bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of User‐Oriented Design on New Product Development: An Examination of Fundamental Relationships*
Authors: Veryzer Robert W. , Borja de Mozota Brigitte 
Published: February 2005

Design offers a potent way to position and to differentiate products and can play a significant role in their success. In many ways it is the focus on deep understanding of the customer or user—what may be termed user‐oriented design (UOD)—that transforms a bundle of technology with the ability to provide functionality into a “product” that people desire to interact with and from which they derive benefits. Even though the importance of this type of design is gaining recognition, several fundamental relationships between user‐oriented design contributions and the new product development (NPD) process and outcomes (i.e., product) remain unresearched, although they are assumed. This article examines the fundamental relationships underlying the incorporation of a user orientation into the NPD process. The discussion is organized around UOD's impact in terms of enhancing collaborative new product development (process oriented), improving idea generation (process oriented), producing superior product or service solutions (product oriented), and facilitating product appropriateness and adoption (product oriented). Each of these is developed and presented in the form of a research proposition relating to the impact of user‐oriented design on product development. The fundamental relationships articulated concerning UOD's impact on NPD form a conceptual framework for this approach to product design and development.For practitioners, the article suggests how user‐oriented design can improve NPD through its more grounded and comprehensive approach, along with the elevated appreciation of design challenges and heightened sense of possibilities for a product being developed. For scholars, the article identifies four important areas for UOD research. In addition to the rich avenues offered for research by each of these, the framework presented provides a foundation for further study as well as the development of new measures and tools for enhancing NPD efforts.
A placebo‐controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments
Authors: Winhusen Theresa M. , Somoza Eugene C. , Harrer Judy M. , Mezinskis Juris P. , Montgomery Margaret A. , Goldsmith R. Jeffrey , Coleman Florence S. , Bloch Daniel A. , Leiderman Deborah B. , Singal Bonita M. , Berger Paul , Elkashef Ahmed 
Published: February 2005

ABSTRACTAims  To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence.Design  A 10‐week out‐patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.Setting  This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio.Participants  Participants met Diagnostic and Statistical Manual version IV (DSM‐IV) criteria for cocaine dependence. Sixty‐seven participants were enrolled with 55 completing final study measures.Intervention  The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.Measurements  Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale–Observer and self‐report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests.Findings  Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5–8 (P = 0.10) and non‐significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures.Conclusions  The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.
Outcome of radioiodine‐131 therapy in hyperfunctioning thyroid nodules: a 20 years’ retrospective study
Authors: Ceccarelli Claudia , Bencivelli Walter , Vitti Paolo , Grasso Lucia , Pinchera Aldo 
Published: February 2005

SummaryObjective  To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules.Design  Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years.Patients  A total of 346 patients treated with 131I in the years 1975–95, for a single hyperfunctioning nodule.Measurements  Hypothyroidism was defined as TSH levels > 3·7 mU/l. Kaplan–Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism.Results  The cumulative incidence of hypothyroidism was 7·6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0·01), 24‐th 131I uptake (P < 0·05) and previous treatment with methimazole (MMI, P < 0·1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0·01).Conclusions  After 20 years of follow‐up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.
The relative importance of genetic and environmental factors in the aetiology of thyroid nodularity: a study of healthy Danish twins
Authors: Hansen Pia Skov , Brix Thomas Heiberg , Bennedbæk Finn Noe , Bonnema Steen Joop , Iachine Ivan , Kyvik Kirsten Ohm , Hegedüs Laszlo 
Published: February 2005

SummaryBackground  A large proportion of healthy, euthyroid, nongoitrous individuals have thyroid nodules. The aetiology of these ultrasonographically detected morphological abnormalities is largely unknown. Factors such as age, gender, iodine intake, smoking and parity are associated with nodularity of the thyroid. Whether there is a genetic susceptibility is unclear.Aim  To gain insight into the aetiology of thyroid nodularity by investigating a large cohort of healthy euthyroid monozygotic and dizygotic twins.Design  A cross‐sectional twin study.Participants  A representative sample of self‐reported healthy twin pairs was identified through the Danish Twin Registry. A total of 520 individuals divided into 104 monozygotic (MZ), 107 dizygotic same sex (DZ) and 49 opposite sex (OS) twin pairs were investigated.Measurements  Probandwise concordance and tetrachoric correlations. Quantitative genetic modelling was used to elucidate the relative importance of genetic and environmental effects for the variation in the liability of nodularity.Results  A higher concordance rate for thyroid nodularity was found in MZ twins [0·57 (95% CI 0·36–0·76)] than in DZ twins [0·36 (95% CI 0·17–0·56, P = 0·074)]. The same was true for tetrachoric correlations: 0·67 (95% CI 0·34–0·87) in MZ twins and 0·17 (CI – 0·28–0·56, P = 0·053) in DZ twins. The difference, although not significant, was more pronounced for multiple nodules than for solitary nodules. Controlling for covariates (age, gender and smoking habits), it was calculated that genetic factors accounted for 67% (95% CI 35–87%) and environmental factors for 33% (95% CI 13–65%) of the individual differences in the liability to thyroid nodularity.Conclusions  This study suggests that genetic factors are of aetiological importance for thyroid nodularity in clinically healthy and euthyroid individuals, and indicates a difference in the aetiology of solitary and multiple thyroid nodules.
Facilitated nitration and oxidation of LDL in cigarette smokers
Authors: Yamaguchi Y. , Haginaka J. , Morimoto S. , Fujioka Y. , Kunitomo M. 
Published: February 2005

