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PubMed1981

Experimental verification of the possibility of in vivo formation of nitrosocompounds upon combined action of dodecylguanidineacetate and sodium nitrite.

The pollution of the environment with pesticides of different chemical classes (amines, carbamates, guanidines, etc.) and nitrogen fertilizers creates the danger of the in vivo formation of carcinogenic nitrosocompounds. The fungicide Dodin represents dodecylguanidineacetate (DGA), whose chemical structure presupposes a possibility for nitrosofication in the presence of nitrites. The experiments were carried out on albino rats in which 1/10 LD50 sodium nitrite and DGA were introduced orally and in combination. On the 1st, 2nd, 4th, 8th, 15th and 30th days after the onset of the effect we determined the activity of the oxidases with mixed function (OMF) at two levels of biological organization: at the level of intact organism after loading with aminopyrine (AP) and subsequent determination of its basic metabolites in the urine; at subcellular level (microsomal liver fraction) - by the velocity of N-demethylation of AP, hydroxylation of aniline and by the cytochrome P-450 content. The independent action of sodium nitrite leads to a slight inhibition of OMF at subcellular level (28--34%) only after a single treatment. DGA does not change the activity of OMF. The combined action of the two agents causes considerable OMF inhibition (63--67 per cent) on the 1st, 2nd, 4th and 15th days at both levels. The concentration of microsomal protein decreases parallel to OMF inhibition. The data obtained suggest that a new compound is formed under the conditions of the experiment, probably through in vivo nitrosification of the pesticide. This is also testified by the established qualitatively different effect of the preliminary induction of OMF with phenobarbital on the acute toxicity of the noxae studied: lack of effect for DGA, increase for sodium nitrite and decrease for their combination.

Animals↗
PubMed1996

A three-step procedure for assessing bioequivalence in the general mixed model framework.

Bioavailability data arising from a standard two-period cross-over study are routinely analysed to establish bioequivalence between test and reference formulations. Current regulatory guidelines only require evidence of equivalence in average bioavailability for the assessment of bioequivalence. Under normality assumptions, this is achieved by demonstrating equivalence between the formulation means (step 1). However, the equivalence of formulation variances should also be assessed to get evidence of population bioequivalence (step 2), since a difference in variability of bioavailability may also pose significant problems in drug safety and efficacy. On the other hand, even population bioequivalence does not ensure that an individual subject could be expected to respond similarly to the two formulations. Therefore, whenever individual bioequivalence is the ultimate goal, the magnitude of intra-subject correlation should always be examined as the final stage (step 3). In this paper, these three successive concepts of bioequivalence are cast into the general mixed model framework and a stepwise testing procedure for the global assessment of bioequivalence is proposed. In addition to this, important issues addressed in the regulatory guidelines, such as verification of the model assumptions and application of the log-transformation, are discussed. Lastly, an example is presented to illustrate the proposed three-step procedure on the original and log-transformed scale of measurement.

Analysis of Variance↗
PubMed1990

Risk factors for nosocomial pneumonia in the elderly.

PURPOSE: Pneumonia is now the second most frequent hospital-acquired infection in acute-care facilities, and recent studies indicate that the incidence rate for nosocomial pneumonia in long-term-care facilities is of similar magnitude. The mortality rate is high, especially in the elderly. With prevention of this complication as an overall priority, this study was designed to determine the risk factors associated with nosocomial pneumonia in the elderly in both acute-care and long-term-care settings. PATIENTS AND METHODS: An epidemiologic case-control study was undertaken to compare patients or residents who developed radiographically confirmed pneumonia with control subjects who did not have and did not develop respiratory infection. Thirty-three cases were identified in the acute-care setting during the 18-week period, and 27 cases were identified in the long-term-care setting. Two matched controls were chosen for each case. Data collection involved review of the medical record and verification by medical personnel while the cases or controls were still institutionalized. Risk factor variables were analyzed using an odds ratio and 95% confidence interval calculation for matched triplets, and chi-square analysis. Selected risk factors were entered into a backward stepwise logistic regression to determine the best combination of risk factors for each setting. RESULTS: In the acute-care setting, current neurologic disease, current renal disease, deteriorating health, altered level of consciousness, disorientation, dependent bathing, dependent bowel function, dependent feeding, aspiration, difficulty with oropharyngeal secretions, and presence of a nasogastric tube were significant risk factors. In the long-term-care setting, deteriorating health, malnourishment, recent weight change, altered level of consciousness, disorientation, aspiration, difficulty with oropharyngeal secretions, suctioning, presence of a nasogastric or gastric tube, upper respiratory infection, inhalation therapy, increased confusion, and increased agitation were determined to be significant. Current pulmonary disease, previous infection, and antibiotic therapy were found not to be associated with the onset of nosocomial pneumonia. Through logistic regression, the best models for prediction of nosocomial pneumonia in the elderly were identified. In the acute-care setting, difficulty with oropharyngeal secretions and presence of a nasogastric tube were the best predictors. In the long-term-care setting, difficulty with oropharyngeal secretions, deteriorating health, and occurrence of an unusual event were the best combination of predictors. CONCLUSION: These data confirm prior findi

