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Attractive Option (attractive + option)
Selected AbstractsHydrophobic pervaporation for environmental applications: Process optimization and integrationENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 4 2002Frank Lipnizki The focus of this paper is on the design of pervaporation units for wastewater treatment taking into account technical, economic, and environmental aspects. Two different sized industrial wastewater streams of water-chloroform, and of water-methyl-isobutylketone (MIBK) are considered. Based on a wastewater stream of 1,500 kg/d, a semi-batch process combining pervaporation with a decanter recycle loop is developed. Using this process, it is possible to recover over 99% of the organic components at concentrations of more than 98 wt. %. The treatment costs are between 0.11 to 0.16 $/kg wastewater. For the treatment of a wastewater stream of 1,000 kg/h, pervaporation combined with a decanter and recycling loop, as well as integrated in a hybrid process with adsorption, is considered. For MIBK, pervaporation with a decanter is the most attractive option taking economic and environmental aspects into account, while, for chloroform, the hybrid process is the better option. Treatment costs in all cases are about 0.03 $/kg wastewater. The recovery rate of the organic compounds is over 99% at concentrations over 98 wt. %. The authors concluded that pervaporation as a stand-alone unit, or integrated into hybrid processes, offers significant advantages over conventional alternatives. [source] Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paperEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008M. Dungarwalla Abstract Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [source] Emergency Medicine Resident Patient Care Documentation Using a Hand-held Computerized DeviceACADEMIC EMERGENCY MEDICINE, Issue 12 2001Steven B. Bird MD Abstract Objective: To determine whether emergency medicine (EM) resident documentation of procedures, patient encounters, and patient follow-ups improved after implementation of a personal digital assistant (PDA) hand-held recording system. Methods: All first-year EM residents were provided a PalmV (Palm, Inc., Santa Clara, CA) PDA. A customized patient procedure and encounter program was constructed using Pendragon Forms (Pendragon Software Corporation, Libertyville, IL) and loaded into each PDA. Residents were instructed to enter information on patients who had any of 21 procedures performed or were considered to be clinically unstable. These data were downloaded to the residency coordinator's desktop computer. The mean number of procedures, encounters, and follow-ups performed per resident were then compared with those of a group of 36 historical controls from the three previous first-year resident classes who recorded the same information using a handwritten card system. Data from the historical controls were combined and the means of each group were compared by Student's t-test. Results: Mean documentation of three procedures was significantly increased in the PDA group versus the index card system: conscious sedation 5.8 vs. 0.03 (p < 0.000005), thoracentesis 2.2 vs. 0.0 (p = 0.002), ultrasound 6.3 vs. 0.0 (p = 0.002). The mean numbers of pericardiocenteses and unstable pediatric surgical patient evaluations were significantly decreased in the hand-held group [from 1.2 to 0.4 (p = 0.03) and from 9.1 to 2.2 (p = 0.02), respectively]. Patient follow-up documentations were not statistically different between the two groups. Conclusions: Use of a hand-held PDA was associated with an increase in first-year EM resident documentation in three of 20 procedures and a decrease in one procedure and the number of unstable surgical pediatric patient resuscitations. The overall time savings in constructing a resident procedure database, as well as the other uses of the PDAs, may make transition to a hand-held computer-based procedure log an attractive option for EM residencies. [source] Usefulness of a malleable penile prosthesis in patients with a spinal cord injuryINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2008Young Dong Kim Objectives: The usefulness of a malleable penile prosthesis was evaluated in patients with spinal cord injury (SCI) by investigating the complications and the patients' satisfaction. Methods: A total of 48 patients with a SCI, who underwent malleable penile prosthesis (AMS 600) insertion from 1990 to 2004 were evaluated by reviewing the patients' medical records and interviewing them via questionnaires. The mean patients age was 58.9 years, and the mean follow-up period was 11.7 years. In 23 patients, penile prosthesis implantation was carried out to improve urinary management and to treat erectile dysfunction (ED). Results: Complications occurred in eight patients (16.7%). Wound infections in four (8.3%). Two patients were treated with conservative management, and two were managed through prostheses removal. Other complications were erosion in two patients (4.2%), uncontrolled penile pain owing to excessive prosthesis length in one patient (2.1%), and supersonic transporter (SST) deformity in one patient (2.1%). The overall patient satisfaction rate was 79.2%. The dissatisfaction was mainly due to the complications that resulted in the removal of the prosthesis, or partner's unnatural sensation. All of the prostheses that were implanted in the patients for the improvement of their urinary management gave them the benefit of convenient urinary management, except for two patients, whose prostheses were removed. Conclusions: The insertion of malleable penile prostheses in patients with SCI is associated with low complication rates and good patient satisfaction. It is therefore still an attractive option. [source] Therapy of metastasized Merkel cell carcinoma with liposomal doxorubicin in combination with radiotherapyJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2009Marion Wobser Summary Background: Merkel cell carcinoma is a rare skin cancer of neuroendocrine origin, which is characterized by a high rate of recurrence, metastatic spread and mortality. Because of its rarity, evidence-based therapeutic regimens are difficult to establish. Merkel cell carcinoma is known to be both radio- and chemosensitive. Toxicity is a key factor in assessing any regimen, as the patients are usually elderly and likely to have other significant medical problems. Patients and Methods: We retrospectively evaluated five patients with metastatic Merkel cell carcinoma to see if liposomal doxorubicin (Caelyx® or Myocet®) in combination with radiotherapy exhibited clinical anti-tumoral effects accompanied by acceptable side effects. Results: The outpatient chemotherapy regimen was tolerated without major side effects and produced good response rates. All patients achieved at least tumor stabilization; four of five had a partial remission. Effects of therapy were usually seen in the first cycle of therapy but the responses were of short duration with an average interval of two months until progression. Conclusions: As combined radiochemotherapy with liposomal doxorubicin is well tolerated even in older patients with other illnesses and can be given on an outpatient basis, it is an attractive option for metastatic Merkel cell carcinoma. Based on response rate or overall survival, it offers no advantages compared to polychemotherapy. [source] Transgenic weed beets: possible, probable, avoidable?JOURNAL OF APPLIED ECOLOGY, Issue 4 2002Benoît Desplanque Summary 1Weed beets pose a serious problem for sugar beet Beta vulgaris crops. Traditionally, the only efficient method of weed control has been manual removal, but the introduction of transgenic herbicide-tolerant sugar beets may provide an alternative solution because non-tolerant weed beets can be destroyed by herbicide. We evaluated the possibility that new, transgenic, weed beets may arise by gene flow between wild and crop plants. 2In a study area in northern France, weed beets were present in variable densities in sugar beet fields of up to 80 weed beet plants m,2. Weed beets arise from a long-lived seed bank, with seeds germinating from depths of 5 cm or less. In addition, diploid F1 crop,wild hybrids and triploid variety bolters (individuals with a low vernalization requirement) were present in low densities in virtually all sugar beet fields. We found gene flow to be possible between all forms, illustrated by both overlapping flowering periods in the field and successful controlled cross-pollinations. 3The F1 crop,wild hybrids result from pollination in the seed-production region by wild plants possessing the dominant bolting allele B for flowering without experiencing a period of cold. In the case of a transgene for herbicide tolerance incorporated into male-sterile seed-bearer plants, such hybrids will contain both the herbicide-tolerance and the bolting allele. Contamination of the fields by transgenic weed beets will be the result unless bolters are removed manually. The same will apply in the case of a cytoplasmically inherited transgene. 4Incorporation of the transgene into the pollinator plants will prevent the immediate formation of transgenic weed beets. However, in sugar beet fields, variety bolters may successfully cross-pollinate with weed beets in neighbouring fields. The use of diploid pollinator plants instead of tetraploids will considerably enhance gene flow towards wild beets, and is not, therefore, an attractive option. 