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Exploratory data analytic techniques to evaluate anticancer agents screened in a cell culture panel.

Information theory is used to provide a measure of selectivity, i.e., the degree to which a drug has preferential toxicity or growth inhibition for one or a few cell lines from a large panel. The selectivity measure is intended to complement a measure of differential growth inhibition in evaluating the drug development potential of a new compound. Also, a similarity measure obtained from information theory is used to classify drugs according to their pattern of responses on the panel. Some structure-activity relations emerge. This work is applied to 176 agents selected to be tested by the National Cancer Institute in about 50 cell lines.

Animals

[Evaluation of the energy concentration of feed mixtures for poultry based on the chemical analytical data].

Based on data material available for 33 feed mixtures, several regression equations were developed which make the estimation of energy concentration (EC) on the basis of the content of crude nutrients possible. The values received from the various equations were compared with those resulting from digestibility experiments with colostomized male and female chickens. An estimation equation is recommended resulting from the regressions for the digestibility of the individual crude nutrients: EC = 0.604 X crude protein content + 2.045 X crude fat content + 0.901 X crude carbohydrate content-158.3.

Animal Feed

A compilation of analytical data from inhibition studies on DNA polymerases and some of its implications.

In connection with the characterization of two DNA polymerases (DPols) of Chlorella, we have extensively surveyed the literature on inhibition studies on DPols in various eukaryotes. By applying Tamiya's plot (1), we have obtained two parameters for each of the inhibitors, phi- and n-values, which express the enzyme sensitivity to the drug and the number of inhibitor molecules present in the enzyme-inhibitor complex that is principally involved in the inhibition, respectively. By inspecting these parameters for the three mammalian DPols, alpha-, beta-, and gamma-pols, as well as other eukaryotic DPols, we have found that: [1] inhibitors commonly utilized for characterizing various DPols can be classified into two major groups, each having two subgroups, on the basis of a comparison of the phi values among alpha-, beta-, and gamma-pols. Moreover, the grouping seems not to be merely coincidental, but to be intrinsically related to facets of the enzyme reaction, which may be taken to reflect evolutionary differences in DPol structure and function among the three DPols; [2] the remarkable n value, n = 1/2, that has been found for the inhibitors competitive with dCTP in Chlorella DPols has also been detected widely in many other eukaryotic DPols. Based on the first finding as well as many other data on various DPols, we have proposed an evolutionary scenario for eukaryotic DPols. Based on the second finding, we have hypothesized a novel role for dCTP as a cofactor, probably an apparent allosteric effector, in the nucleotide transfer reaction mechanism.

Aphidicolin

Protein B1 of ribonucleotide reductase. Direct analytical data and comparisons with data indirectly deduced from the nucleotide sequence of the Escherichia coli nrdA gene.

The total composition, the N-terminal amino acid sequence, and the amino acid sequences of four internal regions have been determined for the ribonucleotide reductase large subunit, protein B1, prepared from a recombinant lambda-lysogenic Escherichia coli K strain, which overproduces the enzyme 30-50-fold. The data have been compared with those previously reported for B1 prepared from a thymine-starved E. coli B strain and with the indirectly derived primary structure of B1 recently reported from the nucleotide sequence of the E. coli K nrdA gene. Two major differences to these results were found. First, the B1 polypeptides started with initiator Met-1 (45%), Asn-2 (30%) or Gln-3 (15%), demonstrating a different type of N-terminal heterogeneity than that found earlier. Secondly, the total amino acid composition as derived from hydrolyzed protein B1 differed substantially from the amino acid composition derived from the nucleotide data. This has the consequence that Cys, Arg, Thr and possibly Val and Ser appear more frequently whereas Asx, Glx, Tyr and possibly Gly appear less frequently in the nucleotide-derived data as compared to direct protein hydrolysates. We suggest usage of other reading frames in the approximate area of residues 630-700 of the primary structure of the nrdA gene to compensate for these discrepancies and for the relatively high incidence of uncommon codons in the reading frame proposed for this area of the gene. Such changes have implications on the previously assigned putative active-site region of protein B1.

Amino Acid Sequence

Clinical course, therapy, outcome and analytical data in amitriptyline and combined amitriptyline/chlordiazepoxide overdose.