Aged↗
PubMed2004

Fluorescent protein tagging in Toxoplasma gondii: identification of a novel inner membrane complex component conserved among Apicomplexa.

Toxoplasma gondii is an obligate intracellular parasite, and its sub-cellular organization shows clear adaptations to this life-style. In addition to organelles shared among all eukaryotes, the organism possesses a number of specialized compartments with important roles in host cell invasion and intra-cellular survival. These unique aspects of the parasite's biology are also reflected in its genome. The ongoing genome sequencing efforts for T. gondii and related apicomplexans predict a high proportion of genes unique to the phylum, which lack homologs in other model organisms. Knowing the sub-cellular localization of these gene products will be an important first step towards their functional characterization. We used a library approach wherein parasite genomic DNA was fused to the yellow fluorescent protein (YFP) gene. Parasites transformed with this library were screened by flow cytometry and fluorescence microscopy. Clones tagged in a wide variety of sub-cellular compartments (nucleus, mitochondria, ER, dense granules (secreted), spliceosome, plasma membrane, apicoplast, inner membrane complex) were isolated and confirmed using compartment specific markers. Clones with tags in parasite-specific localizations were subjected to insert rescue and phenotypic verification using an in vitro recombination system. Among the genes identified is a novel inner membrane complex gene (IMC3) conserved among Apicomplexa.

Amino Acid Sequence↗
PubMed1994

Basic optothermal diffusion theory for interstitial laser photocoagulation.

A theoretical basis for interstitial laser photocoagulation (ILP) practiced with point-emitting fiber tips has been established by solving the bioheat transfer equation, using basic Green's function methods, for steady and instantaneous point sources of both optical energy and direct heat. Three combination optical and thermal parameters have been identified that strongly influence temperature distributions during ILP. These are defined here as optothermal heat capacities and an optothermal diffusion length, all of which characterize how a thermal diffusion temperature profile is flattened and reduced when optical diffusion is added. Relevance and limitations of this theory for practical ILP are discussed. A useful result is a mathematical verification of previous empirical observations that point optical sources heat tissues less than point heat sources of the same power. A comparison of normalized theoretical temperature transients with published measurements suggests that in normal liver, blood perfusion cooling may exceed thermal conduction by a factor of 5.6 +/- 1.7.

Biophysical Phenomena↗
PubMed2001

The transition to first position as nurse practitioner.

The nurse who graduates from a nurse practitioner program leaves a comfort zone of nursing practice to enter a new position where feelings of insecurity and stress are common. Because the role of the nurse practitioner (NP) continues to evolve and is influenced by many environmental issues, the preparation of the NP by the academic institution needs to be assessed on a frequent basis. The purpose of this research was to obtain a better understanding of the transitional phase to the first position as NP after graduation. The perceptions of preparation, gains, losses, barriers, facilitators, and strategies for adjustment were explored. A qualitative approach using focus groups was developed in which 21 recent NP graduates from a large university participated in one of four focus groups. Peer debriefing and participant verification were techniques used to ensure credibility and trustworthiness of the data and subsequent analysis. The themes identified were: loss of personal control of time and privacy; changes and losses in relationships; feelings of isolation and uncertainty in establishing the NP role; and a special bonding with clients. Although the participants perceived they were adequately prepared for their role, they also described feelings of guilt and uncertainty from not knowing information they believed they should know. They concluded that they functioned differently than the physician as well as other nurses and found it necessary to distance themselves from the role of other health care providers. This study has implications for colleagues, academic institutions, and the individual nurse practitioner.

Adaptation, Psychological↗
PubMed2001

Eye-hand coordination in object manipulation.

