bluuebunny/crossref_metadata_2025 huggingface dataset:
Participation in school environment of children and youth with disabilities: A person‐oriented approach
Authors: ALMQVIST LENA , GRANLUND MATS
Published: April 2005

This study investigated patterns of interrelated positive subject and environmental factors related to participation in school activities of pupils with different kinds of disabilities. Questionnaires concerning participation were collected from 472 pupils with disabilities and their teachers, parents and special education consultants. A person‐oriented approach with the aim to identify patterns of variables related to a high degree of participation of pupils with disabilities was used. Cluster‐groups were formed based on scores for individual subjects on factors identified as important for participation. Groups with a high degree of participation were characterized by high scores in autonomy and perceived interaction with peers and teachers and an internal locus of control. Type and degree of disability did not predict cluster group membership. A conclusion is that the outcome participation is better predicted by patterns of interrelated positive subject and environmental factors than by type of disability or any other single factor.
Generalized Additive Models for Location, Scale and Shape
Authors: Rigby R. A. , Stasinopoulos D. M.
Published: April 2005

A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y, as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.
Modelling Association Between Two Irregularly Observed Spatiotemporal Processes by Using Maximum Covariance Analysis
Authors: Salim A. , Pawitan Y. , Bond K.
Published: April 2005

Climatic phenomena such as the El-Niño–southern oscillation and the north Atlantic oscillation are results of complex interactions between atmospheric and oceanic processes. Understanding the interactions has enabled scientists to give early warning of the forthcoming phenomena, thereby reducing damage caused by them. Statistical methods have played an important role in revealing effects of these phenomena on different regions of the world. One such method is maximum covariance analysis (MCA). Two apparent weaknesses are associated with MCA. Firstly, it tends to produce estimates with a low signal-to-noise ratio, especially when the sample size is small. Secondly, there has been no objective way of incorporating incomplete records, which are frequently encountered in climatology and oceanographic data-bases. We introduce an MCA which incorporates a smoothing procedure on the estimates. The introduction of the smoothing procedure is shown to improve the signal-to-noise ratio on the estimates. The estimation of smoothing parameters is carried out by using a penalized likelihood approach, which makes the inclusion of incomplete records quite straightforward. The methodology is applied to investigate the association between Irish winter precipitation and sea surface temperature anomalies around the world. The results show relationships between Irish precipitation anomalies and the El-Niño–southern oscillation and the north Atlantic oscillation phenomena.
Obtaining Cancer Risk Factor Prevalence Estimates in Small Areas: Combining Data from Two Surveys
Authors: Elliott Michael R. , Davis William W.
Published: April 2005

Cancer surveillance research requires accurate estimates of risk factors at the small area level. These risk factors are often obtained from surveys such as the National Health Interview Survey (NHIS) or the Behavioral Risk Factors Surveillance System (BRFSS). The NHIS is a nationally representative, face-to-face survey with a high response rate; however, it cannot produce state or substate estimates of risk factor prevalence because the sample sizes are too small and small area identifiers are unavailable to the public. The BRFSS is a state level telephone survey that excludes non-telephone households and has a lower response rate, but it does provide reasonable sample sizes in all states and many counties and has publicly available small area identifiers (counties). We propose a novel extension of dual-frame estimation using propensity scores that allows the complementary strengths of each survey to compensate for the weakness of the other. We apply this method to obtain 1999–2000 county level estimates of adult male smoking prevalence and mammogram usage rates among females who were 40 years old and older. We consider evidence that these NHIS-adjusted estimates reduce the effects of selection bias and non-telephone coverage in the BRFSS. Data from the Current Population Survey Tobacco Use Supplement are also used to evaluate the performance of this approach. A hybrid estimator that selects one of the two estimators on the basis of the mean-square error is also considered.
A Bayesian Mixture Model for Differential Gene Expression
Authors: Do Kim-Anh , Müller Peter , Tang Feng
Published: April 2005

We propose model-based inference for differential gene expression, using a nonparametric Bayesian probability model for the distribution of gene intensities under various conditions. The probability model is a mixture of normal distributions. The resulting inference is similar to a popular empirical Bayes approach that is used for the same inference problem. The use of fully model-based inference mitigates some of the necessary limitations of the empirical Bayes method. We argue that inference is no more difficult than posterior simulation in traditional nonparametric mixture-of-normal models. The approach proposed is motivated by a microarray experiment that was carried out to identify genes that are differentially expressed between normal tissue and colon cancer tissue samples. Additionally, we carried out a small simulation study to verify the methods proposed. In the motivating case-studies we show how the nonparametric Bayes approach facilitates the evaluation of posterior expected false discovery rates. We also show how inference can proceed even in the absence of a null sample of known non-differentially expressed scores. This highlights the difference from alternative empirical Bayes approaches that are based on plug-in estimates.
Are league tables controlling epidemic of caesarean sections in South Korea?
Authors: Kim Chang‐yup , Ko Su‐Kyoung , Kim Ki‐Young
Published: April 2005

Objective  To assess the impact of the publication of hospital caesarean section rates on the reduction of these rates in South Korea, and explore associated factors contributing to the decrease.

Design  Observational study.

Setting  South Korea.

Sample  Two hundred and sixty‐three hospitals in South Korea.