A total of 103 cases of amitriptyline (AT) overdose (group 1) and 81 cases of overdose with a fixed combination of AT and chlordiazepoxide (CDE) (group 2), treated at our Intensive Care Unit or reported to our Poison Information Center between 1985-1990, were evaluated with respect to clinical course, symptoms and outcome, as well as efficacy of therapy. The mean amount of AT was considerably higher in group 1 compared to group 2 (13 mg kg-1 vs 7.7 mg kg-1). The most frequent symptoms in both groups were impaired consciousness, anticholinergic symptoms, seizures, arrhythmia and hypotension. Respiratory insufficiency necessitated respirator therapy in 63 of the patients. Two patients in group 1 and one patient in group 2 did not survive. Therapy included primary detoxification by gastric lavage and repeated administration of activated charcoal. In four of eight patients with cardiac conduction disturbances, hypertonic sodium bicarbonate led to a significant reduction in QRS duration and AV interval. Physostigmine was effective in eight of 14 patients with pronounced anticholinergic symptoms. No effect was observed in the other six patients. Haemoperfusion, which was performed in five patients, led to rapid improvement of coma after initiation of therapy in four patients. The clinical efficacy of haemoperfusion in AT overdose despite the high volume of distribution of AT deserves further investigation. The rather high average overdose of AT implies that large package sizes of AT were available to the patients. A major step towards prevention of serious AT overdose would be the prescription of package sizes containing a total of less than 500 mg AT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Gas-liquid chromatographic determination of technical chlordane residues in food crops: interpretation of analytical data.

An interlaboratory investigation of technical chlordane residues in food crops was carried out to determine the most practical and consistent method of reporting results. Using a technical chlordane reference standard, 8 gas chromatographic stationary phases were studied for their resolution capabilities. The best separations were obtained with SE-30 and its OV-1 equivalent. Using these columns and electron capture detection, potatoes and carrots from supervised field experiments were analyzed in duplicate and quantitated by using 4 methods of calculation. The data were statistically treated to determine the precision and bias for each method. Also, 1 sample was analyzed in duplicate on 2 different occasions by 6 laboratories to substantiate the initial conclusions. Based on the criterion of high precision it is suggested that a comparison of total area under the chromatogram of the sample with total area of standard technical chlordane be the method of quantitation. Only peaks which are common to both standard and sample have any significance in this type of calculation.

Chlordan

[Acute dietary poisoning by white hellebore (Veratrum album L.). Clinical and analytical data. A propos of 5 cases].

Five cases of acute accidental poisoning with White Hellebore are reported. All cases occurred several minutes after the ingestion of home-made gentian wine. The clinical signs were nausea, vomiting, abdominal pain, hypotension and bradycardia. The initial ECG showed sinus bradycardia in 4 cases. In one patient, complete atrioventricular block with an ectopic atrial bradycardia and an intermittent idioventricular rhythm was recorded. Symptomatic treatment and/or atropine led to recovery within a few hours. These symptoms suggested poisoning with a veratrum alkaloid. The White Hellebore (Veratrum Album L.) and the Yellow Gentian (Gentiana Lutea L.) often grow side by side in the fields; it is easy to confuse the two plants before they flower if one is not a botanist. Each gentian wine was analysed by thin layer chromatography and chemical ionisation spectrometry. All the wines contained Veratrum alkaloids.

Abdomen

Non immunological analytic data for the differential diagnosis between miliary tuberculosis (MTBC) and bird breeder's disease (BBD).

A group of 86 patients diagnosed as having MTBC were compared to a group of 25 patients with BBD on the basis of various blood values included in routine analysis (hemogram, leukocyte count and differential, blood electrolyte values, urea, creatinine, total proteins and proteinogram). After statistical evaluation of the results, we concluded that the finding of low values for hemoglobin, and red blood cell (RBC) count and hematocrit, alterations of leukocyte count and differential, hypoalbuminemia, and hyponatremia, in a patient with fever and a miliary chest X-ray pattern, supports the diagnosis of MTBC. On the other hand, normal values for the above parameters, together with hypergammaglobulinemia favors the diagnosis of BBD. Our data also demonstrated a 79% mortality rate in patients with MTBC and plasma urea levels of more than 55 mg/100 ml (p less than 0.001).

Alveolitis, Extrinsic Allergic

Building a Digital Health Research Platform to Enable Recruitment, Enrollment, Data Collection, and Follow-Up for a Highly Diverse Longitudinal US Cohort of 1 Million People in the All of Us Research Program: Design and Implementation Study.

