bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and pharmacodynamics of cefovecin in dogs
Authors: STEGEMANN M. R. , SHERINGTON J. , BLANCHFLOWER S.
Published: November 2006

A series ofin vivo,ex vivoandin vitrostudies were conducted to determine the pharmacokinetic and pharmacodynamic properties of cefovecin, a new injectable cephalosporin, in dogs. Absolute bioavailability was determined in a two‐phase cross‐over study in dogs receiving 8 mg/kg bodyweight (b.w.) of cefovecin by either subcutaneous (s.c.) or intravenous (i.v.) route. After s.c. administration, cefovecin was fully bioavailable (100%), the mean maximum plasma concentration (Cmax) was 121 μg/mL and the mean apparent elimination half‐life (t1/2) was 133 h. Clearance was measured to be 0.76 mL/h/kg after i.v. dosing. The concentration of cefovecin in urine measured 14 days after s.c. administration was 2.9 μg/mL. Plasma protein binding was determined by equilibrium dialysis; over concentrations ranging from 10 to 100 μg/mL (i.e. up to the approximateCmaxfollowing an 8 mg/kg dose), protein binding of 98.7% to 96.0% was observed, however, binding was lower at higher concentrations. Total and free concentrations of cefovecin were determined in plasma, transudate and exudate collected from dogs previously implanted subcutaneously with tissue cages. Mean peak concentrations of free cefovecin were almost three times higher in transudate than in plasma and remained above 0.25 μg/mL for 19 days. Theex vivoantibacterial killing activity (vs.Staphylococcus intermedius,MIC0.25 μg/mL) was measured in serum, transudate and exudate collected from dogs which had received 8 mg/kg b.w. of cefovecin subcutaneously. Transudate exhibited higher antimicrobial killing activity than serum. Activity in serum and exudate exhibited a mean reduction in bacterial counts ofS. intermediusof at least three log units up to 72 h postadministration. Bactericidal activity (>3 log10reduction of bacterial counts) was observed in transudate up to 12 days postadministration. The slow elimination and long lastingex vivoantibacterial killing activity following administration of cefovecin are desirable pharmacokinetic and pharmacodynamic attributes for an antimicrobial drug with 14‐day dosing intervals.
The role of salicylic acid in the glutathione‐mediated protection against photooxidative stress in rice
Authors: Kusumi Kensuke , Yaeno Takashi , Kojo Kaori , Hirayama Mayuko , Hirokawa Daishirou , Yara Asanori , Iba Koh
Published: November 2006

Salicylic acid (SA) is known to be an essential component responsible for disease resistance in dicotyledonous plants. In rice, however, tissue contains extremely high endogenous levels of SA that do not increase after pathogen infection, suggesting that the SA has other major functions in healthy leaves. Although involvement of SA in oxidative‐stress response is known in some dicotyledonous plants, antioxidative role of SA in rice is obscure. In this study, we examined the involvement of SA in the protection against oxidative stress in rice, using transgenic plants expressing the bacterial nahG gene that encodes salicylate hydroxylase, an SA‐degrading enzyme. In SA‐deficient NahG rice, the glutathione pool size was constitutively diminished as compared with control plants. NahG seedlings showed a delayed development phenotype, an increased susceptibility to oxidative stress and they developed light‐induced lesions in their leaves without pathogen infection. Conversely, treatment with an activator of the SA‐mediated defense‐signaling pathway, probenazole, increased the glutathione pool size and suppressed lesion formation. These results suggest that in rice, SA has an important role in the response to high‐light‐induced oxidative stress, through its regulatory effects on glutathione homeostasis.
Acclimation of Arabidopsis thaliana to long‐term CO2 enrichment and nitrogen supply is basically a matter of growth rate adjustment
Authors: Tocquin Pierre , Ormenese Sandra , Pieltain Alexandra , Detry Nathalie , Bernier Georges , Périlleux Claire
Published: November 2006

The long‐term response of Arabidopsis thaliana to increasing CO2 was evaluated in plants grown in 800 μl l−1 CO2 from sowing and maintained, in hydroponics, on three nitrogen supplies: “low,”“medium” and “high.” The global response to high CO2 and N‐supply was evaluated by measuring growth parameters in parallel with photosynthetic activity, leaf carbohydrates, ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco) messenger RNA and protein, stomatal conductance (gs) and density. CO2 enrichment was found to stimulate biomass production, whatever the N‐supply. This stimulation was transient on low N‐supply and persisted throughout the whole vegetative growth only in high N‐supply. Acclimation on low N–high CO2 was not associated with carbohydrate accumulation or with a strong reduction in Rubisco amount or activity. At high N‐supply, growth stimulation by high CO2 was mainly because of the acceleration of leaf production and expansion while other parameters such as specific leaf area, root/shoot ratio and gs appeared to be correlated with total leaf area. Our results thus suggest that, in strictly controlled and stable growing conditions, acclimation of A. thaliana to long‐term CO2 enrichment is mostly controlled by growth rate adjustment.
Osmotic stress at seedling stage impairs reproductive development in buckwheat (Fagopyrum esculentum)
Authors: Cawoy Valérie , Lutts Stanley , Kinet Jean‐Marie
Published: November 2006

