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A conventional nomogram, based on serum creatinine (sCr) and age, was developed in order to determine the correct initial dosage regimen for meropenem (MEPM) infusions in elderly patients with severe community-acquired pneumonia (CAP), using a target minimum inhibitory concentration (MIC) of 2 mg/L. A correlation between age and actual bodyweight (BW) in a development cohort of 44 males and 45 females was performed by linear regression using the least-squares method (male: y=-0.4676x+80.281, R(2)=0.4888; female: y=-0.4373x+77.502, R(2)=0.3194). There were no significant differences between actual BW and the BW (e-BW) estimated using this equation in this cohort (male: e-BW 41.6±3.1 kg, BW 41.7±3.5 kg, p=0.93; female: e-BW 39.5±2.1 kg, BW 39.5±3.7 kg, p=0.20). By integrating these equations using the Monte Carlo simulation method, a dosage regime was calculated which would have an 80% probability of maintaining plasma drug levels above the MIC for more than 40% of the time (>40%TAM), using only the age and sCr of individual patients. This relationship was summarized as a nomogram. The nomogram was validated using an independent validation cohort (n=28) of patients. An optimized dosage regimen could be predicted in 84 patients (94.4%) in the development cohort and 25 patients (89.3%) in the validation cohort. This nomogram may be a useful tool for clinicians and pharmacists in determining an initial MEPM regimen in elderly patients with severe CAP, based only on age and sCr.

The expression of estrogen receptor-alpha (ER) and progesterone receptor (PR) in normal, hyperplastic, and neoplastic endometrium in rabbits was evaluated by immunohistochemistry. The tissues evaluated were 27 normal uteri, 19 cases with endometrial hyperplasia, and 42 adenocarcinomas. Sixteen of 27 cases of normal uteri (59.3%) and 13 out of 19 hyperplasias (68.4%) stained positive with both ER-alpha and PR. Adenocarcinomas were further subdivided into 26 papillary and 16 tubular/solid adenocarcinomas. Papillary adenocarcinoma infiltrated the myometrium late in the disease and caused attenuation of the myometrium. In contrast, tubular/solid adenocarcinoma invaded into the deep myometrium early in the disease without thinning of the myometrium. Twenty-one cases out of 26 (80.8%) cases of papillary adenocarcinoma were both ER-alpha and PR negative, whereas 15 out of 16 (93.8%) of the tubular/solid adenocarcinomas were positive for ER-alpha, PR, or both. The total immunoreactive scores of ER-alpha, PR, and mode of myometrial invasion were significantly different between histopathologic types. This suggests that there may be 2 different developmental pathways for uterine adenocarcinomas in the rabbit.

In this paper, a method using a subadaptive filter playing the supplementary role of acoustic echo cancellation is discussed. Since the updating state of the adaptive filter can be calculated approximately as a characteristic of the subadaptive filter, the step size parameter can be optimally controlled depending on the estimation accuracy. Also, for prevention of echo path variation, we discuss a variable detector in which the variation of the filter coefficients at the time of variation is considered. The proposed method is found to be robust to channel variations and can improve the ERLE by 10 to 15 dB in comparison with the conventional method. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 90(2): 9–21, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.20231