We analyzed the coordination between gaze behavior, fingertip movements, and movements of the manipulated object when subjects reached for and grasped a bar and moved it to press a target-switch. Subjects almost exclusively fixated certain landmarks critical for the control of the task. Landmarks at which contact events took place were obligatory gaze targets. These included the grasp site on the bar, the target, and the support surface where the bar was returned after target contact. Any obstacle in the direct movement path and the tip of the bar were optional landmarks. Subjects never fixated the hand or the moving bar. Gaze and hand/bar movements were linked concerning landmarks, with gaze leading. The instant that gaze exited a given landmark coincided with a kinematic event at that landmark in a manner suggesting that subjects monitored critical kinematic events for phasic verification of task progress and subgoal completion. For both the obstacle and target, subjects directed saccades and fixations to sites that were offset from the physical extension of the objects. Fixations related to an obstacle appeared to specify a location around which the extending tip of the bar should travel. We conclude that gaze supports hand movement planning by marking key positions to which the fingertips or grasped object are subsequently directed. The salience of gaze targets arises from the functional sensorimotor requirements of the task. We further suggest that gaze control contributes to the development and maintenance of sensorimotor correlation matrices that support predictive motor control in manipulation.

Adult↗
PubMed2004

[Vasaprostan treatment of fibrosing alveolitis in patients with pulmonary hypertension].

AIM: To study clinical efficacy of vasaprostan in patients with fibrosing alveolitis (FA) complicated by pulmonary hypertension (PH), its effect on functional activity of platelets and endothelium, intensity of free radical processes. MATERIAL AND METHODS: Seven FA patients were examined. They had either idiopathic FA or FA with diffuse diseases of the connective tissues. The following methods were used to assess the effect: standard clinical tests, high resolution computer tomography, Doppler echocardiography, definition of the complex thrombin-antithrombin (TAT) and thrombocytic factor 4 (TF-4). Generation of oxygen active forms by leukocytes was measured by luminol-dependent chemiluminescence. Morphological verification of the diagnosis was made by the results of open pulmonary biopsies. RESULTS: Vasaprostan reduced pressure in the pulmonary artery from 31.6 +/- 2.31 to 19.58 +/- 3.90 mm Hg (p < 0.05) and coagulation parameters. TAT decreased after 2 and 8 weeks of treatment from 15.25 +/- 4.5 to 5.1 +/- 0.33 and 2.4 +/- 0.31 pg/ml (p < 0.05). Initially low TF-4 (2.11 +/- 0.39 pg/ml) elevated to the end of the treatment and reached values close to control (4.37 +/- 0.25 pg/ml, p < 0.05). Moreover, vasaprostan enhanced the ability of platelets to inhibit generation of active oxygen forms (from 0.9 +/- 0.18 to 1.23 +/- 0.16 r. u., p < 0.05) and thus depressed activity of lipid peroxidation. CONCLUSION: Good effect of vasaprostan on platelet activity, free radical processes validates its use in combined treatment of various FA forms for correction of PH, its complications and as an antifibrogenic agent.

Adult↗
PubMed1986

[Anxiety structure and catecholamine parameters in patients with rosacea, alopecia areata and lichen ruber planus].

90 patients suffering from selected dermatoses (rosacea, alopecia areata, lichen planus) underwent psychological tests of examination with special regard to verification of their anxiety structures. Urinalysis of catechol amine levels was simultaneously carried out in these patients. The test results proved a marked correlation between psychological factors and the activity of the adrenergic system. High level of activity, emotional unstableness, as well as tendencies to neurotic activities are connected with increased secretion of adrenaline and decreased secretion of noradrenaline++ and dopamine. The lability of catechol amine secretion (statistically significant variation above or below the physiological standard) is the cause of functional disorders.

Adult↗
PubMed1997

Use of a turbine in a breath-by-breath computer-based respiratory measurement system.

The Computer-Based Respiratory Measurement System (CBRMS) is capable of analyzing individual breaths to monitor the kinetics of oxygen uptake, carbon dioxide production, tidal volumes, pulmonary ventilation, and other respiratory parameters during rest, exercise, and recovery. Respiratory gas volumes are measured by a calibrated turbine transducer while the respiratory gas concentrations are measured by a calibrated, fast-responding medical gas analyzer. To improve accuracy of the results, the inspiratory volumes and gas concentrations are measured and not assumed to be equal to expiratory volumes or ambient concentrations respectively. The respiratory gas volumes and concentration signals are digitized and stored in arrays. The gas volumes are converted to flow signals by software differentiation. These digitized data arrays are stored as files in a personal computer. Time alignment of the flow and gas concentration signals is performed at each breath for maximum accuracy in analysis. For system verification, data were obtained under resting conditions and under constant load exercises at 50 W, 100 W, and 150 W. These workloads were performed by a healthy, male subject on a bicycle ergometer. A strong correlation existed between the CBRMS steady-state results and the standard end-expirate bag collection technique. Thus, there is reason to believe that the CBRMS is capable of calculating respiratory transient responses accurately, a significant contribution to an understanding of total respiratory system function.

