Companies are now expected to take explicitly into account all aspects of their performance, i.e., not just their financial results, but also their social and environmental performance. Therefore more organizations are now engaged in serious efforts to define and integrate CSR into all aspects of their businesses. The aim of our study is to understand this trend in Malaysia and specifically to investigate (i) The status of CSR in Malaysia; (ii) Different CSR practices in Malaysia; and (iii) Future diffusion of CSR in Malaysia. To answer these questions, we have conducted interviews with Malaysian leading experts in CSR. Our results suggests that the key issues in the journey toward wider diffusion and acceptance of CSR in Malaysia include current confusion over the meaning of CSR, the prevalent use of CSR as a PR tool, mandatory versus voluntary CSR and the role the National Mirror Committee of ISO/TMB/WG SR in this process. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment. [source] UNITED STATES V. BOOKER AS A NATURAL EXPERIMENT: USING EMPIRICAL RESEARCH TO INFORM THE FEDERAL SENTENCING POLICY DEBATE,CRIMINOLOGY AND PUBLIC POLICY, Issue 3 2007PAUL J. HOFER Research Summary: In United States v. Booker, the U.S. Supreme Court held that the federal sentencing guidelines must be considered advisory, rather than mandatory, if they are to remain constitutional under the Sixth Amendment. Since the decision, the U.S. Sentencing Commission has provided policy makers with accurate and current data on changes and continuity in federal sentencing practices. Unlike previous changes in legal doctrine, Booker immediately increased the rates of upward and downward departures from the guideline range. Government-sponsored downward departures remain the leading category of outside,the-range sentences. The rate of within-range sentences, although lower than in the period immediately preceding Booker, remains near rates observed earlier in the guidelines era. Despite the increase in departures, average sentence lengths for the overall caseload remain stable, because of offsetting increases in the seriousness of the crimes being sentenced and in the severity of penalties for those crimes. Analyses of the reasons that judges reported for downward departures suggest that treatment of criminal history and offender characteristics are the two leading areas of dissatisfaction with the guidelines. Policy Implications: Assessment of changes in sentencing practices following Booker by different observers depends partly on competing institutional perspectives and on different degrees of trust in the judgment of judges, prosecutors, the Sentencing Commission, and Congress. No agreement on whether Booker has bettered or worsened the system can be achieved until agreement exists on priorities among the purposes of sentencing and the goals of sentencing reform. Both this lack of agreement and an absence of needed data make consensus on Booker's effects on important sentencing goals, such as reduction of unwarranted disparity, unlikely in the near future. Similarly, lack of baseline data before Booker on the effectiveness of federal sentencing at crime control makes before-after comparisons impossible. Despite these limitations, research provides a sounder framework for policy making than do anecdotes or speculation and sets valuable empirical parameters for the federal sentencing policy debate. [source] INJUSTICE AND IRRATIONALITY IN CONTEMPORARY YOUTH POLICYCRIMINOLOGY AND PUBLIC POLICY, Issue 4 2004DONNA M. BISHOP Lionel Tate was 12 years old when he killed 6-year-old Tiffany Eunick. Tiffany had been staying at the Tate home and, by all accounts, got along well with Lionel. The two were playing at "wrestling" when Lionel decided to try out some moves that he had seen on television. He threw Tiffany across the room, inflicting fatal injuries. Despite the boy's tender age, the prosecutor transferred Lionel to criminal court on a charge of first-degree murder, an offense carrying a mandatory penalty of life without parole. The boy was given an opportunity to plead guilty to second-degree murder in return for a sentence of three years incarceration, but he rejected the offer. A jury subsequently convicted him of first-degree murder. At sentencing, the prosecution recommended leniency, which drew an angry response from the judge: If the state believed the boy did not deserve to be sent to prison for life, why hadn't it charged him with a lesser offense? Without any inquiry into the boy's cognitive, emotional, or moral maturity, the judge imposed the mandatory sentence.1 Raymond Gardner was 16 years old when he shot and killed 20-year-old Mack Robinson.2 Raymond lived in a violent urban neighborhood with his mother, who kept close watch over him. He had no prior record. He was an A student and worked part-time in a clothing store to earn money for college. On the day of the shooting, a friend came into the store to tell Raymond that Mack had a beef with him about talking to a girl, and was "looking to get him." The victim was known on the street as "Mack the Knife" because he always carried a small machete and was believed to have stabbed several people. To protect himself on the way home, Raymond took the gun kept under the counter of the shop where he worked. As he neared home, Mack and two other men approached and blocked his path. According to eyewitness testimony, Raymond began shaking, then pulled out the gun and fired. Mack ran into the street and fell. Raymond followed and fired five more shots into the victim's back as he lay dying on the ground. Raymond did not run. He just stood there crying. The prosecutor filed a motion in juvenile court to transfer Raymond on a charge of first-degree murder. The judge ordered a psychological evaluation, which addressed the boy's family and social background, medical and behavioral history, intelligence, maturity, potential for future