bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term recombinant human growth hormone use in Australian children with renal disease
Authors: CROMPTON CHARLES H ,   the Australian and New Zealand Paediatric Nephrology Association
Published: October 2004

Background:  Recombinant human growth hormone (rhGH) has been used for 15 years to treat Australian children with short stature caused by chronic kidney disease. The Australia‐wide growth hormone database, OZGROW, has prospectively collected data for all patients treated with rhGH. The impact of rhGH therapy on linear growth in patients with chronic renal failure (CRF) was assessed by retrospectively analysing this data.

Methods:  Growth data prior to and during treatment, bone age, and pubertal data were recorded from the database. Questionnaire data provided further information on underlying renal disease, medication use, bone disease, and final height. Patients were classified according to treatment modality; conservative management of CRF, haemodialysis or peritoneal dialysis, and transplant.

Results:  Data on 183 patients were analysed. The duration of rhGH therapy ranged from 1.2 to 10.5 years (mean 5.3 years). The height standard deviation score (Ht SDS) in each patient group at the start and end of rhGH treatment were as follows: Predialysis: −2.6 to −2.1; dialysis: −2.7 to −2.3; transplant: −3.1 to −2.8 (P = 0.0001). Thirty‐nine patients achieved final adult height, with mean Ht SDS before rhGH therapy being −2.65, and at final height it was 2.3. The mean final height for the males was 161.8 cm and for the females, it was 149.5 cm.

Conclusion:  The effect of treatment with rhGH was less dramatic than reported in the literature. However, the positive benefit of rhGH therapy was apparent both in the short and long‐term. Therapy with rhGH maintained a steady Ht SDS with time; without rhGH, it would be anticipated that many children would show a steady decline in Ht SDS. The maximum benefit was seen in preterminal renal failure, and early therapy (before dialysis or transplantation) is recommended before an irrecoverable loss of height potential occurs.
Macrophage accumulation and renal fibrosis are independent of macrophage migration inhibitory factor in mouse obstructive nephropathy
Authors: RICE EDWINA K , NIKOLIC‐PATERSON DAVID J , DAVID JOHN R , BUCALA RICHARD , METZ CHRISTINE N , ATKINS ROBERT C , TESCH GREGORY H
Published: October 2004

Background and Aim:  The progression of renal injury, initiated by either an immune or non‐immune insult, is closely associated with the accumulation of leucocytes and fibroblasts in the damaged kidney. Macrophage migration inhibitory factor (MIF) regulates leucocyte activation and fibroblast proliferation in vitro. Studies have identified a pathological role for MIF in immune‐initiated renal injury in the rat. In this study, we examined the role of MIF in obstructive nephropathy, where renal injury is initiated by a non‐immune insult.

Methods and Results:  Unilateral ureteric ligation was performed on MIF wildtype (+/+) and MIF deficient (–/–) mice. Groups of five mice were killed at days 0, 1, 5 or 10 after obstruction, and kidneys were examined via immunohistochemistry and northern blotting. In MIF +/+ mice, expression of the MIF protein increased in obstructed kidneys compared to normal control kidneys. Interstitial macrophage and T cell accumulation was significantly increased in obstructed kidneys at day 5 and 10, but was unaffected by MIF deficiency. Osteopontin and macrophage colony stimulating factor (M‐CSF) mRNA expression in obstructed kidneys were equally increased in both genotypes, indicating that expression of these chemokines is not influenced by MIF. No difference was detected in the development of renal fibrosis in obstructed MIF +/+ and MIF –/– kidneys, as assessed by myofibroblast accumulation and proliferation and expression of profibrotic molecules (transforming growth factor‐beta 1(TGF‐β1) and collagen).

Conclusion:  These results demonstrate that MIF expression is increased in obstructive nephropathy without affecting kidney leucocyte accumulation or the development of renal fibrosis. This suggests that the progression of renal injury in obstructive nephropathy is independent of MIF.
A novel NPHS2 gene mutation in Turkish children with familial steroid‐resistant nephrotic syndrome
Authors: OZER ESRA ARUN , AKSU NEJAT , ERDOGAN HAKAN , YAVASCAN ONDER , KARA ORHAN , GRIBOUVAL OLIVIER , GUBLER MARIE‐CLAIRE , ANTIGNAC CORINNE
Published: October 2004

SUMMARY:  We report in this paper two siblings aged 8 and 17 months who were clinically diagnosed with familial steroid‐resistant nephrotic syndrome (SRNS). By mutation screening of the NPHS2 gene, a homozygous missense mutation, P118L, was detected in both children. This study is the first systematic investigation of NPHS2 gene mutations in Turkish children with familial SRNS. If this mutation is a hot spot of mutation in the Turkish population, screening this novel mutation in Turkish children with SRNS may be of great clinical use to prevent unnecessary treatment modalities, provide accurate genetic counselling and predict the prognosis of the disease.
Organizational De‐development*
Authors: Nutt Paul C.
Published: October 2004