Exercise Test↗
PubMed1995

The registration function as a critical dependency in a lifetime clinical record (LCR).

Over the past two years, we have successfully migrated the Regenstrief Clinical Information System into our hospital. Integral to this process was the need to develop interfaces and processes supporting movements of patient identification data between the existing clinical management system (Unity, SMS) and Carebase (RCIS). Critical to the implementation of Carebase was the development of an interface between Carebase and the registration system based upon a unique medical record number. Even more critical was the development of stable processes that supported the accurate patient identification and assignment of medical record numbers. The medical record number at our institution is assigned or verified at the time of registration. Major problems occurred when patients presented during system down-times and existing medical record numbers could not be accessed, resulting in multiple registrations and medical record numbers for the same patient. This resulted in data fragmentation and required merging at a later date. Other more serious problems resulted from the assignment of the same medical record number to separate patients and with the mixing of data from multiple patients into one patient record. This was largely due to the failure of clerical personnel to appropriately identify patients at the time of registration, or multiple patients sharing identification documents, a common problem in our geographic area. Given that clinical data was to be maintained and added to the repository for several decades, errors such as these in registration would prove catastrophic. The interfaces between the various clinical systems that pass data to Carebase are all HL-standard and largely prevent data passage if registration data is inaccurate. During the early stages of implementation, approximately 300 exceptions per day were generated from clinical systems attempting to pass data to the repository. Following re¿engineering of the registration process, education of clerical personnel, and analysis of exception type, the number of exceptions due to faulty registration data fell to less than one per week. To achieve improvement in exception volume, several innovative measures were undertaken. Firstly, down-time procedures were changed to require query of the LCR for existing registration data. The LCR was maintained on a separate platform that experienced essentially no down-time and was available for this purpose. This largely eliminated the need for the use of "down-time numbers" or medical record numbers that could be temporarily assigned to patients registered when the registration system was unavailable (data would subsequently be merged into existing patient records if the patient was found to be currently in the system). If the patient was not in the LCR, then a permanent number was assigned in sequence. A registration dataset was developed and encoded onto a magnetic card (Carecard, Eltrax) and carried by patients. This enabled the rapid verification of registration data on subsequent visits to the parent institution or affiliated clinical sites. The issue of fraudulent use of the card and encoded registration dataset, however, remained problematic. Currently, a new imaging system is being installed that will soon enable the inclusion of a photograph of the patient as a component of the registration dataset. Perhaps the most significant change in the registration process involved the education of central registration and admitting personnel. An educational program was developed that reinforced the need for accuracy in collecting registration data, identifying patients, and assigning medical record numbers; more importantly, it stressed the linkage of the registration function and patient care. Lastly, an aggressive approach to monitoring exceptions resulting from errors in registration was developed. A near real-time process for identifying errors in registrations allowed for rapid intervention and feedback to involved de

Medical Records Systems, Computerized↗
PubMed1994

Changes in transaminases over the course of a 12-week, double-blind nalmefene trial in a 38-year-old female subject.

A 38-year-old female was drinking 30 drinks/week before entering a 12-week, double-blind study of nalmefene for the treatment of alcohol dependence. Liver function tests (LFTs) were within normal limits at baseline and week 4, but on week 8, the ALT showed a 7-fold increase, and the AST showed a 4-fold increase from baseline. A decision was made to continue study medication based on the patient's positive response to this therapy (i.e., achieving complete abstinence) and no known dose-dependent association with liver toxicity in over 1300 patients treated with nalmefene for other indications. LFTs were repeated serially to assess the trend of the LFT values. The patient achieved total abstinence over the course of the study period and at the 3-month posttreatment follow-up was continuing to maintain these gains from the study program, and her LFTs had returned to normal. A gradual return to normal in ALT and AST, while treatment with nalmefene continued, does not support the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the gamma-glutamyltransferase, and verification of sobriety by self-report, significant other, and breathalyzer. A virology panel ruled out the presence of viral hepatitis. Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may be expected to reveal clinically nonsignificant elevations that could potentially be related to exogenous factors, such as dietary composition and should not be reflexively attributed to medication under investigation and/or drinking.

