bluuebunny/crossref_metadata_2025 huggingface dataset:
The Drosophila RNA‐binding protein Lark is required for the organization of the actin cytoskeleton and Hu‐li tai shao localization during oogenesis
Authors: McNeil Gerard P. , Smith Fiona , Galioto Robert
Published: September 2004

Elimination of maternal expression of the Drosophila RNA‐binding protein Lark results in female sterility. Here we show that this is due to a requirement during oogenesis. Developing oocytes from lark1 germline clones (GLCs) are often smaller than normal due to defects in nurse cell cytoplasmic “dumping.” Late‐stage egg chambers from lark1 GLCs contain low levels of cortical and ring canal associated actin and completely lack nurse cell cytoplasmic F‐actin bundles, suggesting the “dumping” phenotype is due to a defect in the actin cytoskeleton. Localization of Hu‐li tai shao (Hts) protein, a component of ring canals, is also disrupted in these mutants. In addition to the dumpless phenotype, we observed a buildup of late‐stage egg chambers, a phenotype that correlates with the decrease in egg‐laying observed in the mutants. We postulate that this phenotype is due to defects in the cytoskeletal integrity of eggs since retained and oviposited eggs are fragile and often deflated. These mutant phenotypes are likely due to disruption of an RNA‐binding function of Lark as similar phenotypes were observed in flies carrying specific RNA‐binding domain mutations. We propose that Lark functions during oogenesis as an RNA‐binding protein, regulating mRNAs required for nurse cell transport or apoptosis. genesis 40:90–100, 2004. © 2004 Wiley‐Liss, Inc.
RNAi‐mediated inhibition of gene function in the follicle cell layer of the Drosophila ovary
Authors: Zhu Xianjun , Stein David
Published: September 2004

RNA‐mediated interference (RNAi) has been reported to be an effective reverse genetic approach for studying gene function in various organisms. To assess RNAi as a means of examining genes expressed in ovarian follicle cells for their involvement in embryonic dorsal–ventral patterning, we tested the ability of transgenically expressed double‐stranded RNA (dsRNA) directed against the dorsal group gene windbeutel to generate phenotypic effects in the progeny of expressing females. We observed that expression in follicle cells under the control of Gal4 transcribed from the strong and widely expressed alphaTub84B or Actin5C promoters led to efficient dorsalization of progeny embryos. Surprisingly, a variety of strongly expressed follicle cell‐specific Gal4 enhancer trap lines failed to elicit an RNAi phenotype in combination with the windbeutel‐specific dsRNA. These results stress the importance of careful choice of expression system and of conditions for use in transgenic RNAi‐mediated studies of gene function. genesis 40:101–108, 2004. © 2004 Wiley‐Liss, Inc.
Sedimentary evidence for the formation mechanism of the Armoy moraine and late Devensian glacial events in the north of Ireland
Authors: Knight Jasper
Published: September 2004

The internal sedimentology of the Armoy moraine, which marks a late Devensian (Weichselian) incursion of Scottish ice into the north of Ireland, is described from a temporary exposure near Armoy village. The exposure (up to 30 m long, 10 m high) comprises folded gravel beds, massive clay grading up to pebbly diamicton, massive gravel, overfolded and deformed sand, and a gravel and massive diamicton cover. These sediments overlie glacially smoothed basalt bedrock. The sediment succession records the interaction of near‐touching Scottish and Irish ice margins, and the formation, infilling and drainage of an ice‐supported proglacial lake. Scottish ice likely advanced into the north of Ireland by a short‐lived glacier surge during the Killard Point Stadial (coeval with Heinrich Event 1 at 14.514C ka BP), forming the Armoy moraine at its maximum extent. The presence of rafted sediment blocks within the moraine suggests ice‐marginal thrusting and deformation of proglacial sands, and syntectonic resedimentation into low points on the sediment surface. Asynchroneity between Scottish and Irish ice‐marginal fluctuations may reflect differing responses to climate forcing during the Killard Point Stadial, or the effects of local factors such as substrate type and basal ice thermal regime. Copyright © 2004 John Wiley & Sons, Ltd.
A rock avalanche deposit in Burtness Comb, Lake District, northwest England
Authors: Clark Richard , Wilson Peter
Published: September 2004

A large tongue‐shaped accumulation of coarse rock debris in Burtness Comb, Lake District, northwest England, previously regarded as a glacial moraine or relict rock glacier, has been examined and is reinterpreted as the product of rock‐slope failure. The debris tongue has morphological similarities with landforms produced by rock avalanches. This is the first rock avalanche deposit to be reported from the Lake District. Schmidt hammer R‐values and morphological contrasts between the upper and lower parts of the debris imply that two stages of slope failure and downslope debris streaming occurred. In the absence of evidence for a Loch Lomond Stade (c. 12.9–11.5 cal. ka BP) glacier in Burtness Comb, the debris may have accumulated at any time since removal of the Dimlington Stade ice cover (c. 16.8 cal. ka BP) and is regarded as a form of paraglacial landscape response to the effects of glaciation. Copyright © 2004 John Wiley & Sons, Ltd.
Devonian–Carboniferous brachiopod zonation in the Tarim Basin, northwest China: implications for biostratigraphy and biogeography
Authors: Chen Zhong‐Qiang
Published: September 2004