Methods  The caesarean section rates of 263 hospitals, before and after the release of caesarean section rates to the public, were obtained. The factors influencing the reduction in hospital caesarean section rates were also explored using multiple logistic regression.

Main outcome measure  Hospital caesarean section rates.

Results  After the release of information in 2000, the total (clinic and hospital) caesarean section rates in 2000 and 2001 decreased to 38.6% and 39.6%, respectively, from 43.0% in 1999. Caesarean section rates for hospitals were 45.9%, 42.7% and 44.6% in 1999, 2000 and 2001, respectively. Hospitals with the highest baseline caesarean section rates (OR 9.4, 95% CI 4.2–21.0) and highest number of deliveries (OR 8.1, 95% CI 2.1–31.1) were significant factors contributing independently to a decrease in caesarean section rates. Market share, competition, characteristics of revenue generation and ownership did not significantly influence the change of rates.

Conclusion  The public release of information on caesarean section rates in Korea has reversed the ever‐increasing trend in these rates. Hospitals with pre‐existing high caesarean section rates or a larger number of deliveries were influenced by the information release and could be the main targets for interventions to decrease these rates.
Obstetric outcome in women with subfertility
Authors: Thomson Fiona , Shanbhag Smrutha , Templeton Allan , Bhattacharya Siladitya
Published: April 2005

Background  It has been suggested that a history of subfertility is associated with increased obstetric and perinatal risks. It is unclear if the cause is inherent characteristics in the women or the fertility treatment.

Objectives  To compare the obstetric and perinatal risks of singleton pregnancies in women with a history of subfertility in comparison with the general population.

Design  Population cohort.

Setting  Aberdeen, Scotland.

Population  Cases were women attending the Fertility Clinic between 1989 and 1999 who subsequently went on to have singleton pregnancies. Controls included the general population of women who delivered singletons over the same period.

Methods  We performed a retrospective cohort study to investigate the obstetric outcome of singleton pregnancies in women with subfertility. The general population of women who delivered singletons over the same period served as controls.

Main outcome measures  Obstetric and perinatal complications in singleton pregnancies.

Results  Maternity records were available for a total of 1437 subfertile women and 21,688 controls. Subfertile women were older [mean (SD) age: 31 (4.7) years vs 27 (5.4) years, P < 0.01] and more likely to be primiparous (70%vs 65%, P < 0.001). After adjusting for age and parity, subfertile women were at increased risk of pre‐eclampsia (OR 1.9, 95% CI 1.5–2.5), placenta praevia (OR 3.9, 95% CI 2.2–7.0) and placental abruption (OR 1.8, 95% CI 1.1–3.0), and more likely to undergo induction of labour (OR 1.5, 95% CI 1.3–1.6), caesarean section (OR 2.1, 95% CI 1.8–2.4) and instrumental delivery (OR 2.2, 95% CI 1.8–2.6), and deliver low birthweight (OR 1.4, 95% CI 1.3–1.7) and preterm (OR 1.7, 95% CI 1.2–2.2) infants. There were no differences between treatment‐related and treatment‐independent pregnancies.

Conclusion  Subfertile women are at higher risk of obstetric complications, which persist after adjusting for age and parity.
The oral direct thrombin inhibitor, ximelagatran, an alternative for anticoagulant treatment during the puerperium and lactation
Authors: Hellgren M. , Johansson S. , Eriksson U.G. , Wåhlander K.
Published: April 2005

Objective To determine the excretion of the oral direct thrombin inhibitor (oral DTI), ximelagatran, and its active form, melagatran, in human milk, and to thus evaluate the potential exposure of breastfed infants to melagatran.

Design An open, single dose, single centre study.

Setting Department of Antenatal Care, Primary Health Care South Bohuslän and Institute for the Health of Woman and Children, Göteborg University, Sweden.

Sample Seven healthy Caucasian breastfeeding women who were at least two months postpartum were studied.

Methods The concentrations of ximelagatran, its two intermediates, and melagatran were determined using liquid chromatography–mass spectrometry, with the limit of quantification of 2 nmol L−1for human milk and 10 nmol L−1for plasma concentrations.

Main outcome measures Concentrations of ximelagatran, its intermediates and melagatran were measured in breast milk over 72 hours, and in plasma over 12 hours, after a single oral 36 mg dose of ximelagatran.

Results Neither ximelagatran nor its intermediates were detected in human breast milk. Only trace amounts of melagatran were detected. The mean cumulative amount of melagatran excreted into breast milk over the 72‐hour period after dosing with oral ximelagatran was 0.00091% of the administered dose of ximelagatran. Ximelagatran was well tolerated, with no clinically relevant changes in laboratory variables or vitals signs.

Conclusions Trace levels of melagatran are excreted in human breast milk following administration of the oral DTI ximelagatran. The exposure of breastfed infants to melagatran appears to be low and is therefore unlikely to be of clinical concern.
Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix
Authors: Flierman P.A. , Oberyé J.J.L. , van der Hulst V.P.M. , de Blok S.
Published: April 2005

Objective  To assess maximal volume reduction of leiomyomas and uterus and the duration of treatment required to reach these reductions with daily GnRH antagonist treatment.

Design  Prospective, open‐label study.

