bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of Clonidine on the naltrexone-induced withdrawal response in morphine-treated guinea-pigs
Authors: Jungnickel Sebastian , Chahl Loris A
Published: October 2002

Rapid opioid withdrawal induced by naltrexone is now used as a treatment for heroin addiction. The α2-adrenoceptor agonist, clonidine, is currently used in clinical practice to reduce opioid withdrawal in humans. However, few studies have been reported on its effectiveness for this purpose. Guinea-pigs were made dependent and tolerant to morphine using a 3-day chronic morphine regimen (total 410 mg kg−1 morphine base), and injected with eitherclonidine(0.1 mg kg−1, s.c.) or saline, 1 h before induction of withdrawal with naltrexone (15 mg kg−1, s.c.). Withdrawal behaviours were measured for 90 min and animals were then euthanased and the brains removed. The presence of the immediate early gene protein product, c-Fos, was detected using immunohistochemical techniques. Clonidine reduced the number of head/body shakes, but had no effect on the total withdrawal behaviour score. In the CNS, clonidine increased the number of Fos-LI neurons in the central amygdala. In conclusion, the modest effect of clonidine in the present experiments suggests that the efficacy of clonidine in humans undergoing naltrexone-induced opioid withdrawal requires further investigation.
Effect of 7-day exposure to midazolam on electroencephalogram pharmacodynamics in rats: a model to study multiple pharmacokinetic-pharmacodynamic relationships in individual animals
Authors: Laurijssens Bart E , Greenblatt David J
Published: October 2002

The objective of this study was to determine the concentration-electroencephalogram (EEG) relationships for midazolam, a full-agonist benzodiazepine ligand, on multiple occasions in individual rats, and to examine the effect of chronic midazolam exposure on that relationship. Rats were chronically instrumented with venous and arterial cannulas, and cortical EEG electrodes. The rats received either: 7 days of midazolam 10 mg kg−1 intravenously once a day (midazolam group); or midazolam on days 1 and 7 and vehicle on days 2–6 (vehicle group). Concentration-effect relationships were determined on days 1, 4 and 7 from multiple blood and EEG samples before and after the administration of the midazolam dose. The concentration-EEG effect relationships were consistent with a sigmoidal Emax (maximal effect) model. No differences in pharmacokinetic or pharmacodynamic parameters were found between day 1 and day 7 in either group. However, in the midazolam group, both the fraction unbound of midazolam in serum and the EC50 (concentration at half-maximal effect) for free midazolam increased from days 1–7 by 35 ± 3% and 54 ± 25%, respectively (means ± s.d., P < 0.05). This may be related to decreased serum albumin levels in the midazolam group (–19 ± 5%, P < 0.05) which, in turn, could be explained by the sedation associated with daily midazolam treatment. We concluded that concentration-EEG effect relationships can be studied on multiple occasions in individual animals, reducing animal use and variability. A modest degree of tolerance to midazolam was found with this paradigm, the effect only being evident after correction for the fraction unbound of midazolam.
FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in rats
Authors: Ohara F , Ohkubo K , Maeda K , Seki J , Goto T
Published: October 2002

The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg−1, 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 ± 16 and 149 ± 23 pg mg−1 protein, respectively), compared with that of the saline-treated group (258 ± 27 pg mg−1 protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83 ± 0.19 unit g−1 weight of tissue in the saline-treated group to 0.36 ± 0.09 and 0.33 ± 0.06 unit g−1 weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg−1, respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 ± 1.5,13.5 ± 1.9% at 1.0 and 3.2 mg kg−1), compared with 22.2 ± 2.7% in the saline-treated group. These results suggest that IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.
Influence of the composition of in-vitro azo-reducing systems on the degradation kinetics of the model compound amaranth
Authors: Maris B , Verheyden L , Samyn C , Augustijns P , Kinget R , Van den Mooter G
Published: October 2002

The purpose of this study was to investigate the influence of the composition of in-vitro azoreducing systems on the degradation kinetics of the model compound amaranth. The degradation kinetics of amaranth were determined under anaerobic conditions both in rat caecal content (ex-vivo) and in a variety of in-vitro degradation media derived from rat caecal content. It was observed that the reducing activity was highly dependent on the preparation method and composition of the degradation medium. In pure rat caecal content, the degradation of amaranth was apparent first order (k = 0.044+0.002 min−1), while dilution of the rat caecal content resulted in an apparentzero-orderdegradation. Both apparentzero- and first-order degradations were also observed in media made up of diluted rat caecal content to which cofactors such as NADP, D-glucose-6-phosphate, glucose-6-phosphate dehydrogenase and Bz were added. This study demonstrates that in-vitro azo-reducing kinetics are dependent on the composition and mode of preparation of the in-vitro media used. This has to be taken into account when evaluating the degradability of azo-aromatic drug delivery systems in-vitro.
Involvement of peripheral cyclooxygenase-1 and cyclooxygenase-2 in inflammatory pain
Authors: Martinez Rosa Ventura , Reval Ma Irene Díaz , Campos Myrna Déciga , Terrón José Antonio , Ramírez Adriana M Domínguez , López-Muñoz Francisco J
Published: October 2002

