bluuebunny/crossref_metadata_2025 huggingface dataset:
A decision theoretic approach to combining information filtering
Authors: Binun Alexander , Shapira Bracha , Elovici Yuval
Published: October 2009

Purpose

The purpose of this paper is to present an extension to a framework based on the information structure (IS) model for combining information filtering (IF) results. The main goal of the framework is to combine the results of the different IF systems so as to maximise the expected payoff (EP) to the user. In this paper we compare three different approaches to tuning the relevance thresholds of individual IF systems that are being combined in order to maximise the EP to the user. In the first approach we set the same threshold for each of the IF systems. In the second approach the threshold of each IF system is tuned independently to maximise its own EP (“local optimisation”). In the third approach the thresholds of the IF systems are jointly tuned to maximise the EP of the combined system (“global optimisation”).

Design/methodology/approach

An empirical evaluation is conducted to examine the performance of each approach using two IF systems based on somewhat different filtering algorithms (TFIDF, OKAPI). Experiments are run using the TREC3, TREC6, and TREC7 test collections.

Findings

The experiments reveal that, as expected, the third approach always outperforms the first and the second, and that for some user profiles, the difference is significant. However, operational goals argue against global optimisation, and the costs of meeting these operational goals are discussed.

Research limitations/implications

One limitation is the assumption of independence of the IF systems: in real life systems usually use similar algorithms, so dependency might occur. The approach also tends to be examined with the assumption of dependency between systems.

Practical implications

The main practical implications of this study lie in the empirical proof that combination of filtering systems improves filtering results and the finding about the optimal combination methods for the different user profiles. Many filtering applications exist (e.g. spam filters, news personalisation systems, etc.) that can benefit from these findings.

Originality/value

The study presents and compares the contribution of three different combination methods of filtering systems to the improvement of filtering results It empirically shows the benefits of each method and draws important conclusions about the combination of filtering systems.
Moderator effects to internal audits' self‐efficacy and job involvement
Authors: Shih Kuang‐Hsun , Hsieh Yin‐Ru , Lin Binshan
Published: October 2009

Purpose

The purpose of this paper is to examine the relationship between two variables, self‐efficacy and job involvement, of internal auditors of companies. It also aims to explore its intervention on self‐efficacy and job involvement using organizational power as another variable.

Design/methodology/approach

A survey is conducted on 600 publicly listed Taiwanese companies that have subsidiaries in China. A total of 600 questionnaires are distributed to their internal auditors.

Findings

The results show that there is a significant and positive correlation between self‐efficacy and job involvement of internal auditors. Organizational control power does not exhibit intervening effects on self‐efficacy or job involvement.

Practical implications

This paper can offer a new perspective for managers of internal auditors because internal auditors' self‐efficacy can influence job involvement. Therefore, at the same time of supervising internal auditors, managers should not overlook the need to strengthen internal auditors' self‐efficacy.

Originality/value

Past discussions on internal auditors are widespread. However, the conclusion of this paper, which is focused on the exploration of the relationship between self‐efficacy and job involvement, can offer a different insight on the internal auditor domain.
Changes in microRNA expression levels correlate with clinicopathological features and prognoses in endometrial serous adenocarcinomas
Authors: Hiroki Eri , Akahira Jun‐ichi , Suzuki Fumihiko , Nagase Satoru , Ito Kiyoshi , Suzuki Takashi , Sasano Hironobu , Yaegashi Nobuo
Published: October 2009

This study aimed to determine the expression profiles of microRNAs (miRNAs) in endometrial serous adenocarcinoma and to examine the association between miRNA expression and clinical outcomes. Twenty‐one patients diagnosed with endometrial serous adenocarcinoma between January 2001 and December 2006 were enrolled. miRNA expression profiles were examined using miRNA microarray and qRT‐PCR. miRNA expression levels were correlated with clinicopathological variables and survival rates. A total of 120 miRNAs were differentially expressed in endometrial serous adenocarcinoma compared to normal endometria. Of these, 54 miRNAs were down‐regulated (>2‐fold), including miR‐101, miR‐10b*, miR‐152, and miR‐29b, and the remainder were up‐regulated (>2‐fold), including miR‐200a, miR‐200b, and miR‐205. Decreased expression of miR‐10b*, miR‐29b, and miR‐455‐5p was correlated with vascular invasion (P = 0.048, P = 0.013, and P = 0.032, respectively). Univariate analysis revealed that lower expression of miR‐101, miR‐10b*, miR‐139‐5p, miR‐152, miR‐29b, and miR‐455‐5p was significantly correlated with poor overall survival (P < 0.05), and reduced expression of miR‐152, miR‐29b, and miR‐455‐5p was significantly correlated with poor disease‐free survival (P < 0.05). Multivariate analysis demonstrated that decreased expression of miR‐152 (P = 0.021) was a statistically independent risk factor for overall survival, and decreased expression levels of miR‐101 (P = 0.016) and miR‐152 (P = 0.010) were statistically independent risk factors for disease‐free survival. In addition, transfection of miR‐101 or miR‐152 precursors into an endometrial serous carcinoma cell line inhibited cell growth (P < 0.0001 and P = 0.01, respectively). Moreover, strong positive immunoreactivity of cyclooxygenase‐2 (COX‐2) was significantly correlated with down‐regulation of miR‐101 (P = 0.035). These findings suggest that the dysregulation of miRNAs is associated with the poor prognosis in endometrial serous adenocarcinoma patients. (Cancer Sci 2009)
Alpha‐eleostearic acid suppresses proliferation of MCF‐7 breast cancer cells via activation of PPARγ and inhibition of ERK 1 / 2
Authors: Moon Hyun‐Seuk , Guo Ding‐Ding , Lee Hong‐Gu , Choi Yun‐Jaie , Kang Jae‐Seong , Jo Kyungmin , Eom Jung‐Min , Yun Cheol‐Heui , Cho Chong‐Su
Published: October 2009