Setting  Large teaching hospital in The Netherlands.

Population  Premenopausal women with symptomatic fibroids, who were scheduled for surgery.

Methods  Twenty women were treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection and weekly during treatment, the volume of leiomyomas and the uterus were assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment and when maximal size reduction was observed by USS, the volume of the leiomyomas and the uterus were also assessed by magnetic resonance imaging (MRI).

Main outcome measures  Leiomyoma and uterine size reduction, time to maximal reduction.

Results  One woman was excluded from the study due to incorrect administration dose of ganirelix. Data on the remaining 19 women (average age 39 years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged from small (3–4 mL) to large (>1000 mL). The median duration of treatment up to maximal leiomyoma size reduction was 19 days (range 1–65 days). The maximal size reduction in leiomyomas measured by USS was −42.7% (−77.0% to 14.1%) and −29.2% (−62.2% to 35.6%) by MRI. Comparable uterine size reductions of −46.6% (−78.6% to −6.1%) and −25.2% (−63.6% to 28.9%) were observed by USS and MRI. During the first three weeks of treatment, 8 out of 19 women reported adverse events related to the induced hypoestrogenic state. Most of these events resolved within one week after treatment was discontinued.

Conclusion  Daily treatment with 2 mg of ganirelix results in rapid reduction of leiomyoma and uterine volume in premenopausal women with minor side effects. If longer‐acting GnRH antagonists become available, pretreatment with GnRH antagonist should be preferred over GnRH agonists prior to surgery.
Agreement studies in obstetrics and gynaecology: inappropriateness, controversies and consequences
Authors: Costa Santos Cristina , Costa Pereira Altamiro , Bernardes João
Published: April 2005

A literature review was performed to assess how agreement has been measured in obstetrics and gynaecology. Inappropriate or controversial measures were often used. The possible consequences of these inadequacies on validity studies and randomised controlled trials are shown in case examples. The association of two measures, proportions of agreement and kappa for categorical variables, and limits of agreement and intraclass correlation coefficient for continuous variables, is encouraged in agreement studies, until new and better ways of assessing agreement are found.
Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus
Authors: Dugas‐Breit Susanne , Schöpf Pia , Dugas Martin , Schiffl Helmut , Ruëff Franziska , Przybilla Bernhard
Published: April 2005

Background: The pathogenesis of pruritus in renal disease is not yet understood. Evidence suggests that mast cells play a role; for example, the number of dermal mast cells is increased in patients on hemodialysis.

Patients and methods: To investigate a possible role of mast cell tryptase in pruritus of patients undergoing chronic hemodialysis, serum mast cell tryptase concentrations were measured in blood samples taken from 93 such patients, 53 of whom also recorded the severity of their pruritus on a visual analogue scale.

Results: Serum mast cell tryptase levels were above 11.4 µg/l (95th percentile) in 84 of 93 hemodialysis patients (90.3 %). The intensity of pruritus correlated significantly (p = 0.014) with the tryptase levels, an associated not yet shown for other mast cell‐related parameters.

Conclusions: Mast cells or even tryptase itself may be involved in the pathogenesis of pruritus of hemodialysis patients.
A NEW TYPE OF RADIOGRAPHIC BONE REMODELING IN THE DISTAL RADIAL AND ULNAR METAPHYSIS IN 54 NEWFOUNDLAND DOGS
Authors: Trangerud Cathrine , Sande Ronald D. , Rorvik A. Magnus , Indrebo Astrid , Grondalen Jorunn
Published: April 2005

In this longitudinal observational study, 118 growing Newfoundland dogs were followed with sequential radiographic examination of the right front limb, which were scheduled at ages 3, 4, 6, 12, 18, and 24 months to record evidence of skeletal changes. All affected dogs had evidence of changes at 6 months and dogs included in this study had radiographic examination at 6 months and at least two other scheduled examinations that included either 4 or 12 months. The dogs were privately owned and had individualized nutrition and environment with no maintenance protocol required by the project leaders. Irregularities in bone remodeling in the distal radius and ulna were seen in radiographs of 54 of 118 (45.8%) dogs. These irregularities differ from changes previously described in the Newfoundland dog. The reported irregularities were seen as islands of reduced opacity outlined by thickened, radiopaque osseous trabeculae, which were aligned with the axis of stress. All the 54 dogs with irregularities during some phase of development consistently had changes at 6 months of age. Reorganization of the changes in the bone was slow, and residual changes were visible at 18–24 months of age in many cases. The significance of these findings may lie in their potential for misinterpretation if they had been discovered in the presence of clinical signs such as any lameness or growth arrest. Radiographic appearance indicates disturbances in the bone maturation. The etiopathogenesis is unclear. Nutritional, environmental and genetic factors have to be studied.
INTEROBSERVER VARIABILITY OF VERTEBRAL HEART SIZE MEASUREMENTS IN DOGS WITH NORMAL AND ENLARGED HEARTS
Authors: Hansson Kerstin , Häggström Jens , Kvart Clarence , Lord Peter
Published: April 2005

The vertebral heart size (VHS) method by Buchanan is based on anatomic landmarks. A potential source of variation among observers is differences in the selection of measurement points. The objective was to test variability between observers with different levels of training in thoracic radiology and small animal clinical practice.

