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Development and characterization of an aerosol time-of-flight mass spectrometer with increased detection efficiency.

This paper describes the development and characterization studies of a more efficient aerosol time-of-flight mass spectrometer (ATOFMS), showing results for the on-line detection and determination of the size and chemical composition of single fine (100-300 nm) and ultrafine (<100 nm) particles. An aerodynamic lens inlet was implemented, replacing the converging nozzle inlet used on conventional ATOFMS instruments. In addition, the light scattering region was modified to enhance the scattering signals for smaller particles. Polystyrene latex spheres (PSL) with aerodynamic diameters ranging from 95 to 290 nm were used to characterize the particle sizing efficiency (product of particle transmission efficiency and particle scattering efficiency), particle detection efficiency (product of particle sizing efficiency and particle hit rate), and particle beam profile and perform instrument calibration. At number concentrations of <20 particles/cm(3), the particle sizing efficiencies were determined to be approximately 0.5% for 95 nm and approximately 47% for 290-nm PSL particles, while the particle detection efficiencies were measured to be approximately 0.3% for 95 nm and 44% for 290-nm PSL particles. This represents a significant increase (i.e., at least 3 orders of magnitude) in detection efficiencies for smaller particles over the conventional ATOFMS. In addition, the beam profiles for PSL particles of various sizes were measured in the ion source of the mass spectrometer and follow a Gaussian distribution with a full width at half-maximum of approximately 0.35 mm. The resulting higher detection efficiencies allow ATOFMS to obtain higher temporal resolution measurements of the composition of fine and ultrafine individual particles as demonstrated in initial ambient measurements in La Jolla, CA. At typical ambient particle number concentrations of 10(2)-10(3) particles/cm(3), approximately 30 000 particles with aerodynamic diameters of <300 nm were detected with average 24-h hit rates of 30% for particles between 50 and 300 nm. This advancement, allowing for high temporal resolution measurements of the composition of smaller particles with higher efficiency, adds to a growing number of instruments that can chemically characterize individual fine and ultrafine particles, with the goal of providing new insights into a number of areas including environmental and material sciences, health effects studies, industrial hygiene, and national security.

Journal Article↗

Phylogenetic analysis of the apolipoprotein B mRNA-editing region. Evidence for a secondary structure between the mooring sequence and the 3' efficiency element.

Apolipoprotein (apo) B mRNA editing is the deamination of C(6666) to uridine, which changes the codon at position 2153 from a genomically encoded glutamine (CAA) to an in-frame stop codon (UAA). The apoB mRNA-editing enzyme complex recognizes the editing region of the apoB pre-mRNA with exquisite precision. Four sequence elements spanning 139 nucleotides (nt) on the apoB mRNA have been identified that specify this precision. In cooperation with the indispensable mooring sequence and spacer element, a 5' efficiency element and a 3' efficiency element enhance editing in vitro. A phylogenetic comparison of 32 species showed minor differences in the apoB mRNA sequence, and the apoB mRNA from 31 species was robustly edited in vitro. However, guinea pig mRNA was poorly edited. Compared with the consensus sequences of these 31 species, guinea pig apoB mRNA has three variations in the 3' efficiency element, and the conversion of these to the consensus sequence increased editing to the levels in the other species. From this information, a model for the secondary structure was formulated in which the mooring sequence and the 3' efficiency element form a double-stranded stem. Thirty-one mammalian apoB mRNA sequences are predicted to form this stem positioning C(6666) two nucleotides upstream of the stem. However, the guinea pig apoB mRNA has a mutation in the 3' efficiency element (C(6743) to U) that predicts an extension of the stem and hence the lower editing efficiency. A test of this model demonstrated that a single substitution at 6743 (U to C) in the guinea pig apoB mRNA, that should reduce the stem, enhanced editing, and mutations in the 3' efficiency element that extended the stem for three base pairs dramatically reduced editing. Furthermore, the addition of a 20-nucleotide 3' efficiency element RNA, to a 58-nucleotide guinea pig apoB mRNA lacking the 3' efficiency element more than doubled the in vitro editing activity. Based on these results, a model is proposed in which the mooring sequence and the 3' efficiency element form a double-stranded stem, thus suggesting a mechanism of how the 3' efficiency element enhances editing.

