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PubMed2000

Treatment of the abdominal wall defects in an ambulatory surgical setting: our experience.

Introduction: The creation of Outpatient Surgery (OPS) units has allowed to reduce the costs and the waiting lists in an efficient fashion. We describe our series of patients operated on for abdominal wall defects, a pathology suitable for ambulatory surgery. Patients and methods: Between May 1994 and March 1998, 206 inguinal hernias, 23 femoral hernias, 47 umbilical-epigastric hernias and nine incisional hernias were operated on in an ambulatory surgical setting. The patients were selected following the selection criteria previously established (related to the patient, the environment and the surgical procedure). The average age was 45 years, and the distribution by sex, 210 men and 75 women. Spinal anesthesia was preferently performed. The surgical techniques employed were Lichtenstein's hernioplasty and Shouldice and Bassini procedures for inguinal hernias; Lichtenstein's plug technique for femoral hernias and simple closure or preperitoneal mesh for the middle line defects. Results: 44 patients needed readmitttance to hospital (failure of OPS), the most important causes being excessive pain, urinary retention and nausea/vomiting. There was no severe morbidity nor mortality. Conclusion: Surgery for abdominal wall defects constitutes a group of procedures suitable for efficient and low risk OPS programs.

Journal Article↗
PubMed2003

Finding signals for plant promoters.

The strongest signal of plant promoter is searched with the model of single motif with two types. It turns out that the dominant type is the TATA-box. The other type may be called TATA-less signal, and may be used in gene finders for promoter recognition. While the TATA signals are very close for the monocot and the dicot, their TATA-less signals are significantly different. A general and flexible multi-motif model is also proposed for promoter analysis based on dynamic programming. By extending the Gibbs sampler to the dynamic programming and introducing temperature, an efficient algorithm is developed for searching signals in plant promoters.

Algorithms↗
PubMed2002

Managing risk, clinical error, and quality of care.

Clinical risk presents enormous challenges for the health profession and governments. Despite excellent national and regional programs focused on the management of obstetrical conditions and prevention of newborn injury, an environment of clinical error persists; according to Canadian Medical Protective Association data, each year 6% of Canadian obstetricians face a legal challenge, with most cases also involving nurses and hospitals. Principles and lessons learned from risk management developed in high reliability organizations (HROs), such as air traffic controllers and nuclear power plants, can be applied to risk management in perinatal/obstetrical units. In 2002, the Society of Obstetricians and Gynaecologists of Canada will launch an obstetrical risk management program called "Managing Obstetrical Risk Efficiently" (MORE), integrating labour and delivery clinical core content with HRO principles and reflective learning and practice modification tools designed to help all obstetrical caregivers build and maintain confidence and competency, improve patient safety and quality of care, and reduce clinical error and adverse events.

Canada↗
PubMed2004

Cost-effectiveness of digital photographic screening for retinopathy of prematurity in the United Kingdom.

OBJECTIVES: To compare the cost-effectiveness of alternative methods of screening for retinopathy of prematurity (ROP) in the United Kingdom, including the existing method of indirect ophthalmoscopy by ophthalmologists and digital photographic screening by nurses. METHODS: A decision tree model was used to compare five screening modalities for the UK population of preterm babies, using a health service perspective. Data were taken from published sources, observation at a neonatal intensive care unit (NICU), and expert judgment. RESULTS: We estimated that use of standard digital cameras by nurses in NICUs would cost more than current methods (pound 371 compared with pound 321 per baby screened). However, a specialist nurse visiting units with a portable camera would be cheaper (pound 172 per baby). These estimates rely on nurses capturing and interpreting the images, with suitable training and supervision. Alternatively, nurses could capture the images then transmit them to a central unit for interpretation by ophthalmologists, although we estimate that this would be rather more expensive (pound 390 and pound 201, respectively, for NICU and visiting nurses). Sensitivity analysis was used to examine the robustness of estimates. CONCLUSIONS: It is likely that there is an opportunity to improve the efficiency of the ROP screening program. We estimate that screening by specialist nurses trained in image capture and interpretation using portable digital cameras is a cost-effective alternative to the current program of direct visualization by ophthalmologists. This option would require the development of a suitable portable machine. Direct comparative research is strongly needed to establish the accuracy of the various screening options.