ABSTRACT Organizational decline prompts leaders to downsize, reducing the size of the workforce in an attempt to cut costs. This paper discusses some of the dangers of downsizing in which organizations experience an unanticipated and unwanted loss of core competencies. An alternative to downsizing is offered, showing how organizations can ‘de‐develop’ by slowly and deliberately moving to a lower order of organized complexity, retaining essential core competencies and supporting functions. To produce a ‘soft‐landing’ that preserves core competencies, a new identity is forged and connections to the new identity are uncovered. The connections point out what must be preserved, such as a crucial channel for key products, for the new identity to survive and flourish. The de‐developed organization preserves customers, products, markets, channels, revenue sources, alliances, skilled people, ways to organize, and/or image crucial to the new strategic identity before letting go of the remaining customers, products, etc. The paper identifies conditions under which de‐development can be desirable and suggests a ‘devolutionary’ process that points out some of the key moves needed to reduce organized complexity and realize a soft landing.
Ownership Types and Strategic Groups in an Emerging Economy*
Authors: Peng Mike W. , Tan Justin , Tong Tony W.
Published: October 2004

ABSTRACT  Existing strategic group studies have rarely examined ownership type as a variable to classify firms in an industry. Using Chinese firms of different ownership types, we suggest that ownership type can be a parsimonious and important variable that managers use to cognitively classify firms into different strategic groups. While ownership itself is an objective variable, we contend that different ownership types lead to different managerial outlook and mentality due to a number of macro and micro foundations giving rise to various managerial cognitions. Employing the Miles and Snow typology, we find that state‐owned enterprises (SOEs) and privately‐owned enterprises (POEs) tend to adopt defender and prospector strategies, respectively, while collectively‐owned enterprises (COEs) and foreign‐invested enterprises (FIEs) exhibit an analyser orientation that falls between defenders and prospectors on the strategy continuum. Three statistical tests suggest that ownership types can be used to successfully predict strategic group memberships in China's emerging economy.
Choosing Constraints as a Third Solution to Agency*
Authors: Michael Steven C. , Pearce John A.
Published: October 2004

ABSTRACT The standard solutions to agency, incentive contracting and monitoring, are degraded by the frequency and the duration of the decisions affected. Decisions of low frequency and long duration are not effectively controlled by either monitoring or incentive contracting. For decisions of low frequency and long duration, constraining the firm's choices significantly reduces agency. Applying the theory, guidelines for choosing constraints are suggested, and propositions advanced. As one application, the mission statement is considered as a vehicle for embedding constraints. The theory is also investigated by examining existing recommendations for both the content and process of mission statements.
Team Learning from Mistakes: The Contribution of Cooperative Goals and Problem‐Solving*
Authors: Tjosvold Dean , Yu Zi‐you , Hui Chun
Published: October 2004

ABSTRACT Although mistakes may have considerable potential for learning, previous research has emphasized that organizational members are often defensive when their mistakes are pointed out and will even continue with their present course of action despite growing costs. Recent research has shown that team‐level variables, such as psychological safety and shared mental model, can help overcome barriers to learning from mistakes. Structural equation analyses on teams working in a sample of organizations in Shanghai, China, suggested that teams were able to learn from their mistakes to the extent that they took a problem solving orientation. This orientation in turn was based on developing cooperative but not competitive goals within the team. Although competitive and independent goals induce blaming, blaming itself was not significantly related to learning. Blaming, especially when conducted openly, may hold individual team members accountable as well as provoke defensiveness. Findings empirically link the theory of cooperation and competition with the organizational learning literature. Results suggest that cooperative goals and problem solving promote learning from mistakes.
Celebrity Politicians: Popular Culture and Political Representation
Authors: Street John
Published: October 2004

Considerable political and media attention has focused on the phenomenon of the ‘celebrity politician’. As this article illustrates, there are two main variants of the phenomenon. The first is the elected politician or candidate who uses elements of ‘celebrityhood’ to establish their claim to represent a group or cause. The second is the celebrity—the star of popular culture—who uses their popularity to speak for popular opinion. Both examples have been seen by critics to debase liberal democratic political representation. This article challenges this critique and argues that the celebrity politician is consistent with a coherent account of political representation. This does not mean that all examples of the celebrity politician are to be seen as legitimate, but that the representative claim has to be analysed more carefully and discriminatingly than the critics typically suppose.
Digital Rank-And-File: Party Activists' Perceptions and Use of the Internet
Authors: Lusoli Wainer , Ward Stephen
Published: October 2004

Political parties are in a transitional phase. A declining, socially restricted membership, decreasing levels of activism and a shift towards more individualistic modes of political engagement threaten the linkage role that parties have played in modern democracy. The development of the Internet in a period of change has meant that it quickly became intertwined with debates about reviving representative political organisations. Using data from a survey of party activists in the UK (N = 4,770), this article answers questions about the perception and use of new media by party activists, the Internet's potential for members' participation and engagement and the penetration of the Internet in pre-existing political careers. In general, the article asks which role new media are playing in the transition of political parties.
What's ‘Social’ about ‘Social Capital’?
Authors: Roberts John Michael
Published: October 2004

Debates around the concept of social capital are often also debates about the level at which social capital can be abstracted for analytical use. Yet while many theorists and commentators involved in these debates implicitly discuss the issue of abstraction it is rarely done explicitly. In this article I attempt to overcome this missing link in the social capital literature by theoretically examining the ‘social’ in ‘social capital’ through interconnected levels of abstraction. In particular, and at a high level of abstraction, I argue that social capital is underpinned by a contradictory relationship associated with what I term as ‘isolated reciprocity’. At lower levels of abstraction I show how isolated reciprocity poses problems for the establishment of ‘good’ social capital in the UK.
‘It's Not Just Tea and Buns’: Women and Pro-union Politics in Northern Ireland
Authors: Ward Rachel J.
Published: October 2004

