bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiplex_QA: An exploratory quality assessment tool for multiplexed electrophoretic assays
Authors: Duewer David L. , Butler John M.
Published: September 2006

Multiplex_QA is a data analysis tool for visualizing short‐ and long‐term changes in the performance of multiplexed electrophoretic assays, particularly the commercial short tandem repeat (STR) kits used by the human forensic identity community. A number of quality metrics are calculated from the signal collected for the internal size standard included in nearly all multiplex assays. These quality metrics are related to the signal intensity, symmetry, retention, resolution, and noise of data collected by capillary electrophoresis systems. Interlocking graphical displays enable the identification of changes in the quality metrics with time, evaluation of relationships among the metrics, and detailed examination of electropherographic features of particularly interesting analyses. While primarily intended for exploring which metrics are most useful for documenting data quality, the current version of the tool is sufficiently robust for use by forensic scientists with an interest in data analysis and access to a fast desktop computer.
A robust cross‐linked polyacrylamide coating for microchip electrophoresis of dsDNA fragments
Authors: Lu Joann J. , Liu Shaorong
Published: September 2006

Surface derivatization plays an important role in microchip electrophoresis. It not only enhances the resolution, but also improves the reproducibility. So far, the most popularly used derivatization method for glass microchannels is to covalently attach a layer of linear polyacrylamide (LPA) to the channel surfaces. However, LPA coating has two problems: incomplete coverage and limited lifetime. To address these issues, we have recently developed a cross‐linked polyacrylamide (CPA) derivatization protocol and demonstrated it for high‐resolution protein separations by CIEF, CGE, and CZE. In this report, we used this protocol to coat microchip channels and exhibited the reliability and robustness of CPA coating for microchip electrophoresis of DNA molecules. dsDNA fragments were used as our test samples. High resolutions were obtained for fragments ranging from 100 bp to 10 kpb. After more than 800 runs, the CPA‐coated microchannels still performed well and comparable resolutions were maintained throughout these runs.
A precise mRNA quantification method using CE‐based SSCP
Authors: Park Young Seoub , Chu Hun Su , Hwang Seung Ha , Seo Jong Hyuk , Choi Cha Yong , Jung Gyoo Yeol
Published: September 2006

Even though mRNA quantification provides significant information for biological analysis, current methods such as Northern blot analysis and real‐time PCR are known to be laborious and lacking in precision. In this study, we demonstrate a new precise mRNA quantification method using CE based on SSCP (CE‐SSCP) coupled with reverse transcription. mRNA samples could be simply analyzed for the quantification directly with reverse transcript obtained from a single reaction. This helps to avoid considerable errors generated by a series of the tedious manual steps. Also, unlike real‐time PCR, reverse transcripts can be directly quantified by CE‐SSCP in this method without further data estimation. Reproducibility and accuracy of CE‐SSCP for mRNA quantification was examined using enhanced green fluorescent protein (eGFP) mRNA transcribedin vitro. Specific reverse transcription primer was determined for the accurate quantification of eGFP mRNA from total RNA obtained from the recombinantEscherichia coli. Using elongation factor Tu mRNA as an internal standard, it was shown that sample‐to‐sample variation could be minimized. Expression kinetics at both mRNA level and protein level was studied and the potential of CE‐SSCP in expression analysis was demonstrated by comparison with the eGFP activity assay.
Scale‐up development of high‐performance polymer matrix for DNA sequencing analysis
Authors: Wan Fen , He Weidong , Zhang Jun , Ying Qicong , Chu Benjamin
Published: September 2006

Linear polyacrylamide (LPA) has been widely used as a replaceable separation matrix in CE. An increase in the molecular weight of the separation medium favors the separation of larger DNA fragments. In order to obtain ultrahigh‐molecular‐weight (UHMW) LPA, a “frozen” method was developed to synthesize the LPA homopolymer. This approach has three major advantages when compared with other existing routes of LPA synthesis: (i) long LPA chains could be obtained easily, with their average molecular weight (MW) being in the high 10 MDa range; (ii) the desired MW could be adjusted over a broad range by controlling the temperature and the concentration of initiators during synthesis; (iii) the product solution contains only a tiny amount of impurity besides the solvent and LPA. Both static and dynamic laser light scattering measurements were carried out to characterize the synthesized LPA in the buffer solution. The DNA sequencing matrix prepared from LPA using this method was studied and the results were compared with the newly developed commercial product POP7 from Applied Biosystems. It should be noted that this approach can be applied to synthesize other water‐soluble polymers, resulting in UHMW products because the chain transfer constant is smaller at lower temperatures.
The relationship between selflessness levels and the severity of anorexia nervosa symptomatology
Authors: Bachner‐Melman Rachel , Zohar Ada H. , Ebstein Richard P. , Bachar Eytan
Published: September 2006