Alpha‐eleostearic acid (α‐ESA) is known to suppress the growth in cancer cells although its underlying molecular mechanisms have not been fully elucidated. The present study was designed to elucidate and evaluate the anticancer mechanism of α‐ESA on MCF‐7 breast cancer cells. Also, an attempt was made to better understand the anticancer mechanism by which α‐ESA activated PPARγ and attenuated the ERK1/2 MAPK phosphorylation state. The MCF‐7 breast cancer cell‐line and nontumorigenic MCF‐10A human mammary epithelial cells were treated with α‐ESA and compared with negative control (without treatment) and positive control groups (treated with rosiglitazone), and changes of apoptosis‐related molecules, PPARγ and pERK1/2 were examined. In MCF‐7 cells treated with α‐ESA, we found that the expression of p53, p21, and Bax was up‐regulated whereas expression of Bcl‐2 and procaspase‐9 was down‐regulated. Moreover, nuclear translocation of PPARγ by α‐ESA positively correlated with inhibition of ERK1/2 activation. Our data suggest that α‐ESA can be considered to be a PPARγ agonist and thus a candidate for a chemotherapeutic agent against breast cancer. (Cancer Sci 2009; 00: 000–000)
Development of novel humanized anti‐CD20 antibodies based on affinity constant and epitope
Authors: Uchiyama Susumu , Suzuki Yasuhiko , Otake Kentaro , Yokoyama Masami , Ohta Mitsuo , Aikawa Shuichi , Komatsu Midori , Sawada Tetsuji , Kagami Yoshitoyo , Morishima Yasuo , Fukui Kiichi
Published: October 2009

We describe novel humanized anti‐CD20 monoclonal antibodies (mAbs) developed for therapeutic use on the basis of their physicochemical properties and cellular cytotoxicity. A distinct correlation between apparent dissociation constants (Kd) and apoptotic activity for eight murine anti‐CD20 mAbs (OUBM1–OUBM8) and previously‐developed murine anti‐CD20 mAbs enabled us to categorize anti‐CD20 mAbs into two groups. Group A mAbs had lower Kd values and did not induce definite apoptosis, while Group B mAbs had greater Kd values and did induce definite apoptosis. A murine version mAb of rituximab, 2B8, belongs to Group B. An epitope analysis showed that the epitope of two murine mAbs, OUBM3 and OUBM6, differed from that of 2B8 or 2F2 (ofatumumab). Two mAbs, OUBM3 from Group A and OUBM6 from Group B, were selected and humanized. As expected, the humanized OUBM3 with the lower Kd did not induce apoptosis, while the humanized OUBM6 (hOUBM6) with the greater Kd did. Both hOUBM3 and hOUBM6 induced highly‐effective, complement‐dependent cytotoxicity and antibody‐dependent, cell‐mediated cytotoxicity against Burkitt’s and follicular lymphomas. Importantly, hOUBM6 exhibited cellular cytotoxicity against diffuse, large B cells that are less effectively depleted by rituximab and also exhibited effective cytotoxicity against tumor cells from human CD20(+) leukemia and lymphoma patients. These results suggest the potential impact of the further development of our anti‐CD20 mAbs. Our study shows that the selection of mAbs based on their physicochemical parameters, followed by the biological activity assessment for the selected mAbs, is a rational and efficient approach for pharmaceutical mAb development. (Cancer Sci 2009)
First insights into the genes that control plant–bacterial interactions
Authors: STASKAWICZ BRIAN
Published: October 2009

The events leading up to the cloning of the first bacterial avirulence gene, avrA, from Pseudomonas syringae pv. glycinea are described. The cloning of this gene marked the beginning of the molecular analyses of bacterial effectors and has paved the way for determining of the role of bacterial effectors in pathogen virulence and the triggering of plant innate immunity.
Irritable bowel syndrome symptoms and health related quality of life in female veterans
Authors: GRAHAM D. P. , SAVAS L. , WHITE D. , EL‐SERAG R. , LADAY‐SMITH S. , TAN G. , EL‐SERAG H. B.
Published: October 2009

Background  The status and determinants of health‐related quality of life (HRQOL) in female veterans with and without irritable bowel syndrome (IBS) are unknown.

Aim  To compare HRQOL in female veterans with and without IBS symptoms and examine the contribution of post‐traumatic stress disorder, depression and anxiety to HRQOL.

Methods  A cross‐sectional study of 339 female veterans. Self‐report questionnaires were used to evaluate IBS symptoms, post‐traumatic stress disorder, depression, anxiety and HRQOL.