Common buckwheat (Fagopyrum esculentum Moench) is highly sensitive to drought. Many studies have investigated the impact of water stresses, applied late during plant development, on seed production by this non‐Poaceae cereal but information concerning the effects of stresses occurring early during plant’s life is essentially lacking. The aim of the present work was to define which yield‐related parameters are more affected by a 4‐day water constraint, applied at three different developmental stages, by transferring buckwheat plants of the cultivar ‘La Harpe’ grown in a hydroponic system to a medium supplemented with polyethylene glycol. Stresses during the vegetative phase, when the shoot apical meristem (SAM) was still initiating leaves, or later, when its activity was stopped after production of approximately 10 inflorescences, were less detrimental than an osmotic constraint applied to plants recently engaged in the reproductive phase, with SAM having initiated six to seven inflorescences. The number of cymes and flowers per inflorescence and the number of pollen grains per anther were decreased. The production of seeds in the first inflorescence was also reduced but this reduction paralleled the decrease in cyme number, suggesting that seed set, per se, was not affected. Pollen viability, female fertility and weight of seeds reaching maturity were not altered by the water deficit. The present work clearly identified two processes that, in buckwheat, are particularly sensitive to an osmotic stress: (1) the activity of reproductive meristems involved in the production of cymes and flowers and (2) male sporogenesis.
Factor structure of the Maslach Burnout Inventory among Finnish nursing staff
Authors: Kanste Outi , Miettunen Jouko , Kyngäs Helvi
Published: November 2006

Abstract The purpose of the study was to investigate the factor structure of the Maslach Burnout Inventory – Human Services Survey (MBI‐HSS) among Finnish nursing staff. Although the factorial validity of the MBI‐HSS has been studied across different countries, the factor structure has never been investigated among Finnish nursing staff. The data were gathered by postal questionnaires from nursing staff working in health‐care organizations around Finland. The sample consisted of 627 nurses and nurse managers. The factor structure was studied by using exploratory and confirmatory factor analysis. The fit of the hypothesized three‐factor model to the data was superior to the alternative one‐factor and two‐factor models. The three‐factor structure (emotional exhaustion, depersonalization, reduced personal accomplishment) showed the best fit, while the internal consistencies of the subscales were satisfactory. The MBI‐HSS is a highly suitable instrument for measuring burnout among nursing staff and it is very applicable to Finnish health‐care research.
Study on the relationship between backpack use and back and neck pain among adolescents
Authors: Navuluri Neelima , Navuluri Ramesh B.
Published: November 2006

Abstract A descriptive correlation study was conducted in Hobbs, New Mexico, USA, to find the relationship between backpack use and back and neck pain among adolescent boys and girls. A higher percentage of girls than boys rated their pain as being moderate to extremely strong. The correlation between pain and backpack weight per body mass index among girls was positive and significant, but negative and non‐significant among boys. The correlation between pain and backpack weight was positive and non‐significant among both boys and girls. The correlation between pain and each of the variables of backpack weight per body weight, backpack weight per height, and backpack weight per body surface area was negative and non‐significant among boys, but positive and non‐significant among girls. Gender‐based research studies with additional variables and safe backpack use education in schools are recommended.
Sensitivity of the population growth rate to demographic variability within and between phases of the disturbance cycle
Authors: Morris W. F. , Tuljapurkar S. , Haridas C. V. , Menges E. S. , Horvitz C. C. , Pfister C. A.
Published: November 2006

For species in disturbance‐prone ecosystems, vital rates (survival, growth and reproduction) often vary both between and within phases of the cycle of disturbance and recovery; some of this variation is imposed by the environment, but some may represent adaptation of the life history to disturbance. Anthropogenic changes may amplify or impede these patterns of variation, and may have positive or negative effects on population growth. Using stochastic population projection matrix models, we develop stochastic elasticities (proportional derivatives of the long‐run population growth rate) to gauge the population effects of three types of change in demographic variability (changes in within‐ and between‐disturbance‐phase variability and phase‐specific changes). Computing these elasticities for five species of disturbance‐influenced perennial plants, we pinpoint demographic rates that may reveal adaptation to disturbance, and we demonstrate that species may differ in their responses to different types of changes in demographic variability driven by climate change.
Impact of carbon metabolism on 13C signatures of cyanobacteria and green non‐sulfur‐like bacteria inhabiting a microbial mat from an alkaline siliceous hot spring in Yellowstone National Park (USA)
Authors: Van Der Meer Marcel T. J. , Schouten Stefan , Damsté Jaap S. Sinninghe , Ward David M.
Published: November 2006