This article assesses the reasons for the ongoing under-representation of women in Northern Ireland politics, with particular reference to women who take a pro-union stance. The stereotype that unionist women ‘just make the tea’ is challenged through evidence that they participate in many different tiers of government and in community organisations. The article draws upon qualitative evidence of pro-union women's political activism and their motivations, analysed through perspectives from the literature on gender, nationalism and participation. The article argues that while women remain under-represented, particularly in the more powerful and salaried regional and national levels of government, they also do more than the stereotype allows.
Assessing Interaction Effects in Linear Measurement Error Models
Authors: Huang Li-Shan , Wang Hongkun , Cox Christopher
Published: October 2004

In a linear model, the effect of a continuous explanatory variable may vary across groups defined by a categorical variable, and the variable itself may be subject to measurement error. This suggests a linear measurement error model with slope-by-factor interactions. The variables that are defined by such interactions are neither continuous nor discrete, and hence it is not immediately clear how to fit linear measurement error models when interactions are present. This paper gives a corollary of a theorem of Fuller for the situation of correcting measurement errors in a linear model with slope-by-factor interactions. In particular, the error-corrected estimate of the coefficients and its asymptotic variance matrix are given in a more easily assessable form. Simulation results confirm the asymptotic normality of the coefficients in finite sample cases. We apply the results to data from the Seychelles Child Development Study at age 66 months, assessing the effects of exposure to mercury through consumption of fish on child development for females and males for both prenatal and post-natal exposure.
Mixture Model on the Variance for the Differential Analysis of Gene Expression Data
Authors: Delmar Paul , Robin Stéphane , Tronik-Le Roux Diana , Daudin Jean Jacques
Published: October 2004

In microarray experiments, accurate estimation of the gene variance is a key step in the identification of differentially expressed genes. Variance models go from the too stringent homoscedastic assumption to the overparameterized model assuming a specific variance for each gene. Between these two extremes there is some room for intermediate models. We propose a method that identifies clusters of genes with equal variance. We use a mixture model on the gene variance distribution. A test statistic for ranking and detecting differentially expressed genes is proposed. The method is illustrated with publicly available complementary deoxyribonucleic acid microarray experiments, an unpublished data set and further simulation studies.
A Survival-Adjusted Quantal Response Test for Comparing Tumour Incidence Rates
Authors: Peddada Shyamal D. , Dinse Gregg E. , Haseman Joseph K.
Published: October 2004

The paper presents a case-study of skin fibromas among male rats in the 2-year cancer bioassay of methyleugenol that was conducted by the US National Toxicology Program (NTP). In animal carcinogenicity experiments such as this one, tumour rates are often compared with the Cochran–Armitage (CA) trend test. The operating characteristics of the CA test, however, can be adversely affected by survival differences across groups and by the assumed dose metric. Survival-adjusted generalizations of the CA test have been proposed, but they are still sensitive to the choice of scores that are assigned to the dose groups. We present an alternative test, which outperforms the survival-adjusted CA test which is currently used by the NTP to compare incidence rates. Simulated data from a wide range of realistic situations show that the operating characteristics of the test proposed are superior to those of the NTP’s survival-adjusted CA test, especially for rare tumours and wide logarithmic spacings of the dose metric.
Limits of Quantitation for Laboratory Assays
Authors: Cox Christopher
Published: October 2004

A common problem with laboratory assays is that a measurement of a substance in a test sample becomes relatively imprecise as the concentration decreases. A standard solution is to establish lower limits for reliable measurement. A quantitation limit is a level above which a measurement has sufficient precision to be reliably reported. The paper proposes a new approach to defining the limit of quantitation for the case where a linear calibration curve is used to estimate actual concentrations from measured values. The approach is based on the relative precision of the estimated concentration, using the delta method to approximate the precision. A graphical display is proposed for the assessment of estimated concentrations, as well as the overall reliability of the calibration curve. Our research is motivated by a clinical inhalation experiment. Comparisons are made between the approach proposed and two standard methods, using both real and simulated data.
An Individual Measure of Relative Survival
Authors: Stare Janez , Henderson Robin , Pohar Maja
Published: October 2004

Relative survival techniques are used to compare survival experience in a study cohort with that expected if background population rates apply. The techniques are especially useful when cause-specific death information is not accurate or not available as they provide a measure of excess mortality in a group of patients with a certain disease. Whereas these methods are based on group comparisons, we present here a transformation approach which instead gives for each individual an outcome measure relative to the appropriate background population. The new outcome measure is easily interpreted and can be analysed by using standard survival analysis techniques. It provides additional information on relative survival and gives new options in regression analysis. For example, one can estimate the proportion of patients who survived longer than a given percentile of the respective general population or compare survival experience of individuals while accounting for the population differences. The regression models for the new outcome measure are different from existing models, thus providing new possibilities in analysing relative survival data. One distinctive feature of our approach is that we adjust for expected survival before modelling. The paper is motivated by a study into the survival of patients after acute myocardial infarction.
Assessing Accuracy of a Continuous Screening Test in the Presence of Verification Bias
Authors: Alonzo Todd A. , Pepe Margaret Sullivan
Published: October 2004

