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PubMed1980

Noise-abatement method for explosives testing.

When Lawrence Livermore Laboratory started detonating explosives at its Site 300 test location in the sparsely populated hills east of the Laboratory, residents in neighboring areas complained of sudden loud noises. A combined literature and research study, coupled with an experimental test program, indicated the combination of air temperatures and winds at various elevations was primarily responsible for blast or sound waves being returned to the surface. To solve the noise problem, the Laboratory devised a method for determining the maximum amount of explosives that could be detonated aboveground under various atmospheric conditions without creating excessive noise in populated areas. This method for predicting explosives weight limits using pressure-distance-weight nomograms and the slope of a sound-velocity curve is described in this paper. The sound-velocity curve is computed with temperature information from the U.S. Weather Bureau and wind data from a target-acquisition radar system. By following this method, the Laboratory has been able to detonate thousands of shots without creating excessive noise in nearby communities.

Explosions↗

PubMed1981

Analysis of methods to construct nomograms in uroflow studies.

A Monte Carlo simulation study to compare the effect of population form on three methods of nomogram construction was performed by taking 2000 random samples of size 5, 20, 50, 100, and 200 from populations with known percentiles. The 10th percentile was estimated by each of the three construction procedures. The three procedures compared were the upper 95 per cent nonparametric tolerance limit technique, the usual percentile approach, and a method which assumes a Gaussian (normal) distribution. Tenth percentile nomograms, classified by volume voided, were calculated by each of the three procedures for maximum flow rate determinations from 356 normal males of ages 1 to 12 years with body surface areas less than 1.1 m2. Nomograms of the three methods are validated with evaluations from two other groups of male children consisting of known abnormals with radiologically proven urethral obstructions and known normals who had repeated at home uroflow rates. The nonparametric tolerance limit approach gives conservative estimates and is superior in all cases from the standpoint of reducing false-negative results.

Child↗

PubMed2026

ZUP1 as a Novel Potential Oncogenic Driver and Prognostic Biomarker in Breast Cancer.

INTRODUCTION: Breast cancer is one of the main causes of cancer death in women globally. Identifying new predictive markers and therapeutic targets is important for improving patient outcomes. Zinc finger-containing U-rich RNA-binding protein 1 (ZUP1) is an RNA-binding protein containing a zinc finger structure that has not been systematically analyzed in breast cancer research. MATERIALS AND METHODS: The study used data from 1,231 samples from the Cancer Genome Atlas (TCGA) database. The ZUP1 expression in tumor tissues and normal tissues was compared. Its predictive value was assessed using survival analysis and regression models. Its biological role was explored through gene functional analysis. The immune cell analysis method was used to study the tumor immune environment, and the drug susceptibility database was used to predict drug responses. Predictive models were also built and validated. RESULTS: ZUP1 expression was significantly higher in breast cancer tissues than in normal tissues. High expression of ZUP1 is related to advanced tumor stage and is an independent indicator of poor survival prognosis in univariate and multivariate analyses. Functional enrichment revealed that ZUP1 is closely linked to cell cycle progression, DNA replication, and the Fanconi anemia (FA) pathway. Immune infiltration analysis demonstrated a significant negative link between ZUP1 levels and the abundance of resting mast cells and activated NK cells. Furthermore, high ZUP1 expression was associated with increased sensitivity to several targeted therapies, including Nutlin-3a and PD-0325901. A clinically applicable nomogram combining ZUP1 expression with key clinical factors (age, stage, T, N, M) was developed to predict 3- and 5-year OS with good calibration and discrimination. DISCUSSION: Our study identifies ZUP1 as a potential oncogenic factor and a robust independent prognostic biomarker in breast cancer. Its involvement in critical cellular processes and modulation of the tumor immune microenvironment highlights its potential as a novel therapeutic target. Functional experiments, including immunohistochemical staining and CCK8 proliferation assays, further supported the oncogenic role of ZUP1. The established nomogram provides a valuable tool for personalized risk assessment and clinical decision-making. CONCLUSION: Our findings suggest that ZUP1 is a novel multifaceted biomarker with significant implications for personalized treatment strategies in breast cancer.

ZUP1↗

PubMed1976

Drug dosage in renal disease.