violence and prospects for treatment. The judge subsequently denied the transfer motion. He found Raymond delinquent and committed him to a private psychiatric treatment facility.3 [source] Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders,CYTOMETRY, Issue 4 2010Bruno Paiva Abstract In recent years, multiparameter flow cytometry (MFC) immunophenotyping has become mandatory in the clinical management of hematological malignancies, both for diagnostic and monitoring purposes. Multiple myeloma (MM) and other clonal plasma cell-related (PC) disorders should be no exception to this paradigm, but incorporation of immunophenotypic studies in the management of patients with PC disorders is still far from being routinely established in many diagnostic flow cytometry laboratories. For clonal PC disorders, MFC is of clear and established clinical relevance in: (1) the differential diagnosis between MM and other PC-related disorders; (2) the identification of high-risk MGUS and smoldering MM; (3) minimal residual disease investigation after therapy; additionally it may also be useful for (4) the definition of prognosis-associated antigenic profiles; and (5) the identification of new therapeutic targets. In this article, we review the clinical value of MFC in the study of PC disorders, with specific emphasis in those areas where consensus exists on the need to incorporate MFC into routine evaluation of MM and other clonal PC-related disorders. © 2010 Clinical Cytometry Society [source] Multiparametric analysis of normal and postchemotherapy bone marrow: Implication for the detection of leukemia-associated immunophenotypes,CYTOMETRY, Issue 1 2008D. Olaru Abstract Background: The knowledge of normal marrow is mandatory to assess the malignant counterpart of normal cells and define leukemia-associated immunophenotypes (LAIPs). In this study, the expression of a variety of antigens expressed in normal and postchemotherapy bone marrow (BM) was analyzed to provide a frame of reference for the identification of myeloid LAIPs. Methods: Multiparameter four- and six-color flow cytometry was used to define antigen combinations totally absent or present at very minimal levels in marrow cells of normal individuals (n = 20) and patients receiving chemotherapy for acute lymphoblastic leukemia (n = 20). Immature (blast) cells were gated according to CD45/SSC properties. Fifty-three acute myeloid leukemia (AML) samples were studied in six-color combinations. Results: In six-color flow cytometry, 47 phenotypes were totally absent from blast gate in all normal samples. Forty-one other phenotypes were identified in less than 0.05% of blast cells. There was no difference between normal and postchemotherapy BMs. The four-color panel allowed to identify only 30 phenotypes present at a frequency <0.05%. Using the six-color panel, 58% of the absent or infrequent phenotypes in normal BM were found in at least one of 53 AML samples. All AML cases exhibited at least one LAIP. Conclusion: Our results show that the ability to distinguish leukemic from healthy cells is considerably increased by a six-color approach. Furthermore, these absent or infrequent phenotypes in normal BM are identified in AML and can be utilized for minimal residual disease study. © 2007 Clinical Cytometry Society [source] An Exploratory Analysis of the Value of the Skills of IT Personnel: Their Relationship to IS Infrastructure and Competitive AdvantageDECISION SCIENCES, Issue 1 2001Terry Anthony Byrd Abstract Determining and assessing the requisite skills of information technology (IT) personnel have become critical as the value of IT has risen in modern organizations. In addition to technical skills traditionally expected of IT personnel, softer skills like managerial, business, and interpersonal skills have been increasingly cited in previous studies as mandatory for these employees. This paper uses a typology of IT personnel skills,technology management skills, business functional skills, interpersonal skills, and technical skills,and investigates their relationships to two information systems (IS) success variables, IS infrastructure flexibility and the competitive advantage provided by IS. The study investigates these relationships using the perceptions of chief information officers (CIOs) from mostly Fortune 2000 companies. The contributions of this study are: IT personnel skills do affect IS success, technical skills are viewed as the most important skill set in affecting IS infrastructure flexibility and competitive advantage, and modularity is viewed as more valuable to competitive advantage than integration. Several explanations are offered for the lack of positive relationships between the softer IT personnel skills and the dimensions of IS success used in this study. [source] Oro-facial injuries in Central American and Caribbean sports games: a 20-year experienceDENTAL TRAUMATOLOGY, Issue 3 2005Enrique Amy Abstract,,, Dental services in sports competitions in the Games sponsored by the International Olympic Committee are mandatory. In every Central American, Pan American and Olympic Summer Games, as well as Winter Games, the Organizing Committee has to take all the necessary measures to assure dental services to all competitors. In all Olympic villages, as part of the medical services, a dental clinic is set up to treat any dental emergency that may arise during the Games. Almost every participating country in the Games has its own medical team and some may include a dentist. The major responsibilities of the team dentist as a member of the national sports delegation include: (i) education of the sports delegation about different oral and dental diseases and the illustration of possible problems that athletes or other personnel may encounter during the Games, (ii) adequate training and management of orofacial trauma during the competition, (iii) knowledge about the rules and regulations of the specific