Pain-induced functional impairment in the rat (PIFIR) is a model of inflammatory and arthritic pain similar to that of clinical gout. Nociception is induced by the intra-articular injection of uric acid into the right hind limb, inducing its dysfunction. Animals then receive analgesic drugs and the recovery of functionality over time is assessed as an expression of antinociception. We have examined the role of peripheral prostaglandins synthesized by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in inflammatory pain using the PIFIR model. Rofecoxib (a selective COX-2 inhibitor) and SC-560 (a selective COX-1 inhibitor) both produced dose-dependent effects. When the inhibitors were administered before uric acid, they showed similar potency, but the antinociceptive efficacy of SC-560 was lower than rofecoxib; the best antinociceptive effects were obtained with the dose of 100 μ g/articulation of each inhibitor (pre-treatment). In post-treatment (inhibitors administered after the uric acid), rofecoxib showed the least antinociceptive effect and SC-560 was more potentthan rofecoxib. The inhibition of both COX-1 and COX-2 produced a more profound analgesic effect than the inhibition of either COX-1 or COX-2 alone. The present data support the idea that both COX isoforms contribute to the development and maintenance of local inflammatory nociception. Thus, it could be expected that inhibition of both COX-1 and COX-2 is required for non-steroidal anti-inflammatory drugs (NSAID)-induced antinociception in the rat. These findings suggest that the therapeutic effects of NSAIDs may involve, at least in part, inhibition of COX-1 and COX-2.
Crystallization conditions and formation of orthorhombic paracetamol from ethanolic solution
Authors: Al-Zoubi N , Nikolakakis I , Malamataris S
Published: October 2002

Orthorhombic paracetamol exhibits far better tabletability than the monoclinic form and its bulk crystallization from solution attracts much interest. In this study, temperature changes in supersaturated ethanolic solution have been recorded after seeding with orthorhombic crystals under different cooling temperatures (TC) and agitation rates (AR). Average cooling rate (CR), time for maximum temperature deviation (tmax) and area confined between curves of measured and reference temperature plots (AUC) were calculated and correlated with crystal yield (Y). The micromeritic (size and shape) and the compression properties, the density and the orthorhombic content of the crystalline product were evaluated and related to the main crystallization conditions applied (TC and AR). Conditions for optimal crystal yield and orthorhombic content were elucidated. It was found that crystal yield (Y) increased with AR and decreased with TC. The ratio tmax/CR provided good prediction of crystal yield (Y = 58.92 −1.386 tmax/CR, r2 = 0.964 and P = 0.0001). TC and AR linearly affected crystal size and the size distribution, probably due to alterations in supersaturation, but they did not affect the crystal shape significantly. Density and compression properties (yield pressure and elastic recovery) were determined by the content of the orthorhombic form, which increased linearly with AR (P = 0.009) and with TC (P = 0.039) when agitation was between 300 and 500 rev min−1, while tmax decreased. At 700 rev min−1 orthorhombic content was maximized and became independent to TC. Higher orthorhombic content and crystal yield was expected for lower TC and for lower tmax, which corresponded to higher AR and might have also been affected by alteration of seeding and harvesting procedure.
Receptor regulatory properties evident in the molecular similarity of dopamine receptor ligands and purine nucleotides
Authors: Williams W R , Pugh W J , Nicholls P J
Published: October 2002

Computational studies have revealed similarities in the relative configurations of purine nucleotides and ligands for histamine, acetylcholine and adrenergic receptors. In common with other G-protein-regulated receptors, dopamine receptors are associated with specific changes in nucleotide levels during signal transduction processes. The purpose of this study was to investigate molecular similarity in dopamine receptor ligands and purine nucleotides. Molecular superimposition and fitting data for D1-like receptor ligands identified a pharmacophore in the adenine and ribose rings of ATP. D2-like agonists and antagonists related to a pharmacophore in the guanine and ribose rings of GTP. The results are consistent with the hypothesis that the dopamine receptor family may have evolved from receptors for the ATP and GTP nucleotides.
Enteric-coating capsulation of insulinomimetic vanadyl sulfate enhances bioavailability of vanadyl species in rats
Authors: Fugono Jun , Yasui Hiroyuki , Sakurai Hiromu
Published: October 2002