BACKGROUND: Longitudinal cohort studies have traditionally relied on clinic-based recruitment models, which limit cohort diversity and the generalizability of research outcomes. Digital research platforms can be used to increase participant access, improve study engagement, streamline data collection, and increase data quality; however, the efficacy and sustainability of digitally enabled studies rely heavily on the design, implementation, and management of the digital platform being used. OBJECTIVE: We sought to design and build a secure, privacy-preserving, validated, participant-centric digital health research platform (DHRP) to recruit and enroll participants, collect multimodal data, and engage participants from diverse backgrounds in the National Institutes of Health's (NIH) All of Us Research Program (AOU). AOU is an ongoing national, multiyear study aimed to build a research cohort of 1 million participants that reflects the diversity of the United States, including minority, health-disparate, and other populations underrepresented in biomedical research (UBR). METHODS: We collaborated with community members, health care provider organizations (HPOs), and NIH leadership to design, build, and validate a secure, feature-rich digital platform to facilitate multisite, hybrid, and remote study participation and multimodal data collection in AOU. Participants were recruited by in-person, print, and online digital campaigns. Participants securely accessed the DHRP via web and mobile apps, either independently or with research staff support. The participant-facing tool facilitated electronic informed consent (eConsent), multisource data collection (eg, surveys, genomic results, wearables, and electronic health records [EHRs]), and ongoing participant engagement. We also built tools for research staff to conduct remote participant support, study workflow management, participant tracking, data analytics, data harmonization, and data management. RESULTS: We built a secure, participant-centric DHRP with engaging functionality used to recruit, engage, and collect data from 705,719 diverse participants throughout the United States. As of April 2024, 87% (n=613,976) of the participants enrolled via the platform were from UBR groups, including racial and ethnic minorities (n=282,429, 46%), rural dwelling individuals (n=49,118, 8%), those over the age of 65 years (n=190,333, 31%), and individuals with low socioeconomic status (n=122,795, 20%). CONCLUSIONS: We built a participant-centric digital platform with tools to enable engagement with individuals from different racial, ethnic, and socioeconomic backgrounds and other UBR groups. This DHRP demonstrated successful use among diverse participants. These findings could be used as best practices for the effective use of digital platforms to build and sustain cohorts of various study designs and increase engagement with diverse populations in health research.

Humans

Some methodological issues in statistical estimation of air pollution and health.

This paper introduces a new method for estimating a dose-response relationship from spatially averaged time series of air pollution and health data. Because time is perceived as a nuisance parameter to be eliminated, least-squares regression and traditional time series methodology (e.g., spectral analysis Box-Jenkins methods) are rejected in favor of a nonparametric estimation procedure based on observing health effects in times of nearly equal pollution. The method requires estimating the ratio of two density functions and avoids problems of aggregation, linearity and normality. In spite of the formal tests described, the procedure seems most useful at present as a data analytic and data display device rather than as an inferential tool.

Air Pollution

SED88: a Pascal program for the analysis of sedimentation equilibrium data.

Analytical ultracentrifugation is commonly used for the determination of molecular weights (sedimentation equilibrium) and sedimentation coefficients (sedimentation rate) of biological macromolecules in solution. A Turbo Pascal program for the analysis of sedimentation equilibrium centrifugation data produced by absorbance optical systems is described. The user may enter data from a scan of absorbance versus distance from the centre of rotation, via a graphics tablet (or ASCII file). This is subsequently manipulated to yield an apparent weight average molecular weight for the given sample. Plots of ln (absorbance) versus (radius2) may also be produced. The method described uses readily available computational equipment requiring only a graphics tablet in addition to an IBM PC compatible computer. This technique and the software developed have been used to investigate the molecular weight range of two International Humic Substances Society (IHSS) reference samples from the Suwannee River.

Absorption

Analytical behavior data for chemicals determined using AOAC multiresidue methodology for pesticide residues in foods.

Analytical methods capable of detecting more than one pesticide residue simultaneously (multiresidue methods) become more effective with an increase in the number of chemicals whose behavior through the various steps of the method has been documented. Since 1970, the method behavior data related to the AOAC official method for residues of 25 chlorinated and phosphated pesticides and polychlorinated biphenyls have been extended to include information on twice as many chemicals as was previously available. The value of having a large bank of method behavior data is outlined and the experimental protocol by which the data were collected is described. A complete listing is included of the available data on the analytical behavior of over 300 pesticidal and/or industrial chemicals.

Chemistry Techniques, Analytical

Bioanalytic considerations for pharmacokinetic and biopharmaceutic studies.

The correct evaluation of pharmacokinetic and biopharmaceutic data can only be achieved if accurate analytic data are obtained. The accuracy of analytic data depends on the criteria used to validate the method. Consequently, careful scrutiny of drug stability, assay sensitivity, selectivity, recovery, linearity, precision, and accuracy is necessary for the proper interpretation of data. The importance of method validation and its influence on pharmacokinetic and biopharmaceutic data evaluation and interpretation will be discussed.

Biopharmaceutics

Pattern recognition used to investigate multivariate data in analytical chemistry.

Pattern recognition and allied multivariate methods provide an approach to the interpretation of the multivariate data often encountered in analytical chemistry. Widely used methods include mapping and display, discriminant development, clustering, and modeling. Each has been applied to a variety of chemical problems, and examples are given. The results of two recent studies are shown, a classification of subjects as normal or cystic fibrosis heterozygotes and simulation of chemical shifts of carbon-13 nuclear magnetic resonance spectra by linear model equations.

Carbon Radioisotopes