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Plutonium oxide benchmark problems for the SOURCES code.

Neutron yields and spectra for nine plutonium oxide (PuO(2)) compositions were calculated with the SOURCES 4C computer code. In addition to five experimental measurements serving as benchmarks for the SOURCES homogenous option, neutron production information for three postulated oxide compositions is also presented. Spectral information for neutrons originating from spontaneous fission and (alpha,n) reactions with light targets is presented in tabular format for further manipulation.

Journal Article↗

Benchmarking a memetic algorithm for ordering microarray data.

This work introduces a new algorithm for "gene ordering". Given a matrix of gene expression data values, the task is to find a permutation of the gene names list such that genes with similar expression patterns should be relatively close in the permutation. The algorithm is based on a combined approach that integrates a constructive heuristic with evolutionary and Tabu Search techniques in a single methodology. To evaluate the benefits of this method, we compared our results with the current outputs provided by several widely used algorithms in functional genomics. We also compared the results with our own hierarchical clustering method when used in isolation. We show that the use of images, corrupted with known levels of noise, helps to illustrate some aspects of the performance of the algorithms and provide a complementary benchmark for the analysis. The use of these images, with known high-quality solutions, facilitates in some cases the assessment of the methods and helps the software development, validation and reproducibility of results. We also propose two quantitative measures of performance for gene ordering. Using these measures, we make a comparison with probably the most used algorithm (due to Eisen and collaborators, PNAS 1998) using a microarray dataset available on the public domain (the complete yeast cell cycle dataset).

Algorithms↗

Atom-based 3D-chiral quadratic indices. Part 2: prediction of the corticosteroid-binding globulinbinding affinity of the 31 benchmark steroids data set.

A quantitative structure-activity relationship (QSAR) study to predict the relative affinities of the steroid 'benchmark' data set to the corticosteroid-binding globulin (CBG) is described. It is shown that the 3D-chiral quadratic indices closely correlate with the measured CBG affinity values for the 31 steroids. The calculated descriptors were correlated with biological data through multiple linear regressions. Two statistically significant models were obtained when non-stochastic (R = 0.924 and s = 0.46) as well as stochastic (R = 0.929 and s = 0.46) 3D-chiral quadratic indices were used. A leave-one-out (LOO) approach to model validation is used here; the best results obtained in the cross-validation procedure with non-stochastic (q2 = 0.781) and stochastic (q2 = 0.735) 3D-chiral quadratic indices are better or similar to most of the 3D-QSAR approaches reported so far. These results support the idea that the 3D-chiral quadratic indices may be helpful in prediction of the corticosteroid-binding affinity for new compounds.

Computational Biology↗

Genome-sequencing-based benchmarking of antimicrobial resistance, treatment outcomes and healthcare transmission events for Clostridioides difficile infection in Australian hospitals.

BACKGROUND: Clostridioides difficile infection (CDI) remains a priority for infection prevention and control in health care, particularly with the emergence of hypervirulent strains and antimicrobial resistance (AMR). AIM: To characterize the genomic epidemiology and AMR profiles of culture-confirmed CDI cases within tertiary hospitals in Australia. METHODS: A total of 155 C. difficile isolates from 142 patients with CDI diagnosed in four hospitals between 2023 and 2025 were studied. Data collected included patient demographics, severity of infection, antibiotic treatment and clinical outcomes at 8 weeks. Phenotypic susceptibility to vancomycin, fidaxomicin, metronidazole, moxifloxacin, meropenem, tetracycline and rifaximin were determined by agar dilution. Isolates underwent whole-genome sequencing (WGS) for genotyping and resistome assessment. FINDINGS: WGS differentiated 39 distinct sequence types among CDI isolates across different healthcare services. In total, 100 isolates were singletons and 55 (35% clustering rate) isolates were considered to be genomically related (difference of two or fewer single-nucleotide polymorphisms). Of these, 12 patients (8.5%) with close hospital contact formed six epidemiologically linked clusters. Phenotypic susceptibility results were obtained for 134 (86.4%) CDI isolates. There was no phenotypic resistance to vancomycin [minimum inhibitory concentration required to inhibit the growth of 90% of isolates (MIC90) 1 mg/L], metronidazole (MIC90 0.5 mg/L) or fidaxomicin (MIC90 0.5 mg/L). There was no association in the study cohort between the presence of resistance genes or reduced phenotypic susceptibility and CDI recurrence. CONCLUSION: Genomic analysis of C. difficile isolates did not identify any outbreaks or an association between the sequence type or presence of a resistance gene and clinical outcomes. High-resolution characterization and identification of antibiotic resistance, CDI clinical relapse and recent transmission offered by genome sequencing can provide important benchmarks for hospital infection control.

