bluuebunny/crossref_metadata_2025 huggingface dataset:
Variance Components Linkage Analysis with Repeated Measurements
Authors: Liang Liming , Chen Wei-Min , Sham Pak C. , Abecasis Gonçalo R.
Published: January 2009

Background: When subjects are measured multiple times, linkage analysis needs to appropriately model these repeated measures. A number of methods have been proposed to model repeated measures in linkage analysis. Here, we focus on assessing the impact of repeated measures on the power and cost of a linkage study. Methods: We describe three alternative extensions of the variance components approach to accommodate repeated measures in a quantitative trait linkage study. We explicitly relate power and cost through the number of measures for different designs. Based on these models, we derive general formulas for optimal number of repeated measures for a given power or cost and use analytical calculations and simulations to compare power for different numbers of repeated measures across several scenarios. We give rigorous proof for the results under the balanced design. Results: Repeated measures substantially improve power and the proportional increase in LOD score depends mostly on measurement error and total heritability but not much on marker map, the number of alleles per marker or family structure. When measurement error takes up 20% of the trait variability and 4 measures/subject are taken, the proportional increase in LOD score ranges from 38% for traits with heritability of ~20% to 63% for traits with heritability of ~80%. An R package is provided to determine optimal number of repeated measures for given measurement error and cost. Variance component and regression based implementations of our methods are included in the MERLIN package to facilitate their use in practical studies.
Haplotyping Methods for Pedigrees
Authors: Gao Guimin , Allison David B. , Hoeschele Ina
Published: January 2009

Haplotypes provide valuable information in the study of diseases, complex traits, population histories, and evolutionary genetics. With the dramatic increase in the number of available single nucleotide polymorphism (SNP) markers, haplotype inference (haplotyping) using observed genotype data has become an important component of genetic studies in general and of statistical gene mapping in particular. Existing haplotyping methods include (1) population-based methods, (2) methods for pooled DNA samples, and (3) methods for family and pedigree data. The methods and computer programs for population data and pooled DNA samples were reviewed recently in the literature. As several authors noted, family and pedigree datasets are abundant and have unique advantages. In the past twenty years, many haplotyping methods for family and pedigree data have been developed. Therefore, in this contribution we review haplotyping methods and the corresponding computer programs suitable for family and pedigree data and discuss their applications and limitations. We explore the connections among these methods, and describe the challenges that remain to be addressed.
Ranking Bias in Association Studies
Authors: Jeffries Neal O.
Published: January 2009

Background: It is widely appreciated that genomewide association studies often yield overestimates of the association of a marker with disease when attention focuses upon the marker showing the strongest relationship. For example, in a case-control setting the largest (in absolute value) estimated odds ratio has been found to typically overstate the association as measured in a second, independent set of data. The most common reason given for this observation is that the choice of the most extreme test statistic is often conditional upon first observing a significant p value associated with the marker. A second, less appreciated reason is described here. Under common circumstances it is the multiple testing of many markers and subsequent focus upon those with most extreme test statistics (i.e. highly ranked results) that leads to bias in the estimated effect sizes. Conclusions: This bias, termed ranking bias, is separate from that arising from conditioning on a significant p value and may often be a more important factor in generating bias. An analytic description of this bias, simulations demonstrating its extent, and identification of some factors leading to its exacerbation are presented.
When a Case Is Not a Case: Effects of Phenotype Misclassification on Power and Sample Size Requirements for the Transmission Disequilibrium Test with Affected Child Trios
Authors: Buyske Steven , Yang Guang , Matise Tara C. , Gordon Derek
Published: January 2009

Phenotype misclassification in genetic studies can decrease the power to detect association between a disease locus and a marker locus. To date, studies of misclassification have focused primarily on case-control designs. The purpose of this work is to quantify the effects of phenotype misclassification on the transmission disequilibrium test (TDT) applied to affected child trios, where both parents are genotyped. We compute the non-centrality parameter of the distribution corresponding to the TDT statistic when there is linkage and association of a marker locus with a disease locus and there is phenotype misclassification. We verify our analytic calculations with simulations and provide an example sample size calculation. In our simulation studies, the maximum absolute difference between statistical power computed by simulation and analytic methods is 0.018. In an example sample size calculation, we observe that to maintain equivalent power, the required sample size increases when the disease prevalence decreases or when the misclassification rate increases. A 39-fold sample size increase is required when the misclassification rate is 5% and the disease prevalence is 1%. Given the potentially substantial power loss for the TDT in the presence of misclassification, we recommend that researchers incorporate phenotype misclassification into their study design for genetic association using trio data. We have developed freely available software that computes power loss for a fixed sample size or sample size for a fixed power in the presence of phenotype misclassification.
Efficacy and Safety of S-1 Monotherapy in Patients with Advanced Biliary Tract Adenocarcinoma
Authors: Park Inkeun , Lee Jae-Lyun , Ryu Min-Hee , Kim Tae-Won , Chang Heung Moon , Lee Sung Sook , Sohn Byeong Seok , Kim Eun Kyoung , Park Do Hyun , Lee Sang Soo , Suh Dong Wan , Lee Sung Koo , Kim Myung-Hwan , Lee Jungshin
Published: January 2009

