bluuebunny/crossref_metadata_2025 huggingface dataset:
Confidence intervals for an effect size measure based on the Mann–Whitney statistic. Part 2: asymptotic methods and evaluation
Authors: Newcombe Robert G.
Published: October 2005

Several asymptotic confidence interval methods for U/mn, the Mann–Whitney U statistic divided by the product of the two sample sizes, are developed and evaluated alongside published methods. Novel methods derived from Gaussian and beta models perform well, though overall a modification of the Hanley–McNeil approach (method 5 in this evaluation) performed better and is recommended for calculating confidence intervals for U/mn for continuously distributed data. Copyright © 2005 John Wiley & Sons, Ltd.
Checking stationarity of the incidence rate using prevalent cohort survival data
Authors: Asgharian Masoud , Wolfson David B. , Zhang Xun
Published: October 2005

When survival data are collected as part of a prevalent cohort study with follow‐up, the recruited cases have already experienced their initiating event, say onset of a disease, and consequently the incidence process is only partially observed. Nevertheless, there are good reasons for interest in certain features of the underlying incidence process, for example whether or not it is stationary. Indeed, the well known relationship between incidence and prevalence, often used by epidemiologists, requires stationarity of the incidence rate for its validity. Also, the statistician can exploit stationarity of the incidence process by improving the efficiency of estimators in a prevalent cohort survival analysis. In addition, whether the incident rate is stationary is often in itself of central importance to medical and other researchers. We present here a necessary and sufficient condition for stationarity of the underlying incidence process, which uses only survival observations, possibly right censored, from a prevalent cohort study with follow‐up. This leads to a simple graphical means of checking for the stationarity of the underlying incidence times by comparing the plots of two Kaplan–Meier estimates that are based on partially observed incidence times and follow‐up survival data. We use our method to discuss the incidence rate of dementia in Canada between 1971 and 1991. Copyright © 2005 John Wiley & Sons, Ltd.
Dichotomizing continuous predictors in multiple regression: a bad idea
Authors: Royston Patrick , Altman Douglas G. , Sauerbrei Willi
Published: October 2005

In medical research, continuous variables are often converted into categorical variables by grouping values into two or more categories. We consider in detail issues pertaining to creating just two groups, a common approach in clinical research. We argue that the simplicity achieved is gained at a cost; dichotomization may create rather than avoid problems, notably a considerable loss of power and residual confounding. In addition, the use of a data‐derived ‘optimal’ cutpoint leads to serious bias. We illustrate the impact of dichotomization of continuous predictor variables using as a detailed case study a randomized trial in primary biliary cirrhosis. Dichotomization of continuous data is unnecessary for statistical analysis and in particular should not be applied to explanatory variables in regression models. Copyright © 2005 John Wiley & Sons, Ltd.
Comparison of predictive values of two diagnostic tests from the same sample of subjects using weighted least squares
Authors: Wang Wenquan , Davis Charles S. , Soong Seng‐Jaw
Published: October 2005

Screening and diagnostic tests are important in disease prevention or control. The predictive values of positive and negative (PPV and NPV) test results are two of four operational characteristics of a screening test. We review an existing method based on the generalized estimating equation (GEE) methodology for comparing predictive values from the same sample of subjects and propose two Wald test statistics derived from the weighted least squares (WLS) method for the analysis of categorical data. Using these results, we propose sample size calculation formulae for this problem. Simulation studies are conducted to compare the performances of the two Wald test statistics (one based on the difference of two PPVs or NPVs, another based on the logarithm of the ratio of two PPVs or NPVs) and the score/Wald test statistic derived from GEE. We recommend using the difference‐based WLS approach. Copyright © 2005 John Wiley & Sons, Ltd.
An efficient design for a study comparing two drugs, their combination and placebo
Authors: Wei Lynn
Published: October 2005

A novel design for a study comparing two drugs (A and B), their combination (AB) and placebo (P) in a stable disease such as chronic asthma is proposed. The primary objectives of the trial are to compare A (a new drug) with placebo and AB with B (an old drug). Other between‐treatment comparisons are secondary. The new design consists of the first 2 sequences of a single 4 × 4 Latin square: (A, AB, P, B|P, B, A, AB|AB, A, B, P|B, P, AB, A). The washout period between A and AB and that between P and B are eliminated based on the assumptions that there is no carry‐over effect from placebo and that the effect of the combination would be approximately same at steady state either starting the 2 drugs at the same time or adding one later. Equal period effect for Periods 1 and 2, and for Periods 3 and 4 are also assumed for all treatment effects being estimable. Advantages and disadvantages of this design were evaluated and compared with other possible designs. Compared with other possible designs, the new design is more efficient. For example, the new design requires less than ¼ of the sample size a parallel design would need and it requires ⅔ of the sample size a 4‐treatment, 3‐period incomplete block design would need for the same power at the same detectable difference. It has a similar efficiency to a 4‐treatment, 4‐period cross‐over design but with a shorter duration. In this design, all between‐treatment comparisons are based on direct within‐subject information. The new design could also potentially decrease the probability of patient's drop‐outs and use of rescue medication due to lack of efficacy during the placebo periods by reducing the number of placebo washout periods. The benefits reaped from the new design seem to outweigh its risks, which include potential bias for the secondary between‐treatment comparisons if the additional assumption about period effects are not satisfied and the incapability of directly assessing the onset of action of the combination of 2 drugs. Copyright © 2005 John Wiley & Sons, Ltd.
Generalizing the TITE‐CRM to adapt for early‐ and late‐onset toxicities
Authors: Braun Thomas M.
Published: October 2005

