bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gα -scheme for Approximation of Fractional Derivatives: Application to the Dynamics of Dissipative Systems
Authors: Galucio A.C. , Deü J.-F. , Dubois F.
Published: September 2008

The Gear scheme is a three-level step algorithm, backward in time and second order accurate, for the approximation of classical time derivatives. In this article, the formal power of this scheme is used to approximate fractional derivative operators, in the context of finite difference methods. Numerical examples are presented and analyzed, in order to show the accuracy of the Gear scheme at the power α (Gα-scheme) when compared to the classical Grünwald-Letnikov approximation. In particular, the combined Gα -Newmark scheme is shown to be second-order accurate for a fractional damped oscillator problem.
Dynamic Measurements in Long-memory Materials: Fractional Calculus Evaluation of Approach to Steady State
Authors: Heymans Nicole
Published: September 2008

Fractional calculus descriptions of polymer viscoelasticity are becoming increasingly popular, as they allow a concise description of non-Debye relaxation and memory of strain history using a minimal parameter set. Use of fractional calculus to this end is frequently restricted to descriptions of dynamic behaviour, for example in dynamic mechanical thermal analysis (DMTA), where the dependence of the complex modulus on frequency can be expressed algebraically in closed form. However, this approach is only valid in the steady state. The material's approach to the steady state, and the effect of the slowly-decaying transient on DMTA measurements, are addressed here. “Data” are generated by integration of the time-domain fractional integral constitutive equation describing the fractional Zener model, and are analysed by a procedure inspired by a commercial DMTA instrument manual. Results show that the frequency dependence of the decay of the initial transient leads to difficulties in retrieving a single parameter set from the data, demonstrating that a specific procedure is required when evaluating long-memory materials.
A Condensation Technique for Finite Element Dynamic Analysis Using Fractional Derivative Viscoelastic Models
Authors: Catania Giuseppe , Sorrentino Silvio , Fasana Alessandro
Published: September 2008

Fractional derivative rheological models are known to be very useful for describing the viscoelastic behaviour of materials, especially of polymers, and when applied to dynamic problems, the resulting equations of motion, after a fractional state-space expansion, can still be studied in terms of modal analysis. The increase in matrix dimensions produced by this expansion, however, is often so fast as to make the calculations too cumbersome for finite element applications. This article presents a condensation technique based on the computation of two reduced-size eigenproblems. The rheological model adopted is the fractional Zener (fractional standard linear solid) model, but the same methodology can be applied to problems using different fractional derivative linear models.
Automatic Loop Shaping in QFT Using CRONE Structures
Authors: Cervera Joaquín , Baños Alfonso
Published: September 2008

This work focuses on the problem of automatic loop shaping in quantitative feedback theory (QFT), where the search for an optimum design (a non-convex and nonlinear optimization problem) is traditionally simplified by linearizing and/or convexifying the problem. In this work, the authors propose a suboptimal solution using a fixed structure in the compensator. In relation to previous work, the main idea consists in the study of the use of fractional compensators, which give singular properties to automatically shape the open loop gain function by using a minimum set of parameters. CRONE controllers, in particular CRONE 2 and CRONE 3, are considered as possible candidate structures, being original structures modified for a better approach to the QFT theoretical optimum. CRONE 3 non-minimum-phase zeros are avoided by constraints on the structure parameters.
Analog Fractional Order Controller in Temperature and Motor Control Applications
Authors: Bohannan Gary W.
Published: September 2008

An analog fractional order PI λ controller, using a circuit element with fractional order impedance, a Fractor (patent pending), is demonstrated in both a simple temperature control application and a more complex motor controller. The performance improvement over a standard PI controller was notable in both reduction of overshoot and decreased time to stable temperature, while retaining long term stability. In the motor controller, set point accuracy was considerably improved over conventional control. The modification of the standard controller to a fractional order controller was as simple as replacing the integrator capacitor with a Fractor. Mixing (i.e., hybridization) of digital and analog control was demonstrated.
Fractional Modelling and Identification of a Thermal Process
Authors: Benchellal Amel , Poinot Thierry , Trigeassou Jean-Claude
Published: September 2008

Heat transfer problems are subject to diffusion phenomenon, and can be modelled with the help of fractional systems. The simulation of these particular systems is based on a fractional integrator, where the non-integer behaviour occurs only within a limited spectral band. A first model, based on the use of one fractional integrator, has been already defined and tested on a thermal pilot. Starting from frequency considerations derived from the analysis of a diffusion problem, a more general approximation of the fractional system is proposed here. The new model is based on the use of two fractional integrator operators. This makes it possible to define a state-space model for simulation of transients, and to use an output-error technique in order to estimate the parameters of the model. Experimental results obtained for a thermal process illustrate the improvements obtained using the proposed model.
Discretization of Complex-order Algorithms for Control Applications
Authors: Barbosa Ramiro S. , Tenreiro Machado J.A. , Silva Manuel F.
Published: September 2008

