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Based on visual observations and tests made of Georgia marble units that have been in service at the historic Minnesota State Capitol for 110 years, a fielddiscernible correlation exists between marble unit mineralogical composition and unit weathering performance. Field studies noted over the course of a five-year restoration project of the capitol exterior were used to categorize the original marble cladding into four perceptible types, which were evaluated by field testing that suggested a correlation between the textural and mineralogical differences within the marble and its long-term durability. To test this theory, field-issued repair assignments made during an exterior marble restoration project at the capitol were examined statistically. The nature and frequency of assigned repairs were compared to the type of marble from which they were originally fabricated to determine whether a correlation existed. The results of this comparison provided convincing statistical verification of the link between mineralogy and durability. This hypothesis was then verified through detailed petrographic analysis in a laboratory setting, which determined that marble consisting of a smaller, more interlocked grain configuration that was more dolomitic than calcitic in its basic chemistry consistently proved to be more durable in weathering performance over time. The paper describes the process followed by the authors to categorize and study the distinct varieties of Georgia marble present on the Minnesota State Capitol, and how this information was used to guide the restoration process with the intent of maximizing the anticipated service life of new marble replacements.

Thalidomide is a racemic glutamic acid derivative approved in the US for erythema nodosum leprosum, a complication of leprosy. In addition, its use in various inflammatory and oncologic conditions is being investigated. Thalidomide interconverts between the (R)- and (S)-enantiomers in plasma, with protein binding of 55% and 65%, respectively. More than 90% of the absorbed drug is excreted in the urine and faeces within 48 hours. Thalidomide is minimally metabolised by the liver, but is spontaneously hydrolysed into numerous renally excreted products. After a single oral dose of thalidomide 200mg (as the US-approved capsule formulation) in healthy volunteers, absorption is slow and extensive, resulting in a peak concentration (Cmax) of 1–2 mg/L at 3–4 hours after administration, absorption lag time of 30 minutes, total exposure (AUC∞) of 18 mg • h/L, apparent elimination half-life of 6 hours and apparent systemic clearance of 10 L/h. Thalidomide pharmacokinetics are best described by a one-compartment model with first-order absorption and elimination. Because of the low solubility of the drug in the gastrointestinal tract, thalidomide exhibits absorption rate-limited pharmacokinetics (the ‘flip-flop’ phenomenon), with its elimination rate being faster than its absorption rate. The apparent elimination half-life of 6 hours therefore represents absorption, not elimination. The ‘true’ apparent volume of distribution was estimated to be 16L by use of the faster elimination-rate half-life. Multiple doses of thalidomide 200 mg/day over 21 days cause no change in the pharmacokinetics, with a steady-state Cmax (Css max) of 1.2 mg/L. Simulation of 400 and 800 mg/day also shows no accumulation, with Css max of 3.5 and 6.0 mg/L, respectively. Multiple-dose studies in cancer patients show pharmacokinetics comparable with those in healthy populations at similar dosages. Thalidomide exhibits a dose-proportional increase in AUC at doses from 50 to 400mg. Because of the low solubility of thalidomide, Cmax is less than proportional to dose, and tmax is prolonged with increasing dose. Age, sex and smoking have no effect on the pharmacokinetics of thalidomide, and the effect of food is minimal. Thalidomide does not alter the pharmacokinetics of oral contraceptives, and is also unlikely to interact with warfarin and grapefruit juice. Since thalidomide is mainly hydrolysed and passively excreted, its pharmacokinetics are not expected to change in patients with impaired liver or kidney function.

Thalidomide is approved in the United States for treating erythema nodosum leprosum, a complication of leprosy. The present study determined the single-dose oral pharmacokinetics and dose proportionality from 50 to 400 mg of Celgene's commercial Thalomid thalidomide formulation in an open-label, single-dose, three-way crossover study. Fifteen healthy subjects were given 50, 200, and 400 mg of thalidomide on three occasions, and blood samples were collected over 48 hours. Pharmacokinetic parameters were determined using noncompartmental methods, and dose proportionality was assessed by linear regression of dose-normalized Cmax and AUC0-infinity. No serious or unexpected adverse events occurred. The most common adverse events were dizziness, somnolence, headache, and nausea. One patient was discontinued because of pharyngitis. There was a significant deviation from proportionality for Cmax with increases being less than proportional than changes in dose. AUC0-infinity increased proportionally with dose, suggesting that the overall amount of thalidomide absorbed, as well as its clearance, is independent of dose over the range used. V/F was found to increase with dose. This was most likely due to the terminal rate constant, which is used to calculate V/F, actually representing the absorption process rather than elimination (i.e., flip-flop phenomenon). The terminal rate constant (absorption rate constant) for the highest dose was 50% less than for the other two lower doses. The less than proportional increases in Cmax were most likely due to thalidomide's low aqueous solubility. Thalidomide shows reasonable dose proportionality with respect to AUC from 50 to 400 mg.