Due to the staggered entry of subjects in phase I trials, some subjects will only be partially through the study when others are ready to be enrolled. Nonetheless, many phase I designs focus solely upon whether or not subjects experience toxicity, thereby determining the maximum tolerated dose (MTD) with a binomial likelihood using data from fully observed subjects. The time‐to‐event continual reassessment method (TITE‐CRM) was the first attempt to incorporate information from partially observed subjects by using a weighted binomial likelihood in which the weights are based upon the actual toxicity time distribution. Unfortunately, it is difficult to accurately estimate the toxicity time distribution because only a small proportion of enrolled subjects will experience toxicity. Creators of the TITE‐CRM propose the simple alternative of weighting subjects by the proportion of time observed, as well as two adaptive weights to adjust for late‐onset toxicities. As a alternative to these approaches, we suggest assuming the toxicity times, as a proportion of the total time under observation, have a Beta distribution with parameters 1.0 and θ; we also allow θ to vary by dose. The value of θ allows us to reflect the occurrence of early‐ or late‐onset toxicities without correctly specifying the actual distribution of toxicity times. Through this model, we do not necessarily expect to improve identification of the MTD, but rather hope to reduce the exposure of subjects to overly toxic doses. Through simulation, we examine how well our model identifies the MTD and allocates dose assignments in three scenarios investigated by previous publications. Copyright © 2005 John Wiley & Sons, Ltd.
The sequential analysis of repeated binary responses: a score test for the case of three time points
Authors: Sooriyarachchi Marina Roshini , Whitehead John , Whitehead Anne , Bolland Kim
Published: October 2005

In this paper a robust method is developed for the analysis of data consisting of repeated binary observations taken at up to three fixed time points on each subject. The primary objective is to compare outcomes at the last time point, using earlier observations to predict this for subjects with incomplete records. A score test is derived. The method is developed for application to sequential clinical trials, as at interim analyses there will be many incomplete records occurring in non‐informative patterns. Motivation for the methodology comes from experience with clinical trials in stroke and head injury, and data from one such trial is used to illustrate the approach. Extensions to more than three time points and to allow for stratification are discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Likelihood approaches to the non‐parametric two‐sample problem for right‐censored data
Authors: Troendle James F. , Yu Kai F.
Published: October 2005

The classical two‐sample problem with random right‐censoring is considered. We show that non‐ parametric likelihood techniques can be used to obtain tests for either the identity hypothesis or the non‐parametric Behrens–Fisher hypothesis (NBFH). In the case of the identity hypothesis, a special imputed permutation distribution is used to estimate the distribution under the null hypothesis. In the case of the NBFH, simulation from the constrained non‐parametric maximum likelihood estimate is used. Simulation shows that the tests using either approximation have excellent control of the type I error rate, even with quite small sample sizes. Further, for Lehmann‐type alternatives the likelihood‐based methods have similar power to the logrank test, while for the non‐Lehmann‐type alternatives tried here the likelihood‐based methods have superior power. Published in 2005 by John Wiley & Sons, Ltd.
Curious phenomena in Bayesian adjustment for exposure misclassification
Authors: Gustafson Paul , Greenland Sander
Published: October 2005

Many epidemiologic investigations involve some discussion of exposure misclassification, but rarely is there an attempt to adjust for misclassification formally in the statistical analysis. Rather, investigators tend to rely on intuition to comment qualitatively on how misclassification might impact their findings. We point out several ways in which intuition might fail, in the context of unmatched case–control analysis with non‐differential exposure misclassification. Particularly, we focus on how intuition can conflict with the results of a Bayesian analysis that accounts for the various uncertainties at hand. First, the Bayesian adjustment for misclassification can weaken the evidence about the direction of an exposure–disease association. Second, admitting uncertainty about the misclassification parameters can lead to narrower interval estimates concerning the association. We focus on the simple setting of unmatched case–control analysis with binary exposure and without adjustment for confounders, though much of our discussion should be relevant more generally. Copyright © 2005 John Wiley & Sons, Ltd.
A multi‐state model for joint modelling of terminal and non‐terminal events with application to Whitehall II
Authors: Siannis F. , Farewell V. T. , Head J.
Published: October 2005

Serious coronary heart disease (CHD) is a primary outcome in the Whitehall II study, a large epidemiological study of British civil servants. Both fatal (F) and non‐fatal (NF) CHD events are of interest and while essentially complete information is available on F events, the observation of NF events is subject to potentially informative censoring. A multi‐state model with an unobserved state is introduced for the joint modelling of F and NF events. Two model‐based assumptions ensure identifiability of the model and a parameter is introduced to allow sensitivity analyses concerning the assumption linked to informative censoring. Weibull transition rates, which include dependence on explanatory variables, are used in the analysis of Whitehall II data with a particular focus on the relationship between civil service grade and CHD events. Copyright © 2005 John Wiley & Sons, Ltd.
Causal conclusions are most sensitive to unobserved binary covariates
Authors: Wang Liansheng , Krieger Abba M.
Published: October 2005

There is a rich literature that considers whether an observed relation between treatment and response is due to an unobserved covariate. In order to quantify this unmeasured bias, an assumption is made about the distribution of this unobserved covariate; typically that it is either binary or at least confined to the unit interval. In this paper, this assumption is relaxed in the context of matched pairs with binary treatment and response. One might think that a long‐tailed unobserved covariate could do more damage. Remarkably that is not the case: the most harm is done by a binary covariate, so the case commonly considered in the literature is most conservative. This has two practical consequences: (i) it is always safe to assume that an unobserved covariate is binary, if one is content to make a conservative statement; (ii) when another assumption seems more appropriate, say normal covariate, there will be less sensitivity than with a binary covariate. This assumption implies that it is possible that a relation between treatment and response that is sensitive to unmeasured bias (if the unobserved covariate is dichotomous), ceases to be sensitive if the unobserved covariate is normally distributed. These ideas are illustrated by three examples. It is important to note that the claim in this paper applies to our specific setting of matched pairs with binary treatment and response. Whether the same conclusion holds in other settings is an open question. Copyright © 2005 John Wiley & Sons, Ltd.
Using the ROC curve for gauging treatment effect in clinical trials
Authors: Brumback Lyndia C. , Pepe Margaret S. , Alonzo Todd A.
Published: October 2005

Non‐parametric procedures such as the Wilcoxon rank‐sum test, or equivalently the Mann–Whitney test, are often used to analyse data from clinical trials. These procedures enable testing for treatment effect, but traditionally do not account for covariates. We adapt recently developed methods for receiver operating characteristic (ROC) curve regression analysis to extend the Mann–Whitney test to accommodate covariate adjustment and evaluation of effect modification. Our approach naturally extends use of the Mann–Whitney statistic in a fashion that is analogous to how linear models extend thet‐test. We illustrate the methodology with data from clinical trials of a therapy for Cystic Fibrosis. Copyright © 2005 John Wiley & Sons, Ltd.
A powerful method of combining measures of association and Hardy–Weinberg disequilibrium for fine‐mapping in case‐control studies
Authors: Song Kijoung , Elston Robert C.
Published: October 2005

We present a new method for fine‐mapping a disease susceptibility locus using a case‐control design. The new method, termed the ‘weighted average (WA) statistic’, averages the Cochran–Armitage (CA) trend test statistic and the difference between the Hardy Weinberg disequilibrium test statistics (the HWD trend) for cases and controls. The main features of the WA statistic are that it mitigates against the weaknesses, and maintains the strong points, of both the CA trend test and the HWD trend test. To allow for the extra variance induced by population structure and cryptic relatedness, the WA statistic can be adjusted for variance inflation. Based on the results of a simulation study, when there is no population structure the WA test statistic shows good performance under a variety of genetic disease models. When there is population structure, the adjusted WA statistic maintains the correct probability of type I error. Under all genetic disease models investigated, the adjusted WA statistic has better power than the adjusted CA trend test, the HWD trend test or the product of the adjusted CA trend test and the HWD trend test statistics. Copyright © 2005 John Wiley & Sons, Ltd.
Effect measures in non‐parametric regression with interactions between continuous exposures
Authors: Cadarso‐Suárez Carmen , Roca‐Pardiñas Javier , Figueiras Adolfo
Published: October 2005

In many biomedical studies, interest is often attached to calculating effect measures in the presence of interactions between two continuous exposures. Traditional approaches based on parametric regression are limited by the degree of arbitrariness involved in transforming these exposures into categorical variables or imposing a parametric form on the regression function. In this paper, we present: (a) a flexible non‐parametric method for estimating effect measures through generalized additive models including interactions; and (b) bootstrap techniques for (i) testing the significance of interaction terms, and (ii) constructing confidence intervals for effect measures. The validity of our methodology is supported by simulations, and illustrated using data from a study of possible risk factors for post‐operative infection. This application revealed a hitherto unreported effect: for patients with high plasma glucose levels, increased risk is associated, not only with low, but also with high percentages of lymphocytes. Copyright © 2005 John Wiley & Sons, Ltd.
Diagnosis using predictive probabilities without cut‐offs
Authors: Choi Young‐Ku , Johnson Wesley O. , Thurmond Mark C.
Published: October 2005

Standard diagnostic test procedures involve dichotomization of serologic test results. The critical value or cut‐off is determined to optimize a trade off between sensitivity and specificity of the resulting test. When sampled units from a population are tested, they are allocated as either infected or not according to the test outcome. Units with values high above the cut‐off are treated the same as units with values just barely above the cut‐off, and similarly for values below the cut‐off. There is an inherent information loss in dichotomization. We thus develop a diagnostic screening method based on data that are not dichotomized within the Bayesian paradigm. Our method determines the predictive probability of infection for each individual in a sample based on having observed a specific serologic test result and provides inferences about the prevalence of infection in the population sampled. Our fully Bayesian method is briefly compared with a previously developed frequentist method. We illustrate the methodology with serologic data that have been previously analysed in the veterinary literature, and also discuss applications to screening for disease in humans. The method applies more generally to a variation of the classic parametric 2‐population discriminant analysis problem. Here, in addition to training data, additional units are sampled and the goal is to determine their population status, and the prevalence(s) of the subpopulation(s) from which they were sampled. Copyright © 2005 John Wiley & Sons, Ltd.
Improving ecological inference using individual‐level data
Authors: Jackson Christopher , Best Nicky , Richardson Sylvia
Published: October 2005

In typical small‐area studies of health and environment we wish to make inference on the relationship between individual‐level quantities using aggregate, or ecological, data. Such ecological inference is often subject to bias and imprecision, due to the lack of individual‐level information in the data. Conversely, individual‐level survey data often have insufficient power to study small‐area variations in health. Such problems can be reduced by supplementing the aggregate‐level data with small samples of data from individuals within the areas, which directly link exposures and outcomes. We outline a hierarchical model framework for estimating individual‐level associations using a combination of aggregate and individual data. We perform a comprehensive simulation study, under a variety of realistic conditions, to determine when aggregate data are sufficient for accurate inference, and when we also require individual‐level information. Finally, we illustrate the methods in a case study investigating the relationship between limiting long‐term illness, ethnicity and income in London. Copyright © 2005 John Wiley & Sons, Ltd.
Full‐service community schools: A strategy—not a program
Authors: Dryfoos Joy
Published: October 2005

Community schools are one solution to the fact that “schools can't do it alone.” Today's youth need comprehensive, coordinated support services provided in schools through partnerships.
The New York City Beacons: Rebuilding communities of support in urban neighborhoods
Authors: Kleinbard Peter
Published: October 2005

In New York City and elsewhere, the experience of Beacons in developing learning environments that are both supportive and challenging is finding its way into public school settings, with promising results.
Full‐service community schools: Cause and outcome of public engagement
Authors: Tagle Richard
Published: October 2005

The public plays a critical role in establishing and sustaining full‐service community schools.
Anchors of the community: Community schools in Chicago
Authors: Swanson Elizabeth F.
Published: October 2005

Chicago Public Schools, in partnership with the greater Chicago community, is implementing the largest‐scale community school initiative in the nation. By bringing together public, private, and nonprofit entities, community schools in Chicago provide quality out‐of‐school‐time activities and services that strive to improve the education, health, and wellness of students, families, and the community.
The school community council: Creating an environment for student success
Authors: Diehl Dan , Gray Cathy , O'Connor Ginny
Published: October 2005

A model of community‐school partnerships is developing in a school district in Evansville, Indiana.
Schools uniting neighborhoods: The SUN initiative in Portland, Oregon
Authors: Iverson Dianne
Published: October 2005

Through Schools Uniting Neighborhoods, county and city, school and community developed a unique collaboration to support fifty‐one community schools.
Myogenic Markers in the Evaluation of Embryonal Botryoid Rhabdomyosarcoma of the Female Genital Tract
Authors: Riedlinger Wolfram F. J. , Kozakewich Harry P. W. , Vargas Sara O.
Published: October 2005

Rhabdomyosarcoma presents special diagnostic problems when it involves the uterine cervix in young children because tumor cells may lack marked atypia and may blend with the normal, immature, condensed, cellular stroma, rendering diagnosis difficult. Myogenic makers are a valuable ancillary technique for establishing a diagnosis of rhabdomyosarcoma. However, desmin positivity has been reported in cervical stromal cells, which can confound diagnosis. To determine whether immunohistochemical markers of skeletal muscle differentiation are helpful in the diagnosis of uterine botryoid rhabdomyosarcoma, we compared the immunohistochemical staining pattern of cervical rhabdomyosarcoma from 3 patients with that of normal uteri from age-matched autopsy controls by using antibodies for desmin, smooth muscle actin, muscle-specific actin, myoD1, myogenin, and WT-1. All tumors demonstrated at least focal immunopositivity for desmin, muscle-specific actin, smooth muscle actin, myoD1, and WT-1, and 1 tumor was also positive for myogenin. Autopsy controls showed only scattered subepithelial stromal immunoreactivity for desmin, muscle-specific actin, smooth muscle actin, and WT-1 and showed cytoplasmic, but not nuclear, immunopositivity for myoD1 and myogenin. Myometrium was diffusely positive for desmin and muscle-specific actin. We conclude that desmin, muscle-specific actin, smooth muscle actin, and WT1 are not specific for discriminating embryonal rhabdomyosarcoma from normal subepithelial cells in the female genital tract of children, although the number of immunopositive cells is consistently larger in rhabdomyosarcoma. Nuclear staining for myoD1 and myogenin appears not to occur in normal tissue, but it may be absent or sparse in embryonal rhabdomyosarcoma. Our findings indicate that, in this anatomic site, the diagnosis of rhabdomyosarcoma and in particular determination of tumor margins remain very reliant on histomorphology.
Primary Sclerosing Cholangitis in Children: A Histologic Follow-up Study
Authors: Batres L. Arturo , Russo Pierre , Mathews Mark , Piccoli David A. , Chuang Emil , Ruchelli Eduardo
Published: October 2005

Primary sclerosing cholangitis (PSC) is rare in the pediatric population. Little information exists on the progression of the disease in children. This study evaluated the experience with PSC at the Children's Hospital of Philadelphia over the past 20 years, with an emphasis on the histologic features at presentation, during disease progression, and after liver transplantation. We retrospectively reviewed the medical records of patients diagnosed with PSC between 1981 and 2001. Nineteen patients met the inclusion criteria with classic radio-graphic evidence of PSC. One additional patient with normal biliary imaging was subsequently diagnosed at the time of liver transplantation. The 20 patients with PSC (14 males) ranged in age from 1 month to 15 years at time of presentation. Inflammatory bowel disease was evident in 50% of patients. Initial histology revealed advanced disease (bridging fibrosis or cirrhosis) in 13 patients and an earlier histologic stage in 7 patients. Of the latter, 3 remain stable, 2 required transplantation, and 2 were lost to follow-up. Seven of the 13 patients with advanced disease required orthotopic liver transplantation, and 3 of these subsequently showed recurrence of primary disease in the allograft. Thus, most subjects presented insidiously at an advanced stage that required transplantation. Subjects who presented at an earlier stage progressed or remained stable, but the histologic findings at diagnosis were generally not predictive of disease progression. Recurrence of PSC after transplantation is a significant complication in children.
UV‐B‐induced plant stress as a possible cause of ten‐year hare cycles
Authors: Selås Vidar
Published: October 2005

Predation has been assumed to be a necessary factor in the ten‐year population cycle of the snowshoe hare (Lepus americanus) and Canadian lynx (Lynx canadensis). The UV‐B‐induced plant stress hypothesis, in contrast, predicts that hare performance, especially reproduction, is negatively related to sunspot numbers, because production of UV‐B‐protective phenolics in food plants in periods of low sunspot activity, when the ozone layer is thin, increases the availability of amino acids and reduces the amount of phenolics that protect against herbivores. In accordance with the UV‐B‐induced plant stress hypothesis, and despite the absence of predators that have been assumed to be necessary for hare cycles, mountain hare (Lepus timidus) populations in Norway fluctuate in close synchrony with snowshoe hare populations in Alberta and the Yukon, Canada. When adjusting for the phase of the hare cycle, the natality of snowshoe hare in Alberta 1962–1976 was negatively related to sunspot numbers with a time lag of two years. It is concluded that delayed responses to UV‐B‐induced changes in plant chemistry during the sunspot cycle is a possible cause of ten‐year cycles of hares and other herbivores, for example grouse and forest moths.
Intracellular processing of the Sendai virus C′ protein leads to the generation of a Y protein module: Structure–functional implications
Authors: de Breyne Sylvain , Stalder Romaine , Curran Joseph
Published: October 2005

The Sendai virus “C‐proteins” (C′, C, Y1 and Y2) are a nested set of non‐structural proteins. The shorter Y proteins arise in vivo both by de novo translation initiation and by proteolytic processing of C′. In this paper, we demonstrate that C′ but not C (differing only by 11 N‐terminal amino acid) serves as an efficient substrate for intracellular processing. However, processing can be mimicked in vitro by the addition of endopeptidases. Under conditions of limited proteolysis we observed that in a fraction of the C′ protein the Y region exists as a proteinase resistant core. This core was conserved in the C protein. We propose that C′ functions as a Pro‐protein delivering the Y module to a specific intracellular location.
Flavonoid components and flower color change in transgenic tobacco plants by suppression of chalcone isomerase gene
Authors: Nishihara Masahiro , Nakatsuka Takashi , Yamamura Saburo
Published: October 2005

A cDNA encoding chalcone isomerase (CHI) was isolated from the petals of Nicotiana tabacum and the effect of its suppression on flavonoid biosynthesis was analyzed in transgenic tobacco plants. CHI‐suppression by RNA interference (RNAi) showed reduced pigmentation and change of flavonoid components in flower petals. The plants also accumulated high levels of chalcone in pollen, showing a yellow coloration. Our results first demonstrated that suppression of CHI by genetic transformation is possible in higher plants. This suggests that CHI plays a major part in the cyclization reaction from chalcone to flavanone, and that spontaneous reactions are few, if any, in tobacco plants.
Protein S attenuates the invasive potential of THP‐1 cells by interfering with plasminogen binding on cell surface via a protein C‐independent mechanism
Authors: Hryszko Tomasz , Suzuki Yuko , Mogami Hideo , Urano Tetsumei
Published: October 2005

Protein S, a cofactor for activated protein C (aPC) to inactivate coagulation factors, also plays a pivotal role in inflammation. Based on our recent findings that aPC and protein S modifies tissue plasminogen activator (tPA)‐catalyzed activation of Glu‐plasminogen (Glu‐plg), we analyzed possible role of protein S in cell‐associated plasminogen activation and invasive potential of inflammatory cells. Monocyte‐like THP‐1 cells, to which both plasminogen and tPA bind, enhanced tPA‐catalyzed plasminogen activation, which was partially abolished by protein S but not by aPC. Protein S attenuated both the plasminogen binding to THP‐1 cells and associated their invasive potential through Matrigel.
Inter-Carpal Soft Tissue Entrapment. A Possible Explanation for Chronic Dorsal Wrist Pain
Authors: TERNG S. C. A. , KUYPERS K. C. , KOCH A. R.
Published: October 2005

This retrospective study evaluates the surgical treatment of a group of patients with unknown chronic dorsal wrist pain. The cause of their symptoms was interpreted as a painful entrapment of fibrous tissue in the radio-carpal and inter-carpal joints during specific movements. Between 1997 and 2001, 30 patients were treated by surgical excision of this tissue and 26 patients were traced for follow-up. Twenty-three patients were symptom free, or experienced major benefit from surgery. Wrist function measurements using the VAS scale showed improvement in 24 patients. Microscopic examination of the removed specimen shows fibrous tissue with non-specific changes. Inter-carpal soft tissue entrapment can explain the typical clinical findings in some patients with unknown chronic dorsal wrist pain. After careful selection, surgical excision of all entrapped tissue in the radio-carpal and mid-carpal joint may give relief of pain and improvement of wrist function.
A Comparison of late Quaternary Forest Changes in New Caledonia and Northeastern Australia
Authors: Stevenson Janelle , Hope Geoffrey
Published: October 2005

A pollen record from Lake Xere Wapo, southeast New Caledonia, is the longest continuous terrestrial record to be recovered from the tropical southwest Pacific and reveals a series of millennial scale changes in vegetation over the last ∼130,000 yr. A comparison of the Lake Xere Wapo record with the key northeast Australian record of Lynch's Crater reveals regional patterns of change. From ∼120,000 to ∼50,000 yr ago the vegetation around Lake Xere Wapo alternated between rainforest and maquis with fire an important disturbance factor. In the last 50,000 yr fire is almost absent from the record and the vegetation assumes a character unprecedented in the preceding 100,000 yr, dominated by Dacrydium and Podocarpus pollen. The most compelling aspect of the comparison with Lynch's Crater is that the much-discussed Araucaria decline at around 45,000 yr ago in northern Queensland is matched by a similar decline in the Lake Xere Wapo record.
Challenges for German Foreign Policy at the Beginning of the 21st Century
Authors: HACKE CHRISTIAN
Published: October 2005

Why is it that the foreign policy of Germany's Red/Green government differs so remarkably from that of earlier German administrations – and what promises and dangers does this hold for the future? A careful analysis of the biographical background of today's German leaders, Chancellor Schröder and foreign minister Fischer in particular, explains the leftist and anti-American twist of current German policy. As children of the radical movement of 1968, these leaders hold a distorted view of Germany's history that ails their foreign policy decision-making. Instead of cultivating the success, the style, and the smoothness of German foreign policy until reunification, they try to distance the new ‘Berlin Republic’ from the old ‘Bonn Republic.’ Moralizing rhetoric and the divide between ambitions (permanent membership of the UN security council, for instance) and capabilities (especially regarding the chronically underfunded military) characterize Schröder's ‘German Way’ – with disastrous consequences. While containment of the Soviet Union was the overarching principle of the Cold War, German leaders today seem determined to contain American influence and to counter the American arrogance of power with the German arrogance of impotence. Thus, they fail to deliver any of the much-needed coherence and clarity about Germany's role in the world.
If You Have No Misgivings: Churchill's Nobel Prize in Literature
Authors: ALLÉN STURE
Published: October 2005

In 1953, Winston Churchill was awarded the Nobel Prize in Literature. Half a year later, I attended a course in English at a British university. We were a group of students from various countries, and we met for social evenings once a week. There were discussions and mutual entertainment as well as just getting together. On one of these occasions, I asked a question relating to the literary aspect of the course: ‘What was the reaction in this country when Winston Churchill got the Nobel Prize in Literature?’ There was complete silence. The main teacher was clearly embarrassed and looked at the other teachers, but not a word was uttered. Finally, he turned to me and said: ‘There was evidently no reaction.’ He looked around once more and added: ‘I think they were glad the old chap got something.’ The man referred to as ‘the old chap’ was about 80 years old at the time, a legend in his own lifetime, the receiver of heaps of distinctions including literary prizes.

Everything that has to do with the Nobel Prize – nominations, reports, discussions – is subject to secrecy for 50 years. This is a blessing for us who are in charge of the Prize. The other side of the coin is that, as far as Churchill is concerned, I am now in a position to account for things that have been hidden so far. Let us see what the archives of the Academy can tell us, bearing in mind that one of the interesting aspects of the Prize is its function in cultural communication.
The Renaissance of Museums in Britain
Authors: BROWN CHRISTOPHER
Published: October 2005

In this paper – given as a lecture at Netherlands Institute for Advanced Study in the summer of 2003 – I survey the remarkable renaissance of museums – national and regional, public and private – in Britain in recent years, largely made possible with the financial support of the Heritage Lottery Fund. I look in detail at four non-national museum projects of particular interest: the Horniman Museum in South London, a remarkable and idiosyncratic collection of anthropological, natural history and musical material which has recently been re-housed and redisplayed; secondly, the nearby Dulwich Picture Gallery, famous for its 17th- and 18th-century Old Master paintings, a masterpiece of 19th-century architecture by Sir John Soane, which has been restored, and modern museum services provided. The third is the New Art Gallery, Walsall, where the Garman Ryan collection of early 20th-century painting and sculpture form the centrepiece of a new building with fine galleries and the forum is the Manchester Art Gallery, where the former City Art Gallery and the Athenaeum have been combined in a single building in which to display the city's rich art collections. The Ashmolean Museum in Oxford, of which I am Director, is the most important museum of art and archaeology in England outside London and the greatest University Museum in the world. Its astonishingly rich collections are introduced and the transformational plan for the museum is described. In July 2005 the Heritage Lottery Fund announced a grant of £15 million and the renovation of the Museum is now underway.
‘The purest examples from antiquity’ – Old Museums in a Modern World
Authors: HALBERTSMA RUURD B.
Published: October 2005

Archaeological museums often came into existence from private collections of curiosities. When official museums were created in the course of the 18th and 19th centuries, the question of which cultures belonged to the ‘ancient world’ (and which not) was hotly debated, as the example of the National Museum of Antiquities in Leiden shows us. In addition, the role of an archaeological collection in society could be regarded in various ways. In the 19th century the ‘purest examples from antiquity’ were used as models for architects, artists and artisans. Nowadays antiquity seems to inspire many aspects of our culture, but much can be argued against the feeling that the classical spirit is enlightening our lives. An important role can be played by archaeological museums and their curators in a world in which the humanities are severely at risk.
Subduction zone guided waves and the heterogeneity structure of the subducted plate: Intensity anomalies in northern Japan
Authors: Furumura T. , Kennett B. L. N.
Published: October 2005

The subducting Pacific plate acts an efficient waveguide for high‐frequency signals and often produces anomalously large intensity on the eastern seaboard of northern Japan during deep earthquakes. The waveform records in the region of high intensity show a low‐frequency (f < 0.25 Hz) onset for both P and S waves, followed by large, high‐frequency (f > 2 Hz) later arrivals with a long coda. This behavior is not explained by a simple subduction zone model comprising a high‐velocity plate with low attenuation. From the analysis of observed broadband waveforms and numerical simulation of seismic wave propagation in the Pacific subduction zone we demonstrate that the high‐frequency guided waves traveling in the subducting plate arise from the scattering of seismic waves by heterogeneity in plate structure. Our preferred model of the heterogeneity has elongated scatterers parallel to the plate margin described by a von Karmann function with a downdip correlation length of about 10 km and much shorter correlation length of about 0.5 km in thickness. The standard deviation of wave speed fluctuations from the averaged background model is about 2%. This new heterogeneous plate model generates significant scattering of seismic waves with wavelengths shorter than correlation distance in thickness, but low‐frequency waves, with long wavelengths, can easy tunnel through such lamina structure. The result is frequency‐selective propagation characteristics with a faster low‐frequency phase followed by large and high‐frequency signals with very long coda. A low‐wave speed channel effect from the former oceanic crust at the top of the subducting slab is not necessary to explain the observed dispersed signals and the very long high‐frequency coda. Three‐dimensional simulations, using the Earth simulator supercomputer for modeling of high‐frequency seismic wave propagation in the Pacific subduction zone including plate heterogeneity, clearly demonstrate the scattering waveguide effects for high‐frequency seismic waves traveling in the plate. The region of large intensity for the heterogeneous model migrates away from the hypocenter into northern Japan with an elongated zone along the Pacific coast, almost comparable to the observations from deep events in the Pacific plate.
Data assimilative hindcast of the Gulf of Maine coastal circulation
Authors: He Ruoying , McGillicuddy Dennis J. , Lynch Daniel R. , Smith Keston W. , Stock Charles A. , Manning James P.
Published: October 2005

A data assimilative model hindcast of the Gulf of Maine (GOM) coastal circulation during an 11 day field survey in early summer 2003 is presented. In situ observations include surface winds, coastal sea levels, and shelf hydrography as well as moored and shipboard acoustic Doppler D current profiler (ADCP) currents. The hindcast system consists of both forward and inverse models. The forward model is a three‐dimensional, nonlinear finite element ocean circulation model, and the inverse models are its linearized frequency domain and time domain counterparts. The model hindcast assimilates both coastal sea levels and ADCP current measurements via the inversion for the unknown sea level open boundary conditions. Model skill is evaluated by the divergence of the observed and modeled drifter trajectories. A mean drifter divergence rate (1.78 km d−1) is found, demonstrating the utility of the inverse data assimilation modeling system in the coastal ocean setting. Model hindcast also reveals complicated hydrodynamic structures and synoptic variability in the GOM coastal circulation and their influences on coastal water material property transport. The complex bottom bathymetric setting offshore of Penobscot and Casco bays is shown to be able to generate local upwelling and downwelling that may be important in local plankton dynamics.
A parameterization of ion‐induced nucleation of sulphuric acid and water for atmospheric conditions
Authors: Modgil M. S. , Kumar Sanjeev , Tripathi S. N. , Lovejoy E. R.
Published: October 2005

This paper describes a five‐dimensional parameterization of ion‐induced nucleation (IIN) that covers the complete range of conditions relevant to the lower atmosphere. The parameters are (1) temperature T (190–300 K), (2) relative humidity RH (0.05–0.95), (3) number concentration of H2SO4 (105–108 cm−3), (4) first‐order loss of H2SO4 to particles (0.00009–0.0245 s−1), and (5) ion source rate (2–50 ion pairs cm−3 s−1). The parameterization is based on a steady state version of the kinetic aerosol model Sulphuric Acid and Water Nucleation (SAWNUC) that uses experimentally measured thermodynamics for the ion clusters. Parameterized formulas are obtained for the following variables: (1) particle nucleation rate (cm−3 s−1), (2) H2SO4 nucleation rate (cm−3 s−1), (3) number of H2SO4 molecules in average nucleating cluster, (4) number of H2O molecules in average nucleating cluster, and (5) radius (nanometers) of average nucleating cluster. The parameterization generally reproduces the modeled nucleation rate to within an order of magnitude over the whole range of conditions, except when the nucleation rate is very low (<10−6 cm−3 s−1), which corresponds to a rate of less than 0.1 particle d−1 cm−3. This parameterization speeds up IIN calculations by a factor of ∼106, as compared to the original SAWNUC model.
Application of spatial cross correlation to detection of migration of submarine sand dunes
Authors: Duffy Garret P. , Hughes‐Clarke John E.
Published: October 2005

Knowledge of migration rates of bedforms provides an indirect indication of the behavior of tidally averaged bottom currents, enables optimization of hydrographic survey frequency and may enable calculation of bedload transport rate. To measure bedform migration rate, we test the use of spatial correlation as a measurement method, which quantifies and locates a region of maximum similarity between two spatial variables. For the latter, we use consecutive eight‐bit images of spatial gradient, derived from bathymetric digital terrain models, carrying out the correlation over this representation of the shape of the seabed rather than the bathymetric surface. The digital terrain models were compiled from six repeat multibeam surveys of a headland‐associated bank near Saint John, New Brunswick, with a roughly 30‐day interval. Vectors are drawn depicting the movement of a sand dune at time t0 toward a point in the spatial correlation array at a later time, t1. A number of different techniques of picking the end of the migration vector were used. The sinuosity of the dune crest at the scale of the correlation window has an impact on which migration vector is the better pick. Averaging of migration vectors from consecutive epochs diminishes random errors in the correlation picks using any single pair of images and creates a more accurate picture of the migration field. Migration rates and crest‐relative migration directions vary substantially across the sand bank, reflecting the high gradients in bottom shear stress around the headland.
Water erosion impact on soil and carbon redistributions within uplands of Mekong River
Authors: Chaplot Vincent A. M. , Rumpel Cornelia , Valentin Christian
Published: October 2005

This study quantified the soil and carbon fluxes caused by water erosion within the sloping uplands of the Mekong River basin, a river system carrying one of the greatest worldwide amounts of sediment to the ocean. Losses of sediment and soil organic carbon (SOC) (including black carbon, BC) were evaluated within an agricultural catchment of 62 ha with steep slopes, on a tributary of the Mekong river, at nested scales of micro‐plot (1 m2), micro‐catchment (0.6 ha) and catchment (62 ha), in an attempt to explain the processes involved in water erosion. In 2002, carbon erosion occurred during 35 rainfall events amounting to 1023 mm of an annual total of 1651 mm. Water erosion removed annually 14.1 t ha−1 of sediment and 0.69 t ha−1 of SOC from the study site. This is equivalent to 7.75 and 0.51 Pg yr−1, respectively, for the uplands of the Mekong basin as a whole. When compared to the bulk soil, the eroded soil material was enriched in SOC and BC by factors of 2.3 and 1.4, respectively. The annual yields of soil material from the micro‐catchment were 3 times lower for sediment and 6 times lower for SOC than those from the micro‐plots. From the micro‐plots to the catchment, the yields decreased by a factor of 25 for sediment and 59 for SOC. Although a considerable amount of soil material is detached from its original site by water erosion, most of this material is redistributed within the landscapes, being deposited in places acting as sinks, such as hillslopes, and valley bottoms where BC is preferentially deposited. The loads from the catchment of 0.56 t ha−1 yr−1 for sediment and 0.016 t ha−1 yr−1 for SOC were considerable, corresponding to 0.31 Pg of sediment and 0.01 Pg of SOC for the Mekong basin uplands as a whole. These results on the selective water erosion of soil material, SOC and BC on sloping lands of Southeast Asia allow the source and sink functions of the sloping lands of tropical landscapes to be better understood.