チーターを始めとする大型肉食ネコ科動物における腸型ヘリコバクターに関する報告は見当たらない。そこで,チーターにおける腸型ヘリコバクターの感染状況と病変との関連を明らかにすることを目的として,本研究を行った。1994年から2002年の間に病性鑑定を行った63頭より今回の検索に適した36頭を選択し,これらの消化管(十二指腸7例[DD],小腸28例[SI],盲腸15例[CC],結腸37例[LI])を検索した。また全ての症例および部位に程度に差があったが,リンパ・プラズマ細胞性腸炎が観察され,特に盲腸で高度であった。糜爛・潰瘍が[DD]1(14%),[SI]2(7%),[CC]10(63%)[LI]12(40%)でみられ,粘膜固有層へのアミロイド沈着が[DD]5(71%),[SI]28(97%),[CC]11(69%)[LI]23(77%)に認められた。ヘリコバクターは,陰窩の拡張を伴って腺底部の腺腔内を中心に21(57%)に観察され,その内訳は[DD]0,[SI]6(21%),[CC]9(56%)[LI]14(47%)であった。ヘリコバクターは直線的で,約3.5×0.3μmで,規則的に密に巻き付く細胞周囲線維を有していた.以上の結果から,H.billsあるいはFlexispira rappiniと考えられるヘリコバクターがチーターに高率に感染していることが明らかになった。ヘリコバクター感染と病変との関連は一見ないようであった。しかしながら,ヘリコバクター感染がリンパ・プラズマ細胞性腸炎や糜爛・潰瘍とどのように関連するか,さらに検討する必要がある。また,調査可能であったチーター全てに認められた消化器症状の発現には,腸炎ないしはアミロイド沈着が重要な役割を担っていることがわかった。特にアミロイド沈着は高度で,他の臓器への沈着とともにチーターの死因として重要な病変と考えた。, There has been no report on the prevalence and pathogenicity of enteric Helicobacter in large felid including cheetahs. The pathogenicity of most eneric Helicobacters remains still unknown. Pathological examination of 63 captive cheetahs revealed a high incidence of lymphocytic enteritis. We therefore studied the prevalence of enteric Helicobacter infection and its pathogenicity in captive cheetahs, in an attempt to identify the cause of this desease. Pathological studies were carried out on 87 interstinal samples from 36 cheetahs that died in captivity (7 duodenun, 28 jejunoileum, 17 colon, 15 cecum, 20 rectum). Immunostain identified enteric Helicobacter in 21 cheetahs out of examined 36 csaes (58%). The site prevalence was 0 duodenum, 6 jejunoileum (21%), 9 cecum (60%), 9 colon (53%) and 8 rectum (40%), Helicobacter spp. Were mostly present in the crypts, either scattering or clumping, and patterns by SEM, they were straight and rodlike in shape and 3～3.5×0.3 microns in size, with regular, densely aligned pericytoplasmic fibers. Intestinal lesions included lymphocytic enteritis, thickened lamina propria, dilatated crypts, amyloid deposition, and erosion and ulceration. In all animals examined, varying lymphocytic enteritis was present at least, in the part of the intestines, and was more prominent in the cecum. Advanced amyloid deposition was also highly prevalent, appearing in 27/28 samples of small intersting (96%) and 38/52 samples of the large intesting (73%). While gastric Helicobacter infection is well known in cheetahs, our results also indicated a high rate (58%) if enteric Helicobacter infection among them. Ultrastructural observation suggested that the bacteria might be H. bilis or Flexispira rappini. Lympho-plasma cytic enteritis and intestinal amyloidosis were also highly prevalent in the animals observed. It seems that there were no relation to Helicobacter infection and the pathological changes. However, will have to consider how helicobacter infection relates to the lesions and ulcer further. Our results therefore suggest that amyloid deposition in the intestines as well as amyloidosis in other organs, will be a major life-threatenining factor in captive cheetahs. (Presented at 52nd ACVP Meeting).

It has been found that alpha-effects in nucleophilic reactions, unexpectedly large nucleophilicity due to adjacent unpaired electrons, are strongly dependent on the structure of substrate. The nucleophilic cleavages of 4-nitrobenzoate esters and 4-methylbenzoate esters by HOO- have been systematically investigated in detail. When the leaving groups of substrates are sufficiently good (aryl, 2,2,2-trifluoroethyl, and 2,2-dichloroethyl esters), alpha-effect is evident. However, this effect drastically decreases as the leaving group gets poorer, and is only marginal for the cleavages of 2-fluoroethyl and methyl esters. In the nucleophilic cleavages by salicylaldoxime and acetohydroxamic acid, alpha-effect is also notable only for the esters having good leaving groups. These enormous dependences of alpha-effects on the substrate-structure have been interpreted in terms of the difference in the position of transition-state in the reaction coordinate.

The subband adaptive Volterra filter (SBAVF), which can assign the filter length of each subband arbitrarily, is proposed. If the frequency characteristics of a system to be identified are shifted to a certain bandwidth, it is usually not possible to carry out efficient identification by taking account of the shift of the bandwidth in a (full band) adaptive Volterra filter. On the other hand, in the proposed SBAVF, efficient system identification is possible by assigning a longer filter length to the dominant frequency range of the system of interest. When the proposed method is applied to a speaker system, it is shown through simulation results that the error attenuation can be improved from 1.5 dB to 7.5 dB in comparison with the conventional method. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(7): 45–54, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10135