In recent years, there have been improvements in the treatment of type 2 diabetes by oral administration of vanadyl sulfate (VOSO4, VS). The maintenance of vanadyl levels in the blood of subjects with type 2 diabetes was found to be important for the insulinomimetic activity of VS. However, owing to low bioavailability of VS and the development of mild gastrointestinal symptoms and side-effects in some subjects, it is necessary to design more effective and safer dosages of VS. After discovering that VS is absorbed more thoroughly at the ileum than at other gastrointestinal sites, we investigated the absorption processes following oral administration of VS by preparing enteric-coated capsules (ECC). Although Cmax values were unchanged by the dosage forms, Tmax and MRT values associated with the enteric-coating capsulation were prolonged when compared with those observed with use of gelatin capsules (GC). An important finding was that the bioavailability of VS from ECC (9.8%) was almost double that of VS from either GC (4.0%) or the solution (4.8%). Administration of VS-containing ECC to diabetic patients is proposed to improve vanadyl absorption over that achieved by the administration of either GC or the solution.
Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands
Authors: Lattmann Eric , Sattayasai Jintana , Billington David C , Poyner David R , Puapairoj Prapawadee , Tiamkao Siriporn , Airarat Wanchai , Singh Harjit , Offel Michael
Published: October 2002

A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepineswas developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-propyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel lig and had ED50 values of 4.7 and 5.2 mg kg−1 in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was observed.
Pharmacokinetic and pharmacodynamic analysis of TS-943, a selective non-peptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, using a nonlinear mixed effect model in dogs
Authors: Furuya A , Nozawa M , Gotoh J , Jingu S , Akimoto M , Higuchi S , Suwa T , Ogata H
Published: October 2002

A simultaneous analysis of the pharmacokinetics and pharmacodynamics of TS-943, a selective non-peptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, was made in dogs using a nonlinear mixed effect model. Plasma concentrations of TS-943 were determined after bolus intravenous injection, constant infusion and bolus plus constant infusion. Pharmacokinetic/pharmacodynamic data were fitted using NONMEM software. The pharmacokinetics of TS-943 fitted a two-compartment open model with first-order elimination. The pharmacodynamic model that best fitted platelet aggregation was an inhibitory sigmoid Emax model. The final estimates for E0 (baseline effect), Emax (maximum effect), IC50 (50% inhibitory concentration) and γ (Hill coefficient) were 66.3%, 64.3%, 104 ng mL−1 and 1.37, respectively. Correlations betweenTS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The TS-943 plasma concentration necessary to double bleeding time (C2-BTE) was approximately 209 ng mL−1. The model estimated that the C2-BTE/IC50 (inhibition of platelet aggregation) ratio was approximately 2.0-fold in dogs. Our results suggest that the ratio values for dogs and man are comparable. A nonlinear mixed effect model was a useful tool for exploring the concentration-effect relationship for both efficacy and safety of TS-943 in dogs and man. In this study, the dog was found to be a useful model for screening of efficacy and safety of TS-943 in man.
Dexamethasone reduces morphine-induced straub reaction in mice
Authors: Capasso Anna , Casciano Carmela , Loizzo Alberto
Published: October 2002

This study examined the effect of dexamethasone on morphine-induced straub reaction in mice. When morphine was administered in doses of 7.5, 15 and 30 mg kg−1 intraperitoneally, a dose-dependent straub reaction was produced. Dexamethasone per-se (0.1–10 mg kg−1 i.p.) did not modify the tail of control mice.

Pre-treatmentwith dexamethasone 120 min before morphine injection caused a dose-dependent reduction of straub reaction. Cycloheximide (1 5 mg kg−1 i.p.) administered 2 h before morphine did not change morphine-induced straub reaction, but was able to prevent the effects of dexamethasone on morphine-induced straub reaction. The glucocorticoid receptor antagonist RU-38486 (15 mg kg−1 i.p.) did not affect morphine-induced straub reaction, whereas it was able to block the effects of dexamethasone on morphine-induced straub reaction. Results of this study indicate that dexamethasone reduced morphine-mediated straub reaction in mice, indicating a further important functional interaction between dexamethasone and the opioid system. The ability of cycloheximide and RU-38486 to block dexamethasone's effects indicates that the steroid's interference with morphine-mediated straub reaction involves a protein-synthesis-dependent mechanism via gluco-corticoid receptors.
Determining convex polygons from their covariograms
Authors: Bianchi Gabriele
Published: October 2002

Knowing the (geometric) covariogram of a convex body is equivalent to knowing, for each direction u, the distribution of the lengths of the chords of that body which are parallel to u. We prove that the covariogram determines convex polygons, among all convex bodies, up to translation and reflection. This gives a partial answer to a problem posed by Matheron.
Simulation of cluster point processes without edge effects
Authors: Brix Anders , Kendall Wilfrid S.
Published: October 2002