This study examined the relationship of selflessness, the tendency to ignore one's own needs and interests and serve others, to the severity of anorexia nervosa (AN) symptomatology. Measures of selflessness, perfectionism, obsessiveness, self‐esteem, disordered eating, body dissatisfaction, drive for thinness and general symptomatology were completed by 205 women with a history of AN (ANh) in various stages of illness and recovery (42 ill, 90 partially recovered and 78 recovered) and 238 female controls. The ANh women's scores on the Selflessness Scale declined significantly as the severity of current pathology decreased. Recovered anorexics scored similarly to female controls. Assertion of one's own needs and interests may be an integral component of recovery from AN, and should be emphasized in therapy. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.
Seeing the NICE side of cost‐effectiveness analysis: a qualitative investigation of the use of CEA in NICE technology appraisals
Authors: Bryan Stirling , Williams Iestyn , McIver Shirley
Published: September 2006

Resource scarcity is the raison d'être for the discipline of economics. Thus, the primary purpose of economic analysis is to help decision‐makers when addressing problems arising due to the scarcity problem. The research reported here was concerned with how cost‐effectiveness information is used by the National Institute for Health & Clinical Excellence (NICE) in national technology coverage decisions in the UK, and how its impact might be increased. The research followed a qualitative case study methodology with semi‐structured interviews, supported by observation and analysis of secondary sources. Our research highlights that the technology appraisal function of NICE represents an important progression for the UK health economics community: new cost‐effectiveness work is commissioned for each technology and that work directly informs national health policy. However, accountability in policy decisions necessitates that the information upon which decisions are based (including cost‐effectiveness analysis, CEA) is accessible. This was found to be a serious problem and represents one of the main ongoing challenges. Other issues highlighted include perceived weaknesses in analysis methods and the poor alignment between the health maximisation objectives assumed in economic analyses and the range of other objectives facing decision‐makers in reality. Copyright © 2006 John Wiley & Sons, Ltd.
Multicenter phase II study of CyclOBEAP regimen for elderly patients with poor‐prognosis aggressive lymphoma
Authors: Niitsu Nozomi , Okamoto Masataka , Kohori Mika , Aoki Sadao , Miura Ikuo , Hirano Masami
Published: September 2006

We treated elderly patients (65–69 years) who had aggressive lymphoma with the CyclOBEAP regimen, and we studied the safety and efficacy of this treatment. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin 40 mg/m2 was given every 2 weeks in combination with either cyclophosphamide 800 mg/m2 or etoposide 70 mg/m2 qd × 3. During the alternate weeks, non‐myelosuppressive vincristine 1.0 mg/m2 was given either with bleomycin 10 mg/m2 or alone. Prednisolone 40 mg/m2 was administered daily for three 14‐day periods during weeks 1–2, 5–6 and 9–10. There were 51 eligible patients. A complete response was achieved in 42 patients (82%). The 5‐year overall survival (OS) rate was 60.6% and progression‐free survival (PFS) rate was 51.8%. WHO grade 4 neutropenia was observed in 32 patients and thrombocytopenia in 8 patients. We showed that the CyclOBEAP regimen can be safely used in the treatment of aggressive lymphoma in elderly patients and it achieved a high rate of remission. Copyright © 2006 John Wiley & Sons, Ltd.
Biodegradable polyurethane cancellous bone graft substitutes in the treatment of iliac crest defects
Authors: Gogolewski Sylwester , Gorna Katarzyna
Published: September 2006

Porous scaffolds were produced from newly designed biodegradable, segmented aliphatic polyurethanes of various chemical compositions and hydrophilic‐to‐hydrophobic segment ratios. The scaffolds were implanted into monocortical defects in the iliac crest of healthy sheep for 6 months. The resected cortex was not repositioned. The ilium defects, which were not implanted with polyurethane scaffolds, were used as controls. In none of the control defects was there bone regeneration at the time of euthanasia. The defects implanted with porous scaffolds from polyurethanes were healed to varying extents with cancellous bone. The structure of the regenerated cancellous bone was radiographically denser than the structure of native bone. New bone that was formed in the scaffolds with a higher amount of hydrophilic component contained more calcium phosphate deposit than the bone formed in the scaffolds with a lower amount of the hydrophilic component. There was no new cortex formed over the defect, but a thin layer of soft tissue covered the newly formed cancellous bone. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Conjugates of poly(DL‐lactide‐co‐glycolide) on amino cyclodextrins and their nanoparticles as protein delivery system
Authors: Gao Hui , Wang Yi‐Nong , Fan Yun‐Ge , Ma Jian‐Biao
Published: September 2006