In this article we describe several methods for the discretization of the differintegral operator sa, where α = u + jv is a complex value. The concept of the conjugated-order differintegral is also introduced, which enables the use of complex-order differintegrals while still producing real-valued time responses and transfer functions. The performance of the resulting approximations is analysed in both the time and frequency domains. Several results are presented that demonstrate its utility in control system design.
Nonconservative Systems within Fractional Generalized Derivatives
Authors: Baleanu Dumitru , Muslih Sami I.
Published: September 2008

A fractional derivative generalizes an ordinary derivative, and therefore the derivative of the product of two functions differs from that for the classical (integer) case; the integration by parts for Riemann-Liouville fractional derivatives involves both the left and right fractional derivatives. Despite these restrictions, fractional calculus models are good candidates for description of nonconservative systems. In this article, nonconservative Lagrangian mechanics are investigated within the fractional generalized derivative approach. The fractional Euler-Lagrange equations based on the Riemann-Liouville fractional derivatives are briefly presented. Using generalized fractional derivatives, we give a meaning for the term which appears in fractional Euler-Lagrange equations and contains the second order fractional derivative. The fractional Lagrangians and Hamiltonians of two illustrative nonconservative mechanical systems are investigated in detail.
Is England's Warm Front Programme Going to Improve the Country's Health?
Authors: Richardson George , Eick Susan
Published: September 2008

There have been a number of initiatives in the UK to increase the energy efficiency of homes by offering improvements to thermal performance through grant schemes. Although the outcomes of these schemes are often linked to health, inherent problems in these schemes mean that is unlikely that there will be any measurable health outcomes.
The Quasi-Market Revolution in the Head
Authors: Carey Malcolm
Published: September 2008

• Summary: The article explores the use of ideology by a group of care managers in the United Kingdom ( n = 44) in their work environments. It draws upon ethnomethodological research which investigated the motivations of qualified employees for entering and remaining within state social work. As well as exploring the impact and uses of ideology, the article also questions the disparagement of universalism in the postmodern inspired critique of welfare. This is sustained by highlighting the broad and universal impact of neoliberalism in relation to the care management labour process.

• Findings: Care managers utilize ideology throughout their practice, although this is predominantly inspired by external factors, notably legislation and policy. Despite this, there is evidence of some application of professional, and/or critical ideologies, which can offer respite from, and act as a form of resistance against neoliberal ideology within the care management labour process. Nevertheless, in practice, such resistance tends to be dispersed, sporadic and often individualistic.

• Applications : It is proposed that the greater use of `emancipatory' ideology in the education and practice of care managers may help in resisting further deskilling and disenfranchisement. Also, the work of Gramsci and Foucault offers a potential framework to contextualize forms of anti-market resistance.
New Leader Assimilation: An Intervention for Leaders in Transition
Authors: Manderscheid Steven V.
Published: September 2008

The problem and the solution . Leader transitions are important passages that have implications for the leader, his or her team, and the organization. Such transitions are more frequent than in the past, and the failure rate of new leaders is high.When leaders transition into a new leadership role in a new organization, there are few formal interventions, like a leader assimilation, to help them learn, adapt, and build relationships quickly with their new teams. Moreover, there is little empirical research documenting the impact of leadership development interventions early in a leader's transition. The purpose of this study was to leverage the observation and interview data of an existing study conducted by the researcher on leader assimilation outcomes.The following study will explain the process of facilitating a leader assimilation and will use research data to provide insights into how human resource development (HRD) practitioners can use leader assimilations more effectively.
Quality assessment of phase I dose-finding cancer trials: proposal of a checklist
Authors: Zohar Sarah , Qing Lian  , Levy Vincent , Cheung Ken , Ivanova Anastasia , Chevret Sylvie
Published: September 2008

Background Qualitative checklists for phase III trials have been proposed, to improve the reporting of such trials and to assess the validity of their results.

Purpose Our objective was to develop such a scale for phase I cancer trials.

Methods From a review of existing guidelines and checklists for phase III clinical trials, a staff team was responsible for the first selection of items and the construction of the questionnaire. The proposed quality assessment measures were rated by the survey respondents comprised of phase I research clinicians and statisticians on a 4-point Likert scale. Selected items from the quantitative analysis of the questionnaires were reviewed by an expert team who was responsible for providing the final items list. This was then applied to 103 recently published cancer phase I trials.

Results Of the 48 initial items proposed by the staff team, 17 were selected from the quantitative analysis of the 99 participants' ratings. After qualitative analysis by the expert team, a 15-item checklist was derived, with 5 items related to trial objective, 5 to design, and 5 to analysis. The application to 103 recent journal articles on phase I cancer trials evaluating cytotoxic drugs showed on average the report of 10 items (range: 6—13) with 4 items reported in more than 95% of papers, while 2 were poorly reported.

Limitations The response rate of participants was 20.7%.