Fourteen brachiopod zones are recognized in the Upper Devonian and Carboniferous successions of the Tarim Basin, northwest China. Of these, the Trifidorostellum longhuiense Zone is established from the Famennian, the Eochoristites neipentaiensis Zone in the lower Tournaisian, the Chuiella aitegouensis Zone from the upper Tournaisian to lowest Viséan; the Brochocarina kunlunensis, Rugosochonetes hardrensis, Buxtonia pseudoscabricula, Vitiliproductus groberi, and Datangia weiningensis zones from the Viséan, the Gigantoproductus edelburgensis Zone from the Serpukhovian age, both Productus productus and Eomarginifera lata zones from the Bashkirian, both Choristites abnormalis and Purdonella artuxensis zones from the Moscovian, and the Linoproductus cora Zone from the Kasimovian–Gzhelian. The faunal characteristics and basin‐wide distributions of these zones are discussed. Close comparisons of the Tarim brachiopod zones with faunas from other regions of China (South China, North China, Tienshan–Junggar, and Tibet), Thailand, Pakistan (Karakorum), Central Asia (Uzbekistan, Kazakhstan, and Afghanistan), and the Urals–Russian Platform suggest that the Tarim faunas were biogeographically closely related to the South Chinese faunas in the late Famennian–Tournaisian and appear to be of a mixture between South Chinese and Central Asian–Uralian faunas, with elements from West Europe, North America, Siberia, and Gondwanaland in the Viséan‐Serpukhovian. The Tarim brachiopods demonstrate stronger links with faunas of the Urals–Russian Platform and Central Asia and, to a lesser extent, with the South Chinese faunas throughout the Bashkirian to Gzhelian. Copyright © 2004 John Wiley & Sons, Ltd.
Mudrock deposition in an ancient dryland system: Moor Cliffs Formation, Lower Old Red Sandstone, southwest Wales, UK
Authors: Marriott Susan B. , Wright V. Paul
Published: September 2004

Studies of the lowermost Old Red Sandstone of South Wales (Pridolian–Lochkovian) have revealed that the mudstones that constitute up to 80% of some of the formations have been deposited in a variety of environments. In addition there is a variety of lithofacies associations present in some mud‐dominated units that suggests diverse mechanisms of deposition. This paper considers the Moor Cliffs Formation and examines four distinct mudrock facies.

The overall depositional environment is considered to have been a multi‐stage, multi‐channel system, similar to a modern dryland river system, with mud‐dominated, moderately sinuous ephemeral rivers that reworked muddy floodplain sediment over a proximal braidplain during seasonal flooding. The alluvial deposits were pedified to varying degrees as calcic Vertisols, which, due to seasonal wetting and drying, provided soil aggregates for reworking by wind and water as sand‐ or silt‐sized pellets. Very infrequent flooding events (superfloods) resulted in extensive stripping of the floodplain surface and the introduction of allochthonous sand sheet deposits over wide areas in this normally sediment‐starved system.

Depressions (pans or waterholes) on the floodplain formed ephemeral lakes following floods, and acted as sediment traps for dust from the frequent dust storms occurring in the system. Copyright © 2004 John Wiley & Sons, Ltd.
Sedimentation and tectonics: the marine Silurian–basal Lower Old Red Sandstone transition in southwest Wales
Authors: Hillier Robert D. , Williams Brian P. J.
Published: September 2004

Both regional and localized tectonic events controlled deposition within the Wenlock and early Ludlow of SW Wales. Estuarine deposits within north–south‐tending incised valleys dominate the youngest (Homerian) Gray Sandstone Group, valley incision being probably related to changing base‐levels associated with Avalonia/Laurentian collision. Available accommodation space was outpaced by sediment supply, with the Red Cliff Formation (Late Ludfordian) defining a conformable transition from marine to Old Red Sandstone (ORS) deposition within the Marloes Peninsula. Sedimentation was dominated by fine‐grained pedified siliciclastics, with subordinate fine‐grained ephemeral sheet‐flood sandstones. Local palaeocurrents indicate sediment transport from the south and west, though long‐distance transport from a distant Laurentian provenance is assumed. A probable tectonically generated sequence boundary marks the base of petrographically distinctive, multi‐storey pebbly sandstones of the Albion Sands Formation, deposited within the hangingwall valley of the active east–west‐trending Wenall Fault. Sediment accommodation space was controlled by proximity to the tip‐point of this important growth fault within the Lower ORS. Debris‐flow‐dominated fans, shed from both the hangingwall and footwall of the Wenall Fault, deposited the Lindsway Bay Formation, an exotic‐clast conglomerate unit sourced predominantly from the south and west. It is uncertain as to whether movement along the Wenall Fault was caused by collision‐related transtension, or rifting associated with the southern margin of Avalonia. Copyright © 2004 John Wiley & Sons, Ltd.
An Early Devonian (Lochkovian) microflora from the Freshwater West Formation, Lower Old Red Sandstone, southwest Wales
Authors: Higgs Kenneth T.
Published: September 2004