Fifty sets of thoracic radiographs of cavalier King Charles spaniels, were divided into five groups; (Normal) normal cardiopulmonary structures, (I) slight cardiomegaly, (II) moderate cardiomegaly, (II+) moderate cardiomegaly with congestive heart failure, and (III+) severe cardiomegaly with congestive heart failure. Cardiomegaly was confirmed by echocardiography to be caused by mitral regurgitation because of myxomatous mitral valve disease. Sixteen observers representing four levels of experience (four observers/level) evaluated the radiographs; (1) European Diplomates in Veterinary Diagnostic Imaging, (2) Experienced small animal clinicians, (3) Trainees in small animal clinical practice (4) Veterinary students.

Almost identical mean VHS values were found among the four experience levels for each of the five groups of radiographs with a low coefficient of variation, range 1.5–3.2%. Mean difference among the 16 observers was 1.05±0.32 vertebrae (v). Mean difference among individuals in each observer group was approximately 0.5 v for all but the groups of trainees were the difference was 0.6–0.9 v.

The conclusion is that VHS method for heart size is independent of observer experience but dependent of individual observers selection of reference points and transformation of long and short axis dimensions into VHS units.
INTRA‐ AND INTEROBSERVER VARIABILITY OF ULTRASONOGRAPHIC MEASUREMENTS OF THE THYROID GLAND IN HEALTHY BEAGLES
Authors: Taeymans Olivier , Duchateau Luc , Schreurs Elke , Kramer Martin , Daminet Sylvie , Saunders Jimmy H.
Published: April 2005

The repeatability of ultrasonographic measurements of the canine thyroid gland was evaluated. The variability of three different parameters (the maximal length, width, and height) within observer, between observer and between dogs was assessed based on three different measurements made by each of three observers in five healthy beagle dogs. From the three parameters, the volume of the gland was estimated using a formula of a rotation ellipse. The height and the volume had the lowest intra‐ and interobserver variability, while measurements of the length had the biggest intra‐ and interobserver variability. The mean values, with their 90% confidence interval were: height=0.53 cm [0.33–0.73], length=2.45 cm [2.04–2.85], width=0.62 cm [0.46–0.78], volume=0.38 cm3[0.20–0.55].
COMPARISON OF CLINICAL, ULTRASONOGRAPHIC, AND POSTOPERATIVE MACROSCOPIC FINDINGS IN COWS WITH BURSITIS
Authors: Seyrek‐Intas Deniz , Celimli Nureddin , Gorgul O. Sacit , Cecen Goksen
Published: April 2005

Clinical, ultrasonographic, and macroscopic findings of bursitis in cows were compared to assess the contribution of diagnosis and therapy planning. Sixteen dairy cows with swelling at the carpal (n=12) or tarsal (n=4) region were examined clinically and ultrasonographically and the findings were compared. In 10 patients the bursae were removed in toto. According to the duration of the disease (history) and clinical findings nine and seven patients had acute and chronic bursitis, respectively. Six had fluctuation and in 10 the bursa was firm. Contents were serous (n=3), serofibrinous (n=4), serohemorrhagic (n=2), or purulent (n=1). Sonographically there was fluid in all bursa except one. Capsule echogenicity varied between hypoechoic and hyperechoic and mean capsule thickness was 9.2±4.1 mm. Fourteen of the bursae contained free‐floating particles. The hyperechoic capsules represented fibrous tissue, and the echogenic/hyperechoic free‐floating particles were erythrocytes, purulent exudate, or fibrin masses. Capsule thickness and large free‐floating particles could not be detected by clinical examination/centesis alone. However, capsule thickness, bursa contents, and the extent of inflammation could be determined ultrasonographically and this made the decision for different invasive/operative procedures easier.
Unveiling the Mechanisms of Cell-Cell Fusion
Authors: Chen Elizabeth H. , Olson Eric N.
Published: April 2005

Cell-cell fusion is fundamental to the development and physiology of multicellular organisms, but little is known of its mechanistic underpinnings. Recent studies have revealed that many proteins involved in cell-cell fusion are also required for seemingly unrelated cellular processes such as phagocytosis, cell migration, axon growth, and synaptogenesis. We review advances in understanding cell-cell fusion by contrasting it with virus-cell and intracellular vesicle fusion. We also consider how proteins involved in general aspects of membrane dynamics have been co-opted to control fusion of diverse cell types by coupling with specialized proteins involved in cell-cell recognition, adhesion, and signaling.
Quantum Phase Transition of a Magnet in a Spin Bath
Authors: Rønnow H. M. , Parthasarathy R. , Jensen J. , Aeppli G. , Rosenbaum T. F. , McMorrow D. F.
Published: April 2005

The excitation spectrum of a model magnetic system, LiHoF
4
, was studied with the use of neutron spectroscopy as the system was tuned to its quantum critical point by an applied magnetic field. The electronic mode softening expected for a quantum phase transition was forestalled by hyperfine coupling to the nuclear spins. We found that interactions with the nuclear spin bath controlled the length scale over which the excitations could be entangled. This generic result places a limit on our ability to observe intrinsic electronic quantum criticality.
Impact of Humans on the Flux of Terrestrial Sediment to the Global Coastal Ocean
Authors: Syvitski James P. M. , Vörösmarty Charles J. , Kettner Albert J. , Green Pamela
Published: April 2005