In the problem of restoration of images degraded by impulsive noise, a method has been proposed to eliminate impulsive noise by using the noise position image formed with noise detectors. However, such a method estimates the signal values of the pixels to be processed by using only the nondegraded pixels within the filter window. Hence, if the majority of the window is occupied by impulsive noise, the signal information needed for estimation becomes insufficient and the estimation accuracy is significantly reduced. In addition, in the previous method, average value filters and median filters are used for estimation of the signal value of the processing points. No processing has been included that takes account of the directionality (shape) of image signals such as edge components and detail components. In the present paper, a new noise elimination filter is proposed that attempts to improve restoration accuracy by addressing these two problems. In the proposed filter, first the degraded pixels within the filter window are precompensated for the problem of insufficient original signal pixels in the filter window, and then the signal values at the processing points are estimated by the filter once sufficient signal information is obtained. Preservation of the directionality of the image signals is improved by extending the directional difference filter. Its effectiveness is verified by real image processing results. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(5): 65–75, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1149

In this paper, an automatic method for the design of compact acoustic systems, using the genetic algorithm, is proposed for improvement of degraded sensitivity caused by leakage. In the present method, an analysis based on the acoustic equivalent circuit is used. The equivalent circuit and the acoustic parameters of the circuit are designed in such a way that the sound pressure frequency characteristics are contained with the range based on the GSM (ETSI EN 300 903) specifications and that the sensitivity deterioration is improved. The PfGA (Parameter-free Genetic Algorithm) is used in the design of the circuit configuration, and the genetic algorithm of Michalewicz is used for the design of acoustic parameters. As a result, an equivalent circuit is obtained that realizes characteristics not significantly affected by leakage. The present method can be applied to various compact acoustic systems such as cellular phones and provides useful information for actual design. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(3): 1–9, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10149

An active noise control (ANC) system is proposed that uses a new frequency domain simultaneous perturbation (FDSP) method automatically controlling the magnitude of perturbation. The proposed method automatically controls the magnitude of perturbation so that the convergence speed can be improved substantially over the conventional case where the magnitude of perturbation is fixed. Specifically, when the error signal is large, the magnitude of the perturbation is made large, while the latter is reduced when the error signal is small. As a result, the present system resolves the problem of instability caused by the block process and also the step size can be set to a larger value. The present control is effective when the magnitude of perturbation needs to be set small. In particular, if the magnitude of perturbation is 0.08, the convergence speed is improved by more than 50 times. Also, the present control is effective for suppression of the noise generated due to addition of perturbation. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 87(2): 43–53, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10112

Since a speaker system has nonlinearity, it is necessary to place a nonlinear inverse system in front of the speaker system so that the nonlinear distortion is corrected. However, in realization with DSP, the amount of computation in the Volterra filter used in the nonlinear inverse system is enormous. There exists a region containing aliasing components in the output signal of the Volterra filter. There is a way to band-limit the input signal in order to avoid aliasing. However, since the sampling frequency is set to twice the Nyquist frequency, an unnecessary band is processed and the efficiency is poor. Hence, in this paper, a configuration is proposed that does not cause aliasing even if the sampling frequency is chosen as the Nyquist frequency in order to reduce the amount of computation in the Volterra filter. Next, an identification method for the speaker system in order to efficiently obtain the Volterra filter used in the proposed configuration is presented. The proposed configuration is applied to the nonlinear inverse system. Finally, the effectiveness of the present method is demonstrated by simulation. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(1): 19–26, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10031

The aim of this study was to analyze the pharmacokinetics and pharmacodynamics (PK/PD) of 6- O-(3-ethoxypropionyl)-3',4'- O-exo-benzylidene-chartreusin (IST-622) and its metabolites, and to develop limited sampling models (LSM). Based on the data from 18 patients with breast cancer who were treated orally with 280 or 525 mg/m(2) of IST-622 once daily after breakfast for five consecutive days, we analyzed the relationship between the area under the plasma concentration versus time curve (AUC) and toxicities using a sigmoid E-max model and logistic regression. Plasma concentrations of IST-622 and its metabolites, 3',4'- O-exo-benzylidene-chartreusin (A-132) and 3"-demethyl-3',4'- O-exo-benzylidene-chartreusin (A-132M), were measured at 1, 2, 4, 8 and 24 h after administration on day 1. The AUC was calculated using the trapezoidal method. We also developed a LSM using stepwise linear regression analysis. IST-622 was detected in very few patients, and its concentration was very low and could be disregarded. It was suggested that meals promoted absorption of IST-622. AUCs of A-132 plus A-132M showed a better correlation with the rates of decrease and nadir counts of leukocytes, neutrophils and platelets than the AUC of each metabolite separately. Patients with the sum of AUCs more than 70 microg.h/ml showed severe myelotoxicities. Moreover, logistic regression analysis showed that grade 4 myelotoxicities would be seen in 30% of patients at an AUC of 65 microg.h/ml. We also developed an unbiased and precise LSM: AUCSUB0-24h/SUB=CSUB8h/SUBx17.6-0.95, where C(8h) denotes the sum of plasma concentrations of A-132 and A-132M. Myelotoxicities showed a good correlation with AUC(0-24h), and based on the results, it was decided that the target AUC was 65 microg.h/ml. The LSM was very convenient for estimating AUC(0-24h) and sufficiently accurate. These results show the possibility of predicting toxicities and dose adaptation for interpatient variability using LSM.