Cohort Studies↗
PubMedDate not supplied

Improving the performance of molecular dynamics simulations on parallel clusters.

In this article a procedure is derived to obtain a performance gain for molecular dynamics (MD) simulations on existing parallel clusters. Parallel clusters use a wide array of interconnection technologies to connect multiple processors together, often at different speeds, such as multiple processor computers and networking. It is demonstrated how to configure existing programs for MD simulations to efficiently handle collective communication on parallel clusters with processor interconnections of different speeds.

Journal Article↗
PubMedDate not supplied

Analysis of a large structure/biological activity data set using recursive partitioning.

Combinatorial chemistry and high-throughput screening are revolutionizing the process of lead discovery in the pharmaceutical industry. Large numbers of structures and vast quantities of biological assay data are quickly being accumulated, overwhelming traditional structure/activity relationship (SAR) analysis technologies. Recursive partitioning is a method for statistically determining rules that classify objects into similar categories or, in this case, structures into groups of molecules with similar potencies. SCAM is a computer program implemented to make extremely efficient use of this methodology. Depending on the size of the data set, rules explaining biological data can be determined interactively. An example data set of 1650 monoamine oxidase inhibitors exemplifies the method, yielding substructural rules and leading to general classifications of these inhibitors. The method scales linearly with the number of descriptors, so hundreds of thousands of structures can be analyzed utilizing thousands to millions of molecular descriptors. There are currently no methods to deal with statistical analysis problems of this size. An important aspect of this analysis is the ability to deal with mixtures, i.e., identify SAR rules for classes of compounds in the same data set that might be binding in different ways. Most current quantitative structure/activity relationship methods require that the compounds follow a single mechanism. Advantages and limitations of this methodology are presented.

Combinatorial Chemistry Techniques↗
PubMed2003

Optimization of the pharmacophore model for 5-HT7R antagonism. Design and synthesis of new naphtholactam and naphthosultam derivatives.

We present in this study an optimization of a preliminary pharmacophore model for 5-HT(7)R antagonism, with the incorporation of recently reported ligands and using an efficient procedure with the CATALYST program. The model consists of five features: a positive ionizable atom (PI), a H-bonding acceptor group (HBA), and three hydrophobic regions (HYD). This model has been supported by the design, synthesis, and biological evaluation of new naphtholactam and naphthosultam derivatives of general structure I (39-72). A systematic structure-affinity relationship (SAFIR) study on these analogues has allowed us to confirm that the model incorporates the essential structural features for 5-HT(7)R antagonism. In addition, computational simulation of the complex between compound 56 and a rhodopsin-based 3D model of the 5-HT(7)R transmembrane domain has permitted us to define the molecular details of the ligand-receptor interaction and gives additional support to the proposed pharmacophore model for 5-HT(7)R antagonism: (i) the HBA feature of the pharmacophore model binds Ser(5.42) and Thr(5.43), (ii) the HYD1 feature interacts with Phe(6.52), (iii) the PI feature forms an ionic interaction with Asp(3.32), and (iv) the HYD3 (AR) feature interacts with a set of aromatic residues (Phe(3.28), Tyr(7.43)). These results provide the tools for the design and synthesis of new ligands with predetermined affinities and pharmacological properties.

Animals↗
PubMed2004

Post-integration stabilization of a transposon vector by terminal sequence deletion in Drosophila melanogaster.

Germline transformation systems for nearly 20 insect species have been derived from transposable elements, allowing the development of transgenic insects for basic and applied studies. These systems use a defective nonautonomous vector that results in stable vector integrations after the disappearance of transiently provided transposase helper plasmid, which is essential to maintain true breeding lines and consistent transgene expression that would otherwise be lost after vector remobilization. The risk of remobilization by an unintended transposase source has so far not been a concern for laboratory studies, but the prospective use of millions of transgenic insects in biocontrol programs will likely increase the risk, therefore making this a critical issue for the ecological safety of field release programs. Here we describe an efficient method that deletes a terminal repeat sequence of a transposon vector after genomic integration. This procedure prevents transposase-mediated remobilization of the other terminal sequence and associated genes, ensuring their genomic stability.

Animals↗
PubMed2000

LC-NMR: a new tool to expedite the dereplication and identification of natural products.

