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Care ethics is an alternative to the better known approaches based on normative principles or virtue. The care ethic is grounded in relationships intended to build others' potential. Five suggestions are offered for applying care ethics in the practice context.
Often, information from a single database cannot answer important clinical outcomes or research questions. This article describes efforts to link multiple databases to extract useful health care information. One project, conducted by the Keystone Peer Review Organization (KePRO), focused on the number of combined right and left heart catheterizations done in patients, who were admitted to the hospital for a diagnostic left heart catheterization, for primary coronary artery disease. The study linked data from hospital billing records, patient records, and insurance companies' records. Another effort involves two studies of Acute Myocardial Infarction (AMI) by KePRO and Pennsylvania Health Care Cost Containment Council. The final case study describes the Crash Outcomes Data Evaluations Systems (CODES) project, conducted by the Pennsylvania Department of Health. To determine if seat belts help to prevent injuries, cut costs, and save lives, it was necessary to build a complete record across multiple sights of care from the crash until final outcome. These examples illustrate the challenges and the advantages of using multiple databases to assess health care outcomes.
The Monte Carlo code PENELOPE has been used to simulate photon flux from the Leksell Gamma Knife, a precision method for treating intracranial lesions. Radiation from a single 6OCo assembly traversing the collimator system was simulated, and phase space distributions at the output surface of the helmet for photons and electrons were calculated. The characteristics describing the emitted final beam were used to build a two-stage Monte Carlo simulation of irradiation of a target. A dose field inside a standard spherical polystyrene phantom, usually used for Gamma Knife dosimetry, has been computed and compared with experimental results, with calculations performed by other authors with the use of the EGS4 Monte Carlo code, and data provided by the treatment planning system Gamma Plan. Good agreement was found between these data and results of simulations in homogeneous media. Owing to this established accuracy, PENELOPE is suitable for simulating problems relevant to stereotactic radiosurgery.
This study examines the potential reuse of textile effluent treatment plant (ETP) sludge in building materials. The physico-chemical and engineering properties of a composite textile sludge sample from the southern part of India have been studied. The tests were conducted as per Bureau of Indian Standards (BIS) specification codes to evaluate the suitability of the sludge for structural and non-structural application by partial replacement of up to 30% of cement. The cement-sludge samples failed to meet the required strength for structural applications. The strength and other properties met the Bureau of Indian Standards for non-structural materials such as flooring tiles, solid and pavement blocks, and bricks. Results generally meet most ASTM standards for non-structural materials, except that the sludge-amended bricks do not meet the Grade NW brick standard. It is concluded that the substitution of textile ETP sludge for cement, up to a maximum of 30%, may be possible in the manufacturing of non-structural building materials. Detailed leachability and economic feasibility studies need to be carried out as the next step of research.
Molecular dynamics simulations without explicit inclusion of solvent molecules have been performed to study the motions of Lewisa and Lewisb blood group oligosaccharides, and two blood group A tetrasaccharides having type I and type II core chains. The blood group H trisaccharide has also been studied and compared with the blood group A type II core chain. The potential energy surface developed by Rasmussen and co-workers was used with the molecular mechanics code CHARMM. The lowest energy minima of the component disaccharide fragments were obtained from conformational energy mapping. The lowest energy minima of these disaccharide fragments were used to build the tri- and tetrasaccharides that were further minimized before the actual heating/equilibration and dynamics simulations. The trajectories of the disaccharide fragments, e.g., Fuc alpha- (1----4)GlcNAc, Gal beta-(1----4)GlcNAc, etc., show transitions among various minima. However, the oligosaccharides were found to be dynamically stable and no transitions to other minimum energy conformations were observed in the time series of the glycosidic dihedral angles even during trajectories as long as 300 ps. The stable conformations of the glycosidic linkages in the oligosaccharides are not necessarily the same as the minimum energy conformation of the corresponding isolated disaccharides. The average fluctuations of the glycosidic angles in the oligosaccharides were well within the range of +/- 15 degrees. The results of these trajectory calculations were consistent with the relatively rigid single-conformation models derived for these oligosaccharides from 1H-nmr data.