In this paper, a formulation of the convergence property of the NLMS method, an updating algorithm for an adaptive Volterra filter, is discussed. To date, much research has been carried out on the convergence property of the updating algorithm in a linear adaptive filter. However, there has been insufficient study of the updating algorithm for the second-order adaptive Volterra filter. In this paper, the convergence property of the E-NLMS method, an updating algorithm in the second-order adaptive Volterra filter, is formulated and the convergence property of the second-order adaptive Volterra filter is theoretically determined. In the formulation of the convergence property we use the first-order recursive filter expression, which is effective for studying various characteristics of the NLMS method in linear adaptive filters. In addition, it is recognized that the nature of the input signal to the diagonal (D) elements of the second-order Volterra system is different from that of the input to the other (ED) components. By means of computer simulation, it is confirmed that the convergence property given by the derived theoretical equation can sufficiently express the actual convergence property. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 85(10): 40–50, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1124

We investigated the livers, spleens, kidneys and lungs collected from 24 cynomolgus macaques (Macaca fascicularis) naturally infected with Ebola virus subtype Reston (EBO-R) during the Philippine outbreak in 1996, in order to reveal the histopathologic findings. These macaques showed necrotic hepatocytes with inclusions, slight to massive fibrin deposition in splenic cords, depletion of lymphoid cells in the white pulp of the spleen, and fibrin thrombi in some organs. Immunohistochemical analysis using anti-leukocyte antigen L1 antibody revealed an increase in blood-derived macrophages/monocytes in the livers, kidneys and lungs of EBO-R infected macaques. EBO-R NP antigens were detected in the macrophages/monocytes, endothelial cells and fibroblasts in the liver, spleen, kidney and lung. These results indicate that EBO-R infection is characterized by systemic coagulopathy and an increase in blood-derived macrophages/monocytes in accordance with the EBO-R propagation in macrophages/monocytes.

In this paper, a new median filter is proposed that has robustness without relying on the noise generation probability. The proposed filter has a configuration with an impulse detector in the prior stage of the filter. Since this detector has a superior signal estimation capability of the directional difference filter, impulse noise can be detected effectively even if generated at a high generating ratio and as a burst. In the median filter in the later stage, inclusion of the output values of the directional filter and successive updating of the signal values (successive process) are introduced. Hence, while the noise elimination capability of the conventional median filter is retained, the signal preservation at the details and edges can be improved. Therefore, the noise elimination filter proposed in this paper is abundant in robustness against variations of the gray scale, the generation probability, and the impulse adding situation. Its restoration results for images with superposed impulse noise at a high generation probability confirm the improvement of performance. In this paper, the effectiveness of the proposed impulse detector is first demonstrated. It is proven through processing examples that a better image processing result can be obtained from its combination with a newly configured median filter. At the same time, the robustness of the proposed procedure under various conditions is demonstrated. The effectiveness of the proposed method in the final restored image is verified. © 2001 Scripta Technica, Electron Comm Jpn Pt 3, 85(3): 22–32, 2002

Previously, a nested polymerase chain reaction (PCR) was employed with consensus degenerate primers targeting highly conserved motifs within herpesviral DNA polymerase genes to detect a newly described tortoise herpesvirus. However, nucleotide sequence information obtained from the final amplified fragment was restricted to a small region of 181 bp. In the present study, additional sequences flanking this segment were determined from a PCR product successfully amplified using a set of known degenerate primers, which covered a 692-bp region within the tortoise herpesviral DNA polymerase gene. Polymerase chain reaction primers for specific amplification of the tortoise herpesviral DNA were designed on the basis of these nucleotide sequences and successfully amplified tortoise herpesviral DNA from the tissues of tortoises that were well characterized histopathologically with herpesviral infection. The lower limit of detection was 1,000 herpesviral DNA equivalents in the presence of normal tortoise genomic DNA. Furthermore, a more sensitive and specific PCR technique for the identification of herpesviral infections in tortoises was developed employing a heminested form, which will enable the detection of latent infections or herpesvirus carriers in tortoises.