5In conclusion, the appearance of transgenic weed beets is possible but can best be retarded if the transgene for herbicide tolerance is incorporated into the tetraploid pollinator breeding line. [source] Lipase-catalyzed production of biodiesel from rice bran oilJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 3 2005Chao-Chin Lai Abstract Biodiesel has attracted considerable attention as an alternative fuel during the past decades. The main hurdle to the commercialization of biodiesel is the cost of the raw material. Use of an inexpensive raw material such as rice bran oil is an attractive option to lower the cost of biodiesel. Two commercially available immobilized lipases, Novozym 435 and IM 60, were employed as catalyst for the reaction of rice bran oil and methanol. Novozym 435 was found to be more effective in catalyzing the methanolysis of rice bran oil. Methanolysis of refined rice bran oil and fatty acids (derived from rice bran oil) catalyzed by Novozym 435 (5% based on oil weight) can reach a conversion of over 98% in 6 h and 1 h, respectively. Methanolysis of rice bran oil with a free fatty acid content higher than 18% resulted in lower conversions (<68%). A two-step lipase-catalyzed methanolysis of rice bran oil was developed for the efficient conversion of both free fatty acid and acylglycerides into fatty acid methyl ester. More than 98% conversion can be obtained in 4,6 h depending on the relative proportion of free fatty acid and acylglycerides in the rice bran oil. Inactivation of lipase by phospholipids and other minor components was observed during the methanolysis of crude rice bran oil. Simultaneous dewaxing/degumming proved to be efficient in removing phospholipids and other minor components that inhibit lipase activity from crude rice bran oil. Copyright © 2005 Society of Chemical Industry [source] Comprehensive process design study for layered-NOX -control in a tangentially coal fired boilerAICHE JOURNAL, Issue 3 2010Wei Zhou Abstract As emissions regulations for coal-fired power plants become stricter worldwide, layering combustion modification and post-combustion NOX control technologies can be an attractive option for efficient and cost-effective NOX control in comparison to selective catalytic reduction (SCR) technology. The layered control technology approach designed in this article consists of separate overfire air (SOFA), reburn, and selective noncatalytic reduction (SNCR). The combined system can achieve up to 75% NOX reduction. The work presented in this article successfully applied this technology to NRG Somerset Unit 6, a 120-MW tangential coal-fired utility boiler, to reduce NOX emissions to 0.11 lb/MMBtu (130 mg/Nm3), well under the US EPA SIP Call target of 0.15 lb/MMBtu. The article reviews an integrated design study for the layered system at Somerset and evaluates the performance of different layered-NOX -control scenarios including standalone SNCR (baseline), separated overfire air (SOFA) with SNCR, and gas reburn with SNCR. Isothermal physical flow modeling and computational fluid dynamics simulation (CFD) were applied to understand the boiler flow patterns, the combustible distributions and the impact of combustion modifications on boiler operation and SNCR performance. The modeling results were compared with field data for model validation and verification. The study demonstrates that a comprehensive process design using advanced engineering tools is beneficial to the success of a layered low NOX system. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Characterisation of an inclusion complex between cladribine and 2-hydroxypropyl-,-cyclodextrin,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2008Valeria Van Axel Castelli Abstract Parenterally administered cladribine (2-chloro-2,-deoxyadenosine) has demonstrated promising efficacy and safety in clinical trials in patients with multiple sclerosis (MS). An oral formulation of this small molecule would be an attractive option for patients. Here, we describe the chemical characterisation of the inclusion complex between cladribine and the drug carrier molecule 2-hydroxypropyl-,-cyclodextrin (2-HP-,-CD). Several techniques were used to analyse the complex both in solution and in the solid state. These analyses provided evidence that the inclusion complex cannot be simply reduced to the sum of the two species, as it shows behaviour different from that of the physical mixture of the two components. Furthermore, solution nuclear magnetic resonance spectroscopy demonstrated the existence of an inclusion complex between cladribine and 2-HP-,-CD. Importantly, analysis of a tablet formulation demonstrated that the chemical characteristics of the inclusion complex are not affected by the manufacturing process, and that the complex is stable during storage. This tablet formulation is currently under investigation for the treatment of patients with MS. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3897,3906, 2008 [source] Use of perfluorocarbon (fluorinert) to enhance reporter gene expression following intratracheal instillation into the lungs of Balb/c mice: Implications for nebulized delivery of plasmidsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2001Aditya Das Abstract Perfluorocarbons combine high respiratory gas dissolving capabilities with extreme chemical and biological inertness and therefore offer an attractive option as an excipient in the area of pulmonary therapeutics. Perfluorocarbons have also been shown to ,float' mucus, because of their high densities (1.9,2.5 g/mL), which may hold potential in gene delivery for cystic fibrosis patients, in terms of enhancing penetration through highly viscous mucus and thereby providing access to target epithelial cells to correct the gene defect. Additionally, their low surface tension allows for better dispersion. A commonly available perflurocarbon, heptacosafluorotributylamine (Fluorinert), was used to deliver either plasmid DNA (pDNA) alone or cationic-lipid-complexed plasmid DNA to the lungs of Balb/c mice by direct intratracheal instillation. The complexes consisted of supercoiled (SC) plasmid DNA (4.7 Kb, 0.625 mg/mL) and lipid (ethyldimyristoyl phosphatidylcholine [EDMPC]/cholesterol [1:1 mole ratio], with pDNA (3:1 mg pDNA/mM EDMPC in 20 mM Tris-HCl pH 8.0) expressing chloramphenicol acetyl transferase (CAT) or ,-galactosidase (,-Gal). pDNA alone was supplemented with 14% w/v Fluorinert. Cationic lipid/pDNA complexes were supplemented with 3, 8, and 14% w/v Fluorinert. Results showed that the CAT expression from pDNA alone was enhanced 24,× using 14% w/v Fluorinert, whereas that from the cationic-lipid-formulated pDNA was enhanced 7,× using 14% w/v Fluorinert. Immunohistochemistry showed that ,-Gal expression was primarily from epithelial cells and not from F4/80 or MAC3 antigen-stained cells (predominantly macrophages), indicating efficient delivery. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1336,1344, 2001 [source] On the Cost of Adverse Selection in Individual Annuity Markets: Evidence From SingaporeJOURNAL OF RISK AND INSURANCE, Issue 2 2002Wai Mun Fong New evidence is presented on the cost of adverse selection in individual annuity markets using Singapore data. The Singapore annuity market is an interesting setting to examine the cost of adverse selection for three reasons. First, unlike many Western countries, the Singapore government provides very limited public financial assistance for retirees. Second, while social security contributions mandated under the Central Provident Fund (CPF) result in a high forced savings rate, a large proportion of CPF savings, are used up for housing. Third, to ensure that retirees have sufficient funds to meet basic needs, individuals who reach age 55 are required to set aside a minimum amount of their CPF savings, which can be withdrawn at age 62. The CPF Board allows various options for investing the minimum sum, but the most attractive option is to purchase an annuity. The institutional setting in Singapore in effect provides insurers with a large captive market for annuities. It is conjectured that this should be reflected in a significantly lower cost of adverse selection for annuities sold in Singapore as compared with other countries. The results herein, using data for CPF-approved insurers, are strongly consistent with this conjecture. On average, money's worth of annuities is higher than annuities sold to a similar age-gender mix in the United States, United Kingdom, and Australia. Adverse selection accounts for less than 13 percent of the cost of longevity insurance compared to 30,50 per- cent documented in many previous studies. These results suggest that one way to resolve the adverse selection problem is to adopt a universal individual defined contribution pension scheme that mandates or provides strong incentives for retirees to purchase annuities. [source] Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancerLASERS IN SURGERY AND MEDICINE, Issue 5 2006K.L. Du MD Abstract Background and Objectives Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. Study Design/Materials and Methods We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. Results We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. Conclusions PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution. Lasers Surg. Med. 38:427,434, 2006. © 2006 Wiley-Liss, Inc. [source] The Cogeneration Potential of the Sugar Industry in VietnamOPEC ENERGY REVIEW, Issue 1 2004Subhes C. Bhattacharyya Vietnam produces about 15 million tons of sugarcane per year and about five mt of bagasse. There is the potential for cogeneration using bagasse, which can also help overcome power shortages in the country. This paper analyses the potential for cogeneration from the sugar industry in Vietnam under three different scenarios and finds that between 100 and 300 megawatts of power-generating capacity could be supported by the bagasse generated from sugar mills, depending on the technology considered for sugar