The Lower Old Red Sandstone deposits occurring to the south of the Ritec Fault on the Pembroke Peninsula in southwest Wales are very poorly age‐constrained. Two moderately well‐preserved spore assemblages have been recovered from the Freshwater West Formation, locally the highest division of the Milford Haven Group. These assemblages contain both cryptospores and trilete spores, with the latter group being dominant. They essentially represent a single microflora which is assigned to the middle part of the Emphanisporites micrornatus–Streelispora newportensis (MN) Spore Zone and is considered to be of Early Devonian (mid‐Lochkovian) age. A new cryptospore species Qualisaspora sinuata and a new trilete spore species Dictyotriletes williamsii are described. The microflora is correlated with similar assemblages from the Dittonian of the main Anglo‐Welsh Basin. Locally, the new biostratigraphic data constrain the age of the rich ichnofauna of the Freshwater West Formation and also date the influx of coarse clastic sediments into the basin following the sedimentary quiescence represented by the underlying Chapel Point Calcrete. Copyright © 2004 John Wiley & Sons, Ltd.
Prediction of response speed by anticipatory high‐frequency (gamma band) oscillations in the human brain
Authors: Gonzalez Andino Sara L. , Michel Cristoph M. , Thut Gregor , Landis Theodor , Grave de Peralta Rolando
Published: September 2004

Response to a stimulus is faster when a subject is attending and knows beforehand how to respond. It has been suggested recently that this occurs because ongoing neuronal activity is spatially and temporally structured during states of expectancy preceding a stimulus. This mechanism is believed to mediate top‐down processing, facilitating the early grouping and selection of distributed neuronal ensembles implicated in ensuing sensory–motor processing. To validate this model, it must be shown that some features of this early ongoing neural activity are correlated with subsequent perceptual decisions or behavioral events. We investigated this hypothesis in an electrophysiologic study in 12 subjects carrying out a simple visuomotor reaction‐time task. Local field potentials (LFP) at each brain voxel were estimated using a linear distributed inverse solution termed “ELECTRA” for each single trial of each subject. The energy of oscillations for different frequency bands was computed for the period between the warning cue and visual stimuli by applying a time–frequency decomposition to the estimated LFP. A nonparametric correlation coefficient was then calculated between energy of oscillations and reaction times for each single sweep. Gamma band oscillatory activity in a frontoparietal network before stimulus onset significantly correlated with reaction time for a significant amount of subjects. These results provide direct evidence for the role of neural oscillations as a top‐down attentional control mechanism that mediates the speed of motor actions. Hum. Brain Mapping 24:50–58, 2005. © 2004 Wiley‐Liss, Inc.
Dissociation of action and object naming: Evidence from cortical stimulation mapping
Authors: Corina David P. , Gibson Erin K. , Martin Richard , Poliakov Andrew , Brinkley James , Ojemann George A.
Published: September 2004

This cortical stimulation mapping study investigates the neural representation of action and object naming. Data from 13 neurosurgical subjects undergoing awake cortical mapping is presented. Our findings indicate clear evidence of differential disruption of noun and verb naming in the context of this naming task. At the individual level, evidence was found for punctuate regions of perisylvian cortex subserving noun and verb function. Across subjects, however, the location of these sites varied. This finding may help explain discrepancies between lesion and functional imaging studies of noun and verb naming. In addition, an alternative coding of these data served to highlight the grammatical class vulnerability of the target response. The use of this coding scheme implicates a role for the supramarginal gyrus in verb‐naming behavior. These data are discussed with respect to a functional–anatomical pathway underlying verb naming. Hum. Brain Mapping 24:1–10, 2005. © 2004 Wiley‐Liss, Inc.
A comparison of the EQ‐5D and SF‐6D across seven patient groups
Authors: Brazier John , Roberts Jennifer , Tsuchiya Aki , Busschbach Jan
Published: September 2004

As the number of preference‐based instruments grows, it becomes increasingly important to compare different preference‐based measures of health in order to inform an important debate on the choice of instrument. This paper presents a comparison of two of them, the EQ‐5D and the SF‐6D (recently developed from the SF‐36) across seven patient/population groups (chronic obstructive airways disease, osteoarthritis, irritable bowel syndrome, lower back pain, leg ulcers, post menopausal women and elderly). The mean SF‐6D index value was found to exceed the EQ‐5D by 0.045 and the intraclass correlation coefficient between them was 0.51. Whilst this convergence lends some support for the validity of these measures, the modest difference at the aggregate level masks more significant differences in agreement across the patient groups and over severity of illness, with the SF‐6D having a smaller range and lower variance in values. There is evidence for floor effects in the SF‐6D and ceiling effects in the EQ‐5D. These discrepancies arise from differences in their health state classifications and the methods used to value them. Further research is required to fully understand the respective roles of the descriptive systems and the valuation methods and to examine the implications for estimates of the impact of health care interventions. Copyright © 2004 John Wiley & Sons, Ltd.
Modelling EuroQol health‐related utility values for diabetic complications from CODE‐2 data
Authors: Bagust Adrian , Beale Sophie
Published: September 2004

Recent research has employed different analytical techniques to estimate the impact of the various long‐term complications of type 2 diabetes on health‐related utility and health status. However, limited patient numbers or lack of variety of patient experience has limited their power to discriminate between separate complications and grades of severity.

In this study alternative statistical model forms were compared to investigate the influence of various factors on self‐assessed health status and calculated utility scores, including the presence and severity of complications, and type of diabetes therapy. Responses to the EuroQol EQ‐5D questionnaire from 4641 patients with type 2 diabetes in 5 European countries were analysed. Simple multiple regression analysis was used to model both visual analogue scale (VAS) scores and time trade‐off index scores (TTO). Also, two complex models were developed for TTO analysis using a structure suggested by the EuroQol calculation algorithm.