Results  Symptoms consistent with IBS were present in 33.5% of participants. Female veterans with IBS symptoms had significant reductions in physical component score and 5 of 8 Health Related Quality of Life subscales and on 7 of 8 Irritable Bowel Syndrome Quality Of Life subscales than female veterans without IBS symptoms. Compared with the US general female population, female veterans had significantly lower Health Related Quality of Life physical component score and mental component scores (MCS) irrespective of IBS symptom status. Differences in the MCS score were most explained by depression, while those in the physical component score were most explained by anxiety.

Conclusions  Irritable bowel syndrome symptoms in female veterans are associated with considerable reduction in HRQOL. However, female veterans, regardless of IBS symptom status, have lower HRQOL compared with the general US female population.

Aliment Pharmacol Ther 31, 261–273
The assessment of regional gut transit times in healthy controls and patients with gastroparesis using wireless motility technology
Authors: SAROSIEK I. , SELOVER K. H. , KATZ L. A. , SEMLER J. R. , WILDING G. E. , LACKNER J. M. , SITRIN M. D. , KUO B. , CHEY W. D. , HASLER W. L. , KOCH K. L. , PARKMAN H. P. , SAROSIEK J. , MCCALLUM R. W.
Published: October 2009

Background  Wireless pH and pressure motility capsule (wireless motility capsule) technology provides a method to assess regional gastrointestinal transit times.

Aims  To analyse data from a multi‐centre study of gastroparetic patients and healthy controls and to compare regional transit times measured by wireless motility capsule in healthy controls and gastroparetics (GP).

Methods  A total of 66 healthy controls and 34 patients with GP (15 diabetic and 19 idiopathic) swallowed wireless motility capsule together with standardized meal (255 kcal). Gastric emptying time (GET), small bowel transit time (SBTT), colon transit time (CTT) and whole gut transit time (WGTT) were calculated using the wireless motility capsule.

Results  Gastric emptying time, CTT and WGTT but not SBTT were significantly longer in GP than in controls. Eighteen percent of gastroparetic patients had delayed WGTT. Both diabetic and idiopathic aetiologies of gastroparetics had significantly slower WGTT (P < 0.0001) in addition to significantly slower GET than healthy controls. Diabetic gastroparetics additionally had significantly slower CTT than healthy controls (P = 0.0054).

Conclusions  In addition to assessing gastric emptying, regional transit times can be measured using wireless motility capsule. The prolongation of CTT in gastroparetic patients indicates that dysmotility beyond the stomach in GP is present, and it could be contributing to symptom presentation.

Aliment Pharmacol Ther 31, 313–322
A comparison of a flexometallic tracheal tube with the intubating laryngeal mask tracheal tube for nasotracheal fibreoptic intubation using the two‐scope technique*
Authors: Rai M. R. , Scott S. H. , Marfin A. G. , Popat M. T. , Pandit J. J.
Published: October 2009

We compared the incidence and site of impingement of a flexometallic tracheal tube with those of the re‐usable intubating laryngeal mask (ILMA) tube in 60 anaesthetised patients undergoing nasotracheal fibreoptic intubation for oral surgery. A two‐scope technique was used, observing the site of impingement with one scope whilst intubating with the other. The tubes were 6.0‐mm in females and 6.5‐mm in males. Impingement occurred with 10 (33%) flexometallic and 2 (7%) ILMA tubes (p < 0.032). In all but one case, the impingement was posterior to the right arytenoid cartilage. When impingement was observed, a single disempaction with a 90° anticlockwise rotational manoeuvre overcame impingement in every case except one, allowing successful intubation. We conclude that the incidence of impingement of the tracheal tube, and therefore of potential laryngeal trauma from nasotracheal fibreoptic intubation, is significantly greater with the flexometallic tube than with the ILMA tube.
Grey plumage colouration in the duck is genetically determined by the alleles on two different, interacting loci
Authors: Gong Y. , Yang Q. , Li S. , Feng Y. , Gao C. , Tu G. , Peng X.
Published: October 2009

Based on the observation of a grey phenotype in the F1 generation from a cross between two white plumage duck varieties, the white Kaiya and the white Liancheng, we hypothesized a possible interaction between two autosomal loci that determine grey plumage. Using the parental and F1 individuals, seven testing combinations including five different F1 intercrosses (F2) and two different backcrosses (BC1 and BC2) were designed to test our hypothesis. It was demonstrated by chi‐squared analysis that six test matings produced offspring in the expected ratios between the grey and white, with P‐values ranging from 0.50 to 0.99. Another mating, where all white offspring were expected, produced 33 white individuals. These results verified that the interaction between two loci produced the grey phenotype. The C locus, which carries the recessive allele (c), was previously thought to be the only gene responsible for white plumage in the duck. This is the first report that an allele (t), carried by the white Liancheng at a different autosomal locus, also determines white plumage in ducks. Furthermore, the dominant alleles at both loci can interact with each other to produce the grey phenotype, and a new dark phenotype, observed in some F2 individuals, can be attributed to the dosage effect of the T allele.
Promoting public awareness of randomised clinical trials using the media: the ‘Get Randomised’ campaign
Authors: Mackenzie Isla S. , Wei Li , Rutherford Daniel , Findlay Evelyn A. , Saywood Wendy , Campbell Marion K. , MacDonald Thomas M.
Published: October 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Recruitment is key to the success of clinical trials.