Here we provide global estimates of the seasonal flux of sediment, on a river-by-river basis, under modern and prehuman conditions. Humans have simultaneously increased the sediment transport by global rivers through soil erosion (by 2.3 ± 0.6 billion metric tons per year), yet reduced the flux of sediment reaching the world's coasts (by 1.4 ± 0.3 billion metric tons per year) because of retention within reservoirs. Over 100 billion metric tons of sediment and 1 to 3 billion metric tons of carbon are now sequestered in reservoirs constructed largely within the past 50 years. African and Asian rivers carry a greatly reduced sediment load; Indonesian rivers deliver much more sediment to coastal areas.
A Pair of Shelled Eggs Inside A Female Dinosaur
Authors: Sato Tamaki , Cheng Yen-nien , Wu Xiao-chun , Zelenitsky Darla K. , Hsiao Yu-fu
Published: April 2005

An oviraptosaurian specimen (Dinosauria, Theropoda) from an Upper Cretaceous formation in China retains a pair of shelled eggs in the pelvis, providing direct evidence that oviraptorosaurian dinosaurs laid paired elongatoolithid eggs. The presence of the paired eggs suggests that theropod dinosaurs had two functional oviducts (like crocodiles) but that each oviduct produced only one egg at a time and that an entire egg clutch was laid through multiple ovipositions (like birds). The orientations of the eggs inside the skeleton and in clutches indicate that the mother came to the center of the nest to lay eggs.
Pathogenesis of Afa/Dr Diffusely AdheringEscherichia coli
Authors: Servin Alain L.
Published: April 2005

Over the last few years, dramatic increases in our knowledge about diffusely adheringEscherichia coli(DAEC) pathogenesis have taken place. The typical class of DAEC includesE. colistrains harboring AfaE-I, AfaE-II, AfaE-III, AfaE-V, Dr, Dr-II, F1845, and NFA-I adhesins (Afa/Dr DAEC); these strains (i) have an identical genetic organization and (ii) allow binding to human decay-accelerating factor (DAF) (Afa/DrDAFsubclass) or carcinoembryonic antigen (CEA) (Afa/DrCEAsubclass). The atypical class of DAEC includes two subclasses of strains; the atypical subclass 1 includesE. colistrains that express AfaE-VII, AfaE-VIII, AAF-I, AAF-II, and AAF-III adhesins, which (i) have an identical genetic organization and (ii) do not bind to human DAF, and the atypical subclass 2 includesE. colistrains that harbor Afa/Dr adhesins or others adhesins promoting diffuse adhesion, together with pathogenicity islands such as the LEE pathogenicity island (DA-EPEC). In this review, the focus is on Afa/Dr DAEC strains that have been found to be associated with urinary tract infections and with enteric infection. The review aims to provide a broad overview and update of the virulence aspects of these intriguing pathogens. Epidemiological studies, diagnostic techniques, characteristic molecular features of Afa/Dr operons, and the respective role of Afa/Dr adhesins and invasins in pathogenesis are described. Following the recognition of membrane-bound receptors, including type IV collagen, DAF, CEACAM1, CEA, and CEACAM6, by Afa/Dr adhesins, activation of signal transduction pathways leads to structural and functional injuries at brush border and junctional domains and to proinflammatory responses in polarized intestinal cells. In addition, uropathogenic Afa/Dr DAEC strains, following recognition of β1integrin as a receptor, enter epithelial cells by a zipper-like, raft- and microtubule-dependent mechanism. Finally, the presence of other, unknown virulence factors and the way that an Afa/Dr DAEC strain emerges from the human intestinal microbiota as a “silent pathogen” are discussed.
Metallo-β-Lactamases: the Quiet before the Storm?
Authors: Walsh Timothy R. , Toleman Mark A. , Poirel Laurent , Nordmann Patrice
Published: April 2005

The ascendancy of metallo-β-lactamases within the clinical sector, while not ubiquitous, has nonetheless been dramatic; some reports indicate that nearly 30% of imipenem-resistantPseudomonas aeruginosastrains possess a metallo-β-lactamase. Acquisition of a metallo-β-lactamase gene will invariably mediate broad-spectrum β-lactam resistance inP. aeruginosa, but the level of in vitro resistance inAcinetobacterspp. and Enterobacteriaceae is less dependable. Their clinical significance is further embellished by their ability to hydrolyze all β-lactams and by the fact that there is currently no clinical inhibitor, nor is there likely to be for the foreseeable future. The genes encoding metallo-β-lactamases are often procured by class 1 (sometimes class 3) integrons, which, in turn, are embedded in transposons, resulting in a highly transmissible genetic apparatus. Moreover, other gene cassettes within the integrons often confer resistance to aminoglycosides, precluding their use as an alternative treatment. Thus far, the metallo-β-lactamases encoded on transferable genes include IMP, VIM, SPM, and GIM and have been reported from 28 countries. Their rapid dissemination is worrisome and necessitates the implementation of not just surveillance studies but also metallo-β-lactamase inhibitor studies securing the longevity of important anti-infectives.
Quantitative health impact assessment: current practice and future directions
Authors: Veerman J L , Barendregt J J , Mackenbach J P
Published: April 2005

Study objective:To assess what methods are used in quantitative health impact assessment (HIA), and to identify areas for future research and development.