Both VAS and TTO models achieved greater explanatory power than in earlier studies. Relative weightings for individual complications differed between VAS and TTO scales, reflecting the strong influence of loss of mobility and severe pain in the EuroQol algorithm. Insulin‐based therapy was uniformly associated with a detrimental effect equivalent to an additional moderate complication. Evidence was found that TTO values are not responsive in cases where 3 or more multiple complications are present, and therefore may underestimate utility loss for patients most adversely affected by complex chronic diseases like diabetes. Copyright © 2004 John Wiley & Sons, Ltd.
The impact of price regulation on the launch delay of new drugs—evidence from twenty‐five major markets in the 1990s
Authors: Danzon Patricia M. , Wang Y. Richard , Wang Liang
Published: September 2004

We analyze the effect of price regulation on delays in launch of new drugs. Because a low price in one market may ‘spill‐over’ to other markets, through parallel trade and external referencing, manufacturers may rationally prefer longer delay or non‐launch to accepting a relatively low price. We analyze the launch in 25 major markets, including 14 EU countries, of 85 new chemical entities (NCEs) launched between 1994 and 1998. Each NCE's expected price and market size in a country are estimated using lagged average price and market size of other drugs in the same (or related) therapeutic class. We estimate a Cox proportional hazard model of launch in each country, relative to first global launch.

Only 55% of the potential launches occur. The US leads with 73 launches, followed by Germany (66) and the UK (64). Only 13 NCEs are launched in Japan, 26 in Portugal and 28 in New Zealand. The results indicate that countries with lower expected prices or smaller expected market size have fewer launches and longer launch delays, controlling for per capita income and other country and firm characteristics. Controlling for expected price and volume, country effects for the likely parallel export countries are significantly negative. Copyright © 2004 John Wiley & Sons, Ltd.
Stochastic league tables: an application to diabetes interventions in the Netherlands
Authors: Hutubessy Raymond C. W. , Niessen Louis W. , Dijkstra Rob F. , Casparie Ton F. , Rutten Frans F.
Published: September 2004

The aim of this paper is to discuss the use of stochastic league tables approach in cost‐effectiveness analysis of diabetes interventions. It addresses the common grounds and differences with other methods of presenting uncertainty to decision‐makers.

This comparison uses the cost‐effectiveness results of medical guidelines for Dutch diabetes type 2 patients in primary and secondary care.

Stochastic league tables define the optimum expansion pathway as compared to baseline, starting with the least costly and most cost‐effective intervention mix. Multi‐intervention cost‐effectiveness acceptability curves are used as a way to represent uncertainty information on the cost‐effectiveness of single interventions as compared to a single alternative. The stochastic league table for diabetes interventions shows that in case of low budgets treatment of secondary care patients is the most likely optimum choice. Current care options of diabetes complications are shown to be inefficient compared to guidelines treatment. With more resources available one may implement all guidelines and improve efficiency.

The stochastic league table approach and multi‐intervention cost‐effectiveness acceptability curves in uncertainty analysis lead to similar results. In addition, the stochastic league table approach provides policy makers with information on affordability by budget level. It fulfils more adequately the information requirements to choose between interventions, using the efficiency criterion. Copyright © 2004 John Wiley & Sons, Ltd.
LigaSure versus clamp‐and‐tie thyroidectomy for benign nodular disease
Authors: Petrakis Ioannis E. , Kogerakis Nektarios E. , Lasithiotakis Kostas G. , Vrachassotakis Nikolaos , Chalkiadakis Georgios E.
Published: September 2004

Background.

LigaSure is an alternative bipolar diathermy system (BDS) combining vessel sealing with reduced thermal spread, which has been successfully used in many abdominal operations; however, there is a little experience in open thyroidectomy. This study compares the efficacy and the advantages of the LigaSure BDS when used for total thyroidectomy for benign thyroid disease with the conventional clamp‐and‐tie technique.

Methods.

Between May 1998 and October 2002, 517 patients underwent total thyroidectomy for benign thyroid multinodular goiter. Among them, from May 1998 until May 2000, 247 patients (group I) were operated on with the conventional clamp‐and‐tie technique, whereas from May 2000 until October 2003, 270 patients (group II) underwent total thyroidectomy for benign multinodular goiter with LigaSure BDS through a 4‐cm transverse suprasternal incision. Demographics, pathologic characteristics, gland mass, operative time, blood loss, and complications were assessed.

Results.

There were no intraoperative complications. Thyroid mass was similar in both groups, but the operative time was shorter in group II than in group I (mean ± standard deviation, 71 ± 14 minutes vs 86 ± 22 minutes; p < .01). Intraoperative total blood loss was similar between the two groups, but postoperative drain volume was less in group II than in group I (21 ± 15 mL; p < .01). Major post‐thyroidectomy complications (ie, laryngeal nerve palsy, hematoma, and hypocalcemia) occurred less frequently in the LigaSure group than in the clamp‐and‐tie group (0.7%, 0.4%, 1.1% vs 4%, 2%, 4.8%, respectively; p < .05). The mean ± standard deviation postoperative hospital stay was significantly less for the patients in group II than for those in group I (2.3 ± 1.7 days vs 2.8 ± 1.3 days; p < .05).

Conclusions.

The use of the LigaSure vessel sealer for thyroid surgery is an effective and safe alternative that reduces the overall operative time and could be successfully applied through a narrow surgical incision. © 2004 Wiley Periodicals, Inc. Head Neck 26: 903–909, 2004
p73 expression for human buccal epithelial dysplasia and squamous cell carcinoma: Does it correlate with nodal status of carcinoma and is there a relationship with malignant change of epithelial dysplasia?
Authors: Chen Yuk‐Kwan , Hsue Shui‐Sang , Lin Li‐Min
Published: September 2004

Background.