The rapid identification of known or undesirable compounds from natural products extracts - "dereplication" - is an important step in an efficiently run natural products discovery program. Dereplication strategies use analytical techniques and database searching to determine the identity of an active compound at the earliest possible stage in the discovery process. In the past few years, advances in technology have allowed the development of tandem analytical techniques such as liquid chromatography mass spectrometry (LC-MS), LC-MS-MS, liquid chromatography nuclear magnetic resonance (LC-NMR), and LC-NMR-MS. LC-NMR, despite its lower sensitivity as compared to LC-MS, provides a powerful tool for rapid identification of known compounds and identification of structure classes of novel compounds. LC-NMR is especially useful in instances where the data from LC-MS are incomplete or do not allow confident identification of the active component of a sample. LC-NMR has been used to identify the marine alkaloid aaptamine as the active component in an extract of the sponge Aaptos sp. This extract had been identified as an enzyme inhibitor by a high throughput screening (HTS) effort. Isolated aaptamine exhibited an IC(50)=120 µM against this enzyme. Strategies for the identification of aaptamine and for the use of LC-NMR in a natural products HTS program are discussed.

Journal Article↗
PubMed2003

[Improvement of care for diabetics using the care model from Saxony].

BACKGROUND AND OBJECTIVE: By promoting the networking of all those involved in caring for diabetics in Saxony, through agreement between those who provide help to them and the organizations which pay the costs, the intention is to improve the overall quality of care of diabetics. It was the aim of this study to evaluate the effectiveness of this integrated health model. PATIENTS AND METHODS: As part of the 3rd Diabetes Agreement in Saxony, a total of 275,804 diabetics were registered, treated and their management costed in the first quarter of 2000 and the fourth quarter of 2001 (56.3% females, 43.7% males; median age 68,7 years). They were patients of 2800 general practitioners and 88 specialist practices. RESULTS: Nearly 80% of all diabetics were included. Taking the level of HbA1c as the criterion of quality achieved, it had decreased from 7,1 +/- 1,3 % in the first 3 months of 2000 to 6,8 +/- 1,3 % in the last 3 months of 2001, and regional differences had been reduced. There was an obvious correlation between early referral to specialist practices and good treatment results, as measured by HbA1c and blood pressure levels. While in 1996 patients were referred when the HbA1c level was 8.8% (median 8.5%), referrals in the last quarter of 2001 were made when the mean was 8,0% (median 7.7%). After two years the risk of inadequate treatment (HbA1c > 7.5% and blood pressure > 140/90 mmHg) had been clearly reduced in about half the cases. CONCLUSIONS: Diabetes agreements, as promulgated in Saxony, have provided effective disease management programs (DMP) for efficacious and efficient integrated diabetic care, so that with continuing effectiveness and further development the St. Vincent targets can be reached. Successful regional diabetes agreements must therefore be maintained within the new, politically centralized, DMPs.

Aged↗
PubMed2005

Coupled cluster methods including triple excitations for excited states of radicals.

We report an extension of the coupled cluster iterative-triples model, CC3, to excited states of open-shell molecules, including radicals. We define the method for both spin-unrestricted Hartree-Fock (UHF) and spin-restricted open-shell Hartree-Fock (ROHF) reference determinants and discuss its efficient implementation in the PSI3 program package. The program is streamlined to use at most O(N(7)) computational steps and avoids storage of the triple-excitation amplitudes for both the ground- and excited-state calculations. The excitation-energy program makes use of a Lowdin projection formalism (comparable to that of earlier implementations) that allows computational reduction of the Davidson algorithm to only the single- and double-excitation space, but limits the calculation to only one excited state at a time. However, a root-following algorithm may be used to compute energies for multiple states of the same symmetry. Benchmark applications of the new methods to the lowest valence (2)B(1) state of the allyl radical, low-lying states of the CH and CO(+) diatomics, and the nitromethyl radical show substantial improvement over ROHF- and UHF-based CCSD excitation energies for states with strong double-excitation character or cases suffering from significant spin contamination. For the allyl radical, CC3 adiabatic excitation energies differ from experiment by less than 0.02 eV, while for the (2)Sigma(+) state of CH, significant errors of more than 0.4 eV remain.

Journal Article↗
PubMed2003

Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part II: Comparison to other measures of executive functioning.