Antibiotic resistance↗

Apparent truth about congenital diaphragmatic hernia: a population-based database is needed to establish benchmarking for clinical outcomes for CDH.

BACKGROUND: The authors hypothesize that recent single or multiinstitution-based reports of improved survival of congenital diaphragmatic hernia (CDH) patients are biased by patient selection, practice, and referral patterns. Here the authors report a population-based analysis of the clinical outcomes of CDH in the province of Ontario for 1996. METHODS: A retrospective analysis of cross-sectional data from the Bureau of Vital Statistics of Ontario and all 5 pediatric surgical institutions in Ontario for 1996 was performed. RESULTS: Twenty-four CDH-associated deaths were registered in Canada in 1996. Fourteen of 24 occurred in Ontario (58.3%). Of 30 institutionally identified CDH in Ontario, 8 patients died (26.7%). CDH-associated infant mortality rate was 6.6 of 100,000 live births in Canada compared with 10 of 100,000 live births for Ontario (Relative risk, 1.4; confidence interval, 0.5, 3.7; P >.01). Neonatal death (<28 postnatal days) accounted for the majority, 13 of 14 (92.8%) of deaths. Six of 14 (42.9%) CDH-associated deaths, however, were not accounted by the institutional-based reporting. In addition, institutional-based survival rates for CDH varied from 62.5% to 100%. CONCLUSIONS: Our results indicate the existing bias associated with institution-based reporting and database of CDH. The "hidden mortality" associated with CDH is still present. A population-based database is needed to establish the benchmarking for management of CDH.

Bias↗

Use of benchmark dose and meta-analysis to determine the most sensitive endpoint for risk assessment for dimethoate.

A meta-analysis of several rat toxicity studies for dimethoate was conducted to determine the most sensitive endpoint for use in risk assessment. The analysis was motivated by a recent developmental neurotoxicity (DNT) study, which identified the same no observed adverse effect level (NOAEL) for pup mortality and cholinesterase inhibition. The pup mortality NOAEL was lower than that determined in a range-finding study for the DNT and other reproduction studies, and was highly influenced by a single total litter loss in the middle dose group, which made interpretation difficult. First, a meta-analysis was conducted of four recent studies by gavage dosing with very similar designs, including the DNT. Benchmark dose (BMD) modeling was used to determine the appropriate point of departure for regulatory purposes, the lower limit of the BMD for a 5% incidence for pup mortality (BMDL(5)) and the lower limit of a 10% inhibition of brain cholinesterase (BMDL(10)*), the asterisk denotes that the BMD is based on continuous response variable as opposed to an incidence level. For pup mortality, the BMDL(5) for post-natal days (PND) 1-4 was 0.64 mg/kg/day. For cholinesterase inhibition, the lowest BMDL(10)* was 0.19 mg/kg/day for the dams at gestation day 20. These results show that the regulatory point-of-departure for cholinesterase inhibition is more than threefold lower than pup mortality. Thus, risk assessments protecting against cholinesterase inhibition are likely to also be protective of pup mortality. In addition, cholinesterase inhibition and pup mortality were evaluated in two 2-generation reproduction studies by dietary exposure. Also, cholinesterase inhibition was evaluated in a 28-day dietary study. Dietary exposure is more relevant than gavage exposures for many human risk assessment scenarios. There was no consistent pup mortality at the highest doses of the two 2-generation dietary studies (6.0 and 6.5mg/kg/day). The average BMD(10)s for brain cholinesterase inhibition for the 2-generation studies was 0.65 mg/kg/day, with a range of 0.49--0.96 mg/kg/day. This suggests that cholinesterase inhibition is at least a 10-fold more sensitive endpoint than pup mortality for dietary exposures. For the 28-day dietary study, the BMD(10) for brain cholinesterase inhibition was 1.1mg/kg/day for males and 0.70 mg/kg/day for females. The exposure duration in the 28-day dietary study is closest to the durations in the gavage studies. Compared to the dams in the gavage studies, which had a BMDL(10) of 0.19 mg/kg/day, the animals were more than threefold more sensitive to cholinesterase inhibition by gavage compared to dietary exposure.

Age Factors↗

The role of the benchmark dose in a regulatory context.