The usual direct method of simulation for cluster processes requires the generation of the parent point process over a region larger than the actual observation window, since we have to allow for all possible parents giving rise to observed daughter points, and some of these parents may fall outwith the observation window. When there is noa prioribound on the distance between parent and child then we have to take care to control approximations arising from edge effects. In this paper, we present a simulation method which requires simulation only of those parent points actually giving rise to observed daughter points, thus avoiding edge effect approximation. The idea is to replace the cluster distribution by one which is conditioned to plant at least one daughter point in the observation window, and to modify the parent process to have an inhomogeneous intensity exactly balancing the effect of the conditioning. We furthermore show how the method extends to cases involving infinitely many potential parents, for example gamma-Poisson processes and shot-noiseG-Cox processes, allowing us to avoid approximation due to truncation of the parent process.
A fluid model with data message discarding
Authors: Liu Bin , Alfa Attahiru Sule
Published: October 2002

In this paper, we study a fluid model with partial message discarding and early message discarding, in which a finite buffer receives data (or information) from N independent on/off sources. All data generated by a source during one of its on periods is considered as a complete message. Our discarding scheme consists of two parts: (i) whenever some data belonging to a message has been lost due to overflow of the buffer, the remaining portion of this message will be discarded, and (ii) as long as the buffer content surpasses a certain threshold value at the instant an on period starts, all information generated during this on period will be discarded. By applying level-crossing techniques, we derive the equations for determining the system's stationary distribution. Further, two important performance measures, the probability of messages being transmitted successfully and the goodput of the system, are obtained. Numerical results are provided to demonstrate the effect of control parameters on the performance of the system.
On the distance between convex-ordered random variables, with applications
Authors: Boutsikas Michael V. , Vaggelatou Eutichia
Published: October 2002

Simple approximation techniques are developed exploiting relationships between generalized convex orders and appropriate probability metrics. In particular, the distance betweens-convex ordered random variables is investigated. Results connecting positive or negative dependence concepts and convex ordering are also presented. These results lead to approximations and bounds for the distributions of sums of positively or negatively dependent random variables. Applications and extensions of the main results pertaining to compound Poisson, normal and exponential approximation are provided as well.
On the stability of a batch clearing system with Poisson arrivals and subadditive service times
Authors: Aldous David , Miyazawa Masakiyo , Rolski Tomasz
Published: October 2002

We study a service system in which, in each service period, the server performs the current set B of tasks as a batch, taking time s(B), where the function s(·) is subadditive. A natural definition of ‘traffic intensity under congestion’ in this setting is ρ := limt→∞t-1Es (all tasks arriving during time [0,t]). We show that ρ > 1 and a finite mean of individual service times are necessary and sufficient to imply stability of the system. A key observation is that the numbers of arrivals during successive service periods form a Markov chain {An}, enabling us to apply classical regenerative techniques and to express the stationary distribution of the process in terms of the stationary distribution of {An}.
Compound Poisson approximation for the Johnson-Mehl model
Authors: Erhardsson Torkel
Published: October 2002

We consider the uncovered set (i.e. the complement of the union of growing random intervals) in the one-dimensional Johnson-Mehl model. Let S(z,L) be the number of components of this set at time z > 0 which intersect (0, L]. An explicit bound is known for the total variation distance between the distribution of S(z,L) and a Poisson distribution, but due to clumping of the components the bound can be rather large. We here give a bound for the total variation distance between the distribution of S(z,L) and a simple compound Poisson distribution (a Pólya-Aeppli distribution). The bound is derived by interpreting S(z,L) as the number of visits to a ‘rare’ set by a Markov chain, and applying results on compound Poisson approximation for Markov chains by Erhardsson. It is shown that under a mild condition, if z→∞ and L→∞ in a proper fashion, then both the Pólya-Aeppli and the Poisson approximation error bounds converge to 0, but the convergence of the former is much faster.
Linear estimation of self-similar processes via Lamperti's transformation
Authors: Nuzman Carl J. , Poor H. Vincent
Published: October 2002

Lamperti's transformation, an isometry between self-similar and stationary processes, is used to solve some problems of linear estimation of continuous-time, self-similar processes. These problems include causal whitening and innovations representations on the positive real line, as well as prediction from certain finite and semi-infinite intervals. The method is applied to the specific case of fractional Brownian motion (FBM), yielding alternate derivations of known prediction results, along with some novel whitening and interpolation formulae. Some associated insights into the problem of discrete prediction are also explored. Closed-form expressions for the spectra and spectral factorization of the stationary processes associated with the FBM are obtained as part of this development.
Asymptotic properties of integral functionals of geometric stochastic processes
Authors: Csáki Endre , Csörgő Miklós , Földes Antónia , Révész Pál
Published: October 2002