Based on the well known linear relationship between the overall drug elimination rate constant and the endogenous creatinine clearance, it is shown how individual drug elimination parameters in patients with renal disease can be estimated from the patient's creatinine clearance or serum creatinine concentration. By means of a simple nomogram the elimination rate fraction is determined which describes the elimination rate of the drug as a fraction of its normal elimination rate constant. Based on the estimated elimination rate fraction the dosage regimen in the patient with renal disease is individually modified according to pharmacokinetic principles. At present the described method can be used with 45 different drugs.

Creatinine↗

PubMed2006

Nomograms of total renal volume, urinary bladder volume and bladder wall thickness index in 3,376 children with a normal urinary tract.

BACKGROUND: We have previously shown that urinary bladder volume index (BVI = length x width x depth of bladder) and bladder volume wall thickness index (BVWI = BVI at full bladder/average bladder wall thickness) are useful indicators of bladder dysfunction in children with enuresis and urinary tract infection. These indices show a good correlation with urodynamic studies. We have expanded the study to include normal paediatric subjects with a wide age range. We illustrate a simple sonography protocol with nomograms of different parameters, which provide useful references for functional assessment in children with urological abnormalities. OBJECTIVE: To construct nomograms of total renal volume, maximum BVI and BVWI based on a Chinese paediatric population with age range from newborn to adolescence. MATERIALS AND METHODS: Sonography was performed in consecutive children with normal urinary tracts on imaging, using a standardized protocol. Data were collected for construction of nomograms for different parameters. RESULTS: Nomograms of total renal volume, BVI and BVWI were constructed based on 3,376 consecutive paediatric subjects. All parameters consistently increased with age. CONCLUSION: Nomograms of total renal volume, BVI and BVWI could provide useful references for studying bladder dysfunction in children using noninvasive dynamic sonography.

Adolescent↗

PubMedDate not supplied

A calculator program for adjusting aminoglycoside regimens that accounts for tissue accumulation in children and adolescents.

The author has developed a program for the Hewlett Packard HP 41C calculator that is used in the analysis of aminoglycoside serum levels for the purpose of generating a personalized dosage regimen. Although other programs have been published, until now none has made adjustments in the half-life of drug elimination due to the tissue accumulation that occurs in the initial phases of dosing. Many of these same programs fail to locate the true peak and trough serum levels, which are essential in the calculation of the volume of distribution of the aminoglycosides. This article is not meant as a method of initial dosing, but rather assumes that the physician has chosen one of the readily usable methods of dosing, such as various nomograms. Patient data taken from published studies were used in generating individual patient parameters. These parameters were compared to those calculated in the studies for means of comparison. While correlation in all parameters was not ideal, the correlation of dose and dosing interval was exact and correlation of predicted peaks and troughs with the given regimen of dosing was excellent.

Adolescent↗

PubMedDate not supplied

Hypothesis for the individualisation of drug dosage.

Computer simulations based on the pharmacokinetics of chloramphenicol and theophylline in patients, indicate a very strong correlation (r = 0.988 for chloramphenicol and r = 0.971 for theophylline) between log maintenance dose required to achieve a desired average drug concentration in serum at steady-state, and the drug concentration in serum 6 hours after an initial test dose administered by constant rate intravenous infusion over 0.5h. Accordingly, we have developed a nomogram to predict individual daily dosing requirements for these drugs in uncomplicated patients from a single serum assay following an initial dose. Within defined limits, predictions made with the nomogram are essentially equivalent to those made by iraditional pharmacokinetic methods which require substantially more drug concentration-time data following a test dose. Predictions based on the nomogram are relatively unaffected by small but typical errors in magnitude of the test dose, infusion time, sampling time and assay. Protocols for the administration of the test dose other than described, e.g. administration of an oral theophylline solution, may be equally useful for dosage predictions. In principle, this approach should apply to other drugs.

Chloramphenicol↗

PubMed1995

Appropriate use of heparin. Empiric vs nomogram-based dosing.