Poly(DL‐lactide‐co‐glycolide) (PLG) was chemically conjugated on two amino cyclodextrins, mono(6‐(2‐aminoethyl)amino‐6‐deoxy)‐β‐cyclodextrin and ethylenediamino bridged bis(β‐cyclodextrin), to afford novel amphiphilic conjugates. Those conjugates were then characterized with infrared spectrometry (IR), proton nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). A repeat‐nanoprecipitation (RP‐NP) method was also developed to fabricate the nanoparticles of the conjugates with a water‐soluble model protein, bovine serum albumin (BSA). At the end of RP‐NP process, the availability of BSA was over 80% while the entrapment efficiency was 40–50% for each nanoprecipitation. The nanoparticles were rigid and spherical with diameters of 110–180 nm determined by transmission electron microscope (TEM), atomic force microscopy (AFM) and particle size analyzer. Nanoparticles possessed good steric stability during freeze‐drying and resuspensions due to the existence of cyclodextrins corona. Interactions between BSA and the conjugates in the nanoparticles were then elucidated with IR experiments. About 25% BSA adsorbed on the surface of nanoparticles due to the interaction and was easy to release in the first day. The release of BSA from the nanoparticles was in three phases: a burst effect in the first day, a followed plateau in about a week, and a sustained release of the protein over 14 days. By changing the lactide/glycolide ratio, the degradation time of the conjugates and the release rate of BSA could be controlled. The loss of CDs content was faster than that of overall Mw during degradation since CDs formed outer corona of the nanoparticles. Both the novel biomaterials and the nanosphere fabrication technique contributed to the maintenance of protein structure. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
PSM/SH2‐B distributes selected mitogenic receptor signals to distinct components in the PI3‐kinase and MAP kinase signaling pathways
Authors: Deng Youping , Xu Hu , Riedel Heimo
Published: September 2006

The Pro‐rich, PH, and SH2 domain containing mitogenic signaling adapter PSM/SH2‐B has been implicated as a cellular partner of various mitogenic receptor tyrosine kinases and related signaling mechanisms. Here, we report in a direct comparison of three peptide hormones, that PSM participates in the assembly of distinct mitogenic signaling complexes in response to insulin or IGF‐I when compared to PDGF in cultured normal fibroblasts. The complex formed in response to insulin or IGF‐I involves the respective peptide hormone receptor and presumably the established components leading to MAP kinase activation. However, our data suggest an alternative link from the PDGF receptor via PSM directly to MEK1/2 and consequently also to p44/42 activation, possibly through a scaffold protein. At least two PSM domains participate, the SH2 domain anticipated to link PSM to the respective receptor and the Pro‐rich region in an association with an unidentified downstream component resulting in direct MEK1/2 and p44/42 regulation. The PDGF receptor signaling complex formed in response to PDGF involves PI 3‐kinase in addition to the same components and interactions as described for insulin or IGF‐I. PSM associates with PI 3‐kinase via p85 and in addition the PSM PH domain participates in the regulation of PI 3‐kinase activity, presumably through membrane interaction. In contrast, the PSM Pro‐rich region appears to participate only in the MAP kinase signal. Both pathways contribute to the mitogenic response as shown by cell proliferation, survival, and focus formation. PSM regulates p38 MAP kinase activity in a pathway unrelated to the mitogenic response. J. Cell. Biochem. 100: 557–573, 2007. © 2006 Wiley‐Liss, Inc.
Immediate early gene IEX‐1 induces astrocytic differentiation of U87‐MG human glioma cells
Authors: You Fukka , Osawa Yosuke , Hayashi Shin‐ichiro , Nakashima Shigeru
Published: September 2006

The immediate early response gene IEX‐1 is involved in the regulation of apoptosis and cell growth. In order to increase the apoptotic sensitivity to chemotherapeutic drugs and γ‐ray, we attempted to establish U87‐MG human glioma cell line expressing IEX‐1. Unexpectedly, however, transfection of IEX‐1 into U87‐MG glioma cells resulted in morphological changes to astrocytic phenotype and increase in glial differentiation marker proteins, S‐100 and glial fibrillary acidic protein (GFAP). Glial cell differentiation was used to examine in rat C6 glioma cell line, since this cell line express astrocytic phenotypes by increase in intracellular cAMP concentration. Stimulation of human U87‐MG glioma cells by membrane‐permeable dibutyryl cAMP (dbcAMP) not only elicited their morphological changes but also induced expression of IEX‐1 as well as S‐100 and GFAP. H89, an inhibitor of protein kinase A (PKA), blocked dbcAMP‐induced morphological changes of U87‐MG cells and expression of IEX‐1. In contrast, morphological changes and expression of S‐100 and GFAP induced by IEX‐1 were not affected by H89. Morphological changes induced by dbcAMP were totally abolished by functional disruption of IEX‐1 expression by anti‐sense RNA. These results indicate that IEX‐1 plays an important role in astrocytic differentiation of human glioma cells and that IEX‐1 functions at downstream of PKA. J. Cell. Biochem. 100: 256–265, 2007. © 2006 Wiley‐Liss, Inc.
Upregulations of Gata4 and oxytocin receptor are important in cardiomyocyte differentiation processes of P19CL6 cells
Authors: Uchida Shizuka , Fuke Satoshi , Tsukahara Toshifumi
Published: September 2006

Oxytocin induces P19 cells to differentiate into cardiomyocytes possibly through the oxytocin/oxytocin receptor system. We added oxytocin to the growth medium of P19CL6, a subline of P19, but they did not differentiate into cardiomyocytes as indicated by RT‐PCR and Western blotting results. During the cardiac commitment time of P19CL6 cells, the mRNA expression levels of the oxytocin receptor were upregulated by the addition of oxytocin as well as DMSO, but an upregulation of Gata4 expression levels was only observed for the cells induced by DMSO. The in silico analysis of the upstream sequence of the oxytocin receptor predicted putative binding sites for Gata4 and Nkx2.5. These results suggest that upregulations of the oxytocin receptor and Gata4 are important for cardiomyocyte differentiation processes. J. Cell. Biochem. 100: 629–641, 2007. © 2006 Wiley‐Liss, Inc.
Lower extremity arterial thrombosis following sonographically guided thrombin injection of a femoral pseudoaneurysm
Authors: Stawicki Stanislaw P. , Hoey Brian A.
Published: September 2006

