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River temperature sensitivity to hydraulic and meteorological parameters.

A sensitivity analysis is performed to evaluate river temperature variations in response to changes in hydraulic and meteorological conditions. The effects of instream flow, river geometry, and weather factors on daily mean and daily maximum river temperatures are quantified by analytical solutions to a simplified model. The influence coefficient method is used to determine river temperature sensitivity. The sensitivity analysis presents quantitative evidence that river temperatures are more sensitive to instream flowrate, upstream inflow temperature, air temperature, humidity and solar radiation than to other parameters including wind speed and channel geometry and morphometry. It is found that the sensitivity of river temperatures to flow is as significant as that to weather. Daily maximum river temperature is more sensitive to flowrate than daily mean temperature. Adapting the concept of 'diminishing returns', a critical instream flowrate is identified, which divides high and low sensitivity of water temperatures to flowrate. The critical flowrate can be used to determine practically achievable and economically feasible flow requirements for summer river temperature control. The sensitivity results can assist in streamflow management and reservoir operation for protections of habitat and aquatic environment.

Environment↗

Chemical C-terminal protein sequence analysis: improved sensitivity, length of degradation, proline passage, and combination with edman degradation.

Use of a C-terminal sequencer with modified solvents, reagent concentrations, chromatographic parameters, temperatures, and reaction cartridge geometry yields four sets of improvements in chemical degradations. They are increased sensitivity, longer runs, passage of Pro residues, and practical combination with N-terminal degradation. Over 200 proteins and protein fragments with sizes between 20 and 600 residues were analyzed. C-terminal sequences could be interpreted for more than 10 residues at high picomole sample levels, while the 10-pmol level gave 4-5 residues. The average initial yield was 15% but up to 30% could be achieved. The improved performance allowed combination of C- and N-terminal degradations from the same sample application. After initial Edman degradation, the sample is moved to the C-terminal instrument for continued sequencing. Proteins available in limited amount are thereby efficiently analyzed. Lys, modified from the N-terminal degradation, may be detected as the alkylated thiohydantoin-phenylthiocarbamyl-Lys derivative in the C-terminal degradation. Notably, C-terminal sequence analysis could be proceeded through Pro residues which unexpectedly were no absolute hindrance. The improved technique provides characterization of truncation patterns and microheterogeneities in proteins down to the 10-pmol level and is a useful approach for analysis of N-terminally blocked polypeptides.

Mass Spectrometry↗

Physical risk factors for neck pain.

To identify physical risk factors for neck pain, a systematic review of the literature was carried out. Based on methodological quality and study design, 4 levels of evidence were defined to establish the strength of evidence for the relationship between risk factors and neck pain. Altogether, 22 cross-sectional studies, 2 prospective cohort studies, and 1 case-referent study were eligible for determining the level of evidence. The results showed some evidence for a positive relationship between neck pain and the duration of sitting and twisting or bending of the trunk. A sensitivity analysis was carried out excluding 3 items of the quality list, the importance of which seemed doubtful. On the basis of this sensitivity analysis, it was concluded that there is some evidence for a positive relationship between neck pain and the following work-related risk factors: neck flexion, arm force, arm posture, duration of sitting, twisting or bending of the trunk, hand-arm vibration, and workplace design.

Evidence-Based Medicine↗

Discussing hidden bias in observational studies.

In observational studies or nonrandomized experiments, treated and control groups may differ in their outcomes even if the treatment has no effect; this may happen if the groups were not comparable before the start of treatment. The groups may fail to be comparable in either of two ways: They may differ with respect to characteristics that have been measured, in which case there is an overt bias, or they may differ in ways that have not been measured, in which case there is a hidden bias. Overt biases are controlled through adjustments, such as matching. Hidden bias is more difficult to address because the relevant measurements are not available. A sensitivity analysis asks how much hidden bias would need to be present if hidden bias were to explain the differing outcomes in the treated and control groups. A sensitivity analysis provides a tangible and specific framework for discussing hidden biases.