The use of no observed adverse effect levels (NOAELs) as a way of interpreting toxicology studies carries a number of problems, and the benchmark dose (BMD), or its lower confidence limit have been proposed as potential replacements. In practice, the theoretical advantages of the BMD approach are often outweighed by the practical disadvantages posed in a regulatory context. Attempts to seek consensus for the routine use of BMD methodology tend to involve diluting its potential advantages as much as they address the disadvantages, resulting in a relatively complex interpolation tool that delivers little more than the NOAEL. It is time to recognise that the BMD will never entirely replace the NOAEL. The two methods can have complementary roles. The NOAEL is well suited as a routine simple summary of effects in toxicology studies, whilst the BMD can be a higher tier approach for the interpretation of the most critical studies in a regulatory data package.

Algorithms↗

Spectrum of surgical risk for left main coronary stenoses: benchmark for potentially competing percutaneous therapies.

Coronary artery bypass grafting is the preferred therapy for left main trunk coronary stenoses because of a demonstrated survival advantage compared with medical therapy. Recently, however, advocates of percutaneous intervention have suggested that stenting or atherectomy may provide acceptable results for these patients. To determine the spectrum of surgical outcome among patients with left main trunk coronary stenoses, we analyzed 14 potential covariates of in-hospital and 3-year mortality for a consecutive series of patients without prior coronary artery bypass grafting treated at our institution from January 1990 to December 1995. In-hospital mortality (2.3%) for 1585 consecutively treated patients correlated independently with renal dysfunction, age, and class III to IV heart failure. A model was constructed that allowed prediction of outcome (c-statistic = 0.77, p < 0.0001), and only the 9% of patients at highest risk were found to be at risk for death >5%. Mortality at 3 years (15.6%+/-2.2%) in a previously specified subgroup (n = 285) correlated independently with baseline age, renal dysfunction, and chronic pulmonary disease. A model was constructed that allowed prediction of outcome for the validation sample (four risk groups with 3-year mortality rates of 4.5%+/-2.5%, 6.5%+/-2.8%, 20.0%+/-4.2%, and 39.8%+/-8.5%; p < 0.0001. These data provide a contemporary benchmark of clinical outcome against which possible competing therapies may be compared.

Aged↗

Clinical benchmark for healing of chronic venous ulcers. Venous Ulcer Study Collaborators.

BACKGROUND: To determine the results of standardized ulcer treatment regimes and effects of the oral thromboxane A2 antagonist Ifetroban (250 mg daily) on healing of chronic lower-extremity venous stasis ulcers. METHODS: In a prospective, randomized, double blind, placebo-controlled multicenter study, 165 patients were randomized to Ifetroban (n = 83) versus placebo (n = 82) for a period of 12 weeks. Both groups were treated with sustained graduated compression and hydrocolloid. Ulcer size was measured weekly by tracings and computerized planimetry. A total of 150 patients completed the study. RESULTS: Complete ulcer healing was achieved after 12 weeks in 55% of patients receiving Ifetroban and in 54% of those taking a placebo with no significant differences; 84% of ulcers in both groups achieved greater than 50% area reduction in size. CONCLUSIONS: These results are likely to be useful as a benchmark for comparison with other treatment protocols concerning the care of chronic lower-extremity stasis ulcers.

Adult↗

Nomographic correspondence between specialist cell responses, electroantennograms and the probability of behavioral response: the importance of comparable stimuli and a benchmark.

Responses from single receptor cells, electroantennograms (EAGs) and the proportion of upwind flight in a wind tunnel elicited by graded stimulus strengths of (Z)-7-dodecenyl acetate (Z7-12:Ac) were measured from male cabbage loopers, Trichoplusia ni (Hübner). The approach that was taken to illustrate the relationship between these three measures on the same scale was to express the airborne stimulus strength for all three measures in molar units. A collateral discovery was finding a linear relationship between spiking activity in the receptor cells and the proportion of the first two stages of upwind flight behavior.Two validations corroborate the approach. The first of these demonstrates that, with only three exceptions, there is agreement between behavioral and electrophysiological measures from several laboratories. At the same time, there is a demonstration highlighting the importance of the use of a stimulus benchmark in establishing the relevancy of an experimental stimulus strength to a natural context. The second validation shows that both electrophysiological and behavioral data can be used to estimate the same emission rate of Z7-12:Ac at low dosages from filter paper.

Journal Article↗

The Olmsted County Benchmark Project: primary study findings and potential implications for corporate America.