TP73, a p53 homologue gene, shares similar structural sequences with p53. The aim of this study was to investigate the p73 expression for human buccal epithelial dysplasia (ED) and squamous cell carcinoma (SCC).

Methods.

Seventy‐five samples of human buccal ED, including mild, moderate, and severe ED (25 samples in each category), were analyzed for p73 protein expression by means of immunohistochemistry. Twenty‐five samples of human buccal SCCs were analyzed for p73 mRNA expression with reverse transcription‐polymerase chain reaction (RT‐PCR) and were also analyzed for protein expression with immunohistochemical analysis.

Results.

By use of immunohistochemical analysis, nuclear staining of p73 protein was detected in a subset of normal mucosa, buccal ED, and SCC specimens. p73 nuclear staining was noted for the basal cells of normal buccal mucosa. For buccal lesions deriving from mild, moderate, and severe ED, p73 protein was observed in basal and parabasal layers and in more superficial cell layers corresponding to the spinous layer. For well‐differentiated carcinomas, p73 immunoreactivity was chiefly observed among the less‐differentiated cells in the periphery of carcinomatous clusters, whereas moderately differentiated carcinomas revealed homogeneous staining, involving nearly all of the tumor cells. On RT‐PCR, the expression of p73 mRNA from buccal SCC was noted to be compatible with the findings of immunohistochemical analysis. An electrophoretic band with a 180‐bp PCR product corresponding to p73 mRNA has been observed. The expression of p73 seemed to be significantly elevated for specimens of buccal ED (protein level) and SCC (protein and mRNA levels) compared with the analogous expression for normal control tissue (Fisher's exact test, p < .001). Also, p73 expression (protein and mRNA levels) correlated significantly with cervical lymph node metastasis for cases of buccal SCC (Fisher's exact test, p < .001). Eight cases of ED (protein level) showing p73 positivity have undergone malignant transformation to develop SCCs in 2 years follow‐up, but no statistical significance was established (Fisher's exact test, p > .05).

Conclusions.

The data suggest that p73 expression may be (1) associated with the differentiation of oral stratified squamous epithelium, (2) an early event in human oral carcinogenesis, and (3) associated with the nodal status of patients with oral carcinoma and a possible indicator for malignant change of oral ED. © 2004 Wiley Periodicals, Inc. Head Neck 26: 945–952, 2004
Mental models, team mental models, and performance: Process, development, and future directions
Authors: Langan‐Fox Janice , Anglim Jeromy , Wilson John R.
Published: September 2004

Since the 1940s, researchers have grappled with the notion of a mental model. The concept is eminently reasonable and somewhat seductive, but presents us with a number of difficulties regarding its incompleteness, multiplicity, and inconsistency. Not the least of these difficulties is the problem of “capturing” (measuring) mental models, and still more difficult, capturing a team mental model, an extension of the earlier term. Once captured, finding an appropriate analytic procedure to analyze team mental models has challenged researchers for a long time. Nonetheless, the literature suggests that the construct is well worth the trouble, with many applied benefits especially to industry. In the present work we set out to (a) review the notion of team mental models (TMM); (b) identify the key concepts and thinking behind their development; (c) demonstrate how they support teamworking performance; and (d) outline a three‐phase model of TMM development. Details on TMM measurement are given, before concluding with a discussion of the difficulties facing researchers who wish to study and utilize the notion, and some of the pressing research issues that need investigation. © 2004 Wiley Periodicals, Inc. Hum Factors Man 14: 331–352, 2004.
Team assessment when members have low reading proficiency
Authors: Littlepage Glenn E. , Brower Grant
Published: September 2004

Work teams sometimes include individuals with low levels of reading proficiency. Traditional team assessment instruments may not be suitable for use with such teams. A well‐known teamwork instrument, the Team Excellence survey (LaFasto & Larson, 1987), was simplified to enhance readability. Fifty‐two participants completed both the original and simplified versions. Analyses indicated that the simplified instrument had psychometric qualities roughly equivalent to the original instrument. The simplified instrument is appropriate for use as a team assessment instrument when the reading level of team members is low.
Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: A comparative population‐based study in Singapore and Sweden
Authors: Chia Kee‐Seng , Reilly Marie , Tan Chuen‐Seng , Lee Jeannette , Pawitan Yudi , Adami Hans‐Olov , Hall Per , Mow Benjamin
Published: September 2004

Breast cancer incidence in Sweden has always been approximately twice as high as in Singapore. In recent years, this difference is limited to postmenopausal women. The aim of this study was to explore the reasons behind these differences through the use of age‐period‐cohort modeling. This population‐based study included all breast cancer cases reported to the Swedish and the Singapore cancer registries from 1968 to 1997, with a total of 135,581 Swedish and 10,716 Singaporean women. Poisson regression using age‐period and age‐cohort models was used to determine the effects of age at diagnosis, calendar period and birth cohort. Incidence rate ratios were used to summarize these effects. An age‐cohort model provided the best fit to the data in both countries, indicating that changes over lifetime, rather than recent differences in medical surveillance, might account for the observed differences in these 2 populations. The changes over birth cohort were much greater among Singaporean women. The relative effect of age was very similar in the 2 countries. Analyses show that age and cohort effects may explain the differences in trends of female breast cancer incidence between Sweden and Singapore. The larger cohort effect seen in Singaporean women may be attributed to more rapid changes in reproduction and lifestyle patterns than that of Swedish women during the period studied. The incidence of breast cancer in postmenopausal women in Singapore will probably continue to rise in the coming decades to match the current Swedish rates.
Mutations of BRAF and RAS are rare events in germ cell tumours
Authors: Sommerer Florian , Hengge Ulrich R. , Markwarth Annett , Vomschloss Susanne , Stolzenburg Jens‐Uwe , Wittekind Christian , Tannapfel Andrea
Published: September 2004