Aim: We investigated the efficacy and safety of S-1 monotherapy for the treatment of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting. Methods: We reviewed clinical data from 217 patients with advanced BTA who were treated with S-1 monotherapy between August 2004 and September 2007. Results: 162 eligible patients were identified. The primary tumors were intrahepatic (n = 57), in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial responses, with a response rate of 13.3% (95% CI 7.2–19.4%). Another 51 patients had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9–64.7%). The median time to progression was 2.7 months and the median overall survival time was 6.9 months. Response rates and survival differed significantly according to the primary site of the tumor (p = 0.002 and p < 0.001, respectively), with extrahepatic bile duct adenocarcinoma having the best prognosis. The treatment regimen produced only mild toxicity in most cases (grade 1 or 2), even for patients with hyperbilirubinemia. Conclusion: S-1 has a favorable toxicity profile and can be safely administered to BTA patients with hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor site and is most effective in patients with extrahepatic BTA.
Acute Renal Failure and Its Risk Factors in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
Authors: Hung Chi-Chih , Liu Wan-Chun , Kuo Mei-Chuan , Lee Chih-Hung , Hwang Shang-Jyh , Chen Hung-Chun
Published: January 2009

Background: Skin lesion is the most frequent manifestation of adverse drug reactions. Drug-induced cutaneous hypersensitivity and drug-induced acute interstitial nephritis might share a similar mechanism involving drug-specific T cells. We thus investigated the renal outcome of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), the most severe drug-induced cutaneous hypersensitivity, and hypothesize that skin detachment in SJS/TEN might be associated with acute renal failure (ARF). Methods: 234 hospitalized patients were retrospectively classified into an SJS/TEN group (skin detachment) or an erythematous multiforme majus group (target-like exanthema alone). Results: Both drugs and chronic kidney disease (CKD) are associated with SJS/TEN. The SJS/TEN group was more likely to develop ARF than the erythematous multiforme majus group (18.8 vs. 4.3%, p < 0.05) despite similar initial creatinine clearance. In the ARF patients, RIFLE-F class, dialysis and long-term dialysis were 25, 15 and 5%, respectively. The offending drugs in ARF were also associated with CKD. Hyponatremia and late hypokalemia were more frequently in the SJS/TEN group (15.6 vs. 2.9%, 7.3 vs. 0.7%, respectively, p < 0.05). Sepsis, allopurinol, antibiotics, NSAIDs, CKD and hypoalbuminemia (OR: 18.8, 9.8, 10.1, 9.0, 5.3 and 3.3, respectively, p < 0.05) were the risk factors of developing ARF. Conclusion: ARF, the need for dialysis, and late hypokalemia could be the consequences of SJS/TEN. Skin detachment after certain medication might implicate the associated ARF, especially in CKD patients.
Angiotensin Blockade Prevents Salt-Induced Injury of the Renal Circulation in Spontaneously Hypertensive Rats
Authors: Susic Dinko , Zhou Xiaoyan , Frohlich Edward D.
Published: January 2009

Background/Aims: We hypothesized that renal damage induced by salt overload may be related to increased activity of the renin-angiotensin system. Thus, we examined the renal effects of angiotensin II receptor blockade in spontaneously hypertensive rats (SHR) with salt overload. Two different blockers were used to demonstrate that the effect depends on receptor blockade per se. Methods: Male, 8-week-old SHR were divided into 4 groups; the control group was given regular chow, the remaining 3 groups were given chow with 8% salt. In addition, the third group was given candesartan (10 mg/kg/day) and the fourth losartan (30 mg/kg/day). Treatment lasted for 8 weeks. Results: Compared with controls, mean arterial pressure increased in salt-loaded rats and was not decreased by candesartan or losartan. Indices of renal function including renal blood flow, glomerular filtration rate, and urinary protein excretion were greatly and adversely affected by salt overload, and they were completely restored with either drug. Conclusion: These results demonstrated that dietary salt excess adversely affected renal function, hemodynamics and structure. Angiotensin receptor blockade did not affect arterial pressure but prevented other adverse effects of salt overload, indicating that renal damage was not dependent on arterial pressure but, more likely, on another mechanism involving the renin-angiotensin system.
Prenatal 3D Ultrasound Diagnostics in Cleidocranial Dysplasia
Authors: Hermann N.V. , Hove H.D. , Jørgensen C. , Larsen P. , Darvann T.A. , Kreiborg S. , Sundberg K.
Published: January 2009