sport that the dentist is working, (iv) understanding of the anti-doping control regulations and procedures, (v) necessary skills to fabricate a custom-made and properly fitted mouthguard to all participants in contact or collision sports of the delegation. This study illustrates the dental services and occurrence of orofacial injury at the Central American and Caribbean Sports Games of the Puerto Rican Delegation for the past 20 years. A total of 2107 participants made up the six different delegations at these Games. Of these 279 or 13.2% were seen for different dental conditions. The incidence of acute or emergency orofacial conditions was 18 cases or 6% of the total participants. The most frequent injury was lip contusion with four cases and the sport that experienced more injuries was basketball with three cases. [source] Pulp capping with adhesive resin-based composite vs. calcium hydroxide: a reviewDENTAL TRAUMATOLOGY, Issue 6 2000A. H. B. Schuurs Abstract , The results of some short-term experiments suggest that direct capping of a vital pulp with the modern resin-based composite systems may be as effective as capping with calcium hydroxide. Total cavity etching with 10% phosphoric acid seems to be safe for the exposed pulp, but unless annulled by calcium hydroxide 35% phosphoric acid may be disastrous. For hemostasis and cleaning of the pulp wound both sodium hypochlorite and saline seem suitable, whereas the effectiveness of a 2% chlorhexidine solution is questionable. Although hard-setting calcium hydroxide cements may induce the formation of dentin bridges, they appear not to provide an effective long-term seal against bacterial factors. Within a few years, the majority of mechanically exposed and capped pulps show infection and necrosis due to microleakage of such capping materials and tunnel defects in the dentin bridges. It is unknown whether newer types of resin containing calcium-hydroxide-products will act as a permanent barrier. The cytotoxicity of the resin-based composites and the temperature rise during polymerisation may not be of concern, but microleakage, sensitisation and allergic reactions may pose problems. Based on available data, pulp capping with resin-based composites may be said to be promising, but more and long-term research is mandatory before the method can be recommended. [source] Lipid-lowering therapy in patients with type 2 diabetes: the case for early interventionDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2008Armin Steinmetz Abstract Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy. Copyright © 2008 John Wiley & Sons, Ltd. [source] Biofeedback for foot offloading in diabetic patients with peripheral neuropathyDIABETIC MEDICINE, Issue 1 2010Z. Pataky Diabet. Med. 27, 61,64 (2010) Abstract Aims, The reduction of high plantar pressure in diabetic patients with peripheral neuropathy is mandatory for prevention of foot ulcers and amputations. We used a new biofeedback-based method to reduce the plantar pressure at an at-risk area of foot in diabetic patients with peripheral neuropathy. Methods, Thirteen diabetic patients (age 60.8 ± 12.3 years, body mass index 29.0 ± 5.0 kg/m2) with peripheral neuropathy of the lower limbs were studied. Patients with memory impairment were excluded. The portable in-shoe foot pressure measurement system (PEDAR®) was used for foot offloading training by biofeedback. The learning procedure consisted in sequences of walking (10 steps), each followed by a subjective estimation of performance and objective feedback. The goal was to achieve three consecutive walking cycles of 10 steps, with a minimum of seven steps inside the range of 40,80% of the baseline peak plantar pressure. The peak plantar pressure was assessed during the learning period and at retention tests. Results, A significant difference in peak plantar pressure was recorded between the beginning and the end of the learning period (when the target for plantar pressure was achieved) (262 ± 70 vs. 191 ± 53 kPa; P = 0.002). The statistically significant difference between the beginning of learning and all retention tests persisted, even at the 10-day follow-up. Conclusions, Terminal augmented feedback training may positively affect motor learning in diabetic patients with peripheral neuropathy and could possibly lead to suitable foot offloading. Additional research is needed to confirm the maintenance of offloading in the long term. [source] Cytological features of lipoblastoma: A report of three casesDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Ph.D., V. Veronika Kloboves-Prevodnik M.D. Abstract Lipoblastoma is a rare benign neoplasm occurring mostly in children under the age of three. Accurate preoperative diagnosis is mandatory for planning the treatment. The main aim of this study is to establish the cytological features of lipoblastoma and to answer the question: "Is cytological diagnosis of lipoblastoma reliable?" Preoperative fine-needle aspiration biopsy (FNAB) and tissue sections of three children treated for lipoblastoma at the Division of Pediatrics, University Medical Center, Ljubljana, Slovenia, in the period from 1997 to 2004 were reexamined. The Giemsa- and Papanicolaou-stained FNAB smears were moderately or poorly cellular and contained lipocytes, lipoblasts, and spindle cells in various proportions. The tumor cells were in clusters and tissue fragments or as single cells. Thin branching capillaries were observed in most of the clusters and tissue fragments. In the background, abundant myxoid extracellular material and naked oval nuclei were present. In the first case, the cytological diagnosis was benign soft-tissue tumor, in the second the diagnosis was not conclusive and the last case was correctly diagnosed as lipoblastoma. In the differential diagnosis of the second case, both lipoblastoma and liposarcoma were considered cytologically as well as histologically. At 7-yr follow-up, there is no evidence of the disease. Thus, we conclude that lipoblastoma with typical cytological features could be accurately diagnosed by FNAB. However, tumors containing numerous lipoblasts could pose a diagnostic problem. Diagn. Cytopathol. 