We study strong asymptotic properties of two types of integral functionals of geometric stochastic processes. These integral functionals are of interest in financial modelling, yielding various option pricings, annuities, etc., by appropriate selection of the processes in their respective integrands. We show that under fairly general conditions on the latter processes the logs of the integral functionals themselves asymptotically behave like appropriate sup functionals of the processes in the exponents of their respective integrands. We illustrate the possible use and applications of these strong invariance theorems by listing and elaborating on several examples.
Quasistationarity in continuous-time Markov chains where absorption is not certain
Authors: Darlington S. J. , Pollett P. K.
Published: October 2002

In a recent paper [4] it was shown that, for an absorbing Markov chain where
absorption is not guaranteed, the state probabilities at time t conditional on non-absorption by t generally depend on t. Conditions were derived under which there can be no initial distribution such that the conditional state probabilities are stationary. The purpose of this note is to show that these conditions can be relaxed completely: we prove, once and for all, that there are no circumstances under which a quasistationary distribution can admit a stationary conditional interpretation.
Reduction techniques for discrete-time Markov chains on totally ordered state space using stochastic comparisons
Authors: Truffet Laurent
Published: October 2002

We propose in this paper two methods to compute Markovian bounds for monotone functions of a discrete time homogeneous Markov chain evolving in a totally ordered state space. The main interest of such methods is to propose algorithms to simplify analysis of transient characteristics such as the output process of a queue, or sojourn time in a subset of states. Construction of bounds are based on two kinds of results: well-known results on stochastic comparison between Markov chains with the same state space; and the fact that in some cases a function of Markov chain is again a homogeneous Markov chain but with smaller state space. Indeed, computation of bounds uses knowledge on the whole initial model. However, only part of this data is necessary at each step of the algorithms.
A stochastic lower bound for assemble-transfer batch service queueing networks
Authors: Economou Antonis
Published: October 2002

Miyazawa and Taylor (1997) introduced a class of assemble-transfer batch service queueing networks which do not have tractable stationary distribution. However by assuming a certain additional arrival process at each node when it is empty, they obtain a geometric product-form stationary distribution which is a stochastic upper bound for the stationary distribution of the original network. In this paper we develop a stochastic lower bound for the original network by introducing an additional departure process at each node which tends to remove all the customers present in it. This model in combination with the aforementioned upper bound model gives a better sense for the properties of the original network.
Optimal strategy in a dice game
Authors: Haigh John , Roters Markus
Published: October 2002

Computer simulations had suggested that the strategy that maximises the score on each turn in the dice game described by Roters (1998) may not be the optimal way to reach a given target in the shortest time. We give an analytical treatment, backed by numerical calculations, that finds the optimal strategy to reach such a target.
Strong ergodicity for single-birth processes
Authors: Zhang Yu-Hui
Published: October 2002

An explicit and computable criterion for strong ergodicity of single-birth processes is presented. As an application, some sufficient conditions are obtained for strong ergodicity of an extended class of continuous-time branching processes and multi-dimensional Q-processes by comparison methods respectively. Consequently strong ergodicity of the Q-process corresponding to the finite-dimensional Schlögl model is proven.
An explicit solution to an optimal stopping problem with regime switching
Authors: Guo Xin
Published: October 2002

We investigate an optimal stopping time problem which arises from pricing Russian options (i.e. perpetual look-back options) on a stock whose price fluctuations are modelled by adjoining a hidden Markov process to the classical Black-Scholes geometric Brownian motion model. By extending the technique of smooth fit to allow jump discontinuities, we obtain an explicit closed-form solution. It gives a non-standard application of the well-known smooth fit principle where the optimal strategy involves jumping over the optimal boundary and by an arbitrary overshoot. Based on the optimal stopping analysis, an arbitrage-free price for Russian options under the hidden Markov model is derived.
Hormone replacement therapy and breast carcinoma risk in Hispanic and non‐Hispanic women
Authors: Li Rui , Gilliland Frank D. , Baumgartner Kathy , Samet Jonathan
Published: October 2002

BACKGROUND

Hormone replacement therapy (HRT) alleviates menopausal symptoms and prevents osteoporosis, but there is concern that long‐term use may have an adverse impact on breast carcinoma risk. Epidemiologic studies report inconsistent findings regarding the relationship between HRT and postmenopausal breast carcinoma risk and there is little information on the HRT‐associated risk among minority women.

METHODS

To investigate the effects of HRT on breast carcinoma risk among Hispanic women, we examined data from the New Mexico Women's Health Study (NMWHS), a statewide case–control study comprising 366 postmenopausal women with breast carcinoma and 403 controls. Conditional logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI).