Inhibitors of farnesyl-protein transferase (FPTase) show promise as anticancer agents. Based on the sequence of the protein substrates of FPTase (the CAAX sequence), potent and selective peptidomimetic inhibitors have been developed; these compounds share with the peptide substrate a free thiol and a C-terminal carboxylate. We have used a synthetic tetrapeptide combinatorial library to screen for new leads devoid of these features: the peptides were C-terminally amidated, and no free thiol was included in the combinatorial building blocks. To compensate for this negative bias, an expanded set of 68 amino acids was used, including both L and D as well as many non-coded residues. Sixteen individual tetrapeptides derived from the consensus were synthesized and tested; all were active, showing IC50 values ranging from low micromolar to low nanomolar. The most active peptide, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid (Ki = 2 nM), is also very selective showing little inhibitory activity against the related enzyme geranylgeranyl-protein transferase type I (IC50 > 50 microM). In contrast to CAAX-based peptidomimetics, D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma-carboxyglut amic acid appeared to mimic the isoprenoid substrate farnesyl diphosphate as determined by kinetic and physical measurements. D-Tryptophan-Dmethionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid was a competitive inhibitor of FPTase with respect to farnesyl diphosphate substrate and uncompetitive with respect to CAAX substrate. Furthermore, we demonstrated that FPTase undergoes ligand dependent conformational changes in its circular dichroism spectrum and that D-tryptophan-D-methionine-D-4-chlorophenylalanine-L-gamma- carboxyglutamic acid induced a conformational change identical to that observed with farnesyl diphosphate ligand.
MOTIVATION: An important application of microarray technology is to predict various clinical phenotypes based on the gene expression profile. Success has been demonstrated in molecular classification of cancer in which different types of cancer serve as categorical outcome variable. However, there has been less research in linking gene expression profile to censored survival outcome such as patients' overall survival time or time to cancer relapse. In this paper, we develop a partial Cox regression method for constructing mutually uncorrelated components based on microarray gene expression data for predicting the survival of future patients. RESULTS: The proposed partial Cox regression method involves constructing predictive components by repeated least square fitting of residuals and Cox regression fitting. The key difference from the standard principal components of Cox regression analysis is that in constructing the predictive components, our method utilizes the observed survival/censoring information. We also propose to apply the time-dependent receiver operating characteristic curve analysis to evaluate the results. We applied our methods to a publicly available dataset of diffuse large B-cell lymphoma. The outcomes indicated that combining the partial Cox regression method with principal components analysis results in parsimonious model with fewer components and better predictive performance. We conclude that the proposed partial Cox regression method can be very useful in building a parsimonious predictive model that can accurately predict the survival of future patients based on the gene expression profile and survival times of previous patients. AVAILABILITY: R codes are available upon request.
Cells are organized through the interactions of proteins with one another, and with phospholipids, nucleic acids and small molecules, suggesting a molecular recognition code for cell assembly. These interactions are mediated by a set of conserved protein interaction domains, which regulate the dynamic behaviour of the cell, and are used to build protein complexes and networks with emergent properties. Cell regulatory proteins have a modular architecture, which may have facilitated the evolution of new signalling pathways, and is exploited by pathogenic micro-organisms and chimeric oncoproteins to re-specify cellular function.
The aim of this work was the Monte Carlo (MC) simulation of the response of commercially available dosimeters based on metal oxide semiconductor field effect transistors (MOSFETs) for radiotherapeutic photon beams using the PENELOPE code. The studied Thomson&Nielsen TN-502-RD MOSFETs have a very small sensitive area of 0.04 mm(2) and a thickness of 0.5 microm which is placed on a flat kapton base and covered by a rounded layer of black epoxy resin. The influence of different metallic and Plastic water build-up caps, together with the orientation of the detector have been investigated for the specific application of MOSFET detectors for entrance in vivo dosimetry. Additionally, the energy dependence of MOSFET detectors for different high-energy photon beams (with energy >1.25 MeV) has been calculated. Calculations were carried out for simulated 6 MV and 18 MV x-ray beams generated by a Varian Clinac 1800 linear accelerator, a Co-60 photon beam from a Theratron 780 unit, and monoenergetic photon beams ranging from 2 MeV to 10 MeV. The results of the validation of the simulated photon beams show that the average difference between MC results and reference data is negligible, within 0.3%. MC simulated results of the effect of the build-up caps on the MOSFET response are in good agreement with experimental measurements, within the uncertainties. In particular, for the 18 MV photon beam the response of the detectors under a tungsten cap is 48% higher than for a 2 cm Plastic water cap and approximately 26% higher when a brass cap is used. This effect is demonstrated to be caused by positron production in the build-up caps of higher atomic number. This work also shows that the MOSFET detectors produce a higher signal when their rounded side is facing the beam (up to 6%) and that there is a significant variation (up to 50%) in the response of the MOSFET for photon energies in the studied energy range. All the results have shown that the PENELOPE code system can successfully reproduce the response of a detector with such a small active area.