In studies to assess the accuracy of a screening test, often definitive disease assessment is too invasive or expensive to be ascertained on all the study subjects. Although it may be more ethical or cost effective to ascertain the true disease status with a higher rate in study subjects where the screening test or additional information is suggestive of disease, estimates of accuracy can be biased in a study with such a design. This bias is known as verification bias. Verification bias correction methods that accommodate screening tests with binary or ordinal responses have been developed; however, no verification bias correction methods exist for tests with continuous results. We propose and compare imputation and reweighting bias-corrected estimators of true and false positive rates, receiver operating characteristic curves and area under the receiver operating characteristic curve for continuous tests. Distribution theory and simulation studies are used to compare the proposed estimators with respect to bias, relative efficiency and robustness to model misspecification. The bias correction estimators proposed are applied to data from a study of screening tests for neonatal hearing loss.
A Hierarchical Bayesian Model for Predicting the Functional Consequences of Amino-Acid Polymorphisms
Authors: Verzilli Claudio J. , Whittaker John C. , Stallard Nigel , Chasman Daniel
Published: October 2004

Genetic polymorphisms in deoxyribonucleic acid coding regions may have a phenotypic effect on the carrier, e.g. by influencing susceptibility to disease. Detection of deleterious mutations via association studies is hampered by the large number of candidate sites; therefore methods are needed to narrow down the search to the most promising sites. For this, a possible approach is to use structural and sequence-based information of the encoded protein to predict whether a mutation at a particular site is likely to disrupt the functionality of the protein itself. We propose a hierarchical Bayesian multivariate adaptive regression spline (BMARS) model for supervised learning in this context and assess its predictive performance by using data from mutagenesis experiments on lac repressor and lysozyme proteins. In these experiments, about 12 amino-acid substitutions were performed at each native amino-acid position and the effect on protein functionality was assessed. The training data thus consist of repeated observations at each position, which the hierarchical framework is needed to account for. The model is trained on the lac repressor data and tested on the lysozyme mutations and vice versa. In particular, we show that the hierarchical BMARS model, by allowing for the clustered nature of the data, yields lower out-of-sample misclassification rates compared with both a BMARS and a frequen-tist MARS model, a support vector machine classifier and an optimally pruned classification tree.
Generalized Additive Modelling of Sample Extremes
Authors: Chavez-Demoulin V. , Davison A. C.
Published: October 2004

We describe smooth non-stationary generalized additive modelling for sample extremes, in which spline smoothers are incorporated into models for exceedances over high thresholds. Fitting is by maximum penalized likelihood estimation, with uncertainty assessed by using differences of deviances and bootstrap simulation. The approach is illustrated by using data on extreme winter temperatures in the Swiss Alps, analysis of which shows strong influence of the north Atlantic oscillation. Benefits of the new approach are flexible and appropriate modelling of extremes, more realistic assessment of estimation uncertainty and the accommodation of complex dependence patterns.
Low Dose Risk Estimation via Simultaneous Statistical Inferences
Authors: Piegorsch Walter W. , Webster West R. , Pan Wei , Kodell Ralph L.
Published: October 2004

The paper develops and studies simultaneous confidence bounds that are useful for making low dose inferences in quantitative risk analysis. Application is intended for risk assessment studies where human, animal or ecological data are used to set safe low dose levels of a toxic agent, but where study information is limited to high dose levels of the agent. Methods are derived for estimating simultaneous, one-sided, upper confidence limits on risk for end points measured on a continuous scale. From the simultaneous confidence bounds, lower confidence limits on the dose that is associated with a particular risk (often referred to as a bench-mark dose) are calculated. An important feature of the simultaneous construction is that any inferences that are based on inverting the simultaneous confidence bounds apply automatically to inverse bounds on the bench-mark dose.
A Unified Model for Covariate Measurement Error Adjustment in an Occupational Health Study While Accounting for Non-Detectable Exposures
Authors: Wannemuehler Kathleen A. , Lyles Robert H.
Published: October 2004

The paper focuses on an occupational health study where the goal is to associate a worker’s true log-normal-scale mean dust exposure over the year with forced expiratory volume. A previous analysis used repeated shift-long dust exposure measurements, taken over a year, as a surrogate to address the issue of the mean exposure being unobservable. However, in this study the associated measurement error is further complicated by the fact that some exposure measurements fall below a detectable limit. We extend the previous analysis via full maximum likelihood, to account appropriately for non-detectable exposures.
Interlanguage Refusals: Linguistic Politeness and Length of Residence in the Target Community
Authors: Félix‐Brasdefer J. César
Published: October 2004

Using role play and verbal‐report data, this study investigates the sequential organization of politeness strategies of 24 learners of Spanish and whether the learners’ ability to negotiate and mitigate a refusal was influenced by length of residence in the target community. Refusal sequences were examined throughout the interaction (head acts, pre‐ and postrefusals) and across conversational turns. Results showed more frequent attempts at negotiation and greater use of lexical and syntactic mitigation among learners who had spent more time in the target community and also revealed a preference for solidarity and indirectness, which approximated native Spanish speaker norms. It is suggested that the variables of proficiency and length of residence should be considered independently. Finally, learners’ perceptions of social status are discussed.
Training English and Chinese Listeners to Perceive Thai Tones: A Preliminary Report
Authors: Wayland Ratree P. , Guion Susan G.
Published: October 2004