2005;33:195,200. © 2005 Wiley-Liss, Inc. [source] A REVIEW OF CURRENT CLINICAL APPLICATIONS OF UPPER GASTROINTESTINAL ZOOM ENDOSCOPYDIGESTIVE ENDOSCOPY, Issue 2005Kenshi Yao Current clinical applications of upper gastrointestinal (GI) zoom endoscopy were reviewed. The objective of upper GI zoom endoscopy has been the diagnosis of neoplastic lesions as well as the diagnosis of minute inflammatory mucosal change. The target organ and pathology of the neoplastic lesions have been squamous cell carcinoma in the oro- and hypo-pharynx and in the esophagus; intestinal metaplasia, dysplasia, and adenocarcinoma in Barrett's esophagus; and adenocarcinoma in the stomach. For analyzing the magnified endoscopic findings, there were two different basic principles (mucosal microstructural change and subepithelial microvascular changes). Overall diagnostic accuracy for diagnosing a neoplastic lesion was above 80% throughout the upper GI tract. Although the diagnostic accuracy of the zoom endoscopy technique seems to be superior to that of the ordinary endoscopy technique alone, the continuous efforts to establish standardized guidelines and procedures are mandatory in order to lead to the routine use of upper GI zoom endoscopy in clinical practice. [source] Epiphrenic diverticula: minimal invasive approach and repair in five patientsDISEASES OF THE ESOPHAGUS, Issue 1 2001D. L. Van Der Peet Epiphrenic esophageal diverticula are rare and often asymptomatic. If surgery is mandatory, a thoracotomy is used to resect the diverticulum. The results of a minimal invasive approach and repair in five patients are presented. These patients, who all presented with an epiphrenic diverticulum, were evaluated using barium swallow study, esophagoscopy, and manometry. The diverticula were approached by thoracoscopy in all patients and a description of the surgical technique is given. The diverticula were resected using a right-sided approach in four patients. One patient with a diverticulum in the distal esophagus required conversion to laparoscopy. A myotomy was performed in two patients because of high pressures in the lower esophageal sphincter. The postoperative course was uncomplicated in four patients. One patient with Ehlers,Danlos disease had a complicated course owing to leakage, resulting in two re-operations by means of thoracotomy. There was no mortality. The minimal invasive approach of epiphrenic diverticula is feasible. The long-term results are awaited. [source] 5 DIAGNOSTIC PITFALLS IN THE ECHOCARDIOGRAPHIC EVALUATION OF HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM) REFERRED FOR CATHETER INTERVENTIONAL THERAPYECHOCARDIOGRAPHY, Issue 1 2004G. Beer Introduction: Generally, the diagnosis of typical HOCM with subaortic obstruction and a dynamic pressure gradient across the left ventricular outflow tract is made by noninvasive diagnostic procedures with great certainty by employing transthoracic (TTE) and/or transoesophageal (TEE) echocardiography. However, in patients with asymmetric septal hypertrophy pitfalls in echocardiographic examination may arise from several additional diseases as described in casuistic reports. To date systematic investigations in patients referred for catheter interventional therapy of HOCM are lacking. Patients and Methods: Therefore we investigated for the first time in a systematic study 200 symptomatic patients. (180 consecutive and 20 nonconsecutive patients; functional class 3 or 4 according to NYHA) with HOCM who were referred for this new catheter interventional therapy. In all patients TTE, bicycle exercise Doppler echocardiography and multiplane TEE were performed. Results: In 4 of 180 consecutive patients. (2.2%) discrete subvalvular membranous aortic stenosis (DSAS) (3 female patients and 1 male patient; age 20 to 58 years; mean septal diameter 19 mm; Sam-like motion in all 4 patients) was made. In all cases the diagnosis could be confirmed by surgical treatment. TEE evaluation was of crucial importance with demonstration of a typical subvalvular membrane that was situated a few millimeters below the aortic valve. In all cases a typical asymmetric septal hypertrophy mimicking HOCM was seen. Additionally, in 2 patients there was a conincidence of severe symptomatic valvular aortic stenosis and HOCM and in 1 patient a tunnel type of subvalvular aortic stenosis was present. Conclusion: These results show the potential pitfalls in echocardiographic diagnosis of HOCM. Especially, the frequency of DSAS in symptomatic patients referred for HOCM is unexpectedly high (2.2%). Especially in patients in whom TTE is of insufficient quality, investigation employing multiplane TEE with careful evaluation of the small poststenotic subvalvular area in HOCM is of crucial importance. This is of special significance prior to catheter interventional therapy, because in these patients surgical treatment is mandatory. [source] Recombinant clotting factor VIII concentrates: Heterogeneity and high-purity evaluationELECTROPHORESIS, Issue 16 2010Gian Maria D'Amici Abstract Factor VIII is an important glycoprotein involved in hemostasis. Insertion of expression vectors containing either the full-length cDNA sequence of human factor VIII (FLrFVIII) or B-domain deleted (BDDrFVIII) into mammalian cell lines results in the production of recombinant factor VIII (rFVIII) for therapeutic usage. Three commercially available rFVIII concentrates (Advate®, Helixate NexGen® and Refacto®), either FLrFVIII or BDDrFVIII, were investigated by 1- and 2-DE and MS. The objective of this study was to compare the heterogeneity and the high purity of both rFVIII preparations before and after thrombin digestion. In particular, the 2-D gel was