Conclusions A quality assessment checklist was developed for improved critical appraisal of the reporting of cytotoxic, dose-finding phase I oncology trials. This may be a first step toward a minimum standard of quality measures for all phase I clinical trial reports. Clinical Trials 2008; 5: 478—485. http://ctj.sagepub.com
Clinical trials in stem cell transplantation: guidelines for scientific and ethical review
Authors: Lo Bernard , Kriegstein Arnold , Grady Deborah
Published: September 2008

Background Transplantation of cells derived through the manipulation of pluripotent stem cells may involve great uncertainty and the possibility of serious risks.

Purpose To develop guidelines for the ethical conduct of clinical trials using such stem cells.

Methods Review of literature on clinical trials ethics and clinical applications of stem cells; critical deliberation on potential guidelines.

Results Such transplantation should be allowed in clinical practice only after clinical trials demonstrate efficacy and safety. These clinical trials should follow ethical principles that guide all clinical research. Additional requirements to strengthen trial design, coordinate scientific and ethics review, verify that participants understand key features of the trial, and ensure publication of findings are also warranted because of the highly innovative nature of the intervention, limited experience in humans, and the high hopes of patients who have no alternative effective treatments.

Limitations These recommendations will need to be modified in light of actual experience with stem cell clinical trials.

Conclusions These recommendations will help guarantee that the efficacy and safety of innovative stem cell interventions will be rigorously established, while also protecting study participants. Clinical Trials 2008; 5: 517—522. http:// ctj.sagepub.com
Magnetic nanoparticle carrier for targeted drug delivery: Perspective, outlook and design
Authors: Misra R. D. K.
Published: September 2008

The primary challenge in the delivery of a drug to a tumour site is to target the anticancer drug specifically into and around tumours at concentrations that will decrease their growth and/or viability. Excellent vehicles to achieve targeted drug delivery are magnetic nanocarriers. A approach to accomplish this objective is to fabricate a novel temperature and pH-responsive magnetic nanocarrier that combines tumour targeting and controlled release. In addition to controlled release, these carriers simultaneously offer the possibility of imaging the delivery process by magnetic resonance imaging. The novel aspect of this approach is the combination of thermal and pH sensitivity of the drug containing shell with magnetic properties of the core in a single unit. Furthermore, application of an external magnetic field will heat the nanoparticles and thus nanoparticle containing cells. The targeted heat will aid in the killing of tumour cells.
Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13
Authors: Fehniger Todd A. , Byrd John C. , Marcucci Guido , Abboud Camille N. , Kefauver Cheryl , Payton Jacqueline E. , Vij Ravi , Blum William
Published: September 2008

Patients with acute myeloid leukemia (AML) frequently fail chemotherapy due to refractory disease, relapse, or toxicity. Among older AML patients (age > 60 years), there are few long-term survivors. Lenalidomide is a candidate for study in AML based on its clinical activity in a related disorder, myelodysplastic syndrome (MDS), with the 5q− chromosomal abnormality. We report induction of sustained morphologic and cytogenetic complete remission in 2 older AML patients treated with high-dose, single-agent lenalidomide; each patient had trisomy 13 as the sole cytogenetic abnormality. We show for the first time that lenalidomide has clinical activity in this poor-risk cytogenetic subset of AML. The clinical trials described in this paper have been registered with www.clinicaltrials.gov under identifiers NCT00466895 and NCT00546897.
Depletion of autoreactive immunologic memory followed by autologous hematopoietic stem cell transplantation in patients with refractory SLE induces long-term remission through de novo generation of a juvenile and tolerant immune system
Authors: Alexander Tobias , Thiel Andreas , Rosen Oliver , Massenkeil Gero , Sattler Arne , Kohler Siegfried , Mei Henrik , Radtke Hartmut , Gromnica-Ihle Erika , Burmester Gerd-Rüdiger , Arnold Renate , Radbruch Andreas , Hiepe Falk
Published: September 2008

Clinical trials have indicated that immunoablation followed by autologous hematopoietic stem cell transplantation (ASCT) has the potential to induce clinical remission in patients with refractory systemic lupus erythematosus (SLE), but the mechanisms have remained unclear. We now report the results of a single-center prospective study of long-term immune reconstitution after ASCT in 7 patients with SLE. The clinical remissions observed in these patients are accompanied by the depletion of autoreactive immunologic memory, reflected by the disappearance of pathogenic anti–double-stranded DNA (dsDNA) antibodies and protective antibodies in serum and a fundamental resetting of the adaptive immune system. The latter comprises recurrence of CD31+CD45RA+CD4+ T cells (recent thymic emigrants) with a doubling in absolute numbers compared with age-matched healthy controls at the 3-year follow-up (P = .016), the regeneration of thymic-derived FoxP3+ regulatory T cells, and normalization of peripheral T-cell receptor (TCR) repertoire usage. Likewise, responders exhibited normalization of the previously disturbed B-cell homeostasis with numeric recovery of the naive B-cell compartment within 1 year after ASCT. These data are the first to demonstrate that both depletion of the autoreactive immunologic memory and a profound resetting of the adaptive immune system are required to reestablish self-tolerance in SLE. This trial was registered at www.clinicaltrials.gov as #NCT00742300.
COPD-related morbidity and mortality after smoking cessation: status of the evidence
Authors: Godtfredsen N. S. , Lam T. H. , Hansel T. T. , Leon M. E. , Gray N. , Dresler C. , Burns D. M. , Prescott E. , Vestbo J.
Published: September 2008

The evidence base for the benefit of quitting smoking as regards morbidity and mortality outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited.