The ability of native English (NE) and native Chinese (NC) speakers to identify and discriminate the mid‐ versus the low‐tone contrast in Thai was investigated before and after auditory training. The variables under investigation were first language background and the interstimulus interval (ISI) of the presentation (500 ms vs. 1500 ms). The NC group outperformed the NE group in its ability to discriminate the two Thai tones under the ISI 500 ms condition before training and under both ISI conditions after training. A significant improvement in identification from the pretest to the posttest was observed in the NC group under both ISI conditions, but not in the NE group. These results suggest that prior experience with the tone system in one tone language may be transferable to the perception of tone in another language.
Differential Employment Patterns for Citizens and Non‐Citizens in Science and Engineering in the United States: Minting and Competitive Effects
Authors: Levin Sharon G. , Black Grant C. , Winkler Anne E. , Stephan Paula E.
Published: October 2004

ABSTRACT  The consequences of the heavy inflow of foreign talent for U.S. scientists and engineers over the period 1973‐1997 are examined using data from the Survey of Doctorate Recipients. Of particular interest is whether non‐citizens trained in the United States have displaced citizens from jobs in science and engineering (S&E). Using a novel adaptation of the shift‐share technique, it is shown that citizen S&E doctorates have fewer jobs in S&E and fewer academic jobs than their non‐citizen counterparts for two reasons: the citizen doctoral population has experienced slower growth than the non‐citizen doctoral population, and citizen S&E doctorates have been displaced. Whether the displacement observed was a voluntary response of citizens to the lure of better opportunities elsewhere or an involuntary response indicative of having been pushed out by foreign talent remains to be determined.
The Location Behavior of the Multinational Enterprise: Some Analytical Issues
Authors: McCann Philip , Mudambi Ram
Published: October 2004

ABSTRACT In the international business literature location behavior has traditionally been analyzed usingDunning's (1977) OLI framework, which focuses on the nature, role, and behavior of multinational enterprise (MNE). In this paper it is argued that this approach is now no longer appropriate for discussing the spatial behavior of MNEs, because of the fundamental changes which have taken place either in MNE organization or in the global and institutional environment for foreign direct investment (FDI). At the same time, the paper argues that current location theory from regional economics and economic geography is also largely unsuitable for discussing these issues, such that the spatial behavior of the MNE provides a set of difficult challenges to location analysts. There appears to have been some response to these issues from the international business and management literature, most notably the Porter literature on clusters. However, it is also argued here that this literature provides few, if any, real answers to the problems set by the geographical behavior of the MNE. It is concluded that a fusion of traditional economic geography approaches with a focus on the information and organizational aspects of the firm and the region under consideration may be a way forward for both theory and empirical analysis.
The Baby Boom and Nonmetropolitan Population Change, 1975‐1990
Authors: Nelson Peter B. , Nicholson James P. , Stege E. Hope
Published: October 2004

ABSTRACT  Both economic and demographic contexts influence aggregate migration streams at the regional scale. The influence of demographic and economic context on aggregate migration at the nonmetropolitan scale, however, remains unstudied. This paper presents analysis based on 1980 and 1990 Public Use Microdata Sample (PUMS) data related to age cohort effects on nonmetropolitan population change. The analysis provides enhanced understanding of how demographic factors like the baby boom might influence population movements into and out of nonmetropolitan regions. Using modified age‐cohort decomposition techniques, the analysis demonstrates how the fluctuations in nonmetropolitan population growth between 1975 and 1990 are tied to the differential migration flows of the peak baby boom years (those born between 1955 and 1964). The analysis further demonstrates how fluctuations in nonmetropolitan population growth across regions are tied to migration flows of these baby boomers. Significant variation remains within regions.
Effects of matrix grain size on the kinetics of intergranular diffusion
Authors: Carlson W. D. , Gordon C. L.
Published: October 2004

A linear relationship exists between the mean volume of garnet porphyroblasts and the squared inverse of mean matrix grain diameter for six samples of garnetiferous mica quartzite with identical thermal histories and similar mineralogy and modes. This relationship accords with theoretical predictions of the dependence of intergranular diffusive fluxes on the volume fraction of grain edges that function as diffusional pathways during porphyroblast growth. The impact of matrix grain size is large: compared to a rock with a 1‐mm matrix, a rock with a 10‐μm matrix would experience rates of diffusion‐controlled porphyroblast growth that are 10 000 times faster, and characteristic length scales for chemical equilibration that are 100 times larger. Precursor grain sizes may therefore exert a major influence on crystallization kinetics. If matrix coarsening occurs during prograde reaction, a decrease in the volume fraction of diffusional pathways will tend to counteract the exponential thermal increase in diffusive fluxes. The impact of such matrix grain growth, although difficult to assess without firm knowledge of coarsening rates in polymineralic aggregates, might be significant for matrices finer than c. 100 μm at temperatures above c. 500–600 °C, but is likely negligible for coarser grain sizes and lower temperatures.
Evidence from Fe‐ and Al‐rich metapelites for thrust loading in the Transangarian region of the Yenisey Ridge, eastern Siberia
Authors: Likhanov I. I. , Polyansky O. P. , Reverdatto V. V. , Memmi I.
Published: October 2004