A 34-year-old Caucasian woman with cleidocranial dysplasia (CCD) and a known family history of CCD was referred for an ultrasound examination in the first trimester of her second pregnancy. Molecular genetic analysis of the RUNX2 gene was non-informative. A routine 2D ultrasound examination carried out at a local hospital at gestational age 12 weeks showed no signs of CCD. A 3D ultrasound examination in week 15+4 showed a fetus with typical CCD features including large fontanelles, lack of nasal bones, clavicles without the typical S-form, as well as severe delay in calvarial ossification, especially in the midline. Serial 3D ultrasound examinations during pregnancy confirmed the diagnosis, and over time the manifestations became even more distinct. The diagnosis was clinically confirmed at birth. This case suggests that the typical craniofacial CCD traits, including wide unmineralized areas in the calvarial midline and missing nasal bones, are easily recognizable using 3D ultrasound as early as in week 15.
Prevalence of Spinocerebellar Degenerations in the Hokuriku District in Japan
Authors: Shibata-Hamaguchi Ayumi , Ishida Chiho , Iwasa Kazuo , Yamada Masahito
Published: January 2009

Background: The prevalence of disease subtypes of spinocerebellar degenerations (SCDs) varies between countries, and even between areas within a country. We report unprecedented epidemiologic data on SCDs in the Hokuriku district, which is located in the central, western part of Japan. Methods: Clinical and genetic data on SCD patients were obtained via questionnaires distributed to all the departments of neurology, psychiatry and internal medicine in the Hokuriku district (n = 418). Results: Among the SCD patients, autosomal dominant cerebellar ataxias (ADCAs) were noted in 40.4%, multiple system atrophy in 24.7%, cortical cerebellar atrophy in 13.3% and autosomal recessive cerebellar ataxia in 0.3%. Genetically confirmed ADCA patients included those with Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3; 63.3%), SCA6 (20.0%), ADCA linked to chromosome 16q22.1 (10.0%), dentatorubral pallidoluysian atrophy (4.4%), SCA1 (1.1%) and SCA2 (1.1%). MJD/SCA3 was highly prevalent in the Toyama prefecture of the Hokuriku district, accounting for 90% of genetically confirmed ADCAs by birthplace; MJD/SCA3 patients were concentrated in the Gosei area, the western part of the Toyama prefecture, giving an estimated prevalence of 19.1 per 100,000 inhabitants. Conclusions: The Hokuriku district, especially the Gosei area of Toyama, had a surprisingly high relative frequency and prevalence of MJD/SCA3, which is comparable to that in the Azores, Portugal.
Community-Based Study of Stroke Incidence in the Valley of Aosta, Italy
Authors: Corso Giovanni , Bottacchi Edo , Giardini Guido , De la Pierre Franz , Meloni Teodoro , Pesenti Campagnoni Massimo , Ponzetti Clemente , Veronese Morosini Massimo
Published: January 2009

The purpose of our study was to determine the incidence of stroke, case-fatality rate and disability at 1 year in the Valley of Aosta (Italy) in the years 2004 and 2005. All suspected strokes occurring between January 1, 2004, and December 31, 2005, in the resident population of the Valley of Aosta were identified according to the WHO criteria for stroke and included in a stroke registry (Cerebrovascular Aosta Registry, CARe) after revision by a clinical panel. Multiple overlapping sources were used to ascertain the cases. In the study period, 553 incident strokes were registered. A CT scan was performed in 94.2% of cases. The crude annual incidence rate was 223 (95% CI 197–249) per 100,000 inhabitants. After age and sex adjustment to the ‘European’ population, the stroke incidence rate was 126 (95% CI 106–146). In the 1-year follow-up, only a small number of patients with a first-ever stroke in their life time suffered a new event. Compared with the previous study performed in our region (Valley of Aosta) in 1989, a marked decline in the incidence rate was seen after adjustment to the ‘European’ population, and the 28-day case-fatality rate declined dramatically between 1989 and 2004–2005.
Smoking Cessation at 5 Years after Stroke in the North East Melbourne Stroke Incidence Study
Authors: Gall Seana L. , Dewey Helen M. , Thrift Amanda G.
Published: January 2009

Background/Aims: There is limited knowledge about smoking cessation after stroke. We examined smoking cessation and recall of smoking cessation advice among 5-year stroke survivors. Methods: Interviews were conducted between May 2002 and May 2004 with 5-year survivors from a population-based stroke incidence study undertaken from May 1 1997 to April 30 1999 in Melbourne, Australia. Data were gathered on smoking status at stroke onset, cessation advice recalled and periods of cessation up to 5 years after stroke. Cessation was determined by examining smoking status at stroke onset and at 5 years after stroke. Results: Of the 441 5-year stroke survivors, 343 (78%) had smoking data at follow-up. Fifty-one people were current smokers at stroke onset and 19 (37%) had quit smoking by 5 years after stroke. Of the 40 ever smokers who responded to a question regarding cessation advice, 40% (n = 16) could not recall receiving any such advice since their stroke. Conclusion: The majority of smokers continued to smoke at 5 years after stroke. Few smokers recalled smoking cessation advice. Given that receiving such advice can be the first step towards cessation, improvements in the delivery of advice to this high-risk group are needed
Amelioration of Diabetic Nephropathy in OLETF Rats by Prostaglandin I2 Analog, Beraprost Sodium
Authors: Watanabe Maho , Nakashima Hitoshi , Mochizuki Shizue , Abe Yasuhiro , Ishimura Atsunori , Ito Kenji , Fukushima Takao , Miyake Katsuhisa , Ogahara Satoru , Saito Takao
Published: January 2009