BACKGROUND: A study involving two groups of patients with cardiovascular disease was conducted to compare empiric (clinician-directed) heparin therapy with therapy based on a nomogram-determined dosage. The comparison was based on (1) the average weight-referenced infusion rate yielding a therapeutic activated partial thromboplastin time (APTT) and (2) the time required to reach a therapeutic APTT (55 to 95 seconds) after empiric or nomogram-based heparin therapy was initiated. METHODS: Data were collected for patients admitted to the cardiology service at a university health science center in two phases: phase 1 (April 1 through June 30, 1992), involving 95 patients receiving heparin therapy, with 88 patients included in the data analysis, and phase 2 (March 11 through June 11, 1993), involving 156 patients receiving heparin therapy, with 45 patients receiving nomogram-guided therapy included in the data analysis. RESULTS: In phase 1, 66 patients (75.0%) achieved a therapeutic APTT some time during their heparin therapy, with an average time to therapeutic APTT of 20.7 + 19.1 hours. Regression analysis demonstrated a statistically significant relationship between the heparin infusion rate at the time of the patient's first therapeutic APTT and the patient's total body weight (r2 = .3043). An initial infusion rate based on total body weight (13 U/kg per hour) was therefore used as the basis for the nomogram in phase 2. In phase 2, 41 patients (91.1%) achieved a therapeutic APTT at some time during their heparin therapy, with an average time to therapeutic APTT of 13.1 + 11.9 hours, statistically significantly shorter than that in phase 1. A greater proportion of patients in phase 2 compared with patients in phase 1 reached the therapeutic range within 12 hours (62.2% vs 34.1%) and within 24 hours (77.8% vs 54.5%). CONCLUSIONS: Use of a weight-based nomogram to determine the initial and maintenance heparin infusion rates was associated with a higher percentage of patients admitted to the cardiology service reaching the targeted therapeutic APTT range at a time earlier in the course of therapy compared with empiric dosing.

Adult↗

PubMed2026

Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma.

Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8+T/M2 macrophage ratio stratified patients into High (> 1.5), Intermediate (0.8-1.5), and Low (< 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, p = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index > 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.

Humans↗

PubMedDate not supplied

Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin.

Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied. One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose-amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate. The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250-1000 microns. Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH. Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules. The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin. To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram was made using pharmacokinetic parameters obtained after administration of a conventional formulation. It is advantageous for the preparation of sustained release microcapsules to chose pharmaceuticals having over about 2 as the ratio of the elimination rate constant, k10, to the release/absorption rate constant, kr, in the rabbit.

Absorption↗

PubMed1989

[A nomogram of vestibular pendular stimulation in guinea pigs].

Vestibular pendular test was performed in 20 guinea pigs of various sexes and weights 250-300 g. The total sum of deviations on the right and on the left was 105-164. According to the standard deviation we have accepted the minimal norm 94 and maximal 183. Taking into consideration this norm we have elaborated the nomogram for the quantitative reaction to pendular excitation. There were 6 positions from 0.7 to 1.2 deviations for sec. and total sum from 94 to 183. The results in guinea pigs were in contrast with those in men. The guinea pig vestibular organ is more susceptible for high-rate excitation (17-12 degrees/sec2) and of minor susceptibility in lower rate of acceleration (12-0 degrees/sec2).

Acceleration↗

PubMed1979

The acute toxicity of ethanol: dosage and kinetic nomograms.

We are concerned with the frequency of potentially lethal ethanol intoxications (about 1 pint of hard liquor) in teenagers. We present 2 illustrative cases, discuss the acute toxicity of ethanol, and present 2 simple calculating charts for dosage and kinetics. The widespread use and economic impact of ethanol have kept this potent sedative-hypnotic free of the same federal regulations that control the availability of other drugs with a similar potency and margin of safety.

Acetaldehyde↗

PubMed2001

Kidney morcellation in laparoscopic nephrectomy for tumor: recommendations for specimen sampling and pathologic tumor staging.