In the Transangarian region of the Yenisey Ridge in eastern Siberia (Russia), Fe‐ and Al‐rich metapelitic schists of the Korda plate show field and petrological evidence of two superimposed metamorphic events. An early middle Proterozoic event with age ofc.1100 Ma produced low‐pressure, andalusite‐bearing assemblages atc.3.5–4 kbar and 540–560 °C. During a subsequent late Proterozoic event atc. 850 Ma, a medium‐pressure, regional metamorphic overprint produced kyanite‐bearing mineral assemblages that replaced minerals formed in the low‐pressure event. Based on the results of geothermobarometry andP–Tpath calculations it can be shown that pressure increased from 4.5 to 6.7 kbar at a relatively constant temperature of 540–600 °C towards a major suture zone called the Panimba thrust. In order to produce such nearly isothermal loading of 1–7 °C km −1, we propose a model for the tectono‐metamorphic evolution of the study area based on crustal thickening caused by south‐westward thrusting of the 5–7 km‐thick upper‐plate metacarbonates over lower‐plate metapelites with velocity ofc.350 m Myr−1. A small temperature increase (up to 20 ± 15 °C) of the upper part of the overlapped plate is explained by specific behaviour of steady‐state geotherms calculated using lower radioactive heat production of metacarbonates as compared with metapelites. The suggested thermal‐mechanical model corresponds well withP–Tpaths inferred from obtained thermobarometric data and correlates satisfactorily withP–Ttrajectories predicted by other two‐dimensional thermal models for different crustal thickening and exhumation histories.
Quartz–garnet isotope thermometry in the southern Adirondack Highlands (Grenville Province, New York)
Authors: Peck W. H. , Valley J. W.
Published: October 2004

Quartz–garnet oxygen isotope thermometry of quartz‐rich metasedimentary rocks from the southern Adirondack Highlands (Grenville Province, New York) yields metamorphic temperatures of 700–800 °C, consistent with granulite facies mineral assemblages. Samples from the Irving Pond quartzite record Δ18O(Qtz–Grt) = 2.68 ± 0.21‰ (1 s.d., n = 15), corresponding to peak metamorphic conditions of 734 ± 38 °C. This agrees well with the estimates from garnet–biotite exchange thermometry. Similar temperature estimates are obtained from Swede Pond (682 ± 47 °C, n = 3) and King's Station (c. 700 °C). The Whitehall area records higher temperatures (798 ± 25 °C, n = 3). All of these temperatures are higher than previous regional temperature estimates. The c. 800 °C temperatures near Whitehall are consistent with preservation of pre‐granulite contact temperatures adjacent to anorthosite. The preservation of peak metamorphic temperatures in garnet of all sizes is consistent with slow oxygen diffusion in garnet, and closure temperatures of at least 730 °C. Peak metamorphic fractionations are preserved in rocks with varying quartz:feldspar ratios, indicating that the modal percentage of feldspar does not affect retrograde oxygen exchange in these rocks. The lack of this correlation suggests slow rates of oxygen diffusion in quartz and feldspar, consistent with the results of anhydrous oxygen diffusion experiments.
Development of a Porcine Model of Type 1 Diabetes by Total Pancreatectomy and Establishment of a Glucose Tolerance Evaluation Method
Authors: Kobayashi Kazuya , Kobayashi Naoya , Okitsu Teru , Yong Chen , Fukazawa Takuya , Ikeda Hideaki , Kosaka Yoshikazu , Narushima Michiki , Arata Takashi , Tanaka Noriaki
Published: October 2004

Abstract:  Purpose: To develop and evaluate the efficacy of diabetes‐targeted cell therapies in humans, a reliable model in larger animals is highly desirable. This article reports the surgical technique of total pancreatectomy in pigs and the biochemical analysis of the characteristics of totally pancreatectomized pigs. Methods: Surgical total pancreatectomy was conducted in 23 pigs. Blood glucose, insulin, biochemistries, activity index, and intravenous glucose tolerance test (IVGTT) were examined to assess the pathophysiological profiles of diabetic pigs. Results: A total of 14 pigs successfully underwent total pancreatectomy without requiring biliary reconstruction and were analyzed in the present study. Activity index was decreased from day 5 on and the mean survival of totally pancreatectomized pigs was 7.6 ± 2.7 days. No endogenous insulin secretion was confirmed in these pigs. Pigs which received total pancreatectomy demonstrated significantly higher levels of ketone bodies. IVGTT performed within 4 days after total pancreatectomy showed a spontaneous decrease in blood glucose levels despite an absence of endogenous insulin secretion. IVGTT on day 5 or later showed continued hyperglycemia in pigs with total pancreatectomy. Histological examination showed atrophy of hepatocytes and decreased glycogen storage in the liver and decreased mucus production of the small intestine. Conclusion: This article describes a porcine model of diabetes created by total pancreatectomy and it analyzes the pathophysiological profiles in the animals. The present study has suggested that IVGTT on day 5 or later after total pancreatectomy is a reliable method to evaluate the efficacy of cell therapies.
Modeling Centrifugal Cell Washers Using Computational Fluid Dynamics
Authors: Kellet Beth E. , Han Binbing , Dandy David S. , Wickramasinghe S. Ranil
Published: October 2004