Sonographically guided percutaneous thrombin injection is a minimally invasive and highly successful treatment of arterial pseudoaneurysms. Despite a very low complication rate, several severe arterial thrombotic events have been reported following thrombin injection of pseudoaneurysms. Native arterial thrombosis, though recognized as a severe complication of thrombin injection, has not been well described in the literature. We report a case of successful surgical management of arterial thrombosis after percutaneous thrombin injection of a femoral artery pseudoaneurysm in a 69‐year‐old woman. The pathophysiology, risk factors, diagnosis, and treatment options for this complication are discussed. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound, 2006.
Character strengths in organizations
Authors: Peterson Christopher , Park Nansook
Published: September 2006

Character refers to qualities within individuals that lead them to desire and to pursue the good. We propose that strengths of character are a neglected but critically important resource for organizations. Character matters because it leads people to do the right thing, and the right thing can be productive and profitable. Copyright © 2006 John Wiley & Sons, Ltd.
Phase-locking in fiber laser arrays
Authors: Kireev A N , Graf Th , Weber H P
Published: September 2006

Evanescently coupled fiber laser arrays are investigated as a powerful and compact all-solid-state source of coherent radiation for high-power applications. The micro-structured multiple-core design provides a novel power scaling technique and overcomes traditional restrictions of single-core fiber lasers. The increased bending loss stability and the mode selectivity of the trigonal array was proven for the first time on the basis of a rigorous vector coupled-mode theory. Phase-locking in the in-phase supermode is predicted as a combined effect of the strong evanescent coupling and the bending loss mode selection. In its simplest configuration with three cores in a trigonal arrangement, a 2.79 fold power scaling is expected with an almost diffraction limited beam quality.
Relation of cerebral small‐vessel disease and brain atrophy to mild parkinsonism in the elderly
Authors: Reitz Christiane , Trenkwalder Claudia , Kretzschmar Konrad , Roesler Andreas , v. Eckardstein Arnold , Berger Klaus
Published: September 2006

The association between cerebral small‐vessel disease, brain atrophy, and the risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective of this study is to examine the effect of lacunar brain infarcts, cerebral white matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This study is a cross‐sectional community‐based cohort study comprising 268 subjects, 65 to 83 years of age, residing in the Augsburg region of southern Germany, and without contraindications for magnetic resonance imaging (MRI) of the brain. Main outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts, and cortical atrophy determined using a standardized MRI protocol developed for the Rotterdam Scan Study and an established rating scale. MPS, assessed in a standardized neurological examination and based on the Unified Parkinson's Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical white matter lesions were associated with an elevated risk of resting tremor. More severe cortical atrophy was related to an increased risk of rigidity and bradykinesia. In a linear regression analysis relating each individual MRI measurement with the severity of MPS, the number of lacunar brain infarcts and the degree of brain atrophy were correlated with the severity of resting tremor, whereas the size of subcortical and periventricular WMLs was correlated with the severity of rigidity. A higher degree of brain atrophy was associated with increased severity of either cardinal sign. In our study, presence and volume of lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with the risk as well as severity of MPS. Determining the presence of these brain changes using brain imaging might contribute to identify persons at risk for MPS. © 2006 Movement Disorder Society
ABO incompatible stem cell transplantation in children does not influence outcome
Authors: Helming A.M. , Brand A. , Wolterbeek R. , van Tol M.J.D. , Egeler R.M. , Ball L.M.
Published: September 2006

Background

Although delayed red cell engraftment and/or hemolysis have been thoroughly documented in association with ABO incompatibility between donor and recipient in patients undergoing hematopoietic stem cell transplantation (HSCT), there are no studies defining the general, long term clinical outcome in a large group of pediatric patients.

Methods

We undertook a retrospective single center analysis of children undergoing pediatric allogeneic stem cell transplantation to determine the influence of ABO donor/recipient incompatibility. Outcome was analyzed according to donor type and included survival, graft versus host disease (GvHD), relapse, days of infection, antibiotic use, transfusion requirement and duration of hospital stay.

Results

Two hundred and sixteen children (136 males; 80 females, aged 0–19) transplanted between January 1992 and December 2003 were included in the study. Indications for transplantation were hematological malignancies (n = 179) and aplastic conditions (n = 37). ABO compatibility was documented in 121 donor/recipient pairs. ABO incompatibility was documented in 95 donor/recipient pairs with 40 major, 40 minor and 15 bi‐directional incompatible pairs. ABO incompatibility did not influence survival rate (P = 0.3762), the incidence of GvHD (P = 0.253) or rate of relapse (P = 0.930). Recovery of leucocytes was influenced by ABO incompatibility (P = 0.0493), but the rate of infection, transfusion requirements and duration of hospital stay are not.