Bias↗

Rapid, sensitive structure analysis of oligosaccharides.

We have developed an efficient method for the derivatization of oligosaccharides, wherein the oligosaccharide is efficiently ligated to a basic aminooxyacetyl peptide by oxime formation. The resulting glycopeptide yields much higher sensitivity in matrix-assisted laser desorption/ionization mass spectrometry than does the underivatized oligosaccharide. Digestion of the glycopeptide by a exoglycosidase array and subsequent mass spectrometric assay of the digestion products provide a sensitive and rapid way to elucidate the structure of the oligosaccharide. In addition to oligosaccharide sequencing, the ligation reaction between an oligosaccharide and an aminooxyacetyl peptide also provides a potentially very convenient and efficient way for the synthesis of glycopeptides or glycoproteins.

Carbohydrate Conformation↗

Cost-effectiveness of antiplatelet agents in secondary stroke prevention: the limits of certainty.

UNLABELLED: Which of the available antiplatelet therapies should be preferred for secondary prevention of recurrent ischemic stroke has been contentious. OBJECTIVE: We applied the Duke Stroke Policy Model (DSPM) to reconsider this issue, paying particular attention to the degree of uncertainty in the estimates of their efficacy. The DSPM is a continuous-time simulation model of stroke development and outcome. METHODS: We modified the inputs to reflect the cost of the drugs aspirin (ASA), extended release dipyridamole/aspirin (DP/A) and clopidogrel (CLO), as well as their relative risk in preventing subsequent ischemic stroke in comparison with placebo (PBO). These relative risks were derived from published reports from the second European Stroke Prevention Study (ESPS-2) and Clopidogrel Versus Aspiring in Patients at Risk of Ischemic Events studies. Precision was addressed by applying bootstrapping to the above estimates of relative risk. The target population was 70-year-old men with nondisabling stroke. The outcome measures were quality-adjusted life-years (QALYs), costs, and costs per QALY. RESULTS: Results of Base Case Analysis: In large part because of its modest drug cost, ASA was cost-effective in comparison with PBO. DP/A tended to have improved outcomes, but at increased costs. CLO was dominated in the base case. RESULTS OF SENSITIVITY ANALYSIS: ASA and DP/A cannot be differentiated on a statistical basis alone. In probabilistic sensitivity analysis, CLO was rarely preferred. CONCLUSIONS: Either DP/A or ASA appear to be a good value in comparison with no treatment, but there is no clear winner between the two. In the absence of a definitive randomized trial, simulation modeling can help clarify the trade-offs between the various antiplatelet agents, but not beyond the constraints imposed by the imprecision in the estimates that can be obtained from the current evidence base.

Aged↗

Cost-utility analysis of orthoptic screening in kindergarten: a Markov model based on data from Germany.

OBJECTIVE: To estimate the long-term cost-effectiveness of a hypothetical screening program for untreated amblyopia in 3-year-old children conducted by orthoptists in all German kindergartens in the year 2000. METHODS: A cost-utility analysis was performed for which a decision tree was combined with a Markov model. Incremental costs and effects during the children's remaining lifetime were estimated. The model took into account the probability of treatment without screening, age-specific treatment success rates, costs of screening and treatment, as well as effects of unilateral and bilateral visual impairment caused by amblyopia and other eye diseases coming along later in life on quality of life (utility). Model parameter values were obtained from a field study of orthoptic screening in kindergarten, from the literature, and from expert interviews. Costs were estimated from a third-party payer perspective. Uncertainty was assessed by univariate and probabilistic sensitivity analysis (Monte Carlo simulation). RESULTS: The incremental cost-effectiveness ratio (ICER) of orthoptic screening was 7397 Euro (euro) per quality-adjusted life year (QALY) when costs and effects were discounted at 5%. In univariate sensitivity analysis, the ICER was sensitive to the uncertainty regarding the utility of unilateral visual impairment and to the discount rate for effects; besides uncertainty regarding the prevalence of untreated amblyopia, the odds ratio of success of treatment when started late, and the probability of treatment without screening had a noticeable but much smaller effect. Monte Carlo simulation yielded a 90% uncertainty interval for the ICER of 3452 euro/QALY to 72 637 euro/QALY; the probability of an ICER <25 000 euro/QALY was 84%. CONCLUSIONS: The ICER of orthoptic screening seems to fall within a range that warrants careful consideration by decision-makers. Much of the uncertainty in results comes from the uncertainty regarding the effect of amblyopia on quality of life. To reduce this uncertainty, the impact of amblyopia on utility should be investigated.