Alkaline siliceous hot spring microbial mats in Yellowstone National Park are composed of two dominant phototropic groups, cyanobacteria and green non‐sulfur‐like bacteria (GNSLB). While cyanobacteria are thought to cross‐feed low‐molecular‐weight organic compounds to support photoheterotrophic metabolism in GNSLB, it is unclear how this could lead to the heavier stable carbon isotopic signatures in GNSLB lipids compared with cyanobacterial lipids found in previous studies. The two groups of phototrophs were separated using percoll density gradient centrifugation and subsequent lipid and stable carbon isotopic analysis revealed that we obtained fractions with a ∼60‐fold enrichment in cyanobacterial and an approximately twofold enrichment in GNSLB biomass, respectively, compared with the mat itself. This technique was used to study the diel cycling and 13C content of the glucose pools in and the uptake of 13C‐bicarbonate by the cyanobacteria and GNSLB, as well as the transfer of incorporated 13C from cyanobacteria to GNSLB. The results show that cyanobacteria have the highest bicarbonate uptake rates and accumulate glucose during the afternoon in full light conditions. In contrast, GNSLB have relatively higher bicarbonate uptake rates compared with cyanobacteria in the morning at low light levels. During the night GNSLB take up carbon that is likely derived through fermentation of cyanobacterial glucose enriched in 13C. The assimilation of 13C‐enriched cyanobacterial carbon may thus lead to enriched 13C‐contents of GNSLB cell components.
The Practical Approach to Lung Health in South Africa (PALSA) intervention: respiratory guideline implementation for nurse trainers
Authors: Bheekie A. , Buskens I. , Allen S. , English R. , Mayers P. , Fairall L. , Majara B. , Bateman E. D. , Zwarenstein M. , Bachmann M.
Published: November 2006

Aim:  This paper describes the design, facilitation and preliminary assessment of a 1‐week cascade training programme for nurse trainers in preparation for implementation of the Practical Approach to Lung Health in South Africa (PALSA) intervention, tested within the context of a pragmatic cluster randomized controlled trial in the Free State province. PALSA combines evidence‐based syndromic guidelines on the management of respiratory disease in adults with group educational outreach to nurse practitioners.

Background:  Evidence‐based strategies to facilitate the implementation of primary care guidelines in low‐ to middle‐income countries are limited. In South Africa, where the burden of respiratory diseases is high and growing, documentation and evaluation of training programmes in chronic conditions for health professionals is limited.

Method:  The PALSA training design aimed for coherence between the content of the guidelines and the facilitation process that underpins adult learning. Content facilitation involved the use of key management principles (key messages) highlighted in nurse‐centred guidelines manual and supplemented by illustrated material and reminders. Process facilitation entailed reflective and experiential learning, role‐playing and non‐judgemental feedback.

Discussion and results:  Preliminary feedback showed an increase in trainers’ self‐awareness and self‐confidence. Process and content facilitators agreed that the integrated training approach was balanced. All participants found that the training was motivational, minimally prescriptive, highly nurse‐centred and offered personal growth.

Conclusion:  In addition to tailored guideline recommendations, training programmes should consider individual learning styles and adult learning processes.
Intraspecific food competition in fishes
Authors: Ward Ashley J. W. , Webster Michael M. , Hart Paul J. B.
Published: November 2006

Intraspecific food competition exerts powerful selective forces on all animals; successful foragers thrive relative to weaker conspecifics. Understanding competition is therefore fundamental both to ecological insight and to conservation efforts. Fish are adaptable and tractable experimental organisms, offering excellent model systems for studies on competition, and they lend themselves to two approaches: (i) studies of short‐term competition, which quantify the components of behavioural interactions; (ii) studies of long‐term interactions, in which the indeterminate nature of fish growth makes it possible to measure rates directly and correlate them with competitive success. The nature and the intensity of competition vary according to resource characteristics and distributions in time and space, the ecological context, and the relative competitive abilities of the foragers. Second‐order effects, such as winner and loser consequences, add to the complexity and frustrated early attempts to develop realistic models of intraspecific competition. Recently, however, considerable advances have been made in both laboratory and field studies on fishes adding to our understanding of these interacting effects. At the same time, the application of individual‐based modelling offers the prospect of progress towards greater realism and accuracy in predicting competitive outcomes. This review draws together a wide and disparate literature on intraspecific competition in fishes to facilitate the work of both empiricists and theoreticians towards these important goals.

In the short term, competing individuals may adopt different behavioural strategies and feeding patterns or establish dominance hierarchies and feeding territories. In the longer term, competition can drive character displacement and the formation of species pairs and fish provide some of the most compelling examples of these processes in evolutionary biology. The challenge for the future is to further develop our understanding of the relationship between the competitive environment and the responses of fishes, particularly with closer co‐operation between empiricists and theoreticians, and to apply this knowledge to aquaculture and to better management of exploited fish stocks.
Support for exclusionism as an independent dimension of social dominance orientation in mainland China
Authors: Li Zheng , Wang Lei , Shi Junqi , Shi Wei
Published: November 2006

Three studies using exploratory and confirmatory factor analyses provided consistent evidence for a three‐factor model of the social dominance orientation (SDO) in Mainland China. Support for exclusionism, which was not found in previous research, emerged as an independent SDO factor (Studies 1, 2, and 3). In Study 2, this factor predicted SDO difference between a high status group (managers) and a low status group (entry‐level employees). In Study 3, this factor correlated positively with authoritarianism and negatively with altruism. These results provided evidence for the validity of this new SDO factor. The findings are discussed in terms of their relations to China’s cultural tradition and contemporary economic development.
Competition between Employed and Unemployed Job Applicants: Swedish Evidence*
Authors: Eriksson Stefan , Lagerström Jonas
Published: November 2006