Conclusion

In the pediatric setting, ABO major and/or minor mismatch between donor and recipient did not significantly influence the outcome of HSCT. The choice of donor should be determined by the degree of HLA match and CMV status in preference to ABO blood group compatibility. Pediatr Blood Cancer 2007;49:313–317. © 2006 Wiley‐Liss, Inc.
Audit of staff knowledge of the correct management of hypoglycaemia in a busy teaching hospital
Authors: Furness C , Baker Helen , Hammersley M , Pal A
Published: September 2006

Hypoglycaemia is a common and potentially serious complication in the treatment of diabetes that is frequently encountered in a hospital environment. A basic understanding of the recognition and immediate treatment of a patient experiencing a hypoglycaemic episode is key to appropriate management. An audit of staff knowledge of appropriate treatment of a hypoglycaemic episode (using a simple questionnaire) was carried out in the John Radcliffe Hospital, Oxford, with the aim of comparing knowledge in area A (wards in the hospital where diabetes education and diabetes specialist nurse input are available) and area B (wards where these services are not yet in place). The mean questionnaire score in area A was 65.6% compared to 45% in area B. Thirty‐three percent of area A nursing staff had attended a diabetes education session in the last year; the mean score for nurses who had attended such a session was 86.7% compared to 62.8% for those who had not. These results have led us to conclude that knowledge was better in areas where diabetes support services are in place and in individuals who have received training. Area B represents a potential target for the implementation of such services, and the continued expansion of the diabetes specialist nurse department in the John Radcliffe is expected to lead to such changes. Currently we do not feel that all hypoglycaemic episodes are being managed appropriately and would encourage widespread education and training for all staff potentially involved in the care of these patients. Copyright © 2006 John Wiley & Sons, Ltd.
What education do people with type 1 diabetes want and how should we provide it?
Authors: Woodward A , Dawes S , Dolan D , Wallymahmed M
Published: September 2006

The National Service Framework advised that continuing education is an essential component of diabetes care and is the cornerstone of treatment for people with diabetes.

An education needs questionnaire was used to survey 100 people with type 1 diabetes attending consultant clinics in a north Liverpool teaching hospital. The aim of the survey was to obtain the views on patient education which would enable us to develop a new patient‐centred education programme.

The questionnaire was given to 100 consecutive people with type 1 diabetes attending both medical and nurse consultant clinics. Newly diagnosed people with diabetes under one year's duration were excluded. The questionnaire was divided into key areas including diabetes core topics, previous education, views on further education and open comments.

There were 95 (95%) completed questionnaires, 52 (55%) completed by women, and the mean (SD) age was 39±14 (range 17–82 years). Eighty‐four (88%) people remembered receiving previous education but 58 (61%) wanted further education on most of the listed topics.

As a result of this survey we have developed an education care pathway for people with newly diagnosed diabetes which will provide initial education and self‐care skills. The next step is to design a more advance programme, for all interested type 1 patients to develop further self‐management skills, with specific information on microvascular and macrovascular disease. Copyright © 2006 John Wiley & Sons, Ltd.
Therapeutic profile of orphan medicines
Authors: de Barros Carla Maria Teixeira , Papoila Ana Luísa
Published: September 2006

Purpose

To characterise the therapeutic profile of orphan medicines.

Materials and Methods

A cross‐sectional study was performed during 2 months in a convenience sample of seven hospital pharmacy services, in the region of Lisbon. Data were collected, from pharmaceutical service's records.

Results

A total of 18 orphan medicines, were dispensed to 355 patients with rare diseases. Most patients were adults (76.4%). Premature and neonates accounted with 50.0% of the paediatric patients. Differences were not found between the proportion of male and female patients across age groups (p = 0.762). Only 18.3% were inpatients. A high proportion of paediatric inpatients (58.3%) were seen in relation to adult inpatients (5.9%) (p = 0.001).

In general, anti‐neoplastic and immunomodulating agents for rare cancers were the most frequent dispensed medicines (51.3%). In relation to paediatrics, Caffeine Citrate for primary apnoea of premature newborns had the higher frequency distribution (57.1%). Five (71.4%) medicines dispensed for paediatrics, do not have market authorisation and the remaining (28.6%) were used off‐label.

For pulmonary arterial hypertension 19 of 27 patients (70.3%) were treated with Bosentan. According to evidence‐based clinical practice guidelines, Bosentan has a good level of evidence and substantial benefit: grade of recommendation A.

Conclusions

Most orphan medicines dispensed to paediatrics and adults were not licensed.

A special pharmacovigilance program and a risk management plan through the entire life cycle should be implemented, towards effectiveness and safety of orphan medicines. Copyright © 2006 John Wiley & Sons, Ltd.
Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000–2004
Authors: Divac Nevena , Toševski Dušica Lečić , Babić Dragan , Djurić Dušan , Prostran Milica , Samardžić Ranka
Published: September 2006

Purpose

To investigate the trends in psychiatric drugs utilization in Serbia and Montenegro over the 5‐years period (2000–2004).