optimized to better highlight the presence of contaminants and many unexpected proteins. Recombinant strategies consisting of insertion of expression vectors containing BDDrFVIII and FLrFVIII resulted in homogeneous and heterogeneous protein products, respectively, the latter consisting in a heterogeneous mixture of various B-domain-truncated forms of the molecule. Thrombin digestion of all the three rFVIII gave similar final products, plus one unexpected fragment of A2 domain missing 11 amino acids. Regarding the contaminants, Helixate NexGen® showed the presence of impurities, such as Hsp70,kDa, haptoglobin and proapolipoprotein; Refacto® showed glutathione S -transferase and ,-lactamase, whereas Advate® apparently did not contain any contaminants. The proteomic approach will contribute to improving the quality assurance and manufacturing processes of rFVIII concentrates. In this view, the 2-DE is mandatory for revealing the presence of contaminants. [source] CE-ESI-MS/MS as a rapid screening tool for the comparison of protein,ligand interactionsELECTROPHORESIS, Issue 7 2010Thomas Hoffmann Abstract In drug development, the combinatorial synthesis of drug libraries is common use, therefore efficient tools for the characterization of drug candidates and the extent of interaction between a drug and its target protein is a central question of analytical interest. While biological activity is tested today by enzyme assays, MS techniques attract more and more attention as an alternative for a rapid comparison of drug,target interactions. CE enables the separation of proteins and drug,enzyme complexes preserving their physiological activity in aqueous media. By hyphenating CE with ESI-MS/MS, the binding strength of enzyme inhibitors can be deduced from MS/MS experiments, which selectively release the inhibitor from the drug,target complex after CID. In this study, ,-chymotrypsin (CT), a serine protease, was chosen as a model compound. Chymostatin is a naturally occurring peptide aldehyde binding to CT through a hemiacetal bond and electrostatic interaction. First, a CE separation was developed, which allows the analysis of ,-CT and a chymotrypsin,chymostatin complex under MS-compatible conditions. The use of neutral-coated CE capillaries was mandatory to reduce analyte,wall interactions. ESI-quadrupole ion trap-MS was worked out to demonstrate the selective drug release after CID. Fragmentation of the drug,enzyme complex was monitored in dependence from the excitation energy in the ion trap, leading to the V50 voltage that enables 50% complex fragmentation as a reference value for chymotrypsin,chymostatin complex. A stable CE-ESI-MS/MS setup was established, which preserves the drug,enzyme complexes during ionization,desolvation processes. With this optimized setup, different CT inhibitors could be investigated and compared. [source] Impact of Mandatory Physician Reporting on Accident Risk in EpilepsyEPILEPSIA, Issue 8 2007Richard S McLachlan Summary:,Background: In some jurisdictions, physicians are required by law to report patients with seizures to the department of motor vehicles. We assessed the hypothesis that mandatory reporting reduces the risk of automobile accidents in people with epilepsy. Methods: A retrospective survey of driving and accident rates was done by mailed questionnaire to two groups of subjects with epilepsy in Canada, one living in Ontario where reporting is mandatory and the other in Alberta where it is not. Responses were obtained from a control group without epilepsy for comparison. Results: The epilepsy (n = 425) and control (n = 375) groups were comparable in age and sex. Seventy-three percent of the epilepsy group were or had been licensed drivers compared to 94% of the controls (rr 0.77, 95% CI 0.73,0.83, p < 0.001). Lifetime accident rate of licensed drivers was 58% in epilepsy and 60% in controls (rr 0.99, 95%CI 0.82,1.19, ns) while 9% of the epilepsy group and 9% of the controls had an accident in the previous year (rr 1.00, 95%CI 0.95,1.06, ns). All those with epilepsy in Ontario (n = 202) and Alberta (n = 223), also comparable in age and sex, had equal lifetime accident rates of 45 and 46% (rr 0.99, 95%CI 0.67,1.47, ns) and 1-year rates of 11 and 8% (rr 1.38, 95%CI 0.59,3.27, ns). In Ontario, 20% of drivers were unlicensed compared to 9% in Alberta (rr 2.39, 95%CI 1.17,4.89, p = 0.01) Conclusion: Although it is clearly dangerous for many people with ongoing seizures to drive, the findings provide no support for the hypothesis that mandatory reporting of patients by physicians reduces accident risk and suggest that concerns about the impact of epilepsy on driving compared to other medical and nonmedical risk factors may be excessive. [source] Agriculture Under the Public Eye: Who Cares for WhatEUROCHOICES, Issue 2 2004Cees Veerman Summary Agriculture Under the Public Eye: Who Cares for What? The new CAP is becoming geared towards a more sustainable agriculture that takes account of the needs of future generations. Achieving sustainability, however, means meeting three challenges-, (a) profit - strengthening the viability and competitiveness of the agricultural sector; (b) planet - the ecological challenge of promoting good environmental practices; and (c) people-the social challenge to improve the living conditions and economic opportunities in rural areas. In the food chain we see responses to consumer concerns about food safety, quality and welfare issues through the development and implementation of mandatory and voluntary quality control and assurance schemes. And the consolidation and internationalisation of the food retailing and the manufacturing industry is expected to continue. An important duality has emerged. On the one side, we find a state system of regulation, on the other a system of self-regulation, largely driven by the major forces in supply chain management, the food retailers in particular. A simple and