• Many clinical trials fail to achieve adequate recruitment.

• Public understanding and engagement in clinical research could be improved.

WHAT THIS STUDY ADDS

• ‘Get Randomised’ is the first campaign of its kind in the UK.

• It is possible to improve public awareness of clinical research using the media.

• Further work is needed to determine whether improved public awareness leads to increased participation in clinical research in the future.

AIM

To increase public awareness and understanding of clinical research in Scotland.

METHODS

A generic media campaign to raise public awareness of clinical research was launched in 2008. The ‘Get Randomised’ campaign was a Scotland‐wide initiative led by the University of Dundee in collaboration with other Scottish universities. Television, radio and newspaper advertising showed leading clinical researchers, general practitioners and patients informing the public about the importance of randomised clinical trials (RCTs). ‘Get Randomised’ was the central message and interested individuals were directed to the http://www.getrandomised.org website for more information. To assess the impact of the campaign, cross‐sectional surveys were conducted in representative samples of 1040 adults in Scotland prior to campaign launch and again 6 months later.

RESULTS

There was an improvement in public awareness of clinical trials following the campaign; 56.7% [95% confidence interval (CI) 51.8, 61.6] of the sample recalled seeing or hearing advertising about RCTs following the campaign compared with 14.8% (10.8, 18.9) prior to the campaign launch (difference = 41.4%; 95% CI for difference 35.6, 48.3; P < 0.01). Of those who recalled the advertising, 49% felt that the main message was that people should take part more in medical research. However, on whether they would personally take part in a clinical trial if asked, there was little difference in response following the campaign [‘yes’ 31.3% (28.4, 34.1) prior; 30.4% (27.6, 33.2) following; difference =−0.9%; 95% CI for difference −4.8, 3.1%; P= 0.92].

CONCLUSIONS

It is possible to raise public awareness of clinical research using the media, but further efforts may be required to influence individuals' decisions to take part in clinical research.
Cleanliness of dentinal tubules following gutta‐percha removal with and without solvents: a scanning electron microscopic study
Authors: Horvath S. D. , Altenburger M. J. , Naumann M. , Wolkewitz M. , Schirrmeister J. F.
Published: October 2009

Aim  To determine the influence of solvents on gutta‐percha and sealer remaining on root canal walls and in dentinal tubules.

Methodology  The root canals of 70 teeth were prepared chemomechanically to apical size 40. In group 1 (n = 10; control group), the canals remained unfilled. In groups 2–4 (n = 20 each), the canals were filled using lateral compaction with gutta‐percha and sealer. Removal of root fillings was undertaken after 2 weeks using Gates Glidden burs and hand files without solvent (group 2), with eucalyptol (60 μL; group 3) and with chloroform (60 μL; group 4) to size 50. After further irrigation using sodium hypochlorite and ethylenediaminetetraacetic acid, the roots were split, photographed and scanning electron microscopy (SEM) was performed. The number of filled dentinal tubules (SEM) and the surface covered by root filling remnants (photographs) were evaluated for the coronal, middle and apical third of each root half. Statistical analysis was performed via mixed model for clustered data followed by Tukey’s test.

Results  After pooling the results of all thirds of the canal, open tubules were more prevalent in the control group, followed by the nonsolvent group, the eucalyptol group and the chloroform group (P < 0.05 between all groups). Less surface was covered by root filling remnants in the nonsolvent group than in the eucalyptol group and the chloroform group (P < 0.05); again, fewer remnants were found in the control group than in all other groups (P < 0.05).

Conclusions  Solvents led to more gutta‐percha and sealer remnants on root canal walls and inside dentinal tubules.
Dental stem cells and their potential role in apexogenesis and apexification
Authors: Friedlander L. T. , Cullinan M. P. , Love R. M.
Published: October 2009

Injury to an immature permanent tooth may result in cessation of dentine deposition and root maturation leaving an open root apex and thin dentinal walls that are prone to fracture. Endodontic treatment is often complicated and protracted with an uncertain prognosis frequently resulting in premature tooth loss. Postnatal stem cells, which are capable of self‐renewal, proliferation and differentiation into multiple specialized cell lineages have been isolated and identified within the dental pulp, apical papilla and periodontal ligament. The ability of these cells to produce pulp‐dentine and cementum‐periodontal ligament complexes in vivo suggest potential applications involving stem cells, growth factors and scaffolds for apexification or apexogenesis. Similar protein expression amongst dental stem cells possibly implicates a common origin; however, the dominant cells to repopulate an open apex will be directed by local environmental cues. A greater understanding of the structure and function of cells within their environment is necessary to regulate and facilitate cellular differentiation along a certain developmental path with subsequent tissue regeneration. This review focuses on development of the apical tissues, dental stem cells and their possible involvement clinically in closing the open root apex. MEDLINE and EMBASE computer databases were searched up to January 2009. Abstracts of all potentially relevant articles were scanned and their contents identified before retrieval of full articles. A manual search of article reference lists as well as a forward search on selected authors of these articles was undertaken. It appears that dental stem cells have the potential for continued cell division and regeneration to replace dental tissues lost through trauma or disease. Clinical applications using these cells for apexogenesis and apexification will be dependent on a greater understanding of the environment at the immature root end and what stimulates dental stem cells to begin dividing and then express a certain phenotype.
Effectiveness of HERO 642 versus Hedström files for removing gutta‐percha fillings in curved root canals: an ex vivo study
Authors: Aydın B. , Köse T. , Çalışkan M. K.
Published: October 2009

Aim  To compare the effectiveness of gutta‐percha removal and the maintenance of canal anatomy when using the HERO 642 system or Hedström files (H‐files) in mandibular molar teeth.