mills and cogeneration and the possibility of renovation of the existing mills. The paper also assesses the expense of cogeneration and finds it to be a cost-effective option for all types of sugar mill. It is found that the cost savings from cogeneration would more than offset the cost of introducing cogeneration in sugar mills with inefficient caneprocessing technologies. Sugar mills with modern technologies would have a significant amount of excess power and most of these plants would break-even if they sold excess power at around 4.5 cents per kilowatt hour. The break-even cost and the average production cost are sensitive to the investment cost assumptions. The paper thus suggests that cogeneration from the sugar industry is an attractive option for investors in existing mills or new sugar mills alike. [source] WHAT ARE DESIRES GOOD FOR?RATIO, Issue 3 2006TOWARDS A COHERENT ENDORSEMENT THEORY Desire-based theories of well-being are often said to accept (G), x is good for a person just in case he wants it, and (B), x is better for a person than y just in case he prefers x to y. I shall argue that (G) and (B) are inconsistent, and this inconsistency resists any plausible refinement of these principles. The inconsistency is brought out by cases in which our wants and preferences for certain life-options are contingent on which life-option we realize. My argument can be generalized to endorsement theories that define a person's good as the right combination of some kind of objective desirability and subjective endorsement, and allow preferences to be tie-breakers when the compared objects are equally desirable (or incommensurable). My conclusions will not just be negative. I shall argue that if the choice is between (G) and (B), the most attractive option is to keep (G), slightly refined, and drop (B).1 [source] Rational development of a HIV-1 gene therapy vectorTHE JOURNAL OF GENE MEDICINE, Issue 10 2003D. S. Anson Abstract Background HIV-1 provides an attractive option as the basis for gene transfer vectors due to its ability to stably transduce non-cycling cell populations. In order to fully utilise the promise of HIV-1 as a vector it is important that the effects of viral cis sequence elements on vector function are carefully delineated. Methods In this study we have systematically evaluated the effect of various cis elements from the HIV-1 YU-2 genome that have been implicated as either affecting vector performance, or HIV-1 replication, on the efficiency of vector production (titre and infectivity). As a measure of the relative safety of vectors their propensity to inadvertently transfer the gagpol gene to transduced cells was assessed. Results Sequences that were found to increase vector titre were from the 5, end of the gag gene, from the 5, and 3, ends of the env gene, from immediately upstream of the polypurine tract, and the central polypurine tract. The substitution of the HIV-1 RRE with heterologous RNA transport elements, or the deletion of the RRE, resulted in greatly reduced vector titres. RNA analysis suggested that the role of the Rev/RRE system extends beyond simply acting as an RNA nuclear export signal. The relative safety of different vector designs was compared and an optimal construct selected. Conclusions Based on our results we have constructed a vector that is both more efficient, and has better safety characteristics, than the widely used pHR, HIV-1 vector construct. Copyright © 2003 John Wiley & Sons, Ltd. [source] Improving the Procedure for Detection of Intrahepatic Transplanted Islets by Magnetic Resonance ImagingAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009M. L. Malosio Islet transplantation is an effective therapy for restoring normoglycemia in type-1 diabetes, but long-term islet graft function is achieved only in a minority of cases. Noninvasive magnetic resonance imaging of pancreatic islets is an attractive option for "real-time" monitoring of graft evolution. So far, previous studies have been performed in the absence of a standardized labeling procedure and, besides a feasibility study in patients, the effectiveness and safety of various labeling approaches were tested only with high field magnets (4.7 T). In this study, we addressed: (a) standardization of a labeling procedure for human islets with clinically-approved contrast agent Endorem®, (b) safety aspects of labeling related to inflammation and (c) quality of imaging both at 7 T and 1.5 T. We have highlighted that the ratio of Endorem®/islet is crucial for reproducible labeling, with a ratio of 2.24 ug/IEQ, allowing successful in vivo imaging both with 1.5 T and 7.0 T magnets up to 143 days after intrahepatic transplant. With this standardized labeling procedure, labeled islets are neither inflamed nor more susceptible to inflammatory insults than unlabeled ones. This report represents an important contribution towards