The effect of food on the oral pharmacokinetics of thalidomide and the relative bioavailability of two oral thalidomide formulations were determined in an open label, single dose, randomized, three-way crossover study. Five male and eight female healthy volunteers received a single oral dose of 200 mg Celgene thalidomide capsules under fasted and non-fasted conditions, and a single dose of 200 mg tablets of Serral thalidomide under fasted conditions. The high-fat meal resulted in a 0.5-1.5 h absorption lag time, an increased mean C(max), a decreased mean AUC and a delay in mean T(max). The Serral tablet formulation resulted in a lower mean C(max), and slower terminal decline in plasma thalidomide concentrations compared with both Celgene treatments. Mean C(max) concentrations were 1.99+/-0.41 microg/mL (range 1.28-2.76) within 4.00+/-1.13 h (2-5) for the Celgene formulation fasted, 2.17+/-0.51 microg/mL (1.43-3.01) within 6.08+/-2.33 h (3-12) for the Celgene formulation with food, and 1. 05+/-0.31 microg/mL (0.62-1.65) within 6.23+/-1.88 h (5-10) for the Serral formulation fasted. Mean terminal half-lives were 13.50+/-6. 77 h for the Serral product, compared with 5.80+/-1.72 h and 5. 09+/-1.03 h for Celgene fasted and fed, respectively. Celgene's formulation exhibited slightly greater bioavailability than Serral's formulation, with mean ratios of 122% and 110% for Ln-transformed AUC(0-t) and AUC(0-infinity), respectively. The mean C(max) for the Celgene formulation was approximately two times greater than Serral's. Food delayed the onset of absorption of by 0.5-1.5 h, but had little effect on the extent of absorption from the Celgene capsule. Under fasted conditions, the Celgene thalidomide resulted in a two-fold greater C(max) and 10% greater AUC(0-infinity) than the Serral formulation.

Objectives To determine the single- and multiple-dose pharmacokinetics of oral thalidomide (200 mg/day, administered for 21 days) and to assess the effects of steady-state plasma concentrations of thalidomide on the single-dose pharmacokinetics of ethinyl estradiol (INN, ethinylestradiol) and norethindrone (INN, norethisterone). Methods A randomized, 2-period crossover study was performed in 10 healthy premenopausal female volunteers. The pharmacokinetic profiles of plasma concentrations of thalidomide were evaluated with both noncompartmental and compartmental methods, whereas those of ethinyl estradiol and norethindrone were calculated with noncompartmental methods. The effects of steady-state plasma thalidomide concentrations on the pharmacokinetics of ethinyl estradiol and norethindrone were determined with use of an ANOVA model that included treatment sequence, subject within sequence, period, and treatment as factors. Results Thalidomide plasma concentrations were best predicted by a 1-compartment model with first-order absorption and elimination and an absorption time-lag. There were no significant differences between pharmacokinetic parameters for thalidomide after 1 dose and those after 18 consecutive doses. Except for a minor decrease of the elimination rate constant (ke) for ethinyl estradiol, coadministration of thalidomide had no significant effects on the pharmacokinetic profiles for either ethinyl estradiol or norethindrone. The change in ke for ethinyl estradiol during thalidomide administration was not associated with any alteration in the clearance or elimination half-life for this hormone. Conclusions Multiple-dose pharmacokinetics of thalidomide is similar to the single-dose profile. This study did not investigate the efficacy of the 21-day fixed ethinyl estradiol–norethindrone regimen, but the results suggest that thalidomide is unlikely to affect the pharmacokinetics of orally administered hormonal contraceptives. Clinical Pharmacology & Therapeutics (1999) 65, 483–490; doi

Physical and mechanical testing was conducted on composite stone faced aluminum honeycomb panels manufactured in the United States for use as exterior veneer panels on buildings. Testing was conducted on specimens cut from new stone faced panels as well as stone faced panels removed from service. For comparison purposes specimens cut from new unfaced honeycomb panels were also tested. The purpose of the testing was to measure certain strength, durability, and performance characteristics of the faced honeycomb panel’s composite construction. The stone faced specimens tested included those faced with travertine, limestone, and granite. Old travertine faced specimens had been in service for more than 18 years. The results very strongly suggest that the structural performance of the composite panel is dominated by the aluminum honeycomb portion. The stone portion is essentially a thin veneer adhered to the honeycomb that provides little if any structural strength.