Laparoscopic nephrectomy is a novel approach for small renal tumors in selected patients; however, removal of the kidney through the small laparoscopic abdominal wall incision site requires the kidney to be morcellated into small fragments while still in situ. Morcellation presents two problems for the pathologist. First, guidelines for optimal sampling of morcellated fragments have not been described. Second, morcellation precludes complete pTNM tumor staging, in particular, tumor size, margins, and renal vein involvement. Based on our initial experience with 23 laparoscopic nephrectomies/nephroureterectomies (13 clinically suspected neoplasms, confirmed pathologically as renal cell carcinoma [RCC, n = 7], urothelial carcinoma of the renal pelvis [n = 3], angiomyolipoma [n = 1], and cystic nephroma [n = 1], and 10 clinically benign entities) and a conservative statistical model, we present a decision analysis model of various specimen sampling protocols that optimize cost, labor, or time to diagnosis (single vs sequential sampling). Using the tumor-to-kidney volume ratio (TKR), calculated from preoperative radiologic imaging and specimen gross weight, several specimen sampling algorithms were compared. For the average situation in which TKR is > or =0.15, the algorithm that most significantly optimizes cost and labor is one that initially samples 5% of the morcellated specimen. However, additional sampling may be required in one fourth of the cases. The optimal amount of sampled tissue may indeed be less than 5% because this assumes no suspicious tissue is grossly visible and in all our cases of RCC grossly visible tumor was identified. Additional nomograms for a spectrum of TKR, sampling success, and cost are presented to allow pathologists their own discretion in determining optimal sampling of the morcellated kidney. Tumor staging is severely limited by morcellation. Tumor size, renal capsule involvement, and renal vein involvement cannot be fully pathologically evaluated for RCC, whereas invasion cannot be definitively assessed for urothelial carcinoma of the renal pelvis. Knowledge of the radiologic features (lesion size, capsule, and vein involvement) is important in sampling and staging morcellated kidneys removed laparoscopically.

Algorithms↗

PubMed2003

Pretreatment nomogram that predicts 5-year probability of metastasis following three-dimensional conformal radiation therapy for localized prostate cancer.

PURPOSE: There are several nomograms for the patient considering radiation therapy for clinically localized prostate cancer. Because of the questionable clinical implications of prostate-specific antigen (PSA) recurrence, its use as an end point has been criticized in several of these nomograms. The goal of this study was to create and to externally validate a nomogram for predicting the probability that a patient will develop metastasis within 5 years after three-dimensional conformal radiation therapy (CRT). PATIENTS AND METHODS: We conducted a retrospective, nonrandomized analysis of 1,677 patients treated with three-dimensional CRT at Memorial Sloan-Kettering Cancer Center (MSKCC) from 1988 to 2000. Clinical parameters examined were pretreatment PSA level, clinical stage, and biopsy Gleason sum. Patients were followed until their deaths, and the time at which they developed metastasis was noted. A nomogram for predicting the 5-year probability of developing metastasis was constructed from the MSKCC cohort and validated using the Cleveland Clinic series of 1,626 patients. RESULTS: After three-dimensional CRT, 159 patients developed metastasis. At 5 years, 11% of patients experienced metastasis by cumulative incidence analysis (95% CI, 9% to 13%). A nomogram constructed from the data gathered from these men showed an excellent ability to discriminate among patients in an external validation data set, as shown by a concordance index of 0.81. CONCLUSION: A nomogram with reasonable accuracy and discrimination has been constructed and validated using an external data set to predict the probability that a patient will experience metastasis within 5 years after three-dimensional CRT.

Adenocarcinoma↗

PubMed1994

[Hemodynamic properties of the hemopump].

The hemopump HP 31 is an improved version of a catheter-mounted, transvalvular, left ventricular assist device, which can be placed into the left ventricle through the ascending aorta. The purpose of this study was to examine the influence of hematocrit and afterload on the pump flow. The hemopump was tested using a flow bench model filled with heparinized bovine blood. The measurements were performed at four various hematocrit values: 16%, 24%, 32%, and 40%. The pump flow was measured at each hematocrit value under increasing afterload pressures (40-120 mm Hg), by all pump speed levels (n = 7). The average pump flow at highest pump speed and lowest afterload was 5.1 +/- 0.3 l/min (mean +/- standard deviation). The influence of afterload on the pump flow was statistically significant (p < 0.001). The highest afterload pressure of 120 mm Hg caused a reduction in pump flow of 24 +/- 5%. The alterations of hematocrit values caused no statistically significant influence on the pump flow (p = 0.72). The results of our study enabled the construction of the nomogram for the in vivo determination of the pump flow. The in vivo performances of the hemopump can be improved through the afterload reduction, especially in the weaning phase of treatment. The oxygen delivery can be improved through the increase in hematocrit values without significant impairment of the pump flow.