Since 1965, expenditures for medical care in the United States have increased 10-fold. As a result, corporate outlays for health benefits have skyrocketed. Employers have instituted various cost-containment measures based in part on reports of wide variations in rates of utilization and the assumption that unnecessary or inappropriate utilization of medical care contributes to increasing costs. Frequently, however, employers lack adequate means for identifying sources of variation or for evaluating its appropriateness. In this article, we report on a project in which hospital utilization among several US corporate populations was compared with that for a geographically defined benchmark population to assist employers in the assessment of their rates of utilization and expenditures and to identify specific areas that merit further investigation. Our findings illuminate the difficulties in constructing valid rates from medical-care claims data and emphasize potential biases due to problems of comparability between populations. We also address the potential value of such comparison for helping corporations identify areas in which cost-containment efforts may be most effective and yet not jeopardize the quality of medical care.

Adolescent↗

Developmental toxicity of carbendazim: comparison of no-observed-adverse-effect level and benchmark dose approach.

The benchmark dose (BD) approach has been applied to foetal data from four gavage segment II studies (rat studies 1 and 2, rabbit study, hamster study) on the teratogenic benzimidazole carbendazim. Nineteen parameters were assessed using the log-normal model as a practical tool to derive BDs; good model fitting was observed for all except two parameters. Data were evaluated on a 'per-implant/foetus' basis; BDs were derived from response rate increases of 1, 5, and 10%. The values were compared to the lowest-observed-adverse-effect levels (LOAELs) and no-observed-adverse effect levels (NOAELs) obtained by Fisher's exact test on a 'per-implant/foetus' basis. Frank effects observed only at the top dose and/or small sample size tended to increase the 95% confidence limits and this influenced the determination of BD. Generally, the BD approach provided slightly more conservative estimates than NOAEL; overall, BD01 and BD05 were similar to NOAEL, or even lower for several parameters. The LOAEL in most cases was similar to BD10. Reference doses obtained by dividing BD01 by a 10 or 100 uncertainty factor, corresponded to residual risks of 10(-5) or below. For two critical parameters (hydrocephalus in rat study 1 and resorption rate in the rabbit study) a NOAEL could not be found, whereas a BD was always determined.

Animals↗

Benchmark measurements for lung dose corrections for X-ray beams.

A well defined set of clinically relevant reference measurements for photon dose calculations in the presence of the lung have been provided. These benchmark data were mainly obtained in low-density (rho = 0.31 gcm-3) lunglike material as well as in waterlike plastic for 4 and 15 MV X-ray beams. Some additional measurements were performed with materials having a density of 0.015 gcm-3 and 0.18 gcm-3. Phantom geometries included simple layered geometries, finite lung cross section geometries, simulated mediastinum geometries, and simulated tumor in lung geometries. The data are reported as central axis depth doses. A number of parameters were varied, including the field size, the lung geometry, and the distance in and behind the lung.

Humans↗

Benchmarking the in vitro activity of moxifloxacin against recent isolates of Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. A European multi-centre study.

To benchmark the activity of moxifloxacin, a European study comprising 900 Streptococcus pneumoniae, 1051 Haemophilus influenzae, and 226 Moraxella catarrhalis referred from 30 institutions during 1998 is described. For S. pneumoniae, moxifloxacin and trovafloxacin MIC(90) and modal MICs values were 0.12 microg/ml and independent of susceptibility to other drug classes, geography, or site of infection. MIC(90)/modal MICs were, respectively, 0.25/0.12 microg/ml for grepafloxacin, 0.25/0.25 microg/ml for sparfloxacin, and 1.0/0.5 microg/ml for levofloxacin. The moxifloxacin C(max):MIC ratio of 20.8-26.3 is higher than comparator fluoroquinolones. Five isolates were intermediate or resistant to grepafloxacin, sparfloxacin, or levofloxacin of which four and three remained susceptible to trovafloxacin and moxifloxacin, respectively. For moxifloxacin, > 90% of S. pneumoniae isolates demonstrated MICs > or =3 dilutions below the susceptibility breakpoint used. Modal MICs and MIC(90) for M. catarrhalis (both 0.03 microg/ml) and H. influenzae (0.03 microg/ml and 0.06 microg/ml) were independent of beta-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future surveillance studies that will be important for detecting and tracking any trends in changing activity of this fluoroquinolone.

Anti-Infective Agents↗

The analysis of clinical outcomes: getting started in benchmarking.