One of the most important aspects of designing dimension stone cladding involves determining the configuration, size, and spacing of the anchorages that will affix the stone panels to the underlying building substrate. Information from many sources, including material strength testing, anchorage strength testing, and knowledge of the stress states created within stone cladding panels by loaded anchorages, is crucial to this process. In this paper, relationships are examined between material strength, anchorage strength, and induced stress states for four common anchorage configurations: edge dowels, Type 31 back anchors, and edge kerfs with strap and split-tail anchors. For each of these four anchor types, the relevant material and anchorage strength test data obtained for a medium-grained granite, in conjunction with finite element computer analyses of the stress states induced in the stone panels by the anchors and within the material strength test specimens, are presented. Material strength test configurations evaluated include ASTM C 880 Standard Test Method for Flexural Strength of Dimension Stone, ASTM C 99 Standard Test Method for Modulus of Rupture of Dimension Stone, and a proposed test for punching shear currently under consideration by ASTM Subcommittee C18.01. All anchorage strength tests were performed in accordance with ASTM C 1354 Standard Test Method for Strength of Individual Stone Anchorages in Dimension Stone.

Natural stone has been used for centuries as building material. In historical time it was mainly used as load bearing elements, but within the past 50 years a new processing technique has made it commercially feasible to produce and use thin facade cladding. Unfortunately, a number of marble facades on buildings in both Europe and elsewhere have had serious problems with deterioration of the stone material. The TEAM (TEAM = TEsting and Assessment of Marble and limestone) project consortium represents nine European countries and comprises 16 partners, representing stone producers and trade associations, testing laboratories, standardization and certificate bodies, consultants, building owners and caretakers and producers of fixing and repair systems. The project had a budget of approximately 5 million dollars and was partly funded by the European Commission under the contract no. G5RD-CT-2000-00233. Two of the main objectives in the TEAM project were: — To understand and explain the mechanisms of the expansion, bowing, and loss of strength leading to degradation of marble and limestone clad facades. — To prevent the use of deleterious marble and limestone by introducing a draft for new European standards. This paper presents some of the important conclusions drawn from a literature review carried out within the TEAM project—and was based on an extensive review of literature on marble and limestone deterioration dating from the late 1800s to 2006 and the results of the TEAM project. The comprehensive information from more than 70 selected literature references is reviewed and discussed in order to describe the present knowledge on the causes and mechanisms responsible for the bowing and strength loss of thin marble cladding. In the following, the literature and TEAM findings are grouped under a number of headings proposed to explain observations. Thus, the information from the literature is compared and supplemented with the results from the TEAM project in order to present a good overview of the existing, most relevant, knowledge in the field. The literature review reveals that only few researchers have examined the durability problem from a broad perspective. In addition, no conclusive answer about the mechanisms and influencing factors can be given. The TEAM project has made it possible to identify several of the key influencing factors in marble degradation, the relative importance of various factors, and to gain a deeper understanding of the mechanisms involved.

(1982). NUMERICAL ANALYSIS OF THE TETON DAM FAILURE FLOOD. Journal of Hydraulic Research: Vol. 20, No. 4, pp. 317-328.

A joint probability analysis of storm tides is made for the Battery, New York (U.S.A.), and Newark Bay, New Jersey (U.S.A.). Storm tides are caused by either low-pressure coastal storms (northeasters) or hurricanes. The analysis uses existing gage data at the Battery to construct frequency/probability curves of peak surge elevations and tidal amplitudes. These are used in a computer program to combine standard storm surge stages and tidal stage curves to produce an artificial storm tide with given peak elevation and incremental frequency. These peak elevations and incremental frequencies are ranked to produce cumulative frequency curves for northeasters and hurricanes. A frequency curve is obtained for Newark Bay via correlation.

Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. Gastric secretions were collected by aspiration using a nasogastric tube placed in the distal part of the stomach. Gastric fluid volume, pH, and acid concentrations were determined for 2 hours before drug administration and over 24 hours after administration on days 1, 7, 14 (the last day of dosing), and 17 (3 days after the last dose). Plasma and urine samples were collected throughout the study for the pharmacokinetic assessment. All subjects completed the study without side effects or clinically significant changes in any of the safety variables. Subjects receiving roxatidine acetate had substantial increases in gastric pH and decreases in acid secretion compared to baseline and to placebo-treated subjects. The duration of effect was approximately 12 hours. Nocturnal pH was greater than or equal to 6.0 in 80% of the roxatidine acetate-treated subjects. When sampled 3 days after the last dose (day 17) no differences in pH, acid secretion, or gastric volume were observed between the roxatidine acetate- and placebo-treated groups. The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and decreases in gastric acid concentration, without affecting gastric fluid volume.