The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. Recently, somatic missense mutations in the BRAF gene have been detected in a variety of human tumors. We have studied male germ cell tumours (GCT) for probable mutations of the BRAF and Ras oncogene. Microsatellite instability (MSI) was analysed using mono‐ or di‐nucleotide marker. Mutational analysis of 62 GCT (30 seminomas and 32 nonseminomas) was performed after microdissection of the different tumour components. The expression of Erk1/2, an important downstream point of convergence in the Ras‐RAF‐MEK‐Erk pathway was assessed immunohistochemically. Activating BRAF missense mutations were identified in 3 out of 32 cases of nonseminomas (9%) but not in seminomas. The mutations were 1796T>A mutations and were found within the embryonic carcinoma component of these tumors. Two out of 30 seminomas (7%) and 3 out of 32 nonseminomas (9%) exhibited KRAS gene mutations. MSI was observed in 4 out 62 tumours (7%) [1 seminoma and 3 nonseminomas (embryonal carcinoma)]. All of the microsatellite instable embryonal carcinomas had a mutated BRAF gene. All 5 GCT with RAS mutations had an intact BRAF gene. We identified constitutively activated Erk in almost all tumours tested. Our data indicate that BRAF gene mutations are a rare event in GCT and are independent of KRAS mutations. In embryonal carcinomas, BRAF mutations may be linked to the proficiency of these tumours in repairing mismatched bases in DNA. The finding of activated Erk suggests a causative role for MAPK activation in GCT independent of activating BRAF or RAS mutations.
Overexpression and significance of prion protein in gastric cancer and multidrug‐resistant gastric carcinoma cell line SGC7901/ADR
Authors: Du Jingping , Pan Yanglin , Shi Yongquan , Guo Changcun , Jin Xiaohang , Sun Li , Liu Na , Qiao Taidong , Fan Daiming
Published: September 2004

In our previous work, cellular prion protein (PrPc) was identified as an upregulated gene in adriamycin‐resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Here we investigate the expression of PrPc in gastric cancer and whether it was involved in multidrug resistance (MDR) of gastric cancer. We demonstrated that PrPc was ubiquitously expressed in gastric cancer cell lines and tissues. PrPc conferred resistance of both P‐glycoprotein (P‐gp)‐related and P‐gp‐nonrelated drugs on SGC7901, which was accompanied by decreased accumulation and increased releasing amount of adriamycin in PrPc‐overexpressing cell line. Inhibition of PrPc expression by antisense or RNAi technology could partially reverse multidrug‐resistant phenotype of SGC7901/ADR. PrPc significantly upregulated the expression of the classical MDR‐related molecule P‐gp but not multidrug resistance associated protein and glutathione S‐transferase pi. The PrPc‐induced MDR could be partially reversed by P‐gp inhibitor verapamil. PrPc could also suppress adriamycin‐induced apoptosis and alter the expression of Bcl‐2 and Bax, which might be another pathway contributing to PrPc‐related MDR. The further study of the biological functions of PrPc may be helpful for understanding the mechanisms of occurrence and development of clinical gastric carcinoma and PrPc‐related MDR and developing possible strategies to treat gastric cancer.
Introduction
Authors: Dalton Jon C. , Fitzgerald Henck Anita
Published: September 2004

The authors examine the importance of character development in higher education today and the challenges of assessing this complex educational outcome.
Gelatin‐embedded cell–polymer constructs for histological cryosectioning
Authors: Brown David A. , Chou Yu Fen , Beygui Ramin E. , Dunn James C.Y. , Wu Benjamin M.
Published: September 2004

Many tissue‐engineering strategies involve the delivery of cells via porous polymer scaffolds. Obtaining histological sections of the emerging tissue is often necessary to analyze numerous characteristics of the microscopic environment. However, difficulties arise upon applying standard histological techniques to cell‐seeded polymer scaffolds. This report describes a simple and reliable method for cryosectioning cell–polymer constructs embedded in gelatin. Solvent‐soluble (PLGA) and insoluble (PGA) scaffolds were cultured in vitro with preosteoblasts, followed by histological processing with paraffin, OCT, or gelatin. Although paraffin‐embedded PGA scaffolds withstood standard sectioning and rinsing steps, paraffin‐embedded PLGA scaffolds were partially dissolved during the clearing step. OCT‐embedded scaffolds produced sections that did not adhere well to slides, and most of the sample was lost during rinsing steps. In contrast, gelatin‐embedded scaffolds exhibited adequate structural integrity during cryosectioning, adhered well to the slides, retained the actual polymer morphology, and exhibited compatibility with common stains. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 79–85, 2005
TNF receptor type 1 regulates RANK ligand expression by stromal cells and modulates osteoclastogenesis
Authors: Abu‐Amer Yousef , Abbas Sabiha , Hirayama Teruhisa
Published: September 2004