We evaluated wiring in multifamily developments containing National Electrical Code(R) (NEC(R)) violations as a source of unusual exposure to 60 Hz magnetic fields. Two methods were used in this evaluation: measurement and modeling. We measured the building wiring as a source of magnetic fields in six multifamily developments in Michigan. In this small sample, building wiring proved to be an important source of exposure in four of the six cases. In all four cases with exposure from building wiring, one or more NEC violations were involved. To supplement our measurement efforts, we used computer modeling to compare magnetic field exposure due to building wiring with magnetic field exposure from external power lines. Our calculations showed that where the building wiring has a NEC violation leading to net current loops, the exposure due to wiring is likely to be more important than that from external power lines. Our results support the results obtained in a recent study of the exposure of Californian K-12 students to magnetic fields, where building wiring with one or more NEC violation was found to be the single most important exposure source. If 60 Hz magnetic fields are important to avoid, then improved enforcement of the NEC, as required by law, is perhaps the single most important mitigation policy to adopt. Bioelectromagnetics 25:102-106, 2004.
The flaviviruses comprise a number of arthropod-transmitted human disease agents that cause significant and increasing health threats in major parts of the world. The development of new vaccines is of vital importance, but the stringent need for safety, efficacy and cost-effectiveness together with the problems associated with the specific immune pathogenesis of some flavivirus infections impose significant challenges to innovative vaccine research. Using tick-borne encephalitis virus (TBEV) as a model, the viral capsid protein gene was recently identified as a novel target for generating flavivirus vaccines. This approach can be applied to produce either attenuated strains that can serve as live vaccines or to make a new type of a genetic vaccine consisting of non-infectious RNA replicons from which subviral particles are synthesized in vivo. Flaviviruses are small, enveloped viruses with an unsegmented positive-stranded RNA genome encoding a single polyprotein that is cleaved into the individual viral proteins. The specific introduction of various deletions and other mutations into the genomic segment coding for the capsid protein C and the biochemical and immunological characterization of the resulting mutants in cell culture and an animal model have revealed remarkable properties of this building block of the nucleocapsid and yielded information that opened the way for new vaccine approaches. In this review the in vitro and in vivo findings with various capsid deletion mutants of TBEV are summarized and discussed in the context of recent structural and biochemical data obtained for protein C of various flaviviruses. Potential benefits of this new strategy for generating flavivirus vaccines as well as hurdles that still have to be overcome are discussed in comparison to conventional or other experimental approaches. Capsid-deletion mutants can be used to rationally design safe and effective vaccine strains or to create new vaccines that combine advantages of genetic vaccination, conventional inactivated, and live vaccines.
Use of methyl bromide for pest control fumigation may result in adverse exposure to three populations: the actual fumigators; other workers not actually involved in the fumigation; and the general public in the vicinity. The risk of exposure of these three target populations in Switzerland was investigated. The methodology was a combination of occupational hygiene surveys, including a preliminary hazard analysis, with a comprehensive assessment of the safety and health systems in use based on the 'Management Oversight and Risk Tree' (MORT) method [Knox and Eicher, MORT User's Manual, Revision 2. DOE 76-45/4 (1983)]. The target populations most concerned depend on the type of fumigation. Fumigators risk severe accidental exposure although they usually wear personal protection devices. In soil and chamber fumigation, workers not involved in the fumigation may undergo high exposure (75-100 pm for 1 h), far greater than the usual time-weighted average and short-term occupational exposure limits (5-20 ppm range). Occupants of premises adjoining the fumigated buildings may also be exposed to significant concentrations (25-50 ppm for 0.1-2 h). Problems originate mainly from a lack of management controls, failure to apply an appropriate code of practice and the use of personnel who are not properly qualified and trained.
Linkage maps are limited by the number of recombinations that can be scored in human pedigrees to a resolution of ca. 1 centimorgan (relative distance between genes on a chromosome having a crossover value of 1%) which is estimated to be about 10 megabases. Molecular maps can be formed at any resolution down to the base sequence. To complement the linkage approach, the most useful molecular map would be one that helped to locate disease loci, by using restriction fragment length polymorphisms (RFLPS) and accurate localization of recombinations, and which then helped to find candidate genes in this region, by providing the positions of coding sequences. This paper discusses the appropriate form and scale of such a map, how it can be produced with methods now available, and the most efficient strategy for building the map, based on present knowledge of the organization of the human genome.