Animals↗

Upstream introns influence the efficiency of final intron removal and RNA 3'-end formation.

For all intron-containing pre-mRNAs of higher eukaryotes that have been examined using either living cells or cell-free extracts, a functional 3' splice site within the 3'-terminal intron is required for efficient RNA 3'-end formation. The mechanism by which intron sequences facilitate RNA 3'-end formation, which is achieved by endonucleolytic cleavage and polyadenylation, is not understood. We report here that in intact cells the efficiency of RNA 3'-end formation correlates with the efficiency of final intron removal, even when the intron is normally a 5'-terminal or internal intron. Therefore, the influence of the 3'-terminal intron on 3'-end formation is likely to be attributable to the determinants of splicing efficiency, which include but are not limited to the 3' splice site. Quantitative RNase mapping and methods that couple reverse transcription and the polymerase chain reaction were used to assess the consequence to RNA 3'-end formation of intron deletions within the human gene for triosephosphate isomerase (TPI). Results indicate that the formation of TPI RNA 3' ends requires TPI gene introns in addition to the last intron, intron 6, to proceed efficiently. These additional TPI gene introns are also required for the efficient removal of intron 6. When introns 1 and 5 were engineered to be the final intron, they were found, as was intron 6, to function in RNA 3'-end formation with an efficiency that correlated with their efficiency of removal. The simultaneous deletion of the 5' and 3' splice sites of intron 6 reduced the efficiencies of both RNA 3'-end formation and the removal of intron 5, which constituted the 3'-most functional intron. Deletion of only the 3' splice site of intron 6 precluded RNA 3'-end formation but had no effect on the efficiency of intron 5 removal. Deletion of only the 5' splice site of intron 6, which resulted in exon 6 skipping (i.e., the removal of intron 5, exon 6, and intron 6 as a single unit), had no effect on the efficiencies of either RNA 3'-end formation or the removal of intron 5-exon 6-intron 6. These results indicate that sequences within the 3'-terminal intron are functionally coupled to both RNA 3'-end formation and removal of the penultimate intron via a network of interactions that form across the last two exons and, most likely, between RNA processing factors.

Base Sequence↗

Detection efficiency of a high-pressure gas scintillation proportional chamber.

The detection efficiency of a high-pressure, gas scintillation proportional chamber (GSPC), designed for medical imaging in the 30-150 keV energy range, has been investigated through measurement and Monte Carlo simulation. Measurements were conducted on a GSPC containing 4 atm of pure xenon separated from a hexagonal array of seven ultraviolet-sensitive photomultiplier tubes by 1.27-cm-thick fused-silica windows. Experimental measurements of the photopeak efficiency, fluorescence escape efficiency, and the energy collection efficiency were obtained. Results were also obtained for different photon energies and different values of temporal resolution. The measurements were compared with the results obtained from a Monte Carlo simulation designed specifically for investigating the imaging of low-energy photons (below 150 keV) with a gas-filled detector. The simulation was used to estimate photopeak efficiency, fluorescence escape efficiency, photopeak-to-fluorescence escape peak ratio, quantum interaction efficiency, energy collection efficiency, and local energy collection efficiency. The photopeak efficiency of the GSPC relative to that of a 3-in. (7.62-cm)-thick sodium iodide crystal was measured to be 0.284 +/- 0.001 at 60 keV and 0.057 +/- 0.001 at 140 keV. Of the 60-keV photons incident upon the detector, 70% +/- 4% interacted in the detector, with 28% +/- 1% being in the photopeak, as estimated both by experimentation and through the simulation. The maximum energy collection efficiency was found to be 65% at 60 keV, with 46% being deposited within 0.2 cm of the initial photon interaction. The information gained from this study is being used to design an optimized detector for use in specialized nuclear medicine studies.