The clinical utility of the Behavioral Dyscontrol Scale (BDS) was compared to that of verbal fluency, the Trail Making Test, and the Stroop Color-Word Test, as well as measures of processing speed/cognitive efficiency and manual dexterity. The ability of these measures to classify 49 TBI patients into frontal versus nonfrontal and mild to moderate versus severe groups was examined. The results showed that the Fluid Intelligence Factor of the BDS improved classifications above and beyond traditional executive measures, but was particularly successful at classifying patients who sustained mild injuries. In contrast, traditional executive instruments were successful at lesion location classifications only among the patients with severe injuries. Severity classifications were successful both for traditional measures of processing speed/cognitive efficiency and for the Motor Programming Factor of the BDS, but only among patients with nonfrontal injuries. These results demonstrate that severity of injury may be an important moderator of tests' sensitivity to frontal lobe involvement.

Adult↗
PubMed2006

Economic evaluation for ophthalmologists.

PURPOSE: This review will describe the basic concepts of economic evaluation, using examples from the ophthalmic literature. The aim is to provide readers with knowledge about the fundamentals of economic evaluation to enable them to read papers critically, make healthcare funding and planning decisions, and understand the economic evaluation of interventions. REVIEW: Ophthalmic services are often constrained by a lack of funding, and this is true in both high- and low-income countries. Ophthalmology also competes with other healthcare specialities for funding. Economic evaluation is used to identify the most efficient way of allocating and planning the use of these scarce resources among alternative activities. An economic evaluation is typically conducted by comparing two or more interventions in terms of their effectiveness and their cost. Cost is the value of all resources used in the intervention. Effects, or consequences of the intervention, can be measured in monetary terms, through disease-specific outcomes or using health-related quality of life measures. The four most commonly used types of economic evaluations are cost-minimization analysis, cost-benefit analysis, cost-effectiveness analysis and cost-utility analysis. There are a variety of intended and unintended consequences of a health intervention, and so the consequences of the intervention may be positive or negative. Economic models, such as decision trees and Markov models, calculate effectiveness and costs, taking into account all the consequences of the intervention, including complications. Uncertainties in the parameters of the models can be expressed through sensitivity analyses and confidence intervals. CONCLUSIONS: Economic evaluation may be used to identify the most efficient way of allocating scarce resources among alternative activities. Its use, if standardized in all areas, can improve the quality of care while enhancing efficiency and thereby enabling more programs to be funded.

Cost-Benefit Analysis↗
PubMed1995

Algorithms for protein structural motif recognition.

The identification of protein sequences that fold into certain known three-dimensional (3D) structures, or motifs, is evaluated through a probabilistic analysis of their one-dimensional (1D) sequences. We present a correlation method that runs in linear time and incorporates pairwise dependencies between amino acid residues at multiple distances to assess the conditional probability that a given residue is part of a given 3D structure. This method is generalized to multiple motifs, where a dynamic programming approach leads to an efficient algorithm that runs in linear time for practical problems. By this approach, we were able to distinguish (2-stranded) coiled-coil from non-coiled-coil domains and globins from nonglobins. When tested on the Brookhaven X-ray crystal structure database, the method does not produce any false-positive or false-negative predictions of coiled coils.

Algorithms↗
PubMed2004

Management of patients with diabetes through information technology: tools for monitoring and control of the patients' metabolic behavior.