Amblyopia↗

Simulating nonequilibrium transport of atrazine through saturated soil.

Atrazine, an herbicide widely used for selective control of grassy weeds in the fields where maize is grown, is a potential ground water contaminant in China and, consequently, there is interest in predicting its mobility in agricultural soils. In this study, we determined the nonequilibrium transport characteristics of atrazine in Shahe soil (Beijing sandy loam) using the advection-dispersion equation, and using a sensitivity analysis, we evaluated the contribution of the uncertainty in a given input parameter to the overall uncertainty in model results. The asymmetrical shape and tailing of the atrazine breakthrough curve (BTC) showed that atrazine was subject to nonequilibrium transport. The observed atrazine BTC was best fitted by the chemical nonequilibrium model with a nonlinear least-squares optimization approach. Results from the sensitivity analysis indicated that the retardation factor was the most sensitive parameter. Considering the reliability of the estimated parameters, the best fit to the atrazine BTC was obtained by fixing the retardation factor based on the linear distribution coefficient, and by calculating the dispersion coefficient from the bromide BTC and the average pore water velocity from the measured data; nonequilibrium parameters were the only unknown parameters that were optimized. Model verification procedures were based on best-fit parameters optimized from one soil column experiment and applied to simulate the transport of atrazine in the duplicate experiment. The results showed there was good agreement between measured and simulated concentrations for atrazine leaching in the soil column.

Atrazine↗

Test and treat strategies for Helicobacter pylori in uninvestigated dyspepsia: a Canadian economic analysis.

BACKGROUND: Recognition of the pivotal role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has revolutionized primary care approaches to dyspepsia. Decision analysis was used to compare the cost effectiveness of empirical ranitidine with a test and treat strategy using either H pylori serology or the 13carbon-urea breath test (13C-UBT). PATIENTS AND METHODS: A cohort of patients under age 50 years presenting with uninvestigated dyspepsia was evaluated. Three initial strategies were compared with respect to direct medical costs and effectiveness in curing H pylori-related ulcers - empirical ranitidine, H pylori serology and UBT. A one-year time horizon and third-party payer perspective were adopted in a Canadian health care setting. RESULTS: UBT was more costly than either serology or ranitidine but was the most effective strategy and required the fewest endoscopies. No strategy demonstrated dominance over another in the base case. The incremental cost effectiveness ratio (ICER) of serology versus ranitidine was $118/cure, and sensitivity analysis induced dominance of serology in several plausible scenarios. The baseline ICER of UBT versus serology was $885/cure but showed substantial variation in sensitivity analysis. Each ICER was highly sensitive to variation in the cost of the tests themselves. At a serology cost of $25, UBT became dominant when its cost fell to $39. CONCLUSIONS: In low risk patients with uninvestigated dyspepsia, testing for H pylori using serology appears to be economically attractive. 13C-UBT may be a cost effective alternative to serology if local conditions closely approximate the model parameters. Future changes in the costs of serology and 13C-UBT may determine the optimal approach.

Anti-Ulcer Agents↗

A model for protein translation: polysome self-organization leads to maximum protein synthesis rates.