effective regulatory environment for the agri-food complex is essential if we are to achieve our competitiveness goals. One of the priorities for discussion by politicians, therefore, should be whether current and expected policy and industry developments should lead to a review of the balance between markets and government, ,who cares for what?' l'agriculture aux yeux des politiques publiques qui doit faire quoi? La nouvelle PAC est maintenant bien orientée vers une agriculture plus durable, en mesure de tenir compte des besoins des générations futures. Une véritable durabilityé suppose cependant que soient relevés trois défis: a) le profit - renforcer la viabilityé et la compétitivité du secteur agricole; b) la planète - le défiécologique de promouvoir des pratiques favorables à l'environnement; c) les gens - le défi social d'améliorer les conditions de vie et les opportunités économiques dans les zones rurales. Du côté des filières alimentaires, la réponse à trouver aux inquiétudes des consommateurs vis à vis de la qualityé sanitaire et organoleptique des produits devrait pouvoir venir de l'élaboration de contrôles de qualityé et de systèmes d'assurances, à appliquer sur la base du volontariat ou à rendre obligatoires. En même temps, il faut s'attendre à la continuation du mouvement vers l'affermissement du rôle des industries alimentaires et du commerce de détail, ainsi qu'à leur internationalisation. Un système dual vient d'émerger: d'un côté, un système de réglementations étatiques, de l'autre, une autodiscipline, pilotée par les plus solides des maillons de la filière, en particulier les grandes surfaces. Un environnement réglementaire à la fois simple et efficace est essentiel pour atteindre l'objectif de compétitivité du complexe agroalimentaire, II en résulte que, pour les pouvoirs publics, une des grandes questions à discuter est de savoir dans quelle mesure l' évolution des conditions politiques et celle du développement industriel imposent une révision de l'équilibre actuel entre les marchés et les autorités gouvernementales; en d'autres termes, qui doit faire quoi ? Landwirtschaft in der öffentlichen Meinung; Wer ist wofür zuständig? Die neue GAP wird gerade auf eine nachhaltigere Landwirtschaft hin ausgerichtet, welche die Bedürfnisse der kommenden Generationen berücksichtigt. Nachhaltigkeit kann jedoch nur erzielt werden, wenn den folgenden drei Herausforderungen Rechnung getragen wird: (a) Ökonomie , Stärkung der Leistungs- und Wettbewerbsfähigkeit des Landwirtschaftssektors; (b) Ökologie , Förderung umweltgerechter Verfahrensweisen; und (c) Soziales - Verbesserung der Lebensbedingungen und der wirtschaftlichen Lage im ländlichen Raum. Im Bereich der Nahrungsmittelkette wird den Bedenken der Verbraucher hinsichtlich der Nahrun gsmittelsicherheit, der Qualität und der Wohlfahrt durch die Entwicklung und Implementierung von obligatorischen und freiwilligen Qualitätskontrollen und Sicherheitsprogrammen Rechnung getragen. Es ist davon auszugehen, dass sich die Konsolidierung und Lnternationalisierung im Bereich des Lebensmitteleinzel-handels und der weiterverarbeitenden Industrie fortsetzen wird. Es ist eine bedeutsame Dualität entstanden. Auf der einen Seite erfolgt eine Regulierung seitens des Staates, auf der anderen Seite erfolgt eine Selbstregulierung durch die Vermarktungskette, insbesondere durch den Lebensmitteleinzelhandel. Eine sowohl einfache als auch wirksame Regulierung der Agrar- und Ernährungswirtschaft ist von grundlegender Bedeutung für das Erreichen unserer Wettbewerbsziele. Daher sollte in der Politik mit Priorität diskutiert werden, ob die gegenwärtige und zukünftige Politik und auch die industrielle Entwicklung zu einem neuen Gleichgewicht zwischen Markt und Staatseingriffen führen sollte: Wer ist wofür zuständig? [source] Bradycardia and sinus arrest during percutaneous ethanol injection therapy for hepatocellular carcinomaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2004A. Ferlitsch Abstract Background, Percutaneous ethanol injection (PEI) is an established method in the treatment of hepatocellular carcinoma (HCC) and considered a safe procedure, with severe complications occurring rarely. Cardiac arrhythmias have not been reported to date. Aim of the study was to investigate the occurrence of dysrhythmias during PEI. Patients and methods, Twenty-six consecutive patients with inoperable HCC were included. During ultrasound-guided PEI with 95% ethanol, electrocardiogram (ECG) monitoring was performed before starting and continuously during PEI. Results, During PEI a significant reduction in mean heart rate (> 20%) was seen in 15 of 26 (58%) patients. In 11 of 26 patients (42%) occurrence of sinuatrial block (SAB) or atrioventricular block (AVB) was observed after a median time of 9 s (range 4,50) from the start of PEI with a median length of 24 s (range 12,480). Clinical symptoms were seen in two patients, including episodes of unconsciousness, seizure-like symptoms in both and a respiratory arrest during PEI in one patient, requiring mechanical ventilation. In four of 12 patients with repeat interventions, dysrhythmias were reproducible during monthly performed procedures. There was a significant association between the occurrence of SAB or AVB and the amount of instilled alcohol (P = 0·03) and post-PEI serum ethanol levels (P = 0·03). Conclusions, Bradycardia and block formation occur frequently during PEI. These symptoms could be explained by a vasovagal reaction and/or the direct effect of ethanol on the sinus node or the right atrial conduction system. Ethanol dose is an important factor for the occurrence of SAB/AVB. ECG-monitoring seems mandatory during PEI. Prophylactic use of intravenously administered Atropine might be useful. [source] Basal TSH levels compared with TRH-stimulated TSH levels to diagnose different degrees of TSH suppression: diagnostic and therapeutic impact of assay performanceEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2002M. Christ-Crain Abstract Background The estimated prevalence of endogenous subclinical hyperthyroidism varies from 4% to 6% and a basal thyroid stimulating hormone (TSH) level < 0·5 mU L,1 may be associated with increased mortality in subjects over 60 years of age who are not on thyroid medication. Exogenous TSH suppression is a mainstay in the treatment of thyroid cancer. Because of recent concerns about potential adverse effects, especially of endogenous TSH suppression on bone, the cardiovascular system and cognitive functions, subclinical hyperthyroidism obtained new clinical importance. We therefore re-evaluated the diagnostic value of basal and thyrotrop in TRH-stimulated serum TSH measurements using TSH assays with different sensitivities. Materials and methods A total of 805 oral and nasal TRH stimulation tests were performed on 409 ambulatory subjects with low basal serum TSH concentrations of less than 0·1 mIU L,1. Basal serum TSH was measured either using a second generation assay (functional sensitivity > 0·03 mIU L,1) or two third generation assays (functional sensitivity 0·01 mIU L,1 and 0·007 mU L,1, respectively). Serum TSH concentration was determined before and 3 h after oral administration of 40 mg of TRH and before and 30 min after nasal administration of 2 mg of TRH. Results In the oral testing group, the basal TSH levels measured by the different TSH assays were 0·06 ± 0·03, 0·04 ± 0·02 and 0·03 ± 0·02, respectively, whereas the peak TSH levels were 0·4 ± 0·6, 0·4 ± 0·6 and 0·3 ± 0·5 in the patients with subclinical hyperthyroidism. In overt hyperthyroidism, the basal TSH levels were 0·06 ± 0·02, 0·03 ± 0·02 and 0·03 ± 0·02, whereas the peak TSH levels were 0·19 ± 0·3, 0·16 ± 0·3 and 0·15 ± 0·2, respectively. Basal TSH values could discriminate between different degrees of TSH suppression if measured with a third generation assay (P < 0·001), but not with a second generation assay. There was only a weak correlation between basal TSH and peak TSH when measured by a second generation assay (n = 126; r = 0·3; P < 0·001) in contrast to the strong correlation found using the third generation assays (n = 128; r = 0·7; P < 0·001 and n = 69; r = 0·8; P < 0·001, respectively). Conclusions In view of the recent concerns about potential adverse effects in TSH suppression and based on our data, it is mandatory to select a TSH assay with a functional sensitivity of , 0·01 mIU L,1 for optimal titration of L-T4 suppressive therapy, especially in patients with thyroid cancer. If, however, only a second generation TSH assay is available, additional TRH testing allows a more careful titration of suppressive thyroxine therapy. [source] The germinal center response is impaired in the absence of T cell-expressed CXCR5EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Carrie Abstract Germinal centers support the differentiation of memory B cells and long-lived antibody-secreting cells during infection or upon vaccination. Here, we constructed mice with T cells that selectively lack the chemokine receptor CXCR5 to determine if expression of this receptor by T cells is mandatory for germinal center formation and function. In these animals, germinal centers that are properly localized in B cell follicles and contain T cells do form after immunization with a thymus-dependent antigen. However, fewer and smaller germinal centers form, resulting in a significant reduction in the frequency of germinal center B cells. The defect in germinal center formation is paralleled by decreased frequencies of isotype-switched antibody-secreting cells in the spleen and bone marrow and reduced serum concentrations of total and high-affinity hapten-specific IgG1. The results demonstrate that although CXCR5-dependent T cell positioning is important for maximal induction and expansion of germinal centers, stimulation of isotype class switching, and development of antibody-secreting cells that seed the spleen and bone marrow, it is not absolutely required for the formation and function of follicular germinal centers. [source] A strategy for correlative microscopy of large skin samples: towards a holistic view of axillary skin complexityEXPERIMENTAL DERMATOLOGY, Issue 1 2008Katrin Wilke Abstract:, Knowledge about the structural elements of skin and its appendices is an essential prerequisite for understanding their complex functions and interactions. The hence necessary morphological description across several orders of scale not only requires the investigation at the light microscopic level but also ultrastructural investigation, ideally on the identical sample. For a correlative and multimodal observation one unique preparation protocol is mandatory. As a compromise between sample sizes of >500 ,m in diameter on the one hand and optimal preservation of antigenicity and morphology on the other, we developed a new preparation protocol that allows (i) 3D reconstruction of the resin-embedded sample by confocal light microscopy prior to (ii) direct immunolocalization of target proteins within selected sample planes by light and fluorescence microscopy or transmission electron microscopy. Alternatively, (iii) serial cryosections of the frozen sample can be taken for characterizing the sample in toto. With this unique approach we were able to fully demonstrate the structural complexity of axillary skin samples, increasing the structural resolution from 3D reconstruction of the whole gland up to ultrastructural investigations at the subcellular level. We could demonstrate that axillary sweat glands are not separately distributed, as has been assumed to date; instead, they seem to be intricately twisted into one another. This promotes the concept of a complex axillary sweat gland organ instead of single sweat gland entities. [source] Surgical treatment of acne inversa (hidradenitis suppurativa): a 20-year experienceEXPERIMENTAL DERMATOLOGY, Issue 