We use the Swedish Applicant Database to investigate empirically whether being unemployed per se reduces the probability of getting contacted by a firm. All searchers looking for a new job are invited to submit their personal details to this database over the internet. Since we have access to exactly the same information as the firms, we can minimize the problems associated with unobserved heterogeneity. Our results show that an unemployed applicant faces a lower contact probability than an otherwise identical employed applicant, thus supporting the notion that firms view employment status as a signal of productivity.
Systematic review: Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature
Authors: Stokes‐Lampard H , Wilson S , Waddell C , Ryan A , Holder R , Kehoe S
Published: November 2006

Background  Vaginal vault smears are used to detect persisting neoplasia of the lower genital tract after hysterectomy. Recent data suggest both widespread use and uncertain evidence of their effectiveness.

Objectives  To identify and synthesise evidence on the use and effectiveness of vaginal vault smears and to assess the quality.

Search strategy  ‘vault smear’ OR ‘vaginal vault smear’ OR ‘cervical vault smear’ OR (‘Hysterectomy’) AND (‘Follow up’ OR ‘Smear’).

Selection criteria  Primary research, women who had a hysterectomy and were followed up by vault cytology.

Data collection and analysis  Systematic search (eight electronic databases), supplemented by contact with experts and review of bibliographies. Two independent reviewers determined eligibility/validity and extracted data concerning test performance characteristics. Quality was assessed according to the established criteria.

Results  Of 441 unique references, only 19 were suitable. Quality of studies varied considerably and few were of ‘high’ methodological quality. Studies were geographically diverse, and were published over more than 40 years in 16 journals. From the higher scoring papers, there were 11 659 hysterectomies [6546, benign; 76, cervical intraepithelial neoplasia (CIN) I/CIN II; 5037, CIN III]. Proportions of abnormal vault smears and abnormal biopsies during follow up increased with worsening histology at hysterectomy (P < 0.0001 and P= 0.0001). There was only one report of vaginal cancer subsequent to hysterectomy for CIN and insufficient data to allow for reliable meta‐analysis.

Conclusions  Vault smears cause anxiety, consume resources and their value is largely unproven. Inconsistency of study design and limited methodological quality means that the value of vault smears could not be established. High‐quality research is required to ensure that the guidelines are evidence based.
Women’s experience of decision making about mode of delivery after a previous caesarean section: the role of health professionals and information about health risks
Authors: Emmett CL , Shaw ARG , Montgomery AA , Murphy DJ ,   DiAMOND study group
Published: November 2006

Objective To explore women’s experiences of decision making about mode of delivery after previous caesarean section.

Design A qualitative interview study.

Setting Two city maternity units in southwest England and Eastern Scotland.

Sample Twenty‐one women who had recently delivered a baby and whose previous child was delivered by caesarean section.

Methods Semi‐structured interviews analysed using the framework approach.

Main outcome measures Women’s views on the influence of uncertainty on decision making, issues concerning information provision and decision‐making roles.

Results Experiences of decision making varied considerably. Some women were certain about choosing either vaginal birth after caesarean or repeat elective caesarean section, others were very uncertain and for some this uncertainty persisted after the birth. Information was most commonly provided by hospital doctors (mainly consultants) and more often related to procedural issues rather than possible health risks and benefits. Women felt they had to actively seek information rather than it being provided routinely. Most women were able to make their own decision about mode of delivery. Health professionals generally took a supportive role whichever mode of delivery was chosen. Although many women were comfortable with this approach, some felt they would have liked more guidance.

Conclusion On the whole, women experienced having control over the decision about planned mode of delivery. For many, making this decision was difficult and for some it was the cause of prolonged anxiety. Women were often making the decision without being provided with comprehensive and specific information about possible health risks and benefits. We are currently conducting a randomised controlled trial to investigate whether access to a decision aid is beneficial to women in this situation.
Late termination of pregnancy: law, policy and decision making in four English fetal medicine units
Authors: Statham H , Solomou W , Green J
Published: November 2006

Objective  UK abortion law allows terminations for fetal abnormality without gestational limit. This study aimed to understand the decision‐making experiences of fetal medicine professionals working within this legal framework.

Design  Qualitative study using semistructured interviews.

Setting  Four English fetal medicine units.

Sample  Fifteen doctors and midwives working in fetal medicine units and the Director of a related voluntary sector group.

Methods  Thematic analysis of transcribed interviews.

Main outcome measures  Attitudes to abortion legislation; how decisions are made about the offer of late abortion and feticide.

Results  Fetal medicine specialists acknowledged the difficulties of ensuring that they worked within the law and within their own ethical frameworks when making decisions about offering terminations after viability. Practice regarding which abnormalities meet the legal criteria appeared to be governed largely by consensus between colleagues within their own and other units and in discussion with other specialists. Study participants reported individual differences about abnormalities where they personally would not wish to be involved in a termination, and also noted a shift in general attitudes over time as to conditions that meet the legal criteria. A proscribed list was believed to be both unworkable, given the variability in diagnoses and unhelpful, leading to reduced patient care.