RESULTS

After adjustment for sociodemographic, medical, and reproductive factors, we found an increased risk associated with long‐term users of estrogen replacement therapy (ERT; OR for ERT use longer than 140 months was 2.57, 95%CI, 1.25–5.28, compared with ERT use shorter than 17 months). In addition, there was a positive trend with the duration of ERT use (P < 0.01). Hispanic postmenopausal women appeared to be at a significantly greater risk than non‐Hispanic white women (OR for ERT use longer than 140 months in Hispanics was 5.53, 95%CI, 1.47–20.87; OR in non‐Hispanics was 2.65, 95%CI, 0.95–7.34, compared with ERT use shorter than 17 months). In contrast, no significant association was observed for combined estrogen‐progesterone use in either Hispanic or non‐Hispanic women.

CONCLUSIONS

The results of this study indicated that postmenopausal women had significantly increased breast carcinoma risk for long‐term ERT use. The risks among Hispanic women were substantially higher than among non‐Hispanic white women although they were not statistically significant. Cancer 2002;95:960–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10791
Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan
Authors: Kobayashi Mariko , Arase Yasuji , Ikeda Kenji , Tsubota Akihito , Suzuki Yoshiyuki , Saitoh Satoshi , Kobayashi Masahiro , Suzuki Fumitaka , Akuta Norio , Someya Takashi , Matsuda Marie , Sato Junko , Takagi Kimiko , Miyakawa Yuzo , Kumada Hiromitsu
Published: October 2002

Acute hepatitis B virus (HBV) infection was diagnosed in 57 adults admitted to Toranomon Hospital in Tokyo, Japan. Genotypes of HBV were determined by a serological method and compared to those in 1,077 patients with chronic hepatitis B. The distribution of genotypes were: genotype A (acute, 22.8% vs. chronic, 1.9%; P < 0.00001); B (14.0% vs. 9.4%); C (43.9% vs. 87.7%, P = 0.004); D (1.8% vs. 0.2%); F (1.8% vs. 0.2%); and unable to be typed (15.8% vs. 0.6%, P = 0.001). The infection persisted in seven (12%) of them. They included six (86%) of the seven patients who received prednisolone or glycyrrhizin during an acute phase of illness and one of the 41 (2%) who did not (P = 0.01). Interferon was given to the seven patients with acute prolonged HBV infection, and four of them responded by clearing hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) from serum. Of the four responders, one was infected with HBV genotype B and three with genotype C. HBsAg persisted in the remaining three patients all of whom were infected with HBV genotype A, and HBeAg stayed positive in one of them. These results indicate that HBV genotype A prevails in Japanese patients with acute hepatitis B, and suggest a high efficacy of interferon in the adult patients with acute prolonged HBV infection, except in those infected with HBV genotype A. J. Med. Virol. 68:522–528, 2002. © 2002 Wiley‐Liss, Inc.
An expectancy‐equity model of productive system performance
Authors: Powell Gary N. , Johnson George A.
Published: October 2002

Although numerous behavioral variables (e.g., personality traits, incentives, nature of supervision) have documented relationships with quantity and quality of output, i.e., performance, in production systems, existing production and operations management models are dominated by technological variables. The article addresses three questions: 1. Which technological and behavioral variables influence productive system performance? 2. How do behavioral and technological variables interact? 3. Which variables are most important under different circumstances in determining performance?

An expectancy‐equity model, patterned on research by Lawler [22], presents proposed relationships among variables in production systems, which are classified along a continuum from high to low process predictability. Predominant determinants of performance in various types of systems (e.g., continuous process, job shop, R&D project) are considered in light of the model. Implications for designers and analysts of productive systems and for future research are discussed.
A study of the MRP implementation process
Authors: White Edna M. , Anderson John C. , Schroeder Roger G. , Tupy Sharon E.
Published: October 2002

This paper reports on a large‐scale survey of companies involved in MRP implementation. Survey responses are used to develop a profile of problems typically encountered during the implementation process. Discriminant analysis is used to determine which of those problems, and additional factors, appear to affect the success or failure of MRP implementation. Finally, comparisons are made between the problems encountered during implementation and problems which were found to significantly discriminate between successful and unsuccessful MRP implementors.
An availability model for the evaluation of equipment alternatives
Authors: Lingaraj B.P. , Kuo Way
Published: October 2002

An availability based model for the evaluation of alternatives in equipment replacement analysis is presented. The expected annual cost of an equipment alternative is developed as a function of availability. The least cost alternative for the desired availability is identified from cost vs. availability curves of the alternatives. A simulation approach is used to determine the availability of existing equipment. The methodology is applied to the evaluation of alternate equipment for the analysis of serum samples in a hospital laboratory.
Job shop scheduling with modified due dates
Authors: Baker Kenneth R. , Kanet John J.
Published: October 2002

This paper introduces a new dispatching rule to job shop scheduling, extending earlier results to a multi‐machine environment. This new rule, which uses modified due dates is compared to other popular dispatching methods over a range of due date tightnesses at two utilization levels. The results for mean tardiness indicate that the modified operation due date (MOD) rule compares very favorably with other prominent dispatching methods.