The genetic information in DNA is transcribed to mRNA and then translated to proteins, which form the building blocks of life. Translation, or protein synthesis, is hence a central cellular process. We have developed a gene-sequence-specific mechanistic model for the translation machinery, which accounts for all the elementary steps of the translation mechanism. We performed a sensitivity analysis to determine the effects of kinetic parameters and concentrations of the translational components on protein synthesis rate. Utilizing our mathematical framework and sensitivity analysis, we investigated the translational kinetic properties of a single mRNA species in Escherichia coli. We propose that translation rate at a given polysome size depends on the complex interplay between ribosomal occupancy of elongation phase intermediate states and ribosome distributions with respect to codon position along the length of the mRNA, and this interplay leads to polysome self-organization that drives translation rate to maximum levels.

Computer Simulation↗

[Effect of composition of reagents for activated partial thromboplastin time on their sensitivity during analysis of blood coagulation factors].

Brain cephaline-based reagents for evaluating activated partial thromboplastin time (APTT) and soybean phosphatides with ellagic acid complex activator with intermediate metal ions have been studied. The sensitivity of these reagents to internal clotting factors (VIII and IX) and heparin is determined by phospholipid nature and type of metal. The results help obtain highly active and sensitive APTT reagents.

Factor IX↗

Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.

BACKGROUND AND OBJECTIVES: Studies of diagnostic accuracy most often report pairs of sensitivity and specificity. We demonstrate the advantage of using bivariate meta-regression models to analyze such data. METHODS: We discuss the methodology of both the summary Receiver Operating Characteristic (sROC) and the bivariate approach by reanalyzing the data of a published meta-analysis. RESULTS: The sROC approach is the standard method for meta-analyzing diagnostic studies reporting pairs of sensitivity and specificity. This method uses the diagnostic odds ratio as the main outcome measure, which removes the effect of a possible threshold but at the same time loses relevant clinical information about test performance. The bivariate approach preserves the two-dimensional nature of the original data. Pairs of sensitivity and specificity are jointly analyzed, incorporating any correlation that might exist between these two measures using a random effects approach. Explanatory variables can be added to the bivariate model and lead to separate effects on sensitivity and specificity, rather than a net effect on the odds ratio scale as in the sROC approach. The statistical properties of the bivariate model are sound and flexible. CONCLUSION: The bivariate model can be seen as an improvement and extension of the traditional sROC approach.

Data Interpretation, Statistical↗

The cost utility analysis of riluzole for the treatment of amyotrophic lateral sclerosis in the UK.

This study reports the results of a long-term economic evaluation of riluzole in the treatment of amyotrophic lateral sclerosis (ALS) versus best supportive care in the United Kingdom. The aim was to assess the cost implications of the life extension offered by riluzole through cost utility analysis based on patient assessed utilities of different health states.A Markov model was used to assess the cost-effectiveness of Rilutek with best supportive care. Transition possibilities and the distribution of patients by health states were taken from a cohort of 954 patients drawn from a large randomised, double blind, placebo-controlled, multicentre trial between 1992 and 1994 in the first 18 months and used to extrapolate the model to assess the long-term prolongation of life. Four distinct health states were used corresponding to mild, moderate, severe and terminal states. Costs associated with Rilutek included the acquisition cost and bi-monthly monitoring for raised ALT levels. Patient assessed utilities were collected by use of the standard gamble technique. 77 patients were entered into the study from two centres (King's, London and Preston) in the UK. Mean utilities for each of the health states was generated and, given that the data were skewed, a sensitivity analysis was undertaken with the median utility values. The implications of life extension offered by riluzole versus best supportive care were assessed both in terms of life extension projected and quality adjusted survival using patient based utilities. Using the Markov model and the transitional probabilities the base case cost per life year gained was estimated at pound sterlings 14,370 and applying Standard Gamble utility scores, the base case cost per QALY was assessed as pound sterlings 20,904. The effect of discounting costs and benefits altered the cost effectiveness analysis to pound sterlings 17,760 per life year gained while a sensitivity analysis around median or mean scores for the utility weight resulted in a range of pound sterlings 19,020 to pound sterlings 25,794 per QALY gained.