AbstractBackground  Cigarette smoking increases the risk of developing atherosclerosis and ischaemic heart disease. Smoking‐induced oxidative stress is considered to favour oxidation of low‐density lipoprotein (LDL) and subsequently promotes the atherogenic process. We investigated whether peroxynitrite, a reaction product of cigarette smoke, is involved in facilitated oxidation of LDL in smokers.Materials and methods  Plasma LDL was obtained from 10 healthy asymptomatic cigarette smokers and 10 healthy nonsmokers. The state of enhanced oxidative stress in the plasma was assessed by LDL subfraction assay using anion‐exchange high‐performance liquid chromatography (AE‐HPLC) and measurements of thiobarbituric acid‐reactive substances (TBARS), 8‐hydroxydeoxyguanosine (8‐OHdG), vitamin E, 3‐nitrotyrosine and 3‐chlorotyrosine.Results  Smokers showed a significantly higher level of TBARS and 8‐OHdG as well as a significantly lower level of vitamin E than nonsmokers, even after stopping smoking for 10 h or more. The LDL subfraction assay demonstrated an increase in oxidatively modified LDL, as expressed by lower levels of LDL1 and higher levels of LDL2. The 3‐nitrotyrosine levels in apolipoprotein B in LDL were significantly higher in smokers than nonsmokers, while the 3‐chlorotyrosine levels remained unchanged. In addition, these changes observed in the smokers were further accelerated within 30 min after resumption of cigarette smoking when compared with the levels before smoking resumption.Conclusion  The present study suggests that peroxynitrite plays a significant role in oxidative modification of plasma LDL induced by cigarette smoking.
Comparative chromosomal studies of E. caballus (ECA) and E. przewalskii (EPR) in a female F1 hybrid
Authors: Ahrens E. , Stranzinger G. 
Published: February 2005

SummaryPrevious research revealed that the karyotypes of Equus przewalskii (2n = 66) and Equus caballus (2n = 64) differ by one pair of metacentric chromosomes, present in ECA but not in EPR, and two pairs of acrocentric chromosomes found only in the EPR karyotype. The formation of a trivalent during meiosis in a male F1 hybrid and the homologies in G‐banding patterns suggest that ECA 5 corresponds to two acrocentric EPR chromosomes resulting from a Robertsonian fusion or fission event. Chromosomal investigations of a female interspecies F1 hybrid including banded karyograms and fluorescence in situ hybridization (FISH) studies focusing on the p and q arm of ECA 5 were conducted. Q‐ and G‐banding patterns of E. caballus, E. przewalskii and the hybrid revealed interspecies homology between all chromosome pairs except for ECA 5, EPR 23 and EPR 24, which were unique for that particular species. Furthermore, they indicated homology between ECA 5p and EPR 23 as well as between ECA 5q and EPR 24. FISH revealed hybridization of the BACs laminin beta 3 (LAM B3) and laminin gamma 2 (LAM C2) to ECA 5p and EPR 23. However, nuclear factor I (NFIA) and immunoglobulin lambda (IGL@), primarily assigned to ECA 5q, mapped to ECA 7 and EPR 6 respectively. Thus the karyotypes of E. caballus and E. przewalskii differ solely by one Robertsonian translocation (ECA 5 =EPR 23 + EPR 24).
Close genetic relationship of early Neolithic cattle from Ziegelberg (Freising, Germany) with modern breeds
Authors: Kühn R. , Ludt C. , Manhart H. , Peters J. , Neumair E. , Rottmann O. 
Published: February 2005