The modified due date is a job's original due date or its early finish time, whichever is larger. For an individual operation, it is the operation's original due date or the operation's early finish time, whichever is larger. A comparison of the job‐based version with the operation‐based version indicated that the operation‐based version tended to be more effective at meeting due dates.

The main performance measure was mean job tardiness, although the proportion of tardy jobs was also reported, and the two measures together imply the conditional mean tardiness. The MOD rule was compared to several well‐known tardiness‐oriented priority rules, such as minimum slack‐per‐operation (S/OPN), smallest critical ratio (SCR), and COVERT. The MOD rule tended to achieve lower levels of mean tardiness than the other rules, except under conditions where due dates were quite loose. In this situation, very little tardiness occurs for any of the rules. The MOD rule appeared to be more robust than the other rules to changes in the tightness of due dates, and similar results occurred at both high and low utilizations.
Two heuristics for the deterministic, single operator, multiple machine, multiple run cyclic scheduling problem
Authors: Aronson Jay E.
Published: October 2002

The semiautomatic nature of machinery often makes it economical to assign more than one machine to a single operator. Multi‐machine assignments are common in the textile, tooling and molding industries. They are also found where numerically controlled (NC) machinery are used and, more recently, where flexible manufacturing systems (FMS) are employed. Previous work on deterministic cyclic scheduling models has focused on determining the optimal number of usually identical machines with single runs to assign to an operator. In practice, the schedules are represented by man/machine charts.

When, due to production requirements, we mix different types of runs with known times on non‐identical machines, we have the deterministic, single operator, multiple machine, multiple run, cyclic scheduling problem. We present two heuristics for solving this more realistic generalization of earlier problems. For the nonidentical, multiple run case, the scheduling of the runs is crucial in minimizing the cycle time of the system. The integer programming formulation of small problems is large, and solving it directly could require excessive computation time on a large mainframe computer.

Heuristic 1 selects the next machine run to schedule by minimizing the total immediate waiting cost of the operator and machines. The hourly machine costs reflect the relative merit of utilizing certain machines over others. Heuristic 2 first schedules the machine with the longest automatic processing time of run one. It then follows Heuristic 1 until the long processing time of the first run has ended. The next available run with the longest automatic processing time is then scheduled, and the process repeats. The underlying notion is that many short runs may be performed during the long automatic run of a machine.

The heuristics are polynomially bounded, can be easily implemented on a mini‐ or micro‐computer and in practice should be much faster than integer programming methods. In addition to the heuristics, we compute a lower bound on the cycle time. We use this bound as a measure of the effectiveness of a solution. If for a given schedule, the cycle time equals its lower bound, then the solution is optimal.

Both heuristics were coded in FORTRAN on a CDC‐6600 computer. An interactive version was also developed for a DEC PDP11/70. A detailed computational study is presented. In it, both heuristics solved 50 machine, 5 run problems in less than 10 CPU seconds on the CDC‐6600. Computational experience indicates that the heuristics are efficient and often find schedules which have cycle times within 10% the lower bound.
A vacation scheduling algorithm for military flight crews: Maximizing satisfaction while maintaining military preparedness
Authors: Chong Philip S. , Strevell Michael W.
Published: October 2002

This article develops a quantitative method of assigning leave to crewmembers in an operational military flying squadron. The objective of the assignment process is to maximize crew preferences. This objective is limited by manning constraints which limit the number of crews that can be on leave at the same time. The basis of the assignment process is a point system which allows each crew to bid for the periods they prefer. The periods are then assigned to the highest bidder. In this way, each crew is assured of an influence in the leave assignment process, and the results are entirely in the hands of the crews themselves. The method now used to assign leave was developed and refined during a three year period from 1981 to 1983. The 1983 method includes a two‐phase partially open bidding system.

In Phase I, crews signed up on a posted calendar for the periods they wanted, but they did not assign points to the periods. During this phase, crews could change their period request as they saw what other crews requested. This allows crews to sequence themselves to avoid conflicts. At the end of Phase I, the juggling process was closed, and crews could no longer change their period request. Crews were given a week between the close of Phase I and the start of Phase II to see how many other crews they were competing with. Then in Phase II, they submitted their points via closed bid.

This system was very effective in both distributing the demand and preventing “gaming.” There was a strong disincentive from changing a period request at the last minute. If they did, the competition had a week to see whom they were competing with and could then bid accordingly. It was to everyone's advantage to avoid competition.