Background: Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I2 analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Method: Fifty-week-old OLETF rats were divided into three groups according to treatment; 400 μg/kg body weight (BW) BPS, 200 μg/kg BW BPS, and 0.9% saline administration. Kidney histology, index of glomerulosclerosis, and glomerular volume were determined, and urine and serum chemistry were assessed. Results: The values for urine protein excretion and serum blood urea nitrogen in BPS-treated rats were significantly lower than those in untreated rats. In rats treated with 400 μg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration were observed. Index of glomerulosclerosis and glomerular volume were also significantly reduced compared with untreated rats. Intriguingly, BPS reduced the level of serum triglyceride. In the glomerulus of treated rats, advanced glycation end product formation and macrophage influx were suppressed in a dose-dependent manner. Conclusion: These findings indicate that BPS has a therapeutic effect on diabetic nephropathy in the OLETF rat, which suggests a potential application of this drug in the treatment of human diabetic nephropathy.
Protective Effect of Fish Consumption on Colorectal Cancer Risk
Authors: Jedrychowski Wieslaw , Maugeri Umberto , Pac Agnieszka , Sochacka-Tatara Elzbieta , Galas Aleksander
Published: January 2009

Background/Aims: Current epidemiologic studies investigating the effect of fish intake on colorectal cancer (CRC) risk are scarce. Therefore, the aim of this study was to elucidate the relationship between fish consumption and CRC risk. Methods: This hospital-based case-control study was performed in 548 CRC patients (Surgery Clinic, University Hospital in Krakow, Poland) between November 2000 and May 2008. Histological findings, information on anatomic location and stage of cancer were available for all the patients enrolled in this study. The control group consisted of 745 patients of the same hospital with no history of cancer admitted for treatment of non-neoplastic conditions. During the 5-year study period, the food frequency questionnaire used focused on the reference period that was defined as 1–5 years prior to CRC diagnosis for the CRC cases and the date of hospital admission for the controls. Results: Thecrude odds ratio (OR) was inversely related to fish consumption (z for trend in quartiles of intake = –2.31, p = 0.021; OR = 0.89; 95% confidence interval, CI: 0.81–0.98). The risk of CRC increased with intake of stewed or cooked meat (z for trend in quartiles of intake = 2.14; p = 0.032; OR = 1.11; 95% CI: 1.01–1.23). The adjusted OR showed a significant reduction in CRC already at the moderate fish intake of one or two servings per week (OR = 0.70; 95% CI: 0.51–0.94), but it was even lower at higher fish intake (OR = 0.56; 95% CI: 0.39–0.86). All multivariate statistical models employed in the analysis considered potential confounders, such as demographic characteristics of subjects, body mass index, smoking status, leisure time physical activity, energy consumption and intake of meat products. Conclusions: The study results indicate that increased fish intake may have a preventive effect on CRC and modulate the effect of meat consumption. To our knowledge, this is the first large epidemiologic study on dietary habits and CRC incidence in Eastern Europe.
The Army's Hispanic Future
Authors: Dempsey Jason K. , Shapiro Robert Y.
Published: January 2009

Using data from the Citizenship & Service: 2004 Survey of Army Personnel, a probability sample of active duty soldiers and officers, this study examines key questions concerning success in the military for racial and ethnic minorities. It focuses on the degree to which Hispanics are integrated into the Army and compares the experiences of Hispanics to the experiences of whites and blacks. After assessing why Hispanics join the Army and choose their occupational specialties, the study looks at how Hispanics perceive Army life, their personal experiences with discrimination, and the progress of the Army in the area of racial and ethnic integration. By comparing the attitudes of Hispanics to those of whites and blacks, it explores the degree to which race and ethnicity influence life in the Army and the implication of this for the military's future.
The Long History of Molecular Electronics
Authors: Choi Hyungsub , Mody Cyrus C.M.
Published: January 2009

Long before nanotechnology, the semiconductor industry was miniaturizing microelectronic components. Since the late 1950s, that industry's dominant material has been silicon. Yet there have always been competitors to silicon that supporters hope will upend the semiconductor industry. It is impossible to understand this industry without a more complete picture of these alternatives — how they come about, how they capture organizational support, why they fail. It is equally impossible to understand nanotechnology without a focus on these alternatives, since research communities devoted to perfecting them today form the backbone of the nanotechnology field. We trace the history of the longest lived silicon alternative — molecular electronics. Molecular electronics arose in the late 1950s as a visionary program conducted by Westinghouse on behalf of the Air Force. We attribute its failure to the difficulties inherent in matching a futuristic vision to a bureaucratically accountable, incremental program that could compete with silicon. Molecular electronics reappeared again at IBM in the 1970s and at the Naval Research Laboratory in the 1980s. In each of these incarnations, molecular electronics' charismatic champions failed to gain the organizational support to make it a mainstream technology. Only at the turn of the century, with new nanotechnology institutions and new models of industry—university collaboration, has some form of molecular electronics neared acceptance by the semiconductor industry.
DNA Behind Bars
Authors: Prainsack Barbara , Kitzberger Martin
Published: January 2009

This paper explores `other' ways of knowing DNA in the field of criminal investigation. Drawing upon 26 in-depth interviews with prisoners in Austria, it illustrates how this group knows and conceptualizes DNA traces and forensic DNA technologies. These understandings and conceptualizations are both nuanced and ambiguous. While on the one hand, DNA traces and forensic DNA technologies were not treated as categorically different from other types of traces and technologies in the prisoners' accounts, they were seen as `unique' in one respect: respondents experienced DNA traces as beyond their control because they were virtually impossible to avoid (in contrast to, for example, fingerprints). Furthermore, the scientific rigour that our interviewees assumed to underpin forensic DNA technologies rendered these technologies as impenetrable and intimidating, and as effectively challenging many offenders' expert knowledge on how to manage crime scenes and avoid convictions. Finally, due to coming `from the inside' of the body, forensic DNA technologies were seen as `deepening' the stigma of delinquency in many of our interviewees' bodies and selves. For our interviewees, forensic DNA technologies assumed the role of institutionalized memories of their delinquency.
The Career Paths of Women (and Men) in French Research
Authors: de Cheveigné Suzanne
Published: January 2009

This paper presents results from a qualitative study of perceptions of science careers in the Centre National de la Recherche Scientifique (CNRS), the main research institution in France. Its aim is to understand the `glass ceiling' effect, which reduces the proportion of women at the higher levels of the career hierarchy. Long interviews were carried out with men, as well as women, support staff and researchers. Factors such as tension between individual and collective dimensions of research activity, and long-term time-management problems, were identified: these affect both men and women but in different ways. Organizations bear an important responsibility through the way they reinforce or alleviate difficulties that women and men face in contributing to scientific research at all levels.
Scientific Technologies of National Identity as Colonial Legacies
Authors: Medina-Doménech Rosa
Published: January 2009

This paper examines how Spanish techno-scientific discourses and practices shaped metropolitan Spanish and colonial Guinean bodies and identities. It focuses on the range of technologies of biopower — from fingerprinting and blood testing to racial and geographic discourses — that constituted Guinean bodies in ambivalent ways during two periods: the first decades of the 20th century, and the post-Civil War period of the Francoist regime. In the first decades of the 20th century, blood tests were imposed on the local population as a legal requirement for obtaining identity cards in colonial Guinea; the identity cards offered them a severely restricted citizen status, especially if they were female. Indeed, the new blood testing technologies played a key role in efforts to control, reform and identify `natives', less as subjects than as labouring bodies. During Franco's dictatorship, following the end of the Spanish Civil War (1939), the colonies became a space for the reconstruction of a unified Spanish national identity through two key strategies: `detribalization' and `hispanicization', which were carried out through a web of techno-scientific practices — in medicine and psychology as well as geography and anthropology — that included fingerprinting, blood testing, measurements of intelligence and racial discourses. Under the Franco regime, these practices not only justified violent, racist forms of exploitation, but were also used to stake a claim on Guinean colonial territories and bodies by emptying them of their existing identities and then reconstituting them under a single Spanish national identity.
Shifts in Guidelines for Ethical Scientific Conduct
Authors: Montgomery Kathleen , Oliver Amalya L.
Published: January 2009

We analyze the activities and actors involved in articulating and diffusing guidelines for ethical scientific conduct from 1975 to the present. We use a theoretical framework of institutional change at the organizational-field level to examine the co-evolution of the structure of the organizational field of `scientific research' and its institutional logic. Public agencies have long provided funding to US universities to support faculty research, expecting that implicit norms of scientific conduct would guide behavior. Growing publicity about research fraud in the late 1960s and early 1970s triggered a shift from implicit norms to explicit behavioral proscriptions, with strong administrative oversight. As private sources of research funding exert new pressures on research behavior, public—private partnerships are emerging to articulate explicit, yet voluntary prescriptive norms of research integrity. The analysis demonstrates the co-evolution and co-dependence of changes in the identity and strength of influential actors in the field of scientific research and changes in the norms of scientific conduct. We examine how the normative guidelines have been constructed over time, illustrating the persistence of earlier norms as the foundation for current guidelines. We conclude with implications for future research conduct.
Open Source Knowledge and University Rankings
Authors: Marginson Simon
Published: January 2009

The fecund growth of open source knowledge goods in the global communicative environment underlines their public good character. Once knowledge goods are disseminated, their cost and price tend towards zero. It is now obvious (as apparent in recent OECD policy documents) that commercial research and trade in intellectual property capture only a small fraction of open source knowledge, which is expanding even more rapidly than global markets. But for policy makers this poses the problem of how to assign stable and defensible value to free floating knowledge goods. Across the world, research universities have been positioned in a networked competition of institutions with globally mobile personnel and converging goals and organizational cultures. In rapid time global university ranking and the associated technologies of publication and citation ordering and counting have proved potent in arranging status, assigning value and shaping behaviours in higher education. We find that public goods are readily annexed to the longer-standing projects of producing university status and sustaining an imperial global geo-politics of knowledge. Here the relation between status production and free open source cultural production is not so much a contradiction as an antinomy. These issues are discussed in the light of the flourishing and fall of the lowland city-states of the Maya in Mesoamerica, a notable example of a status economy and of the interplay between status reproduction and cultural goods, a dynamic only partly nested in economic production. The article reviews the rankings technologies, led by the Shanghai Jiao Tong University research metrics, the global strategies of university executives, changing national policies on universities and research, and the aggregation of these effects in the emerging `arms race' in investment in innovation.
Education, Creativity and the Economy of Passions: New Forms of Educational Capitalism
Authors: Peters Michael A.
Published: January 2009

This article reviews claims for creativity in the economy and in education distinguishing two accounts: 'personal anarcho-aesthetics' and 'the design principle'. The first emerges in the psychological literature from sources in the Romantic Movement emphasizing the creative genius and the way in which creativity emerges from deep subconscious processes, involves the imagination, is anchored in the passions, cannot be directed and is beyond the rational control of the individual. This account has a close fit to business as a form of 'brainstorming', 'mind-mapping' or 'strategic planning', and is closely associated with the figure of the risk-taking entrepreneur. By contrast, 'the design principle' is both relational and social and surfaces in related ideas of 'social capital', 'situated learning', and 'P2P' (peer-to-peer) accounts of commons-based peer production. It is seen to be a product of social and networked environments — rich semiotic and intelligent environments in which everything speaks. The article traces the genealogies of these two contrasting accounts of creativity and their significance for educational practice before showing how both notions are strongly connected in accounts of new forms of capitalism that require a rethinking of the notion of creativity and its place in schools and institutions of higher education. The article begins by providing a context in terms of a history of the knowledge economy and the historical tendency toward aesthetic or designer capitalism.
Innovation and Creativity: Beyond Diffusion — On Ordered (Thus Determinable) Action and Creative Organization
Authors: Michelsen Anders
Published: January 2009

The article confronts Cornelius Castoriadis's philosophy of 'the imaginary institution of society' with issues of innovation in a knowledge society and outlines a new notion of innovation as creative organization. It will take a critical approach to innovation from a historical perspective of postwar systems theory and introduce Castoriadis's philosophy as an interesting option in this regard. It proceeds in four parts: (a) First, it debates the limits of the commonplace metaphor of diffusion and adoption in today's debate on innovation. (b) Second, it will present aspects of Castoriadis's thought as an alternative, in particular his debate on imagination and the proto-institution of legein/teukhein — ordered action. (c) On this background it will treat a case from the Danish innovation industry, the firm Zentropa WorkZ's programme of 'Dramatic Innovation' as an interesting example of an innovation format addressing creativity. (d) In conclusion, it will briefly debate creative knowledge formation in a knowledge society by pondering relations between innovation and current science.
The Act of Collaborative Creation and the Art of Integrative Creativity: Originality, Disciplinarity and Interdisciplinarity
Authors: Rhoten Diana , O'Connor Erin , Hackett Edward J.
Published: January 2009

Csikszentmihalyi (1999: 314) argues that 'creativity is a process that can be observed only at the intersection where individuals, domains, and fields intersect'. This article discusses the relationship between creativity and interdisciplinarity in science. It is specifically concerned with interdisciplinary collaboration, interrogating the processes that contribute to the collaborative creation of original ideas and the practices that enable creative integration of diverse domains. It draws on results from a novel real-world experiment in which small interdisciplinary groups of graduate students were tasked with producing an innovative scientific research problem and an integrative research proposal. Results show that while bisociative thinking assists in the creation of original research problems, both disciplinary skills and an interdisciplinary disposition are core to the integration of creative research proposals. Extrapolating from the results of this experiment, the article discusses the feasibility of preparing students for such work and the implications for universities and other intellectual centers.
A Transgressive Global Research Imagination
Authors: Kenway Jane , Fahey Johannah
Published: January 2009

In this article we explore the ways in which the notion of the imagination might be mobilized to support researchers to develop transgressive research imaginations and communities with the capacities to think, 'be' and 'become' differently in a world of research increasingly governed by rampant reductionist rationality. To assist us we draw from the evocative views of imagination developed by Cornelius Castoriadis, the imagination's most radical exponent. In this article his ideas about knowledge and its links to the imagination will be deployed as we discuss the following questions: What does the notion of the imagination mean in the everyday world of university research? Is all research an act of the imagination? What might it mean to globalize the research imagination? We will also illustrate the ways in which the imagination is mobilized in (globalizing) research practice.
From Wilderness to Megalopolis
Authors: Boeckel Mark A. , Otterstrom Samuel M.
Published: January 2009

Using a historical Geographic Information System (GIS) and statistical measures, this research examines the sex ratios of the United States between 1790 and 1910 to determine whether men truly outnumbered women on the American Frontier. We used United States Census data combined with historical digital county maps to calculate male-to-female sex ratios by county and settlement density class. We analyzed these ratios using descriptive statistics, the Games-Howell analysis of variance (ANOVA) test, and comparisons of historical GIS maps. We found that gender ratios on the American Frontier were extremely high throughout the study period and were significantly different from those in more densely populated areas. In addition, sex ratios declined as population density increased in each decade of this study. However, frontier areas still had fairly high gender ratios in 1910, thus showing ongoing significant demographic differences between those sparsely settled counties and more urbanized regions.
The Administration of rt-PA (Activase®) for the Treatment of Empyema in an Adult Patient
Authors: Emerson Christopher R. , Bercume Christine M. , Antonopoulos Marilena S. , Marzella Nino
Published: January 2009

The administration of various fibrinolytic agents for the treatment of empyema has been reported in past studies. Most of the current literature has shown favorable outcomes in terms of increased tube drainage, improved chest radiography, and reduction in surgical intervention. However, a randomized controlled trial that compared streptokinase to placebo showed no significant reduction in mortality. To date, there have been no randomized controlled trials evaluating the safety, efficacy, and administration of recombinant tissue plasminogen activator for the treatment of empyema in the adult population. The authors report the use of a 10 mg daily dose of intrapleural recombinant tissue plasminogen activator for 6 days in a 57-year-old, white, male patient with empyema that was unresponsive to antibiotic therapy and chest tube drainage. They conclude that intrapleural administration of recombinant tissue plasminogen activator in conjunction with antibiotic therapy for the treatment of empyema in this patient resulted in increased chest tube drainage and provided complete resolution of all signs and symptoms of his infection.
Brainhood, anthropological figure of modernity
Authors: Vidal Fernando
Published: January 2009

If personhood is the quality or condition of being an individual person, brainhood could name the quality or condition of being a brain. This ontological quality would define the `cerebral subject' that has, at least in industrialized and highly medicalized societies, gained numerous social inscriptions since the mid-20th century. This article explores the historical development of brainhood. It suggests that the brain is necessarily the location of the `modern self', and that, consequently, the cerebral subject is the anthropological figure inherent to modernity (at least insofar as modernity gives supreme value to the individual as autonomous agent of choice and initiative). It further argues that the ideology of brainhood impelled neuroscientific investigation much more than it resulted from it, and sketches how an expanding constellation of neurocultural discourses and practices embodies and sustains that ideology.
The curious rise and fall of experimental psychology in Mind
Authors: Green Christopher D.
Published: January 2009

The journal Mind is now a wholly philosophical journal. At the time of its founding, in 1876, however, its mission was rather different in character. Its aim was to discover whether scientific psychology was a truly viable enterprise and, if so, what its boundaries with philosophy, with other scientific disciplines, and with the earlier generation of discredited attempts at `scientific' studies of the mind (e.g. phrenology, mesmerism) might be. Although at first Mind published mostly philosophical pieces and literature reviews, by the mid-1880s it was publishing primary experimental research, mostly by American psychologists who as yet had few outlets of their own. For a time it was the leading journal of experimental psychology in the English-speaking world. As the international competition among scientific and scholarly journals intensified in the 1890s, however, Mind started to lose its share of experimental contributions, and with the editorial takeover of the journal of George Stout in 1892, the journal soon became one dedicated purely to philosophy.
From (B)edouin to (A)borigine: the myth of the desert noble savage
Authors: Graulund Rune
Published: January 2009

This article examines the myth of the supposed superiority of the desert noble savage over civilized man. With the Bedouin of Arabia and the Aborigines of Australia as its two prime examples, the article argues that two versions of this myth can be traced: one in which the desert noble savage is valorized due to his valour, physical prowess and martial skill (Bedouin); and another, later version, where the desert noble savage is valorized as a pacifist, an ecologist and a mythmaker/storyteller (Aborigines). The article concludes by examining the way in which this turn from one type of desert noble savage to another reflects the manner in which western modernity has shifted its values from Cartesian dualities and Enlightenment rationalism to that of networks, potentialities, ecology and myth.
Cultural encounters in the social sciences and humanities: western émigré scholars in Turkey
Authors: Ergin Murat
Published: January 2009

Turkish modernization relied on the western social sciences and humanities not only as an abstract and distant model, but also in the form of close encounters and interactions with western refugee scholars. This article examines the activities of western intellectuals and experts who visited Turkey in the early republican era (1923—50), especially focusing on a group of émigré scholars who were employed in Turkey after the university reform of 1933. While European and North American social scientists were drawn to meticulous comparisons of `East' and `West' in this period, elites in the former component of this comparative dichotomy were seeking creative ways to turn this taxonomy to their advantage. In the Turkish case, the project of adopting modernity contained universalistic aspects intended to function for particular local needs. A body of racial, historical and linguistic theories attempted to create and sustain a nationally homogeneous society while, at the same time, emphasizing the contributions of Turkishness to western and modern history. Republican scholars tried to establish the Turkish origins of western civilization with the help of western social sciences in general and of western émigré scholars in particular. In the process of facilitating the local efforts to import western modernity into the specificity of Turkishness, refugee scholars encountered contradictory demands and employed different strategies to respond to these demands.
Thyroid Involvement in Disseminated Zygomycosis by Cunninghamella bertholletiae: 2 Cases and Literature Review
Authors: Mayayo Emilio , Klock Clóvis , Goldani Luciano
Published: January 2009

Thyroid involvement is very rare in disseminated zygomycosis. We describe two cases of thyroiditis due to Cunninghamella bertholletiae diagnosed though a necropsy study and the only five previous cases of thyroid zygomycosis reported in the literature are revised.
Process Validation and Screen Reproducibility in High-Throughput Screening
Authors: Coma Isabel , Clark Liz , Diez Emilio , Harper Gavin , Herranz Jesus , Hofmann Glenn , Lennon Mark , Richmond Nicola , Valmaseda Manuel , Macarron Ricardo
Published: January 2009

The use of large-scale compound screening has become a key component of drug discovery projects in both the pharmaceutical and the biotechnological industries. More recently, these activities have also been embraced by the academic community as a major tool for chemical genomic activities. High-throughput screening (HTS) activities constitute a major step in the initial drug discovery efforts and involve the use of large quantities of biological reagents, hundreds of thousands to millions of compounds, and the utilization of expensive equipment. All these factors make it very important to evaluate in advance of the HTS campaign any potential issues related to reproducibility of the experimentation and the quality of the results obtained at the end of these very costly activities. In this article, the authors describe how GlaxoSmithKline (GSK) has addressed the need of a true validation of the HTS process before embarking in full HTS campaigns. They present 2 different aspects of the so-called validation process: (1) optimization of the HTS workflow and its validation as a quality process and (2) the statistical evaluation of the HTS, focusing on the reproducibility of results and the ability to distinguish active from nonactive compounds in a vast collection of samples. The authors describe a variety of reproducibility indexes that are either innovative or have been adapted from generic medical diagnostic screening strategies. In addition, they exemplify how these validation tools have been implemented in a number of case studies at GSK. ( Journal of Biomolecular Screening 2009:66-76)
Isolation of Novel EGFR-Specific VHH Domains
Authors: Gottlin Elizabeth B. , Xiangrong Guan  , Pegram Charles , Cannedy Allen , Campa Michael J. , Patz Edward F.
Published: January 2009

Epidermal growth factor receptor (EGFR) is overexpressed or mutated in a high percentage of tumors. EGFR has long been considered a promising target for cancer diagnostic and therapeutic applications. However, monoclonal antibodies and other large antibody constructs diffuse into tumors slowly, limiting their efficacy. To develop lower molecular weight probes for EGFR and other tumor cell receptors, the authors immunized a llama with the extracellular domains (ECDs) of EGFR and an oncogenic mutant receptor, EGFRvIII, and with extracts of tumor cell lines. From the immune repertoire of the llama, the authors constructed a heavy chain variable domain (VHH domain)—phage library. At ~16 kDa, the VHH domain is a tenth of the size of a monoclonal antibody and is the smallest antibody fragment that retains specificity. By affinity selection from this library, the authors isolated many VHH domains with specificity for EGFR. The VHH domains bind to whole cells expressing the receptor but not to control cells lacking the receptor and can immunoprecipitate EGFR from cell lysates. Some VHH domains have cross-specificity with existing anti-EGFR monoclonal antibodies and have reasonably high (nM) affinities. The llama-VHH domain library is also potentially a rich source of targeting agents directed toward other tumor cell receptors. ( Journal of Biomolecular Screening 2009:77-85)
Genome-wide Linkage Analysis with Clustered SNP Markers
Authors: Selmer Kaja K. , Brandal Kristin , Olstad Ole K. , Birkenes Bård , Undlien Dag E. , Egeland Thore
Published: January 2009

Single nucleotide polymorphisms (SNPs) have recently replaced microsatellites as the genetic markers of choice in linkage analysis, primarily because they are more abundant and the genotypes more amenable for automatic calling. One of the most recently launched linkage mapping sets (LMS) is the Applied Biosystems Human LMS 4K, which is a genome-wide linkage set based on the SNPlex™technology and the use of clustered SNPs. In this article the authors report on their experience with this set and the associated genotyping software GeneMapper®version 4.0, which they have used for linkage analyses in 17 moderate to large families with assumed monogenic disease. For comparison of methods, they also performed a genome-wide linkage analysis in 1 of the 17 families using the Affymetrix GeneChip®Human Mapping 10K 2.0 array. The conclusion is that both methods performed technically well, with high call rates and comparable and low rates of Mendelian inconsistencies. However, genotyping is less automated in GeneMapper®version 4.0 than in the Affymetrix software and thus more time consuming. ( Journal of Biomolecular Screening 2009:92-96)