The present article is a review of the existing literature. A systematic literature search in medical databases was performed until March 2006, and subsequently until September 1, 2007. The outcomes examined were COPD-related morbidity and mortality (including all-cause mortality) in COPD patients in connection with smoking cessation.

A total of 21 and 27 published articles on morbidity and mortality, respectively, were identified and reviewed. For both outcomes, only a few of the studies included patients with severe COPD. Most of the studies reported a beneficial effect of smoking cessation compared with continued smoking, whereas a few found no improvement. Methodological problems, including small study sizes, poor data quality, possibility of reverse causality and incomplete ascertainment of cause of death, limit interpretation of some of the studies.

The evidence as a whole supports the conclusion that, even in severe chronic obstructive pulmonary disease, smoking cessation slows the accelerated rate of lung function decline and improves survival compared with continued smoking.
Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases
Authors: Burgel P-R. , Nadel J. A.
Published: September 2008

Inhaled air is contaminated with pathogens and particulates that may deposit in the airways and damage the host. In response to these invaders, the airway epithelium has developed innate immune responses that provide a defence against the invaders and protect the airway structure and function. Thus, the epithelium of conducting airways becomes the “battleground” between the invaders and the host.

Recent evidence suggests that airway epithelial surface signalling through the epidermal growth factor receptor (EGFR) is a convergent pathway producing innate immune responses to a variety of infectious and noninfectious noxious stimuli. In the present review, the EGFR signalling pathways leading to airway mucin production, neutrophil recruitment (viainterleukin-8 production) and airway epithelial repair were examined.

The importance of these findings in human airway diseases was also investigated. The current authors suggest that the exaggerated innate immune responses found in chronic inflammatory airway diseases (e.g.chronic obstructive pulmonary disease, cystic fibrosis and severe asthma) contribute to the pathogenesis or the aggravation of these diseases. Potential therapies include inhibition of the various elements of the described epidermal growth factor receptor cascade. In considering each therapeutic intervention, the potential benefits must be considered in relation to potential deleterious effects.
Immunoaffinity purification and characterization of mitochondrial membrane-bound D-3-hydroxybutyrate dehydrogenase from Jaculus orientalis
Authors: Mountassif Driss , Andreoletti Pierre , El Kebbaj Zakaria , Moutaouakkil Adnane , Cherkaoui-Malki Mustapha , Latruffe Norbert , El Kebbaj M'hammed Saïd
Published: September 2008

Background

The interconversion of two important energy metabolites, 3-hydroxybutyrate and acetoacetate (the major ketone bodies), is catalyzed by D-3-hydroxybutyrate dehydrogenase (BDH1: EC 1.1.1.30), a NAD+-dependent enzyme. The eukaryotic enzyme is bound to the mitochondrial inner membrane and harbors a unique lecithin-dependent activity. Here, we report an advanced purification method of the mammalian BDH applied to the liver enzyme from jerboa (Jaculus orientalis), a hibernating rodent adapted to extreme diet and environmental conditions.

Results

Purifying BDH from jerboa liver overcomes its low specific activity in mitochondria for further biochemical characterization of the enzyme. This new procedure is based on the use of polyclonal antibodies raised against BDH from bacterial Pseudomonas aeruginosa. This study improves the procedure for purification of both soluble microbial and mammalian membrane-bound BDH. Even though the Jaculus orientalis genome has not yet been sequenced, for the first time a D-3-hydroxybutyrate dehydrogenase cDNA from jerboa was cloned and sequenced.

Conclusion

This study applies immunoaffinity chromatography to purify BDH, the membrane-bound and lipid-dependent enzyme, as a 31 kDa single polypeptide chain. In addition, bacterial BDH isolation was achieved in a two-step purification procedure, improving the knowledge of an enzyme involved in the lipid metabolism of a unique hibernating mammal. Sequence alignment revealed conserved putative amino acids for possible NAD+ interaction.
Transferability and polymorphism of barley EST-SSR markers used for phylogenetic analysis in Hordeum chilense
Authors: Castillo Almudena , Budak Hikmet , Varshney Rajeev K , Dorado Gabriel , Graner Andreas , Hernandez Pilar
Published: September 2008

Background

Hordeum chilense, a native South American diploid wild barley, is a potential source of useful genes for cereal breeding. The use of this wild species to increase genetic variation in cereals will be greatly facilitated by marker-assisted selection. Different economically feasible approaches have been undertaken for this wild species with limited direct agricultural use in a search for suitable and cost-effective markers. The availability of Expressed Sequence Tags (EST) derived microsatellites or simple sequence repeat (SSR) markers, commonly called as EST-SSRs, for barley (Hordeum vulgare) represents a promising source to increase the number of genetic markers available for the H. chilense genome.