Abstract:  Reinfusion of shed blood during surgery could avoid the need for blood transfusions. Prior to reinfusion of the red blood cells, the shed blood must be washed in order to remove leukocytes, platelets, and other contaminants. Further, the hematocrit of the washed blood must be increased. The feasibility of using computational fluid dynamics (CFD) to guide the design of better centrifuges for processing shed blood is explored here. The velocity field within a centrifuge bowl and the rate of protein removal from the shed blood has been studied. The results obtained indicate that CFD could help screen preliminary centrifuge bowl designs, thus reducing the number of initial experimental tests required when developing new centrifuge bowls. Although the focus of this work is on washing shed blood, the methods developed here are applicable to the design of centrifuge bowls for other blood‐processing applications.
A Tensor‐based Measure for Estimating Blood Damage
Authors: Arora Dhruv , Behr Marek , Pasquali Matteo
Published: October 2004

Abstract:  Implantable ventricular assist devices give hope of a permanent clinical solution to heart failure. These devices, both pulsatile‐ and continuous‐flow, are presently used as medium‐term bridge to heart transplant or recovery. While long‐term use of continuous‐flow axial and centrifugal pumps is being explored, the excessive level of blood damage in these devices has emerged as a design challenge. Blood damage depends both on shear stress and exposure time, and device designers have relied traditionally on global space‐ and time‐averaged estimates from experimental studies to make design decisions. Measuring distributions of shear stress levels and the blood cell's exposure to these conditions in complex rotary pump flow is difficult. On the other hand, computational fluid dynamics (CFD) is now being used as a tool for designing viable devices, offering more detailed information about the flow field. A tensor‐based blood damage model for CFD analysis is proposed here. The model estimates the time‐ and space‐dependent strain experienced by individual blood cells and correlates it to blood damage data from steady shear flow experiments. The blood cells are modeled as deforming droplets and their deformation is tracked along the pathlines of a computed flow. The model predicts that blood cells in a rapidly fluctuating shear flow can sustain high shear stress levels for very short exposure time without deforming considerably. In the context of mechanical modeling of the implantable Gyro blood pump being developed at Baylor College of Medicine, this suggests that blood cells traversing regions of highly fluctuating shear stress rapidly may not hemolyze significantly.
Comparison of a New Heparin‐coated Dense Membrane Lung with Nonheparin‐coated Dense Membrane Lung for Prolonged Extracorporeal Lung Assist in Goats
Authors: Ichinose Keisuke , Okamoto Taisuke , Tanimoto Hironari , Yoshitake Atsushi , Tashiro Masafumi , Sakanashi Yuji , Kuwana Katsuyuki , Tahara Koichiro , Kamiya Masahiro , Terasaki Hidenori
Published: October 2004

Abstract:  Thrombosis and bleeding are major complications in cases of prolonged extracorporeal lung assist (ECLA) with an artificial‐membrane lung. Antithrombogenic treatment of the artificial‐membrane oxygenator and circuits is indispensable for safe ECLA. The efficacy of a new heparin‐coated membrane lung with minimal systemic heparinization was evaluated for 7 days and compared with a nonheparin‐coated membrane lung in goats. The animals were randomly assigned to either the heparin‐coated membrane group (HM group, n = 5) or nonheparin‐coated membrane group (NHM group, n = 5). Activated coagulation time (ACT) during ECLA was controlled to below 150 s in the HM group, and to near 200 s in the NHM group. All goats in the HM group were sustained on ECLA for 7 days, but two goats in the NHM group died on the 4th and 6th days, respectively. The mean systemic administration rate of heparin during ECLA was 22.4 ± 4.4 U/kg/h in the HM group and 39.0 ± 10.0 U/kg/h in the NHM group. There was a significant difference between the two groups (P < 0.05). The oxygen transfer rate, the Pco2 difference, the perfusion resistance, and platelet counts showed no significant changes. There was no plasma leakage from the artificial lung. Although several clots were observed in the stagnant areas of the artificial lung, they did not lead to deterioration of the function of the artificial lung. The excellent antithrombogenicity, gas exchange ability, and durability of this new artificial lung with circuits might contribute to successful prolonged ECLA with minimal systemic heparinization.
Clinical efficacy of postoperative autologous transfusion of filtered shed blood in hip and knee arthroplasty
Authors: Strümper D. , Weber E.W.G. , Gielen‐Wijffels S. , Drumpt R. Van , Bulstra S. , Slappendel R. , Durieux M.E. , Marcus M.A.E.
Published: October 2004

BACKGROUND:  Total knee arthroplasty (TKA) or total hip arthroplasty (THA) regularly results in postoperative requirement of blood transfusion. Because of the disadvantages of allogeneic blood transfusion (ABT) such as the risk of transfusion‐associated infections, incompatibility‐related transfusion fatalities, or immunomodulatory effects, a continuing effort to reduce allogeneic blood transfusion is important. For this purpose, the effect of reinfusion of drain blood, via a postoperative wound drainage and reinfusion system, on the need for allogeneic blood transfusion was evaluated.