6 2006Wolfgang Hartschuh Acne inversa (AI) is caused by follicular hyperkeratosis in intertriginous areas rich in apocrine glands followed by occlusion and rupture of the follicle and inflammation. Sinus tracts, scarring and often contraction with limitation in mobility may occur. There is a world-wide consensus that in chronic disease surgical removal of all involved tissue as early as possible is the most effective treatment modality. The aim of this study is to demonstrate our operative strategy, including postoperative wound care and prevention, the results and pitfalls in the treatment of AI. The operations are increasingly performed in tumescence anaesthesia, followed by secondary healing. Only removal of extended skin areas in the inguino-genital and ano-perineal regions demand general anaesthesia. In axillary regions, all hair-bearing skin including the sweat glands is removed to obtain a hair-free, dry skin area. In the other regions with ill-defined hair and apocrine gland areas, only involved indurated skin is excised. For early limited disease with fluctuant abscesses, unroofing instead of mere incision and drainage is a good first option. Professional wound care with shaving and stretching of the wound margins is very important to avoid premature wound closure. Locally applied disinfectant soaps and 2% triclosane ointments are effective in pre- and postoperative skin care. Follow-up evaluation and collaboration among surgeons and dermatologists and an improved insight in the pathogenesis of AI are mandatory for the successful long-term management of patients afflicted with this complex and debilitating disease. [source] Materials Selection Process for Compound-Extruded Aluminium Matrix Composites,ADVANCED ENGINEERING MATERIALS, Issue 12 2005A. Weidenmann Compound extrusion is a near-net-shape process allowing for the rapid and flexible in-line production of unidirectionally-reinforced profiles. Regarding the use of this technology for the production of reinforced lightweight profiles for structural applications, no materials combination has yet been systematically assessed or examined since the first investigations on compound conductor rails starting in the 1970s. On this account, a materials selection process respecting the compound extrusion demands is mandatory. [source] Potamogeton -Hybriden in Deutschland,FEDDES REPERTORIUM, Issue 5-6 2008G. Wiegleb Prof. Dr. Alle in Deutschland nachgewiesenen Potamogeton -Hybriden werden aufgelistet und beschrieben. Bestimmungsprobleme, Verbreitung und Häufigkeit werden jeweils diskutiert. Potamogeton -Hybriden sind seit mehr als 200 Jahren aus Deutschland bekannt. Insgesamt sind 16 Taxa sicher nachgewiesen. Davon sind nur P. × angustifolius, P. × nitens und P. × salicifolius verbreitet und häufig und treten in vitalen Populationen auf. Drei weitere Taxa kommen wahrscheinlich vor, bedürfen aber noch der endgültigen Bestätigung. Fünf in der Literatur genannte Taxa wurden gestrichen. Weitere Aufsammlungen und molekulargenetische Untersuchungen der kritischen Fälle sind notwendig. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) Potamogeton hybrids in Germany All Potamogeton hybrids occurring in Germany are listed and described. Identification problems, distribution and frequency are discussed for each taxon. Potamogeton hybrids from Germany have been studied since more than 200 years. Today the occurrence of 16 taxa has been verified beyond doubt. Only P. × angustifolius, P. × nitens, and P. × salicifolius are widely distributed and occur frequently in vital populations. Three additional taxa are likely to occur but need further verification. Five taxa reported in literature are excluded. Further collections and molecular biological investigations of critical taxa are mandatory. [source] Improvement of the comprehension of written information given to healthy volunteers in biomedical research: a single-blind randomized controlled studyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Adeline Paris Abstract Writing an informed consent form (ICF) for biomedical research is a difficult task. We conducted a multicenter single-blind randomized controlled trial to identify whether a working group or the systematic improvement in lexico-syntactic readability or an association of the two could increase the comprehension of the written information given to healthy volunteers enrolled in biomedical research. Participants were randomized to read one of four versions of the ICF: unchanged ICF (A), ICF with systematic lexico-syntactic readability improvement (B), ICF modified by a working group (C), and ICF modified by the working group followed by systematic lexico-syntactic improvement (D). The primary end-point was the objective comprehension score at day 0 for each study group. The scores of objective comprehension at day 0 were statistically different between the four study groups (anovaP = 0.020). The pairwise analysis showed an improvement in the working group vs. the unchanged group (P = 0.003), and a tendency to improvement in the group who read the ICF modified using lexico-syntactic readability and in the group who read the ICF modified using the two methods (P = 0.020 and 0.027 respectively). We conducted a two-way anova to identify some characteristics of the population which could explain this score. There was a significant interaction between the type of informed consent document (ICD) and the gender. Improving the ICD in phase I biomedical research leads to better comprehension, whether the method used is systematic lexico-syntactic improvement or a review by a working group. The improvement is specifically observed in men compared with women. Conversely, while both methods diverge in their effect on lexico-syntactic readability, their association is not mandatory. We suggest that in all phase I clinical trials, the ICF be improved by either method. [source] | ||||||||||||||||||||||||||||