Adult↗
PubMed2006

Gene expression profiles of vitrified in vivo derived 8-cell stage mouse embryos detected by high density oligonucleotide microarrays.

Very little is known about the effect of vitrification on gene functions after warming. The goals of our study were to compare the gene expression patterns, and identify those most affected. For this, 8-cell stage embryos were collected from ICR mice and vitrified with solid surface vitrification technique, while maintaining equal numbers of embryos as control. Total RNAs were extracted and two rounds of amplification were employed. Finally three micrograms of contrasting RNA samples were hybridized on the Agilent Mouse 22 K oligonucleotide slides and the results were analyzed with subsequent verification by independent real-time PCR analyses. The two rounds of amplification with 5 ng tRNA input have yielded 15-16 microg of cRNA. The analyses of repeated hybridizations showed 20,183 genes/ESTs as common signatures, and unsupervised analysis identified 628 differentially expressed (P < 0.01) genes. However, with at least 1.5-fold change considerations, 183 genes were differentially expressed (P < 0.01) out of which 107 were upregulated. The independent analysis with real-time PCR and unamplified samples fully confirmed the results of microarray, indicating the linearity of amplification. Furthermore, this novel gene expression study for vitrified embryos identified many new candidate genes with overrepresentation in some important biological processes. Thus, it is possible to conclude that the expression pattern reflected a broad spectrum of consequences of vitrification on embryos, with most effects on metabolism, regulatory role and stress response genes and allowed the identification of new candidate marker genes for cryosurvival.

Animals↗
PubMed1992

Protein design on computers. Five new proteins: Shpilka, Grendel, Fingerclasp, Leather, and Aida.

What is the current state of the art in protein design? This question was approached in a recent two-week protein design workshop sponsored by EMBO and held at the EMBL in Heidelberg. The goals were to test available design tools and to explore new design strategies. Five novel proteins were designed: Shpilka, a sandwich of two four-stranded beta-sheets, a scaffold on which to explore variations in loop topology; Grendel, a four-helical membrane anchor, ready for fusion to water-soluble functional domains; Finger-clasp, a dimer of interdigitating beta-beta-alpha units, the simplest variant of the "handshake" structural class; Aida, an antibody binding surface intended to be specific for flavodoxin; Leather--a minimal NAD binding domain, extracted from a larger protein. Each design is available as a set of three-dimensional coordinates, the corresponding amino acid sequence and a set of analytical results. The designs are placed in the public domain for scrutiny, improvement, and possible experimental verification.

Algorithms↗
PubMed1996

Physiologically based pharmacokinetic/pharmacodynamic modeling of the toxicologic interaction between carbon tetrachloride and Kepone.

Carbon tetrachloride (CCl4) lethality in Sprague-Dawley rats is greatly amplified by pretreatment of Kepone (decachlorooctahydro-1,3,2-metheno-2H-cyclobuta[cd] pentalen-2-one). The increase in lethality was attributed to the obstruction of liver regenerative processes. These processes are essential for restoring the liver to its full functional capacity following injury by CCl4. Based on the available mechanistic information on Kepone/CCl4 interaction, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was constructed where the following effects of Kepone on CCl4 toxicity are incorporated: (1) inhibition of mitosis; (2) reduction of repair mechanism of hepatocellular injury; (3) suppression of phagocytosis. The PBPK/PD model provided computer simulation consistent with previously published time-course results of hepatotoxicity (i.e., pyknotic, injured and mitotic cells) of CCl4 with or without Kepone. As a further verification of this model, the computer simulations were also consistent with exhalation kinetic data for rats injected with different intraperitoneal (i.p.) doses of CCl4 in our laboratory. Subsequently, the PBPK/PD model, coupled with Monte Carlo simulation, was used to predict lethalities of rats treated with CCl4 alone and CCl4 in combination with Kepone. The experimental lethality studies performed in our laboratories were as follows: Sprague-Dawley rats were given either control diet or diet containing 10 ppm Kepone for 15 days. On day 16, rats in the Kepone treated group were given i.p. doses of 0, 10, 50, and 100 microliters/kg CCl4 (n = 9) while control rats were exposed to 0, 100, 1000, 3000, and 6000 microliters/kg CCl4 (n = 9). Lethality was observed at the 1000 (1/9), 3000 (4/9), and 6000 (8/9) microliters/kg doses for the control group and at the 50 (4/9) and 100 (8/9) microliters/kg for the treated group. Based on Monte Carlo simulation, which was used to run electronically 1000 lethality experiments for each dosing situation, the LD50 estimates for CCl4 toxicity with and without Kepone pretreatment were 47 and 2890 microliters/kg, respectively. Monte Carlo simulation coupled with the PBPK/PD model produced lethality rates which were not significantly different from the observed mortality, with the exception of CCl4 at very high doses (e.g., 6000 microliters/kg, p = 0.014). Deviation at very high doses of the predicted mortality from the observed may be attributed to extrahepatic systemic toxicities of CCl4, or solvent effects on tissues at high concentrations, which were not presently included in the model. Our modeling and experimental results verified the earlier findings of Mehendale (1990) for the 67-fold amplification of CCl4 lethality in the presence of Kepone. However, much of this amplification of CCl4 lethality with Kepone pretreatment was probably due to pharmacokinetic factors, because when target tissue dose (i.e., model estimated amount of CCl4 metabolites) was used to evaluate lethality, this amplification was reduced to 4-fold.