Animals↗

PubMed2004

The volume kinetics of acetated Ringer's solution during laparoscopic cholecystectomy.

We studied the distribution and elimination of an IV infusion of 20 mL/kg of acetated Ringer's solution (approximately 1500 mL) over 60 min in 12 women undergoing laparoscopic cholecystectomy. A plasma dilution of 4.2% developed during the induction of general anesthesia, even though fluid was withheld. The additional plasma dilution induced by the subsequent volume expansion was slightly larger than expected from previous volunteer experiments and averaged 18%. The diuretic response to intravascular fluid administration was small, and only 20% of the infused fluid had been excreted 4 h later. Volume kinetic analysis showed that the IV fluid expanded a central body fluid space by 3.2 L. The clearance constants for distribution and elimination averaged 115 mL/min and 6.8 mL/min, respectively. These data represent a half-life of the fluid in the patients that is 17 times longer (median, 4.5 h) than the half-life of the plasma dilution (16 min), indicating a strong tendency to the formation of peripheral edema. A nomogram based on the kinetic variables suggests that infusion rates should be relatively rapid early on during surgery but slower later. This strategy creates a constant plasma dilution at any desired level without causing undue peripheral accumulation of fluid.

Acetates↗

PubMed1992

The effects of positive expiratory pressure on peritoneovenous shunt flow.

Cirrhotic patients with peritoneovenous shunts may require mechanical ventilation. Despite the importance of flow to shunt patency and the relevance of intrathoracic pressure to that flow, the relationship between shunt flow and positive airway pressure has not been documented. To study the effects of positive expiratory pressure (PEEP) on shunt flow, models of ascites (n = 8) were created in adult male mongrel dogs. Each animal was anesthetized, intubated, and mechanically ventilated. Peritoneovenous shunts with in-line electromagnetic flow meters were surgically placed. Shunt flow, central venous pressure (CVP), and intraabdominal pressure (IAP) were monitored. Initial intraabdominal pressures were adjusted by infusion of warmed saline and positive expiratory airway pressures were added in increments. Changes in pressures (IAP, CVP) and shunt flow were tabulated and analyzed with linear and polynomial regression. Intraabdominal and central venous pressures increased linearly with PEEP at different rates such that IAP-CVP varied inversely with PEEP. Shunt flow varied inversely as a polynomial function of PEEP. Analyses of these relationships allowed creation of a nomogram which can be interpolated to indicate required intraabdominal pressure needed to maintain shunt flow throughout the clinically useful range of positive airway pressure.

Animals↗

PubMed2006

[Evaluation of mitral regurgitation severity using a simplified method based on proximal flow convergence].

INTRODUCTION AND OBJECTIVES: Calculation of the effective regurgitant orifice (ERO) is regarded as the most accurate way of assessing the severity of mitral regurgitation (MR), but the technique's complexity limits its use. Our objective was to modify and validate a previously published semiquantitative method of assessment based on measurement of the proximal isovelocity surface area (PISA) in order to adapt it to recent recommendations from American and European cardiology societies. METHODS: In the PISA method, maximum regurgitant flow (MRF) is a function of the radius and aliasing velocity (AV). Using this relationship, it is possible to construct a nomogram formed by lines of different MRF value, which can be easily derived by looking for radius values on the graph and observing where they cross with AV values. The MR severity limits on the nomogram were set to reflect the different severity grades and limits recommended for use with ERO measurements by American and European cardiology societies. RESULTS: We studied 76 patients with MR using Doppler echocardiography. There was an excellent correlation between MRF and ERO (r=0.98, P< .001). Estimates of MR severity made using the new nomogram were in good agreement with those derived from the ERO: for a scale with three severity grades, kappa was 0.951 and the standard error was 0.11; for four grades, kappa was 0.969 and the standard error, 0.11. CONCLUSIONS: Estimates of MR severity derived semiquantitatively from MRF using the nomogram proposed here were in excellent agreement with quantitative estimates obtained using the ERO, and the method was faster and easier to use.

Adult↗