Conclusions  Research is needed to monitor attitudes to, and interpretation of, UK abortion legislation, which permits termination after a late diagnosis of fetal abnormality without gestational limit. If attitudes are changing, it is important to understand why, and what the consequences will be for parents and for health professionals.
The social and educational impacts of the first national Down Syndrome support group in the UAE
Authors: Gaad Eman
Published: November 2006

Although there is a fairly extensive literature on social and educational inclusion of individuals with Down Syndrome (DS) in many countries, very little is produced on the life and education of such individuals in the United Arab Emirates. There is an apparent lack of societal interest in the quality of lives of people with DS. The condition of DS is nearly a taboo subject in this part of the world. With only a handful of pupils with DS included in regular schools, and with many myths and misconceptions surrounding the syndrome and individuals, particularly children with the syndrome, the first ever national support group for individuals with DS, their families and their carers was formed in late 2004 in the United Arab Emirates. This paper examines and evaluates the social and educational impact of the support group. The study particularly focuses on the role of such group in promoting social inclusion and inclusion of pupils with DS in regular schools in the UAE. Members (mainly parents of individuals with DS) of the newly‐established group participated in two interviews six months apart and the researcher observed group meetings, recorded activities and events over the same period. Views of individuals with DS on the effects and the activities of the group were also gathered through semi‐structured interviews.

Participants reported significant benefits from participating in the group, particularly in the areas of promoting social acceptance for individuals with DS. The study found that the group also helped in eliminating and correcting some of the myths surrounding the syndrome and played a role in promoting social and educational inclusion of such individuals. The study ends with a discussion of the findings and recommendations for future practice.
Role of protein kinase C‐dependent A‐kinase anchoring proteins in lysophosphatidic acid‐induced cAMP signaling in human diploid fibroblasts
Authors: Rhim Ji‐Heon , Jang Ik‐Soon , Yeo Eui‐Ju , Song Kye‐Yong , Park Sang Chul
Published: November 2006

Previously, we reported that lysophosphatidic acid (LPA)‐induced adenosine 3′,5′‐cyclic monophosphate (cAMP) production by human diploid fibroblasts depends on the age of the fibroblasts. In this study, we examined the role of A‐kinase anchoring proteins (AKAP) in the regulation of LPA‐stimulated cAMP production in senescent fibroblasts. We found that levels of protein kinase C (PKC)‐dependent AKAPs, such as Gravin and AKAP79, were elevated in senescent cells. Co‐immunoprecipitation experiments revealed that Gravin and AKAP79 do not associate with adenylyl cyclase type 2 (AC2) but bind to AC4/6, which interacts with calcium‐dependent PKCs α/β both in young and senescent fibroblasts. When the expression of Gravin and AKAP79 was blocked by small interference RNA transfection, the basal level of cAMP was greatly reduced and the cAMP status after LPA treatment was also reversed. Protein kinase A showed a similar pattern in terms of its basal activity and LPA‐dependent modulation. These data suggest that Gravin and to a lesser extent, AKAP79, may play important roles in maintaining the basal AC activity and in coupling the AC systems to inhibitory signals such as Giα in young cells, and to stimulatory signals such as PKCs in senescent cells. This study also demonstrates that Gravin is especially important for the long‐term activation of PKC by LPA in senescent cells. We conclude that LPA‐dependent increased level of cAMP in senescent human diploid fibroblasts is associated with increases in Gravin levels resulting in its increased binding with and activation of calcium‐dependent PKC α/β and AC4/6.
Stress, social rank and leukocyte telomere length
Authors: Lansdorp Peter M.
Published: November 2006

Blood leukocytes are a heterogeneous mixture of cell types whose telomere lengths differ greatly, reflecting variation in stem cell turnover and recruitment, expansion and replacement of more mature cell types as well as variable telomere loss and telomere repair. These differences in cell and telomere length dynamics, together with the evidence that telomere length is influenced strongly by genetic polymorphisms, greatly complicate the interpretation of claims that socio‐economic status modulates the rate of telomere attrition.
A life course perspective on telomere length and social inequalities in aging
Authors: Kuh Diana
Published: November 2006

Longitudinal studies will be needed to test the idea that social class in adult life, or in childhood, influences the rate of change in telomere length in peripheral blood samples.
THE USE OF ACQUISITIONS AND JOINT VENTURES BY U.S. BANKS EXPANDING ABROAD
Authors: Gleason Kimberly C. , Mathur Ike , Wiggins Roy A.
Published: November 2006

We examine international bank expansions, which are classified as banking (scale related) or nonbanking (complementary) moves into developed or developing markets. The market responds favorably to expansions through joint ventures by U.S. banks, and insignificantly to expansions through acquisitions. Accounting and operating performances (for joint venture banks) and long‐period holding returns (for acquisitions) show improvement in the two years following the announcement. Systematic risk declines for the sample overall, for acquisitions, and for expansions into developing countries. In general, scale or developing expansions are better pursued through acquisitions, whereas complementary or developed expansions are best pursued through joint ventures.
Development and Evaluation of a DNA Vaccine Based on Helicobacter pylori urease B: Failure to Prevent Experimental Infection in the Mouse Model
Authors: Zavala‐Spinetti Livania , Breslin Mary B. , Correa Hernán , Bégué Rodolfo E.
Published: November 2006

Background:  The development of a vaccine against Helicobacter pylori has become a priority to prevent major morbidity and mortality associated with this infection. Our goal was to prepare and evaluate a DNA vaccine based on the urease B gene (ureB).