Methodology  The root canals of 40 mandibular molar teeth were instrumented using H‐files and filled with gutta‐percha and sealer. After 1 year in storage, the roots were sectioned horizontally to provide apical, middle and coronal root thirds. Sections were photographed, and an individual muffle was produced for each tooth. Teeth were randomly divided into four groups (n = 10) and the gutta‐percha removed using either the HERO 642 system or H‐files, with or without solvent. Digital images of the root canals were then re‐taken. Root thirds were inspected for lateral perforations, and the percentage of the residual canal filling was determined on postoperative images. Transportation and centring ratio were calculated using preoperative and postoperative images of the cross‐sections of root thirds.

Results  H‐files groups were associated with less filling material than the HERO 642 system (H‐files–HERO 642 P = 0.056, H‐files–HERO 642+solvent P = 0.041, H‐files + solvent–HERO 642 P = 0.018, H‐files + solvent–HERO 642 + solvent P = 0.016). The percentage of residual filling material was similar in the apical thirds, and the contribution of solvent to canal debridement was not statistically significant (P > 0.05). Perforation occurred mesiobuccally in 48% of specimens in the apical sections of mesial roots. There were no significant differences for centring ratio, transportation and perforation rate between groups.

Conclusions  H‐files left less gutta‐percha overall; however, there was no difference in the apical third. The effect of solvent was not remarkable. Both instrument systems created a large number of perforations.
Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm‐blooded animals
Authors: Nicholls Susan , Leach Michelle D. , Priest Claire L. , Brown Alistair J. P.
Published: October 2009

All organisms have evolved mechanisms that protect them against environmental stress. The major fungal pathogen of humans, Candida albicans, has evolved robust stress responses that protect it against human immune defences and promote its pathogenicity. However, C. albicans is unlikely to be exposed to heat shock as it is obligatorily associated with warm‐blooded animals. Therefore, we examined the role of the heat shock transcription factor (Hsf1) in this pathogen. We show that C. albicans expresses an evolutionarily conserved Hsf1 (orf19.4775) that is phosphorylated in response to heat shock, induces transcription via the heat shock element (HSE), contributes to the global transcriptional response to heat shock, and is essential for viability. Why has Hsf1 been conserved in this obligate animal saprophyte? We reasoned that Hsf1 might contribute to medically relevant stress responses. However, this is not the case, as an Hsf1‐specific HSE‐lacZ reporter is not activated by oxidative, osmotic, weak acid or pH stress. Rather, Hsf1 is required for the expression of essential chaperones in the absence of heat shock (e.g. Hsp104, Hsp90, Hsp70). Furthermore, Hsf1 regulates the expression of HSE‐containing genes in response to growth temperature in C. albicans. Therefore, the main role of Hsf1 in this pathogen might be the homeostatic modulation of chaperone levels in response to growth temperature, rather than the activation of acute responses to sudden thermal transitions.
An intricate network of regulators controls biofilm formation and colonization by Vibrio fischeri
Authors: Visick Karen L.
Published: October 2009

The initial encounter between a microbe and its host can dictate the success of the interaction, be it symbiosis or pathogenesis. This is the case, for example, in the symbiosis between the bacterium Vibrio fischeri and the squid Euprymna scolopes, which proceeds via a biofilm‐like bacterial aggregation, followed by entry and growth. A key regulator, the sensor kinase RscS, is critical for symbiotic biofilm formation and colonization. When introduced into a fish symbiont strain that naturally lacks the rscS gene and cannot colonize squid, RscS permits colonization, thereby extending the host range of these bacteria. RscS controls biofilm formation by inducing transcription of the symbiosis polysaccharide (syp) gene locus. Transcription of syp also requires the σ54‐dependent activator SypG, which functions downstream of RscS. In addition to these regulators, SypE, a response regulator that lacks an apparent DNA binding domain, exerts both positive and negative control over biofilm formation. The putative sensor kinase SypF and the putative response regulator VpsR, both of which contribute to control of cellulose production, also influence biofilm formation. The wealth of regulators and the correlation between biofilm formation and colonization adds to the already considerable utility of the V. fischeri–E. scolopes model system.
Plasma levels and skin‐eosinophil‐expression of vascular endothelial growth factor in patients with chronic urticaria
Authors: Tedeschi A. , Asero R. , Marzano A. V. , Lorini M. , Fanoni D. , Berti E. , Cugno M.
Published: October 2009

Background:  Although chronic urticaria (CU) is often regarded as autoimmune in nature, only less than 50% of sera from CU patients contain histamine‐releasing autoantibodies. This suggests that other factors may contribute to its pathogenesis. We evaluated the possible involvement of vascular endothelial growth factor (VEGF), one of the major mediators of vascular permeability, in CU.