SummaryIn 2003 a variety of crafts and bone specimens were found during excavations of a Neolithic settlement near Freising, the southernmost site of the Linear Pottery Culture in Bavaria. Six cattle bones were used to extract ancient DNA (aDNA). Applying nested and touchdown PCR, two fragments of the mitochondrial (mt) DNA control region could be amplified from specimen 533/III which yielded a total of 230 base pairs (bp). The sequence was compared with the homologous part of 40 extant breeds of Bos taurus and B. indicus and related species, such as Banteng (B. javanicus), Gaur (B. gaurus), the European bison (Bison bonasus) and the aurochs (B. primigenius). A neighbour joining tree was constructed based on the appropriate model of sequence evolution. The control region sequence of the 533/III cattle bone, whose age was determined by radiocarbon dating, clusters close to the extant European breeds, but distinctly apart from the basal aurochs and far distant from the B. indicus group. The archaeological and genetic analyses of Bos Ziegelberg demonstrate that domesticated cattle reached southern Bavaria at least 7000 years ago.
Genetic variability of seven dog breeds based on microsatellite markers
Authors: Schelling C. , Gaillard C. , Dolf G. 
Published: February 2005

SummaryThe present study, compared the genetic variability of seven dog breeds and a test sample from Switzerland by means of 26 microsatellite markers. Five loci were excluded from further analyses because one was monomorphic, one not in Hardy–Weinberg equilibrium in all breeds and three in linkage disequilibrium with linked loci. The proportion of shared alleles at the individual level of the remaining 21 microsatellite markers combined with the neighbour‐joining method allowed for the clustering of the large majority of the individuals in accordance to their breed. The results were confirmed by analyses using a Bayesian approach for clustering and a Monte Carlo re‐sampling method for individual assignment or exclusion to a given population.
Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model
Authors: Ledingham Janet M , Laverty Richard 
Published: February 2005

SUMMARY1. The aims of the present study were to investigate, in the New Zealand genetically hypertensive (GH) rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance.2. Genetically hypertensive rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly.3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross‐sectional area (CSA), lumen diameter and the ratio of media width/lumen diameter.4. Simvastatin monotherapy did not lower BP at either dose. In the high‐ and low‐dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower‐dose group.5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen ratio, with the greatest effect observed in the high‐dose groups.6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling.7. In the basilar artery, high‐dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen ratio independently of any change in BP.8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and ratio. In combination with enalapril, there was little consistent additional effect.9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.
Oral implant restoration for enhanced oral function
Authors: Henry Patrick J 
Published: February 2005

SUMMARY1. The present paper reviews the clinical applications of implant‐anchored restorations replacing teeth and defects of the craniofacial skeleton resultant from congenital, traumatic and surgical tissue loss.2. Different categories of tooth and tissue loss were treated in controlled multicentre prospective clinical trials. More recent developments have been the subject of limited pilot studies.3. Long‐term results and meta‐analysis reviews have shown that osseointegrated implant‐supported restorations were at least equal to, and in some applications superior to, traditional treatment methods.4. Based on the outcome of a 30 year research and development programme and validation in numerous clinical trials, osseointegrated implant dental rehabilitation has become a viable treatment alternative for missing teeth and, for some applications, is considered to be a standard of care.
Does permanent carotid artery occlusion produce a ‘preconditioning‐like’ effect towards more severe hypotension in energy metabolites? Role of cerebral adenosine
Authors: Plaschke Konstanze , Kreutzer Stefan , Sommer Clemens , Martin Eike , Bardenheuer Hubert J 
Published: February 2005

SUMMARY1. The aim of the present study was to investigate the potential energy preserving effect of permanent bilateral common carotid artery occlusion (BCCAO) towards additional systemic hypotension of severe duration (30 min). In addition, the role of adenosine A1 receptors in cerebral ischaemic preconditioning was investigated in male Wistar rats. Thus, oligaemic rats were assigned randomly to continuous treatment with the adenosine A1 receptor agonist 2‐chloro‐N6‐cyclopentyladenosine (CCPA) or the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT), receiving daily intraperitoneal infusions of 0.1 mg/kg bodyweight CCPA or CPT or placebo (200 µL aqueous 2‐hydropropyl‐β‐cyclodextrin) at a delivery rate of 0.5 µL/h over 14 days.2. Haemodynamic parameters and arterial blood gases were monitored. Rat cortical energy metabolites ATP, ADP, AMP, phosphocreatine and adenosine were measured using HPLC techniques. Adenosine A1 receptor expression was determined by immunhistochemistry and quantified by western blotting.3. Two weeks of permanent BCCAO induced an ‘energy saving’ effect in rat cortical ATP concentrations. Under subchronic conditions, significant increases were detected in ADP and AMP concentrations after CCPA compared with placebo. Because similar changes were also seen after CPT, this adenosine A1 receptor‐mediated effect does not seems to be specific. Furthermore, no differences in adenosine A1 receptor expression could be detected.4. Adenosine was not specifically involved in the ‘preconditioning‐like’ effect via the modulation of the adenosine A1 receptor in the present oligaemia model. Obviously, adenosine A1 receptor‐specific effects after delayed cerebral ischaemic preconditioning do not seem to play an essential role if BCCAO is followed by a prolonged additional severe ischaemic event.
Comparative study of genotype B and C hepatitis B virus‐induced chronic hepatitis in relation to the basic core promoter and precore mutations
Authors: WATANABE KOJI , TAKAHASHI TORU , TAKAHASHI SUMIO , OKOSHI SHOGO , ICHIDA TAKAFUMI , AOYAGI YUTAKA 
Published: February 2005

AbstractBackground: The clinicopathological profiles and outcome of chronic hepatitis B can differ by hepatitis B virus (HBV) genotypes. In Japan, genotype B and C are two major HBV genotypes. The basic core promoter and precore mutations are other known viral factors for disease activity, although the relationship between HBV genotypes and these mutations is not fully understood.Methods: The HBV genotypes in 90 patients with chronic hepatitis B were determined using an ELISA. Obtained data were correlated with clinicopathological parameters, basic core promoter, precore and the nucleotide 1858 mutations of the HBV genome.Results: Among 90 cases, 20 (22.2%) had genotype B and 70 (77.8%) had genotype C HBV. Genotype B patients were older than genotype C patients (44.0 ± 13.9 vs 34.7 ± 11.0 P = 0.0022). The HBeAg was more prevalent in genotype C than B patients (P = 0.0008) while anti‐HBe was more common in genotype B than C patients (P = 0.0002). Serum aspartate aspartate aminotransferase/alanine aminotransferase levels (B: 220.7 ± 612.8/257.0 ± 498.0 IU/L vs C: 111.3 ± 122.8/201.6 ± 229.4 IU/L, P = 0.16/0.48) and HBV viral loads in blood (B: 6.1 ± 3.1 log genome equivalent [LGE]/mL vs C: 6.7 ± 2.3 LGE/mL, P = 0.42) were equivalent. The seroconversion from HBeAg to anti‐HBe occurred significantly earlier in genotype B than C patients (62 ± 53 months vs 136 ± 54 months, P = 0.0028) during the mean observation period of 149 ± 82 months even under various therapeutic modalities. The categories III and IV of the histological activity index in genotype C were higher (III: P < 0.005, IV: P < 0.05, n = 68) than that in B patients whereas category II was higher in genotype B than C patients (P < 0.05). The double mutation (1762T/1764A) in the basic core promoter was more frequently found in genotype C than in B HBV (P = 0.0068), whereas the precore mutation (1896A) was more common in genotype B than C HBV (P = 0.0233). The incidence of 1858C that was complementary to the precore mutation site in the stem‐loop structure ∈, was equally rare in both genotype B and C HBV.Conclusions: Genotype B patients were older, had earlier HBeAg seroconversion and exhibited more severe lobular necroinflammation, less portal inflammation and fibrosis than genotype C patients. This genotypic difference is related to the basic core promoter and precore mutations irrespective of 1858C.© 2004 Blackwell Publishing Asia Pty Ltd
Factors associated with response to lamivudine: Retrospective study in a tertiary care clinic serving patients with chronic hepatitis B
Authors: HANN HIE‐WON L , JONSSON FUNK MICHELE L , ROSENBERG DANIEL M , DAVIS RANDY 
Published: February 2005

AbstractBackground and Aims: Chronic hepatitis B (CHB) is an important cause of end stage liver disease and hepatocellular carcinoma. Controlled clinical trials indicate treatment with lamivudine results in positive clinical responses. The study goal was to determine if the response to lamivudine treatment (HBeAg loss, HBV DNA loss and alanine aminotransferase [ALT] reduction) differs according to pretherapy (pre‐tx) ALT levels.Methods: This was a retrospective review of medical record data. All CHB patients at all stages of disease (including cirrhotic) with more than two visits to the clinic were included in the study (n = 719). Kaplan‐Meier survival and Cox proportional hazards were estimated.Results: Of the total 719 HBsAg (+) patients, 317 were treated with lamivudine 150 mg or 100 mg daily. Among HBeAg positive patients, at 3 years, Kaplan‐Meier estimates of the loss of HBeAg were 40%, 57% and 61% for pre‐tx ALT < upper limit of normal (ULN), 1–2 × ULN and >2 × ULN, respectively. Similar results of HBV‐DNA loss were seen in HBeAg negative patients.Conclusions: In this setting, we observed that pre‐tx ALT levels were not associated with response to lamivudine, but that lower platelet count and female sex in HBeAg (+) patients were important predictive factors of a favorable response to lamivudine therapy.