Methods:  The ureB gene of H. pylori was amplified and cloned into the eukaryotic expression vector pcDNA3.1/TOPO. Plasmid DNA was purified from transformed Escherichia coli cells and used to immunize mice by the intragastric, intramuscular, intrarectal (40 µg each) and intranasal (16 µg) route, three doses every 2 weeks, with CpG oligodeoxynucleotide (ODN) as adjuvant. Four weeks after the third dose, animals were orally challenged with Helicobacter felis and were sacrificed 6 weeks later. The stomach was stained to detect the presence of infection.

Results:  Despite in vitro confirmation of successful cloning and functionality of the ureB gene with expression of a protein morphologically and antigenically identical to urease B, the DNA vaccine did not perform well in vivo. Immunization of mice produced a weak immune response. Overall, intrarectal and intranasal administration seemed more immunogenic than other routes. Protection against challenge was modest and nonsignificant, and slightly better on animals immunized by the intramuscular and intranasal route.

Conclusion:  A DNA vaccine based on H. pylori urease B was poorly immunogenic and nonprotective at the conditions evaluated. Higher doses, better adjuvants or a prime‐boost approach may circumvent these limitations.
Helicobacter pylori Infection: Further Evidence for the Role of Feco‐Oral Transmission
Authors: De Schryver Antoon , Van Winckel Myriam , Cornelis Kathleen , Moens Guido , Devlies Gery , De Backer Guy
Published: November 2006

Background:  Helicobacter pylori infection is recognized as a major cause of chronic digestive diseases with a major public health impact, yet the knowledge of transmission pathways is limited. We studied the transmission in employees taking care of institutionalized persons with mental disabilities with a documented high prevalence of H. pylori.

Materials and methods:  Six hundred and seventy‐one health‐care workers were screened for H. pylori serology. For each employee, information was collected on age, sex, father's and mother's education level, number of household members and number of children sleeping in the same bedroom during childhood, as well as lifestyle factors such as smoking and tropical journeys and occupational exposure data such as type of contact with inhabitants (changing napkins with stools, washing inhabitants, feeding inhabitants, personal contact) and seniority in the institution.

Results:  Seroprevalence for H. pylori increased significantly with age. In univariate analysis, risk factors for H. pylori positivity were (age‐adjusted): father's education, mean length of employment, smoking, contact with fecal materials of inhabitants, washing and feeding of inhabitants.

Controlling for confounders, in multiple logistic regression analysis, only fecal contact remained as a significant risk factor for H. pylori infection.

Conclusions:  In health‐care workers caring for a population with a high prevalence of H. pylori infection, there is an association with fecal transmission. This, however, does not rule out the possibility of other ways of transmission.
The Influence of Helicobacter pylori Infection on the Prevalence of Endoscopic Erosive Esophagitis
Authors: Unal Selahattin , Karakan Tarkan , Dogan Ibrahim , Cindoruk Mehmet , Dumlu Sukru
Published: November 2006

Objectives:  This study aimed to determine the frequency of endoscopic esophagitis and Helicobacter pylori infection in a large Turkish population over a 6‐year period.

Methods:  We studied a consecutive series of 14,380 patients who had been newly referred for diagnostic esophagogastroduodenoscopy from 2000 to 2006. The mean age value was 45 ± 10 (18–89) years. All endoscopic findings were retrospectively evaluated. Two antral and two corpus biopsies were taken from patients for rapid urease test. Endoscopic esophagitis was defined as the presence of erosions and/or ulceration. The relationship between erosive esophagitis and various relevant factors was analyzed.

Results:  The overall prevalence of endoscopic esophagitis was 7.8% (95% CI, 6.9–8.1). The prevalence of positive rapid urease test was 49% (95% CI, 38–53) in patients with esophagitis and 85% (95% CI, 70–96) in patients without esophagitis (p < .001). From 2000 to 2006, the frequency of endoscopic esophagitis and the rate of positive rapid urease test remained unchanged. After adjusting for the effects of mean age, male gender, and percentage of hiatal hernia, there was a 0.785% risk reduction in esophagitis with every 1% increase in the rate of positive rapid urease test result.

Conclusions:  The frequency of endoscopic esophagitis is significantly lower in patients with a positive rapid urease test result. This negative correlation with H. pylori infection reflects a protective effect of H. pylori from endoscopic esophagitis in a Turkish population and deserves further investigation.
Incidence and Predictors of Very Late Recurrence of Atrial Fibrillation After Ablation
Authors: MAINIGI SUMEET K. , SAUER WILLIAM H. , COOPER JOSHUA M. , DIXIT SANJAY , GERSTENFELD EDWARD P. , CALLANS DAVID J. , RUSSO ANDREA M. , VERDINO RALPH J. , LIN DAVID , ZADO ERICA S. , MARCHLINSKI FRANCIS E.
Published: November 2006

Introduction: Radiofrequency catheter ablation can effectively treat patients with refractory atrial fibrillation (AF). Very late AF recurrence (≥12 months post‐ablation) is uncommon and may represent a unique patient cohort.