Methods:  Eighty consecutive adult patients with CU and 53 healthy subjects were studied. VEGF and prothrombin fragment F1+2 were measured by enzyme immunoassays. Autologous plasma skin test (APST) was performed in CU patients and, in six of them, skin biopsy specimens were taken from wheals to evaluate the immunohistochemical expression of VEGF and eosinophil cationic protein (ECP).

Results:  Plasma VEGF concentrations were higher in CU patients (8.00 ± 0.90 pmol/l) than in controls (0.54 ± 0.08 pmol/l) (P = 0.0001) and tended to parallel both the severity of CU and to correlate with F1+2 levels. APST was positive in 85.1% of patients. VEGF concentration was significantly higher in APST‐positive than in APST‐negative patients (P = 0.0003). Immunohistochemically, all specimens from patients with CU showed a strong expression of VEGF (P = 0.002) that colocalized with ECP, a classic eosinophil marker.

Conclusions:  VEGF plasma levels are elevated in CU and parallel the disease severity. This supports a possible role of this molecule in CU pathophysiology. Eosinophils are the main cellular source of VEGF in CU lesional skin.
Association and interaction analyses of eight genes under asthma linkage peaks
Authors: Ferreira M. A. R. , Zhao Z. Z. , Thomsen S. F. , James M. , Evans D. M. , Postmus P. E. , Kyvik K. O. , Backer V. , Boomsma D. I. , Martin N. G. , Montgomery G. W. , Duffy D. L.
Published: October 2009

Background:  Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits.

Methods:  Ninety‐five single nucleotide polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in >5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor‐diagnosed asthma, atopy, airway obstruction, total serum immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene‐wide thresholds for significance determined through simulation. Gene‐by‐gene and gene‐by‐environment analyses were also performed.

Results:  There was no overall evidence for association with seven of the eight genes tested when considering all genetic variation assayed in each gene. The exception was MS4A2 on chromosome 11q13, which showed weak evidence for association with IgE (gene‐wide P < 0.05, rs502581). There were no significant gene‐by‐gene or gene‐by‐environment interaction effects after accounting for the number of tests performed.

Conclusions:  The individual variants genotyped in the 2q33, 9p21 and 20q13 regions do not explain a large fraction of the variation in the quantitative traits tested or have a major impact on asthma or atopy risk. Our results are consistent with a weak effect of MS4A2 polymorphisms on the variation of total IgE levels.
GA2LEN skin test study III: Minimum battery of test inhalent allergens needed in epidemiological studies in patients
Authors: Bousquet P.‐J. , Burbach G. , Heinzerling L. M. , Edenharter G. , Bachert C. , Bindslev‐Jensen C. , Bonini S. , Bousquet‐Rouanet L. , Demoly P. , Bresciani M. , Bruno A. , Gjomarkaj M. , Canonica G. W. , Darsow U. , Durham S. , Fokkens W. J. , Giavi S. , Gramiccioni C. , Papadopoulos N. G. , Haahtela T. , Kowalski M. L. , Magyar P. , Muraközi G. , Orosz M. , Röhnelt C. , Stingl G. , Todo‐Bom A. , Von Mutius E. , Wiesner A. , Wöhrl S. , Bousquet J. , Zuberbier T.
Published: October 2009

Background:  The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost‐effective approach in epidemiological studies.

Objective:  To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan‐European GA2LEN skin prick test study.

Method:  In a large Pan‐European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection.

Result:  Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects.

Conclusion:  Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.
Update on pediatric lung allocation in the United States
Authors: Sweet Stuart C.
Published: October 2009

Abstract:  In May 2005, a system was established to allocate deceased donor lungs to adolescents and adults in the United States based on models of waiting list mortality and one‐yr transplant survival benefit. The goal of the new system is to reduce the mortality of patients awaiting lung transplant and maximize the survival benefit of lung transplantation. This article discusses the considerations given to pediatric candidates during the development of the LAS, early outcome observations with emphasis on pediatric candidates and finally, future changes and impact on pediatric lung transplantation.
Bacterial tracheobronchitis. A rare cause of adult airway stenosis
Authors: KADOWAKI Toru , HAMADA Hironobu , FUJIWARA Ai , MIYOSHI Seigo , HAMAGUCHI Naohiko , ITO Ryoji , HIGAKI Jitsuo
Published: October 2009

Bacterial tracheobronchitis is a rare cause of airway stenosis in adults. This report describes a 73‐year‐old woman with a recent history of polysialadenitis, who presented with severe airway obstruction due to infection and stenosis of tracheal and bronchial tissue. Tissue culture of the bronchial mucosa showed growth of methicillin resistant Staphylococcus epidermidis (MRSE). Sputum culture showed growth of MRSE, Pseudomonas aeruginosa, Enterobacter cloacae and Enterococcus faecalis; the same organisms were cultured from the salivary glands. Tracheostomy and antibiotic therapy were effective in controlling the disease.
Evaluation of an information booklet for caregivers of people with dementia: An Australian perspective
Authors: Chang Esther , Easterbrook Sally , Hancock Karen , Johnson Amanda , Davidson Patricia
Published: October 2009