Materials and methods

The wholesale data issued by the manufacturers or distributors were used. Also, the lists of drugs used from the Institute of Mental Health (institution which provides primary, secondary and tertiary psychiatric care) were used to corroborate the wholesale data. The utilization of drugs in general population was calculated using ATC/DDD methodology, and was expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The utilization of drugs in the Institute of Mental Health was calculated from the hospital pharmacy records and was expressed as the number of DDDs per 100 bed‐days. The statistics was performed using standard statistical methods.

Results

The general consumption of psychiatric drugs in Serbia and Montenegro significantly increased during the 2000–2004 period (from 45.1 DDD/1000 inhabitants/day in 2000 to 69.1 DDD/1000 inhour/day in 2004). The general utilization of anxiolytic/hypnotic drugs surged significantly, but the inhospital use remained rather stable. The most prominent changes were noted in the utilization of antidepressants, which doubled in that period, both in general and inhospital settings. Among antipsychotics in general population, there is a significant increase in the utilization of clozapine. In inhospital setting, there is a significant increase of total utilization of antipsychotic drugs, but this is also mainly on the account of atypicals.

Conclusions

The total consumption of psychiatric drugs significantly increased. The utilization of anxiolytic/hypnotic drugs in 2004 reached 60 DDDs/1000 inhabitants/day, which is in collision with the trend in developed countries. It is necessary to form national guidelines for prescribing anxiolytic/hypnotic drugs, in order to rationalize their use. More favourable is the antidepressant (SSRIs in particular) and atypical antipsychotic drugs utilization increase. Copyright © 2006 John Wiley & Sons, Ltd.
Insecure attachment and personality disorder: a twin study of adults
Authors: Crawford Thomas N. , John Livesley W. , Jang Kerry L. , Shaver Phillip R. , Cohen Patricia , Ganiban Jody
Published: September 2006

This study used 239 twin pairs from a volunteer community sample to investigate how anxious and avoidant attachment are related to personality disorder (PD). Factor analysis showed that self‐reported anxious attachment and 11 PD scales from the Dimensional Assessment of Personality Problems loaded onto one factor (emotional dysregulation), and avoidant attachment and four PD scales loaded onto a second factor (inhibitedness). Biometric models indicated that 40% of the variance in anxious attachment was heritable, and 63% of its association with corresponding PD dimensions was attributable to common genetic effects. Avoidant attachment was influenced by the shared environment instead of genes. Correlations between avoidance and corresponding PD dimensions were attributable to experiences in the nonshared environment that influenced both variables. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of nano‐SiC dispersion on thermoelectric properties of Bi2Te3 polycrystals
Authors: Li Jing‐Feng , Liu Jing
Published: September 2006

Nano‐SiC dispersed Bi2Te3 was synthesized by mechanical alloying (MA) followed by spark plasma sintering (SPS). The effects of SiC dispersion on the thermoelectric properties of the SPS‐sintered Bi2Te3 alloys were investigated. The results revealed that SiC dispersion in the Bi2Te3 matrix increased the absolute value of Seebeck coefficient. Although the electrical resistance was increased somewhat, Bi2Te3 with 0.1 wt% SiC showed a higher power factor than Bi2Te3 without SiC. Because the dispersion of SiC nano‐particles reduced the thermal conductivity at the same time, 0.1 wt% (∼0.24 vol% SiC) addition of SiC nano‐particles increased the figure of merit of Bi2Te3 by 18%. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Magnetization reversal in micron‐sized stripes of epitaxial (110) YFe2 films
Authors: Wang K. , Martin K. N. , Morrison C. G. , Ward R. C. C. , Bowden G. J. , de Groot P. A. J.
Published: September 2006

Arrays of micron‐sized stripes of epitaxial (110) Laves phase YFe2 films have been fabricated using a UV laser direct write system and etching process. The magnetization reversal of the stripe arrays in the sample plane is investigated by magneto‐optical Kerr magnetometry. The measured MO Kerr hysteresis loops reveal that a uniaxial magnetic anisotropy can be induced in the materials by the shape of the stripes. The easy axis is found to be rigidly confined parallel to the length axis of the stripe and the hard axis is perpendicular to it. This is correlated with the induced uniaxial anisotropy which dominates the intrinsic four‐fold magnetocrystalline anisotropy of the cubic Laves phase structure. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Incorporating prior information via shrinkage: a combined analysis of genome‐wide location data and gene expression data
Authors: Xie Yang , Pan Wei , Jeong Kyeong S. , Khodursky Arkady
Published: September 2006