Statistical analysis and positive feedback from crews and scheduling personnel have proven this method to be significantly superior to the former system.
Staffing and equipment decisions for services: An experimental analysis
Authors: Mabert Vincent A.
Published: October 2002

Many service‐oriented firms face demand/work load variations that occur both within and between days, and seasonally during the year. These service firms tend to develop staffing plans based on peak periods, resulting in substantial idle time during low demand periods. To counter this, some firms hire part‐time employees to work peak periods to improve productivity. In this way, the cost per customer/transaction (unit) can be reduced.

However, the staffing decision is more complex than just determining the number and timing of the work force. The development of good staffing plans must consider the impact of available work stations like telephone consoles and data entry terminals. To use effectively more personnel during peak periods, the firm must have sufficient work stations to assign this work force. Effective staff scheduling must consider simultaneously the work load variations, employ capabilities, and equipment requirements. This article presents a model that incorporates these factors into the decision‐making process and examines their interaction.

The model analysis illustrates how uncertainty in work load forecasts and staffing flexibility influence expected cost performance and equipment requirements. A set of computer simulation experiments are conducted using operating data from the proof and encoding departments for Ohio National Bank and Chemical Bank. The results suggest that increased staffing flexibility reduces the needed equipment investment, since part time staff can be scheduled more conveniently to meet varying work loads. Also, basing capital equipment decisions on peak work load levels can substantially increase total operating costs. With these costs explicitly estimated, managers can weigh them against desired service level goals to determine the appropriate balance.
The use of simulation in system design: A case study using the precision location strike system
Authors: Clark Thomas D. , Arnett Gary W. , Reybrock Nicholas W.
Published: October 2002

The purpose of the article is to illustrate the use of computer simulation study and modeling in the design of complex systems. When new systems are designed, decision‐makers rely heavily upon judgment, intuition and experience. The method discussed is intended to enhance these executive attributes by providing a vehicle with which the decision‐maker may be proactive before implementing the system rather than being solely reactive after implementation.

The application of a method known as the “systems science paradigm” is discussed and illustrated using the U.S. Air Force's Precision Location Strike System. The problem was to design a logistical support structure for the Strike System. The three major options proposed were to locate repair and resupply structures at the point of equipment use in Europe, to have a mixed system, or to locate support at a base in the continental United States.

The research employed the paradigm suggested to develop an experimental Q‐GERT simulation model of the processes and structures envisioned. Data development for abstract systems is illustrated and methods to experiment with alternate structures are developed and discussed. The concept of multiechelon inventory and repair are addressed within the problem's context.

A proposed design alternative resulted from application of the process. Methods, other than cost effectiveness, to evaluate the system are also suggested. Implementing the design process for ill‐defined systems appears to be an effective method for dealing with such design problems.
Exponentially smoothed regression analysis for demand forecasting
Authors: Roodman Gary M.
Published: October 2002

This article proposes a new technique for estimating trend and multiplicative seasonality in time series data. The technique is computationally quite straightforward and gives better forecasts (in a sense described below) than other commonly used methods. Like many other methods, the one presented here is basically a decomposition technique, that is, it attempts to isolate and estimate the several subcomponents in the time series. It draws primarily on regression analysis for its power and has some of the computational advantages of exponential smoothing. In particular, old estimates of base, trend, and seasonality may be smoothed with new data as they occur. The basic technique was developed originally as a way to generate initial parameter values for a Winters exponential smoothing model [4], but it proved to be a useful forecasting method in itself.

The objective in all decomposition methods is to separate somehow the effects of trend and seasonality in the data, so that the two may be estimated independently. When seasonality is modeled with an additive form (Datum = Base + Trend + Seasonal Factor), techniques such as regression analysis with dummy variables or ratio‐to‐moving‐average techniques accomplish this task well. It is more common, however, to model seasonality as a multiplicative form (as in the Winters model, for example, where Datum = [Base + Trend] ∗ Seasonal Factor). In this case, it can be shown that neither of the techniques above achieves a proper separation of the trend and seasonal effects, and in some instances may give highly misleading results. The technique described in this article attempts to deal properly with multiplicative seasonality, while remaining computationally tractable.

The technique is built on a set of simple regression models, one for each period in the seasonal cycle. These models are used to estimate individual seasonal effects and then pooled to estimate the base and trend. As new data occur, they are smoothed into the least‐squares formulas with computations that are quite similar to those used in ordinary exponential smoothing. Thus, the full least‐squares computations are done only once, when the forecasting process is first initiated. Although the technique is demonstrated here under the assumption that trend is linear, the trend may, in fact, assume any form for which the curve‐fitting tools are available (exponential, polynomial, etc.).

The method has proved to be easy to program and execute, and computational experience has been quite favorable. It is faster than the RTMA method or regression with dummy variables (which requires a multiple regression routine), and it is competitive with, although a bit slower than, ordinary triple exponential smoothing.