Methods and Results: A nested case‐control study was performed in the cohort who underwent AF ablation at the University of Pennsylvania to characterize patients who develop very late AF recurrence after ablation. The procedure consisted of isolation of pulmonary veins (PVs) demonstrating triggers and elimination of non‐PV triggers initiating AF. Twenty‐seven (7.9%) patients with very late recurrence were compared to 219 patients without recurrence and ≥12 months of follow‐up. The mean age was 54.6 ± 11.3 years and 79% were men. Very late recurrence patients more likely weighed >200 lbs (70% vs 55%, P = 0.01); during initial ablation had fewer PVs isolated (2.8 ± 1.1 vs 3.3 ± 1.0, P = 0.03); and were less likely to have right inferior PV isolation (37% vs 61%, P = 0.02), less likely to have isolation of all PVs (30% vs 56%, P = 0.01), and more likely to have non‐PV triggers (30% vs 11% OR 3.4(95% CI, 1.3–8.7), P = 0.01). PV reconnectivity and new triggers were found in the majority of patients with very late recurrence of AF who underwent repeat ablation.

Conclusion: Very late recurrence of AF more likely occurred in patients >200 lbs who demonstrated non‐PV triggers and did not undergo right inferior PV isolation. The majority of patients undergoing repeat ablation for very late recurrence demonstrated PV reconnectivity and new non‐PV and PV triggers not observed during the initial ablation.
Newly Detected Atrial Fibrillation Following Dual Chamber Pacemaker Implantation
Authors: CHEUNG JIM W. , KEATING RICHARD J. , STEIN KENNETH M. , MARKOWITZ STEVEN M. , IWAI SEI , SHAH BINDI K. , LERMAN BRUCE B. , MITTAL SUNEET
Published: November 2006

Introduction: Pacemaker (PPM)‐detected atrial high‐rate episodes (AHREs) of even 5‐minute duration may identify patients at increased risk for stroke and death. In this study, we sought to determine the incidence of newly detected atrial fibrillation (AF defined as an AHRE ≥5 minutes) in patients following dual‐chamber PPM implantation and to define the clinical predictors of developing AF.

Methods and Results: We evaluated 262 patients (142 male; age 74 ± 12 years) without documented AF who underwent PPM implantation for sinus node dysfunction (n = 122) or atrioventricular block (n = 140). Information regarding patient demographics, cardiovascular diseases, and medication history was obtained. The cumulative percentages of ventricular pacing as well as the frequency, duration, and time to first episode of an AHRE were also determined. During follow‐up of 596 ± 344 days, an AHRE ≥5 minutes was detected in 77 (29%) patients. Of these, 47 (61%) patients had an AHRE ≥1 hour, 22 (29%) patients had an AHRE ≥1 day, and 12 (16%) patients had an AHRE ≥1 week. An AHRE ≥5 minutes was seen in 24% and 34% of patients at 1 year and 2 years, respectively. Among patients with sinus node dysfunction, ≥50% cumulative ventricular pacing was the only significant predictor of an AHRE ≥5 minutes (HR 2.2; CI 1.0–4.7; P = 0.04).

Conclusions: Within 1 year of PPM implantation, AF is detected in 24% of patients without history of AF. In patients with sinus node dysfunction, ≥50% cumulative right ventricular pacing is associated with a 2‐fold increase in risk of developing AF.
Characteristics of Patients Undergoing Atrial Fibrillation Ablation: Trends Over a Seven‐Year Period 1999–2005
Authors: GERSTENFELD EDWARD P. , CALLANS DAVID , DIXIT SANJAY , LIN DAVID , COOPER JOSHUA , RUSSO ANDREA M , VERDINO RALPH , WEINER MARK , ZADO ERICA , MARCHLINSKI FRANCIS E.
Published: November 2006

Background: Catheter ablation procedures for treating atrial fibrillation (AF) have dramatically increased since triggers of AF were first described in 1998.

Objective: We explored changes in patient characteristics in patients referred for catheter ablation of AF over a seven‐year period from 1999 through 2005.

Methods: Patient characteristics were examined for all patients undergoing AF ablation from 1999 through 2005 at the University of Pennsylvania Health System (UPHS). The gender of patients undergoing ablation was also compared with outpatients seen at UPHS with a primary diagnosis of AF.

Results: From 1999 to 2005 the number of patients undergoing ablation has increased steadily, from 29 patients in 1999 to 265 patients in 2005 (P < 0.01). Patients have become older (47 to 56 years; P < 0.01), with more persistent or permanent AF (17% to 45%; P < 0.01), larger left atrial size (4.0 to 4.4 cm; P < 0.01), and fewer antiarrhythmic drugs used prior to ablation (3.9 to 2.0 drugs; P < 0.01). Patients undergoing ablation have been predominantly male, with a significantly higher male prevalence than patients seen in the UPHS outpatient primary care clinic with AF (77% vs 59% male; P < 0.001).