Biophysical Phenomena↗

Decreased mechanical efficiency in clinically stable patients with COPD.

BACKGROUND: It has recently been reported that total daily energy expenditure (TDE) is increased in patients with chronic obstructive pulmonary disease (COPD) and it was hypothesised that these patients may have a decreased mechanical efficiency during activities. The purpose of the present study was to measure the mechanical efficiency of submaximal leg exercise, and to characterise patients with a potentially low efficiency in terms of body composition, resting energy expenditure, lung function, and symptom limited exercise performance. METHODS: Metabolic and ventilatory variables were measured breath by breath during submaximal cycle ergometry exercise performed at 50% of symptom limited achieved maximal load in 33 clinically stable patients with COPD (23 men) with forced expiratory volume in one second (FEV1) of 40 (12)% predicted. Net mechanical efficiency was calculated adjusting for resting energy expenditure (REE). RESULTS: Median mechanical efficiency was 15.5% and ranged from 8.5% to 22.7%. Patients with an extremely low mechanical efficiency (< 17%, n = 21) demonstrated an increased VO2/VE compared with those with a normal efficiency (median difference 4.7 ml/l, p = 0.005) during submaximal exercise. There was no difference between the groups differentiated by mechanical efficiency in blood gas tensions at rest, airflow obstruction, respiratory muscle strength, hyperinflation at rest, resting energy expenditure or body composition. There was a significant difference in total airways resistance (92% predicted, p = 0.03) between the groups differentiated by mechanical efficiency. CONCLUSIONS: It is concluded that many patients with severe COPD have decreased mechanical efficiency. Furthermore, based on the results of this study it is hypothesised that an increased oxygen cost of breathing during exercise contributes to the decreased mechanical efficiency.

Adult↗

Simulated efficiency of range beef production. III. Culling strategies and nontraditional management systems.

A modified version of the Texas A&M Beef Cattle Production Model was used to simulate life-cycle biological and economic efficiency of various culling strategies and non-traditional management systems in a northern plains, range environment. Biological efficiency was defined as the ratio of TDN input (kg) to product output (kg), and economic efficiency was defined as the ratio of cost ($) to product output (100 kg), where products were live weight at weaning (LWW), empty body weight at slaughter (EBW) and fat-free weight at slaughter (FFW). Several economic scenarios were simulated. Culling cows at younger ages increased biological efficiency, but not necessarily economic efficiency. The simulated optimal age at culling was 8 yr, the same age at which simulated feed intake and milk production began to decline. Finishing young cows in the feedlot had little effect on biological efficiency and generally increased economic efficiency, although specific results depended on feed prices and relative values of cull cows vs fed animals. A simulated sex-controlled system in which only heifer calves were produced, while extremely biologically efficient for production of lean, resulted in relatively little output and was not economically efficient in most cases. Sex control combined with feeding of 2-yr-old cows was economically efficient, but not markedly more efficient than a conventional system. Results suggest that sex-controlled systems may be more appropriate where emphasis is on lean product and heifers can be bred at very early ages. General results indicate that producers should pay attention to relative values of cull cows and fed animals in choosing culling strategies and management systems.

Animal Husbandry↗

Apparent sensitivity of human K lymphocytes to the spatial orientation and organization of target cell-bound antibodies as measured by the efficiency of antibody-dependent cellular cytotoxicity (ADCC).