Loss of electronic equilibrium in lung tissue causes a build-up region in the tumor. Increasing the photon energy increases the depth at which electronic equilibrium is reestablished within the lung tumor. This study uses the Monte Carlo code PENELOPE for simulations of radiation treatment of tumor surrounded by lung. Six MV photons were compared to 15 MV photons using four beam arrangements in both homogeneous and heterogeneous media. The experimental results demonstrate that for every beam arrangement in heterogeneous media 15 MV photons delivered 5% to 10% lower dose to the tumor periphery than 6 MV photons. The simulations also show that in axial coplanar treatment plans, the loss of electronic equilibrium was greatest in the coronal plane. In conclusion there is a tumor sparing effect at the tumor-lung interface that is a function of beam energy. As an alternative to increasing beam energy, the addition of multiple beam angles with lower energy photons improved target coverage. If higher energy beams are required for patients with large separation, then adding multiple beam angles does offer some improved target coverage. The non-coplanar technique with the lower energy photons covered the tumor with a greatest isodose at the tumor periphery without tangential sparing in the coronal plane.
This is a 1999 update of an original article based on 1989-90 data published in the Journal of Hospital Marketing. The adoption of hospital information technologies shows that most of these technologies were no longer in the innovator or early adopter stages. Infrastructure building technologies such as clinical information links, PC networking with the mainframe, MD links between doctors and hospital and E-mail showed the highest percentage of increase. Bar coding for inventory (transactional) also made great increases. Opinions on barriers to the adoption of hospital information technology are ranked and are studied by age of respondent, public vs. private hospitals, and job function.
International monitoring of the ICIDH has begun in earnest. The momentum from these new activities and organizations has worked towards the unification and harmonization of statistics and information devoted to the study of disablement, further enhancing the interdisciplinary nature of the study of disability and advancing its recognition both at the national and international level. This article introduces the reader to the definitions and concepts of the ICIDH. In addition, problems confronted when applying the ICIDH in policy formulation, programme implementation and evaluation and in research are reviewed. There are three main types of problem: (i) the difficulty in differentiating each of the concepts of impairment, disability and handicap at the operational level of human function and behaviour; (ii) the diversity of training and instructions required in order to orchestrate the use of the codes and classification schemes with persons having a wide range of expertise and analytical interests; and (iii) the need for consistency of use of the ICIDH for model-building and testing of different theoretical frameworks. Increased institutional development at the global level through the establishment of international networks, and regional and interregional programmes, have further clarified strengths and weaknesses of the ICIDH and have increased support of its use. These efforts suggest the increasing importance of the ICIDH for the future development of international statistical standards and recommendations in the field of disablement.
The electronic medical record (EMR), while having acknowledged advantages over the paper record and powerful constituencies advocating its adoption, is not in widespread use. One significant obstacle to its acceptance by physicians has not been addressed--its failure to provide easy input for the patients exact diagnoses and for the retrieval of those diagnoses during subsequent patient care. Furthermore, our system designers have failed to respond to the expansion of the use of the medical record from its origin as simply the physician's memory and communication tool to becoming the building block for our Medical Record Health Information System (MRHIS), where it also supplies the justification for payment for care and is the source of fundamental statistics about health and healthcare. These problems reflect a basic flaw in the application of available information technology to EMR design and data management: We use output codes--the category codes from ICD-9-CM--for input of diagnoses. This fact imposes the tyranny. Our medical record must have these ICD-9-CM codes for the reimbursement system. But, to be accepted as the basic record for medical care, and at the same time, to be truly useful for case retrieval and statistics, medical informatics experts recognize that our EMR must have codes for the exact diagnoses of the patient (diagnosis entities). But no practical method for their input and management has been offered This paper proposes a way to provide easy input of diagnosis entities, and their permanent coding as a workable solution to the problem.
The CCA-adding enzyme builds and repairs the 3' terminus of tRNA. Approximately 65% of mature human U2 small nuclear RNA (snRNA) ends in 3'-terminal CCA, as do all mature tRNAs; the other 35% ends in 3' CC or possibly 3' C. The 3'-terminal A of U2 snRNA cannot be encoded because the 3' end of the U2 snRNA coding region is CC/CC, where the slash indicates the last encoded nucleotide. The first detectable U2 snRNA precursor contains 10-16 extra 3' nucleotides that are removed by one or more 3' exonucleases. Thus, if 3' exonuclease activity removes the encoded 3' CC during U2 snRNA maturation, as appears to be the case in vitro, the cell may need to build or rebuild the 3'-terminal A, CA, or CCA of U2 snRNA. We asked whether homologous and heterologous class I and class II CCA-adding enzymes could add 3'-terminal A, CA, or CCA to human U2 snRNA lacking 3'-terminal A, CA, or CCA. The naked U2 snRNAs were good substrates for the human CCA-adding enzyme but were inactive with the Escherichia coli enzyme; activity was also observed on native U2 snRNPs. We suggest that the 3' stem/loop of U2 snRNA resembles a tRNA minihelix, the smallest efficient substrate for class I and II CCA-adding enzymes, and that CCA addition to U2 snRNA may take place in vivo after snRNP assembly has begun.