The need for improved communication around end‐of‐life issues has been identified in cancer care. However, caregivers assisting those with dementia have been given scant attention. This study investigated the application of a new dementia information booklet for family caregivers, accessing those that were both community‐based and linked to a residential aged‐care facility through the distribution of 672 information booklets. This occurred via 14 dementia advisory services and 48 residential aged‐care facilities throughout New South Wales, Australia. A total of 233 carers (33%) completed the booklet questionnaire evaluation. The descriptive statistics indicated that most carers found the booklet useful and thought that the booklet should be freely available to them. Almost half of the carers said that they wanted to receive the information at the time of, or soon after, the diagnosis of dementia. Only a small group of respondents considered the information to be confronting. The reported anxiety was thought to be part of a larger issue of dementia education and dealing with loss and not specifically related to the booklet itself.
Effects of raloxifene on the renin–angiotensin–aldosterone system and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women
Authors: Sumino Hiroyuki , Ichikawa Shuichi , Kasama Shu , Takahashi Takashi , Kumakura Hisao , Takayama Yoshiaki , Kanda Tsugiyasu , Murakami Masami , Kurabayashi Masahiko
Published: October 2009

Aim:  An increase in blood pressure after menopause has been documented. The renin–angiotensin–aldosterone system (RAAS) plays a central role in the regulation of blood pressure and in the pathophysiology of hypertension. This study investigated the effects of raloxifene, a selective estrogen receptor modulator, on components of the RAAS and blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.

Methods:  A total of 41 hypertensive or normotensive postmenopausal women with osteoporosis or osteopenia were divided into four groups. Eleven hypertensive and eight normotensive women received raloxifene hydrochloride (60 mg/day) p.o. for 6 months, and 12 hypertensive and 10 normotensive women did not receive raloxifene hydrochloride for 6 months. In all of the hypertensive women, blood pressure had been controlled prior to the start of the study using a variety of antihypertensive drugs other than angiotensin‐converting enzyme (ACE) inhibitors, angiotensin (Ang)II type 1 receptor antagonists or diuretics. Plasma renin activity (PRA), serum ACE activity, plasma AngI, AngII and aldosterone concentrations, and blood pressure were measured before and 6 months after the start of the study.

Results:  No significant changes in PRA, ACE activity, or the AngI, AngII or aldosterone levels were observed in any of the groups. In all the groups, blood pressure remained unchanged.

Conclusion:  Raloxifene may have no significant effect on the RAAS or blood pressure in hypertensive and normotensive osteoporotic postmenopausal women.
Repeat dynamic sentinel node biopsy in locally recurrent penile carcinoma
Authors: Graafland Niels M. , Leijte Joost A.P. , Valdés Olmos Renato A. , Van Boven Hester H. , Nieweg Omgo E. , Horenblas Simon
Published: October 2009

Study Type – Diagnosis (case series) Level of Evidence 4

OBJECTIVE

To explore the role of repeat dynamic sentinel‐node biopsy (SNB) in clinically node‐negative patients with locally recurrent penile carcinoma after previous penile surgery and SNB.

PATIENTS AND METHODS

Between 1994 and 2008, 12 patients (4% of the 304 in our prospectively maintained dynamic sentinel node database) with clinically node‐negative groins had a repeat SNB for locally recurrent penile carcinoma after previous penile surgery and SNB. Five of these patients had previously had a unilateral inguinal node dissection for groin metastases. The median disease‐free interval was 18 months. The protocol and technique of primary dynamic SNB and the repeat procedure were similar, including preoperative lymphoscintigraphy and blue‐dye injection. Completion inguinal node dissection was only done if there was an involved sentinel node.

RESULTS

No sentinel nodes were seen on preoperative lymphoscintigraphy in the five groins that had previously been dissected. A sentinel node was visualized on lymphoscintigraphy in the remaining 19 undissected groins. In 15 of these groins (79%) the sentinel node was identified during surgery. Histopathological analysis showed involved sentinel nodes in four groins of three patients. Additional metastatic nodes were found in one completion inguinal lymph node dissection specimen. During a median follow‐up of 32 months after the repeat SNB, one patient developed a groin recurrence 14 months after a tumour‐negative sentinel node procedure.

CONCLUSIONS

Repeat dynamic SNB is feasible in clinically node‐negative patients with locally recurrent penile carcinoma despite previous SNB.
Comparison of the thermal and histopathological effects of bipolar and monopolar electrosurgical resection of the prostate in a canine model
Authors: Ko Raymond , Tan Andrew H.H. , Chew Ben H. , Rowe P. Elaine , Razvi Hassan
Published: October 2009

OBJECTIVES

To compare the thermal and histopathological effects of two commercially available bipolar systems and conventional monopolar transurethral resection of the prostate (TURP) in a canine model. Bipolar TURP is an alternative to monopolar electrosurgery for treating benign prostatic hyperplasia and has several potential clinical advantages, including the ability to use normal saline irrigation, enhanced haemostasis and less collateral thermal damage.