Design:HIA reports were assessed for (1) methods used to quantify effects of policy on determinants of health (exposure impact assessment) and (2) methods used to quantify health outcomes resulting from changes in exposure to determinants (outcome assessment).

Main results:Of 98 prospective HIA studies, 17 reported quantitative estimates of change in exposure to determinants, and 16 gave quantified health outcomes. Eleven (categories of) determinants were quantified up to the level of health outcomes. Methods for exposure impact assessment were: estimation on the basis of routine data and measurements, and various kinds of modelling of traffic related and environmental factors, supplemented with experts’ estimates and author’s assumptions. Some studies used estimates from other documents pertaining to the policy. For the calculation of health outcomes, variants of epidemiological and toxicological risk assessment were used, in some cases in mathematical models.

Conclusions:Quantification is comparatively rare in HIA. Methods are available in the areas of environmental health and, to a lesser extent, traffic accidents, infectious diseases, and behavioural factors. The methods are diverse and their reliability and validity are uncertain. Research and development in the following areas could benefit quantitative HIA: methods to quantify the effect of socioeconomic and behavioural determinants; user friendly simulation models; the use of summary measures of public health, expert opinion and scenario building; and empirical research into validity and reliability.
Bidirectional regulation of monocyte chemoattractant protein-1 gene at distinct sites of its promoter by nitric oxide in vascular smooth muscle cells
Authors: Kodama Ken-ichi , Nishio Yoshihiko , Sekine Osamu , Sato Yoshinori , Egawa Katsuya , Maegawa Hiroshi , Kashiwagi Atsunori
Published: April 2005

We have previously reported that chronic activation of phosphatidylinositol 3-kinase (PI3-kinase) by the overexpression of membrane-targeted p110CAAX induced proinflammatory gene expression in rat vascular smooth muscle cells (VSMCs) through the induction of CCAAT/enhancer binding protein-β (C/EBP-β) and C/EBP-δ. To examine the anti-inflammatory effect of nitric oxide (NO) on proinflammatory gene expression, we have investigated the effects of sodium nitroprusside (SNP) on the monocyte chemoattractant protein-1 (MCP-1) gene expression in VSMCs under chronic activation of PI3-kinase. At low concentrations (0.05 mM) of SNP, but not at high concentrations (0.5–1.0 mM), MCP-1 mRNA and protein expression as well as its transcriptional activity were significantly reduced. We found that SNP induced C/EBP homologous protein (CHOP) expression, which inhibited C/EBP binding activity and reduced the C/EBP activity induced by chronic activation of PI3-kinase in a dose-dependent manner up to 1.0 mM. Consistently, the increase in CHOP expression significantly reduced the MCP-1 promoter activity induced by PI3-kinase. However, the overexpression of CHOP alone upregulated MCP-1 promoter activity in a dose-dependent manner up to high concentrations. Deletion analysis of MCP-1 promoter and electrophoretic mobility shift assay identified the CHOP-response element (CHOP-RE) at the region between −190 and −179 bp of MCP-1 promoter. By using CHOP-RE as a decoy, we significantly suppressed the increase in promoter activity of MCP-1 induced by either CHOP or SNP. Thus CHOP induced by an NO donor has bidirectional effects on MCP-1 gene expression: it decreases gene expression by inhibition of C/EBPs, and it increases the gene expression through CHOP-RE.
Gastrointestinal tract innervation of the mouse: afferent regeneration and meal patterning after vagotomy
Authors: Powley Terry L. , Chi Michael M. , Baronowsky Elizabeth A. , Phillips Robert J.
Published: April 2005

Mice, with the variety of genotypes they provide, should be particularly useful for studies of growth factors and gene products in regeneration of autonomic pathways such as the vagus nerve. To provide a foundation for examinations of mouse vagal reorganization, two experiments assessed the rate, extent, and accuracy of afferent reinnervation of the stomach after vagotomy and related these patterns to feeding behavior. In experiment 1, the pattern of afferent regrowth into the gut after unilateral truncal vagotomy was characterized by labeling of these afferents with wheat germ agglutinin-horseradish peroxidase and Micro-Ruby. Regenerating neurites had reached and, in some cases, already reinnervated the stomach by 4 wk after axotomy. By 8 wk, regrowth was more extensive, and many fibers had redifferentiated terminals in the smooth muscle. By 16 wk, vagal projections had reached or exceeded normal density in the corpus, density in the forestomach was still reduced, and regrowth in the antrum was minimal. At all time points, not only appropriate terminals, but also growth cones and aberrant endings, were observed. In experiment 2, meal patterns of vagotomized mice were evaluated using a solid diet over the period of regeneration; cholecystokinin suppression of a liquid meal after unilateral and bilateral truncal vagotomies was also evaluated. Unilaterally, as well as bilaterally, vagotomized animals ate smaller and more frequent meals. These disturbed patterns became more pronounced in the first 8 wk after vagotomy, during regeneration. Cholecystokinin inhibition of intake was attenuated by bilateral, but not unilateral, vagotomy. Overall, the spatial and temporal patterns of structural and functional changes observed during regeneration verify that the mouse provides a useful preparation for examining the control of vagal plasticity.
Metabolic equivalent: one size does not fit all
Authors: Byrne Nuala M. , Hills Andrew P. , Hunter Gary R. , Weinsier Roland L. , Schutz Yves
Published: April 2005

The metabolic equivalent (MET) is a widely used physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RMR). The value equating 1 MET (3.5 ml O2·kg−1·min−1 or 1 kcal·kg−1·h−1) was first derived from the resting O2 consumption (V̇o2) of one person, a 70-kg, 40-yr-old man. Given the extensive use of MET levels to quantify physical activity level or work output, we investigated the adequacy of this scientific convention. Subjects consisted of 642 women and 127 men, 18–74 yr of age, 35–186 kg in weight, who were weight stable and healthy, albeit obese in some cases. RMR was measured by indirect calorimetry using a ventilated hood system, and the energy cost of walking on a treadmill at 5.6 km/h was measured in a subsample of 49 men and 49 women (26–45 kg/m2; 29–47 yr). Average V̇o2 and energy cost corresponding with rest (2.6 ± 0.4 ml O2·kg−1·min−1 and 0.84 ± 0.16 kcal·kg−1·h−1, respectively) were significantly lower than the commonly accepted 1-MET values of 3.5 ml O2·kg−1·min−1 and 1 kcal·kg−1·h−1, respectively. Body composition (fat mass and fat-free mass) accounted for 62% of the variance in resting V̇o2 compared with age, which accounted for only 14%. For a large heterogeneous sample, the 1-MET value of 3.5 ml O2·kg−1·min−1 overestimates the actual resting V̇o2 value on average by 35%, and the 1-MET of 1 kcal/h overestimates resting energy expenditure by 20%. Using measured or predicted RMR (ml O2·kg−1·min−1 or kcal·kg−1·h−1) as a correction factor can appropriately adjust for individual differences when estimating the energy cost of moderate intensity walking (5.6 km/h).
GABAergic Modulation of the Activity of Globus Pallidus Neurons in Primates: In Vivo Analysis of the Functions of GABA Receptors and GABA Transporters
Authors: Galvan Adriana , Villalba Rosa M. , West Sara M. , Maidment Nigel T. , Ackerson Larry C. , Smith Yoland , Wichmann Thomas
Published: April 2005

Neurons in the external and internal segment of the globus pallidus (GPe and GPi, respectively) receive substantial GABAergic inputs from the striatum and through axon collaterals of neighboring pallidal neurons. The effects of GABA on pallidal activity depend on the synaptic localization of GABA receptors and the distribution and activity of GABA transporters (GATs). To explore the contribution of GABA receptors and transporters to pallidal function, we recorded the activity of single neurons in GPe or GPi before, during, and after local microinjections of GABAergic compounds in awake rhesus monkeys. Activation of GABAA or GABAB receptors with muscimol or baclofen, respectively, inhibited pallidal activity. These effects were reversed by concomitant infusion of the respective GABA receptor antagonists, gabazine and CGP-55845. Given alone, the antagonists were without consistent effect. Application of the selective GAT-1 inhibitor, SKF-89976A, and the semiselective GAT-3 blocker, SNAP-5114, decreased pallidal activity. Both GAT inhibitors increased GABA levels in the pallidum, as measured by microdialysis. Electron microscopic observations revealed that these transporters are located on glial processes and unmyelinated axonal segments, but rarely on terminals. Our results indicate that activation of GABAA and GABAB receptors inhibits neuronal activity in both segments of the pallidum. GAT-1 and GAT-3 are involved in the modulation of endogenous GABA levels and may be important in regulating the extrasynaptic levels of GABA. Together with previous evidence that a considerable proportion of pallidal GABA receptors are located outside the synaptic cleft, our experiments strongly support the importance of extrasynaptic GABAergic transmission in the primate pallidum.
Regulation of Vascular Calcification
Authors: Giachelli Cecilia M. , Speer Mei Y. , Li Xianwu , Rajachar Rupak M. , Yang Hsueh
Published: April 2005

Vascular calcification is prevalent in aging as well as a number of pathological conditions, and it is now recognized as a strong predictor of cardiovascular events in the general population as well as diabetic and end-stage renal disease patients. Vascular calcification is a highly regulated process involving inductive and inhibitory mechanisms. This article focuses on two molecules, phosphate and osteopontin, that have been implicated in the induction or inhibition of vascular calcification, respectively. Elevated phosphate is of interest because hyperphosphatemia is recognized as a major nonconventional risk factor for cardiovascular disease mortality in end-stage renal disease patients. Studies to date suggest that elevated phosphate stimulates smooth muscle cell phenotypic transition and mineralization via the activity of a sodium-dependent phosphate cotransporter. Osteopontin, however, appears to block vascular calcification most likely by preventing calcium phosphate crystal growth and inducing cellular mineral resorption.
Negley K. Teeters (1896-1971): Pioneeer in Penology
Authors: Geis Gilbert
Published: April 2005

Negley K. Teeters (1896-1971) was a leading academic figure in the crusade for prison reform. This article reviews Teeters’s career and summarizes his publications on the social history of early prisons, his writings on international penology, and his review of the work of the Pennsylvania Prison Society. The relevance of Teeters’s work to contemporary scholarship and policy is noted. In addition, this article offers observations by Teeters on prisons, crime, and the academic life in his correspondence with the author.
Kinetics and Dynamics of Intravenous Adinazolam, N‐Desmethyl Adinazolam, and Alprazolam in Healthy Volunteers
Authors: Venkatakrishnan Karthik , Culm Kerry E. , Ehrenberg Bruce L. , Harmatz Jerold S. , Corbett Kathleen E. , Fleishaker Joseph C. , Greenblatt David J.
Published: April 2005

The pharmacokinetics and pharmacodynamics of adinazolam mesylate (10 mg), N‐desmethyl adinazolam mesylate (NDMAD, 10 mg), and alprazolam (1 mg) were investigated in 9 healthy male subjects in a randomized, blinded, single‐dose, 4‐way crossover study. All drugs were intravenously infused over 30 minutes. Plasma adinazolam, NDMAD, and alprazolam concentrations, electroencephalographic (EEG) activity in the β (12–30 Hz) range, performance on the Digit Symbol Substitution Test (DSST), and subjective measures of mood and sedation were monitored for 12 to 24 hours. Mean pharmacokinetic parameters for adinazolam, NDMAD, and alprazolam, respectively, were as follows: volume of distribution (L), 106, 100, and 77; elimination half‐life (hours), 2.9, 2.8, and 14.6; and clearance (mL/min), 444, 321, and 84. More than 80% of the total infused adinazolam dose was converted to systemically appearing NDMAD. All 3 benzodiazepine agonists significantly increased β EEG activity, with alprazolam showing the strongest agonist activity and adinazolam showing the weakest activity. Alprazolam and NDMAD significantly decreased DSST performance, whereas adinazolam had no effect relative to placebo. Adinazolam, NDMAD, and alprazolam all produced significant observer‐rated sedation. Plots of EEG effect versus plasma alprazolam concentration demonstrated counterclockwise hysteresis, consistent with an effect site delay. This was incorporated into a kinetic‐dynamic model in which hypothetical effect site concentration was related to pharmacodynamic EEG effect via the sigmoid Emax model, yielding an effect site equilibration half‐life of 4.8 minutes. The exponential effect model described NDMAD pharmacokinetics and EEG pharmacodynamics. The relation of both alprazolam and NDMAD plasma concentrations to DSST performance could be described by a modified exponential model. Pharmacokinetic‐dynamic modeling was not possible for adinazolam, as the data did not conform to any known concentration‐effect model. Collectively, these results indicate that the benzodiazepine‐like effects occurring after adinazolam administration are mediated by mainly NDMAD.
Individual and Combined Effects of Peroxisome Proliferator‐Activated Receptor α and γ Agonists, Fenofibrate and Rosiglitazone, on Biomarkers of Lipid and Glucose Metabolism in Healthy Nondiabetic Volunteers
Authors: Wagner J. A. , Larson P. J. , Weiss S. , Miller J. L. , Doebber T. W. , Wu M. S. , Moller D. E. , Gottesdiener K. M.
Published: April 2005

This open‐label, randomized, placebo‐controlled, incomplete‐block, 3‐period crossover pilot study investigated the effects of peroxisome proliferator‐activated receptor α‐ and γ‐agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14‐day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P <.074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C‐III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C‐III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglyoerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature.
Tolerability, Gut Effects, and Pharmacokinetics of Methylnaltrexone Following Repeated Intravenous Administration in Humans
Authors: Yuan Chun‐Su , Doshan Harold , Charney Martha R. , O'Connor Michael , Karrison Theodore , Maleckar S. A. , Israel Robert J. , Moss Jonathan
Published: April 2005

Previous studies have shown that a single dose of methylnaltrexone, a unique peripheral opioid antagonist, reverses opioid‐induced gut hypomotility in humans. Because repeated drug doses are likely to be needed to treat patients with opioid‐induced or postsurgical bowel dysfunction, the authors have now examined the safety, pharmacological activity, and pharmacokinetics of a multiple‐dose regimen of methylnaltrexone, administered as 12 consecutive intravenous doses (0.3 mg/kg every 6 hours) in 12 healthy subjects. Steady state was achieved rapidly, and after repeated dosing for 3 days, methylnaltrexone decreased oral‐cecal transit time from a pretreatment baseline value of 101.3 ± 29.4 min (mean ± SD) to 82.5 ± 20.7 min. Maximum observed plasma concentrations, measured 5 minutes postdose, were 538 ± 237 and 675 ± 180 ng/mL after doses 1 and 2, respectively. Based on 6‐hour sampling periods, the plasma half‐life, 2.5 ± 0.5 and 2.9 ± 0.9 hours following the 1st and 12th doses, respectively, was unchanged at steady state. There was essentially no accumulation of methylnaltrexone, based on the ratio of AUC values after doses 12 and 1. This study showed that repeated administration of intravenous methylnaltrexone is well tolerated in humans, with no significant adverse events or changes in opioid subjective ratings and no clinically noteworthy alterations in pharmacokinetics. The observation of a significant reduction in the gut transit time after repeated administration of methylnaltrexone to these opioid‐naive volunteers suggests that endogenous opioids modulate human gut motility.