the development of a standardized and safe clinical protocol for the noninvasive imaging of transplanted islets in humans. [source] Animal behaviour and marine protected areas: incorporating behavioural data into the selection of marine protected areas for an endangered killer whale populationANIMAL CONSERVATION, Issue 2 2010E. Ashe Abstract Like many endangered wildlife populations, the viability and conservation status of ,southern resident' killer whales Orcinus orca in the north-east Pacific may be affected by prey limitation and repeated disturbance by human activities. Marine protected areas (MPAs) present an attractive option to mitigate impacts of anthropogenic activities, but they run the risk of tokenism if placed arbitrarily. Notwithstanding recreational and industrial marine traffic, the number of commercial vessels in the local whalewatching fleet is approaching the number of killer whales to be watched. Resident killer whales have been shown to be more vulnerable to vessel disturbance while feeding than during resting, travelling or socializing activities, therefore protected-areas management strategies that target feeding ,hotspots' should confer greater conservation benefit than those that protect habitat generically. Classification trees and spatially explicit generalized additive models were used to model killer whale habitat use and whale behaviour in inshore waters of Washington State (USA) and British Columbia (BC, Canada). Here we propose a candidate MPA that is small (i.e. a few square miles), but seemingly important. Killer whales were predicted to be 2.7 times as likely to be engaged in feeding activity in this site than they were in adjacent waters. A recurring challenge for cetacean MPAs is the need to identify areas that are large enough to be biologically meaningful while being small enough to allow effective management of human activities within those boundaries. Our approach prioritizes habitat that animals use primarily for the activity in which they are most responsive to anthropogenic disturbance. [source] Managed Care expansion to Asia: a critical reviewASIAN-PACIFIC ECONOMIC LITERATURE, Issue 2 2009Daniel Simonet The paper examines the concept of Managed Care as practised in Southeast Asia and argues that Managed Care insurers are unlikely to spread further. The first part of the paper reviews individual country experience (Indonesia, Philippines, Malaysia, Hong Kong and Singapore) followed by a summary of difficulties that Managed Care has encountered. Among these are increasing public defiance, opposition by physicians and the already low costs that are unlikely to make Managed Care an attractive option. [source] Imputation Strategies for Missing Continuous Outcomes in Cluster Randomized TrialsBIOMETRICAL JOURNAL, Issue 3 2008Monica Taljaard Abstract In cluster randomized trials, intact social units such as schools, worksites or medical practices , rather than individuals themselves , are randomly allocated to intervention and control conditions, while the outcomes of interest are then observed on individuals within each cluster. Such trials are becoming increasingly common in the fields of health promotion and health services research. Attrition is a common occurrence in randomized trials, and a standard approach for dealing with the resulting missing values is imputation. We consider imputation strategies for missing continuous outcomes, focusing on trials with a completely randomized design in which fixed cohorts from each cluster are enrolled prior to random assignment. We compare five different imputation strategies with respect to Type I and Type II error rates of the adjusted two-sample t -test for the intervention effect. Cluster mean imputation is compared with multiple imputation, using either within-cluster data or data pooled across clusters in each intervention group. In the case of pooling across clusters, we distinguish between standard multiple imputation procedures which do not account for intracluster correlation and a specialized procedure which does account for intracluster correlation but is not yet available in standard statistical software packages. A simulation study is used to evaluate the influence of cluster size, number of clusters, degree of intracluster correlation, and variability among cluster follow-up rates. We show that cluster mean imputation yields valid inferences and given its simplicity, may be an attractive option in some large community intervention trials which are subject to individual-level attrition only; however, it may yield less powerful inferences than alternative procedures which pool across clusters especially when the cluster sizes are small and cluster follow-up rates are highly variable. When pooling across clusters, the imputation procedure should generally take intracluster correlation into account to obtain valid inferences; however, as long as the intracluster correlation coefficient is small, we show that standard multiple imputation procedures may yield acceptable type I error rates; moreover, these procedures may yield more powerful inferences than a specialized procedure, especially when the number of available clusters is small. Within-cluster multiple imputation is shown to be the least powerful among the procedures considered. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Logistic Equations Effectively Model Mammalian Cell Batch and Fed-Batch Kinetics by Logically Constraining the FitBIOTECHNOLOGY PROGRESS, Issue 4 2005Chetan T. Goudar A four-parameter logistic equation was used to fit batch and fed-batch time profiles of viable cell density in order to estimate net growth rates from the inoculation through the cell death phase. Reduced three-parameter forms were used for nutrient uptake and metabolite/product formation rate calculations. These logistic equations constrained the fits to expected general concentration trends, either increasing followed by decreasing (four-parameter) or monotonic (three-parameter). The applicability of this approach was first verified for Chinese hamster ovary (CHO) cells cultivated in 15-L batch bioreactors. Cell density, metabolite, and nutrient concentrations were monitored over time and used to estimate the logistic parameters by nonlinear least squares. The logistic models fit the experimental data well, supporting the validity of this approach. Further evidence to this effect was obtained by applying the technique to three previously published batch studies for baby hamster kidney (BHK) and hybridoma cells in bioreactors ranging from 100 mL to 300 L. In 27 of the 30 batch data sets examined, the logistic models provided a statistically superior description of the experimental data than polynomial fitting. Two fed-batch experiments with hybridoma and CHO cells in benchtop bioreactors were also examined, and the logistic fits provided good representations of the experimental data in all 25 data sets. From a computational standpoint, this approach was simpler than classical approaches involving Monod-type kinetics. Since the logistic equations were analytically differentiable, specific rates could be readily estimated. Overall, the advantages of the logistic modeling approach should make it an attractive option for effectively estimating specific rates from batch and fed-batch cultures. [source] Use of IL-2 receptor antagonists to reduce delayed graft function following renal transplantation: a reviewCLINICAL TRANSPLANTATION, Issue 6 2005Silvio Sandrini Abstract:, Delayed graft function (DGF) occurs in approximately 30% of renal transplant patients, and significantly increases risk of long-term graft loss. This article reviews the potential for use of interleukin-2 receptor (IL-2R) antagonists to reduce the burden of DGF. IL-2R antagonists decrease incidence of acute rejection without increasing risk of cytomegalovirus infection or malignancy, and show equivalent efficacy to lymphocyte-depleting antibody agents in standard risk patients with immediate graft function. The nephrotoxicity associated with calcineurin inhibitors (CNIs) has led to use of delayed or low-dose CNI regimens with induction therapy in patients with DGF. In this setting, use of an IL-2R antagonist with mycophenolate mofetil and steroids with delayed cyclosporine appears to be associated with a low incidence of biopsy-proven rejection and comparable renal function to patients with immediate function. Additionally, there is intriguing evidence to suggests that IL-2R antagonists may reduce risk of DGF occurring. A number of large-scale and smaller studies have reported a trend to reduced incidence of DGF or improved early renal function using IL-2R antagonists compared with placebo, although data are not entirely consistent. In conclusion, the ability of IL-2R antagonists to reduce acute rejection with no additional safety concerns makes them an attractive option for patients with DGF. [source] Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced complianceJOURNAL OF INTERNAL MEDICINE, Issue 4 2008S. Boonen Abstract. Bisphosphonates are the current mainstay of treatment for postmenopausal osteoporosis. Although daily oral dosing is effective, it is associated with poor compliance, partly because of the pre and postdose fasting and posture requirements. This negatively impacts treatment outcomes, leading to a reduced clinical benefit. Improved, yet still suboptimal adherence has been noticed with less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral regimens. The recently approved quarterly intravenous (i.v.) injection regimen of ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in the management of postmenopausal osteoporosis. These regimens may assure quarterly and year long compliance. [source] | ||||||||||||||||||||||