Transcriptional control is a critical step in regulation of gene expression. Understanding such a control on a genomic level involves deciphering the mechanisms and structures of regulatory programmes and networks. A difficulty arises due to the weak signal and high noise in various sources of data while most current approaches are limited to analysis of a single source of data. A natural alternative is to improve statistical efficiency and power by a combined analysis of multiple sources of data. Here we propose a shrinkage method to combine genome‐wide location data and gene expression data to detect the binding sites or target genes of a transcription factor. Specifically, a prior ‘non‐target’ gene list is generated by analysing the expression data, and then this information is incorporated into the subsequent binding data analysis via a shrinkage method. There is a Bayesian justification for this shrinkage method. Both simulated and real data were used to evaluate the proposed method and compare it with analysing binding data alone. In simulation studies, the proposed method gives higher sensitivity and lower false discovery rate (FDR) in detecting the target genes. In real data example, the proposed method can reduce the estimated FDR and increase the power to detect the previously known target genes of a broad transcription regulator, leucine responsive regulatory protein (Lrp) inEscherichia coli. This method can also be used to incorporate other information, such as gene ontology (GO), to microarray data analysis to detect differentially expressed genes. Copyright © 2006 John Wiley & Sons, Ltd.
Twin reversed arterial perfusion: fetoscopic laser coagulation of placental anastomoses or the umbilical cord
Authors: Hecher K. , Lewi L. , Gratacos E. , Huber A. , Ville Y. , Deprest J.
Published: September 2006

Objective

To assess the feasibility and outcome of fetoscopic laser coagulation in pregnancies with twin reversed arterial perfusion (TRAP) sequence.

Methods

In a prospective multicenter study, percutaneous fetoscopic laser coagulation of placental anastomoses (n = 18) or the umbilical cord of the acardiac twin (n = 42) was performed in 60 consecutive pregnancies at a median gestational age of 18.3 (range, 14.3–24.7) weeks under local or locoregional anesthesia.

Results

Vascular coagulation with arrest of blood flow was achieved in 82% (49/60) of cases by laser alone and in a further 15% (9/60) by laser coagulation in combination with bipolar forceps. The overall survival rate of the pump twin was 80% (48/60). Median gestational age at delivery was 37.4 (range, 23.7–41.4) weeks and the median interval between the procedure and delivery was 18.2 (range, 1.1–25.7) weeks. Median birth weight was 2720 (range, 540–3840) g. Preterm premature rupture of membranes before 34 weeks' gestation occurred in 18% (11/60) at a median of 62 (range, 1–102) days after the procedure. However, only two (3%) women delivered within 28 days of the procedure.

Conclusions

Fetoscopic laser coagulation of placental vascular anastomoses or the umbilical cord of the acardiac twin is an effective treatment of TRAP sequence, with a survival rate of 80%, and 67% of pregnancies with surviving pump twins going beyond 36 weeks' gestation without further complications. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.
Analysis of a biphase mark protocol with U
ppaal
and PVS
Authors: Vaandrager F. W. , de Groot A. L.
Published: September 2006

The biphase mark protocol is a convention for representing both a string of bits and clock edges in a square wave. The protocol is frequently used for communication at the physical level of the ISO/OSI hierarchy, and is implemented on microcontrollers such as the Intel 82530 Serial Communications Controller. An important property of the protocol is that bit strings of arbitrary length can be transmitted reliably, despite differences in the clock rates of sender and receiver (drift), variations of the clock rates (jitter), and distortion of the signal after generation of an edge. In this article, we show how the protocol can be modelled naturally in terms of timed automata. We use the model checker
Uppaal
to derive the maximal tolerances on the clock rates, for different instances of the protocol, and to support the general parametric verification that we formalized using the proof assistant PVS. Based on the derived parameter constraints we propose instances of BMP that are correct (at least in our model) but have a faster bit rate than the instances that are commonly implemented in hardware.
Copepods associated with Phallusia mamillata and Ciona intestinalis (Tunicata) in the area of Taranto (Ionian Sea, southern Italy)
Authors: Pastore Michele
Published: September 2006

Commensal and parasitic copepods (Arthropoda: Crustacea: Copepoda) of two common species of sea squirts, Phallusia mamillata and Ciona intestinalis have been investigated in the sea of Taranto (southern Italy).

A total of 2590 specimens of copepods were collected (five families, eight genera and 13 species). The sex ratio on 2582 specimens was 1228 males (47·56%) to 1354 females (52·44%).

The species were identified by the hosts in which they were found, their sex ratio host by host, and the specific variability and affinity analysis by means of the Sørensen index and the diversity index by means of the Shannon application.

Some species of copepods have been found for the first time as in Ciona intestinalis (Hermannella rostrata) and in Phallusia mamillata (Notodelphys canui, Doropygus pulex, Pachypygus gibber, Notopterophorus auritus, Lichomolgus albens, Hersiliodes latericia). The association Notodelphys canui–Doropygus pulex—Notopterophorus auritu–Lichomolgus albens is noted for the first time in the Mediterranean Sea.
Reproduction, seasonality, and copper toxicity in the coastal mysid Praunus flexuosus
Authors: Garnacho E. , Tyler P.A. , Peck L.S.
Published: September 2006

The reproductive biology, in response to temperature, season and copper, of a coastal population of opossum shrimps (Crustacea: Mysidacea) was measured. The reproductive pattern for Praunus flexuosus at Keyhaven (west Solent, southern England) has maximum activity in April and maximum reproductive effort in May/June. Increasing temperature decreases incubation time and the reproductive pattern is adapted to compensate for temperature effects. Reproduction was inhibited with copper exposure. Fertilization of the eggs did not occur in any copper treatment (5, 25, 75, 200 μg l−1 copper added). Brooding females exposed to copper suffered a high abortion rate. The inability to produce broods, appears to be a long-term effect, as specimens previously exposed to copper did not produce any broods after two weeks in seawater controls.
Morphometric variability in UK populations of the European lobster
Authors: Debuse Valerie J. , Addison Julian T. , Reynolds John D.
Published: September 2006