BACKGROUND: The junction of telemedicine home monitoring with multifaceted disease management programs seems nowadays a promising direction to combine the need for an intensive approach to deal with diabetes and the pressure to contain the costs of the interventions. Several projects in the European Union and the United States are implementing information technology-based services for diabetes management using a comprehensive approach. Within these systems, the role of tools for data analysis and automatic reminder generation seems crucial to deal with the information overload that may result from large home monitoring programs. The objective of this study was to describe the automatic reminder generation system and the summary indicators used in a clinical center within the telemedicine project M2DM, funded by the European Commission, and to show their usage during a 7-month on-field testing period. METHODS: M2DM is a multi-access service for management of patients with diabetes. The basic functionality of the technical service includes a Web-based electronic medical record and messaging system, a computer telephony integration service, a smart-modem located at home, and a set of specialized software modules for automated data analysis. The information flow is regulated by a software scheduler, called the Organizer, that, on the basis of the knowledge on the health care organization, is able to automatically send e-mails and alerts notifications as well as to commit activities to software agents, such as data analysis. Thanks to this system, it was possible to define an automatic reminder system, which relies on a data analysis tool and on a number of technologies for communication. Within the M2DM system, we have also defined and implemented a number of indexes able to summarize the patients' day-by-day metabolic control. In particular, we have defined the global risk index (GRI) of developing microangiopathic complications. RESULTS: The system for generating automatic alarms and reminders coupled with the indexes for evaluating the patients' metabolic control has been used for 7 months at the Fondazione Salvatore Maugeri (FSM) in Pavia, Italy. Twenty-two patients (43 +/- 16 years old, 12 men and 10 women) have been involved; six dropped out from the study. The average number of monthly automatic messages was 29.44 +/- 9.83, i.e., about 1.8 messages per patient per month. The number of monthly alarm reminders generated by the system was 16.44 +/- 4.39, so that the number of alarms per patient was about 1. The number of messages sent by patients and physicians during the project was about 13 per month. The GRI analysis shows, during the last trimester, a slight improvement of the performance of the FSM clinic, with a decrease in the percentage of badly controlled values from 33% to 27%. Finally, we found the presence of a linear increasing correlation between the mean GRI values and the number of alarms generated by the system. CONCLUSIONS: A telemedicine system may incorporate features that make it a suitable technological backbone for implementing a disease management program. The availability of data analysis tools, automated messaging system, and summary indicators of the effectiveness of the health care program may help in defining efficient clinical interventions.

Diabetes Mellitus↗
PubMed1995

Cost of providing pharmaceutical services to hospice patients.

The cost to a hospital pharmacy department of providing pharmaceutical services for a hospice program was studied. Drug acquisition costs were tabulated for all prescriptions dispensed to patients in the hospice program from April 1, 1992, to March 31, 1993. Direct time studies were conducted to determine the average personnel time involved in dispensing a prescription for a hospice patient. To determine the personnel time associated with auxiliary activities, self-reporting and work-sampling techniques were used. Indirect and delivery costs were also calculated. Relevant resource inputs were identified, measured, and valued by using both observation and pharmacy records. A total of 5640 hospice prescriptions were dispensed by the outpatient pharmacy; these represented 30% of all prescriptions dispensed. The average cost of dispensing a hospice prescription was $14.91 (total annual costs less drug acquisition costs). The total annual cost of providing pharmaceutical services to the hospice's patients was $196,607, and the total annual reimbursement received from the hospice program and self-paying patients was $155,623; therefore, costs exceeded revenues by $40,984. The cost to a pharmacy department of providing pharmaceutical services to patients in a hospice program substantially exceeded revenues. Greater efficiencies, a change in the pricing structure, or both may be necessary.

Contract Services↗
PubMed2003

Greedy method for inferring tandem duplication history.

MOTIVATION: Genome analysis suggests that tandem duplication is an important mode of evolutionary novelty by permitting one copy of each gene to drift and potentially to acquire a new function. With more and more genomic sequences available, reconstructing duplication history has received extensive attention recently. RESULTS: An efficient method is presented for inferring the duplication history of tandemly repeated sequences based on the model proposed by Fitch (1977). We validate the method by using simulation results and real data sets of mucin genes, ZNF genes, and olfactory receptors genes. The agreement with conclusions drawn by other biological researchers strongly indicates that our method is efficient and robust. AVAILABILITY: The program is available by request.

Algorithms↗
PubMed1997

Marker-assisted introgression of quantitative trait loci.

The use of molecular markers for the introgression of one or several superior QTL alleles into a recipient line is investigated using analytic and simulation results. The positions of the markers devoted to the control of the genotype at the QTLs in a "foreground selection" step are optimized given the confidence interval of the QTL position. Results demonstrate that using at least three markers per QTL allows a good control over several generations. Population sizes that should be recommended for various numbers of QTLs are calculated and are used to determine the limit in the number of QTLs that can be monitored simultaneously. If "background selection" devoted to accelerate the return to the recipient parent genotype outside the QTL regions is applied, the positions of the markers devoted to the control of the QTLs have to be reconsidered. When several QTLs are monitored simultaneously, background selection among the limited number of individuals resulting from the foreground selection step accelerates the increase in genomic similarity with the recipient parent, with only limited costs. Background selection is even more efficient in a pyramidal backcross program where QTLs are first monitored one by one.

Alleles↗