STUDY DESIGN AND METHODS:  Using a prospective observational quality assessment design, we compared 135 patients scheduled for TKA or THA with a historic group of 96 patients. In the study group the Bellovac ABT autotransfusion system was used. The shed blood was returned either when 500 mL were collected or at most 6 hours after surgery.

Compared were the preoperative, postoperative, and discharge hemoglobin, as well as the number of allogeneic blood transfusions.

RESULTS:  There were no statistical differences between preoperative, postoperative, and discharge hemoglobin levels. Autologous transfusion reduced the number of patients receiving ABT overall from 35 percent (control) to 22 percent (study).

The decrease of allogeneic transfusion requirement was most significant after TKA: from 18 percent to 6 percent (p < 0.001).

CONCLUSION:  We conclude that the Bellovac ABT device reduces allogeneic blood transfusions in TKA and THA.
Factors affecting the efficacy of peripheral blood progenitor cells collections by large‐volume leukaphereses with standardized processing volumes
Authors: Cassens Uwe , Barth Ingo Mathias , Baumann Claudia , Fischer Rudolf‐Josef , Kienast Joachim , Vormoor Josef , Sibrowski Walter
Published: October 2004

BACKGROUND:  Peripheral blood progenitor cell (PBPC) collections should be safe and efficient. Therefore, the influence and risk factors in large‐volume leukaphereses (LVL) with standardized blood volumes was investigated.

STUDY DESIGN AND METHODS:  In a total of 724 autologous LVL performed at our center, either 4× or 6× the patient's blood volume (PBV) was processed. The group with processing 4× the PBV showed a median of 31 circulating CD34+ cells per µL, and the group with processing 6× the PBV had a median of 13 CD34+ cells per µL before LVL. Individual clinical factors, laboratory factors, and apheresis run variables influencing the yields of PBPCs were retrospectively analyzed. Furthermore, the changes of laboratory variables and adverse effects during LVL were investigated.

RESULTS:  Multivariate analysis identified “age,”“circulating CD34+ cells,” and “percentage of mononuclear cells” as only factors influencing the yields of PBPCs. Altogether, processing 6× versus 4× the PBV did not result in significantly higher yields of CD34+ cells for the total group, but requested PBPC yields were achieved more often after processing 6× the PBV in patients below 20 CD34+ cells per µL blood. Processing 6× versus 4× the PBV showed a significant difference for the decrease of platelets, but not for any other laboratory variable. Adverse effects were recorded in 4.97 percent of LVL without accumulation in one group.

CONCLUSION:  In particular, patients with low amounts of circulating CD34+ cells profited from enlarged LVL demonstrating higher PBPC yields but comparable rates of adverse effects.
Extended storage of AS‐1 and AS‐3 leukoreduced red blood cells for 15 days after deglycerolization and resuspension in AS‐3 using an automated closed system
Authors: Bandarenko Nicholas , Hay Shauna N. , Holmberg Jerry , Whitley Pam , Taylor Harry L. , Moroff Gary , Rose Leslie , Kowalsky Richard , Brumit Marla , Rose Michael , Sawyer Sherrie , Johnson Adrienne , McNeil Deanna , Popovsky Mark A.
Published: October 2004

BACKGROUND:  The utilization of cryopreserved red blood cell (RBC) units had been limited by a maximum postdeglycerolization storage of 24 hours at 1 to 6°C until the recent development of a closed system for the glycerolization and deglycerolization process.

STUDY DESIGN AND METHODS:  Sixty leukoreduced additive solution (AS), AS‐1 (n = 30) and AS‐3 (n = 30) RBC units from 500‐mL whole blood (WB) collections were stored for 6 days, glycerolized, frozen at −70 ± 5°C for at least 14 days, thawed, deglycerolized, and stored for 15 days at 1 to 6°C. Glycerolization and deglycerolization were performed with the ACP 215. In‐vitro variables were tested before glycerolization, on Day 0, and Day 15 after deglycerolization storage. Forty donors were assessed for double‐label 24‐hour percent recovery, and T1/2 survival time was measured for 20 donors.

RESULTS:  Postdeglycerolization mean ± standard deviation in‐vitro RBC mass recoveries were 93 ± 5 percent for AS‐1 and 95 ± 4 percent for AS‐3. Mean hemoglobin ± standard deviation after deglycerolization was 50.5 ± 5.5g for AS‐1 and 50.1 ± 3.5g for AS‐3. Mean hemolysis (Day 15) was 0.36 ± 0.11 percent for AS‐1 and 0.38 ± 0.13 percent for AS‐3. Double‐label 24‐hour in‐vivo recoveries were 82.5 ± 7.8 percent for AS‐1 and 81.4 ± 7.1 percent for AS‐3. The 51Cr T1/2 value was 41.8 ± 3.97 for AS‐1 and 40.6 ± 7.11 for AS‐3. Other in‐vitro variables were as expected.

CONCLUSION:  Leukoreduced AS‐1 and AS‐3 RBCs after frozen storage at −70 ± 5°C can be stored for up to 14 days when processing is performed with the ACP 215 system with resuspension of deglycerolized RBCs in AS‐3.