BACKGROUND: Computerized clinical outcomes measurement systems are now routinely available to help physicians and hospital administrators assess and improve the quality of care in their organizations. The Voluntary Hospitals of America, Pennsylvania (VHA/PA), used MedisGroups data to help understand the processes of care that contributed to different clinical outcomes at different network hospitals. METHOD: A physician subcommittee decided early on (1) to focus on the best outcomes rather than the poorest and (2) to determine the variations in processes of care that might have led to either superior or inferior clinical outcomes. For two common procedures, appendectomy and cesarean section, the subcommittee identified variation within comparative outcomes data, evaluated that variation, and studied and communicated to the rest of the hospital network the process that produced the best outcomes. CONCLUSION: These pilot projects set the stage for current clinical benchmarking within the VHA/PA system. The committee of physicians learned that each hospital develops its own approach to common clinical conditions. These approaches become standardized at each hospital in the form of institutional attitudes, beliefs, policies, and procedures. The methods of evaluation and treatment by hospital staff can significantly alter the clinical outcomes for the populations served.

Appendectomy↗

A survey-based benchmarking approach for health care using the Baldrige quality criteria.

BACKGROUND: Since 1988, manufacturing and service industries have been using the Malcolm Baldrige National Quality Award to assess their management processes (for example, leadership, information, and analysis) against critical performance criteria. Recognizing that the typical Baldrige assessment is time intensive and dependent on intensive training, The Pacer Group, a consulting firm in Dayton, Ohio, developed a self-assessment tool based on the Baldrige criteria which provides a snapshot assessment of an organization's management practices. STUDY: The survey was administered at 25 hospitals within a health care system. Hospitals were able to compare their scores with other hospitals in the system, as well as the scores of a Baldrige award winner. Results were also analyzed on a systemwide basis to identify strengths and weaknesses across the system. RESULTS: For all 25 hospitals, the following areas were identified as strengths: management of process quality, leadership, and customer focus and satisfaction. Weaknesses included lack of employee involvement in the quality planning process, poor design of quality systems, and lack of cross-departmental cooperation. EXAMPLE: One of the surveyed hospitals launched improvement initiatives in knowledge of improvement tools and methods and in a patient satisfaction focus. A team was formed to improve the human resource management system. Also, a new unit was designed using patient-centered care principles. A team re-evaluated every operation that affected patients on the unit. CONCLUSION: A survey modeled after the Baldrige Award criteria can be useful in benchmarking an organization's quality improvement practices.

Attitude of Health Personnel↗

Benchmark for Quantitative Global and Redox Proteomics Analysis by Combining Protein-Aggregation Capture and Data Independent Acquisition.

Oxidative damage plays a critical role in various diseases including cardiovascular and neurological disorders. Thiol redox reactions, acting as oxidative stress sensors, influence protein structure and function. Redox proteomics, based on the differential alkylation of cysteine sites followed by mass spectrometry, enables the comprehensive analysis of thiol redox status in cells and tissues. However, these approaches require extensive sample manipulation and are not compatible with data-independent acquisition techniques. Here, we introduce PACREDOX, an innovative strategy based on protein aggregation capture (PAC), and demonstrate its compatibility with library-free DIA. Compared with traditional methods such as FASILOX, PACREDOX reduces preparation time and costs while maintaining thiol and proteome coverage. To enable library-free DIA, we corrected in silico spectral libraries in DIA-NN using experimental retention time data from methylthiolated-Cys peptides. PACREDOX with DIA was benchmarked against FASILOX in a myocardial infarction model, yielding the same biological insights, while enhancing peptide and protein coverage. Our results underscore the potential and efficiency of this methodology for studying oxidative damage. Overall, PACREDOX offers an automatable, high-throughput, and cost-effective strategy for redox proteomics.

Proteomics↗

Benchmarking state-of-the-art ab initio thermochemical predictions with accurate pulsed-field ionization photoion-photoelectron measurements.

This Account presents a comparison between highly precise thermochemical data, including ionization energies, 0 K dissociative photoionization thresholds, and 0 K bond dissociation energies, of selected radicals and molecules and their cations obtained by pulsed field ionization photoion-photoelectron measurements and state-of-the-art thermochemical predictions calculated by the wavefunction-based ab initio CCSD(T)/CBS procedures with high-level corrections. The CCSD(T)/CBS method combines the coupled cluster approach including single, double, and quasi-perturbative triple excitations [CCSD(T)] and the complete basis set (CBS) extrapolation approximation. This benchmarking effort indicates that the CCSD(T)/CBS procedures together with high-level corrections are capable of yielding reliable thermochemical predictions with error limits < or =10 meV for small radicals and molecules and their cations. The error limits increase to approximately 35 meV for larger molecular species, such as phenyl and benzyl radicals.

Journal Article↗