TNFα is a major osteoclastogenic cytokine and a primary mediator of inflammatory osteoclastogenesis. We have previously shown that this cytokine directly targets osteoclasts and their precursors and that deletion of its type‐1 receptor (TNFr1) lessens osteoclastogenesis and impacts RANK signaling molecules. Osteoclastogenesis is primarily a RANK/RANKL‐dependent event and occurs in an environment governed by both hematopoietic and mesenchymal compartments. Thus, we reasoned that TNF/TNFr1 may regulate RANKL and possibly RANK expression by stromal cells and osteoclast precursors (OCPs), respectively. RT‐PCR experiments reveal that levels of RANKL mRNA in WT stromal cells are increased following treatment with 1,25‐VD3 compared to low levels in TNFr1‐null cells. Expression levels of OPG, the RANKL decoy protein, were largely unchanged, thus supporting a RANKL/OPG positive ratio favoring WT cells. RANK protein expression by OCPs was lower in TNFr1‐null cells despite only subtle differences in mRNA expression in both cell types. Mix and match experiments of different cell populations from the two mice phenotypes show that WT stromal cells significantly, but not entirely, restore osteoclastogenesis by TNFr1‐null OCPs. Similar results were obtained when the latter cells were cultured in the presence of exogenous RANKL. Altogether, these findings indicate that in the absence of TNFr1 both cell compartments are impaired. This was further confirmed by gain of function experiments using TNFr1‐ null cultures of both cell types at which exogenous TNFr1 cDNA was virally expressed. Thus, restoration of TNFr1 expression in OCPs and stromal cells was sufficient to reinstate osteoclastogenesis and provides direct evidence that TNFr1 integrity is required for optimal RANK‐mediated osteoclastogenesis. © 2004 Wiley‐Liss, Inc.
Modulation of O‐GlcNAc glycosylation during Xenopus oocyte maturation
Authors: Lefebvre Tony , Baert Frédéric , Bodart Jean‐François , Flament Stéphane , Michalski Jean‐Claude , Vilain Jean‐Pierre
Published: September 2004

O‐linked N‐acetylglucosamine (O‐GlcNAc) glycosylation is a post‐translational modification, which is believed antagonises phosphorylation. We have studied the O‐GlcNAc level during Xenopus oocyte meiotic resumption, taking advantage of the high synchrony of this model which is dependent upon a burst of phosphorylation. Stimulation of immature stage VI oocytes using progesterone was followed by a 4.51 ± 0.32 fold increase in the GlcNAc content, concomitantly to an increase in phosphorylation, notably on two cytoplasmic proteins of 66 and 97 kDa. The increase of O‐GlcNAc for the 97 kDa protein, which we identified as β‐catenin was partly related to its accumulation during maturation, as was demonstrated by the use of the protein synthesis inhibitor—cycloheximide. Microinjection of free GlcNAc, which inhibits O‐glycosylated proteins–lectins interactions, delayed the progesterone‐induced maturation without affecting the O‐GlcNAc content. Our results suggest that O‐GlcNAc glycosylation could regulate protein–protein interactions required for the cell cycle kinetic. © 2004 Wiley‐Liss, Inc.
Quantitative structure–activity relationships for phenyl triazolinones of protoporphyrinogen oxidase inhibitors: A density functional theory study
Authors: Wan Jian , Zhang Li , Yang Guangfu
Published: September 2004

The equilibrium geometries, electronic structures, and electrostatic potentials of a series of substituted phenyl triazolinones of protoporphyrinogen oxidase (PPO) inhibitors have been investigated by using the density functional theory (DFT) method. The quantum chemical descriptors, highest occupied molecular orbital and lowest unoccupied molecular orbital energy gap (ΔE), weighted electrophilic, and nucleophilic atomic frontier electron density (F and F), and net atomic charge (QA), were computed at the same DFT level. Based on these precise quantum chemical descriptors, a quantitative structure–activity relationships study has been carried out and shown that Q, F, F, and ΔE of individual molecules are most likely to be responsible for the in vitro biological activity and greenhouse preemergence activity of phenyl triazolinones. The ability to quite accurately predict the biological activity of phenyl triazolinones by using DFT‐based QSAR can be expected to help facilitate the design of additional substituted phenyl triazolinones as PPO inhibitors with good biological activity. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1827–1832, 2004
Simultaneously multi‐parameter determination of hematonosis cell apoptosis by two‐photon and confocal laser scanning microscopy
Authors: Wang Yi , Wang Xue‐Feng , Wang Chen , Ma Hui
Published: September 2004

Flow cytometry (FCM), TdT‐mediated dUTP Nick End Labeling (TUNEL), and DNA ladder are conventional methods to detect apoptosis of drug‐treated cells. However, the assumption of cell number restricts their applications in clinics. In this paper, we report a cell‐saving imaging method for quick identification of the hematonosis cell apoptosis induced by chemotherapeutic drugs. By the combination of two‐photon and confocal microscopy, three main apoptosis parameters (the change of nuclear morphology, collapse of mitochondrial membrane potential, and increase of intracellular calcium) were recorded simultaneously for single As2O3‐induced Molt‐4 cells. The results are highly in accordance with those produced by classical flow cytometry. This work suggests that this new imaging method would be promising in the quick identification of hematonosis cell apoptosis. J. Clin. Lab. Anal. 18:271–275, 2004. © 2004 Wiley‐Liss, Inc.
Urokinase gene 3′‐UTR T/C polymorphism is associated with oral cancer
Authors: Tsai Ming‐Hsui , Chen Wen‐Chi , Chen Huey‐Yi , Tsai Fuu‐Jen
Published: September 2004

Urokinase is thought to be involved in the formation of oral cancer, although there is a lack of genetic evidence. Our aim was to study single nucleotide polymorphisms in order to investigate the possibility. A total of 130 oral cancer patients and 105 controls were studied. Polymerase chain reaction (PCR) based restriction analysis was used to identify the C/T polymorphism of the urokinase gene, which is located on the 3′‐untranslated region (3′‐UTR) of chromosome 10. There was a significant difference in the distribution of the urokinase gene 3′‐UTR C/T polymorphism frequency between cancer patients and the normal control group (P<0.05). The “T” allele was prominent in the cancer group. The odds ratio for the risk of the “T” allele in cancer patients was 2.71 (95% CI=1.325∼5.562). The cancer patients were further categorized according to gender and whether or not they were habitual smokers or betel nut chewers. These clinical parameters were then compared with tumor cell differentiation and tumor progression. No significant differences were found. Therefore, the urokinase gene 3′‐UTR “T” allele is associated with oral cancer and may play a role in oral cancer formation. However, we did not find the relationship between tumor progression and this polymorphism. J. Clin. Lab. Anal. 18:276–279, 2004. © 2004 Wiley‐Liss, Inc.
Measurement of C‐reactive protein: Two high sensitivity methods compared
Authors: Dominici Roberto , Luraschi Paola , Franzini Carlo
Published: September 2004

C‐reactive protein (CRP) is an acute phase marker and a predictor of the risk of developing atherosclerotic complications. However, as a predictor of this risk, high sensitivity measurements are needed, and high sensitive CRP (hsCRP) assays have been developed. In this study, we experimentally compared two hsCRP assays, based on nephelometry and turbidimetry, both implemented on automated analyzers. Linearity, imprecision, turbidity interference, and results in the assay of 96 samples have been compared. Method comparison of the same two analytical systems in the assay of CRP was also performed on the basis of results in an interlaboratory external quality assessment scheme (EQAS). The two systems were found to perform substantially equally, both in hsCRP and in CRP measurement, but in the hsCRP assay the precision of nephelometry (CV% in the interval 3.0–5.8) was lower than that of turbidimetry (CV% in the interval 1.8–2.3). The classification of results by the two methods into three predefined relative risk classes gave 18% rate of discordance, in any case by one class only. The two methods proved reliable and comparable in the measurement of hsCRP, but precision should be improved. J. Clin. Lab. Anal. 18:280–284, 2004. © 2004 Wiley‐Liss, Inc.
Challenges in treating obsessive‐compulsive disorder: Introduction
Authors: Wilhelm Sabine , Tolin David F. , Steketee Gail
Published: September 2004

This issue of In Session is devoted to challenges in the treatment of obsessive‐compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises. Articles focus on the treatment of OCD with comorbid depression, compulsive hoarding, incompleteness, and repugnant obsessions, and on treatment of children who have OCD. The final article describes pharmacotherapy for OCD. All articles feature case vignettes and provide practitioners with clinical recommendations. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Treatment of compulsive hoarding
Authors: Saxena Sanjaya , Maidment Karron M.
Published: September 2004

Compulsive hoarding and saving symptoms, found in many patients who have obsessive‐compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to antiobsessional medications and cognitive‐behavioral therapy (CBT). Specific CBT strategies targeting the characteristic features of the compulsive hoarding syndrome have had better results. This article provides an overview of the compulsive hoarding syndrome, a review of treatment approaches and their efficacy, a case presentation, and a detailed discussion of intensive, multimodal CBT for compulsive hoarding. New insights into the neurobiological characteristics of compulsive hoarding that might direct future treatment development are also presented. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Cognitive‐behavioral treatment of repugnant obsessions
Authors: Purdon Christine
Published: September 2004

Obsessions often occur in the form of repugnant sexual, aggressive, or blasphemous thoughts, images, impulses, or doubts. This article describes the phenomenon of repugnant obsessions and reviews the cognitive‐behavioral model of obsessive‐compulsive disorder (OCD). Caveats and recommendations are provided and a case illustration is presented. Repugnant obsessions are highly amenable to treatment; but developing an idiographic conceptualization of the client's obsessive‐compulsive cycle is important. Treatment resources are presented throughout. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.
Pharmacotherapy for obsessive‐compulsive disorder
Authors: Dougherty Darin D. , Rauch Scott L. , Jenike Michael A.
Published: September 2004

Pharmacotherapeutic options for obsessive‐compulsive disorder (OCD) have expanded over the past half‐century since medications were first found to be effective for the treatment of OCD. Currently, the serotonin reuptake inhibitors (SRIs) represent the first‐line pharmacotherapy for OCD. High dosages and long trials of the SRIs are needed for adequate treatment of OCD. The use of SRIs for the treatment of OCD is reviewed, then other pharmacotherapeutic treatment options, including SRI augmentation and alternative monotherapies, are discussed. The preponderance of data demonstrates that SRI augmentation with neuroleptics is efficacious for treatment‐refractory OCD. There is substantially less evidence supporting other alternative strategies. Finally, neurosurgical and device‐based approaches for treatment‐refractory OCD are reviewed. © 2004 Wiley Periodicals, Inc. J Clin Psychol/In Session.