Conclusions: Patients undergoing AF ablation from 1999 to 2005 are older, with larger left atrial size, more persistent/permanent AF, and fewer prior antiarrhythmic agents used. Compared with the gender‐specific rates of AF in the population, the majority of patients referred for ablation are men, suggesting a referral bias against this invasive procedure for women. These findings are important for interpreting the outcome of ablation in the current era, and for designing prospective randomized trials.
Extensive Changes in the Locations and Sequence Content of Developmentally Deleted DNA Between Tetrahymena thermophila and its Closest Relative, T. malaccensis
Authors: HUVOS PIROSKA E.
Published: November 2006

ABSTRACT. Tetrahymena thermophila has two different types of nuclei in a single cell. The development of the transcriptionally active macronucleus from a transcriptionally inert micronucleus is accompanied by the elimination of numerous DNA segments, called deletion elements or internally eliminated sequences (IESs). To try to distinguish between alternative modes for the generation of IESs during evolution, DNA sequences at three loci that contain IESs in T. thermophila were examined in Tetrahymena malaccensis, the closest relative of T. thermophila. In T. malaccensis, two loci examined do not seem to contain IESs. At one of these sites, the presence of the IES in T. thermophila can be accounted for either by insertion of a novel IES into T. thermophila or its precise deletion from T. malaccensis. At a third locus, the newly discovered EFZ IES (named after neighboring EF‐hand/Zinc finger genes), both T. thermophila and T. malaccensis contain IESs, but of different length and sequence content. If the three locations examined are a representative sample, the evolution of IESs seems to have been very rapid, and has led to substantial changes in the IES content of these two closely related species. Although insertion‐deletion events are likely to have shaped IES evolution, none of the IESs examined here could be identified as transposon‐like elements.
Reverse Arrangement of rRNA Subunits in the Microsporidium Glugoides intestinalis
Authors: REFARDT DOMINIK , MOUTON LAURENCE
Published: November 2006

ABSTRACT. The rRNA gene cluster of microsporidia is typically arranged in the order small subunit‐internal transcribed spacer‐large subunit, which conforms with the general arrangement of these genes in nearly all organisms. We found a rearrangement of the cluster in the microsporidium Glugoides intestinalis, where the large subunit precedes the small subunit. Such a rearrangement has already been reported for several species in the microsporidian genus Nosema, and we provide evidence that the arrangement reported here is a second, independent event.
Discovery and Barcoding by Analysis of Spliced Leader RNA Gene Sequences of New Isolates of Trypanosomatidae from Heteroptera in Costa Rica and Ecuador
Authors: MASLOV DMITRI A. , WESTENBERGER SCOTT J. , XU XING , CAMPBELL DAVID A. , STURM NANCY R.
Published: November 2006

ABSTRACT. Trypanosomatid diversity in Heteroptera was sampled using a culture‐independent approach based on amplification and sequencing of Spliced Leader RNA gene repeats from environmental samples. By combining the data collected herein with that of previous work, the prevalence of parasites was found to be 22%–23%. Out of approximately 170 host species investigated nearly 60 were found to harbor trypanosomatids. The parasites found were grouped by cluster analysis into 48 typing units. Most of these were well separated from the known groups and, therefore, likely represent new trypanosomatid species. The sequences for each typing unit serve as barcodes to facilitate their recognition in the future. As the sampled host species represent a minor fraction of potential hosts, the entire trypanosomatid diversity is far greater than described thus far. Investigations of trypanosomatid diversity, host‐specificity, and biogeography have become feasible using the approach described herein.
IMAGE FUSION OF COMPUTED TOMOGRAPHIC AND MAGNETIC RESONANCE IMAGES FOR THE DEVELOPMENT OF A THREE‐DIMENSIONAL MUSCULOSKELETAL MODEL OF THE EQUINE FORELIMB
Authors: ZARUCCO LAURA , WISNER ERIK R. , SWANSTROM MICHAEL D. , STOVER SUSAN M.
Published: November 2006

Biomechanical models that compute the lengths and forces of muscle–tendon units are broadly applicable to the study of factors that promote injury and the planning and effects of orthopedic surgical procedures in equine athletes. A three‐dimensional (3D) generic musculoskeletal model of the equine forelimb comprised of bony segment, muscle–tendon, and ligament information, was developed based on high‐resolution computed tomographic (CT) and T1‐weighted magnetic resonance (MR) images from an isolated forelimb of a Thoroughbred racehorse. Image fusion was achieved through coregistration of CT and MR images with an image analysis program (Analyze™) by adjustment of the relative position and orientation of fiducial markers visible in both modalities until the mutual information between the images was maximized. 3D surfaces of the bones and origin/insertion sites, centroid paths and volumes of the muscle–tendon and ligamentous structures were obtained from the multimodal (CT/MR) images using semiautomated and manual segmentation combined with sagittal and transverse color‐cryosection anatomic images obtained from three other cadaveric equine forelimbs. Once bony and soft‐tissue structures were reconstructed in the same coordinate system, data were imported to a software package for interactive musculoskeletal modeling (SIMM®). The combination of integrated CT and MR acquisitions and anatomical images provided an accurate and efficient means of generating a 3D model of the musculoskeletal structures of an average‐sized equine adult horse.