Animals↗
PubMed2004

Sequential memory: a developmental perspective on its relation to frontal lobe functioning.

The multidimensional nature of the frontal lobes serves to organize and coordinate brain functionings playing a central and pervasive role in human cognition. The executive processes implicated in complex cognition such as novel problem solving, modifying behavior as appropriate in response to changes in the environment, inhibiting prepotent or previous responses, and the implementation of schemas that organize behavior over time are believed to be mediated by the frontal regions of the brain. Overall, the functioning of the frontal lobes assists individuals in goal directed and self-regulatory behavior. Additional theories of frontal lobe functioning have focused on its involvement in temporal, or time-related domains. The organizational and strategic nature of frontal lobe functioning affects memory processes by enhancing the organization of to-be-remembered information. Among the specific memory systems presumed to be based on anterior cerebral structures is the temporal organization of memory. An essential component of memory that involves temporal organization is sequential ordering entailing the ability to judge which stimuli were seen most recently and the temporal ordering of events in memory. Focal lesion studies have demonstrated the importance of the frontal lobes on retrieval tasks in which monitoring, verification, and placement of information in temporal and spatial contexts of critical importance. Similarly, frontal lobe damage has been associated with deficits in memory for the temporal ordering, or sequencing, of events. The acquisition of abilities thought to be mediated by the frontal lobes, including sequential memory, unfolds throughout childhood, serving to condition patterns of behavior for the rest of the brain. Development of the frontal regions of the brain is known to continue through late adolescence and into early adulthood, in contrast to the earlier maturation of other cortical regions. The developmental patterns of the frontal lobes are thought to involve a hierarchical, dynamic, and multistage process.

Child↗
PubMed2004

Single nucleotide polymorphisms associated with rat expressed sequences.

Single nucleotide polymorphisms (SNPs) are the most common source of genetic variation in populations and are thus most likely to account for the majority of phenotypic and behavioral differences between individuals or strains. Although the rat is extensively studied for the latter, data on naturally occurring polymorphisms are mostly lacking. We have used publicly available sequences consisting of whole-genome shotgun (WGS), expressed sequence tag (EST), and mRNA data as a source for the in silico identification of SNPs in gene-coding regions and have identified a large collection of 33,305 high-quality candidate SNPs. Experimental verification of 471 candidate SNPs using a limited set of rat isolates revealed a confirmation rate of approximately 50%. Although the majority of SNPs were identified between Sprague-Dawley (EST data) and Brown Norway (WGS data) strains, we found that 66% of the verified variations are common among different rat strains. All SNPs were extensively annotated, including chromosomal and genetic map information, and nonsynonymous SNPs were analyzed by SIFT and PolyPhen prediction programs for their potential deleterious effect on protein function. Interestingly, we retrieved three SNPs from the database that result in the introduction of a premature stop codon and that could be confirmed experimentally. Two of these "in silico-identified knockouts" reside in interesting QTL regions. Data are publicly available via a Web interface (http://cascad.niob.knaw.nl), allowing simple and advanced search queries.

Animals↗
PubMed1985

Managing the inventory control system.

The four functions of management--planning, organizing, directing, and controlling--are described in relation to the hospital pharmacy inventory control system. Planning includes the development of inventory system objectives and identification of the resources needed to complete them. Organizing requires the manager to decide on the best method of grouping system activities and resources to complete the objectives in order of priority. Directing is a continual activity that involves obtaining optimal performance from the inventory system resources available. Controlling consists of regulation and verification of inventory system activities. The effective inventory system manager integrates planning, organizing, directing, and controlling in a continuous cycle.

Costs and Cost Analysis↗