Results

All of the 82 barley EST-derived SSR primer pairs tested for transferability to H. chilense amplified products of correct size from this species. Of these 82 barley EST-SSRs, 21 (26%) showed polymorphism among H. chilense lines. Identified polymorphic markers were used to test the transferability and polymorphism in other Poaceae family species with the aim of establishing H. chilense phylogenetic relationships. Triticum aestivum-H. chilense addition lines allowed us to determine the chromosomal localizations of EST-SSR markers and confirm conservation of the linkage group.

Conclusion

From the present study a set of 21 polymorphic EST-SSR markers have been identified to be useful for diversity analysis of H. chilense, related wild barleys like H. murinum, and for wheat marker-assisted introgression breeding. Across-genera transferability of the barley EST-SSR markers has allowed phylogenetic inference within the Triticeae complex.
Cloning, characterisation and comparative analysis of a starch synthase IV gene in wheat: functional and evolutionary implications
Authors: Leterrier Marina , Holappa Lynn D , Broglie Karen E , Beckles Diane M
Published: September 2008

Background

Starch is of great importance to humans as a food and biomaterial, and the amount and structure of starch made in plants is determined in part by starch synthase (SS) activity. Five SS isoforms, SSI, II, III, IV and Granule Bound SSI, have been identified, each with a unique catalytic role in starch synthesis. The basic mode of action of SSs is known; however our knowledge of several aspects of SS enzymology at the structural and mechanistic level is incomplete. To gain a better understanding of the differences in SS sequences that underscore their specificity, the previously uncharacterised SSIVb from wheat was cloned and extensive bioinformatics analyses of this and other SSs sequences were done.

Results

The wheat SSIV cDNA is most similar to rice SSIVb with which it shows synteny and shares a similar exon-intron arrangement. The wheat SSIVb gene was preferentially expressed in leaf and was not regulated by a circadian clock. Phylogenetic analysis showed that in plants, SSIV is closely related to SSIII, while SSI, SSII and Granule Bound SSI clustered together and distinctions between the two groups can be made at the genetic level and included chromosomal location and intron conservation. Further, identified differences at the amino acid level in their glycosyltransferase domains, predicted secondary structures, global conformations and conserved residues might be indicative of intragroup functional associations.

Conclusion

Based on bioinformatics analysis of the catalytic region of 36 SSs and 3 glycogen synthases (GSs), it is suggested that the valine residue in the highly conserved K-X-G-G-L motif in SSIII and SSIV may be a determining feature of primer specificity of these SSs as compared to GBSSI, SSI and SSII. In GBSSI, the Ile485 residue may partially explain that enzyme's unique catalytic features. The flexible 380s Loop in the starch catalytic domain may be important in defining the specificity of action for each different SS and the G-X-G in motif VI could define SSIV and SSIII action particularly.
Setting up a Paediatric Rapid Access Outpatient Unit: Views of general practice teams
Authors: Williams Lisa , Fryer Jane , Andrew Rachel , Powell Colin , Pink Jim , Elwyn Glyn
Published: September 2008

Background

Rapid Access Outpatient Units (RAOUs) have been suggested as an alternative to hospital inpatient units for the management of some acutely unwell children. These units can provide ambulatory care, delivered close to home, and may prevent unnecessary hospital admission. There are no qualitative data on the views of primary care practitioners regarding these types of facilities. The aim of the study was to explore the opinions of primary care practitioners regarding a newly established RAOU.

Methods

The RAOU was established locally at a district general hospital when inpatient beds were closed and moved to an inpatient centre, based six miles away at the tertiary teaching hospital.

Qualitative, practice based group interviews with primary care practitioners (general practitioners (GPs), nurse practitioners and practice nurses) on their experiences of the RAOU. The data collection consisted of three practice based interviews with 14 participants. The interviews were recorded and transcribed verbatim. Thematic content analysis was used to evaluate the data.

Results

There was positive feedback regarding ease of telephone access for referral, location, and the value of a service staffed by senior doctors where children could be observed, investigated and discharged quickly. There was confusion regarding the referral criteria for the assessment unit and where to send certain children. A majority of the practitioners felt the utility of the RAOU was restricted by its opening hours. Most participants felt they lacked sufficient information regarding the remit and facilities of the unit and this led to some uneasiness regarding safety and long term sustainability.

Conclusion

Practitioners considered that the RAOU offered a rapid senior opinion, flexible short term observation, quick access to investigations and was more convenient for patients. There were concerns regarding opening hours, safety of patients and lack of information about the unit's facilities. There was confusion about which children should be sent to the unit. This study raises questions regarding policy in regard to the organisation of paediatric services. It highlights that when establishing alternative services to local inpatient units, continual communication and engagement of primary care is essential if the units are to function effectively.
The effect of menopause and hysterectomy on systemic vascular endothelial growth factor in women undergoing surgery for breast cancer
Authors: Lowery Aoife J , Sweeney Karl J , Molloy Alan P , Hennessy Emer , Curran Catherine , Kerin Michael J
Published: September 2008

Background

Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine produced physiologically by the uterus. Pathological secretion by tumours promotes growth and metastasis. High circulating VEGF levels potentially have a deleterious effect on breast cancer by promoting disease progression.

The aims of this study were to investigate circulating VEGF levels in breast cancer patients and assess the effect of menopause or hysterectomy on systemic VEGF.

Methods

Patients undergoing primary surgery for breast cancer and controls matched for age, menopausal and hysterectomy status were prospectively recruited. Serum VEGF, FSH, LH, estrogen, progesterone and platelet levels were measured. Serum VEGF was corrected for platelet load (sVEGFp) to provide a biologically relevant measurement of circulating VEGF. SVEGFp levels were analyzed with respect to tumor characteristics, menopausal status and hysterectomy status.

Results

Two hundred women were included in the study; 89 breast cancer patients and 111 controls. SVEGFp levels were significantly higher in breast cancer patients compared to controls (p = 0.0001), but were not associated with clinico-pathological tumor characteristics. Systemic VEGF levels reduced significantly in the breast cancer patients following tumor excision (p = 0.018). The highest systemic VEGF levels were observed in postmenopausal breast cancer patients. Postmenopausal women who had had a previous hysterectomy had significantly higher VEGF levels than those with an intact postmenopausal uterus (p = 0.001).

Conclusion

This study identifies an intact postmenopausal uterus as a potential means of reducing circulating levels of VEGF which could confer a protective effect against breast cancer metastatic potential.
Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model
Authors: Dohare Preeti , Garg Puja , sharma Uma , Jagannathan NR , Ray Madhur
Published: September 2008

Background

Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil).

Method

In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters.

Results

C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis.

Conclusion

Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons.
Sample size determination for bibliographic retrieval studies
Authors: Yao Xiaomei , Wilczynski Nancy L , Walter Stephen D , Haynes R Brian
Published: September 2008

Background

Research for developing search strategies to retrieve high-quality clinical journal articles from MEDLINE is expensive and time-consuming. The objective of this study was to determine the minimal number of high-quality articles in a journal subset that would need to be hand-searched to update or create new MEDLINE search strategies for treatment, diagnosis, and prognosis studies.

Methods

The desired width of the 95% confidence intervals (W) for the lowest sensitivity among existing search strategies was used to calculate the number of high-quality articles needed to reliably update search strategies. New search strategies were derived in journal subsets formed by 2 approaches: random sampling of journals and top journals (having the most high-quality articles). The new strategies were tested in both the original large journal database and in a low-yielding journal (having few high-quality articles) subset.

Results

For treatment studies, if W was 10% or less for the lowest sensitivity among our existing search strategies, a subset of 15 randomly selected journals or 2 top journals were adequate for updating search strategies, based on each approach having at least 99 high-quality articles. The new strategies derived in 15 randomly selected journals or 2 top journals performed well in the original large journal database. Nevertheless, the new search strategies developed using the random sampling approach performed better than those developed using the top journal approach in a low-yielding journal subset. For studies of diagnosis and prognosis, no journal subset had enough high-quality articles to achieve the expected W (10%).

Conclusion

The approach of randomly sampling a small subset of journals that includes sufficient high-quality articles is an efficient way to update or create search strategies for high-quality articles on therapy in MEDLINE. The concentrations of diagnosis and prognosis articles are too low for this approach.
A quantitative PCR method to detect blood microRNAs associated with tumorigenesis in transgenic mice
Authors: Fan Alice C , Goldrick Marianna M , Ho Jennifer , Liang Yu , Bachireddy Pavan , Felsher Dean W
Published: September 2008

MicroRNA (miRNA) dysregulation frequently occurs in cancer. Analysis of whole blood miRNA in tumor models has not been widely reported, but could potentially lead to novel assays for early detection and monitoring of cancer. To determine whether miRNAs associated with malignancy could be detected in the peripheral blood, we used real-time reverse transcriptase-PCR to determine miRNA profiles in whole blood obtained from transgenic mice with c-MYC-induced lymphoma, hepatocellular carcinoma and osteosarcoma. The PCR-based assays used in our studies require only 10 nanograms of total RNA, allowing serial mini-profiles (20 – 30 miRNAs) to be carried out on individual animals over time. Blood miRNAs were measured from mice at different stages of MYC-induced lymphomagenesis and regression. Unsupervised hierarchical clustering of the data identified specific miRNA expression profiles that correlated with tumor type and stage. The miRNAs found to be altered in the blood of mice with tumors frequently reverted to normal levels upon tumor regression. Our results suggest that specific changes in blood miRNA can be detected during tumorigenesis and tumor regression.
Index medicus for the Eastern Mediterranean region
Authors: Al-Shorbaji Najeeb
Published: September 2008

The study provides the rationale, history and current status of the Index Medicus for the World Health Organization Eastern Mediterranean Region. The Index is unique in combining the geographic coverage of peer-reviewed health and biomedical journals (408 titles) from the 22 countries of the Region. Compiling and publishing the Index coupled with a document delivery service is an integral part of the WHO Regional Office's knowledge management and sharing programme. In this paper, bibliometric indicators are presented to demonstrate the distribution of journals, articles, languages, subjects and authors as well as availability in printed and electronic formats. Two countries in the Region (Egypt and Pakistan) contribute over 50% of the articles in the Index. About 90% of the articles are published in English. Epidemiology articles represent 8% of the entire Index. 15% of the journals in the Index are also indexed in MEDLINE, while 7% are indexed in EMBASE. Future developments of the Index will include covering more journals and adding other types of health and biomedical literature, including reports, theses, books and current research. The challenges and lessons learnt are discussed.
Does language matter? A case study of epidemiological and public health journals, databases and professional education in French, German and Italian
Authors: Baussano Iacopo , Brzoska Patrick , Fedeli Ugo , Larouche Claudia , Razum Oliver , Fung Isaac C-H
Published: September 2008

Epidemiology and public health are usually context-specific. Journals published in different languages and countries play a role both as sources of data and as channels through which evidence is incorporated into local public health practice. Databases in these languages facilitate access to relevant journals, and professional education in these languages facilitates the growth of native expertise in epidemiology and public health. However, as English has become the lingua franca of scientific communication in the era of globalisation, many journals published in non-English languages face the difficult dilemma of either switching to English and competing internationally, or sticking to the native tongue and having a restricted circulation among a local readership. This paper discusses the historical development of epidemiology and the current scene of epidemiological and public health journals, databases and professional education in three Western European languages: French, German and Italian, and examines the dynamics and struggles they have today.
Association of MUTYH Gln324His and APEX1 Asp148Glu with colorectal cancer and smoking in a Japanese population
Authors: Kasahara Mayumi , Osawa Kayo , Yoshida Kana , Miyaishi Aiko , Osawa Yasunori , Inoue Natsuko , Tsutou Akimitsu , Tabuchi Yoshiki , Tanaka Kenichi , Yamamoto Masahiro , Shimada Etsuji , Takahashi Juro
Published: September 2008

Background

Genetic polymorphisms of DNA repair enzymes may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interactions between polymorphisms of repair genes and tobacco smoking in colorectal cancer.

Methods

The case-control study involved sixty-eight colorectal cancer patients and 121 non-cancer controls divided into non-smokers and smokers according to pack-years of smoking. The genetic polymorphisms of DNA repair enzymes,OGG1 Ser326Cys, MUTYH Gln324His, APEX1 Asp148Glu and XRCC1 Arg399Gln, were examined using PCR-RFLP.

Results

The MUTYH Gln324His showed strong significant associations with a risk of colorectal cancer (crude odds ratio [OR] 3.30, 95% confidence interval [95%CI] 1.44–7.60, p = 0.005; adjusted OR3.53, 95%CI 1.44–8.70, p = 0.006). The ORs for the APEX1 Asp148Glu were statistically significant (crude OR 2.69, 95%CI 1.45–4.99, p = 0.002; adjusted OR 2.33, 95%CI 1.21–4.48, p = 0.011). The ORs for the MUTYH Gln324His and the APEX1 Asp148Glu were statistically significant for colon cancer (adjusted OR 3.95, 95%CI 1.28–12.20, p = 0.017 for MUTYH Gln324His ; adjusted OR 3.04, 95%CI 1.38–6.71, p = 0.006 for APEX1 Asp148Glu). The joint effect of tobacco exposure and the MUTYH Gln324His showed a significant association with colorectal cancer risk in non-smokers (adjusted OR 4.08, 95%CI 1.22–13.58, p = 0.022) and the APEX1 Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95%CI 1.80–13.99, p = 0.002). However, the distributions of OGG1 Ser326Cys and XRCC1 Arg399Gln were not associated with a colorectal cancer risk.

Conclusion

Our findings suggest that the MUTYH Gln324His and the APEX1 Asp148Glu constitutes an increased risk of colorectal cancer, especially colon cancer. The MUTYH Gln324His is strongly associated with colorectal cancer susceptibility in never smoking history, whereas the APEX1 Asp148Glu genotype constitutes an increased risk of colorectal cancer when accompanied by smoking exposure.
Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression
Authors: Hayashi Masaya , Muneta Takeshi , Ju Young-Jin , Mochizuki Tomoyuki , Sekiya Ichiro
Published: September 2008

Introduction

We investigated the ability of a weekly intra-articular injection of bone morphogenetic protein (BMP)-7 to prevent osteoarthritis in rabbits with anterior cruciate ligament transections.

Methods

First, 36 knee joints were randomly divided into four groups: 50, 500, 5,000 ng BMP-7, and control. Knee cartilage was evaluated at 4, 8, and 12 weeks. Then, in order to control for individual differences, 500 ng BMP-7 was injected into one knee and phosphate-buffered saline (PBS) into the other, and the two knees were compared at 4, 8, and 12 weeks (n = 5). For pharmacokinetic analysis, cartilage was harvested at 1 hour and 1, 2, 4, and 7 days after knee injection of 500 ng BMP-7 or PBS (n = 3).

Results

Histological scores in the 500 and 5,000 ng BMP-7 groups were significantly better than those in the other groups at 12 weeks. Matched pair analysis demonstrated that both macroscopic and histological scores in the 500 ng BMP-7 group were better than those in the control group. Immunohistochemical analysis revealed higher BMP-7 expression by chondrocytes in the BMP-7 injected knees. Histology of whole knee and quantitative micro computed tomography analysis showed that weekly injections of 500 ng BMP-7 did not induce synovial fibrosis, ectopic bone, or osteophyte formation. As detected by enzyme-linked immunosorbent assay, BMP-7 concentration in the cartilage tissue was still higher in the BMP-7 treated group 7 days after the injection.

Conclusions

Weekly intra-articular injections of BMP-7 inhibited progression of osteoarthritis. Obvious adverse effects were not observed. BMP-7 concentration and expression in cartilage were still higher 7 days after injection.
Gene products of chromosome 11q and their association with CCND1gene amplification and tamoxifen resistance in premenopausal breast cancer
Authors: Lundgren Katja , Holm Karolina , Nordenskjöld Bo , Borg Åke , Landberg Göran
Published: September 2008

Introduction

The amplification event occurring at chromosome locus 11q13, reported in several different cancers, includes a number of potential oncogenes. We have previously reported amplification of one such oncogene, namely CCND1, to be correlated with an adverse effect of tamoxifen in premenopausal breast cancer patients. Over-expression of cyclin D1 protein, however, confers tamoxifen resistance but not a tamoxifen-induced adverse effect. Potentially, co-amplification of an additional 11q13 gene, with a resulting protein over-expression, is required to cause an agonistic effect. Moreover, during 11q13 amplification a deletion of the distal 11q region has been described. In order to assess the potential impact of the deletion we examined a selected marker for this event.

Method

Array comparative genomic hybridization analysis was employed to identify and confirm changes in the gene expression of a number of different genes mapping to the 11q chromosomal region, associated with CCND1 amplification. The subsequent protein expression of these candidate genes was then examined in a clinical material of 500 primary breast cancers from premenopausal patients who were randomly assigned to either tamoxifen or no adjuvant treatment. The protein expression was also compared with gene expression data in a subset of 56 breast cancer samples.

Results

Cortactin and FADD (Fas-associated death domain) over-expression was linked to CCND1 amplification, determined by fluorescence in situ hybridization, but was not associated with a diminished effect of tamoxifen. However, deletion of distal chromosome 11q, defined as downregulation of the marker Chk1 (checkpoint kinase 1), was associated with an impaired tamoxifen response, and interestingly with low proliferative breast cancer of low grade. For Pak1 (p21-activated kinase 1) and cyclin D1 the protein expression corresponded to the gene expression data.

Conclusions

The results indicate that many 11q13 associated gene products are over-expressed in conjunction with cyclin D1 but not linked to an agonistic effect of tamoxifen. Finally, the deletion of distal 11q, linked to 11q13 amplification, might be an important event affecting breast cancer outcome and tamoxifen response.
Neurotoxic effects of ecstasy on the thalamus
Authors: de Win Maartje M. L. , Jager Gerry , Booij Jan , Reneman Liesbeth , Schilt Thelma , Lavini Cristina , Olabarriaga Sílvia D. , Ramsey Nick F. , den Heeten Gerard J. , van den Brink Wim
Published: September 2008

Background

Neurotoxic effects of ecstasy have been reported, although it remains unclear whether effects can be attributed to ecstasy, other recreational drugs or a combination of these.

Aims

To assess specific/independent neurotoxic effects of heavy ecstasy use and contributions of amphetamine, cocaine and cannabis as part of The Netherlands XTC Toxicity (NeXT) study.

Method

Effects of ecstasy and other substances were assessed with1H-magnetic resonance spectroscopy, diffusion tensor imaging, perfusion weighted imaging and [123I]2β-carbomethoxy-3β-(4-iodophenyl)-tropane ([123I]β-CIT) single photon emission computed tomography (serotonin transporters) in a sample (n=71) with broad variation in drug use, using multiple regression analyses.

Results

Ecstasy showed specific effects in the thalamus with decreased [123I]β-CIT binding, suggesting serotonergic axonal damage; decreased fractional anisotropy, suggesting axonal loss; and increased cerebral blood volume probably caused by serotonin depletion. Ecstasy had no effect on brain metabolites and apparent diffusion coefficients.

Conclusions

Converging evidence was found for a specific toxic effect of ecstasy on serotonergic axons in the thalamus.