Although monoclonal antibodies (mAb) can elicit potent ADCC by human K lymphocytes, different mAb, even of the same antibody subclass or even of the same target antigen specificity, vary considerably as to their efficiency in eliciting ADCC. The extensive variability in ADCC efficiencies of murine IgG2a mAb is analyzed here. In cold-target inhibition experiments it was found that only cells coated with "ADCC-efficient" IgG2a mAb, and not "ADCC-inefficient" IgG2a mAb, inhibit K effector cell lysis of radiolabeled target cells by ADCC. This result indicates that the spatial orientation of the antibodies on the target cell membrane influences the net efficiency of ADCC reactions by affecting the efficiency of interaction between antibody and the Fc receptors (FcR) of K cells. It is proposed that a "favorable" orientation of antibodies on the target cell membrane is required for efficient ADCC reactions. This proposal is directly supported by the observation that one IgG2a mAb (20.8.4), which cross-reacts with several different H-2 alloantigens, was found to elicit efficient ADCC only when bound to certain of its possible target cell antigens. It was also observed in these studies that the organization of antibodies on a target cell membrane influences the net efficiency of ADCC reactions. It is proposed that a "favorable" antibody organization on the target cell membrane is also required for efficient ADCC reactions. This proposal is supported by the observation that certain antihuman beta 2m (anti-Hu beta 2m) IgG2a mAb, which elicit efficient ADCC lysis of human target cells, fail to elicit the lysis of murine cells having Hu beta 2m molecules coupled randomly to their external membrane surfaces. The differences in the way the Hu beta 2m was organized on the surfaces of the human cells and the murine-Hu beta 2m cell conjugates presumably caused differences in the way the bound antibodies were organized on the cell surfaces, which in turn resulted in the ADCC efficiency differences observed for the same mAb with the different target cell types. Because ADCC reactions appear to be sensitive to both the orientation and the organization of cell surface-bound antibodies, certain types of structural alterations or variations in the membrane molecules (relative to other neighboring structures on the target cell membrane) are potentially detectable by quantitative differences or variations in ADCC reactions.

Antibodies, Monoclonal↗

Quality assurance, efficiency indicators and cost-utility of the evaluation workup for liver transplantation.

We report the results of a retrospective review of the outpatient pretransplantation workup for United Network for Organ Sharing (UNOS) 3 patients adopted at a liver transplantation (LT) center and illustrate the efficiency indicators used for quality evaluation and cost-analysis. A single-center, pre-LT evaluation workup was performed on an outpatient basis at a cost per patient evaluation of 2,770 Euros (). Objective measures were: the number of patients admitted to and excluded from each phase of the algorithm; the rate of patients admitted to pre-LT evaluation out of the total of referred patients (the referral efficiency rate); the rate of waitlisted patients out of those admitted to pre-LT evaluation (the evaluation efficiency rate); the rate of waitlisted patients out of those referred for LT (the process efficiency rate); and the cost per waitlisted patient, as the ratio of the cost per patient evaluation to the evaluation efficiency rate. From January 1, 1996, to October 1, 2004, 1,837 patients were referred for LT on an outpatient basis. Based on preemptive evaluation of the available clinical data, 412 patients (22.4%) were excluded from pre-LT evaluation and 1,425 (77.6%) were admitted to preliminary consultation. Among these, 603 (42.3%) were excluded from and 822 (57.7%) were admitted to pre-LT evaluation with a referral efficiency rate of 44.7% (822 of 1,837). Out of the patients evaluated for LT, 484 were waitlisted with a cost-utility and evaluation efficiency rate of 58.8% each (484 of 822). Of the 1,837 patients originally addressed for LT 484 were waitlisted, yielding a process efficiency rate of 26.3% (484 of 1,837) and a cost per waitlisted patient of 4,710.8. In conclusion, the 3 indicators allowed monitoring of the efficiency of the pre-LT evaluation algorithm. The current process efficiency rate at our center is low (26.3%), but avoiding early referrals we might increase it to 31.6%, with a 12% net saving on costs per waitlisted patient (from 4,710.8 to 4,165.4).

Costs and Cost Analysis↗

Measuring hospital efficiency in Austria--a DEA approach.