Amyotrophic Lateral Sclerosis↗

Effects of extended problem-based learning interventions on undergraduate nursing education: A systematic review.

OBJECTIVE: Exploring the effects of long-term PBL (problem-based learning) intervention on undergraduate nursing students. METHODS: The article retrieved literature from CINAHL Complete, Academic Search Complete, Web of Science, PubMed, EMBASE, OVID, and Cochrane Library up to January 2025. Studies had to meet all of these criteria: (1) They used a randomized controlled trial (RCT) and quasi-experimental design. (2) The PBL pedagogy intervention lasted 4&#xa0;weeks or longer. (3) The participants were undergraduate nursing students. (4) They reported primary outcomes. These included critical thinking, problem-solving skills and self-directed learning. Two researchers screened articles, extracted data, and assessed quality independently using blinding. They used Cochrane ROB2 for RCTs and ROBINS-I for quasi-experimental studies to judge bias risk. Meta-analysis was performed using RevMan 5.4 software. For continuous variables, standardized mean difference (SMD) and 95% confidence interval were calculated. Heterogeneity was assessed by I2 statistic. When I2&#xa0;>&#xa0;50%, sensitivity analysis was conducted. The source of heterogeneity was explored by excluding studies one by one. The primary outcomes included standardized critical thinking, problem-solving, and self-directed learning assessment results. RESULTS: A total of 11 randomized controlled trials and quasi-experimental studies were retrieved and included for meta-analysis. The experimental group significantly outperformed the control group in critical thinking, problem-solving, and self-directed learning, with differences being statistically significant (P&#xa0;&#x2264;&#xa0;0.05). However, high heterogeneity was observed. After sensitivity analysis, the heterogeneity was reduced and the results remained statistically significant, indicating that the findings were not solely dependent on the excluded studies.

Problem-Based Learning↗

Cost effectiveness of treatment for amblyopia: an analysis based on a probabilistic Markov model.

AIMS: To estimate the long term cost effectiveness of treatment for amblyopia in 3 year old children. METHODS: A cost utility analysis was performed using decision analysis including a Markov state transition model. Incremental costs and effects during the children's remaining lifetime were estimated. The model took into account the costs and success rate of treatment as well as effects of unilateral and bilateral visual impairment caused by amblyopia and other eye diseases coming along later in life on quality of life (utility). Model parameter values were obtained from the literature, and from a survey of experts. For the utility of unilateral visual impairment a base value of 0.96 was assumed. Costs were estimated from a third party payer perspective for the year 2002 in Germany. Costs and effects were discounted at 3%. Uncertainty was assessed by univariate and probabilistic sensitivity analysis (Monte-Carlo simulation). RESULTS: The incremental cost effectiveness ratio (ICER) of treatment was euro2369 per quality adjusted life year (QALY). In univariate sensitivity analysis the ICER was most sensitive to uncertainty concerning the utility of unilateral visual impairment-for example, if this utility was 0.99, the ICER would be euro9148/QALY. Monte-Carlo simulation yielded a 95% uncertainty interval for the ICER of euro710/QALY to euro38 696/QALY; the probability of an ICER smaller than euro20 000/QALY was 95%. CONCLUSION: Treatment for amblyopia is likely to be very cost effective. Much of the uncertainty in results comes from the uncertainty regarding the effect of amblyopia on quality of life. In order to reduce this uncertainty the impact of amblyopia on utility should be investigated.

Amblyopia↗

Wavelet analysis can sensitively describe dynamics of ethanol evoked local field potentials of the slug (Limax marginatus) brain.