MATERIAL AND METHODS

In all, 12 adult male beagles were studied. After midline laparotomy and exposure of the bladder and prostate, two fibre‐optic thermosensors were placed to record tissue temperatures; one sensor was placed into the substance of the prostate 2 cm from the urethra and the second in the prostatic‐rectal groove on the capsular surface of the prostate to measure temperatures in the region of the neurovascular bundles. Through a midline cystotomy, antegrade TURP was performed using two different bipolar systems (Gyrus PlasmaKinetic and Vista, both from Gyrus‐ACMI Corporation, Maple Grove, MN, USA) or a monopolar device (ForceTM 2, Valleylab, Boulder, CO, USA). TURP was performed in each lateral lobe using 24 F resection loops. The dogs were humanely killed acutely and the prostates excised for histopathological assessment.

RESULTS

When comparing intraprostatic temperature data, the mean (sem) temperature changes recorded for the monopolar group were significantly higher than in either the Gyrus or Vista bipolar groups, at 24.2 (3.9) °C vs 8.1 (1.5) °C and 6.8 (1.8) °C, respectively (P < 0.001). No measurable temperature elevations were recorded near the neurovascular bundles with any of the electrosurgery devices. The depth of thermal damage was greatest in the monopolar group at 0.59 (0.27) mm compared with the Gyrus and Vista groups at 0.07 (0.08) mm and 0.15 (0.02) mm, respectively (P < 0.001).

CONCLUSION

Bipolar TURP generated significantly less heat and histopathological evidence of thermal damage compared with monopolar TURP in the present canine model.
Long‐term glycaemic effects of pioglitazone compared with placebo as add‐on treatment to metformin or sulphonylurea monotherapy in PROactive (PROactive 18)
Authors: Scheen A. J. , Tan M. H. , Betteridge D. J. , Birkeland K. , Schmitz O. , Charbonnel B. ,   on behalf of the PROactive investigators
Published: October 2009

Aims  To assess the long‐term glycaemic effects, concomitant changes in medications and initiation of permanent insulin use (defined as daily insulin use for a period of ≥ 90 days or ongoing use at death/final visit) with pioglitazone vs. placebo in diabetic patients receiving metformin or sulphonylurea monotherapy at baseline in the PROspective pioglitAzone Clinical Trial in macroVascular Events (PROactive).

Methods  In PROactive, patients with Type 2 diabetes and macrovascular disease were randomized to pioglitazone (force titrated to 45 mg/day) or placebo, in addition to other existing glucose‐lowering therapies. In a post‐hoc analysis, we categorized patients not receiving insulin at baseline and treated by oral monotherapy into two main cohorts: add‐on to metformin alone (n = 514) and sulphonylurea alone (n = 1001). The follow‐up averaged 34.5 months.

Results  There were significantly greater reductions in glycated haemoglobin (HbA1c) with pioglitazone than with placebo and more pioglitazone‐treated patients achieved HbA1c targets, irrespective of the baseline oral glucose‐lowering regimen and despite a decrease in the use of other glucose‐lowering agents. Approximately twice as many in the placebo groups progressed to permanent insulin use than in the pioglitazone groups across the two cohorts: 3.4% for pioglitazone and 6.5% for placebo when added to metformin monotherapy and 6.3% and 14.8%, respectively, when added to sulphonylurea monotherapy. The overall safety of both dual therapies was good.

Conclusions  Intensifying an existing oral monotherapy regimen to a dual oral regimen by adding pioglitazone resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The efficacy and safety of adding pioglitazone to either metformin monotherapy or sulphonylurea monotherapy were good.
The effect of biopsy‐positive silent coeliac disease and treatment with a gluten‐free diet on growth and glycaemic control in children with Type 1 diabetes
Authors: Sun S. , Puttha R. , Ghezaiel S. , Skae M. , Cooper C. , Amin R. ,   on behalf of the North West England Paediatric Diabetes Network
Published: October 2009

Objective  To determine the effect of coeliac disease and treatment with a gluten‐free diet on growth and glycaemic control in asymptomatic children with Type 1 diabetes.

Methods  Data were compared in children with coeliac disease diagnosed by annual antibody screening and jejunal biopsy and treated with a gluten‐free diet (n = 49) against individuals who were antibody negative (n = 49) matched for age, sex and duration of diabetes.

Results  No differences in growth were observed. In the years prior to diagnosis of coeliac disease, mean glycated haemoglobin (HbA1c) was lower in cases compared with control subjects [8.3 ± 1.1% vs. 8.7 ± 0.9%, P = 0.02 (mean ± sd)]. In cases, HbA1c deteriorated 12 months from the start of a gluten‐free diet to levels similar to control subjects (8.9 ± 1.5% vs. 8.8 ± 1.5%, P‐value for analysis of variance = 0.9). In regression analysis, the diagnosis of coeliac disease and start of a gluten‐free diet was associated with a rise in HbA1c in the first year of treatment [odds ratio 1.56 (95% confidence intervals 1.16–2.10), P = 0.003] after adjusting for insulin dose and regimen and other variables.

Conclusions  In children with Type 1 diabetes, lower HbA1c prior to diagnosis of silent coeliac disease rises following treatment with a gluten‐free diet to levels similar to those without coeliac disease. Although unproven, these observations may relate to abnormalities at the small bowel mucosa before the appearance of circulating coeliac antibodies.