We investigate the evolution of efficiency and productivity in the hospital sector of an Austrian province for the time period 1994-1996. We use panel data to design non-parametric frontier models (Data Envelopment Analysis) and compare efficiency scores and time patterns of efficiency across medical fields. As health outcomes hardly can be measured in a direct way we make use of two different approaches for output measurement: In a first approach, we employ the number of case mix-adjusted discharges and of inpatient days, in a second we use credit points, which are calculated in course of the newly introduced diagnosis related group-type financing system. We calculate and compare individual efficiency scores for hospital wards as decision making units (DMU) in specified medical fields. To our knowledge the calculation of ward-specific efficiency scores has not up till now been the unit of non-parametric efficiency analysis. Our two models find different results: Model 1 with conservative output measurement calculates an average efficiency level of 96%, while model 2 with credit points for output measurement puts average efficiency at 70%. Whereas average efficiency in model 1 hardly changes and in model 2 increases modestly in the period 1994-1996, a closer look at single hospitals displays a variety of different efficiency developments over time.

Austria↗

Data envelopment analysis to determine efficiencies of health maintenance organizations.

We use Data Envelopment Analysis (DEA) to measure the relative technical efficiencies of 164 HMOs licensed to practice in the United States in 1995 with data collected from the American Association of Health Plans. Health care output measures used in the analysis are the number of commercial, Medicare and Medicaid lives covered in each plan. Inputs to the model are health care utilization measures such as the number of medical and surgical inpatient days, number of maternity and newborn stays in days, number of outpatient and emergency room visits and the number of non-invasive and invasive procedures performed on patients in an ambulatory setting. Mean efficiency of health plans was 40% (of the most efficient). We use multivariate analysis to try and explain variations in efficiency. Enrollment influences efficiency, with larger HMOs being more efficient than those with fewer enrollees. Plans with a more even distribution of Commercial, Medicare and Medicaid patients were more efficient on average than plans with heterogeneous mixes in enrollment. HMOs with Medicare patients are significantly less efficient, with efficiency decreasing with increasing Medicare participation in plan membership. Health plans in operation for longer periods of time had greater outputs with the same inputs. Health plans that had a majority of their enrollees in network or IPA type arrangements were more efficient as were for-profit plans compared to not-for-profits. Policy implications are discussed.

Chi-Square Distribution↗

Does the implementation of responsibility centers, total quality management, and physician fee programs improve hospital efficiency? Evidence from Taiwan hospitals.

OBJECTIVES: This study evaluates whether the implementation of various types of hospital-physician integration strategies, such as the responsibility centers system, total quality management, and physician fee programs, enhance efficiency for Taiwan hospitals. Because hospitals in Taiwan are structurally similar to staff-model HMOs, the study has implications beyond Taiwan. RESEARCH DESIGN: The Data Envelopment Analysis model is applied to measure hospital efficiency. Hospital efficiency refers to the ability to produce more outputs (eg, ambulatory and emergency visits, inpatient days, and inpatient visits) with the same inputs (eg, physicians, nurses, ancillary labor, and hospital beds). The sample consists of 90 general hospitals in Taiwan from 1994 to 1996. In addition, multitobit regression analysis is used to simultaneously estimate the effects of the hospital-physician integration strategies and provide better control for the effect of other factors (eg, size, degree of competition, ownership structure, teaching status, and the change in regulatory regime) that may also affect hospital efficiency. RESULTS: When evaluating the hospital-physician integration strategies individually, hospitals that implemented the responsibility centers system, total quality management, and physician fee programs were more efficient than hospitals that did not. Controlling for other factors using the multitobit model, hospitals that implemented physician fee programs remained significantly more efficient than others. In addition, hospitals that implemented total quality management were more efficient when they had implemented the strategy for at least 2 years. Hospitals that implemented the responsibility centers system were more efficient but only when integrating the system with formal incentive schemes. CONCLUSIONS: Physician fee programs seem to provide the most direct and robust incentives to enhance hospital efficiency under a fee-for-service regime like that in Taiwan. Because of time-lagged effects, hospitals that implemented the total quality management programs were more efficient but only when the programs had been implemented for at least 2 years. The responsibility centers system can also be effective when the system was associated with formal incentive schemes. The results indicate the importance of having both the individual-based and team-based incentives in place. Finally, the hospital-physician integration strategies appear to be effective individually, but the results change significantly when they are evaluated simultaneously, together with other control variables, in the tobit model. This indicates the importance of investigating hospital-physician integration strategies as a portfolio instead of a single tool.

Decision Making, Organizational↗

The defibrillation success rate versus energy relationship: Part I--Curve fitting and the most efficient defibrillation energy.

The effect of applying an energy pulse to the heart during ventricular fibrillation is described by the probability of successful defibrillation or success rate. Seven to ten (8.60 +/- 0.84: mean +/- standard deviation) defibrillation trials per energy were randomly attempted at energies which span the defibrillation success rate versus energy curve. We obtained 70.0 +/- 8.4 episodes per dog. We fit the defibrillation success rate versus energy relationship from ten dogs (20.5 +/- 1.5 kg) to four types of curves: linear, exponential, probit transformed linear, and logit transformed linear. The correlation coefficients for each fit are 0.917 +/- 0.057, 0.944 +/- 0.014, 0.926 +/- 0.51, and 0.889 +/- 0.098, respectively. We therefore conclude that the exponential curve best describes the DSRE relationship. This suggests the existence of an energy below which defibrillation does not occur. At higher energies, the exponential curve asymptotically approaches a 100% success rate, which indicates that increasing the energy produces a diminishing benefit to defibrillation success rate. The estimated energies with a 0% defibrillation success rate are surprisingly consistent among dogs, with 2.072 +/- 0.553 J. The estimated energy with an 80% defibrillation success rate is 5.217 +/- 1.091 J. The estimated defibrillation success rate corresponding to the defibrillation threshold of 3.59 +/- 1.06 J is consistent with 0.516 +/- 0.144. The estimated energies with a 0% success rate correlate well with the defibrillation thresholds with R = 0.772; P = 0.0088. Since implantable defibrillators have a limited energy supply, we determined energy efficiency by dividing defibrillation success rate by the applied energy and energy consumption by dividing the applied energy by the defibrillation success rate. The most efficient defibrillation energy occurs at the maximum energy efficiency and the minimum energy consumption. The most efficient defibrillation energy of 4.34 +/- 0.97 J determined from the exponential fit has a success rate of 0.70 +/- 0.06. The most efficient defibrillation energy can be predicted from the defibrillation threshold. Clinically, a 70% success rate may not be adequate. We, therefore, compared the energy efficiency and consumption of energies with 90% and 95% success rates to the most efficient defibrillation energy. About a 50% increase in energy from the most efficient defibrillation energy is necessary for a 90% success rate which results in about a 13% loss in energy efficiency and about a 16% increase in energy consumption. About an 84% energy increase is necessary for a 95% success rate which results in about a 24% loss in energy efficiency and about a 33% increase in energy consumption.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Productive efficiency and its determinants in the Finnish Public Dental Service.

OBJECTIVE: Our objective was to investigate the cost efficiency of the Public Dental Service (PDS), which, until 2000, was responsible for organising dental care for children and younger adults born in 1956 and later. METHODS: Input and output data and information on various organisational and environmental characteristics were collected from 228 municipal PDS units in Finland. First, non-parametric data envelopment analysis (DEA) was employed to assess efficiency. In the second stage, econometric Tobit analysis was used to explore various predictors of cost efficiency, technical efficiency and allocative efficiency. As input in the DEA model we used personnel full-time equivalents and material and other costs expressed in monetary terms, and as output we used the number of treated patients. RESULTS: The study showed big differences in cost efficiency between the PDS units studied. The average cost inefficiency was 30%. Approximately two-thirds of the observed cost inefficiency was because of technical inefficiency and one-third because of allocative inefficiency. High state-subsidy levels, and a high proportion of young patients predicted inefficiency, and young population and low socioeconomic conditions in the municipality predicted efficiency. The results also indicated that many PDS units could have improved allocative efficiency by increasing the relative numbers of auxiliaries in relation to dentists. On the other hand, some units were too small to employ full-time dental hygienists efficiently. CONCLUSIONS: In the Finnish PDS, there are uncommitted resources that could be reallocated so as to improve overall efficiency.

Adolescent↗

Electrical membrane activity and intracellular calcium buffering control exocytosis efficiency in Xenopus melanotrope cells.

In neural and neuroendocrine cells, Ca(2+) influx is essential for exocytosis. Ca(2+) influx takes place through electrical membrane activity, which often occurs in bursts of action potentials that lead to intracellular Ca(2+) oscillations. Cytoplasmic Ca(2+) buffers and intracellular Ca(2+) stores are involved in the propagation of the oscillations through the cell. Studies focused on action potential bursts with a high frequency up to 20 Hz indicate that, depending on the cell type under investigation, bursts either enhance or reduce exocytosis efficiency. In many cell types, the bursting frequency can be as low as 1 Hz, although no information is present on whether this influences exocytosis efficiency. The present study addresses the role of low-frequency bursts around 1 Hz and cytoplasmic Ca(2+) buffering in the regulation of exocytosis efficiency, using neuroendocrine melanotrope cells of the amphibian Xenopus laevis. Exocytosis efficiency was determined by membrane capacitance measurements. Mimicking the bursting activity of 1 Hz (typical for this cell type) by repetitive depolarizing pulses enhanced exocytosis efficiency by 58% compared to application of only one single depolarizing pulse. This increase appears to be particularly due to a small number of distinct depolarizing pulses within a burst. Including the fast Ca(2+) buffer BAPTA in the intracellular solution reduced exocytosis efficiency by 60% in the first part of a burst, whereas during the later part of the burst, stimulation (+50%) took place. We conclude that low-frequency bursting in the Xenopus melanotrope cell strongly promotes exocytosis efficiency and that this efficiency also depends on the capacity of the cytoplasm to buffer the intracellular Ca(2+) signal; strong Ca(2+) buffering during a short burst will decrease exocytosis efficiency, whereas with prolonged bursts, buffering capacity will be overcome, leading to Ca(2+) accumulation and thus enhanced exocytosis efficiency.

Animals↗

Profiling resource use: do different outcomes affect assessments of provider efficiency?

OBJECTIVES: To examine whether 2 outcome measures result in different assessments of efficiency across 22 service networks within the Department of Veterans Affairs (VA). STUDY DESIGN: A retrospective analysis using VA inpatient and outpatient administrative databases. METHODS: A 60% random sample of veterans who used healthcare services during fiscal year 1997 was split into a 40% sample (n = 1,046,803) for development and a 20% sample (n = 524,461) for validation. Weighted concurrent case-mix models using adjusted clinical groups were developed to explain variation in 2 outcomes: "days of care"--the sum of a patient's inpatient and outpatient annual visit days, and "average accounting costs"--the sum of the average service costs multiplied by the units of service for each patient. Two profiling indicators were calculated for each outcome: an unadjusted efficiency index and an adjusted efficiency index. These indices were compared to examine network efficiency. RESULTS: Although about half the networks were identified as "efficient" before and after case-mix adjustment, assessments of individual network efficiency were affected by the adjustment. The 2 outcomes differed on which networks were efficient. For example, 4 networks that appeared as efficient based on days of care appeared as inefficient based on average costs. CONCLUSIONS: Assessments of provider efficiency across the 22 networks depended on the outcome measure used. Knowledge about the extent to which assessments of provider efficiency depend on the outcome measure used is an important step toward improved and more equitable comparisons across providers.

Adult↗

Muscle efficiency: the controversial role of elasticity and mechanical energy conversion in stretch-shortening cycles.

The analysis of muscle efficiency was performed on a variety of simulated muscle stretch-shortening cycles of in situ rat gastrocnemius muscle. The processes of biochemical energy conversions (phosphorylation and contraction-coupling) and mechanical conversions (internal work to external work) were incorporated in the efficiency calculations. Metabolic cost was determined using a simple linear model. Special attention was drawn to the interacting roles of series elastic compliance and contraction dynamics. The results showed that series elastic compliance affected the efficiency of muscle contraction to a great extent. Stiff muscle was well designed to perform efficient contractions in which muscle merely shortened while active. Compliant muscle performed best in true stretch-shortening contractions utilising the storage and release of series elastic energy effectively. However, both stiff and compliant series elastic elements showed similar optimal muscle efficiency values in shortening contractions and stretch-shortening contractions, respectively. The findings indicate that the storage and re-utilisation of series elastic energy does not enhance overall muscle efficiency, but that optimal efficiency is obtained by a proper design of the muscle with regard to the dynamics of the movement task. Furthermore, it was found that although biochemical efficiency determined the feasible range of muscle efficiency, mechanical work conversions had the strongest influence on the exact value of overall muscle efficiency in stretch-shortening contractions.

Animals↗

The efficiency of aerodynamic force production in Drosophila.

Total efficiency of aerodynamic force production in insect flight depends on both the efficiency with which flight muscles turn metabolic energy into muscle mechanical power and the efficiency with which this power is converted into aerodynamic flight force by the flapping wings. Total efficiency has been estimated in tethered flying fruit flies Drosophila by modulating their power expenditures in a virtual reality flight simulator while simultaneously measuring stroke kinematics, locomotor performance and metabolic costs. During flight, muscle efficiency increases with increasing flight force production, whereas aerodynamic efficiency of lift production decreases with increasing forces. As a consequence of these opposite trends, total flight efficiency in Drosophila remains approximately constant within the kinematic working range of the flight motor. Total efficiency is broadly independent of different profile power estimates and typically amounts to 2-3%. The animal achieves maximum total efficiency near hovering flight conditions, when the beating wings produce flight forces that are equal to the body weight of the insect. It remains uncertain whether this small advantage in total efficiency during hovering flight was shaped by evolutionary factors or results from functional constraints on both the production of mechanical power by the indirect flight muscles and the unsteady aerodynamic mechanisms in flapping flight.

Animals↗

A novel method to compensate for different amplification efficiencies between patient DNA samples in quantitative real-time PCR.

Quantification of residual disease by real-time polymerase chain reaction (PCR) will become a pivotal tool in the development of patient-directed therapy. In recent years, various protocols to quantify minimal residual disease in leukemia or lymphoma patients have been developed. These assays assume that PCR efficiencies are equal for all samples. Determining t(14;18) and albumin reaction efficiencies for sixteen follicular lymphoma patient samples revealed higher efficiencies for blood samples than for lymph node samples in general. However, within one sample both reactions had equivalent efficiencies. Differences in amplification efficiencies between patient samples (low efficiencies) and the calibrator in quantitative analyses result in the underestimation of residual disease in patient samples whereby the weakest positive patient samples are at highest error. Based on these findings for patient samples, the efficiency compensation control was developed. This control includes two reference reactions in a multiplex setting, specific for the beta-actin and albumin housekeeping genes that are present in a constant ratio within DNA templates. The difference in threshold cycle values for both reference reactions, ie, the Ct(2) value, is dependent on the amplification efficiency, and is used to compensate for efficiency differences between patient samples and the calibrator. The beta-actin reference reaction is also used to normalize for DNA input. Furthermore, the efficiency compensation control facilitates identification of patient samples that are so contaminated with PCR inhibitory compounds that different amplification reactions are affected to a different extent. Accurate quantitation of residual disease in these samples is therefore impossible with the current quantitative real-time PCR protocols. Identification and exclusion of these inadequate samples will be of utmost importance in quantitative retrospective studies, but even more so, in future molecular diagnostic analyses.

Actins↗