Odorants evoke characteristic, but complex, local field potentials (LFPs) in the molluscan brain. Wavelet tools in combination with Fourier analysis can detect and characterize hitherto unknown discrete, slow potentials underlying the conspicuous oscillations. Ethanol was one of the odorants that we have extensively studied (J. Neurosci. Methods, 119 (2002) 89). To detect new features and to elucidate their functions, we tested the wavelet tools on the ethanol-evoked LFP responses of the slug (Limax) procerebrum. Recordings were made in vitro from the neuropile and the cell layer. The present study led to the following findings: (i) Mutual exclusion. Energy concentrated mainly in two ranges, (a) 0.1-0.4 Hz and (b) 1.56-12.5 Hz, and the sum of energy remained constant throughout experiments regardless of the condition. A redistribution of relative energy within this sum seemed to occur in the course of main, possible interactions between the two components excluding each other ('mutual exclusion'). (ii) Transient signal ordering and disordering. Ethanol stimulation alternatingly evoked periods of strongly time evolving oscillation dominated by the energy of 1.56-12.5 Hz (increase of entropy=disordered or complexly ordered state) and those of near-silence were predominated by the energy of 0.1-0.4 Hz (decrease of entropy=ordered state). (iii) About 0.1 Hz slow wave oscillation. It was robust. The dominant energy oscillation and the resulting large entropy fluctuation were negatively correlated to each other, and revealed strong frequency-tuning or synchronization at this frequency. Our findings suggest that discrete slow waves play functionally important roles in the invertebrate brain, as widely known in vertebrate EEG. Wavelet tools allow an easy interpretation of several minutes of frequency variations in a single display and give precise information on stimulus-evoked complex change of the neural system describing the new state 'more ordered' or 'non-ordered or more complexly ordered'.

Animals↗

Modelling and costing the consequences of using an ACE inhibitor to slow the progression of renal failure in type I diabetic patients.

Antihypertensive drugs slow the progressive decline in renal function seen in patients with insulin-dependent diabetes and nephropathy. In a recent study, the ACE inhibitor captopril protected against this deterioration in renal function. We developed an economic model to analyse the cost impact of ACE inhibitor treatment on progression to endstage renal failure (ESRF) in diabetic patients over 4 years. Two scenarios were compared: one describing the progression of a cohort of 1000 patients receiving 25 mg captopril three times daily, and the other for an equivalent cohort without such prophylactic treatment. Previously published data were used to estimate the transition rates for each stage from the onset of renal failure until death. All direct costs were discounted by an annual rate of 6%, and were subjected to sensitivity analysis. The discounted cost saving of ACE inhibitor treatment for a cohort of 1000 patients was estimated as 0.95 million pounds over 4 years. Under sensitivity analysis, these results were very robust to variations in the costs of ESRF treatment. Prophylactic treatment with ACE inhibitors was predicted to provide substantial increases in life expectancy and reduction in the incidence of ESRF, while also providing significant economic savings.

Adolescent↗

Role of antibiotics in acute pancreatitis: A meta-analysis.

In an attempt to decrease the infectious complications of acute pancreatitis and its high mortality, many investigators have conducted randomized prospective trials on the efficacy of prophylactic antibiotics. The results of these studies are conflicting, and many have called for a large multicenter study. Because multicenter trials are costly and difficult to organize, we believe that meta-analysis is a reasonable alternative. A meta- analysis of all eight previously published trials of prophylactic antibiotics in acute pancreatitis was performed. The end point was death. The Mantel-Haenszel statistic was used to summarize odds ratios across studies in a fixed effects model, after homogeneity was assessed. Sensitivity analysis was performed as appropriate. The meta-analysis of all eight trials showed a positive benefit for antibiotics in reducing mortality. Sensitivity analysis showed that the advantage was limited to patients with severe pancreatitis who received broad- spectrum antibiotics that achieve therapeutic pancreatic tissue levels. It is recommended that all patients with severe pancreatitis be treated with broad- spectrum antibiotics that achieve therapeutic levels in pancreatic tissue.

Acute Disease↗