European lobsters (Homarus gammarus) were sampled from nine sites around the UK coast to determine whether populations could be differentiated on the basis of morphometric variability, and to relate this to depth and indices of population size at each site. Discriminant analysis indicated that exoskeleton damage was the only characteristic that could distinguish males between sites. In contrast, females were distinguished between sites on the basis of variation in exoskeleton damage, claw spines and rostrum teeth, which tended to be positively correlated to indices of population density. This study suggests that female morphology may respond more strongly than male morphology to local selection pressures, albeit in a limited capacity.
Interference competition in the intertidal mud snail Hydrobia ulvae: egestion rates revisited
Authors: Barnes R.S.K.
Published: September 2006

Egestion in the intertidal mud snail Hydrobia ulvae was investigated under conditions in which coprophagy did not occur, both in laboratory populations (comprising 11 experimental densities from 1000 to 120,000 ind m−2) and in a field population with an average density of 50,000 ind m−2 (24 test densities spanning the local range of <5000–>120,000 ind m−2). In contrast to an earlier study that suggested marked reduction in egestion rate in H. ventrosa as a consequence of interference competition, no such effect occurred in the natural population of H. ulvae, or in the experimental populations except at densities of at least 100,000 ind m−2. Neither did any significant increase in inactivity or movement off the experimental substrata occur with increasing density. These results are discussed in relation to resource limitation in natural densities of mud snails.
Reproductive biology of the intertidal sea cucumber Actinopyga mauritiana in the Solomon Islands
Authors: Ramofafia Christain , Byrne Maria , Battaglene Stephen
Published: September 2006

Over a four year period, gonad index, examination of gonad tubules, and histology were used to study the reproduction in the sea cucumber Actinopyga mauritiana. This species reproduced annually during the warmer months of the year in Solomon Islands. This annual reproductive cycle progressed through five maturity stages: recovery, growing, mature, partly-spawned and spent. The recovery stage (March–May) was marked by initiation of gametogenesis and coincided with decreasing day length. The growing stage (June–September) was characterized by development of gametes through to the mature stage (October–December). Spawning occurred October through December and coincided with increased water temperature and day length. Spent gonads (January–March) contained a few unspawned gametes or completely lacked gametes. Although A. mauritiana had annual reproduction, individuals lacking or having indeterminate gonads were present year-round. Macroscopic examination of gonad tubules after biopsy provides a practical tool for assessing maturity condition of broodstock in the field during the reproductive season.
Boat traffic affects the acoustic behaviour of Pacific humpback dolphins, Sousa chinensis
Authors: Van Parijs Sofie M. , Corkeron Peter J.
Published: September 2006

In this study, the indirect (i.e. boats not involved in dolphin viewing activities) impacts of boat traffic on the acoustic behaviour of Pacific humpback dolphins, Sousa chinensis, were assessed in Moreton Bay, Australia. Humpback dolphin acoustic behaviour is affected by transiting boat traffic. Boats' passage did not affect the rates at which dolphins produced click trains and burst pulse vocalizations. However, dolphins significantly increased their rate of whistling immediately after a boat moved through the area. This increase occurred only when boats were less than 1·5 km from the groups. Groups including mother–calf pairs showed an increase in whistles in response to boats' passage. Groups with no calves produced significantly fewer whistles. This evidence suggests that the noise from transiting vessels affects dolphins' group cohesion. Mother–calf pairs appear to be most disturbed by transiting vessels, and exhibit an increased need to re-establish vocal contact.
Benefits of swarming: mysids in larger swarms save energy
Authors: Ritz D.A. , Foster E.G. , Swadling K.M.
Published: September 2006

Mysids have previously been shown to consume oxygen at much lower rates when in a swarm (cohesive group in which individuals are evenly spaced but not polarized) than when in uncohesive small groups. Thus the swarm represents a strategy for conserving energy. In this study different swarm sizes of mysids were forced to perform escape responses by exposing them to jets of ammonium hydroxide, while measuring their oxygen uptake. Swarms of 200 individuals showed no significant difference in oxygen consumption with or without the ammonium treatment. In contrast, swarms of 100 showed a significant increase of around 45% oxygen uptake when exposed to ammonium. In conjunction with earlier demonstrations of increased feeding success and lower oxygen uptake when aggregated, this work clearly confirms the energetic benefits of being in a larger social group rather than a smaller one or remaining solitary.
Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters with major depression
Authors: KEILP JOHN G. , GORLYN MARIANNE , OQUENDO MARIA A. , BRODSKY BETH , ELLIS STEVEN P. , STANLEY BARBARA , JOHN MANN J.
Published: September 2006

Background. Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals.

Method. Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status.

Results. As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness.

Conclusions. Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk.